Anti-TL1A antibodies or antigen-binding fragments thereof and uses thereof

Abstract

The invention discloses an anti-TL1A antibody or an antigen binding fragment thereof and application of the anti-TL1A antibody or the antigen binding fragment thereof. The anti-TL1A antibody or the antigen binding fragment thereof comprises HCDR1: X1YX2MH, hCDR2: X < 3 > X < 4 > NPYX < 5 > X < 6 > X < 7 > TX < 8 > YX < 9 > X < 10 > KFKG; hCDR3: X < 11 > X < 12 > X < 13 > X < 14 > X < 15 > X < 16 > X < 17 > X < 18 > X < 19 > Y; lCDR1: X < 20 > ASX < 21 > X < 22 > VX < 23 > X < 24 > X < 25 > X < 26 > X < 27 >; lCDR2: X < 28 > X < 29 > X < 30 > X < 31 > X < 32 > X < 33 > X < 34 >; and LCDR3: QQX35SSX36PX37T, and LCDR3: The anti-TL1A antibody or the antigen binding fragment thereof provided by the invention has TL1A binding affinity, especially can be specifically bound with TL1A, and can be used for detecting TL1A; the compound also can block the activity of a TL1A activated transcription factor NF [kappa] B, has an effect of inhibiting IFN-gamma, and can be used for preventing and / or treating TL1A mediated related diseases.

Description

Technical Field

[0001] This application belongs to the technical field of biopharmaceuticals, and specifically relates to anti-TL1A antibodies or antigen-binding fragments thereof and their uses. More specifically, it relates to anti-TL1A antibodies or antigen-binding fragments thereof, nucleic acid molecules, expression vectors, recombinant cells, conjugates, reagents or kits, pharmaceutical compositions and their uses, and methods for detecting TL1A. Background Art

[0002] The tumor necrosis factor (TNF) and TNF-receptor (TNFR) superfamilies, namely TNFSF and TNFRSF, play a key role in the establishment and function of the immune system. TL1A is a TNF-like cytokine, which is a type II membrane protein encoded by the TNFSF15 gene. TL1A can exist in a membrane-bound form or a soluble form, and both forms have biological activities and play an immunomodulatory function. TL1A and its functional receptor death receptor 3 (DR3, also known as TNFRSF25) are the molecules with the highest homology to TNFR1 among the TNFRSF members. The TL1A / DR3 cytokine system is a key factor in mucosal immunity and intestinal homeostasis. Preclinical studies have found that TL1A plays a key and multifaceted role in the immune response during the inflammatory process, which reveals the potential of targeting TL1A for the treatment of inflammatory bowel disease (IBD).

[0003] In a steady-state environment or various inflammatory environments, the interaction between TL1A and its functional receptor DR3 deeply affects intestinal mucosal immunity; many genetic studies have demonstrated that TL1A and DcR3 (TNFRSF6B, decoy receptor 3) have genetic polymorphisms, and they may be either protective factors or risk factors; after TL1A binds to DR3, the TRADD signal is activated, causing the cell to activate the NFκB signaling pathway through TRAF2 on the one hand, leading to the expression of a series of pro-inflammatory factors; on the other hand, the Caspase-3 / 7 apoptosis signaling pathway is activated via FADD inside the cell, initiating apoptosis. Thus, blocking the TL1A signaling pathway can reduce the inflammatory response and achieve a therapeutic effect.

[0004] The antibody PF-06480605, which is advancing relatively fast at present, is an anti-TL1A monoclonal antibody that can block the TL1A signaling pathway and has shown good safety and tolerance in clinical trials. It has demonstrated significant efficacy in the 12-week treatment of ulcerative colitis (UC). Another blocking anti-TL1A monoclonal antibody, PRA023, successfully reached the primary endpoint of clinical remission at the 12th week in the clinical trial of moderate to severe ulcerative colitis. These studies all support that TL1A is a potential target for the treatment of IBD. Therefore, it is very important to develop a novel anti-TL1A antibody or its antigen-binding fragment. SUMMARY OF THE INVENTION

[0005] This application aims to solve at least one of the technical problems existing in the prior art to at least a certain extent. For this purpose, this application provides an anti-TL1A antibody or its antigen-binding fragment.

[0006] In a first aspect of the present application, the present application provides an anti-TL1A antibody or an antigen-binding fragment thereof. According to an embodiment of the present application, the anti-TL1A antibody or an antigen-binding fragment thereof includes HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3; the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by any one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by any one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ IDNO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ IDNO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42. The anti-TL1A antibody or an antigen-binding fragment thereof of the present application has a binding affinity for TL1A, especially can specifically bind to TL1A, and can be used for detecting TL1A; it can also block the activity of TL1A-activated transcription factor NFκB, has an inhibitory effect on IFN-γ, and can be used for preventing and / or treating related diseases mediated by TL1A.

[0007] In the second aspect of the present application, the present application provides an anti-TL1A antibody or an antigen-binding fragment thereof. According to an embodiment of the present application, the anti-TL1A antibody or an antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3; HCDR1: X1YX2MH, wherein X1 is S, G, R or V, and X2 is I or T; HCDR2: X3X4NPYX5X6X7TX8YX9X 10 KFKG, wherein X3 is Y or L, X4 is V or I, X5 is N or S, X6 is D or G, X7 is V or G, X8 is N, T or K, X9 is I or N, X 10 is E or Q; HCDR3: X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 Y, wherein X 11 is Y, V or H, X 12 is Y, Q or R, X 13 is Y or L, X 14 is G or R, X 15 is N, Y, H, A, R, E, M or P, X 16 is P, D, V, L or S, X 17 is G or W, X 18 is F, L, M or Y, X 19 is A or D; LCDR1: X 20 ASX 21 X 22 VX 23 X 24 X 25 X 26 X 27 wherein X 20 is K or S, X 21 is Q or S, X 22 is D or S, X 23 is G, T or S, X 24 is T, Y or A, X 25 is M or A, X 26 is V or H, X 27 is A or empty; LCDR2: X 28 X 29 X 30 X 31 X 32 X 33 X 34 wherein X 28 is W or D, X29 is T or A, X 30 is S or A, X 31 is T or K, X 32 is R or L, X 33 is H or A, X 34 is T or S; LCDR3: QQX 35 SSX 36 PX 37 T, wherein, X 35 is Y, W or H, X 36 is Y, D or S, X 37 is Y or W. The anti-TL1A antibody or its antigen-binding fragment of the present application has TL1A-binding affinity, especially can specifically bind to TL1A, can be used for detecting TL1A; can also block the activity of TL1A-activated transcription factor NFκB, has the effect of inhibiting IFN-γ, and can be used for preventing and / or treating TL1A-mediated related diseases.

[0008] In the third aspect of the present application, the present application provides a nucleic acid molecule. According to an embodiment of the present application, the nucleic acid molecule encodes the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect.

[0009] In the fourth aspect of the present application, the present application provides an expression vector. According to an embodiment of the present application, the expression vector carries the nucleic acid molecule described in the third aspect.

[0010] In the fifth aspect of the present application, the present application provides a recombinant cell. According to an embodiment of the present application, the recombinant cell comprises carrying the nucleic acid molecule described in the third aspect or the expression vector described in the fourth aspect; or expressing the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect.

[0011] In the sixth aspect of the present application, the present application provides a conjugate. According to an embodiment of the present application, the conjugate comprises the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect; and a conjugate moiety, the conjugate moiety being linked to the anti-TL1A antibody or its antigen-binding fragment. The conjugate of the present application has TL1A-binding affinity and can be used for detecting TL1A, or for preventing and / or treating TL1A-mediated related diseases.

[0012] In the seventh aspect of the present application, the present application provides a reagent or a kit. According to an embodiment of the present application, the reagent or the kit comprises the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the nucleic acid molecule described in the third aspect, the expression vector described in the fourth aspect, the recombinant cell described in the fifth aspect or the conjugate described in the sixth aspect. The kit of the present application has TL1A-binding affinity and can effectively detect TL1A.

[0013] In the eighth aspect of the present application, a pharmaceutical composition is provided. According to an embodiment of the present application, the pharmaceutical composition comprises the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the nucleic acid molecule described in the third aspect, the expression vector described in the fourth aspect, the recombinant cell described in the fifth aspect, or the conjugate described in the sixth aspect. The pharmaceutical composition of the present application has TL1A-binding affinity and can effectively prevent and / or treat TL1A-mediated related diseases.

