Antibodies to connective tissue growth factor (ctgf) and uses thereof

Abstract

The present disclosure relates generally to anti-CTGF (connective tissue growth factor) antibodies or antigen-binding fragments thereof. The exemplary anti-CTGF antibodies disclosed herein address the need for treating disorders modulated by CTGF signaling. In some aspects, the anti-CTGF antibodies or antigen-binding fragments thereof are used for diagnostic and / or therapeutic uses, e.g., in a subject, such as a human, in need thereof.

Description

[0001] As part of this disclosure, this application includes “Sequence List XML” pursuant to 37 CFR § 1.831(a), which is submitted in XML file format as a file named “09-0753-US-1.xml”, created on February 26, 2025, and of size 203,535 bytes, which is hereby incorporated herein by reference in its entirety. Technical Field

[0002] This invention generally relates to anti-connective tissue growth factor (CTGF) antibodies. More specifically, this invention relates to anti-CTGF antibodies or antigen-binding fragments thereof, and methods for using them to treat various diseases or conditions (e.g., respiratory diseases, fibrosis, or cancer). Pharmaceutical compositions and kits comprising anti-CTGF antibodies or antigen-binding fragments thereof are also disclosed. Background Technology

[0003] Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial pneumonia of unknown etiology. It is characterized by dyspnea and progressive deterioration of lung function, with a poor prognosis. Standard care (nintedanib, pirfenidone) can reduce the decline; however, life expectancy after diagnosis remains significantly shortened.

[0004] Progressive pulmonary fibrosis (PPF) (of which IPF is the prototype) is a deadly condition that can develop in a variety of diseases, including inflammatory diseases such as rheumatoid arthritis or scleroderma.

[0005] CTGF is a secreted growth factor that regulates many pro-fibrotic processes and is strongly upregulated in IPF and PPF. CTGF consists of two N-terminal domains (together CTGF-NTF) and two C-terminal domains (together CTGF-CTF), which are bound by hinge peptides containing cleavage sequences of matrix metalloproteinases (MMPs). CTGF is secreted as a full-length 38 kDa protein and is rapidly cleaved into CTGF-NTF and CTGF-CTF upon exposure to activated MMPs. These proteases are known to be increased in disease.

[0006] CTGF has been proposed as a prognostic biomarker for the progression of IPF. However, the exact mechanism by which CTGF or CTGF fragments contribute to the pathology of pulmonary fibrosis remains unclear.

[0007] Current treatments for IPF and PPF (nintedanib and pirfenidone) slow the progression of pulmonary fibrosis. However, the median duration of treatment with these two antifibrotic agents is less than one year. Therefore, there is an unmet need for additional therapies for IPF and PPF. Summary of the Invention

[0008] This invention addresses the aforementioned needs and other problems by providing reagents that specifically bind to CTGF, particularly antibodies or antigen-binding fragments thereof. Specifically, antibodies or antigen-binding fragments thereof, as disclosed herein, specifically bind to human CTGF, such as full-length CTGF (e.g., having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2) or the N-terminal fragment of CTGF (CTGF-NTF) (e.g., having the amino acid sequence of SEQ ID NO: 3). In some aspects, the antibody or antigen-binding fragment thereof blocks the proteolytic cleavage of CTGF, for example, by matrix metalloproteinase 7 (MMP7). In some aspects, the antibody or antigen-binding fragment thereof blocks the interaction of CTGF with cells expressing CTGF receptors (such as type II alveolar cells, fibroblasts, and A549 cells). In some aspects, the antibody or antigen-binding fragment thereof blocks the interaction of CTGF-NTF with cells expressing CTGF receptors (such as type II alveolar cells, fibroblasts, and A549 cells).

[0009] Cleavage of CTGF by proteases such as MMP7 activates the CTGF pathway because the fragments are biologically active. The exemplary anti-CTGF antibody of the present invention binds to CTGF and inhibits this cleavage. Therefore, it reduces the occurrence of fragments. The exemplary anti-CTGF antibody of the present invention also specifically binds to CTGF-NTF. Therefore, this inhibition of cleavage and binding of full-length CTGF and CTGF-NTF reduces fibrosis and the production of fibrillary collagen. The exemplary anti-CTGF antibody of the present invention can reduce the levels of human fibrosis biomarkers such as ProC3.

[0010] Macrophage phagocytosis of CTGF fragments demonstrates reduced potential for cytotoxicity. Consequently, dead / senescent cells accumulate and maintain fibrosis signaling. Exemplary anti-CTGF antibodies inhibit the production of CTGF fragments. This, in turn, promotes macrophage homeostasis.

[0011] In pulmonary fibrosis, alveolar cells undergo an epithelial-mesenchymal transition (EMT), which prevents progenitor cells from repairing the alveoli. The exemplary anti-CTGF antibody of this invention inhibits this EMT in alveolar cells. This promotes the maintenance and function of alveolar stem cells, and consequently, promotes epithelial repair.

[0012] In some aspects, an anti-CTGF antibody or its antigen-binding fragment comprises: a light chain variable region comprising: a light chain complementarity-determining region 1 (L-CDR1) having the amino acid sequence Y1-SSQSIVHYN-Y2-Y3-TYLE (SEQ ID NO: 10), wherein Y1 is K or R, Y2 is A, E, G or T and Y3 is K or N; a light chain complementarity-determining region 2 (L-CDR2) having the amino acid sequence KVS-Z1-R-Z2-S (SEQ ID NO: 11), wherein Z1 is N or S and Z2 is A or F; and a light chain complementarity-determining region 3 (L-CDR3) having the amino acid sequence FQGSHFPLT (SEQ ID NO: 12); and a heavy chain variable region comprising: a heavy chain complementarity-determining region 1 (H-CDR1) having the amino acid sequence DYYMA (SEQ ID NO: 15); and a heavy chain complementarity-determining region 2; (H-CDR2), which has the amino acid sequence NINY-X1-GSRTDLL-X2-SLKS (SEQ ID NO: 16), wherein X1 is D, E or Y and X2 is A, D or E; and heavy chain complementarity-determining region 3 (H-CDR3), which has the amino acid sequence DTSRGSYFDV (SEQ ID NO: 17).

[0013] In some aspects, the anti-CTGF antibody or its antigen-binding fragment comprises six CDRs (L-CDR1, L-CDR2, L-CDR3, H-CDR1, H-CDR2, and H-CDR3) (as defined in Kabat) of any of antibodies A1-A127 as specified in Table 13. Preferably, the antibody comprises six CDRs (L-CDR1, L-CDR2, L-CDR3, H-CDR1, H-CDR2, and H-CDR3) (as defined in Kabat) of any of antibodies A1-A25, A41-A44, A46, A48-A85, or A87-A127 as specified in Table 13. More preferably, the antibody comprises six CDRs (L-CDR1, L-CDR2, L-CDR3, H-CDR1, H-CDR2, and H-CDR3) of antibody A97 as specified in Table 13 (as defined in Kabat). Although the specific CDR sequences mentioned in Table 13 are defined according to Kabat, it should be understood that the CDR sequences of antibodies A1-A127 in Table 13 may also be determined based on the full-length sequences or variable region sequences of the heavy and light chains listed in Table 13 for antibodies A1-A127, according to another numbering rule (such as the rule described herein), for example referring to the CDR sequences shown in Tables 3-8, and the light and heavy chains corresponding to the antibodies shown in Tables 9-12.

[0014] In some aspects, the anti-CTGF antibody or its antigen-binding fragment comprises a light chain variable region and a heavy chain variable region, each having at least 95% identity with the light chain variable region and the corresponding heavy chain variable region of any of the antibodies A1-A127 specified in Table 13. Preferably, the antibody comprises a light chain variable region and a heavy chain variable region, each having at least 95% identity with the light chain variable region and the corresponding heavy chain variable region of any of the antibodies A1-A25, A41-A44, A46, A48-A85, or A87-A127 specified in Table 13. Most preferably, the antibody comprises a light chain variable region and a heavy chain variable region, each having at least 95% identity with the light chain variable region and the corresponding heavy chain variable region of antibody A97 specified in Table 13.

[0015] In some aspects, the anti-CTGF antibody or its antigen-binding fragment comprises a light chain variable region and a corresponding heavy chain variable region of any of antibodies A1-A127 as specified in Table 13. Preferably, the antibody comprises a light chain variable region and a corresponding heavy chain variable region of any of antibodies A1-A25, A41-A44, A46, A48-A85, or A87-A127 as specified in Table 13. Most preferably, the antibody comprises a light chain variable region and a corresponding heavy chain variable region of antibody A97 as specified in Table 13.

[0016] In some aspects, the anti-CTGF antibody or its antigen-binding fragment comprises a light chain and a heavy chain, each having at least 95% identity with the light chain and corresponding heavy chain of any of the antibodies A1-A127 specified in Table 13. Preferably, the antibody comprises a light chain and a heavy chain, each having at least 95% identity with the light chain and corresponding heavy chain of any of the antibodies A1-A25, A41-A44, A46, A48-A85, or A87-A127 specified in Table 13. Most preferably, the antibody comprises a light chain and a heavy chain, each having at least 95% identity with the light chain and corresponding heavy chain of antibody A97 specified in Table 13.

[0017] In some aspects, the anti-CTGF antibody or its antigen-binding fragment comprises a light chain and a corresponding heavy chain of any of antibodies A1-A127 as specified in Table 13. Preferably, the antibody comprises a light chain and a corresponding heavy chain of any of antibodies A1-A25, A41-A44, A46, A48-A85, or A87-A127 as specified in Table 13. Most preferably, the antibody comprises a light chain and a corresponding heavy chain of antibody A97 as specified in Table 13.

[0018] In some aspects, the anti-CTGF antibody or its antigen-binding fragment as described herein comprises a heavy chain constant region selected from IgG1, IgG2, IgG3, IgG4, IgM, IgA, and IgE or variants thereof. Preferably, the anti-CTGF antibody or its antigen-binding fragment as described herein comprises an IgG1 heavy chain constant region.

[0019] In some respects, anti-CTGF antibodies or their antigen-binding fragments contain heavy chains lacking C-terminal lysine residues.

[0020] In some respects, anti-CTGF antibodies or their antigen-binding fragments contain a heavy chain constant region, wherein the heavy chain constant region is IgG1 with L234A and L235A substitutions.

[0021] In some respects, anti-CTGF antibodies or their antigen-binding fragments contain a light chain constant region selected from the group consisting of κ and λ light chains.

[0022] In some respects, anti-CTGF antibodies or their antigen-binding fragments are monoclonal antibodies.

[0023] In some respects, anti-CTGF antibodies or their antigen-binding fragments are monospecific antibodies.

[0024] In some aspects, an anti-CTGF antibody or its antigen-binding fragment binds to the full-length human CTGF of SEQ ID NO: 2 with a binding affinity of 50 pM or less, 25 pM or less, 15 pM or less, 10 pM or less, 5 pM or less, or 2 pM or less.

[0025] In some aspects, anti-CTGF antibodies or their antigen-binding fragments bind to human CTGF-NTF of SEQ ID NO: 3 with binding affinity of 10 nM or less, 5 nM or less, 2.5 nM or less, 1 nM or less, 0.5 nM or less, or 0.2 nM or less.

[0026] In some respects, anti-CTGF antibodies or their antigen-binding fragments are at 5 pM or lower K. D Combined with human CTGF of SEQ ID NO:2.

[0027] In some respects, anti-CTGF antibodies or their antigen-binding fragments are present at 0.5 nM or lower KJ. D Combined with the N-terminal fragment of human CTGF in SEQ ID NO: 3.

[0028] In some respects, anti-CTGF antibodies or their antigen-binding fragments reduce or block the binding of human CTGF to primary human fibroblasts.

[0029] In some respects, anti-CTGF antibodies or their antigen-binding fragments reduce or block the cleavage of human CTGF by MMP7.

[0030] In some respects, anti-CTGF antibodies or their antigen-binding fragments block or inhibit the increase in COL1A1 expression induced by human TGFβ in lung epithelial cells.

[0031] In some respects, anti-CTGF antibodies or their antigen-binding fragments block or inhibit the interaction of CTGF with type II alveolar cells, fibroblasts, and / or A549 cells.

[0032] In some respects, anti-CTGF antibodies or their antigen-binding fragments block or inhibit the interaction between CTGF-NTF and type II alveolar cells, fibroblasts, and / or A549 cells.

[0033] In some aspects, the present invention provides a pharmaceutical composition comprising an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein and a pharmaceutically acceptable carrier.

[0034] In some aspects, the present invention provides an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein, which is intended for use as a medicament.

[0035] In some aspects, the present invention provides an anti-CTGF antibody or its antigen-binding fragment as disclosed herein, for the treatment or prevention of CTGF-related conditions, fibrotic diseases, hypertension, diabetes, myocardial infarction, arthritis, CTGF-related proliferative diseases, atherosclerosis, glaucoma, or cancer. The fibrotic diseases may include idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF), pulmonary fibrosis with interstitial lung disease (PF-ILD), systemic scleroderma (SSc), diabetic nephropathy, diabetic retinopathy, osteoarthritis, scleroderma, chronic heart failure, cirrhosis, or renal fibrosis. The cancers may include acute lymphoblastic leukemia, dermatofibroma, breast cancer, angiolipoma, angioleiomyoma, connective tissue-producing cancers, prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastrointestinal cancer, or liver cancer. The anti-CTGF antibody or its antigen-binding fragment may be administered parenterally or by inhalation.

[0036] In some aspects, the present invention provides a method for treating or preventing CTGF-related conditions, fibrotic diseases, hypertension, diabetes, myocardial infarction, arthritis, CTGF-related proliferative diseases, atherosclerosis, glaucoma, or cancer, comprising administering to a patient in need an effective amount of an anti-CTGF antibody or its antigen-binding fragment as disclosed herein. The fibrotic disease may be idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF), pulmonary fibrosis with interstitial lung disease (PF-ILD), systemic scleroderma (SSc), diabetic nephropathy, diabetic retinopathy, osteoarthritis, scleroderma, chronic heart failure, cirrhosis, or renal fibrosis. The cancer may be acute lymphoblastic leukemia, dermatofibroma, breast cancer, angiolipoma, angioleiomyoma, connective tissue-producing cancer, prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastrointestinal cancer, or liver cancer. The antibody or its antigen-binding fragment may be administered via parenteral or inhalation.

[0037] In some aspects, the present invention provides the use of the anti-CTGF antibody or its antigen-binding fragment as disclosed herein for the preparation of medicaments for the treatment or prevention of CTGF-related conditions, fibrotic diseases, hypertension, diabetes, myocardial infarction, arthritis, CTGF-related proliferative disorders, atherosclerosis, glaucoma, or cancer. The fibrotic diseases may include idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF), pulmonary fibrosis with interstitial lung disease (PF-ILD), systemic scleroderma (SSc), diabetic nephropathy, diabetic retinopathy, osteoarthritis, scleroderma, chronic heart failure, cirrhosis, or renal fibrosis. The cancers may include acute lymphoblastic leukemia, dermatofibroma, breast cancer, angiolipoma, angioleiomyoma, connective tissue-producing cancers, prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastrointestinal cancer, or liver cancer. The anti-CTGF antibody or its antigen-binding fragment may be administered via parenteral or inhalation.

[0038] In some aspects, the present invention provides an isolated polynucleotide or a plurality of isolated nucleotides encoding a sequence comprising a heavy chain variable region and / or a light chain variable region comprising an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein.

[0039] In some aspects, the present invention provides one or more vectors comprising a light chain and / or a heavy chain of polynucleotides encoding an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein. The vector may comprise an expression vector or multiple expression vectors. The polynucleotides may be functionally associated with one or more expression control sequences.

[0040] In some aspects, the present invention provides a host cell comprising a light chain and / or a heavy chain of polynucleotides or multiple nucleotides encoding an anti-CTGF antibody as disclosed herein or an antigen-binding fragment thereof, or a vector or multiple vectors.

[0041] In some aspects, the present invention provides a method for generating an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein, comprising the steps of: (a) culturing a host cell under conditions that allow expression of the anti-CTGF antibody or an antigen-binding fragment thereof, the host cell comprising a polynucleotide or multiple nucleotides, or a vector or multiple vectors, encoding a light chain and / or a heavy chain of the anti-CTGF antibody or an antigen-binding fragment thereof; and (b) recovering the anti-CTGF antibody or an antigen-binding fragment thereof.

[0042] In some aspects, the present invention provides a method for inhibiting the interaction between human CTGF and cells, comprising contacting the human CTGF with (an effective amount) an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein.

[0043] In some aspects, the present invention provides a method for inhibiting the interaction between human CTGF-NTF and cells, comprising contacting the human CTGF-NTF with (an effective amount) an anti-CTGF antibody or an antigen-binding fragment thereof as disclosed herein. Attached Figure Description

[0044] Figure 1 Normalized full-length intact CTGF signal compared to each reaction with added MMP7 and MMP7+ antibodies. Antibody 97 compared to isotype control: (p<0.005). Antibody F1 compared to isotype control: (p<0.01).

[0045] Figures 2A to 2B N-terminal CTGF (H / V) in samples from healthy volunteers (“H / V”) and IPF patients (“IPF”) Figure 2A ) and full-length CTGF ( Figure 2B The concentration of N-terminal CTGF was significantly elevated in IPF patients (p≤0.05).

[0046] Figure 3 Measurement of MMP7 in samples from healthy volunteers (“H / V”) and IPF patients (“IPF”). MMP7 concentration was significantly elevated in IPF patients (p≤0.0001).

[0047] Figure 4A and Figure 4BMSD-ELISA analysis of smooth muscle actin (a-SMA) in an IPF small respiratory tract epithelial cell (SAEC) air-liquid interface (ALI) co-culture system. Fold-change expression values ​​are shown, normalized against untreated control fibroblast lysate samples. Note the elevated levels of the pro-fibrotic marker a-SMA in the IPF mixture-treated co-cultures after 72 hours. Anti-CTGF antibody and allotype controls were added 24 hours after IPF mixture stimulation. Antibody A97 ( Figure 4A ) and antibody A13 ( Figure 4B Each assay showed a dose-dependent decrease in α-SMA expression, while antibody F1 and the corresponding isotype control antibody showed no significant effect. (n=3 biological replications were performed in n=3 separate experiments). Analytical points represent co-culture wells. (*** p<0.001, **p < 0.01, *p < 0.05; one-way ANOVA).

