Anti-chitinase-3-like protein 1 antibody

Abstract

The anti-chitinase-3-like protein 1 antibody or antigen-binding fragment thereof of the present invention comprises a light chain variable region comprising the CDRs of Table 1 and a heavy chain variable region comprising the CDRs of Table 2.

Description

Technical Field

[0001] The present invention relates to an anti-chitinase-3-like protein 1 antibody. More specifically, the present invention relates to an antibody that can specifically bind to chitinase-3-like protein 1 (CHI3L1) and can be used for the prevention or treatment of CHI3L1-related diseases or the diagnosis of said diseases.

Background Art

[0002] Chitinase-3-like protein 1 (CHI3L1) is known to induce the promotion of cancer metastasis, the suppression of immune function, and the suppression of cell death, and is known to be very importantly involved in the onset and progression of cancer diseases such as inflammatory reactions and angiogenesis processes.

[0003] Although CHI3L1 is expressed at a low level in the normal state, it has been reported that its expression is significantly increased in the blood and tissues of cancer patients or patients with inflammatory diseases, and the possibility as a diagnostic index for various types of diseases is emerging.

[0004] Therefore, the present inventors attempted to develop an antibody or antibody-related molecule that can be used for the prevention, treatment, or diagnosis of CHI3L1-related diseases by specifically binding to CHI3L1 as described above.

[0005] As a related prior art document, there is US Registered Patent No. 7,670,599.

Summary of the Invention

Problems to be Solved by the Invention

[0006] The main object of the present invention is to provide a new antibody that can specifically bind to chitinase-3-like protein 1 (CHI3L1).

[0007] Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of CHI3L1-related disease, a diagnostic composition for the disease, a diagnostic kit for the disease, and a method for providing information for the diagnosis of the disease, by using the antibody.

[0008] A further object of the present invention is to provide polynucleotides, vectors, and cells that can be used to produce antibodies. [Means for solving the problem]

[0009] According to one aspect of the present invention, the present invention is an anti-chitinase-3-like protein 1 (anti-CHI3L1) antibody or an antigen-binding fragment thereof, comprising a variable light chain region including CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3, and a variable heavy chain region including CDR1 of SEQ ID NO: 31, CDR2 of SEQ ID NO: 32, and CDR3 of SEQ ID NO: 33, a variable light chain region including CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6, and CDR1 of SEQ ID NO: 34, CDR2 of SEQ ID NO: 35, and CDR3 of SEQ ID NO: 36 Includes a variable region of the heavy chain, a variable region of the light chain including CDR1 of SEQ ID NO: 7, CDR2 of SEQ ID NO: 8 and CDR3 of SEQ ID NO: 9, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 37, CDR2 of SEQ ID NO: 38 and CDR3 of SEQ ID NO: 39, a variable region of the light chain including CDR1 of SEQ ID NO: 10, CDR2 of SEQ ID NO: 11 and CDR3 of SEQ ID NO: 12, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 40, CDR2 of SEQ ID NO: 41 and CDR3 of SEQ ID NO: 42, CDR1 of SEQ ID NO: 13, CDR2 of SEQ ID NO: 14 and CDR3 of SEQ ID NO: 15 A variable light chain region including CDR3, and a variable heavy chain region including CDR1 of SEQ ID NO: 43, CDR2 of SEQ ID NO: 44 and CDR3 of SEQ ID NO: 45, a variable light chain region including CDR1 of SEQ ID NO: 16, CDR2 of SEQ ID NO: 17 and CDR3 of SEQ ID NO: 18, and a variable heavy chain region including CDR1 of SEQ ID NO: 46, CDR2 of SEQ ID NO: 47 and CDR3 of SEQ ID NO: 48, a variable light chain region including CDR1 of SEQ ID NO: 19, CDR2 of SEQ ID NO: 20 and CDR3 of SEQ ID NO: 21, and CDR1 of SEQ ID NO: 49 and CDR2 of SEQ ID NO: 50 This includes a variable heavy chain region containing CDR3 of SEQ ID NO: 51, a variable light chain region containing CDR1 of SEQ ID NO: 22, CDR2 of SEQ ID NO: 23 and CDR3 of SEQ ID NO: 24, and a variable heavy chain region containing CDR1 of SEQ ID NO: 52, CDR2 of SEQ ID NO: 53 and CDR3 of SEQ ID NO: 54, a variable light chain region containing CDR1 of SEQ ID NO: 25, CDR2 of SEQ ID NO: 26 and CDR3 of SEQ ID NO: 27, and a variable heavy chain region containing CDR1 of SEQ ID NO: 55, CDR2 of SEQ ID NO: 56 and CDR3 of SEQ ID NO: 57, or CDR1 of SEQ ID NO: 28,The present invention provides an antibody or its antigen-binding fragment, comprising a variable light chain region containing CDR2 of SEQ ID NO: 29 and CDR3 of SEQ ID NO: 30, and a variable heavy chain region containing CDR1 of SEQ ID NO: 58, CDR2 of SEQ ID NO: 59, and CDR3 of SEQ ID NO: 60.