[0014] In the ninth aspect of the present application, there is provided the use of the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the nucleic acid molecule described in the third aspect, the expression vector described in the fourth aspect, the recombinant cell described in the fifth aspect, the conjugate described in the sixth aspect, or the pharmaceutical composition described in the seventh aspect in the preparation of a multispecific antibody, a fusion protein, a drug or a kit, or a medicament.

[0015] In the tenth aspect of the present application, a method for detecting TL1A is provided. According to an embodiment of the present application, the method comprises: contacting a sample to be detected with the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the conjugate described in the sixth aspect, or the reagent or kit described in the seventh aspect to form an immune complex. As known from the foregoing, the anti-TL1A antibody or its antigen-binding fragment, conjugate, reagent or kit all have TL1A-binding affinity. Thus, the anti-TL1A antibody or its antigen-binding fragment, conjugate, reagent or kit can be effectively used to detect TL1A, especially for in vitro detection (such as detection for non-disease diagnosis and treatment purposes), and has the advantages of high detection accuracy and the like.

[0016] The additional aspects and advantages of the present application will be partly given in the following description, partly become apparent from the following description, or be learned through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above and / or additional aspects and advantages of the present application will become apparent and be readily understood from the description of the embodiments in conjunction with the following drawings, wherein:

[0018] Figure 1 Blocking ability of different anti-TL1A antibodies in Example 4 of the present application on human TL1A-activated NFκB signaling pathway;

[0019] Figure 2 Blocking ability of antibody HC503H6M in Example 10 of the present application on human TL1A-activated NFκB signaling pathway;

[0020] Figure 3Solubility results of antibody HC503H6M in Example 12 of the present application;

[0021] Figure 4 Ability of each antibody in Example 13 of the present application to block the ability of TL1A and IL12 / 18 to co-stimulate human PBMC to produce IFN-γ. Detailed implementation manners

[0022] The embodiments of the present application are described in detail below. The embodiments described below are exemplary and are only used to explain the present application and should not be construed as a limitation to the present application.

[0023] It should be noted that the terms "first" and "second" are only used for descriptive purposes and should not be construed as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. Further, in the description of the present application, unless otherwise stated, the meaning of "a plurality" is two or more.

[0024] Detailed description of the present application

[0025] Definitions and general terms

[0026] In this document, the term "comprising" or "including" is an open expression, that is, it includes the content specified in the present application, but does not exclude other aspects of the content.

[0027] In this document, the terms "optionally", "optional" or "option" generally mean that the subsequent events or conditions may or may not occur, and this description includes the cases where such events or conditions occur, as well as the cases where such events or conditions do not occur.

[0028] In this document, the term "fragment" refers to a target protein or polypeptide, and a target protein or polypeptide with an N-terminal (N-terminus) or C-terminal (C-terminus) truncation, and / or internal deletion.

[0029] To make it easier to understand the present application, certain technical and scientific terms are specifically defined below. Unless otherwise clearly defined elsewhere in this document, all other technical and scientific terms used herein have the meanings commonly understood by those of ordinary skill in the art to which the present application pertains. The abbreviations of amino acid residues are the standard 3-letter and / or 1-letter codes used in the art to refer to one of the 20 common L-amino acids.

[0030] The antibodies or antigen-binding fragments described in the present application are generally prepared by biosynthetic methods. Based on the nucleotide sequences described in the present application, those skilled in the art can conveniently obtain the encoding nucleic acids of the present application by various known methods. These methods include, for example, but are not limited to: PCR, DNA chemical synthesis, etc. For specific methods, reference can be made to J. Sambrook, "Molecular Cloning: A Laboratory Manual". As an embodiment of the present application, the encoding nucleic acid sequence of the present application can be constructed by segmentally synthesizing the nucleotide sequence and then performing overlap extension PCR. Among them, the antibody or antigen fragment is numbered and defined using the Kabat numbering system.

[0031] As used herein, the term "conservative modified form of an amino acid sequence" refers to an amino acid modification that does not significantly affect or alter the binding properties of an antibody comprising the amino acid sequence, and such modifications include amino acid substitutions, additions, and deletions. The modifications can be introduced into the antibodies of the present application by standard techniques such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are substitutions in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been identified in the art. These families include amino acids with basic side chains (such as lysine, arginine, histidine), amino acids with acidic side chains (such as aspartic acid, glutamic acid), amino acids with uncharged polar side chains (such as glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), amino acids with nonpolar side chains (such as alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), amino acids with β-branched side chains (such as threonine, valine, isoleucine), and amino acids with aromatic side chains (such as tyrosine, phenylalanine, tryptophan, histidine).

[0032] As used herein, the terms "identity", "homology", or "similarity" are used to describe an amino acid sequence or a nucleic acid sequence relative to a reference sequence, and refer to the percentage of identical amino acids or nucleotides between two amino acid sequences or nucleic acid sequences determined by conventional methods, see, for example, Ausubel et al., eds. (1995), Current Protocols in Molecular Biology, Chapter 19 (Greene Publishing and Wiley-Interscience, New York); and the ALIGN program (Dayhoff (1978), Atlas of Protein Sequence and Structure 5: Suppl. 3 (National Biomedical Research Foundation, Washington, D.C.)). There are many algorithms for aligning sequences and determining sequence identity, including, the homology alignment algorithm of Needleman et al. (1970) J. Mol. Biol. 48: 443; the local homology algorithm of Smith et al. (1981) Adv. Appl. Math. 2: 482; the similarity search method of Pearson et al. (1988) Proc. Natl. Acad. Sci. 85: 2444; the Smith-Waterman algorithm (Meth. Mol. Biol. 70: 173-187 (1997); and the BLASTP, BLASTN, and BLASTX algorithms (see Altschul et al. (1990) J. Mol. Biol. 215: 403-410). Computer programs utilizing these algorithms are also available and include, but are not limited to: ALIGN or Megalign (DNASTAR) software, or WU-BLAST-2 (Altschul et al., Meth. Enzym., 266: 460-480 (1996)); or GAP, BESTFIT, BLAST Altschul et al., supra, FASTA, and TFASTA, available in the Genetics Computing Group (GCG) package, version 8, Madison, Wisconsin, USA; and CLUSTAL in the PC / Gene program provided by Intelligenetics, Mountain View, California.

[0033] As used herein, the term "at least 80% identity" refers to at least 80% identity with each reference sequence, which can be 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% identity.

[0034] As used herein, the term "at least 90% identity" refers to at least 90% identity with each reference sequence, which can be 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% identity.

[0035] As used herein, the term "fusion protein" refers to a novel protein formed by the fusion of at least two proteins or polypeptides. Usually, the above fusion operation can be achieved by techniques such as genetic engineering. For example, the expression product after recombination of two genes obtained by DNA recombination technology. As used herein, it refers to the state where an anti-TL1A antibody or its antigen-binding fragment is in a fused state with a bioactive protein or its fragment.

[0036] As used herein, the term "expression vector" generally refers to a nucleic acid molecule that can self-replicate after being inserted into a suitable host. The nucleic acid molecule contains a nucleotide sequence capable of expressing the target protein, and can transfer the nucleic acid molecule into host cells and / or between host cells. The expression vector can include vectors mainly used for inserting DNA or RNA into cells, vectors mainly used for replicating DNA or RNA, and vectors mainly used for the transcription and / or translation of DNA or RNA. The expression vector also includes vectors having multiple above functions. The expression vector can be a polynucleotide that can be transcribed and translated into a polypeptide when introduced into a suitable host cell. Usually, by culturing a suitable host cell containing the expression vector, the expression vector can produce the desired expression product.

[0037] As used herein, the term "recombinant cell" generally refers to a cell obtained by modifying or recombining the genetic material of a recipient cell (or host cell) using genetic engineering techniques or cell fusion techniques, and having unique traits with stable inheritance. Among them, the term "host cell" refers to a prokaryotic cell or a eukaryotic cell that can introduce a recombinant expression vector. The terms "transformed" or "transfected" used herein refer to the introduction of nucleic acids (such as expression vectors) into cells by various techniques known in the art. Suitable host cells can be transformed or transfected with the DNA sequence of the present application and can be used for the expression and / or secretion of the target protein. Examples of suitable host cells that can be used in the present application include immortalized hybridoma cells, NS / 0 myeloma cells, 293 cells, Chinese hamster ovary (CHO) cells, HeLa cells, Cap cells (human amniotic fluid-derived cells), and CoS cells.