[0048] Figure 5 Vimentin staining intensity per nucleus in 2D cultured alveolar EMT analysis following treatment with TGFβ1. (* p<0.05)

[0049] Figure 6 COL1A1 expression levels in AT2 EMT cells cultured for 2D. MSD-ELISA analysis of collagen 1a1 in the AT2 EMT system cultured for 2D. Fold-change expression values ​​are shown, normalized against untreated control AT2 cell lysate samples. TGFβ1 treatment induced increased COL1A1 expression. Antibody A97 significantly inhibited collagen production compared to the corresponding isotype control (n=2 donors, measured in 3 individual replicates). Each analytical point represents the lysate sample from the technique well (***p < 0.001; one-way ANOVA; ns: not significant).

[0050] Figure 7 Results of inhibition of collagen III (ProC3) production in the supernatant of cell cultures at the gas-liquid interface are shown in arbitrary units. Fibrosis and collagen III production were stimulated by IPF-mixture. As shown in the figure, anti-CTGF antibody A97 or F1 was used at concentrations of 1 μM, 500 nM, or 100 nM. (***p<0.001; **p<0.01; ns: not significant).

[0051] Figure 8Global protein expression correlation analysis of the supernatant at the gas-liquid interface. Magnified protein clusters containing CTGF (gene name: CCN2) showed strong correlations with collagen and other extracellular markers. According to Pearson analysis, all proteins highlighted in this cluster had extremely high protein expression profile correlations with each other, with >0.8. Note that the black coloring on the diagonal lines only reflects a Pearson correlation of 1 between each protein and itself.

[0052] Figure 9A and Figure 9B Free CTGF concentrations were determined in samples from IPF SAEC ALI co-culture assays using ligand binding analysis on the Gyrolab platform. CTGF levels were determined using a biotinylated derivative of F1 for CTGF immobilization and an Alexa-Fluor conjugate of A97 bound to a complementary epitope. Equal concentrations of A97 (…) were separately… Figure 9A ) and A13 ( Figure 9B Compared to F1, this assay showed that A97 and A13 bound to CTGF significantly more strongly. The bar graph shows the average of up to 54 individual data points, and the error bars represent the standard deviation. Samples shown on the x-axis (y=0) have values ​​equal to or below the limit of quantitation.

[0053] Figure 10 Primary human lung fibroblasts (N=2-6, different shapes represent different replications) were exposed to labeled CTGF or a mixture of labeled CTGF pre-incubated with an allotype control or anti-CTGF antibody, as shown on the X-axis (empty label indicates no antibody control). After 1 hour of incubation, cells were washed three times with PBS, and RPE signal was scanned using Incucyte. Results show the level of labeled CTGF binding to cells, normalized to cell density, and relative to the control. Mean values ​​were compared using one-way ANOVA; **p≤0.01.

[0054] Figure 11 Primary human type II alveolar cells (N=2-3, different shapes represent different replications) were exposed to labeled CTGF or a mixture of labeled CTGF pre-incubated with an allotype control or anti-CTGF antibody, as shown on the X-axis (empty label indicates no antibody control). After 4 hours of incubation, cells were washed three times with PBS, and RPE signal was scanned using Incucyte. Results show the level of labeled CTGF binding to cells, normalized to cell density, and relative to the control. Mean values ​​were compared using one-way ANOVA; *p≤0.05.

[0055] Figure 12A549 cells (N=2-10, different shapes represent different replications) were exposed to labeled CTGF or a mixture of labeled CTGF pre-incubated with an allotype control or anti-CTGF antibody, as shown on the X-axis (empty label indicates no antibody control). After 1 hour of incubation, cells were washed three times with PBS, and RPE signal was scanned using Incucyte. Results show the level of labeled CTGF binding to cells, normalized to cell density, and relative to the control. Mean values ​​were compared using one-way ANOVA; *p≤0.05, ****p≤0.0001.

[0056] Figure 13 QPCT gene expression in IDM stimulated by homeostatic (IL4 / 13). No fragment (-), FLCTGF and NTFCTGF fragments.

[0057] Figures 14A to 14B Cell burial effect IDM (n=4, Figure 14A ) and MDM (n=2, Figure 14B One-way ANOVA and Tukey's multiple comparison test, ** p ≤ 0.01. Invention Content

[0058] The following numbered paragraphs (para) describe specific aspects and embodiments of the invention: 1. An anti-CTGF antibody or its antigen-binding fragment, comprising: The light chain variable region comprises: a light chain complementarity-determining region 1 (L-CDR1) having the amino acid sequence Y1-SSQSIVHYN-Y2-Y3-TYLE (SEQ ID NO: 10), wherein Y1 is K or R, Y2 is A, E, G or T, and Y3 is K or N; a light chain complementarity-determining region 2 (L-CDR2) having the amino acid sequence KVS-Z1-R-Z2-S (SEQ ID NO: 11), wherein Z1 is N or S and Z2 is A or F; and a light chain complementarity-determining region 3 (L-CDR3) having the amino acid sequence FQGSHFPLT (SEQ ID NO: 12); and The heavy chain variable region comprises: a heavy chain complementarity-determining region 1 (H-CDR1) having the amino acid sequence DYYMA (SEQ ID NO: 15); a heavy chain complementarity-determining region 2 (H-CDR2) having the amino acid sequence NINY-X1-GSRTDLL-X2-SLKS (SEQ ID NO: 16), wherein X1 is D, E, or Y and X2 is A, D, or E; and a heavy chain complementarity-determining region 3 (H-CDR3) having the amino acid sequence DTSRGSYFDV (SEQ ID NO: 17). 2. The anti-CTGF antibody or its antigen-binding fragment as described in paragraph 1, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or ii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or iii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or iv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or v. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or vi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or vii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or viii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or ix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or x. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xl. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xli. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xliii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xliv. light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlix. Light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or 1. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or li. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or liii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or liv. light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lv. Light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lix. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lxi. Light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lxiv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xc. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xci. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xcii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xciii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xciv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xcv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xcvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or xcvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xcviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xcix. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or c. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or ci. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or ciii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or civ. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cix. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cx. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cxi. light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or cxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxiv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 140, L-CDR2 having the amino acid sequence of SEQ ID NO: 141, and L-CDR3 having the amino acid sequence of SEQ ID NO: 142; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxix. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxi. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177. 3. An anti-CTGF antibody or its antigen-binding fragment according to any of the preceding paragraphs, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxxi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xlii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xliii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xlv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xlvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xlvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xlviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xlix. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or liii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and heavy chain variable region, comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lix. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lx. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lxiv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxix. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or xc. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or xci. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or xcii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or xciii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or xciv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or xcv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or xcvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or xcvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xcviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xcix. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or c. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or ci. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or ciii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or civ. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or cvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cvii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cix. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cx. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cxi. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or cxii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or cxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxiv. light chain variable region, which contains at least 95% identical amino acid sequence to SEQ ID NO: 113; and heavy chain variable region, which contains at least 95% identical amino acid sequence to SEQ ID NO: 178; or cxv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cxvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxvii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxix. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxx. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxiv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cxxvii. a light chain variable region containing at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region containing at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178. 4. An anti-CTGF antibody or its antigen-binding fragment according to any of the preceding paragraphs, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxvi. Light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxvii. Light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxix. Light chain variable region, comprising the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxxi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxix. Light chain variable region, comprising the amino acid sequence of SEQ ID NO: 163; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xlii. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 193; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 128; or xliii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 128; or xlv. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 128; or xlvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xlvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xlviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xlix. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or liii. Light chain variable region, comprising the amino acid sequence of SEQ ID NO: 143; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 153; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, comprising the amino acid sequence of SEQ ID NO: 163; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lvii. Light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lix. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 138; or lx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lxi. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or lxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lxiv. light chain variable region containing the amino acid sequence of SEQ ID NO: 253; and heavy chain variable region containing the amino acid sequence of SEQ ID NO: 138; or lxv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxix. light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxiv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxix. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxxi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxix. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xc. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xci. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xcii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xciii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xciv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xcv. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 158; or xcvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or xcvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xcviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xcix. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 168; or c. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or ci. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or ciii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or civ. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cix. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cxi. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 168; or cxii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or cxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxiv. light chain variable region containing the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region containing the amino acid sequence of SEQ ID NO: 178; or cxv. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 178; or cxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 143; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxix. light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxxi. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 183; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 178; or cxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxxiv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxxv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cxxvii. light chain variable region containing the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region containing the amino acid sequence of SEQ ID NO: 178. 5. The anti-CTGF antibody or its antigen-binding fragment, based on any of the preceding paragraphs, comprises: i. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or v. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or vi. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or vii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or viii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or ix. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or x. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xi. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xiv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xvi. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xvii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xix. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xx. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxiv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxvi. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxix. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxx. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxxi. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxxii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxiv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxv. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvi. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxvii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxviii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxix. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xl. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xli. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xliii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xliv. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlix. light chain, comprising at least 95% identical amino acid sequence to SEQ ID NO: 104; and heavy chain, comprising at least 95% identical amino acid sequence to SEQ ID NO: 139; or 1. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or li. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liv. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lxii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxix. light chain, comprising at least 95% identical amino acid sequence to SEQ ID NO: 144; and heavy chain, comprising at least 95% identical amino acid sequence to SEQ ID NO: 149; or lxx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxix. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxix. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xc. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xci. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xcii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xciii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xciv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xcv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xcvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or xcvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xcviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xcix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or c. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or ci. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or cii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or ciii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or civ. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cviii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cix. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cxii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or cxiii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxiv. a light chain comprising at least 95% identical amino acid sequence to SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to SEQ ID NO: 179; or cxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 144; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxviii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxiii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cxxvii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179. 6. The anti-CTGF antibody or its antigen-binding fragment, based on any of the preceding paragraphs, comprises: i. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or v. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or vi. A light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or vii. A light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or viii. A light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or ix. A light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or x. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xi. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xii. A light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xiii. A light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xiv. A light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xv. a light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xvi. A light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or xvii. A light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xviii. A light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xix. a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xx. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxi. a light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxii. A light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxiii. A light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxiv. A light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxv. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxvii. a light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxviii. A light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxix. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxx. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxxi. a light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxxii. A light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 119; or xxxiii. A light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xxxiv. A light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xxxv. a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xxxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xxxvii. a light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xxxviii. A light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xxxix. a light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xl. a light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xli. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xlii. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xliii. a light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xliv. light chain, comprising the amino acid sequence of SEQ ID NO: 214; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 129; or xlv. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xlvi. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xlvii. a light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xlviii. a light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 129; or xlix. light chain, comprising the amino acid sequence of SEQ ID NO: 104; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 139; or 1. A light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or li. a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lii. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or liii. a light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or liv. light chain, comprising the amino acid sequence of SEQ ID NO: 154; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 139; or lv. a light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lvi. a light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lvii. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lviii. A light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lix. light chain, comprising the amino acid sequence of SEQ ID NO: 204; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 139; or lx. a light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lxi. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lxii. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lxiii. A light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lxiv. a light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139; or lxv. a light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxvii. a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxviii. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxix. light chain, comprising the amino acid sequence of SEQ ID NO: 144; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 149; or lxx. a light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxi. a light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxii. a light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxiii. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxiv. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxv. a light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxvii. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxviii. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxix. a light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxx. a light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 149; or lxxxi. a light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxii. a light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxiii. a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxiv. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxv. a light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxvii. a light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxviii. A light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or lxxxix. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xc. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xci. a light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xcii. a light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xciii. A light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xciv. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xcv. a light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xcvi. a light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 159; or xcvii. a light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or xcviii. A light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or xcix. light chain, comprising the amino acid sequence of SEQ ID NO: 124; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 169; or c. A light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or ci. a light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cii. a light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or ciii. A light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or civ. a light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cv. light chain comprising the amino acid sequence of SEQ ID NO: 184; and heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cvi. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cvii. a light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cviii. a light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cix. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cx. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cxi. a light chain comprising the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cxii. a light chain comprising the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; or cxiii. a light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxiv. a light chain containing the amino acid sequence of SEQ ID NO: 114; and a heavy chain containing the amino acid sequence of SEQ ID NO: 179; or cxv. a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxvii. a light chain comprising the amino acid sequence of SEQ ID NO: 144; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxviii. a light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxix. light chain, comprising the amino acid sequence of SEQ ID NO: 164; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 179; or cxx. a light chain comprising the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxi. a light chain comprising the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxii. a light chain comprising the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxiii. a light chain comprising the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxiv. a light chain comprising the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxv. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxvi. a light chain comprising the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 179; or cxxvii. light chain, comprising the amino acid sequence of SEQ ID NO: 244; and heavy chain, comprising the amino acid sequence of SEQ ID NO: 179. 7. An anti-CTGF antibody or its antigen-binding fragment according to any of the preceding paragraphs, comprising: a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107. 8. An anti-CTGF antibody or its antigen-binding fragment according to any of the preceding paragraphs, comprising: a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108. 9. An anti-CTGF antibody or its antigen-binding fragment according to any of the preceding paragraphs, comprising: a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109. 10. An anti-CTGF antibody according to any of the preceding paragraphs, wherein (a) the antibody contains a heavy chain constant region selected from IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE or variants thereof; (b) the antibody is a monoclonal antibody; and / or (c) the antibody is a human, humanized or chimeric antibody, preferably a humanized antibody. 11. Anti-CTGF antibody according to any of the preceding paragraphs, wherein the antibody (a) is at 5 pM or lower K D (b) Combined with human CTGF; (c) with 0.5 nM or less K D (c) Binding to the N-terminal fragment of human CTGF; (d) Reducing or blocking the binding of human CTGF to primary human fibroblasts; (e) Reducing or blocking the cleavage of human CTGF by MMP7; (f) Blocking or inhibiting the increase in COL1A1 expression induced by human TGFβ in lung epithelial cells; (g) Blocking or inhibiting the interaction of CTGF with type II alveolar cells, fibroblasts and A549 cells; and / or (g) Blocking or inhibiting the interaction of CTGF-NTF with type II alveolar cells, fibroblasts and A549 cells. 12. A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof according to any of the preceding paragraphs and a pharmaceutically acceptable carrier. 13. An antibody or antigen-binding fragment thereof as described in any of paragraphs 1 to 11, or a composition as described in paragraph 12, is intended for use as a medicine. 14. An antibody or antigen-binding fragment thereof as described in any of paragraphs 1 to 11, or a composition as described in paragraph 12, for the treatment or prevention of CTGF-related conditions, fibrosis, hypertension, diabetes, myocardial infarction, arthritis, CTGF-related proliferative disorders, atherosclerosis, glaucoma, or cancer. 15. The antibody or antigen-binding fragment or composition thereof provided for use as in paragraph 13 or 14, wherein the fibrotic disease is idiopathic pulmonary fibrosis (IPF), progressive pulmonary fibrosis (PPF), pulmonary fibrosis with interstitial lung disease (PF-ILD), systemic scleroderma (SSc), Duchenne muscular dystrophy, diabetic nephropathy, diabetic retinopathy, osteoarthritis, scleroderma, chronic heart failure, cirrhosis, or renal fibrosis, or wherein the cancer is acute lymphoblastic leukemia, dermatofibroma, breast cancer, angiolipoma, angioleiomyoma, connective tissue-producing cancer, prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastrointestinal cancer, or liver cancer. 16. A single polynucleotide or multiple single polynucleotides encoding a sequence comprising a heavy chain variable region and / or a light chain variable region of an antibody or an antigen-binding fragment thereof, as described in any of paragraphs 1 to 11. 17. A vector or multiple vectors comprising a polynucleotide or multiple polynucleotides as described in paragraph 16, preferably an expression vector or multiple expression vectors, more preferably a vector or multiple vectors comprising the polynucleotide or multiple polynucleotides functionally associated with one or more expression control sequences. 18. A host cell containing polynucleotides or multiple nucleotides as described in paragraph 17. 19. A method for generating an anti-CTGF antibody or an antigen-binding fragment thereof as described in any of paragraphs 1 to 11, comprising the steps of: (a) Culture host cells as described in paragraph 18 under conditions that allow expression of the anti-CTGF antibody or its antigen-binding fragment; and (b) Recover the anti-CTGF antibody or its antigen-binding fragment. 20. A method for inhibiting the interaction between human CTGF or human CTGF-NTF and cells, comprising contacting the human CTGF with an effective amount of an anti-CTGF antibody or an antigen-binding fragment thereof, as described in any of paragraphs 1 to 11. Detailed Implementation

[0059] This invention generally relates to anti-CTGF antibodies or antigen-binding fragments thereof. The exemplary anti-CTGF antibodies disclosed herein address a need for the treatment of conditions regulated by CTGF signaling. In some aspects, anti-CTGF antibodies or antigen-binding fragments thereof are used for diagnostic and / or therapeutic purposes, such as for subjects with this need, such as humans.

[0060] In some aspects, the present invention provides an anti-CTGF antibody, particularly a monoclonal anti-CTGF antibody, such as a human or humanized monoclonal anti-CTGF antibody having one or more of the properties described herein.

[0061] In some respects, anti-CTGF antibodies or their antigen-binding fragments reduce or prevent the cleavage of full-length CTGF by proteases such as MMP7.

[0062] In some respects, anti-CTGF antibodies or their antigen-binding fragments reduce or block the interaction between CTGF and cells expressing one or more CTGF receptors, such as type II alveolar cells, fibroblasts, and A549 cells.

[0063] In some respects, anti-CTGF antibodies or their antigen-binding fragments reduce or prevent the inhibition of macrophage burial by CTGF-NTF.