[0010] According to another aspect of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of CHI3L1-related diseases comprising the antibody or antigen-binding fragment thereof.

[0011] According to yet another aspect of the present invention, the present invention provides a diagnostic composition for CHI3L1-related diseases comprising the antibody or antigen-binding fragment thereof.

[0012] According to yet another aspect of the present invention, the present invention provides a diagnostic kit for CHI3L1-related diseases comprising the diagnostic composition of the present invention.

[0013] According to yet another aspect of the present invention, the present invention provides an information-providing method for diagnosing CHI3L1-related diseases, comprising the steps of contacting an antibody or antigen-binding fragment of the present invention with a sample isolated from a test subject, and measuring a complex of the antibody or antigen-binding fragment formed by the contact with CHI3L1.

[0014] According to yet another aspect of the present invention, the present invention provides a polynucleotide encoding an antibody or an antigen-binding fragment thereof.

[0015] According to yet another aspect of the present invention, the present invention provides a vector comprising the polynucleotide of the present invention.

[0016] According to yet another aspect of the present invention, the present invention provides cells transformed with the vector of the present invention. [Effects of the Invention]

[0017] The antibody or antigen-binding fragment of the present invention can specifically bind to chitinase-3-like protein 1 (CHI3L1) and can be used for the prevention or treatment of CHI3L1-related diseases and for the diagnosis of said diseases. Therefore, the composition, kit, and information-providing method of the present invention can be used to effectively prevent, treat, or diagnose CHI3L1-related diseases. Furthermore, the polynucleotide, vector, and cells of the present invention can be used to efficiently produce the antibody or antigen-binding fragment of the present invention having the excellent effects described above. [Brief explanation of the drawing]

[0018] [Figure 1] Figure 1A is a schematic diagram showing the process of selecting antibodies that show significant binding affinity to human CHI3L1 (hCHI3L1) via phage display, while Figures 1B to 1D show the results of panning titration for Fab-I and Fab-II, respectively. [Figure 2] Figure 2 shows the results of examining the amino acid length distribution of the heavy chain CDR3 (HCDR3) of 10 antibodies against hCHI3L1 selected from phage display (A5, A7, D2, F2, E7, F4, H1, 1E12, C5, and H7). [Figure 3] Figure 3A shows the SDS-PAGE results for confirming IgG production from 10 clones (A5, A7, D2, F2, E7, F4, H1, 1E12, C5, and H7) that possess antibodies against hCHI3L1, while Figure 3B shows the results of measuring IgG production. [Figure 4] Figures 4A-4B show the results of measuring the EC50 values ​​of 10 antibodies against hCHI3L1 via ELISA. [Figure 5] Figure 5 shows the results of measuring the number of migrated cells after treating the A549 cell line with candidate antibodies against hCHI3L1: A5, A7, D2, F2, E7, F4, H1, 1E12, C5, and H7. [Embodiments for Carrying out the Invention]

[0019] The antibody or antigen-binding fragment thereof of the present invention was discovered through phage display panning using chitinase-3-like protein 1 (CHI3L1) as an antigen, and can specifically bind to CHI3L1.

[0020] CHI3L1, also known as YKL-40, is known to be involved in various cancers, cancer metastasis, immune function, and cell death.

[0021] The present invention provides ten types of antibodies or antigen-binding fragments thereof.