[0038] As used herein, the term "pharmaceutical composition" generally refers to a unit dosage form and can be prepared by any of the methods well known in the pharmaceutical art. All methods include the step of combining an active ingredient with a carrier that constitutes one or more accessory ingredients. Generally, the composition is prepared by uniformly and sufficiently combining the active antibody or antigen-binding fragment with a liquid carrier, a finely divided solid carrier, or both.

[0039] As used herein, the term "pharmaceutically acceptable excipient" can include any solvent, solid excipient, diluent, or other liquid excipient, etc., suitable for a particular target dosage form. Their use is also contemplated by the present application, except to the extent that any conventional excipient is incompatible with the antibody or antigen-binding fragment of the present application, such as any adverse biological effect produced or any interaction with any other component of the pharmaceutically acceptable composition in a harmful manner.

[0040] As used herein, the term "administering" refers to introducing a predetermined amount of a substance into a patient by a suitable means. The antibody or antigen-binding fragment, bispecific antibody, or pharmaceutical composition of the present application can be administered by any common route as long as it can reach the intended tissue. Various modes of administration are contemplated, including intraperitoneal, intravenous, intramuscular, subcutaneous injection, etc., but the present application is not limited to the exemplified modes of administration. Preferably, the composition of the present application is administered by intravenous injection or subcutaneous injection.

[0041] As used herein, the term "treatment" refers to obtaining a desired pharmacological and / or physiological effect. The effect can be prophylactic in terms of completely or partially preventing a disease or its symptoms, and / or therapeutic in terms of partially or completely curing a disease and / or an adverse effect caused by the disease. "Treatment" as used herein covers diseases in mammals, particularly humans, including: (a) preventing the occurrence of a disease or disorder in an individual who is susceptible to the disease but has not been diagnosed with the disease; (b) inhibiting a disease, such as arresting the development of the disease; or (c) alleviating a disease, such as reducing the symptoms associated with the disease. "Treatment" as used herein covers any administration of a drug or antibody or antigen-binding fragment to an individual to treat, cure, alleviate, improve, reduce, or inhibit a disease in the individual, including but not limited to administering a drug containing the antibody or antigen-binding fragment described herein to an individual in need thereof.

[0042] Detailed description of the anti-TL1A antibody or its antigen-binding fragment of the present application and its uses

[0043] The present application provides an anti-TL1A antibody or its antigen-binding fragment, a nucleic acid molecule, an expression vector, a recombinant cell, a conjugate, a reagent or a kit, a pharmaceutical composition, and their uses, as well as a method for detecting TL1A. The following will describe them in detail respectively.

[0044] Anti-TL1A antibody or its antigen-binding fragment

[0045] In the first aspect of the present application, the present application provides an anti-TL1A antibody or its antigen-binding fragment. According to an embodiment of the present application, the anti-TL1A antibody or its antigen-binding fragment includes HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3; the HCDR1, HCDR2, HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, HCDR3 of the heavy chain variable region defined by any one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41; the LCDR1, LCDR2, LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, LCDR3 of the light chain variable region defined by any one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42.

[0046] The anti-TL1A antibody or antigen-binding fragment thereof of the present application has TL1A binding affinity, especially can specifically bind to TL1A, and can be used for detecting TL1A; it can also block the activity of TL1A-activated transcription factor NFκB, has the effect of inhibiting IFN-γ, and can be used for preventing and / or treating related diseases mediated by TL1A.

[0047] According to an embodiment of the present application, the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 1; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 2; or

[0048] the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 3; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 4; or

[0049] the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 5; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 6; or

[0050] the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 7; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 8; or

[0051] the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 9; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 10; or

[0052] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 10; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 12; or

[0053] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 13; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 14; or

[0054] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 15; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 16; or

[0055] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 17; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 18; or

[0056] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 19; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 20; or

[0057] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 21; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 22; or

[0058] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 23; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 24; or

[0059] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 25; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 26; or

[0060] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 27; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 28; or

[0061] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 29; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 30; or

[0062] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 31; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 32; or

[0063] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 33; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 34; or

[0064] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 35; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 36; or

[0065] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 37; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 38; or

[0066] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 39; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 40; or

[0067] The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 41; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 42.

[0068] According to an embodiment of the present application, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are defined by the Kabat, Chothia, AbM, Contact, or IMGT system.

[0069] According to an embodiment of the present application, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are defined by the same system.

[0070] In a second aspect of the present application, the present application provides an anti-TL1A antibody or an antigen-binding fragment thereof. According to an embodiment of the present application, the anti-TL1A antibody or the antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3;

[0071] HCDR1: X1YX2MH, where X1 is S, G, R or V, and X2 is I or T;

[0072] HCDR2: X3X4NPYX5X6X7TX8YX9X 10 KFKG, where X3 is Y or L, X4 is V or I, X5 is N or S, X6 is D or G, X7 is V or G, X8 is N, T or K, X9 is I or N, X 10 is E or Q;

[0073] HCDR3: X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 Y, where X 11 is Y, V or H, X 12 is Y, Q or R, X 13 is Y or L, X 14 is G or R, X 15 is N, Y, H, A, R, E, M or P, X 16 is P, D, V, L or S, X 17 is G or W, X 18 is F, L, M or Y, X 19 is A or D;

[0074] LCDR1: X 20 ASX 21 X 22 VX 23 X 24 X 25 X 26 X 27 where X 20 is K or S, X 21 is Q or S, X 22 is D or S, X 23 is G, T or S, X 24 is T, Y or A, X 25 is M or A, X 26 is V or H, X 27 is A or empty;

[0075] LCDR2: X 28 X 29 X 30 X 31 X 32 X 33 X 34 where X 28 is W or D, X29 is T or A, X 30 is S or A, X 31 is T or K, X 32 is R or L, X 33 is H or A, X 34 is T or S;

[0076] LCDR3: QQX 35 SSX 36 PX 37 T, wherein, X 35 is Y, W or H, X 36 is Y, D or S, X 37 is Y or W.

[0077] The anti-TL1A antibody or antigen-binding fragment thereof of the present application has TL1A binding affinity, in particular, it can specifically bind to TL1A and can be used for detecting TL1A; it can also block the activity of TL1A-activated transcription factor NFκB, has the effect of inhibiting IFN-γ, and can be used for preventing and / or treating TL1A-mediated related diseases.

[0078] As used herein, the term "antigen-binding fragment" refers to a fragment that contains part or all of an antibody, lacks at least some of the amino acids present in the full-length chain but still has the performance activity of specifically binding to an antigen. For example, the fragment may contain part or all of the antibody CDR. Such fragments are biologically active because they bind to the antigen and can compete with other antigen-binding molecules (including intact antibodies) for binding to a given epitope. Such fragments are selected from Fab, Fv, or scFv. Such fragments can be produced by recombinant nucleic acid technology or can be produced by enzymatic cleavage or chemical cleavage of antigen-binding molecules (including intact antibodies).

[0079] As used herein, the term "antibody" is used in the broadest sense and may include full-length monoclonal antibodies, multispecific antibodies (abbreviated as polyclonal antibodies), and chimeric antibodies. The specific structure is not limited as long as they exhibit the required biological activity. It generally includes a light chain with a relatively low molecular weight and a heavy chain with a relatively high molecular weight. The antibody molecule is formed by the heavy chain (H chain) and the light chain (L chain) linked by disulfide bonds. Among them, the amino-terminal (N-terminal) amino acid sequence of the peptide chain varies greatly and is called the variable region (V region); the carboxyl-terminal (C-terminal) is relatively stable and varies little, and is called the constant region (C region). The V regions of the L chain and the H chain are called VL and VH, respectively.