[0064] In some respects, anti-CTGF antibodies or their antigen-binding fragments reduce or prevent the progression of fibrosis in human small respiratory cells that are elevated at the air-liquid interface and exposed to pro-fibrotic cytokines such as the IPF cytokine mixture (IPF-RC) described in Example 5 of this paper.

[0065] In some aspects, preferably when measured by surface plasmon resonance at 25°C, the anti-CTGF antibody or its antigen-binding fragment exhibits a binding affinity (K0) to full-length human CTGF of less than 50 pM, less than 25 pM, less than 15 pM, less than 10 pM, less than 5 pM, or less than 2 pM (K0). D ).

[0066] In some aspects, preferably when measured by surface plasmon resonance at 25°C, the anti-CTGF antibody or its antigen-binding fragment exhibits a binding affinity (K0) to human CTGF-NTF of less than 10 nM, less than 5 nM, less than 2.5 nM, less than 1 nM, less than 0.5 nM, or less than 0.2 nM. D ).

[0067] In some aspects, the anti-CTGF antibody or its antigen-binding fragment of the present invention has favorable pharmacokinetic properties. In some aspects, the anti-CTGF antibody of the present invention has favorable biophysical properties, such as yield, quality, stability, or solubility.

[0068] Numerous specific details are set forth in this detailed description to provide a full understanding of the invention. However, it will be apparent to those skilled in the art that the invention may be practiced without some of these specific details. In other instances, well-known structures and techniques have not been shown in detail so as not to obscure the invention. Unless the context otherwise indicates, preferences and options for a given aspect, feature, embodiment, or parameter should be considered as disclosed in combination with any and all preferences and options for all other aspects, features, embodiments, and parameters of the invention.

[0069] Antibody

[0070] The general structure of antibodies or immunoglobulins is well known to those skilled in the art; these molecules are typically heterotetrameric glycoproteins of about 150,000 Daltons, consisting of two identical light (L) chains and two identical heavy (H) chains. Each light chain is covalently linked to the heavy chain via a disulfide bond to form a heterodimer, and heterotrimer molecules are formed through covalent disulfide bonds between the two identical heavy chains of the heterodimer. Although the light and heavy chains are linked together by a disulfide bond, the number of disulfide bonds between the two heavy chains varies depending on the immunoglobulin isotype. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has a variable domain (V) at its amino terminus. H (for variable heavy chains), followed by three or four constant fields (C H 1. C H 2. C H 3 and optional location C H 4), and C H 1 and C H The hinge region between 2. Each light chain has two domains, an amino-terminal variable domain (V L (for variable light chains) and carboxyl-terminal constant domain (C L V L Domain and V H Domains are non-covalently bound, however C L Domains are typically covalently linked to C via disulfide bonds. H 1. Domain. It is believed that specific amino acid residues form interfaces between the variable domains of the light and heavy chains (Chothia et al., 1985, J. Mol. Biol. 186:651-663, Vargas-Madrazo E, Paz-García E. J MolRecognit. 2003;16(3):113-120). Variable domains are also referred to as variable regions in this paper, and constant domains are referred to as constant regions.

[0071] Some domains within a variable domain vary significantly between different antibodies; these are termed "highly variable." These highly variable domains contain residues directly involved in the binding and specificity of each antibody to its specific antigenic determinant. The high variability in both light and heavy chain variable domains is concentrated in three regions called complementarity-determining regions (CDRs) or highly variable loops (HVLs). CDRs are defined by sequence comparison (Kabat et al., 1991, Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, Md.), while HVLs are structurally defined based on the three-dimensional structure of the variable domain, as described by Chothia and Lesk, 1987, J. Mol. Biol. 196: 901-917. As defined by Kabat, in the light chain variable domain, CDR-L1 is located at approximately residues 24-34, CDR-L2 at approximately residues 50-56, and CDR-L3 at approximately residues 89-97; in the heavy chain variable domain, CDR-H1 is located at approximately residues 31-35, CDR-H2 at approximately residues 50-65, and CDR-H3 at approximately residues 95-102. Unless otherwise indicated, CDR sequences mentioned herein refer to CDR sequences as defined by Kabat. IMGT and NORTH provide alternative definitions of CDR (see Lefranc MP. Uniquedatabase numbering system for immunogenetic analysis. Immunol Today (1997) 18:509; and North B, Lehmann A, Dunbrack RLJ. A new clustering of antibody CDRloop conformations. J Mol Biol. (2011) 406:228-56). Furthermore, CDRs can be defined according to the Chemical Computation Group (CCG) numbering (Almagro et al., Proteins 2011; 79:3050-3066 and Maier et al., Proteins 2014; 82:1599-1610). Therefore, the CDR1, CDR2, and CDR3 definitions for the heavy and light chains possess specific and functional characteristics for a given antibody. Those skilled in the art can determine the CDR sequence from a specific VH and / or VL sequence according to the aforementioned numbering scheme.Unless otherwise indicated, this invention has been disclosed with reference to the CDRs as defined in Kabat, but it should be understood that this invention may also be determined with reference to other CDR numbering schemes, such as those CDRs disclosed in Tables 3 through 8 herein (e.g., Chothia, CCG, IMGT, or Aho).

[0072] The three CDRs within each of the heavy and light chains are separated by frame regions (FRs), which contain sequences that tend to be less variable. From the amino terminus to the carboxyl terminus of the variable domains of both the heavy and light chains, the FRs and CDRs are arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The dominant β-sheet conformation of the FRs brings the CDRs within each chain close to each other and close to CDRs from the other chain. This conformation facilitates antigen-binding sites (see Kabat et al., 1991, NIH Publication No. 91-3242, Vol. I, pp. 647-669), but not all CDR residues are necessarily directly involved in antigen binding. Given the amino acid sequence of the variable region of the antibody, those skilled in the art can determine in a conventional manner which residues contain specific CDRs. Therefore, the definitions of CDR1, CDR2, and CDR3 in the heavy and light chains have a specific uniqueness and functional character for a given antibody.

[0073] FR residues and Ig constant domains generally do not directly participate in antigen binding, but they contribute to antigen binding and / or mediate antibody effector functions. Some FR residues are considered to significantly influence antigen binding in at least three ways: non-covalent direct binding to epitopes, interaction with one or more CDR residues, and influencing the interface between heavy and light chains. Constant domains do not directly participate in antigen binding, but mediate various Ig effector functions, such as antibody-dependent cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent phagocytosis (ADCP).

[0074] The light chains of vertebrate immunoglobulins are classified into two distinct classes, κ and λ, based on the amino acid sequence of their constant domains. By comparison, the heavy chains of mammalian immunoglobulins are assigned to one of five main classes based on the sequence of their constant domains: IgA, IgD, IgE, IgG, and IgM. IgG and IgA are further subdivided into subtypes (isotypes), such as IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2, respectively. As described herein, antibodies may possess any of these classes or subtypes. Preferably, the antibody is of the IgG type, more preferably IgG1. The constant domains of the heavy chains corresponding to the different classes of immunoglobulins are referred to as α, δ, ε, γ, and μ, respectively. The subunit structures and three-dimensional configurations of these classes of native immunoglobulins are well known.

[0075] definition

[0076] The terms “antibody” and “anti-CTGF antibody” are used interchangeably herein and encompass monoclonal antibodies (including full-length monoclonal antibodies), multispecific antibodies (e.g., bispecific antibodies), antibodies with minor modifications (such as N-terminal or C-terminal truncation) and antibody fragments (such as variable domains), and other portions of antibodies that exhibit the desired biological activity (e.g., CTGF binding).

[0077] The term "monoclonal antibody" refers to antibodies derived from a substantially homogeneous population of antibody molecules, meaning that the individual antibodies comprising the population are identical, except for possible well-known alterations (such as removal of the C-terminal lysine from the antibody heavy chain) or post-translational modifications (such as possible amino acid isomerization or deamidation, methionine oxidation, or asparagine or glutamine deamidation). Monoclonal antibodies typically bind to one antigenic epitope. Bispecific monoclonal antibodies bind to two different antigenic epitopes. Monoclonal antibodies can be monospecific or multispecific, such as bispecific, monovalent, bivalent, or multivalent. It should be understood that monoclonal antibodies can be prepared by any technique or method known in the art; including, for example, hybridoma methods (Kohler et al., 1975, Nature 256:495), or recombinant DNA methods known in the art (see, for example, U.S. Patent No. 4,816,567), or methods using phage antibody libraries to isolate monoclonal antibodies generated in a recombinant manner using the techniques described in Clackson et al., 1991, Nature 352:624-628 and Marks et al., 1991, J.Mol. Biol. 222:581-597.

[0078] Chimeric antibodies consist of variable regions of the heavy and light chains of an antibody from one species (e.g., a non-human mammal, such as a mouse) and constant regions of the heavy and light chains of an antibody from another species (e.g., a human), and can be obtained by linking a DNA sequence encoding the variable region of an antibody from the first species (e.g., a mouse) to a DNA sequence encoding the constant region of an antibody from the second species (e.g., a human), and transforming a host with an expression vector containing the linked sequence to produce the chimeric antibody. Alternatively, chimeric antibodies may also be antibodies whose heavy and / or light chains are identical, homologous, or variants of corresponding sequences from another immunoglobulin class or isotype, or from common or germline sequences in a monoclonal antibody. Chimeric antibodies may include fragments of such antibodies, provided that the antibody fragment exhibits the desired biological activity of its parent antibody, such as binding to the same epitope (see, for example, U.S. Patent No. 4,816,567; and Morrison et al., 1984, Proc. Natl. Acad. Sci. USA 81: 6851-6855).

[0079] The terms "antibody fragment," "antigen-binding fragment," "anti-CTGF antibody fragment," and "engineered anti-CTGF antibody fragment" refer to a portion of a full-length anti-CTGF antibody that retains variable regions or functional capabilities, such as CTGF binding. Examples of antibody fragments include (but are not limited to) Fab, Fab', F(ab')2, Fd, Fv, scFv and scFv-Fc fragments, bifunctional antibodies, linear antibodies, single-chain antibodies, microantibodies, bifunctional antibodies formed from antibody fragments, and multispecific antibodies formed from antibody fragments.

[0080] Antibody fragments can be obtained, for example, by treating a full-length antibody with an enzyme such as papain or pepsin to produce a suitable antibody fragment. Papain digestion produces two identical antigen-binding antibody fragments (called "Fab" fragments), each with a single antigen-binding site, and a residual "Fc" fragment. The Fab fragment also contains a constant domain of the light chain and a C-terminal domain of the heavy chain. H Domain 1. Pepsin treatment produces the F(ab')2 fragment, which has two antigen-binding sites and can still cross-link antigens.

[0081] An example of the antibody fragment of the present invention is the Fab' fragment. The Fab' fragment differs from the Fab fragment in that it... H The C-terminus of the 1 domain contains additional residues, including one or more cysteine ​​residues from the antibody hinge region. The F(ab')2 antibody fragment is a Fab' fragment pair linked by cysteine ​​residues in the hinge region. Other chemical couplings of antibody fragments are also known.

[0082] The “Fv” fragment contains a complete antigen recognition and binding site, which is a dimer composed of a heavy chain variable domain and a light chain variable domain tightly bound together nonvalently. In this configuration, the three CDRs of each variable domain interact to define V. H -V L Antigen-binding sites on the surface of the dimer. The six CDRs collectively confer antigen-binding specificity to the antibody.

[0083] Antibody fragments may also include "single-chain Fv" or "scFv" fragments. "Single-chain Fv" or "scFv" antibody fragments are V-type fragments containing antibodies. H and V L Single-chain Fv variants, wherein these domains are present within a single polypeptide chain. Single-chain Fvs are capable of recognizing and binding antigens. scFv polypeptides may also optionally contain domains located at V... H With V LThe peptide linkers between domains facilitate the formation of the three-dimensional structure required for antigen binding via scFv (see, for example, Pluckthun, 1994, The Pharmacology of monoclonal Antibodies, Vol. 113, edited by Rosenburg and Moore, Springer-Verlag, New York, pp. 269-315).

[0084] Antibody fragments can also form tandem Fd regions, which contain a pair of tandem Fd regions (V H -C H 1-V H -C H 1) To form a pair of antigen-binding regions. These “linear antibodies” can be bispecific or monospecific, as described, for example, in Zapata et al., 1995, Protein Eng. 8(10):1057-1062.

[0085] As used herein, the term "human antibody" includes antibodies or fragments thereof derived from human germline immunoglobulin sequences. The term "human antibody" is not intended to include antibodies in which a CDR sequence derived from another (mammal) species (such as a mouse, rat, or rabbit) has been grafted onto a human frame sequence. Therefore, as used herein, the term "human antibody" refers to a protein (e.g., CDR, frame, C...) in which... L C H Domain (e.g., C) H 1. C H 2. C H 3) Hinges, V L V H Each part of the antibody is substantially non-immunogenic in humans, consisting only of antibodies or fragments thereof with minor sequence variations or mutations as further described below.

[0086] Techniques for forming such “human antibodies” have been described and include (but are not limited to) phage display or the use of transgenic animals (www.Ablexis.com / technology-alivamab.php; WO 90 / 05144; D. Marks, HR Hoogenboom, TP Bonnert, J. McCafferty, AD Griffiths and G. Winter (1991) “By-passing immunisation. Human antibodies from V-gene libraries displayed onphage”. J.Mol.Biol., 222, 581-597; Knappik et al., J. Mol. Biol. 296: 57-86, 2000; S. Carmen and L. Jermutus, “Concepts in antibody phage display”. Briefingsin Functional Genomics and Proteomics 2002 1(2):189-203; Lonberg N, Huszar D. “Human antibodies from transgenic mice". Int Rev Immunol. 1995;13(1):65-93.; Brüggemann M, Taussig MJ. "Production of human antibody repertoires intransgenic mice". Curr Opin Biotechnol. 1997 Aug;8(4):455-8.).

[0087] Therefore, human antibodies differ from, for example, chimeric or humanized antibodies. It should be noted that human antibodies can be produced by non-human animals or prokaryotic or eukaryotic cells capable of expressing functionally rearranged human immunoglobulin (e.g., heavy chain and / or light chain) genes.

[0088] In some respects, anti-CTGF antibodies are humanized antibodies or antibody fragments thereof. Humanized antibodies or humanized antibody fragments are specific types of chimeric antibodies comprising immunoglobulin amino acid sequence variants or fragments thereof capable of binding to a predetermined antigen and comprising one or more FRs substantially having the amino acid sequence of human immunoglobulins and one or more CDRs substantially having the amino acid sequence of non-human immunoglobulins. This non-human amino acid sequence, often referred to as the “introducing” sequence, is typically derived from the “introducing” antibody domain, particularly the variable domain. Generally, humanized antibodies comprise at least a CDR or HVL of a non-human antibody inserted between FRs of human heavy or light chain domains. Methods for humanizing antibodies are described, for example, in Almagro et al., (2008) Frontiers in Bioscience 13, 1619-1633 or WO12092374 A2.

[0089] The chimeric antibodies, humanized antibodies, or human antibodies or their antigen-binding fragments of the present invention may be further engineered. Such engineering includes (but is not limited to) the removal or exchange of unwanted amino acids, for example, to reduce immunogenicity in humans, or to avoid deamidation, unwanted charges, or lipophilic or nonspecific binding. Such removal or exchange of unwanted amino acids may be introduced, for example, by inducing random or site-specific mutations in vitro or by somatic mutations in vivo. Furthermore, regarding chimeric or humanized antibodies, it should be understood that certain mouse FR residues may be retained in the antibody or its fragments.

[0090] In some aspects, anti-CTGF antibodies substantially comprise all of at least one and usually two variable domains (such as those contained in fragments of, for example, Fab, Fab', F(ab')2, ScFv, and Fv). In some aspects, anti-CTGF antibodies also comprise at least a portion of the Fc region of an immunoglobulin, typically at least a portion of a human immunoglobulin. Generally, the antibody will contain both a light chain and at least a variable domain of the heavy chain. Where appropriate, the antibody may also include the C-terminal region of the heavy chain. H 1. Hinges, C H 2. C H 3 and / or C H One or more of the four zones.

[0091] In some aspects, anti-CTGF antibodies may be selected from any class of immunoglobulins, including IgM, IgG, IgD, IgA, and IgE, and any isotypes, including IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. Alternative anti-CTGF antibodies may comprise sequences from more than one immunoglobulin class or isotype, and specific modified or unmodified constant domains may be selected to optimize the desired effector function, which is within the scope of ordinary skill in the art.

[0092] For example, the Fc region of an antibody mediates its serum half-life and effector functions, such as complement-dependent cytotoxicity (CDC), antibody-dependent cytotoxicity (ADCC), and antibody-dependent phagocytosis (ADCP). Fc engineering can be used to optimize antibody properties to suit desired pharmacological activities. When such cytotoxic activity is undesirable, such as targeting immune cells in cancer treatment, the constant domain can be modified with an isoform that reduces effector function, such as IgG4, and / or with known modifications that reduce effector function. When such cytotoxic activity is desirable, such as for destroying targeted tumor cells, the constant domain can be modified with an isoform that increases effector function and / or with known modifications that increase effector function. Several mutations are known to reduce or increase effector function. See, for example, "The future of antibodies as cancer drugs" Janice M Reichert, Eugen Dhimolea, Drug Discov Today (2012) Sep;17(17-18):954-63; PMID: 22561895, "Antibody Drug Discovery" (Volume 4 of Molecular medicine and medicinal chemistry) Clive R. Wood, World Scientific, 2012 ISBN1848166281, 9781848166288; "FcγR requirements leading to successful immunotherapy" Immunol Rev. (2015) Nov;268(1):104-22; PMID: 26497516.

[0093] In some aspects, the constant domain of the antibody of the present invention is human IgG1 with two modifications, Leu234Ala and Leu235Ala, in the constant region. These modifications in the constant region reduce effector function.