[0022] As shown in Tables 1 to 4 for the ten types, they are respectively named "A5", "A7", "D2", "F2", "E7", "F4", "H1", "1E12", "C5", "H7". The CDR1, CDR2, and CDR3 of the variable region of the light chain of each type of antibody or antigen-binding fragment thereof (in Table 1, it means the CDR of the variable region of the light chain, and is represented by "CDRL1", "CDRL2", "CDRL3" respectively) amino acid sequences are as shown in Table 1, and the CDR1, CDR2, and CDR3 of the variable region of the heavy chain thereof (in Table 2, it means the CDR of the variable region of the heavy chain, and is represented by "CDRH1", "CDRH2", "CDRH3") amino acid sequences are as shown in Table 2.

[0023]

[0024] ​The antibody or antigen-binding fragment of the present invention may be in various forms that satisfy the above conditions. For example, it may be an antibody selected from the group consisting of IgG, IgA, IgM, IgE, and IgD, or it may be a fragment selected from the group consisting of Fab (fragment antigen binding), Fab', F(ab')2, scFv, scFv-Fc, diabody, minibody, and triabody.

[0025] The antibody or antigen-binding fragment of the present invention may be labeled for detection. In this case, the labeling may consist of, for example, direct or indirect binding of a detectable labeling substance.

[0026] Experiments have demonstrated that the antibody or antigen-binding fragment of the present invention can bind specifically to CHI3L1 with high binding affinity. Therefore, the antibody or antigen-binding fragment of the present invention may be used to prevent or treat CHI3L1-related diseases, or to diagnose CHI3L1-related diseases.

[0027] Therefore, the present invention provides a pharmaceutical composition for the prevention or treatment of CHI3L1-related diseases comprising the antibody or antigen-binding fragment thereof.

[0028] Furthermore, the present invention provides a diagnostic composition for CHI3L1-related diseases comprising the antibody or antigen-binding fragment thereof.

[0029] Furthermore, the present invention provides a diagnostic kit for CHI3L1-related diseases comprising the antibody or antigen-binding fragment thereof, or the diagnostic composition of the present invention.

[0030] Furthermore, the present invention provides a method for treating CHI3L1-related disease comprising the steps of contacting the antibody or antigen-binding fragment of the present invention with a sample isolated from a test subject, and measuring the complex of the antibody or antigen-binding fragment formed by the contact with chitinase-3-like protein 1. To provide a method for providing information for diagnosis.

[0031] In one embodiment, the CHI3L1-related disease is, but is not limited to, cancer, cancer metastasis, arthritis, or dementia. In one embodiment, the CHI3L1-related disease is lung cancer metastasis.

[0032] The pharmaceutical composition for the prevention or treatment of CHI3L1-related disease of the present invention is characterized by comprising the antibody of the present invention or its antigen-binding fragment as described above. The pharmaceutical composition of the present invention may contain at least one type of the antibody of the present invention or its antigen-binding fragment, or may contain all 10 types. The pharmaceutical composition of the present invention may be in the form of the antibody of the present invention or its antigen-binding fragment itself, or in a form mixed with a pharmaceutically acceptable carrier. The pharmaceutical composition of the present invention may be administered orally or parenterally at the time of clinical administration, or may be used in the form of a general pharmaceutical formulation. The pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, radiotherapy, hormone therapy, chemotherapy, and biological reaction modifiers. The pharmaceutical composition of the present invention may be administered at the same dosage as a normal antibody preparation based on the antibody of the present invention or its antigen-binding fragment contained herein. For example, it may be administered at about 1 to 10 mg per kg of body weight based on the antibody of the present invention or its antigen-binding fragment, but the range varies depending on the weight, age, sex, health status, diet, administration time, administration method, excretion rate, and disease severity of the recipient. For clinical administration, the drug may be formulated in various forms, either orally or parenterally. In this case, commonly used fillers, bulking agents, binders, wetting agents, disintegrants, surfactants, and other diluents or excipients may be used.

[0033] The diagnostic composition for CHI3L1-related diseases of the present invention is characterized by comprising the antibody of the present invention or its antigen-binding fragment as described above. Similar to the pharmaceutical composition, the diagnostic composition of the present invention may contain at least one type of the antibody or its antigen-binding fragment, or all ten types. The diagnostic composition of the present invention may also contain other antibodies or their antigen-binding fragments other than the antibody or its antigen-binding fragment of the present invention. Furthermore, it may further contain substances necessary for the binding reaction between the antibody or its antigen-binding fragment and the antigen, such as reagents. It may also further contain substances necessary for detecting this binding, substances for stabilizing the antibody or its antigen-binding fragment, and so on.