[0080] In this text, the heavy chain complementarity determining regions (CDRs of the heavy chain variable region) are denoted by "HCDRs" or "HCDR", which include HCDR1 (also known as CDR-H1), HCDR2 (also known as CDR-H2), and HCDR3 (also known as CDR-H3); the light chain complementarity determining regions (CDRs of the light chain variable region) are denoted by "LCDRs" or "LCDR", which include LCDR1 (also known as CDR-L1), LCDR2 (also known as CDR-L2), and LCDR3 (also known as CDR-L3). Commonly used CDR definition schemes in the art include: Kabat definition, Chothia definition, IMGT definition, Contact definition, and AbM definition.

[0081] However, the above-mentioned CDRs of the heavy chain variable region (amino acid sequences shown in SEQ ID NO: 1-3, or SEQ ID NO: 7-9) and the CDRs of the light chain variable region (amino acid sequences shown in SEQ ID NO: 4-6, or SEQ ID NO: 10-12) in this application are numbered and defined using the Kabat numbering system. A person of ordinary skill in the art can fully convert the CDR sequences of the heavy chain variable region and the light chain variable region obtained according to the Kabat numbering in this application into "HCDRs" and / or "LCDRs" under other numbering systems (including but not limited to IMGT, Kabat, Chothia, Contact). The CDRs determined according to other rules publicly available in the art based on the heavy chain variable region and the light chain variable region disclosed in this application also fall within the protection scope of this application.

[0082] As described herein, the "Kabat definition" refers to the definition system described by Kabat et al., U.S. Dept. of Health and Human Services, "Sequence of Proteins of Immunological Interest" (1983). The "IMGT" definition refers to the definition system described by Lefranc et al., "Dev. Comp. Immunol.", 2003, 27: 55-77. For the "Chothia definition", see Chothia et al., J Mol Biol 196: 901-917 (1987). For the "Contact definition", see MacCallum et al., 1996, "Molecular Biology" 262: 732-745. The "AbM definition" refers to the CDRs defined by the "AbM" antibody modeling software of Oxford Molecular.

[0083] According to the embodiments of this application, in the said HCDR1, X1 is G, R, or V, and X2 is T; or

[0084] X1 is S and X2 is I.

[0085] According to an embodiment of the present application, in the HCDR2, X3 is L, X4 is I, X5 is S, X6 is G, X7 is V, X8 is T, X9 is N, X 10 is Q; or

[0086] X3 is Y, X4 is V or I, X5 is N, X6 is D, X7 is G, X8 is N or K, X9 is I, X 10 is E.

[0087] According to an embodiment of the present application, in the HCDR3, X 11 is V, X 12 is Q or R, X 13 is Y or L, X 14 is R, X 15 is Y, A, R, E, M or P, X 16 is D, V, L or S, X 17 is G, X 18 is L, M or Y, X 19 is A or D; or

[0088] X 11 is Y or H, X 12 is Y, X 13 is Y or L, X 14 is G, X 15 is N or H, X 16 is P, X 17 is W, X 18 is F, X 19 is A.

[0089] According to an embodiment of the present application, in the LCDR1, X 20 is S, X 21 is S, X 22 is S, X 23 is T, X 24 is Y, X 25 is M, X 26 is H, X 27 is empty; or

[0090] X 20 is K, X 21 is Q, X 22 is D, X 23 is G or S, X 24 is T or A, X 25 is A, X 26 is V, X 27 is A.

[0091] In an embodiment of the present application, in the LCDR2, X 28 is D, X 29 is T, X 30 is S, X 31 is K, X 32 is L, X 33 is A, X 34 is S; or

[0092] X 28 is W, X 29 is T or A, X 30 is S or A, X 31 is T, X 32 is R, X 33 is H, X 34 is T.

[0093] In an embodiment of the present application, in the LCDR3, X 35 is W, X 36 is D, X 37 is Y; or

[0094] X 35 is Y or H, X 36 is Y or S, X 37 is Y or W.

[0095] In an embodiment of the present application, HCDR1: X1YTMH, where X1 is G, R or V;

[0096] HCDR2: LINPYSGVTTYNQKFKG;

[0097] HCDR3: VX 12 X 13 RX 15 X 16 GX 18 X 19 Y, where X 12 is Q or R, X 13 is Y or L, X 15 is Y, A, R, E, M or P, X 16 is D, V, L or S, X 18 is L, M or Y, X 19 is A or D;

[0098] LCDR1: SASSSVTYMH;

[0099] LCDR2: DTSKLAS;

[0100] LCDR3: QQWSSDPYT.

[0101] According to an embodiment of the present application, the anti-TL1A antibody or antigen-binding fragment thereof described in the above first aspect and second aspect may further include at least one of the following technical features:

[0102] According to an embodiment of the present application, the anti-TL1A antibody or antigen-binding fragment thereof includes:

[0103] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO: 43, an HCDR2 shown by the amino acid sequence of SEQ ID NO: 44, an HCDR3 shown by the amino acid sequence of SEQ ID NO: 45, and an LCDR1 shown by the amino acid sequence of SEQ ID NO: 46, an LCDR2 shown by the amino acid sequence of SEQ ID NO: 47, and an LCDR3 shown by the amino acid sequence of SEQ ID NO: 48; or

[0104] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO: 49, an HCDR2 shown by the amino acid sequence of SEQ ID NO: 50, an HCDR3 shown by the amino acid sequence of SEQ ID NO: 51, and an LCDR1 shown by the amino acid sequence of SEQ ID NO: 52, an LCDR2 shown by the amino acid sequence of SEQ ID NO: 53, and an LCDR3 shown by the amino acid sequence of SEQ ID NO: 54; or

[0105] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO: 43, an HCDR2 shown by the amino acid sequence of SEQ ID NO: 55, an HCDR3 shown by the amino acid sequence of SEQ ID NO: 56, and an LCDR1 shown by the amino acid sequence of SEQ ID NO: 57, an LCDR2 shown by the amino acid sequence of SEQ ID NO: 58, and an LCDR3 shown by the amino acid sequence of SEQ ID NO: 59; or

[0106] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO: 60, an HCDR2 shown by the amino acid sequence of SEQ ID NO: 50, an HCDR3 shown by the amino acid sequence of SEQ ID NO: 51, and an LCDR1 shown by the amino acid sequence of SEQ ID NO: 52, an LCDR2 shown by the amino acid sequence of SEQ ID NO: 53, and an LCDR3 shown by the amino acid sequence of SEQ ID NO: 54; or

[0107] having an HCDR1 shown by the amino acid sequence of SEQ ID NO:61, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:51, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0108] having an HCDR1 shown by the amino acid sequence of SEQ ID NO:49, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:62, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0109] having an HCDR1 shown by the amino acid sequence of SEQ ID NO:49, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:63, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0110] having an HCDR1 shown by the amino acid sequence of SEQ ID NO:49, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:64, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0111] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO:49, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:65, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0112] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO:49, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:66, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0113] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO:49, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:67, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0114] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO:60, an HCDR2 shown by the amino acid sequence of SEQ ID NO:50, an HCDR3 shown by the amino acid sequence of SEQ ID NO:68, and an LCDR1 shown by the amino acid sequence of SEQ ID NO:52, an LCDR2 shown by the amino acid sequence of SEQ ID NO:53, an LCDR3 shown by the amino acid sequence of SEQ ID NO:54; or

[0115] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO: 60, an HCDR2 shown by the amino acid sequence of SEQ ID NO: 50, an HCDR3 shown by the amino acid sequence of SEQ ID NO: 69, and an LCDR1 shown by the amino acid sequence of SEQ ID NO: 52, an LCDR2 shown by the amino acid sequence of SEQ ID NO: 53, and an LCDR3 shown by the amino acid sequence of SEQ ID NO: 54; or

[0116] Having an HCDR1 shown by the amino acid sequence of SEQ ID NO: 60, an HCDR2 shown by the amino acid sequence of SEQ ID NO: 50, an HCDR3 shown by the amino acid sequence of SEQ ID NO: 65, and an LCDR1 shown by the amino acid sequence of SEQ ID NO: 52, an LCDR2 shown by the amino acid sequence of SEQ ID NO: 53, and an LCDR3 shown by the amino acid sequence of SEQ ID NO: 54.