[0094] The FR and CDR or HVL of an engineered anti-CTGF antibody or its antigen-binding fragment do not need to correspond precisely to the parental sequence, i.e., the antibody sequence isolated before engineering. For example, the parental sequence can be altered (e.g., induced by mutation) through substitution, insertion, or deletion, such that the resulting amino acid residues no longer correspond to the original residues at the corresponding positions in any parental sequence, but the antibody still retains its function of binding to CTGF. Such alterations are usually not widespread. Such alterations are usually conserved. Typically, at least 75% of the engineered antibody residues will correspond to those residues in the parental sequence, more typically at least 90%, and most often greater than 95%, or greater than 98%, or greater than 99%.

[0095] The interface (“V”) between the heavy chain variable region and the light chain variable region affects L -V H Immunoglobulin residues at the interface are residues that affect the proximity or orientation of two chains relative to each other. Some residues that can participate in interchain interactions include V... L Residues 34, 36, 38, 44, 46, 87, 89, 91, 96, 98, and V H Residues 35, 37, 39, 45, 47, 91, 93, 95, 100, and 103 (using the numbering system described in Kabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md., 1987)). US Patent No. 6,407,213 also discusses residues such as V... L Residues 43 and 85 and V H Residues 43 and 60 may also be involved in this interaction. Although these residues are only indicated for human IgG, they are applicable to all species. Important antibody residues reasonably expected to participate in interchain interactions are selected and substituted into the common sequence.

[0096] The terms “shared sequence” and “shared antibody” refer to an amino acid sequence containing the most frequently occurring amino acid residues at various positions in all immunoglobulins of any particular class, isotype, or subunit structure (e.g., human immunoglobulin variable domain). Shared sequences may be based on immunoglobulins of a specific species or many species. It should be understood that a “shared” sequence, structure, or antibody encompasses shared human sequences as described in some examples and refers to an amino acid sequence containing the most frequently occurring amino acid residues at various positions in all human immunoglobulins of any particular class, isotype, or subunit structure. Thus, a shared sequence contains an amino acid sequence having amino acids present in one or more known immunoglobulins at various positions, but it may not completely replicate the entire amino acid sequence of any single immunoglobulin. Variable region shared sequences are not derived from any naturally occurring antibody or immunoglobulin. Kabat et al., 1991, Sequences of Proteins of Immunological Interest, 5th ed. Public Health Service, National Institutes of Health, Bethesda, Md., and variants thereof. FRs and their variants, which share a common heavy and light chain sequence, provide sequences suitable for the preparation of human or humanized anti-CTGF antibodies. See, for example, U.S. Patent Nos. 6,037,454 and 6,054,297.

[0097] "Isolated" antibodies are antibodies that have been identified, isolated, and / or recovered from components of their native environment or from cell cultures in which they are expressed. Isolated antibodies or antibody fragments may have one or more co-translational or post-translational modifications that occur during the production, purification, and / or storage of the antibody or antibody fragment. Contaminants from the antibody's native environment are substances that can interfere with the diagnostic or therapeutic use of the antibody and may be enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In some aspects, the antibody will be purified to a separation of at least 95% by weight of the antibody, for example, to at least 95%, 96%, 97%, 98%, or 99%.

[0098] The isolated antibodies include in situ antibodies from recombinant cells, because at least one component of the antibody's native environment will be absent. However, the isolated antibodies are typically prepared through at least one purification step in which the recombinant cellular material is removed.

[0099] "Multispecificity" refers to proteins that specifically bind to two or more different antigens or two or more different epitopes within the same antigen, such as antibodies.

[0100] "Bispecificity" refers to proteins that specifically bind to two different antigens or two different epitopes within the same antigen, such as antibodies.

[0101] In some embodiments, the antibody that specifically binds to CTGF or its antigen-binding fragment is a monospecific antibody. In some embodiments, the antibody that specifically binds to CTGF or its antigen-binding fragment is a bispecific antibody. In some embodiments, the antibody or its antigen-binding fragment is a multispecific antibody. Monospecific antibodies that specifically bind to CTGF as described herein may be engineered into bispecific antibodies, which are also covered within the scope of this invention.

[0102] Full-length bispecific antibodies can be used, for example, between two monospecific bivalent antibodies using Fab arm exchange (e.g., half-molecule exchange, exchanging a heavy chain-light chain pair) via the heavy chain C in each half-molecule. H Substitution is introduced at the 3-interface to facilitate the formation of heterodimers from two co-expressed antibody half-molecules with different specificities in an in vitro cell-free environment. The Fab arm exchange reaction is a product of disulfide bonds.

[0103] Bispecific antibodies can also be generated using designs such as Triomab / Quadroma (TrionPharma / Fresenius Biotech), Knob-in-Hole (Genentech), CrossMAb (Roche), and electrostatically induced C... H 3. Interactions (Chugai, Amgen, NovoNordisk, Oncomed), LUZ-Y (Genentech), SEED (EMD Serono), Biclonic (Merus), and DuoBody® products (Genmab A / S).

[0104] As used herein, in the case of two or more nucleic acid or polypeptide sequences, the term "consistency" or "percentage of consistency" refers to two or more sequences or subsequences that are identical or have a specified percentage of identical nucleotide or amino acid residues for maximum correspondence comparison and alignment. To determine the percentage of consistency, sequences are aligned for optimal comparison purposes (e.g., vacancies may be introduced in the first amino acid sequence or nucleic acid sequence to best align with the second amino acid or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid or nucleotide positions are then compared. If a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, the molecule is consistent at that position. The percentage of consistency between two sequences is a function of the number of identical positions shared by these sequences (i.e., consistency % = number of identical positions / total number of positions (i.e., overlapping positions) × 100). In some embodiments, where appropriate, the two sequences being compared are of the same length after vacancies are introduced within the sequences (e.g., excluding any additional sequences extending beyond the compared sequences). For example, when comparing variable region sequences, leader and / or constant domain sequences are not considered. For sequence comparisons between two sequences, the "corresponding" CDR refers to the CDR at the same position in the two sequences (e.g., CDR-H1 of each sequence).

[0105] Mathematical algorithms can be used to determine the percentage similarity or identity between two sequences. Preferred, non-limiting examples of mathematical algorithms for comparing two sequences are those described in Karlin and Altschul, 1990, Proc. Natl. Acad. Sci. USA 87:2264-2268, modified as described in Karlin and Altschul, 1993, Proc. Natl. Acad. Sci. USA 90:5873-5877. Such algorithms are incorporated into the NBLAST and XBLAST procedures of Altschul et al., 1990, J. Mol. Biol. 215:403-410. BLAST nucleotide searches can be performed using the NBLAST procedure (score=100, word length=12) to obtain nucleotide sequences homologous to the nucleic acid encoding the protein of interest. BLAST protein searches can be performed using the XBLAST procedure (score=50, word length=3) to obtain amino acid sequences homologous to the protein of interest. To obtain vacancy alignments for comparison purposes, vacancy-based BLAST can be used, as described in Altschul et al., 1997, Nucleic Acids Res. 25:3389-3402. Alternatively, iterative searching using PSI-Blast can be performed to detect distant relationships between molecules (as above). When using BLAST, vacancy-based BLAST, and PSI-Blast programs, the preset parameters of their respective programs (e.g., XBLAST and NBLAST) can be used. Another preferred, non-limiting example of a mathematical algorithm for comparing sequences is the algorithm of Myers and Miller, CABIOS (1989). Such algorithms are incorporated into the ALIGN program (version 2.0), which is part of the GCG sequence alignment software package. When using the ALIGN program to compare amino acid sequences, the PAM120 weighted residue table, vacancy length penalty of 12, and interstitial penalty of 4 can be used. Additional algorithms used for sequence analysis include ADVANCE and ADAM, as described in Torellis and Roboti, 1994, Comput. Appl. Biosci. 10:3-5; and FASTA, as described in Pearson and Lipman, 1988, Proc. Natl. Acad. Sci. USA 85:2444-8. Within FASTA, ktup is a control option for setting the sensitivity and speed of the search. If ktup = 2, similar regions in the two compared sequences are obtained by observing aligned residue pairs; if ktup = 1, single aligned amino acids are examined. For protein sequences, ktup can be set to 2 or 1, or for DNA sequences, it can be set to 1 through 6.If ktup is not specified, the default value is 2 for proteins and 6 for DNA. Alternatively, the CLUSTAL W algorithm can be used for protein sequence alignment, as described by Higgins et al., 1996, Methods Enzymol. 266:383-402.

[0106] For diagnostic and therapeutic monitoring purposes, the antibodies or antigen-binding fragments of the present invention may also be bound to a label (labeled alone or labeled with an additional second agent (prodrug, chemotherapeutic agent, and the like)). The label, distinct from other second agents, refers to a reagent that acts as a detectable compound or composition and can bind directly or indirectly to the anti-CTGF antibody or antigen-binding fragment of the present invention. The label itself may be detectable (e.g., radioisotope labeling or fluorescent labeling), or, in the case of enzyme labeling, catalyze a detectable chemical change in the substrate compound or composition. The labeled anti-CTGF antibody or antigen-binding fragment can be prepared and used in a variety of applications, including in vitro and in vivo diagnostics.

[0107] In various aspects of this invention, one or more domains of an anti-CTGF antibody or its antigen-binding fragment are expressed in a recombinant manner. Such recombinant expression may employ one or more control sequences, i.e., polynucleotide sequences necessary for the expression of an operatively linked coding sequence in a particular host organism. Control sequences suitable for prokaryotic cells include, for example, promoter, operator, and ribosome-binding site sequences. Eukaryotic control sequences include (but are not limited to) promoters, polyadenylation signals, and enhancers. These control sequences can be used to express and generate anti-CTGF antibodies or their antigen-binding fragments in prokaryotic and eukaryotic host cells.

[0108] A nucleic acid sequence is "operably linked" when it is in a functional relationship with another nucleic acid sequence. For example, if a pre-nucleic acid sequence or secretory leader sequence is expressed as a protein involved in the secretion of a polypeptide, it is operably linked to the nucleic acid encoding that polypeptide; if a promoter or enhancer affects the transcription of a coding sequence, it is operably linked to that sequence; or if a ribosome binding site is positioned to facilitate translation, it is operably linked to the coding sequence. Generally, "operably linked" means that the linked DNA sequences are adjacent, and in the case of a secretory leader sequence, adjacent and within the reading frame. However, enhancers are optionally adjacent. Linkage can be achieved by joining at a suitable restriction site. If such a site is not present, synthetic oligonucleotide adaptors or linkers can be used.

[0109] As used herein, the terms “cell,” “cell line,” and “cell culture” are used interchangeably and all such designations include their descendants. Thus, “transformant” and “transformed cell” include primary target cells and cultures derived therefrom, regardless of the number of transformations, which may be transfected, for example, with one or more expression vectors encoding one or more amino acid sequences of the antibody or its antigen-binding fragment of the present invention.

[0110] For the therapeutic purposes according to the invention, the term "mammal" means any animal classified as a mammal, including humans, domestic and agricultural animals, and zoo, sporting, or companion animals, such as dogs, horses, cats, cows, and similar animals. Preferably, the mammal is a human.

[0111] As used herein, “symptom” means any condition that benefits from treatment with the anti-CTGF antibody or its antigen-binding fragment described herein. This symptom includes chronic and acute conditions or diseases, including those pathological conditions that make mammals susceptible to the conditions discussed. Non-limiting examples or conditions to be treated herein include CTGF-related conditions.

[0112] As used herein, the term "CTGF-related condition" or "CTGF-related disease" refers to a condition that can be alleviated by inhibiting CTGF cleavage and / or by inhibiting CTGF signaling, such as CTGF-NTF signaling. The term "CTGF-related condition" or "CTGF-related disease" includes inflammatory diseases, respiratory diseases, or fibrotic conditions. CTGF-related conditions include progressive pulmonary fibrosis, idiopathic pulmonary fibrosis, arthritis, atherosclerosis, cardiac fibrosis, connective tissue fibrosis, Duchenne muscular dystrophy, diabetic nephropathy, diabetic retinopathy, diffuse scleroderma, endothelial fibrosis, epithelial fibrosis, fibrotic diseases, glaucoma, joint fibrosis, renal fibrosis, localized scleroderma, liver fibrosis, macular degeneration, ocular fibrosis, osteoarthritis, proliferative vitreoretinopathy, pulmonary fibrosis, and systemic fibrosis. CTGF-related conditions include the following cancers: acute lymphoblastic leukemia, dermatofibroma, breast cancer, breast cancer, glioma and glioblastoma, rhabdomyosarcoma and fibrosarcoma, connective tissue hyperplasia, angiolipoma, angioleiomyoma, connective tissue proliferative cancers and prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastrointestinal cancer and liver cancer, as well as other tumor growth and metastasis.

[0113] In the case of conjugates (e.g., antibodies or antigen-binding fragments thereof), the term "specifically binds" or "specific binding" refers to a conjugate that binds more frequently, more rapidly, for a longer duration, with greater affinity, or a combination thereof to an antigen or an epitope within an antigen other than an unrelated antigen. In some embodiments, the antibody or antigen-binding fragment thereof is used at about 0.1 mM or less, preferably less than about 1 μM K. D Specific binding to an antigen or an epitope within an antigen. Due to sequence similarity between homologous proteins in different species or variants of proteins within a single species, specific binding may include antibodies or antigen-binding fragments thereof that recognize proteins in more than one species. It should be understood that in some embodiments, antibodies or antigen-binding fragments thereof that specifically bind to a first protein may or may not specifically bind to a second protein. Therefore, “specific binding” does not necessarily require (although it may include) exclusive binding, i.e., binding to a single protein. Thus, in some embodiments, antibodies or antigen-binding fragments thereof may specifically bind to more than one protein.

[0114] Methods for determining whether two molecules specifically bind to a protein are described herein or are well known in the art, and include, for example, equilibrium dialysis, surface plasmon resonance, and the like. In one embodiment, according to the affinity binding method described in the Examples section of this document, specific binding is characterized by K D Approximately 1 × 10 -7 M (100 nM) or lower. In one embodiment, according to the affinity binding method described in the Examples section of this document, the specific binding is characterized by K D Approximately 5 × 10 -8 M (50 nM) or lower. In one embodiment, according to the affinity binding method described in the Examples section of this document, the specific binding is characterized by K D Approximately 1 × 10 -8 M (10 nM) or lower. In one embodiment, according to the affinity binding method described in the Examples section of this document, the specific binding is characterized by K D Approximately 5 × 10 -9 M (5 nM) or lower.

[0115] The term "subcutaneous administration" refers to the introduction of a drug, such as the anti-CTGF antibody of the present invention or its antigen-binding fragment, under the skin of a subject (such as an animal or human patient). Subcutaneous administration can be performed within a cavity between the skin and subcutaneous tissue. Subcutaneous administration can be performed by relatively slow, continuous delivery from a drug container. Pinching or pulling the skin away from the subcutaneous tissue can create a cavity.

[0116] The term "subcutaneous infusion" refers to the introduction of a drug (e.g., the anti-CTGF antibody or its antigen-binding fragment of the present invention) under the skin of a subject, preferably within a cavity between the skin and underlying tissue, by relatively slow, continuous delivery from a drug container for a period of time (including, but not limited to, 30 minutes or less, or 90 minutes or less). Optionally, the infusion can be performed by implanting a drug delivery pump under the skin of the subject via subcutaneous implantation, wherein the pump aspirates and delivers a predetermined amount of drug for a predetermined period of time, such as 30 minutes, 90 minutes, or a period spanning the length of a treatment regimen.

[0117] The term "subcutaneous injection" refers to the administration of a drug under the skin of a subject, wherein the drug delivery is performed in less than about 15 minutes; in some aspects, less than 5 minutes, and in some aspects, less than 60 seconds. In some aspects, the administration is performed in a depression between the skin and subcutaneous tissue, wherein the depression can be created by pinching or pulling the skin away from the subcutaneous tissue. For example, "subcutaneous injection" means administering the anti-CTGF antibody or its antigen-binding fragment of the present invention to a subject in less than about 15 minutes; in some aspects, less than 5 minutes, and in some aspects, less than 60 seconds.

[0118] The term "therapeuticly effective dose" refers to the amount of anti-CTGF antibody or its antigen-binding fragment that relieves or improves one or more symptoms of the condition being treated. Therefore, it is a dose that has beneficial outcomes for the patient. Efficacy can be measured in conventional ways, depending on the condition being treated.

[0119] As used herein, the terms “treatment” and “therapeutic approach” and similar terms mean measures to treat, prevent, or suppress a disease or condition, thereby producing any clinically desired or beneficial effect, including (but not limited to) relieving or reducing one or more symptoms, resolving, slowing, or stopping the progression of the disease or condition. Thus, by way of example, the term treatment includes administering an anti-CTGF antibody or its antigen-binding fragment before or after the onset of symptoms of a disease or condition, thereby preventing or removing one or more signs of the disease or condition. As an example, the term includes administering an anti-CTGF antibody or its antigen-binding fragment after the clinical manifestation of a disease to combat the symptoms of the disease. Furthermore, administering an anti-CTGF antibody or its antigen-binding fragment after the onset of symptoms and after the appearance of clinical symptoms includes “treatment” or “therapeutic approach” as used herein, wherein the administration affects clinical parameters of the disease or condition, such as the degree of tissue damage or the amount or extent of cancer metastasis, regardless of whether the treatment results in disease improvement. Furthermore, any treatment of the underlying condition shall be deemed effective if the composition of the present invention, alone or in combination with another therapeutic agent, alleviates or improves at least one symptom of the treated condition compared to the symptoms without the use of anti-CTGF antibodies or their antigen-binding fragment compositions or their antigen-binding fragments, regardless of whether all symptoms of the condition are alleviated.

[0120] "Prevention" refers to preventive or therapeutic measures to prevent and / or slow the development of a targeted pathological symptom or condition. Therefore, those requiring prevention include those predisposed to or susceptible to the disease. In some embodiments, the methods provided herein successfully prevent the disease or condition (preferably CTGF-related conditions) if a patient experiences, transiently or permanently, symptoms associated with the disease or condition (e.g., fewer or less severe symptoms) compared to a patient who has not yet experienced the methods of the present invention.