[0034] The diagnostic kit for CHI3L1-related diseases of the present invention is characterized by comprising the diagnostic composition of the present invention. In addition to the diagnostic composition of the present invention, the diagnostic kit of the present invention may further comprise reagents, instruments, etc., necessary for diagnosing CHI3L1-related diseases using the diagnostic composition of the present invention, such as reagents and instruments necessary for detecting the binding of the antibody or antigen-binding fragment of the present invention to the antigen.

[0035] The present invention provides a method for providing information for diagnosing CHI3L1-related diseases, comprising the steps of: contacting an antibody or antigen-binding fragment of the present invention with a sample isolated from a test subject; and measuring a complex of the antibody or antigen-binding fragment formed by the contact with CHI3L1. In the present invention's method for providing information, the test subject may be a mammal, preferably a human. In the present invention's method for providing information, the sample may be a biological sample, such as a tissue, cell, or body fluid sample isolated from a test subject, or it may be blood or serum. In the present invention's method for providing information, the measurement of the complex can be achieved using a conventional method used to measure a binding complex between an antibody or antibody-related molecule and an antigen.

[0036] The present invention also provides polynucleotides encoding the antibody or its antigen-binding fragment.

[0037] In one embodiment, the polynucleotide of the present invention has the base sequences of the CDR1, CDR2, and CDR3 coding regions of the light chain variable region (represented as "CDRL1", "CDRL2", and "CDRL3" in Table 5, meaning the CDR of the light chain variable region) as shown in Table 5, and the base sequences of the CDR1, CDR2, and CDR3 coding regions of the heavy chain variable region (represented as "CDRH1", "CDRH2", and "CDRH3" in Table 6, meaning the CDR of the heavy chain variable region) as shown in Table 6.

[0038] In one embodiment, the polynucleotide encoding each type of antibody or antigen-binding fragment of the present invention has the coding base sequence of the variable region of the light chain as shown in Table 7, and the coding base sequence of the variable region of the heavy chain as shown in Table 8.

[0039] The present invention also provides vectors comprising the polynucleotide of the present invention. In one embodiment, the vector of the present invention is configured such that an antibody or antigen-binding fragment encoded by the polynucleotide is expressed in a host cell. In one embodiment, the vector of the present invention includes a replication origin, promoter, selection marker, etc., suitable for replication and expression in a host cell.

[0040] The present invention also provides cells transformed with the vector of the present invention. In one embodiment, the cells of the present invention are cells that can express an antibody or its antigen-binding fragment encoded by a polynucleotide contained in the vector of the present invention, and are cells that can replicate the vector of the present invention.

[0041] Using the amino acid sequence and base sequence information related to the antibody or antigen-binding fragment of the present invention as described above, the polynucleotide, vector, or cell of the present invention, the antibody or antigen-binding fragment of the present invention can be produced.

[0042] [Table 1]

[0043] [Table 2]

[0044] [Table 3]

[0045] [Table 4]

[0046] [Table 5]

[0047] [Table 6]

[0048] [Table 7]

[0049] [Table 8]

[0050] The present invention will be described in more detail below through the examples. These examples are merely illustrative and should not be construed as limiting the scope of the present invention.

[0051] [Examples] Example 1. Selection of Fab antibody clones against CHI3L1 To discover antibodies that specifically bind to CHI3L1, immunotube and magnetic bead-based phage display panning was performed using CHI3L1 as the antigen, and monoclonal phage ELISA was performed to select clones that specifically bind to CHI3L1 (Figure 1).

[0052] Clones that tested positive in monoclonal phage ELISA were selected for a total of 10 Fab clones through nucleotide and amino acid sequence analysis. Examination of the heavy chain CDR3 (HCDR3) length distribution of the selected Fab clones revealed that 70% had 8 residues, and 10% each had 6, 7, or 11 residues (Figure 2).

[0053] Example 2. Expression and purification of IgG antibodies In Example 1, the selected clones were converted to the IgG form of human antibodies, and experiments were conducted to verify this. Ten types of anti-CHI3L1 antibodies were co-transplanted into ExpiCHO-S cells and cultured, and IgG was purified using a Protein A resin column. The molecular weight and purity of the purified IgG antibodies were confirmed by SDS-PAGE (Figure 3).