[0117] As used herein, "shown by the amino acid sequence of SEQ ID NO: A" or "amino acid sequence as shown by SEQ ID NO: A" in the present application includes the amino acid sequence of SEQ ID NO: A or the amino acid sequence of a conservative modification form of SEQ ID NO: A, both of which are within the protection scope of the present application. Exemplarily, "HCDR1 shown by the amino acid sequence of SEQ ID NO: 43" means that HCDR1 is the amino acid sequence of SEQ ID NO: 43 or the amino acid sequence of a conservative modification form of SEQ ID NO: 43 (for example, an amino acid sequence having 1 to 2 amino acid differences from SEQ ID NO: 43), both of which are within the protection scope of the present application; the same as "amino acid sequences of SEQ ID NOs: 44 to 69".

[0118] As used herein, the term "or an amino acid sequence having 1 to 2 amino acid differences therefrom" means having 1 or 2 amino acid differences compared with the foregoing amino acid sequence, and such differences do not significantly affect or change the binding properties of the antibody containing the amino acid sequence, and such modifications include amino acid substitution, addition, and deletion.

[0119] Among them, the amino acid sequences shown by SEQ ID NOs: 43 to 69 are shown in the following table:

[0120]

[0121]

[0122]

[0123] According to an embodiment of the present application, the anti-TL1A antibody or its antigen-binding fragment comprises a heavy chain framework region and / or a light chain framework region.

[0124] According to an embodiment of the present application, at least a part of the heavy chain framework region and / or the light chain framework region is derived from at least one of a murine antibody, a primate antibody, a bovine antibody, a horse antibody, a dairy cow antibody, a porcine antibody, a sheep antibody, a goat antibody, a dog antibody, a cat antibody, a rabbit antibody, a camel antibody, a donkey antibody, a deer antibody, a mink antibody, a chicken antibody, a duck antibody, a goose antibody, a turkey antibody, a fighting chicken antibody or a mutant thereof.

[0125] According to an embodiment of the present application, at least a part of the heavy chain framework region and / or the light chain framework region is derived from at least one of a rabbit antibody or a mutant thereof, a murine antibody or a mutant thereof, and a human antibody or a mutant thereof.

[0126] According to an embodiment of the present application, the heavy chain framework region and / or the light chain framework region is derived from a human antibody.

[0127] Exemplarily, as shown by the HC503H6M antibody, the framework regions are selected from HFR1 shown by the amino acids of SEQ ID NO:72, HFR2 shown by the amino acids of SEQ ID NO:73, HFR3 shown by the amino acids of SEQ ID NO:74, HFR4 shown by the amino acids of SEQ ID NO:75, and LFR1 shown by the amino acids of SEQ ID NO:76, LFR2 shown by the amino acids of SEQ ID NO:77, LFR3 shown by the amino acids of SEQ ID NO:78, LFR4 shown by the amino acids of SEQ ID NO:79.

[0128] EVQLVQSGAEVKKPGASVKVSCKASGYTFT(SEQ ID NO:72);

[0129] WVRQAPGQGLEWMG(SEQ ID NO:73);

[0130] KVTMTVDTSTSTVYMELSSLRSEDTAVYYCAR(SEQ ID NO:74);

[0131] WGQGTLVTVSS(SEQ ID NO:75);

[0132] DIQMTQSPSSLSASVGDRVTITC(SEQ ID NO:76);

[0133] WYQQKPGKAPKLLIY (SEQ ID NO:77);

[0134] GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:78);

[0135] FGQGTKLEIK (SEQ ID NO:79).

[0136] According to an embodiment of the present application, the anti-TL1A antibody or its antigen-binding fragment comprises:

[0137] A heavy chain variable region as shown by the amino acid sequence of any one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41; and

[0138] A light chain variable region as shown by the amino acid sequence of any one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42.

[0139] As used herein, the "heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:1" refers to the heavy chain variable region being the amino acid sequence of SEQ ID NO:1 or an amino acid sequence of a conservative modification form of SEQ ID NO:1 (for example, an amino acid sequence having 1 to 20 (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) amino acid differences from SEQ ID NO:1), all within the scope of protection of this application; the same as the "amino acid sequence of any one of SEQ ID NOs:2 to 42".

[0140] According to an embodiment of the present application, the anti-TL1A antibody or its antigen-binding fragment comprises:

[0141] a heavy chain variable region as shown in the amino acid sequence of any one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41 or an amino acid sequence having at least 80% identity thereto; and

[0142] a light chain variable region as shown in the amino acid sequence of any one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42 or an amino acid sequence having at least 80% identity thereto.

[0143] According to an embodiment of the present application, the anti-TL1A antibody or its antigen-binding fragment comprises:

[0144] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:1 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:2 or an amino acid sequence having at least 80% identity thereto; or

[0145] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:3 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:4 or an amino acid sequence having at least 80% identity thereto; or

[0146] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:5 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:6 or an amino acid sequence having at least 80% identity thereto; or

[0147] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:7 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:8 or an amino acid sequence having at least 80% identity thereto; or

[0148] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:9 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:10 or an amino acid sequence having at least 80% identity thereto; or

[0149] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:11 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:12 or an amino acid sequence having at least 80% identity thereto; or

[0150] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:13 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:14 or an amino acid sequence having at least 80% identity thereto; or

[0151] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:15 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:16 or an amino acid sequence having at least 80% identity thereto; or

[0152] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:17 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:18 or an amino acid sequence having at least 80% identity thereto; or

[0153] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:19 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:20 or an amino acid sequence having at least 80% identity thereto; or

[0154] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:21 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:22 or an amino acid sequence having at least 80% identity thereto; or

[0155] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:23 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:24 or an amino acid sequence having at least 80% identity thereto; or

[0156] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:25 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:26 or an amino acid sequence having at least 80% identity thereto; or

[0157] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:27 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:28 or an amino acid sequence having at least 80% identity thereto; or

[0158] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:29 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:30 or an amino acid sequence having at least 80% identity thereto; or

[0159] A heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:31 or an amino acid sequence having at least 80% identity thereto, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:32 or an amino acid sequence having at least 80% identity thereto; or

[0160] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 33 or an amino acid sequence having at least 80% identity thereto, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence having at least 80% identity thereto; or

[0161] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence having at least 80% identity thereto, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence having at least 80% identity thereto; or

[0162] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 37 or an amino acid sequence having at least 80% identity thereto, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 38 or an amino acid sequence having at least 80% identity thereto; or

[0163] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 39 or an amino acid sequence having at least 80% identity thereto, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 40 or an amino acid sequence having at least 80% identity thereto; or

[0164] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence having at least 80% identity thereto, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 42 or an amino acid sequence having at least 80% identity thereto.

[0165] According to an embodiment of the present application, the anti-TL1A antibody or an antigen-binding fragment thereof comprises:

[0166] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 1, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 2; or

[0167] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 3, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 4; or

[0168] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 5, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 6; or

[0169] The heavy chain variable region shown by the amino acid sequence of SEQ ID NO: 7, and the light chain variable region shown by the amino acid sequence of SEQ ID NO: 8; or

[0170] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:9, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:10; or

[0171] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:11, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:12; or

[0172] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:13, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:14; or

[0173] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:15, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:16; or

[0174] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:17, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:18; or

[0175] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:19, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:20; or

[0176] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:21, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:22; or

[0177] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:23, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:24; or

[0178] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:25, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:26; or

[0179] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:27, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:28; or

[0180] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:29, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:30; or

[0181] The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:31, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:32; or

[0182] A heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:33, and a light chain variable region as shown in the amino acid sequence of SEQ ID NO:34; or

[0183] A heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:35, and a light chain variable region as shown in the amino acid sequence of SEQ ID NO:36; or

[0184] A heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:37, and a light chain variable region as shown in the amino acid sequence of SEQ ID NO:38; or

[0185] A heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:39, and a light chain variable region as shown in the amino acid sequence of SEQ ID NO:40; or

[0186] A heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:41, and a light chain variable region as shown in the amino acid sequence of SEQ ID NO:42.

[0187] Among them, the amino acid sequences shown in SEQ ID NO:1-2 (see antibody C2C1L in the examples) are as follows:

[0188] EVQLQQSGPELVKPGASVKMSCKASGYTFTSYIMHWVKQKPGQGLEWIGYVNPYNDGTNYIEKF KGKATLTSDKSSSTAYLELSSLASEDSAVYYCARYYYGNPWFAYWGQGTLVTVSA (SEQ ID NO:1);

[0189] DIVMTQSHKFMSTSVGDRVSITCKASQDVGTAVAWYQQKPGQSPKLLIYWTSTRHTGVPDRFTGS GSGTDFTLTISNVQSEDLTHYFCQQYSSYPYTFGGGTKLEIQ (SEQ ID NO:2).