[0121] The “effective amount” of a drug (such as a pharmaceutical composition) refers to the amount that is effective in dosage and for the desired period of time to achieve the desired therapeutic or preventive result.

[0122] Throughout this specification and the appended claims, unless otherwise specified herein, the term "comprise" and its variations (such as "comprises" and "comprising") shall be understood to imply inclusion of the stated members, wholes, or steps but not to exclude any other unstated members, wholes, or steps. The term "composes of" is a specific embodiment of the term "comprise," wherein any other unstated members, wholes, or steps are excluded. In the context of this invention, the term "comprise" encompasses the term "composes of." Thus, the term "comprise" encompasses both "comprising" and "composes of," for example, a composition "comprising" X may consist of only X, or may include something additional, such as X+Y. For instance, unless the context otherwise requires, an antibody chain disclosed as "comprising" a specified amino acid sequence encompasses an antibody chain "composed of that amino acid sequence." Optionally, the antibody chain may be glycosylated at one or more sites and / or may have one or more post-translational modifications.

[0123] The term “about” for the numerical value x means x plus or minus (±) 10%, for example x±1%, or x±2%, or x±3%, or x±4%, or x±5%, or x±6%, or x±7%, or x±8%, or x±9%, or x±10%.

[0124] Antibody preparation

[0125] In other aspects, the present invention provides a method for generating the anti-CTGF antibody of the present invention and its antigen-binding fragment, comprising culturing recombinant host cells expressing heavy and light chains and isolating the antibody or its antigen-binding fragment produced by the cells.

[0126] Preferably, the method for generating an antibody or an antigen-binding fragment thereof comprises (a) culturing host cells and (b) isolating the antibody or antigen-binding fragment thereof expressed from the cells. Alternatively, the method may include a step (c) of purifying the antibody or antigen-binding fragment thereof.

[0127] The antibodies of this invention can be produced by transfecting host cells with one or more vectors containing polynucleotides encoding respective antibodies or fragments, culturing the host cells (especially under conditions that allow for the synthesis of the antibody molecule), and recovering the antibody molecule from the culture. It should be understood that the heavy and light chains of the antibody can be encoded by individual polynucleotides. Therefore, this document also provides (by individual polynucleotides) multiple polynucleotides encoding the heavy and light chains of antibodies or their antigen-binding fragments as described herein. Such multiple polynucleotides can be contained in a (single) vector or multiple vectors.

[0128] Antibodies or antigen-binding fragments thereof (e.g., as monoclonal antibodies) can be prepared using recombinant DNA methods as described in U.S. Patent No. 4,816,567, which is incorporated herein by reference.

[0129] Isolated polynucleotides encoding the heavy and light chains can be transfected into host cells (such as E. coli cells that do not produce additional immunoglobulins, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells) to produce monoclonal antibodies. For example, isolated polynucleotides encoding the heavy and light chains can be stably transfected into suitable host cells (e.g., CHO cells) for antibody production.

[0130] Various techniques for generating antibody fragments are known. Conventionally, these fragments are derived via proteolytic digestion of intact antibodies, as described, for example, by Morimoto et al., J. Biochem. Biophys. Meth. 24:107-117 (1993) and Brennan et al., Science 229:81 (1985). In some embodiments, anti-CTGF antibody fragments are generated recombinantly. Fab, Fv, and scFv antibody fragments can all be expressed and secreted from E. coli or other host cells, thus allowing for the generation of large quantities of these fragments. Other techniques for generating antibody fragments will be apparent to those skilled in the art. For example, antibody fragments can be generated by techniques known in the art, including (but not limited to): F(ab')2 fragments generated by pepsin digestion of antibody molecules; Fab fragments generated by reducing disulfide bridges in F(ab')2 fragments; and Fab fragments generated by treating antibody molecules with papain and a reducing agent. According to the invention, the technique can be adapted to generate single-chain antibodies specific to CTGF (see, for example, U.S. Patent No. 4,946,778).

[0131] Exemplary anti-CTGF antibody of the present invention

[0132] The anti-CTGF antibodies described and disclosed herein, particularly human anti-CTGF antibodies, and compositions and articles comprising the anti-CTGF antibodies of the present invention are also described. Antigen-binding fragments of the anti-CTGF antibodies are also described. Anti-CTGF antibodies and their antigen-binding fragments can be used to treat a variety of diseases or conditions, particularly CTGF-related conditions. Each anti-CTGF antibody and its antigen-binding fragment includes at least a portion that specifically binds to CTGF, or a fragment thereof (e.g., CTGF-NTF, preferably human CTGF or human CTGF-NTF).

[0133] The generation and characterization of anti-CTGF antibodies are described in the examples. Representative anti-CTGF antibodies of the present invention have CDRs disclosed in Tables 1 to 8 below. Heavy chain CDRs-1, CDR-2, and CDR3 (H-CDR1-3) and light chain CDRs-1, CDR-2, and CDR3 (L-CDR1-3) are provided according to the Kabat, Aho, CCG, and Chothia numbering system.

[0134] Table 1. According to Kabat's light chain CDR

[0135] Table 2. Heavy chain CDRs based on Kabat

[0136] Table 3. CDR of light chain according to Aho

[0137] Table 4. Heavy chain CDRs based on Aho

[0138] Table 5. Light chain CDRs according to CCG

[0139] Table 6. Heavy chain CDRs based on CCG

[0140] Table 7. According to Chothia's light chain CDR

[0141] Table 8. Heavy chain CDRs according to Chothia

[0142] amino acid sequence variants

[0143] Variant anti-CTGF antibodies and their fragments can be engineered based on a set of CDRs depicted in Tables 1 through 8. It should be understood that in variant anti-CTGF antibodies and fragments, the amino acid sequence of the CDR remains unchanged or has minimal changes (e.g., 1–5 changes), but surrounding regions (e.g., FR regions) can be engineered. Amino acid sequence variants of anti-CTGF antibodies can be prepared by introducing appropriate nucleotide changes into the anti-CTGF antibody DNA or through peptide synthesis. Such variants include, for example, deletions and / or insertions and / or substitutions of residues within the amino acid sequence of the anti-CTGF antibody as exemplified herein. Any combination of deletions, insertions, and substitutions can be performed to obtain the final construct, subject to the constraint that the final construct possesses the desired characteristics. Amino acid changes can also alter the post-translational processes of humanized or variant anti-CTGF antibodies, such as changing the number or location of glycosylation sites.

[0144] In some embodiments, the present invention includes an anti-CTGF antibody or an antibody fragment thereof having a variable heavy chain (also referred to as a "heavy chain variable region") and a variable light chain (also referred to as a "light chain variable region"), wherein the amino acid sequences of the variable heavy chain and the variable light chain are at least 90%, preferably at least 92.5%, more preferably at least 95%, even more preferably at least 98%, or even more preferably at least 99% of the amino acid sequences disclosed in Tables 9 to 10, subject to the limitation that the antibody or the fragment thereof remains bound to CTGF.

[0145] Table 9. Light chain variable region sequence of anti-CTGF antibody

[0146] Table 10. Variable region sequence of anti-CTGF antibody heavy chain

[0147] Table 11. Light chain sequence of anti-CTGF antibody

[0148] Table 12. Heavy chain sequence of anti-CTGF antibody

[0149] The combinations of light chain variable regions and heavy chain variable regions shown in Tables 9 and 10, or the light chain and heavy chain shown in Tables 11 and 12, produce certain antibodies of the present invention shown in Table 13.

[0150] Table 13. SEQ ID NO of exemplary antibodies according to the present invention.

[0151] In some embodiments, the present invention includes an anti-CTGF antibody or antibody fragment thereof having a variable heavy chain and a variable light chain, wherein the amino acid sequence of the variable heavy chain is at least 80% or at least 85%, preferably at least 90%, more preferably at least 92.5%, even more preferably at least 95%, even more preferably at least 98%, or most preferably at least 99% of the amino acid sequence of SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 178, and the amino acid sequence of the variable light chain is at least 80% or at least 85%, preferably at least 90%, more preferably at least 92.5%, even more preferably at least 95%, even more preferably at least 98%, or most preferably at least 99% of the amino acid sequence of SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, or 253, preferably at least 90%, more preferably at least 92.5%, even more preferably at least 95%, even more preferably at least 98%, or most preferably at least 99%.

[0152] In some embodiments, the present invention includes an anti-CTGF antibody having a heavy chain and a light chain, wherein the heavy chain amino acid sequence and the light chain amino acid sequence are at least 95%, preferably at least 98%, or more preferably at least 99% identical to the amino acid sequences disclosed in Tables 11 and 12, subject to the limitation that the antibody or a fragment thereof remains bound to CTGF.

[0153] In some embodiments, the anti-CTGF antibody or antibody fragment thereof comprises a variable heavy chain sequence comprising an amino acid sequence having at least about 95%, preferably about 96%, more preferably about 97%, even more preferably about 98%, or even more preferably about 99% sequence identity with the amino acid sequence set forth in SEQ ID NO: 100, 101, 102, 103, 110, 111, 112, 113, 114, 115, 116, 117, 104, 118, 119, 120, 121, 122, 123, 124, or 221. Preferably, the anti-CTGF antibody or antibody fragment thereof retains the binding and / or functional activity of the anti-CTGF antibody or antibody fragment thereof comprising the variable heavy chain sequence of SEQ ID NO: 100, 101, 102, 103, 110, 111, 112, 113, 114, 115, 116, 117, 104, 118, 119, 120, 121, 122, 123, 124 or 221. In some embodiments, the anti-CTGF antibody or antibody fragment thereof comprises the variable heavy chain sequence of SEQ ID NO: 108, 118, 128, 138, 148, 158, 168 or 178, and has one or more conserved amino acid substitutions in the variable heavy chain sequence, such as 1, 2, 3, 4, 5, 1-2, 1-3, 1-4 or 1-5 conserved amino acid substitutions. In some embodiments, one or more conserved amino acid substitutions fall within one or more framework regions of SEQ ID NO: 108, 118, 128, 138, 148, 158, 168 or 178 (based on the Kabat numbering system).

[0154] In some embodiments, the anti-CTGF antibody or antibody fragment thereof comprises a variable heavy chain sequence having at least about 95%, preferably about 96%, more preferably about 97%, further preferably about 98%, or even more preferably about 99% sequence identity with the anti-CTGF heavy chain variable region sequence described in SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 178, comprising one or more conserved amino acid substitutions (based on the Kabat numbering system) in the frame region, and retaining the binding and / or functional activity of the anti-CTGF antibody or antibody fragment thereof. The antibody or antibody fragment comprises the variable heavy chain sequence described in SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 178 and the variable heavy chain sequence described in SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 178, ... 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243 or 253 are variable light chain sequences as described herein.

[0155] In some embodiments, the anti-CTGF antibody or antibody fragment thereof comprises a variable light chain sequence having at least about 95%, preferably about 96%, more preferably about 97%, even more preferably about 98%, or even more preferably about 99% sequence identity with the amino acid sequence shown in SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, or 253. Preferably, the anti-CTGF antibody or antibody fragment thereof retains the binding and / or functional activity of the anti-CTGF antibody or antibody fragment thereof comprising the variable light chain sequence of SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, or 253. In some embodiments, the anti-CTGF antibody or antibody fragment thereof comprises a variable light chain sequence of SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, or 253, and has one or more conserved amino acid substitutions in the variable light chain sequence, such as 1, 2, 3, 4, 5, 1-2, 1-3, 1-4, or 1-5 conserved amino acid substitutions. In some embodiments, the one or more conserved amino acid substitutions fall within one or more frame regions of SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, or 253 (based on the Kabat numbering system).

[0156] In some embodiments, the anti-CTGF antibody or antibody fragment thereof comprises a variable light chain sequence having at least about 95%, preferably about 96%, more preferably about 97%, even more preferably about 98%, or even more preferably about 99% sequence identity with the anti-CTGF light chain variable region sequence shown in SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, or 253, comprising one or more conserved amino acid substitutions (based on the Kabat numbering system) in the frame region, and retaining the binding and / or functional activity of the anti-CTGF antibody or antibody fragment thereof. The antibody or antibody fragment thereof comprises a variable heavy chain sequence as described in SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 178, and a variable heavy chain sequence as described in SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 178, and a variable heavy chain sequence as described in SEQ ID NO: 108, 118, 128, 138, 148, 158, 168, or 253 ... 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243 or 253 are variable light chain sequences as shown.

[0157] In some embodiments, the present invention includes anti-CTGF antibodies or antigen-binding fragments thereof having amino acid substitutions. These variants remove at least one amino acid residue from the anti-CTGF antibody or antigen-binding fragment thereof and insert a different residue at its position. Substitution mutation inducing sites of greatest concern include highly variable regions, but FR variations are also considered. Conserved substitutions are shown under the heading “Preferred Substitutions” in Table 14. If such substitutions cause changes in biological activity, further substantial changes, designated as “Exemplary Substitutions” or as further described below with respect to amino acid categories, may be introduced, and products screened.

[0158] Table 14. Exemplary amino acid substitutions

[0159] Based on common side chain characteristics, naturally occurring amino acid residues are divided into the following groups:

[0160] (1) Hydrophobicity: ortholeucine, met, ala, val, leu, ile;

[0161] (2) Neutral hydrophilicity: cys, ser, thr;

[0162] (3) Acidic: asp, glu;

[0163] (4) Alkaline: asn, gin, his, lys, arg;

[0164] (5) Residues that affect chain orientation: gly, pro; and

[0165] (6) Fang ethnic group: trp, tyr, phe.

[0166] Conservative substitution necessarily involves the exchange of a member from one of these categories with a member from another category. Non-conservative substitution necessarily involves the exchange of a member from one of these categories with a member from another category.

[0167] Any cysteine ​​residues that do not participate in maintaining the proper conformation of the anti-CTGF antibody or its antigen-binding fragment may generally be substituted with serine to improve the oxidative stability of the molecule, prevent undesirable cross-linking, or provide established binding sites for cytotoxic or cell growth-inhibiting compounds. Conversely, one or more cysteine ​​bonds may be added to the antibody or its antigen-binding fragment to improve its stability (especially when the antibody is an antibody fragment such as an Fv fragment).

[0168] Another type of antibody variant involves altering the antibody's original glycosylation pattern. In this context, the term "alter" means the deletion of one or more carbohydrate moieties found in the antibody and / or the addition of one or more glycosylation sites not previously present in the antibody. For example, an antibody may contain an amino acid substitution at position 297 of the human IgG1 heavy chain to eliminate oligosaccharide transferase complex-mediated glycosylation by replacing asparagine 297 (e.g., N297A, N297G).

[0169] In some aspects, the present invention includes nucleic acid molecules encoding amino acid sequence variants of the anti-CTGF antibody or its antigen-binding fragment as described herein. Nucleic acid molecules encoding amino acid sequence variants of the anti-CTGF antibody or its antigen-binding fragment are prepared by a variety of methods known in the art. These methods include (but are not limited to) isolation from natural sources (in the case of naturally occurring amino acid sequence variants) or preparation by inducing previously prepared variant or non-variant forms of the anti-CTGF antibody or its antigen-binding fragment by oligonucleotide-mediated (or site-directed) mutagenesis, PCR mutagenesis, and cassette mutagenesis. For example, nucleic acid molecules according to the invention also encompass nucleic acid molecules that hybridize under stringent conditions to nucleic acid molecules as disclosed herein, wherein the term "stringent conditions" within the scope of the invention may include, for example, hybridization at 42°C in a buffer containing 50% formamide, 5×SSC, and 1% SDS, or hybridization at 65°C in a buffer containing 5×SSC and 1% SDS, both followed by washing at 65°C with 0.2×SSC and 0.1% SDS. Exemplary stringent hybridization conditions may also include hybridization at 37°C in a buffer of 40% formamide, 1 M NaCl and 1% SDS, followed by washing at 45°C in 1×SSC.

[0170] In some embodiments, the anti-CTGF antibody is an antibody fragment. Techniques for generating antibody fragments have been developed. Fragments can be derived via proteolytic digestion of the intact antibody (see, for example, Morimoto et al., 1992, Journal of Biochemical and Biophysical Methods 24:107-117; and Brennan et al., 1985, Science 229:81). Alternatively, fragments can be generated directly in recombinant host cells. For example, the Fab'-SH fragment can be directly recovered from *E. coli* and chemically coupled to form the F(ab')2 fragment (see, for example, Carter et al., 1992, Bio / Technology 10:163-167). Alternatively, the F(ab')2 fragment can be isolated directly from recombinant host cell cultures. Other techniques for generating antibody fragments will be readily apparent to those skilled in the art.

[0171] In some respects, anti-CTGF antibodies and their antigen-binding fragments may include modifications such as glycosylation, oxidation, or deamidation.

[0172] In some embodiments, it may be necessary to use an anti-CTGF antibody fragment instead of the complete antibody. The antibody fragment may need to be modified to increase its serum half-life. This can be achieved, for example, by incorporating a rescue receptor-binding epitope into the antibody fragment. In one approach, a suitable region of the antibody fragment may be altered (e.g., mutated), or the epitope may be incorporated into a peptide tag, subsequently fused to the antibody fragment at either end or in the middle, for example, via DNA or peptide synthesis (see, for example, WO 96 / 32478). For instance, if the full-length IgG architecture is undesirable, the antibody fragment of the present invention may also be fused to human serum albumin to increase the serum half-life. Such fusion proteins of antibody fragments and human serum albumin may be advantageous in cases where it is necessary to fuse two different antibody fragments to increase affinity or to produce a bispecific binding protein with an extended serum half-life (see, for example, WO 05 / 077042 A2).

[0173] The removal of any carbohydrate moieties present on antibodies can be achieved chemically or enzymatically. Chemical deglycosylation is described in Hakimuddin et al., 1987, Arch. Biochem. Biophys. 259:52 and Edge et al., 1981, Anal. Biochem., 118:131. Enzymatic cleavage of carbohydrate moieties on antibodies can be achieved using various endoglycosidases and exoglycosidases, as described by Thotakura et al., 1987, Meth. Enzymol 138:350.