[0054] Example 3. ELISA analysis of antibodies EC for each antibody via ELISA 50 An experiment was conducted to measure antigen affinity by examining the values. The results confirmed that all 10 antibodies bound to the CHI3L1 antigen protein. EC 50 Looking at the values, the C5, F4, and 1E12 antibodies showed particularly excellent binding affinity (Figure 4).

[0055] Example 4. Analysis of the anticancer efficacy of antibodies An experiment was conducted to determine whether treating lung cancer cell lines with antibodies against CHI3L1 has an effect in suppressing cancer metastasis. The migration of human lung cancer cell lines, specifically the A549 cell line, was quantitatively measured using a permeable insert. The results showed that when treated with 10 antibodies against human CHI3L1 (hCHI3L1), the number of migrating cells in the A549 cell line decreased compared to the control group (Figure 5). (Note) This disclosure includes the following aspects: Item 1: As an anti-chitinase-3-like protein 1 antibody or its antigen-binding fragment, A variable region of the light chain including CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 31, CDR2 of SEQ ID NO: 32, and CDR3 of SEQ ID NO: 33. A variable region of the light chain including CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 34, CDR2 of SEQ ID NO: 35, and CDR3 of SEQ ID NO: 36. A variable region of the light chain including CDR1 of SEQ ID NO: 7, CDR2 of SEQ ID NO: 8, and CDR3 of SEQ ID NO: 9, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 37, CDR2 of SEQ ID NO: 38, and CDR3 of SEQ ID NO: 39. A variable region of the light chain including CDR1 of SEQ ID NO: 10, CDR2 of SEQ ID NO: 11, and CDR3 of SEQ ID NO: 12, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 40, CDR2 of SEQ ID NO: 41, and CDR3 of SEQ ID NO: 42. A variable region of the light chain including CDR1 of SEQ ID NO: 13, CDR2 of SEQ ID NO: 14, and CDR3 of SEQ ID NO: 15, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 43, CDR2 of SEQ ID NO: 44, and CDR3 of SEQ ID NO: 45. A variable region of the light chain including CDR1 of SEQ ID NO: 16, CDR2 of SEQ ID NO: 17, and CDR3 of SEQ ID NO: 18, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 46, CDR2 of SEQ ID NO: 47, and CDR3 of SEQ ID NO: 48. A variable region of the light chain including CDR1 of SEQ ID NO: 19, CDR2 of SEQ ID NO: 20, and CDR3 of SEQ ID NO: 21, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 49, CDR2 of SEQ ID NO: 50, and CDR3 of SEQ ID NO: 51. A variable region of the light chain including CDR1 of SEQ ID NO: 22, CDR2 of SEQ ID NO: 23, and CDR3 of SEQ ID NO: 24, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 52, CDR2 of SEQ ID NO: 53, and CDR3 of SEQ ID NO: 54. A variable light chain region including CDR1 of SEQ ID NO: 25, CDR2 of SEQ ID NO: 26, and CDR3 of SEQ ID NO: 27, and a variable heavy chain region including CDR1 of SEQ ID NO: 55, CDR2 of SEQ ID NO: 56, and CDR3 of SEQ ID NO: 57, or An antibody or its antigen-binding fragment, comprising a variable light chain region containing CDR1 of SEQ ID NO: 28, CDR2 of SEQ ID NO: 29, and CDR3 of SEQ ID NO: 30, and a variable heavy chain region containing CDR1 of SEQ ID NO: 58, CDR2 of SEQ ID NO: 59, and CDR3 of SEQ ID NO: 60. Item 2: Including the variable region of the light chain in SEQ ID NO: 61 and the variable region of the heavy chain in SEQ ID NO: 71, Including the variable region of the light chain in SEQ ID NO: 62 and the variable region of the heavy chain in SEQ ID NO: 72, Including the variable region of the light chain in SEQ ID NO: 63 and the variable region of the heavy chain in SEQ ID NO: 73, Including the variable region of the light chain in SEQ ID NO: 64 and the variable region of the heavy chain in SEQ ID NO: 74, Including the variable region of the light chain in SEQ ID NO: 65 and the variable region of the heavy chain in SEQ ID NO: 75, Including the variable region of the light chain in Sequence ID No. 66 and the variable region of the heavy chain in Sequence ID No. 76, Including the variable region of the light chain in Sequence ID No. 67 and the variable region of the heavy chain in Sequence ID No. 77, Including the variable region of the light chain in Sequence ID No. 68 and the variable region of the heavy chain in Sequence ID No. 78, Including the variable region of the light chain in SEQ ID NO: 69 and the variable region of the heavy chain in SEQ ID NO: 79, or The antibody or antigen-binding fragment described in item 1, comprising the variable light chain region of SEQ ID NO: 70 and the variable heavy chain region of SEQ ID NO: 80. Item 3: A pharmaceutical composition for the prevention or treatment of chitinase-3-like protein 1-related disease, comprising an antibody or antigen-binding fragment described in item 1 or 2. Item 4: The aforementioned chitinase-3-like protein 1-related disease is cancer, cancer metastasis, arthritis, or dementia, as described in item 3 of the pharmaceutical composition. Item 5: The aforementioned chitinase-3-like protein 1-related disease is lung cancer metastasis, as described in item 4 of the pharmaceutical composition. Item 6: A diagnostic composition for chitinase-3-like protein 1-related disease comprising the antibody or antigen-binding fragment described in item 1 or 2. Item 7: The composition according to item 6, wherein the chitinase-3-like protein 1-related disease is cancer, cancer metastasis, arthritis, or dementia. Item 8: A diagnostic kit for chitinase-3-like protein 1-related disease comprising the composition described in item 6. Item 9: The aforementioned chitinase-3-like protein 1-related disease is cancer, cancer metastasis, arthritis, or dementia, as described in item 8 of the kit. Item 10: The steps include: contacting the antibody or antigen-binding fragment described in item 1 or 2 with a sample