[0190] Among them, the amino acid sequences shown in SEQ ID NO:3-4 (see antibody C5A8A in the examples) are as follows:

[0191] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA(SEQ ID NO:3);

[0192] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:4).

[0193] Among them, the amino acid sequences shown in SEQ ID NO:5-6 (see antibody C19E58 in the examples) are as follows:

[0194] EVQLQQSGPELVKPGASVKMSCKASGYTFTSYIMHWVKQKPGQGLEWIGYINPYNDGTKYIEKF KGKATLTSDKSSSTAYMELNSLTSEDSAVYYCARHYYGHPWFAYWGQGTLVTVSA(SEQ ID NO:5);

[0195] DIVMTQSHKFMSTSVGDRVTITCKASQDVSAAVAWYQQRPGQSPKLLIYWAATRHTGVPDRFTGS GSGTDYTLTISSVQAEDLALYYCQQHSSSPWTFGGGTKLEIK(SEQ ID NO:6).

[0196] Among them, the amino acid sequences shown in SEQ ID NO:7-8 (see antibody PO16-C5AA in the examples) are as follows:

[0197] EVQLQQSGPELVKPGASMKISCKASGYYFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA(SEQ ID NO:7);

[0198] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK (SEQ ID NO:8).

[0199] Among them, the amino acid sequences shown in SEQ ID NO:9-10 (see antibody PO16-C5AB in the examples) are as follows:

[0200] EVQLQQSGPELVKPGASMKISCKASWYYFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA (SEQ ID NO:9);

[0201] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK (SEQ ID NO:10).

[0202] Among them, the amino acid sequences shown in SEQ ID NO:11-12 (see antibody PO16-C5AC in the examples) are as follows:

[0203] EVQLQQSGPELVKPGASMKISCKASGYSFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA (SEQ ID NO:11);

[0204] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK (SEQ ID NO:12).

[0205] Among them, the amino acid sequences shown in SEQ ID NO:13-14 (see antibody PO16-C5AD in the examples) are as follows:

[0206] EVQLQQSGPELVKPGASMKISCKASGYSFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA(SEQ ID NO:13);

[0207] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIHDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:14).

[0208] Among them, the amino acid sequences shown in SEQ ID NO:15-16 (see antibody PO16-C5AE in the examples) are as follows:

[0209] EVQLQQSGPELVKPGASMKISCHASGYSFTVYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA(SEQ ID NO:15);

[0210] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIHDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:16).

[0211] Among them, the amino acid sequences shown in SEQ ID NO:17-18 (see antibody C5T5 in the examples) are as follows:

[0212] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARVQYRAVGLDYWGQGTLVTVSS(SEQ ID NO:17);

[0213] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK (SEQ ID NO:18).

[0214] Among them, the amino acid sequences shown in SEQ ID NOs: 19-20 (see antibody C5T15 in the examples) are as follows:

[0215] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARVQYRRDGLDYWGQGTLVTVSS (SEQ ID NO:19);

[0216] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK (SEQ ID NO:20).

[0217] Among them, the amino acid sequences shown in SEQ ID NOs: 21-22 (see antibody C5T18 in the examples) are as follows:

[0218] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARVQYRELGLDYWGQGTLVTVSS (SEQ ID NO:21);

[0219] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK (SEQ ID NO:22).

[0220] Among them, the amino acid sequences shown in SEQ ID NOs: 23-24 (see antibody C5T20 in the examples) are as follows:

[0221] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARVRLRYDGLDYWGQGTLVTVSS(SEQ ID NO:23);

[0222] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:24).

[0223] Among them, the amino acid sequences shown in SEQ ID NO: 25-26 (see antibody C5T28 in the examples) are as follows:

[0224] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARVQYRMLGYDYWGQGTLVTVSS(SEQ ID NO:25);

[0225] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:26).

[0226] Among them, the amino acid sequences shown in SEQ ID NO: 27-28 (see antibody C5T35 in the examples) are as follows:

[0227] EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARVQYRPDGMDYWGQGTLVTVSS(SEQ ID NO:27);

[0228] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:28).

[0229] Among them, the amino acid sequences shown in SEQ ID NO:29-30 (see antibody C50301 in the examples) are as follows:

[0230] EVQLQQSGPELVKPGASMKISCKASGYYFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCASVQYRYDGLAYWGQGTLVTVSA(SEQ ID NO:29);

[0231] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:30).

[0232] Among them, the amino acid sequences shown in SEQ ID NO:31-32 (see antibody C5033307 in the examples) are as follows:

[0233] EVQLQQSGPELVKPGASMKISCKASGYSFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCARVQYRYSGYDYWGQGTLVTVSS(SEQ ID NO:31);

[0234] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:32).

[0235] Among them, the amino acid sequences shown in SEQ ID NO:33-34 (see antibody C503H6M in the examples) are as follows:

[0236] EVQLQQSGPELVKPGASMKISCKASGYSFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCARVQYRPDGLDYWGQGTLVTVSS(SEQ ID NO:33);

[0237] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:34).

[0238] Among them, the amino acid sequences shown in SEQ ID NO:35-36 (see antibody C503H4 in the examples) are as follows:

[0239] EVQLQQSGPELVKPGASMKISCKASGYSFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCARVRLRYDGLDYWGQGTLVTVSS(SEQ ID NO:35);

[0240] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:36).

[0241] Among them, the amino acid sequences shown in SEQ ID NO:37-38 (see antibody C50301H6M in the examples) are as follows:

[0242] EVQLQQSGPELVKPGASMKISCKASGYYFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCARVQYRPDGLDYWGQGTLVTVSS(SEQ ID NO:37);

[0243] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:38).

[0244] Among them, the amino acid sequences shown in SEQ ID NO: 39-40 (see antibody C503013307 in the examples) are as follows:

[0245] EVQLQQSGPELVKPGASMKISCKASGYYFTRYTMNWVKQSHGKNLEWIGLINPYSGVTTYNQKF KGKATLTVDKSFSTAYMELLSLTSEDSAVYYCARVQYRYSGYDYWGQGTLVTVSS(SEQ ID NO:39);

[0246] QIVLTQSPAIMSASPGEKVTMTCSASSSVTYMHWYQQKSGTSPKRWIYDTSKLASGVPARFSGSGS GTSYSLTISTMEAEDAATYYCQQWSSDPYTFGGGTKLEIK(SEQ ID NO:40).

[0247] Among them, the amino acid sequences shown in SEQ ID NO: 41-42 (see antibody HC503H6M in the examples) are as follows:

[0248] EVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMNWVRQAPGQGLEWMGLINPYSGVTTYNQK FKGKVTMTVDTSTSTVYMELSSLRSEDTAVYYCARVQYRPDGLDYWGQGTLVTVSS(SEQ ID NO:41);

[0249] DIQMTQSPSSLSASVGDRVTITCSASSSVTYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGS GTDFTLTISSLQPEDFATYYCQQWSSDPYTFGQGTKLEIK(SEQ ID NO:42).

[0250] According to the embodiments of the present application, it further includes a heavy chain constant region and / or a light chain constant region.

[0251] According to an embodiment of the present application, at least a part of at least one of the heavy chain constant region and the light chain constant region is derived from at least one of a murine antibody, a primate antibody, a bovine antibody, a horse antibody, a dairy cow antibody, a pig antibody, a sheep antibody, a goat antibody, a dog antibody, a cat antibody, a rabbit antibody, a camel antibody, a donkey antibody, a deer antibody, a mink antibody, a chicken antibody, a duck antibody, a goose antibody, a turkey antibody, a fighting chicken antibody or a mutant thereof.

[0252] According to an embodiment of the present application, the heavy chain constant region includes a heavy chain constant region selected from IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE or IgD.

[0253] According to an embodiment of the present application, the light chain constant region includes a light chain constant region selected from κ-type or λ-type.