[0174] One type of applicable modification involves linking the antibody to one of a variety of non-protein polymers, such as polyethylene glycol, polypropylene glycol, or polyoxyethylene, in a manner as described in one or more of U.S. Patent Nos. 4,640,835, 4,496,689, 4,301,144, 4,670,417, 4,791,192, and 4,179,337.

[0175] The present invention also provides an anti-CTGF antibody or an antigen-binding fragment thereof that competes with the anti-CTGF antibody according to the present invention for binding to CTGF. In one embodiment, the present invention provides an anti-CTGF antibody or an antigen-binding fragment thereof that competes with antibodies A1-A128 for binding to CTGF. The competition analysis may be performed, for example, using a biosensor as described in PLoS One. 2014; 9(3): e92451, or PLoS One March 5, 2020; 15(3): e0229206, or by the methods disclosed herein.

[0176] Therapeutic uses

[0177] In one embodiment, the anti-CTGF antibody or its antigen-binding fragment of the present invention is suitable for treating and / or preventing CTGF-related conditions. In some embodiments, the anti-CTGF antibody or its antigen-binding fragment of the present invention is suitable as a medicine.

[0178] This invention provides antibodies for the treatment of various diseases and conditions associated with CTGF. The antibodies of this invention reduce the harmful effects of CTGF production or activity in several diseases. Furthermore, the antibodies exhibit favorable pharmacokinetics and / or pharmacodynamics, making them excellent therapeutic agents for treating CTGF-related conditions.

[0179] The anti-CTGF antibody of this invention inhibits the development of fibrosis. This invention is intended to treat patients with CTGF-related conditions using anti-CTGF antibodies to improve or stabilize lesions, restore organ function, improve quality of life, and prolong survival.

[0180] The antibodies of this invention are suitable for therapeutic applications to prevent or treat CTGF-related conditions involving fibrosis. In some aspects, administering the antibodies of this invention to a subject to prevent or treat CTGF-related conditions, including (but not limited to) conditions exhibiting altered expression and deposition of extracellular matrix-related proteins, such as fibrosis. In various aspects, fibrosis can be localized to specific tissues, such as epithelium, endothelium, or connective tissue; or organs, such as the kidneys, lungs, or liver. Fibrosis can also occur in the eyes and joints. In other aspects, fibrosis can be systemic and involve multiple organ and tissue systems. CTGF-related conditions include, for example, atherosclerosis, arthritis, retinopathy (such as diabetic retinopathy); nephropathy (such as diabetic nephropathy); Duchenne muscular dystrophy, myocardial fibrosis, pulmonary fibrosis, liver fibrosis, and renal fibrosis; and diseases associated with chronic inflammation and / or infection.

[0181] Furthermore, the antibodies of this invention are suitable for therapeutic applications to prevent or treat CTGF-related conditions in subjects. Such conditions include (but are not limited to) conditions characterized by angiogenesis and other processes that play a central role in the disease and cancer, such as atherosclerosis, glaucoma, etc.; these cancers include acute lymphoblastic leukemia, dermatofibroma, breast cancer, breast cancer, glioma and glioblastoma, rhabdomyosarcoma and fibrosarcoma, connective tissue hyperplasia, angiolipoma, angioleiomyoma, connective tissue proliferative cancers and prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastrointestinal cancer and liver cancer, and other tumor growth and metastasis.

[0182] In some aspects, the present invention provides antibodies for reducing the incidence of or preventing CTGF-related diseases in subjects with a predisposition to develop such diseases. Predisposition may include, for example, hyperglycemia, hypertension, or obesity in the subject. Such diseases may occur, for example, due to diabetes, obesity, etc., and include diabetic nephropathy, retinopathy, and cardiovascular disease. Additionally, a suspected predisposition may be due to events in the subject, such as myocardial infarction, surgery, peritoneal dialysis, chronic and acute transplant rejection, chemotherapy, radiation therapy, trauma, orthopedic surgery or paralytic immobilization, congestive heart failure, pregnancy, or varicose veins.

[0183] In certain embodiments, as exemplified herein, the antibodies of the present invention are administered to a subject to treat fibrosis of organs, such as the lungs or kidneys. In other embodiments, the antibodies are administered to a subject to treat or prevent eye conditions, such as proliferative vitreoretinopathy, diabetic retinopathy, or macular degeneration. Because CTGF involves a wide range of conditions, the present invention is intended to treat patients with CTGF-related conditions using the antibodies of the present invention to improve or stabilize disease and organ function, improve quality of life, and prolong survival.

[0184] For therapeutic applications, the antibodies of the present invention are administered to mammals, preferably humans, in pharmaceutically acceptable dosage forms. The antibodies can be administered intravenously. The antibodies can be administered intravenously as a bolus injection or by continuous infusion over a period of time. The antibodies can be administered via intramuscular, subcutaneous, intra-articular, intrasynovial, intrathecal, intravitreal, intracranial, oral, local, or inhalation routes. Subcutaneous administration is possible. When the antibodies have suitable activity, they can also exert local and systemic therapeutic effects through intratumoral, peritumoral, intralesional, or perilesional administration routes.

[0185] These dosage forms encompass pharmaceutically acceptable, non-toxic, and non-therapeutic carriers. When present in aqueous formulations rather than lyophilized, antibodies are typically formulated at concentrations ranging from approximately 0.1 mg / ml to 100 mg / ml, but wide variations outside these ranges are permissible.

[0186] For the prevention or treatment of disease, the appropriate dosage of the antibody will depend on the type of disease to be treated, the severity and duration of the disease, whether the antibody is administered for preventative or therapeutic purposes, the course of prior therapy, the patient's clinical history and response to the antibody, and the judgment of the attending physician. The antibody may be administered to the patient in a single dose or as part of a series of treatments.

[0187] Depending on the type and severity of the disease, an initial candidate dose of antibody of approximately 0.015 to 25 mg per kg of patient body weight may be administered to the patient, whether by single or multiple separate administrations or by continuous infusion. For repeated administration over several days or longer, treatment may be repeated until the desired suppression of disease symptoms is achieved, depending on the condition. However, other dosage regimens may be applicable and are not excluded from this invention.

[0188] According to some embodiments of the invention, the effectiveness of an antibody in preventing or treating a disease can be improved by administering the antibody sequentially or in combination with another agent effective for the same clinical target, such as another antibody targeting an epitope different from the primary antibody, or one or more conventional therapeutic agents known for the intended therapeutic indication, such as prevention or treatment of symptoms associated with excessive extracellular matrix production (e.g., fibrosis or sclerosis), inhibition of tumor cell growth or cancer metastasis, inhibition of angiogenesis, or reduction of inflammation. Such agents can improve symptoms or outcomes via similar mechanisms of action (e.g., anti-TGFβ antibodies) or through different mechanisms (e.g., interferon-γ). Such agents can also improve symptoms directly or indirectly related to CTGF-related conditions or a predisposition to developing CTGF-related conditions, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (Arb).

[0189] Non-therapeutic use

[0190] The antibodies described herein are suitable as affinity purification agents. In this process, the antibody is immobilized on a solid phase, such as a protein A resin, using methods well known in the art. The immobilized antibody is contacted with a sample containing the CTGF protein (or a fragment thereof, such as CTGF-NTF) to be purified, and the support is subsequently washed with a suitable solvent that will remove substantially all matter from the sample except for the CTGF protein bound to the immobilized antibody. Finally, the support is washed with another suitable solvent that releases the CTGF protein from the antibody.

[0191] The CTGF antibodies and fragments of the present invention disclosed herein are also suitable for diagnostic analysis to detect and / or quantify CTGF proteins, such as detecting CTGF expression in specific cells, tissues or serum.

[0192] In some embodiments, it is advantageous to use detectable labeled antibodies, for example, for diagnostic purposes. Many detectable labels are available, including radioisotopes, fluorescent labels, enzyme substrate labels, quantum dots, and the like. Labels can be indirectly bound to antibodies using various known techniques. For example, antibodies can bind to biotin, and any of the three classes of labels mentioned above can bind to avidin, or vice versa. Biotin selectively binds to avidin, and therefore the label can bind to the antibody indirectly in this way. Alternatively, to achieve indirect binding between the label and the antibody, the antibody can bind to a small hapten (such as digoxin), and one of the different types of labels mentioned above can bind to an anti-hapten antibody (e.g., an anti-digoxin antibody). Thus, indirect binding between the label and the antibody can be achieved.

[0193] Diagnostic kits

[0194] Anti-CTGF antibodies or fragments thereof can be used in diagnostic kits, i.e., packaged combinations of pre-quantitative reagents with instructions for performing diagnostic analyses, such as, for example, the analysis of full-length CTGF and CTGF-NTF in plasma. Therefore, this document also provides the use of antibodies or antigen-binding fragments thereof as described herein for the diagnosis of CTGF-related conditions. If the antibody is enzyme-labeled, the kit may include the substrate and cofactors required for the enzyme, such as substrate precursors providing detectable chromophores or fluorophores. Additionally, other additives may be included, such as stabilizers, buffers (e.g., blocking buffers or lysis buffers), and the like. The relative amounts of various reagents can vary widely to provide concentrations in the reagent solution that substantially optimize analytical sensitivity. Reagents may be provided in dry powder (typically lyophilized) form, including excipients that provide a reagent solution with an appropriate concentration upon dissolution.

[0195] Compositions, combinations and their application

[0196] Compositions comprising an anti-CTGF antibody or an antigen-binding fragment thereof according to the present invention may be administered to subjects suffering from or at risk of CTGF-related diseases and / or conditions as described herein. The present invention provides the use of an anti-CTGF antibody or an antigen-binding fragment thereof for the manufacture of medicaments for the prevention or treatment of CTGF-related diseases or conditions. As used herein, the term “subject” means any mammalian patient to whom an anti-CTGF antibody or an antigen-binding fragment thereof may be administered, including, for example, humans and certain non-human mammals such as domesticated animals (e.g., cattle, sheep, pigs, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). Subjects specifically intended to be treated using the methods described herein include humans.

[0197] Anti-CTGF antibodies or their antigen-binding fragments may be administered alone or in combination with one or more additional therapeutic agents, such as this technology or standard care compounds, such as antifibrotic agents, steroids, immunomodulators, checkpoint inhibitors, cell proliferation inhibitors, anti-angiogenic substances, cell growth inhibitors or cytotoxic substances and their analogues.

[0198] In some aspects, the present invention also provides pharmaceutical compositions that are administered as pharmaceutical compositions comprising a therapeutically effective amount of an anti-CTGF antibody or an antigen-binding fragment thereof and optionally one or more additional therapeutic agents.

[0199] Some aspects of the present invention provide a binding molecule for treating CTGF-related diseases, wherein the therapy comprises one or more pharmacologically active substances.

[0200] Some aspects of the present invention provide the use of one or more active ingredients in the manufacture of a medicament for treating CTGF-related diseases, wherein the medicament comprises the binding molecule of the present invention.

[0201] In some aspects of the invention, anti-CTGF antibodies or their antigen-binding fragments may optionally be administered in combination with additional therapeutic agents. These additional therapeutic agents may be phosphodiesterase 4 inhibitors, tyrosine kinase inhibitors, lysophosphatidic acid receptor 1 (LPA1) antagonists, Src and Abl kinase inhibitors, prostacyclin vasodilators, angiotensin II type 2 receptor agonists (ATRAG), c-Jun N-terminal kinase inhibitors, analgesics, opioids, P2X3 homotrimer receptor antagonists, N-methyl-D-aspartate (NMDA) receptor inhibitors, additional CTGF inhibitors, anxiolytics, proton pump inhibitors, antifibrotics, or any combination thereof. Additional therapeutic agents may include 9MW3811 (Mabwell Shanghai Bioscience Co., Ltd.), ANG-3070 (Angion Biomedica), AP01 (Avalyn Pharma), autoantibody reduction therapy, autologous lung spheroid stem cells (University of North Carolina, Chapel Hill), AZD5055 (AstraZeneca), AZD8965 (AstraZeneca), BBT-877 (Bridge Biotherapeutics), belumosudil (KD025, Kadmon), BG00011 (Biogen, STX-100), BI 1819479 (Boehringer Ingelheim), BI 1839100 (Boehringer Ingelheim), BLD-0409 (Blade Therapeutics), BLD-2660 (Blade), BLU-5937, and BMS-986020 (Bristol Myers). Squibb), BMS-986278 (Bristol-Myers Squibb), BNC 1021 (BONAC / Toray, TRK-250, PK-7010), bosentan, buloxibutid (Vicore Pharma AB, C21), buspirone, C106 (Vicore Pharma AB), CAL101 (Calluna Pharma AS), carlumab (Janssen,CNTO-888), CC-90001 (Celgene), clonazepam, CMR316 (Calibr), codeine, dasatinib, decttrekumab (Novartis, QAX576), desvenlafaxine, deupirfenidone (PureTech, LYT-100), DWN12088 (Daewoong Pharmaceutical Co., Ltd.), Taladegib (Endeavor Biomedicines, ENV-101), epigallocatechin-3-gallium (University of California, San Francisco), fipaxalparant (Horizon Therapeutics, HZN-825), fluoxetine, gabapentin, garadacimab (CSL, CSL312), GB2064 (Galecto, PAT-1251), GB0139 (Galecto), gefapixant, GLPG1690 (Galapagos), GSK3915393 (GlaxoSmithKline), HEC 68498 (HEC Pharm), HEC-866 (HECPharm), HSK44459 (Haisco Pharmaceutical Group Limited), HuL001 (HuniLife Biotechnology), Human Umbilical Cord Mesenchymal Stem Cell Injection (Shanghai Life Science & Technology), ifenprodil, ifetroban (Cumberland Pharmaceuticals), imatinib, indolinone, ISM001-055 (InSilicoMedicine Hong Kong Limited).INS018_055), IW001 (ImmuneWorks), lanalumab (Novartis), lebrikizumab, leramistat (Modern Biosciences), letemovir, lorazepam, LTI-03 (Lung Therapeutics), LTP001 (Novartis), macitentan, minocycline, N-acetylcysteine ​​(NAC), nalbuphine (Trevi Therapeutics), ND-L02-50201 (Nitto Denko), nerandomilast (Boehringer Ingelheim, BI1015550), nintedanib (Boehringer Ingelheim), NIP292 (CR Pharma, The National Institutes of Pharmaceutical Industry). R&D Limited, China), olokizumab (R-Pharm International, LLC), omeprazole, ORIN1001 (Fosun, Orinove), orvepitant, pamrevlumab (FibroGen), pantoprazole, pirfenidone, PLN-74809 (Pliant Therapeutics, bexotegrast), prednisone, pregabalin, PRM-151 (recombinant human pentacyclic protein-2 protein, Genentech, Promedior), PRS-220 (Pieris Australia Pty Ltd), quercetin, rabeprazole, rituximab, RSN0402 (Shenzhen) Resproly Biopharmaceutical LLC), saracatinib, SB17170 (SPARKBiopharma), setanaxib (Genkyotex),GKT137831), setogepram (ProMetic, PBI-4050), SHR-1906 (Hengrui Pharmaceuticals LLC), sildenafil, simtuzumab (Gilead, GS-6624), sirolimus, SM-04646 (Samumed), tanzisertib (Celgene, CC-930), thalidomide, tipelukast (MediciNova, MN-001), treprostinil (United Therapeutics), TRK-250 (Toray, BNC-1021), TTI-101 (Tvardi Therapeutics, valganciclovir, vixarelimab (Genentech), voxelotor (GBT446), zileuton, zinc and nicotinamide riboside (Cedars-Sinai Medical Center), or any combination thereof. Additional treatment agents are preferably nintedanib, nelamilast, pirfenidone, or any combination thereof.

[0202] Various delivery systems are known and can be used to administer anti-CTGF antibodies or their antigen-binding fragments. Methods of administration include, but are not limited to, intravitreal, ophthalmic, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes. Anti-CTGF antibodies or their antigen-binding fragments can be administered, for example, by infusion, bolus, or injection, and can be administered together with other bioactive agents. Administration can be systemic or local. Formulations for such injections can be prepared, for example, in pre-filled syringes. Therefore, in one aspect of the invention, a pre-filled syringe comprising an anti-CTGF antibody or its antigen-binding fragment is provided.

[0203] For therapeutic use, the anti-CTGF antibody of the present invention is formulated into a pharmaceutical composition suitable for administration to animals or humans. Typical formulations of the binding molecule or antibody molecule described herein can be prepared by mixing the binding molecule or antibody molecule with a physiologically acceptable carrier, excipient, or stabilizer in the form of a lyophilized or otherwise dried formulation, an aqueous solution, or an aqueous or non-aqueous suspension. The carrier, excipient, modifier, or stabilizer is non-toxic at the doses and concentrations used.

[0204] In typical embodiments, the pharmaceutical composition is formulated according to standard procedures for intravenous or subcutaneous administration to a subject. Typically, compositions administered by injection are solutions in sterile isotonic aqueous buffer solutions. If necessary, the pharmaceutical composition may also include a solubilizer and a local anesthetic such as lidocaine to reduce pain at the injection site. Generally, the components are provided separately or mixed together in unit dosage forms, such as in the form of dry lyophilized powders or anhydrous concentrates, in hermetically sealed containers (such as ampoules or capsules) indicating the amount of active agent. When administered by infusion, it can be prepared using infusion bottles containing sterile pharmaceutical-grade water or physiological saline. When administered by injection, ampoules of sterile water or physiological saline for injection can be provided so that the components can be mixed prior to administration.

[0205] In addition, the pharmaceutical composition may be provided as a pharmaceutical kit comprising (a) a container containing a lyophilized form of an anti-CTGF antibody or an antigen-binding fragment thereof, and (b) a second container containing a pharmaceutically acceptable diluent for injection (e.g., sterile water). The lyophilized anti-CTGF antibody or its antigen-binding fragment may be reconstituted or diluted using the pharmaceutically acceptable diluent. As required, precautions may be associated with the container in the form prescribed by a government agency regulating the manufacture, use, or sale of pharmaceutical or biological products, reflecting the approval of the manufacturing, use, or sale organization for human application.