isolated from the test subject; The steps include measuring the complex of the antibody or its antigen-binding fragment formed by the aforementioned contact with the chitinase-3-like protein 1, A method for providing information for the diagnosis of chitinase-3-like protein 1-related diseases, including those involving this protein. Item 11: The information provision method described in item 10, wherein the chitinase-3-like protein 1-related disease is cancer, cancer metastasis, arthritis, or dementia. Item 12: A polynucleotide encoding the antibody or its antigen-binding fragment as described in item 1 or 2. Item 13: A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 81, the CDR2 code sequence of sequence number 82, and the CDR3 code sequence of sequence number 83, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 111, the CDR2 code sequence of sequence number 112, and the CDR3 code sequence of sequence number 113, A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 84, the CDR2 code sequence of sequence number 85, and the CDR3 code sequence of sequence number 86, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 114, the CDR2 code sequence of sequence number 115, and the CDR3 code sequence of sequence number 116. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 87, the CDR2 code sequence of sequence number 88, and the CDR3 code sequence of sequence number 89, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 117, the CDR2 code sequence of sequence number 118, and the CDR3 code sequence of sequence number 119. A variable region code sequence of the light chain including the CDR1 code sequence of SEQ ID NO: 90, the CDR2 code sequence of SEQ ID NO: 91, and the CDR3 code sequence of SEQ ID NO: 92, and a variable region code sequence of the heavy chain including the CDR1 code sequence of SEQ ID NO: 120, the CDR2 code sequence of SEQ ID NO: 121, and the CDR3 code sequence of SEQ ID NO: 122. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 93, the CDR2 code sequence of sequence number 94, and the CDR3 code sequence of sequence number 95, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 123, the CDR2 code sequence of sequence number 124, and the CDR3 code sequence of sequence number 125. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 96, the CDR2 code sequence of sequence number 97, and the CDR3 code sequence of sequence number 98, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 126, the CDR2 code sequence of sequence number 127, and the CDR3 code sequence of sequence number 128, A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 99, the CDR2 code sequence of sequence number 100, and the CDR3 code sequence of sequence number 101, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 129, the CDR2 code sequence of sequence number 130, and the CDR3 code sequence of sequence number 131. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 102, the CDR2 code sequence of sequence number 103, and the CDR3 code sequence of sequence number 104, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 132, the CDR2 code sequence of sequence number 133, and the CDR3 code sequence of sequence number 134. A variable region code sequence of the light chain including the CDR1 code sequence of SEQ ID NO: 105, the CDR2 code sequence of SEQ ID NO: 106, and the CDR3 code sequence of SEQ ID NO: 107, and a variable region code sequence of the heavy chain including the CDR1 code sequence of SEQ ID NO: 135, the CDR2 code sequence of SEQ ID NO: 136, and the CDR3 code sequence of SEQ ID NO: 137, or The polynucleotide described in item 12, comprising a light chain variable region coding sequence including the CDR1 coding sequence of SEQ ID NO: 108, the CDR2 coding sequence of SEQ ID NO: 109, and the CDR3 coding sequence of SEQ ID NO: 110, and a heavy chain variable region coding sequence including the CDR1 coding sequence of SEQ ID NO: 138, the CDR2 coding sequence of SEQ ID NO: 139, and the CDR3 coding sequence of SEQ ID NO: 140. Item 14: Includes the variable region code sequence of the light chain of sequence number 141 and the variable region code sequence of the heavy chain of sequence number 151. Includes the variable region code sequence of the light chain of sequence number 142 and the variable region code sequence of the heavy chain of sequence number 152. Includes the variable region code sequence of the light chain of sequence number 143 and the variable region code sequence of the heavy chain of sequence number 153. Includes the variable region code sequence of the light chain of sequence number 144 and the variable region code sequence of the heavy chain of sequence number 154. Includes the variable region coding sequence of the light chain of sequence number 145 and the variable region coding sequence of the heavy chain of sequence number 155. Includes the variable region coding sequence of the light chain of sequence number 146 and the variable region coding sequence of the heavy chain of sequence number 156. Includes the variable region code sequence of the light chain of sequence number 147 and the variable region code sequence of the heavy chain of sequence number 157. Includes the variable region code sequence of the light chain (SEQ ID NO: 148) and the variable region code sequence of the heavy chain (SEQ ID NO: 158). Including the variable region coding sequence of the light chain of SEQ ID NO: 149 and the variable region coding sequence of the heavy chain of SEQ ID NO: 159, or The polynucleotide described in item 13, comprising the variable region coding sequence of the light chain of sequence number 150 and the variable region coding sequence of the heavy chain of sequence number 160. Item 15: A vector containing the polynucleotides described in item 12. Item 16: Cells transformed with the vector described in item 15.