[0254] According to an embodiment of the present application, both the light chain constant region and the heavy chain constant region are derived from at least one of a rabbit antibody or a mutant thereof, a murine antibody or a mutant thereof, and a human antibody or a mutant thereof.

[0255] According to an embodiment of the present application, the heavy chain constant regions are all derived from a human wild-type IgK antibody or a mutant thereof.

[0256] According to an embodiment of the present application, the heavy chain constant regions are all derived from a human wild-type IgK antibody.

[0257] According to an embodiment of the present application, the heavy chain constant region is a human IgK mutant.

[0258] According to an embodiment of the present application, the heavy chain constant region has the amino acid sequence shown in SEQ ID NO: 70:

[0259] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:70).

[0260] According to an embodiment of the present application, the light chain constant region has the amino acid sequence shown in SEQ ID NO:71.

[0261] RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST YSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:71).

[0262] According to an embodiment of the present application, the N-terminus of the heavy chain constant region is connected to the C-terminus of the heavy chain variable region; and / or

[0263] The N-terminus of the light chain constant region is connected to the C-terminus of the light chain variable region.

[0264] According to an embodiment of the present application, the antibody includes at least one selected from polyclonal antibody, full-length monoclonal antibody, Fab antibody, Fab’ antibody, F(ab’)2 antibody, Fv antibody, single-chain antibody, and minimal recognition unit; or

[0265] The antigen-binding fragment includes at least one selected from F(ab’)2 fragment, Fab’ fragment, Fab fragment, F(ab)2 fragment, Fv fragment, scFv fragment, scFv-Fc fusion protein, scFv-Fv fusion protein, and minimal recognition unit.

[0266] As used herein, the terms "full-length antibody", "full-length monoclonal antibody", or "full-length monoclonal antibody" are each composed of at least two identical light chains and at least two identical heavy chains linked by interchain disulfide bonds, such as immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin D (IgD), or immunoglobulin E (IgE).

[0267] As used herein, the terms "polyclonal antibody" and "multispecific antibody" are synonymous and both refer to antibodies that can recognize multiple antigenic epitopes, such as antibodies that can recognize two antigenic epitopes (bispecific antibodies, abbreviated as bispecific antibodies), antibodies that can recognize three antigenic epitopes, or antibodies that can recognize four antigenic epitopes. This is a broad understanding, and the specific structure is not limited as long as it can recognize multiple antigenic epitopes. In this application, at least one of the multiple antigenic epitopes is derived from TL1A.

[0268] As used herein, the term "Fab antibody" or "Fab fragment" generally refers to an antibody or fragment containing only the Fab molecule, which is composed of VH and CH1 of the heavy chain and the complete light chain, and the light chain and the heavy chain are linked by a disulfide bond.

[0269] As used herein, the term "F(ab’)2 antibody" or "F(ab’)2 fragment" has two antigen-binding F(ab’) parts linked together by disulfide bonds.

[0270] As used herein, the term "Fv antibody" or "Fv fragment" generally refers to an antibody or fragment composed only of the variable region of the light chain (VL) and the variable region of the heavy chain (VH) linked by non-covalent bonds, which is the smallest functional fragment of the antibody molecule that retains the complete antigen-binding site.

[0271] As used herein, the terms "single-chain antibody" and "scFv fragment" are antibodies or fragments formed by linking the variable region of the heavy chain and the variable region of the light chain of an antibody with a short peptide.

[0272] As used herein, the terms "minimal recognition unit" and "MRU" both refer to an antibody or fragment composed of only one CDR, and its molecular weight is very small, only about 1% of the complete antibody.

[0273] Nucleic acid molecules, expression vectors, and recombinant cells

[0274] In the third aspect of the present application, the present application provides a nucleic acid molecule. According to an embodiment of the present application, the nucleic acid molecule encodes the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect. The nucleic acid molecule of the present application can encode the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect.

[0275] According to an embodiment of the present application, the nucleic acid molecule is DNA.

[0276] It should be noted that for the nucleic acid molecules mentioned in this article, those skilled in the art should understand that it actually includes either any one of the complementary double strands or both. For convenience, in this specification and the claims, although only one strand is given in most cases, the other complementary strand is actually also disclosed. In addition, the nucleic acid sequences in this application include DNA or RNA forms, and disclosing one means the other is also disclosed.

[0277] In the fourth aspect of this application, an expression vector is proposed. According to the embodiments of this application, the expression vector carries the nucleic acid molecule described in the third aspect. When connecting the above-mentioned nucleic acid molecule to the expression vector, the nucleic acid molecule can be directly or indirectly connected to the control elements on the expression vector, as long as these control elements can control the translation and expression of the nucleic acid molecule, etc. Of course, these control elements can come directly from the expression vector itself or be exogenous, that is, not from the expression vector itself. Of course, the nucleic acid molecule only needs to be operably connected to the control elements.

[0278] "Operably connected" herein means connecting a foreign gene to an expression vector such that the control elements in the expression vector, such as transcription control sequences and translation control sequences, etc., can perform their expected functions of regulating the transcription and translation of the foreign gene. Commonly used expression vectors can be, for example, plasmids, phages, etc.

[0279] According to some specific embodiments of this application, after the expression vector is introduced into a suitable recipient cell, it can effectively achieve the expression of the aforementioned anti-TL1A antibody or its antigen-binding fragment under the mediation of a regulatory system, and then a large amount of the anti-TL1A antibody or its antigen-binding fragment can be obtained in vitro.

[0280] According to the embodiments of this application, the expression vector includes those selected from eukaryotic expression vectors or prokaryotic expression vectors.

[0281] In an alternative embodiment of this application, the expression vector is a plasmid expression vector, a viral expression vector, such as a lentiviral expression vector.

[0282] In the fifth aspect of this application, a recombinant cell is proposed. According to the embodiments of this application, the recombinant cell includes carrying the nucleic acid molecule described in the third aspect or the expression vector described in the fourth aspect; or expressing the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect. Using this recombinant cell under suitable conditions, it can effectively express the aforementioned anti-TL1A antibody or its antigen-binding fragment intracellularly.

[0283] According to some specific embodiments of the present application, the recombinant cells can highly and abundantly express an antibody or an antigen-binding fragment thereof under suitable conditions, and the antibody or the antigen-binding fragment thereof has stronger specificity and higher potency, and can effectively treat or prevent TL1A-mediated diseases with a smaller dosage.

[0284] It should be noted that "suitable conditions" refer to the conditions suitable for the expression of the anti-TL1A antibody or its antigen-binding fragment described in the present application. It is easily understood by those skilled in the art that the conditions suitable for the expression of the anti-TL1A antibody or its antigen-binding fragment include but are not limited to suitable transformation or transfection methods, suitable transformation or transfection conditions, healthy host cell states, suitable host cell densities, appropriate cell culture environments, and appropriate cell culture times. "Suitable conditions" are not particularly limited, and those skilled in the art can optimize the most suitable conditions for the expression of the above anti-TL1A antibody or its antigen-binding fragment according to the specific environment of the laboratory.

[0285] According to an embodiment of the present application, the recombinant cells are obtained by introducing the expression vector described in the fifth aspect into a host cell.

[0286] It should be noted that the recombinant cells described in the present application are not particularly limited and can be prokaryotic cells, eukaryotic cells or phages. The prokaryotic cells can be Escherichia coli, Bacillus subtilis, Streptomyces or Proteus mirabilis, etc. The eukaryotic cells include fungi such as Pichia pastoris, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Trichoderma, insect cells such as Spodoptera frugiperda, plant cells such as tobacco, and mammalian cells such as BHK cells, CHO cells, COS cells, and myeloma cells. In some embodiments, the recombinant cells described in the present application are preferably mammalian cells, including BHK cells, CHO cells, NSO cells or COS cells, and do not include animal germ cells, fertilized eggs or embryonic stem cells.

[0287] According to an embodiment of the present application, the recombinant cells are eukaryotic cells, preferably mammalian cells.

[0288] Conjugates, pharmaceutical compositions, and reagents or kits

[0289] In the sixth aspect of the present application, the present application provides a conjugate. According to an embodiment of the present application, the conjugate comprises the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect; and a conjugate moiety, which is linked to the anti-TL1A antibody or its antigen-binding fragment. The conjugate of the present application has TL1A binding affinity and can be used for detecting TL1A, or for preventing and / or treating related diseases mediated by TL1A.