[0206] In some embodiments, the antibody of the present invention may be formulated into a dose comprising, for example, a dose from 1 mg / kg to 200 mg / kg, including, for example, 1 mg / kg to 25 mg / kg, 25 mg / kg to 50 mg / kg, 50 mg / kg to 75 mg / kg, 75 mg / kg to 100 mg / kg, 100 mg / kg to 125 mg / kg, 125 mg / kg to 150 mg / kg, 150 mg / kg to 175 mg / kg, or 175 mg / kg to 200 mg / kg. Regarding treatment regimens for combination administration, in a particular embodiment, the anti-CTGF antibody or its antigen-binding fragment is administered simultaneously with a second and / or third therapeutic agent. In some embodiments, the second and / or third therapeutic agent is administered before or after administration of the anti-CTGF antibody or its antigen-binding fragment.

[0207] Polynucleotides, vectors and host cells

[0208] This invention relates to (isolated) polynucleotides comprising sequences encoding anti-CTGF antibodies or antigen-binding fragments thereof, vectors and host cells containing polynucleotides, and recombinant technologies for antibody production. As described above, antibodies or antigen-binding fragments thereof, as described herein, may encode on a single polynucleotide or on multiple polynucleotides (e.g., encoding heavy and light chains on a single polynucleotide). (Isolated) polynucleotides may encode any desired form of anti-CTGF antibody, including, for example, full-length monoclonal antibodies, Fab, Fab', F(ab')2 and Fv fragments, bifunctional antibodies, linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.

[0209] As is known in the art, polynucleotides comprising sequences encoding anti-CTGF antibodies or fragments or chains thereof may be fused to one or more regulatory or control sequences and may be contained in expression vectors or host cells as known in the art. Each of the polynucleotide molecules encoding heavy or light chain variable domains may be independently fused to a polynucleotide sequence encoding a constant domain (such as a human constant domain), thereby enabling the generation of a complete antibody. Alternatively, polynucleotides or portions thereof may be fused together to provide a template for the generation of single-chain antibodies.

[0210] For recombinant production, a polynucleotide encoding an antibody is inserted into a reproducible vector used for cloning (DNA amplification) or for expression. Many suitable vectors for expressing recombinant antibodies are available. Vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence.

[0211] Anti-CTGF antibodies can also be produced in fusion polypeptide form, where the antibody is fused with a heterologous polypeptide (such as a signal sequence or other polypeptides having a specific cleavage site at the amino terminus of a mature protein or polypeptide). The selected heterologous signal sequence is typically a signal sequence that is recognized and processed by the host cell (i.e., cleaved by a signal peptidase). For prokaryotic host cells that do not recognize and process the anti-CTGF antibody signal sequence, the signal sequence may be replaced by a prokaryotic signal sequence. The signal sequence may be, for example, alkaline phosphatase, penicillinase, lipoprotein, heat-stable enterotoxin II precursor, and analogues thereof. For yeast secretion, the native signal sequence may be replaced by, for example, a precursor sequence derived from yeast convertase α-factor (including yeast (Saccharomyces) and Kluyveromyces) α-factor precursor), acid phosphatase, Candida albicans amylase, or a signal sequence described in WO 90 / 13646. In mammalian cells, mammalian signal sequences and viral secretory precursors, such as the herpes simplex virus gD signal, may be used. Previously, DNA from the body region was linked to DNA encoding anti-CTGF antibodies within the reading frame.

[0212] It can control the transcription of anti-CTGF antibodies in mammalian host cells, for example, through promoters derived from the genomes of viruses such as: polyomavirus, fowlpox virus, adenovirus (such as adenovirus 2), bovine papillomavirus, avian sarcoma virus, cytomegalovirus, retrovirus, hepatitis B virus, and simian virus 40 (SV40); heterologous mammalian promoters, such as actin promoters or immunoglobulin promoters; or heat shock promoters, provided that such promoters are compatible with the host cell system.

[0213] The suitable host cells used in this article for cloning or expressing DNA in a vector are the prokaryotic, yeast, or higher eukaryotic cells described above. Prokaryotes suitable for this purpose include eubacteria, such as Gram-negative or Gram-positive organisms, such as those from the family Enterobacteriaceae, such as *Escherichia* (e.g., *Escherichia coli*), *Enterobacter*, *Erwinia*, *Klebsiella*, *Proteus*, *Salmonella* (e.g., *Salmonella typhimurium*), *Serratia* (e.g., *Serratia marcescans*), and *Shigella*; and *Bacilli* (such as *B. subtilis* and *B. licheniformis*) (e.g., *B. licheniformis* disclosed in DD 266,710, published on April 12, 1989). Pseudomonas (such as Pseudomonas aeruginosa) and Streptomyces. A preferred Escherichia coli cloning host is Escherichia coli 294 (ATCC 31,446), but other strains such as Escherichia coli B, Escherichia coli X1776 (ATCC 31,537) and Escherichia coli W3110 (ATCC 27,325) are suitable. These examples are illustrative and not limiting.

[0214] Besides prokaryotes, eukaryotic microorganisms such as filamentous fungi or yeasts are suitable cloning or expression hosts for vectors encoding anti-CTGF antibodies. Among lower eukaryotic host microorganisms, *Saccharomyces cerevisiae* or *Bakery's yeast* are most commonly used. However, many other genera, species, and strains are generally available and applicable to this study, such as *Schizosaccharomyces pombe*; hosts of the genus *Kluyveromyces*, such as *Kluyveromyces lactis*, *Kluyveromyces fragilis* (ATCC 12,424), *Kluyveromyces bulgaricus* (ATCC 16,045), *Kluyveromyces wickeramii* (ATCC 24,178), *Kluyveromyces waltii* (ATCC 56,500), *Kluyveromyces drosophilarum* (ATCC 36,906), *Kluyveromyces thermotolerans*, and *Kluyveromyces marxianus*; *Yarrowia* (EP 402,226); and *Pichia pastors* (EP 402,226). 183,070); Candida; Trichoderma reesia (EP 244,234); Neurospora crassa; Schwanniomyces, such as Schwanniomyces occidentalis; and filamentous fungi, such as hosts of Neurospora, Penicillium, Tolypocladium and Aspergillus, such as Aspergillus nidulans and Aspergillus niger.

[0215] Suitable host cells for expressing glycosylated anti-CTGF antibodies are derived from multicellular organisms. Examples of invertebrate cells include plant and insect cells, including, for example, numerous baculovirus strains and variants, and corresponding permissible insect host cells from hosts such as: armyworm (Spodoptera frugiperda), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruit fly), and Bombyx mori (silkworm). Various viral strains for transfection are publicly available, such as the L-1 variant of Autographa californica NPV and the Bm-5 strain of Bombyx mori NPV, and these viruses are particularly useful for transfecting armyworm cells.

[0216] Plant cell cultures of cotton, corn, potatoes, soybeans, petunias, tomatoes, and tobacco can also be used as hosts.

[0217] Anti-CTGF antibodies or their antigen-binding fragments can also be incorporated into viral vectors, for example, by introducing a polynucleotide encoding an anti-CTGF antibody or its antigen-binding fragment into a viral vector, and then expressing it in the subject after viral infection.

[0218] In some respects, the expression of anti-CTGF antibodies or their antigen-binding fragments occurs in vertebrate cells. The propagation of vertebrate cells in cultures (tissue cultures) has become a routine procedure and is a widely available technique. Examples of suitable mammalian host cell lines include monkey kidney CV1 cell lines transformed with SV40 (COS-7, ATCC CRL 1651), human embryonic kidney cell lines (293 or 293 cells subcloned for growth in suspension culture, Graham et al., 1977, J. Gen Virol. 36: 59), juvenile hamster kidney cells (BHK, ATCC CCL 10), Chinese hamster ovary cells / -DHFR1 (CHO, Urlaub et al., 1980, Proc. Natl. Acad. Sci. USA 77: 4216; e.g. DG44), mouse sertoli cells (TM4, Mather, 1980, Biol. Reprod. 23:243-251), monkey kidney cells (CV1 ATCC CCL 70), and African green monkey kidney cells (VERO-76, ATCC). The cell lines used include: CRL-1587, human cervical cancer cells (HELA, ATCC CCL 2), canine kidney cells (MDCK, ATCC CCL 34), buffalo rat liver cells (BRL 3A, ATCC CRL 1442), human lung cells (W138, ATCC CCL 75), human hepatocytes (Hep G2, HB8065), mouse mammary tumor cells (MMT 060562, ATCC CCL51), TR1 cells (Mather et al., 1982, Annals N.Y. Acad. Sci. 383: 44-68), MRC 5 cells, FS4 cells, and human liver tumor cell line (Hep G2).

[0219] This also includes nucleic acids that hybridize under low, medium, and high stringency conditions, particularly under high stringency conditions as defined herein, with the entire or a portion (e.g., a portion encoding a variable region) of a separated polynucleotide sequence encoding an anti-CTGF antibody or antibody fragment. The hybridization portion of the hybrid nucleic acid is typically at least 15 (e.g., 20, 25, 30, or 50) nucleotides in length. The hybridization portion of the hybrid nucleic acid has at least 80%, for example, at least 90%, at least 95%, at least 98%, or at least 99%, identity with a portion or all of the nucleic acid encoding an anti-CTGF polypeptide (e.g., a heavy or light chain variable region) or its complementary sequence. Hybrid nucleic acids of the types described herein can be used, for example, as cloning probes, primers, such as PCR primers, or diagnostic probes. In some aspects, "highly stringent conditions" means prehybridizing and hybridizing probes of at least 100 nucleotides in length at 42°C in 5×SSPE, 0.3% SDS, 200 μg / ml cleaved and modified salmon sperm DNA, and 50% formamide, followed by a standard Southern blotting procedure for 12 to 24 hours. Finally, the carrier material is washed three times at 65°C with 0.2×SSC and 0.2% SDS for 15 minutes each time.

[0220] In one embodiment, the present invention relates to an isolated polynucleotide comprising a nucleotide sequence encoding a heavy chain variable region comprising an amino acid sequence of any one of SEQ ID NO: 108, 118, 128, 138, 148, 158, 168 or 178.

[0221] In one embodiment, the present invention relates to an isolated polynucleotide comprising a nucleotide sequence encoding a light chain variable region comprising an amino acid sequence of any one of SEQ ID NO: 103, 113, 123, 133, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243 or 253.

[0222] In one embodiment, the present invention relates to an isolated polynucleotide comprising a nucleotide sequence encoding a heavy chain region comprising an amino acid sequence of any one of SEQ ID NO: 109, 119, 129, 139, 149, 159, 169 or 179.

[0223] In one embodiment, the present invention relates to an isolated polynucleotide comprising a nucleotide sequence encoding a light chain region comprising an amino acid sequence of any one of SEQ ID NO: 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244 or 254.

[0224] Products

[0225] In some aspects, this includes articles containing materials suitable for treating the conditions described above. The articles include containers and labels. Suitable containers include, for example, bottles, vials, syringes, and test tubes. Containers can be formed from various materials, such as glass or plastic. The container holds the composition effectively treating the condition and may have a sterile dispensing port. For example, the container may be an intravenous solution bag or vial with a stopper that can be punctured by a subcutaneous needle. The active agent in the composition is an anti-CTGF antibody or its antigen-binding fragment. A label on or associated with the container indicates that the composition is intended to treat the selected condition. The articles may further include a second container containing pharmaceutically acceptable buffer solutions, such as phosphate-buffered saline, Ringer's solution, and dextran solution. They may further include other materials desirable from a commercial and user's point of view, including other buffer solutions, diluents, filters, needles, syringes, and packaging inserts with instructions for use.

[0226] Additional exemplary anti-CTGF antibody and compound sequences

[0227] The sequences of some exemplary anti-CTGF antibodies and compounds used in the working examples of this paper are provided below.

[0228] Antibody F1 light chain: DIQMTQSPSSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPPTFGQGTK LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 20).

[0229] Antibody F1 heavy chain: EGQLVQSGGGLVHPGGSLRLSCAGSGFTFSSYGMHWVRQAPGKGLEWVSGIGTGGGTYSTDSVKGRFTISRDNAKNSLYLQMNSLRAEDMAVYYCARGDYYGSGSFFDCWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 21).

[0230] Antibody H1 light chain: ETVVTQEPSLTVSPGGTVTLTCRSSIGAVTTSNYANWVQQKPGQAFRGLIGGTSNRAPWTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSTHYVFGGGTKLTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 22).

[0231] Antibody H1 heavy chain: EVTLKESGPVLVKPTETLTLTCTVSGFSLSTFGVHWIRQPPGKGLEWLGVIWRRGGTDYNAAFMSRLTISKDTSKSQVVFTMTNMDPVDTATYYCARDGGFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 23).

[0232] Antibody H2 light chain: EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWFQQKPGQSPKLWIYSTSNLASGVPARFSGSGSGTDYTLTISSLEPEDFAVYYCQQRSSYPLTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 24).

[0233] Antibody H2 heavy chain: EVQLVESGGGLVQPGGSLRLSCAASGFSFNTYAMNWVRQAPGKGLEWVARIRTKSNNYATYYADSVKDRFTISRDDSESSLYLQMNSLKTEDTAVYYCVETGFAYWDQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 25).

[0234] Compound P1: QDSTSDLIPAPPLSKVPLQQNFQDNQFQGKWYVVGVAGNAILRPDKQPAKMFATIYELKEDKSYDVTSVRFEAKSCKYTIKTFVPGSQPGEFTSGQIKSAPGQTSTLVRVVSTNYNQHAMVFFKHVSQNREIFVITLYGRTKELTSELKENFIRFSKSLGLPENHIVFPVPIDQCIDGHHHHHHHHHH (SEQ ID NO: 26).

[0235] Sequences of human CTGF and CTGF-NTF

[0236] The wild-type human CTGF sequence is available as NCBI accession number NP_001892.2 and has the following amino acid sequence (including the signal peptide): MTAASMGPVRVAFVVLLALCSRPAVGQNCSGPCRCPDEPAPRCPAGVSLVLDGCGCCRVCAKQLGELCTERDPCDPHKGLFCHFGSPANRKIGVCTAKDGAPCIFGGTVYRSGESFQSSCKYQCTCLDGAVGCMPLCSMDVRLPSPDCPFPRRVKLPGKCCEEWVCDEPKDQTVVGPALAAYRLEDTFGPDPTMIRANCLVQTTEWSACSKTCGMGISTRVTNDNASCRLEKQSRLCMVRPCEADLEENIKKGKKCIRTPKISKPIKFELSGCTSMKTYRAKFCGVCTDGRCCTPHRTTTLPVEFKCPDGEVMKKNMMFIKTCACHYNCPGDNDIFESLYYRKMYGDMA (SEQ ID NO: 1).

[0237] The full-length human CTGF used in the working example of this article has the following amino acid sequence, corresponding to NCBI accession number NP_001892.1 (signal peptide omitted): QNCSGPCRCPDEPAPRCPAGVSLVLDGCGCCRVCAKQLGELCTERDPCDPHKGLFCDFGSPANRKIGVCTAKDGAPCIFGGTVYRSGESFQSSCKYQCTCLDGAVGCMPLCSMDVRLPSPDCPFPRRVKLPGKCCEEWVCDEPKDQTVVGPALAAYRLEDTFGPDPTMIRANCLVQTTEWSACSKTCGMGISTRVTNDNASCRLEKQSRLCMVRPCEADLEENIKKGKKCIRTPKISKPIKFELSGCTSMKTYRAKFCGVCTDGRCCTPHRTTTLPVEFKCPDGEVMKKNMMFIKTCACHYNCPGDNDIFESLYYRKMYGDMA (SEQ ID NO:2), which was purchased from R&D Systems (catalog number 9190-CC).

[0238] The human N-terminal fragment of CTGF (CTGF-NTF) used in this working example has the following amino acid sequence: QNCSGPCRCPDEPAPRCPAGVSLVLDGCGCCRVCAKQLGELCTERDPCDPHKGLFCDFGSPANRKIGVCTAKDGAPCIFGGTVYRSGESFQSSCKYQCTCLDGAVGCMPLCSMDVRLPSPDCPFPRRVKLPGKCCEEWVCDEPKDQTVVGPALAENLYFQ (SEQ ID NO: 3), which is expressed in a recombinant manner. The last 6 amino acids at the C-terminus of the CTGF-NTF sequence are the TEV protease cleavage sites retained after purification.

[0239] Example

[0240] Example 1. Generation of anti-CTGF antibodies

[0241] method

[0242] Mice were immunized with the human N-terminal fragment of CTGF (CTGF-NTF). B cells were collected and used to generate fusion tumors by fusing with PAI myeloma cells. The resulting antibodies were screened for binding to recombinant human, cynomolgus monkey, and mouse CTGF-NTF. Antibodies were purified from serum-free fusion tumor supernatant using MabSelectSuRe resin (GE Healthcare). The binding of purified antibodies to human and cynomolgus monkey CTGF-NTF was analyzed on an Octet QK system (ForteBio) equipped with a streptavidin (SA) biosensor tip (ForteBio). Variable gene sequences were recovered from the fusion tumors, and chimeric antibodies containing these variable gene sequences were generated.

[0243] result ...

Claims

1. An anti-CTGF antibody or its antigen-binding fragment, comprising: The light chain variable region comprises: a light chain complementarity-determining region 1 (L-CDR1) having the amino acid sequence Y1-SSQSIVHYN-Y2-Y3-TYLE (SEQ ID NO: 10), wherein Y1 is K or R, Y2 is A, E, G or T, and Y3 is K or N; a light chain complementarity-determining region 2 (L-CDR2) having the amino acid sequence KVS-Z1-R-Z2-S (SEQ ID NO: 11), wherein Z1 is N or S and Z2 is A or F; and a light chain complementarity-determining region 3 (L-CDR3) having the amino acid sequence FQGSHFPLT (SEQ ID NO: 12); and The heavy chain variable region comprises: a heavy chain complementarity-determining region 1 (H-CDR1) having the amino acid sequence DYYMA (SEQ ID NO: 15); a heavy chain complementarity-determining region 2 (H-CDR2) having the amino acid sequence NINY-X1-GSRTDLL-X2-SLKS (SEQ ID NO: 16), wherein X1 is D, E, or Y and X2 is A, D, or E; and a heavy chain complementarity-determining region 3 (H-CDR3) having the amino acid sequence DTSRGSYFDV (SEQ ID NO: 17).