Claims

1. An anti-chitinase-3-like protein 1 antibody or its antigen-binding fragment for the prevention or treatment of lung cancer metastasis, A variable region of the light chain including CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 31, CDR2 of SEQ ID NO: 32, and CDR3 of SEQ ID NO:

33. A variable region of the light chain including CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6, and a variable region of the heavy chain including CDR1 of SEQ ID NO: 34, CDR2 of SEQ ID NO: 35, and CDR3 of SEQ ID NO:

36. A variable light chain region including CDR1 of SEQ ID NO: 7, CDR2 of SEQ ID NO: 8, and CDR3 of SEQ ID NO: 9, and a variable heavy chain region including CDR1 of SEQ ID NO: 37, CDR2 of SEQ ID NO: 38, and CDR3 of SEQ ID NO:

39. A variable light chain region including CDR1 of SEQ ID NO: 13, CDR2 of SEQ ID NO: 14, and CDR3 of SEQ ID NO: 15, and a variable heavy chain region including CDR1 of SEQ ID NO: 43, CDR2 of SEQ ID NO: 44, and CDR3 of SEQ ID NO:

45. A variable light chain region including CDR1 of SEQ ID NO: 16, CDR2 of SEQ ID NO: 17, and CDR3 of SEQ ID NO: 18, and a variable heavy chain region including CDR1 of SEQ ID NO: 46, CDR2 of SEQ ID NO: 47, and CDR3 of SEQ ID NO: 48, or An antibody or its antigen-binding fragment, comprising a variable light chain region including CDR1 of SEQ ID NO: 25, CDR2 of SEQ ID NO: 26, and CDR3 of SEQ ID NO: 27, and a variable heavy chain region including CDR1 of SEQ ID NO: 55, CDR2 of SEQ ID NO: 56, and CDR3 of SEQ ID NO:

57.