2. The anti-CTGF antibody or its antigen-binding fragment according to claim 1, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or ii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or iii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or iv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or v. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 130, L-CDR2 having the amino acid sequence of SEQ ID NO: 131, and L-CDR3 having the amino acid sequence of SEQ ID NO: 132; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or vi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or vii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or viii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or ix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or x. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 105, H-CDR2 having the amino acid sequence of SEQ ID NO: 106, and H-CDR3 having the amino acid sequence of SEQ ID NO: 107; or xvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 115, H-CDR2 having the amino acid sequence of SEQ ID NO: 116, and H-CDR3 having the amino acid sequence of SEQ ID NO: 117; or xxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xxxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xl. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xli. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xlii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xliii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 125, H-CDR2 having the amino acid sequence of SEQ ID NO: 126, and H-CDR3 having the amino acid sequence of SEQ ID NO: 127; or xliv. light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or xlv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or xlvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or xlvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or xlviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or xlix. Light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or 1. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or li. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or liii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or liv. light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lv. Light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 135, H-CDR2 having the amino acid sequence of SEQ ID NO: 136, and H-CDR3 having the amino acid sequence of SEQ ID NO: 137; or lviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lix. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lx. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxi. Light chain variable region, comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and heavy chain variable region, comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxiv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 145, H-CDR2 having the amino acid sequence of SEQ ID NO: 146, and H-CDR3 having the amino acid sequence of SEQ ID NO: 147; or lxxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxx. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxiii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 155, H-CDR2 having the amino acid sequence of SEQ ID NO: 156, and H-CDR3 having the amino acid sequence of SEQ ID NO: 157; or lxxxiv. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or lxxxv. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or lxxxvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or lxxxvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or lxxxviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or lxxxix. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xc. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xci. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xcii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xciii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xciv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xcv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xcvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 250, L-CDR2 having the amino acid sequence of SEQ ID NO: 251, and L-CDR3 having the amino acid sequence of SEQ ID NO: 252; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 165, H-CDR2 having the amino acid sequence of SEQ ID NO: 166, and H-CDR3 having the amino acid sequence of SEQ ID NO: 167; or xcvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 100, L-CDR2 having the amino acid sequence of SEQ ID NO: 101, and L-CDR3 having the amino acid sequence of SEQ ID NO: 102; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or xcviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 110, L-CDR2 having the amino acid sequence of SEQ ID NO: 111, and L-CDR3 having the amino acid sequence of SEQ ID NO: 112; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or xcix. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 120, L-CDR2 having the amino acid sequence of SEQ ID NO: 121, and L-CDR3 having the amino acid sequence of SEQ ID NO: 122; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or c. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 150, L-CDR2 having the amino acid sequence of SEQ ID NO: 151, and L-CDR3 having the amino acid sequence of SEQ ID NO: 152; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or ci. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 160, L-CDR2 having the amino acid sequence of SEQ ID NO: 161, and L-CDR3 having the amino acid sequence of SEQ ID NO: 162; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 170, L-CDR2 having the amino acid sequence of SEQ ID NO: 171, and L-CDR3 having the amino acid sequence of SEQ ID NO: 172; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or ciii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 180, L-CDR2 having the amino acid sequence of SEQ ID NO: 181, and L-CDR3 having the amino acid sequence of SEQ ID NO: 182; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or civ. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 190, L-CDR2 having the amino acid sequence of SEQ ID NO: 191, and L-CDR3 having the amino acid sequence of SEQ ID NO: 192; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cv. light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 200, L-CDR2 having the amino acid sequence of SEQ ID NO: 201, and L-CDR3 having the amino acid sequence of SEQ ID NO: 202; and heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cvi. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 210, L-CDR2 having the amino acid sequence of SEQ ID NO: 211, and L-CDR3 having the amino acid sequence of SEQ ID NO: 212; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cvii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 220, L-CDR2 having the amino acid sequence of SEQ ID NO: 221, and L-CDR3 having the amino acid sequence of SEQ ID NO: 222; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cviii. A light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 230, L-CDR2 having the amino acid sequence of SEQ ID NO: 231, and L-CDR3 having the amino acid sequence of SEQ ID NO: 232; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO: 177; or cix. a light chain variable region comprising L-CDR1 having the amino acid sequence of SEQ ID NO: 240, L-CDR2 having the amino acid sequence of SEQ ID NO: 241, and L-CDR3 having the amino acid sequence of SEQ ID NO: 242; and a heavy chain variable region comprising H-CDR1 having the amino acid sequence of SEQ ID NO: 175, H-CDR2 having the amino acid sequence of SEQ ID NO: 176, and H-CDR3 having the amino acid sequence of SEQ ID NO:

177.

3. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xv. a light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxv. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxvi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxix. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xxxix. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xlii. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xliii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlv. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlvi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or xlvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or xlviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or xlix. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or liii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or lvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lix. light chain variable region, the light chain variable region containing at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, the heavy chain variable region containing at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lx. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxiii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxiv. a light chain variable region containing at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region containing at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxv. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxvi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxix. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxx. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxiii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxiv. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxv. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxvi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxviii. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxix. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxx. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiv. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxv. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxvi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxix. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or xc. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or xci. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or xcii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or xciii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or xciv. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcv. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcvi. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 168; or xcvii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or xcviii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or xcix. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or c. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or ci. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or cii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or ciii. A light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or civ. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or cv. light chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, which contains at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cvi. The light chain variable region, comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 213; and the heavy chain variable region, comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or cvii. a light chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 178; or cviii. A light chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cix. a light chain variable region containing at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region containing at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

178.

4. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xi. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xv. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxv. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 118; or xxvi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxix. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xxxi. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xxxii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xxxix. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xlii. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xliii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlv. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlvi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlvii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or xlviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlix. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or liii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or lvii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 148; or lix. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 148; or lx. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 148; or lxi. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 148; or lxii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxiii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxiv. a light chain variable region containing at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region containing at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxv. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxvi. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxix. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 148; or lxx. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 158; or lxxii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxiii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxiv. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxv. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxvi. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxix. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxx. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxxi. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 158; or lxxxiv. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or lxxxv. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or lxxxvi. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or lxxxvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or lxxxviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or lxxxix. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xc. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xci. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 168; or xcii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xciii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xciv. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcv. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcvi. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcvii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or xcviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or xcix. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or c. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or ci. a light chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of SEQ ID NO: 178; or cii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or ciii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or civ. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cv. light chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, which contains at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cvi. The light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 213; and the heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cvii. a light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cviii. A light chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cix. a light chain variable region containing at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region containing at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

178.

5. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or xi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or xv. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxvi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxix. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xxxix. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xlii. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xliii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, which contains an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or xlv. light chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlvi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or xlvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or xlviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or xlix. light chain variable region, which contains an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and heavy chain variable region, which contains an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or liii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or lvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lix. light chain variable region, the light chain variable region containing an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, the heavy chain variable region containing an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lx. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxiii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxiv. a light chain variable region containing at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region containing at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxv. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxvi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxix. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxx. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxiii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxiv. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxv. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxvi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxix. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxx. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiv. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxv. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxvi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxix. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or xc. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or xci. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or xcii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or xciii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or xciv. light chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcv. light chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcvi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 168; or xcvii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or xcviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or xcix. light chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or c. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or ci. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or cii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or ciii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or civ. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or cv. light chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, which contains at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cvi. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or cvii. a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or cviii. A light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 178; or cix. a light chain variable region containing an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region containing an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

178.

6. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, wherein the anti-CTGF antibody or its antigen-binding fragment comprises: i. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xxxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xlii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xliii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or xlvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or xlvii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or xlviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or xlix. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 173; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or liii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lix. light chain variable region, the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lx. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxiv. a light chain variable region containing at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region containing at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 148; or lxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxix. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxix. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxx. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; or lxxxiv. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxv. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxvi. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or lxxxix. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xc. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xci. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xcii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xciii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xciv. light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xcv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 168; or xcvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168; or xcvii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or xcviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or xcix. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or c. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or ci. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or ciii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or civ. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cv. light chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, which contains at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 178; or cvi. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cvii. a light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cviii. A light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178; or cix. a light chain variable region containing at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region containing at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

178.

7. The anti-CTGF antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the anti-CTGF antibody or antigen-binding fragment thereof comprises: i. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or ii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or iii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or iv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or v. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 133; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or vi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or vii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or viii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or ix. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or x. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108; or xvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xix. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xx. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxvi. Light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxvii. Light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 118; or xxix. Light chain variable region, comprising the amino acid sequence of SEQ ID NO: 253; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 118; or xxx. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xxxix. Light chain variable region, which contains the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 128; or xl. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xli. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xlii. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 128; or xliii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; or xliv. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 103; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 138; or xlv. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or xlvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or xlvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or xlviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or xlix. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 173; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or 1. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or li. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or liii. Light chain variable region, comprising the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 138; or liv. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 223; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 138; or lv. Light chain variable region, which contains the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 138; or lvi. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lvii. Light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 138; or lviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lix. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 113; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 148; or lx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxi. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 163; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 148; or lxii. Light chain variable region, which contains the amino acid sequence of SEQ ID NO: 173; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 148; or lxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxiv. light chain variable region containing the amino acid sequence of SEQ ID NO: 193; and heavy chain variable region containing the amino acid sequence of SEQ ID NO: 148; or lxv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxix. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 148; or lxx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 148; or lxxi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxiv. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxix. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxx. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 243; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxiii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 158; or lxxxiv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or lxxxv. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or lxxxvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or lxxxvii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or lxxxviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or lxxxix. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xc. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xci. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 203; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xcii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xciii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xciv. light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xcv. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 168; or xcvi. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 168; or xcvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 103; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or xcviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 113; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or xcix. light chain variable region, comprising the amino acid sequence of SEQ ID NO: 123; and heavy chain variable region, comprising the amino acid sequence of SEQ ID NO: 178; or c. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 153; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or ci. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 163; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 173; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or ciii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 183; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or civ. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 193; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cv. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 203; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO: 178; or cvi. light chain variable region comprising the amino acid sequence of SEQ ID NO: 213; and heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cvii. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cviii. A light chain variable region comprising the amino acid sequence of SEQ ID NO: 233; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 178; or cix. light chain variable region, which contains the amino acid sequence of SEQ ID NO: 243; and heavy chain variable region, which contains the amino acid sequence of SEQ ID NO:

178.

8. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, comprising: i. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or v. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 109; or vi. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or vii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or viii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ix. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or x. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xiii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xiv. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xv. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xvi. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xvii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xviii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xix. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 119; or xx. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiv. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxv. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvi. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxviii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxix. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxx. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiv. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxv. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvi. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxviii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxix. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xl. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 129; or xli. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xlii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xliii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xliv. light chain, comprising at least 80% identical amino acid sequence to SEQ ID NO: 104; and heavy chain, comprising at least 80% identical amino acid sequence to SEQ ID NO: 139; or xlv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 139; or xlvi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or xlvii. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 139; or xlviii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 139; or xlix. light chain, comprising at least 80% identical amino acid sequence to SEQ ID NO: 174; and heavy chain, comprising at least 80% identical amino acid sequence to SEQ ID NO: 139; or 1. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or li. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liv. light chain, comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 224; and heavy chain, comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 139; or lv. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lviii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lix. light chain, comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 114; and heavy chain, comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 149; or lx. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxiii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxiv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 149; or lxv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 149; or lxvi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxvii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxviii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxix. light chain, comprising at least 80% identical amino acid sequence to SEQ ID NO: 244; and heavy chain, comprising at least 80% identical amino acid sequence to SEQ ID NO: 149; or lxx. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxxi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxiv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxvi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxvii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxviii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxix. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxx. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxxi. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxxiv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxvi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or lxxxvii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or lxxxviii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxix. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or xc. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or xci. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or xcii. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or xciii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or xciv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or xcv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 169; or xcvi. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or xcvii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or xcviii. A light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 179; or xcix. light chain, comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 124; and heavy chain, comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 179; or c. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or ci. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or cii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or ciii. A light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or civ. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 179; or cv. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 179; or cvi. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 179; or cvii. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or cviii. a light chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 80% identical amino acid sequence to that of SEQ ID NO: 179; or cix. a light chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 80% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

179.

9. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, comprising: i. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or v. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or vi. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or vii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or viii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ix. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or x. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or xi. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xiii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or xiv. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 109; or xvi. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xvii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 119; or xviii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 119; or xix. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 119; or xx. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 119; or xxii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiv. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 119; or xxvi. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 119; or xxviii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxix. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxx. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxi. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiv. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxv. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvi. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxviii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxix. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xl. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 129; or xli. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 129; or xlii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xliii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xliv. light chain, comprising at least 85% identical amino acid sequence to SEQ ID NO: 104; and heavy chain, comprising at least 85% identical amino acid sequence to SEQ ID NO: 139; or xlv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or xlvi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or xlvii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or xlviii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or xlix. light chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 174; and heavy chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or 1. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or li. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liv. light chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 224; and heavy chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 139; or lv. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvi. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lviii. A light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lix. light chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 114; and heavy chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lx. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxiii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxiv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxvi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxvii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxviii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxix. light chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 244; and heavy chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 149; or lxx. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxxi. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxvi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxvii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxviii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxix. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxx. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxvi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxvii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxviii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxix. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xc. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xci. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xcii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xciii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xciv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xcv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xcvi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 169; or xcvii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or xcviii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or xcix. light chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 124; and heavy chain, comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or c. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or ci. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or cii. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or ciii. A light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or civ. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or cv. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or cvi. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or cvii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or cviii. a light chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 85% identical amino acid sequence to that of SEQ ID NO: 179; or cix. a light chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 85% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

179.

10. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, comprising: i. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 109; or v. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 109; or vi. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or vii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 109; or viii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ix. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or x. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 109; or xi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xiii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xiv. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xv. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xvi. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xvii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 119; or xviii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xix. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 119; or xx. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxi. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 119; or xxii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiv. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxv. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvi. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxviii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxix. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 119; or xxx. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiv. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 129; or xxxv. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvi. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxviii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxix. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xl. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 129; or xli. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 129; or xlii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xliii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xliv. light chain, comprising at least 90% identical amino acid sequence to SEQ ID NO: 104; and heavy chain, comprising at least 90% identical amino acid sequence to SEQ ID NO: 139; or xlv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 139; or xlvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or xlvii. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 139; or xlviii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 139; or xlix. light chain, comprising at least 90% identical amino acid sequence to SEQ ID NO: 174; and heavy chain, comprising at least 90% identical amino acid sequence to SEQ ID NO: 139; or 1. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 139; or li. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liv. light chain, comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 224; and heavy chain, comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 139; or lv. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lviii. A light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lix. light chain, comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 114; and heavy chain, comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 149; or lx. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxi. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 149; or lxii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxiii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 149; or lxiv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 149; or lxv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 149; or lxvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxvii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxviii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 149; or lxix. light chain, comprising at least 90% identical amino acid sequence to SEQ ID NO: 244; and heavy chain, comprising at least 90% identical amino acid sequence to SEQ ID NO: 149; or lxx. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 149; or lxxi. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 159; or lxxvii. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxviii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxix. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxx. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxi. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or lxxxvii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or lxxxviii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxix. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or xc. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or xci. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or xcii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or xciii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or xciv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or xcv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 169; or xcvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 169; or xcvii. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or xcviii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or xcix. light chain, comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 124; and heavy chain, comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or c. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or ci. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or cii. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or ciii. A light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or civ. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or cv. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or cvi. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or cvii. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or cviii. a light chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 90% identical amino acid sequence to that of SEQ ID NO: 179; or cix. a light chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 90% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

179.

11. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, comprising: i. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or v. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 134; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or vi. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or vii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or viii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or ix. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or x. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xi. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 109; or xii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xiv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 109; or xvi. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xvii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xix. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xx. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxiv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxvi. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxvii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxviii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 119; or xxix. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 119; or xxx. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxi. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxiv. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxv. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxvi. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxvii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xxxviii. A light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xxxix. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 129; or xl. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xli. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xlii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xliii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 129; or xliv. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or xlv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or xlvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or xlvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or xlviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or xlix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or 1. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or li. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or liii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or liv. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lv. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 139; or lvii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 139; or lviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxvii. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 149; or lxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 149; or lxxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxix. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxx. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 159; or lxxxiv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or lxxxix. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xc. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xci. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xcii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xciii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xciv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xcv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xcvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 254; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 169; or xcvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 104; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or xcviii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 114; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or xcix. light chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 124; and heavy chain, comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or c. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 154; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or ci. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 179; or cii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 174; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or ciii. A light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 184; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or civ. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 194; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cv. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 204; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cvi. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 214; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cvii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 224; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cviii. a light chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 234; and a heavy chain comprising at least 95% identical amino acid sequence to that of SEQ ID NO: 179; or cix. a light chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO: 244; and a heavy chain comprising at least 95% identical amino acid sequence to the amino acid sequence of SEQ ID NO:

179.

12. The anti-CTGF antibody or its antigen-binding fragment according to any one of the preceding claims, comprising: i. a light chain comprising the amino acid sequence of SEQ ID NO: 224; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or ii. A light chain comprising the amino acid sequence of SEQ ID NO: 104; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or iii. A light chain comprising the amino acid sequence of SEQ ID NO: 114; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or iv. A light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or v. a light chain comprising the amino acid sequence of SEQ ID NO: 134; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or vi. A light chain comprising the amino acid sequence of SEQ ID NO: 154; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 109; or vii. A light chain comprising the amino acid sequence of SEQ ID NO: 164; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 1...

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