2. Including the variable region of the light chain of Sequence ID No. 61 and the variable region of the heavy chain of Sequence ID No. 71, Including the variable region of the light chain in Sequence ID No. 62 and the variable region of the heavy chain in Sequence ID No. 72, Including the variable region of the light chain in Sequence ID No. 63 and the variable region of the heavy chain in Sequence ID No. 73, Including the variable region of the light chain of Sequence ID No. 65 and the variable region of the heavy chain of Sequence ID No. 75, Including the variable region of the light chain in SEQ ID NO: 66 and the variable region of the heavy chain in SEQ ID NO: 76, or The antibody or antigen-binding fragment according to claim 1, comprising the variable light chain region of SEQ ID NO: 69 and the variable heavy chain region of SEQ ID NO:

79.

3. A pharmaceutical composition for the prevention or treatment of lung cancer metastasis, comprising the antibody or antigen-binding fragment described in claim 1 or 2.

4. A diagnostic composition for lung cancer metastasis comprising the antibody or antigen-binding fragment described in claim 1 or 2.

5. A diagnostic kit for lung cancer metastasis comprising the composition described in claim 4.

6. The steps of contacting the antibody or antigen-binding fragment according to claim 1 or 2 with a sample separated from the test subject, The steps include measuring the complex of the antibody or its antigen-binding fragment formed by the aforementioned contact with the chitinase-3-like protein 1, A method for providing information for the diagnosis of lung cancer metastasis, including the treatment of lung cancer.

7. A polynucleotide encoding the antibody or its antigen-binding fragment according to claim 1 or 2.

8. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 81, the CDR2 code sequence of sequence number 82, and the CDR3 code sequence of sequence number 83, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 111, the CDR2 code sequence of sequence number 112, and the CDR3 code sequence of sequence number 113, A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 84, the CDR2 code sequence of sequence number 85, and the CDR3 code sequence of sequence number 86, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 114, the CDR2 code sequence of sequence number 115, and the CDR3 code sequence of sequence number 116. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 87, the CDR2 code sequence of sequence number 88, and the CDR3 code sequence of sequence number 89, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 117, the CDR2 code sequence of sequence number 118, and the CDR3 code sequence of sequence number 119. A variable region code sequence of the light chain including the CDR1 code sequence of sequence number 93, the CDR2 code sequence of sequence number 94, and the CDR3 code sequence of sequence number 95, and a variable region code sequence of the heavy chain including the CDR1 code sequence of sequence number 123, the CDR2 code sequence of sequence number 124, and the CDR3 code sequence of sequence number 125. A variable region code sequence of the light chain including the CDR1 code sequence of SEQ ID NO: 96, the CDR2 code sequence of SEQ ID NO: 97, and the CDR3 code sequence of SEQ ID NO: 98, and a variable region code sequence of the heavy chain including the CDR1 code sequence of SEQ ID NO: 126, the CDR2 code sequence of SEQ ID NO: 127, and the CDR3 code sequence of SEQ ID NO: 128, or The polynucleotide according to claim 7, comprising a light chain variable region coding sequence including the CDR1 coding sequence of SEQ ID NO: 105, the CDR2 coding sequence of SEQ ID NO: 106, and the CDR3 coding sequence of SEQ ID NO: 107, and a heavy chain variable region coding sequence including the CDR1 coding sequence of SEQ ID NO: 135, the CDR2 coding sequence of SEQ ID NO: 136, and the CDR3 coding sequence of SEQ ID NO:

137.

9. A sequence including the variable region code sequence of the light chain of sequence number 141 and the variable region code sequence of the heavy chain of sequence number 151. A sequence including the variable region code sequence of the light chain of sequence number 142 and the variable region code sequence of the heavy chain of sequence number 152. A sequence including the variable region code sequence of the light chain of sequence number 143 and the variable region code sequence of the heavy chain of sequence number 153. A sequence including the variable region code sequence of the light chain of sequence number 145 and the variable region code sequence of the heavy chain of sequence number 155. A sequence including the variable region code sequence of the light chain of sequence number 146 and the variable region code sequence of the heavy chain of sequence number 156, or The polynucleotide according to claim 8, comprising the variable region coding sequence of the light chain of SEQ ID NO: 149 and the variable region coding sequence of the heavy chain of SEQ ID NO:

159.

10. A vector comprising the polynucleotide described in claim 7.

11. Cells transformed with the vector according to claim 10.

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