[0290] According to an embodiment of the present application, the coupling moiety is selected from at least one of a purification tag or label, a carrier, a drug, a toxin, a cytokine, and a modifier.

[0291] As used herein, the carrier can be a substance capable of being suspended or dispersed in a liquid phase (e.g., a solid-phase carrier such as particles, magnetic beads, etc.), or a solid phase capable of accommodating or carrying a liquid phase (e.g., a support such as a plate, a membrane, a test tube, etc., and a container such as a microtiter plate, a microfluidic channel, a glass capillary, a nano-column, a monolithic column, etc.); it can also be a labeling carrier for labeling an anti-TL1A antibody or its antigen-binding fragment, fusion protein, or multispecific antibody, such as an enzyme (e.g., peroxidase, alkaline phosphatase, luciferase, β-galactosidase), an affinity substance (e.g., one of streptavidin and biotin, one of nucleic acids of complementary sense and antisense strands), a fluorescent dye (e.g., fluorescein, fluorescein isothiocyanate, rhodamine, green fluorescent protein, red fluorescent protein), a luminescent substance (e.g., luciferin, Aequorin, acridinium ester, tris(2,2'-bipyridine)ruthenium, luminol), a radioisotope (e.g., 3H, 14C, 32P, 35S, 125I), and gold colloid, etc.

[0292] According to an embodiment of the present application, the carrier includes a fluorescent dye.

[0293] According to an embodiment of the present application, the carrier is selected from at least one of magnetic microspheres, plastic microspheres, plastic microparticles, microtiter plates, glass, capillaries, nylon, and nitrocellulose membranes.

[0294] According to an embodiment of the present application, the drug is a small molecule drug capable of binding to an anti-TL1A antibody or its antigen-binding fragment.

[0295] According to an embodiment of the present application, the purification tag or label is selected from at least one of a protein tag, colloidal gold, a radioactive label, a luminescent substance, a colored substance, an enzyme, biotin / avidin, and a spin label.

[0296] According to an embodiment of the present application, the purification tag or label is selected from at least one of a fluorescent label, a chromophore label, and an electron-dense label.

[0297] According to an embodiment of the present application, the protein tag includes but is not limited to His tag, Flag tag, GST tag, MBP tag, SUMO tag, C-Myc tag, etc.

[0298] According to an embodiment of the present application, the modifier should be understood in a broad sense and can refer to a substance for modifying a protein. Exemplarily, it can be polyethylene glycol or its derivative.

[0299] It should be noted that the coupling method between the coupling part and the anti-TL1A antibody or its antigen-binding fragment, fusion protein or multispecific antibody can use methods well-known in the art. For example, physical adsorption method, covalent binding method, method using affinity substances (such as biotin, streptavidin), and ionic binding method can be cited.

[0300] According to an embodiment of the present application, the conjugate is a staining reagent, and the coupling part is a fluorescent dye.

[0301] According to an embodiment of the present application, the fluorescent dye includes any one or more of FITC, PE, Cy5, PI, 7-AAD, APC, AlexaFluor, eFluor, PE-Cy7, APC-Cy7, PerCP, PerCPcy5.5, PB, BV series, QDot series, and BUV series dyes.

[0302] In the seventh aspect of the present application, the present application provides a reagent or a kit. According to an embodiment of the present application, the reagent or the kit includes the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the nucleic acid molecule described in the third aspect, the expression vector described in the fourth aspect, the recombinant cell described in the fifth aspect, or the conjugate described in the sixth aspect. The kit of the present application has a TL1A binding affinity and can effectively detect TL1A.

[0303] As described above, the anti-TL1A antibody or its antigen-binding fragment in some specific embodiments of the present application can effectively bind to the human TL1A protein. Therefore, the reagent or the kit containing the anti-TL1A antibody or its antigen-binding fragment can effectively qualitatively or quantitatively detect the human TL1A protein. The reagent or the kit provided by the present application can be used, for example, in immunoblotting, immunoprecipitation, etc., which are reagents or kits related to detecting by using the specific binding of human TL1A and the antibody. These kits can include any one or more of the following: antagonists, anti-TL1A antibodies, or drug reference materials; protein purification columns; immunoglobulin affinity purification buffers; cell assay diluents; instructions or literature, etc. The anti-TL1A antibody can be used in different types of diagnostic tests. For example, it can detect the presence of drugs, toxins, or other proteins in vitro. For example, it can be used in scientific research to detect the human TL1A protein in a test sample by using the kit. For the above application scenarios, the binding molecule is equally applicable and will not be repeated here.

[0304] According to some specific embodiments of the present application, the kit may further include those commonly used for detecting TL1A, such as coating solutions, etc.

[0305] In the eighth aspect of the present application, the present application provides a pharmaceutical composition. According to an embodiment of the present application, the pharmaceutical composition comprises the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the nucleic acid molecule described in the third aspect, the expression vector described in the fourth aspect, the recombinant cell described in the fifth aspect, or the conjugate described in the sixth aspect. The pharmaceutical composition of the present application has TL1A-binding affinity and can effectively prevent and / or treat TL1A-mediated related diseases.

[0306] According to an embodiment of the present application, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0307] The administration of the pharmaceutical composition of the present application can be carried out by any acceptable administration method. The pharmaceutical composition of the present application can be formulated into preparations in solid, semi-solid, liquid or gas forms, such as injections, lyophilized powders. The current methods for preparing these dosage forms are known or will be apparent to those skilled in the art. Typical routes for administering such pharmaceutical compositions include, but are not limited to, subcutaneous injection, intravenous, intramuscular, intradermal, intrasternal injection or infusion techniques. The pharmaceutical composition of the present application is formulated to allow the bioactive ingredients contained therein to be bioavailable after administration to a patient.

[0308] Use

[0309] In the ninth aspect of the present application, the present application provides the use of the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the nucleic acid molecule described in the third aspect, the expression vector described in the fourth aspect, the recombinant cell described in the fifth aspect, the conjugate described in the sixth aspect, or the pharmaceutical composition described in the seventh aspect in the preparation of multispecific antibodies, fusion proteins, drugs or kits, or drugs.

[0310] According to an embodiment of the present application, the kit is used for detecting TL1A.

[0311] According to an embodiment of the present application, the drug is used for preventing and / or treating TL1A-mediated related diseases.

[0312] According to an embodiment of the present application, the TL1A-mediated related diseases include inflammatory or immune diseases.

[0313] According to an embodiment of the present application, the TL1A-mediated related diseases include allergy, asthma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, fibrosis-related diseases, systemic lupus erythematosus, psoriasis, type 1 diabetes and transplant rejection.

[0314] According to embodiments of the present application, the inflammatory or immune diseases include Crohn's disease, ulcerative colitis, medically refractory ulcerative colitis (MR-UC), intestinal fibrosis, pulmonary fibrosis, and liver fibrosis.

[0315] The present application provides an anti-TL1A antibody or an antigen-binding fragment thereof described in the first aspect or the second aspect, a nucleic acid molecule described in the third aspect, an expression vector described in the fourth aspect, a recombinant cell described in the fifth aspect, or a conjugate described in the sixth aspect, for detecting TL1A or preventing and / or treating TL1A-mediated related diseases.

[0316] According to embodiments of the present application, the TL1A-mediated related diseases include inflammatory or immune diseases.

[0317] According to embodiments of the present application, the TL1A-mediated related diseases include allergy, asthma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, fibrosis-related diseases, systemic lupus erythematosus (SLE), psoriasis, type 1 diabetes, and transplant rejection.

[0318] According to embodiments of the present application, the inflammatory or immune diseases include Crohn's disease, ulcerative colitis, medically refractory ulcerative colitis (MR-UC), intestinal fibrosis, pulmonary fibrosis, and liver fibrosis.

[0319] The present application provides the use of an anti-TL1A antibody or an antigen-binding fragment thereof described in the first aspect or the second aspect, a nucleic acid molecule described in the third aspect, an expression vector described in the fourth aspect, a recombinant cell described in the fifth aspect, or a conjugate described in the sixth aspect in detecting TL1A or preventing and / or treating TL1A-mediated related diseases.

[0320] According to embodiments of the present application, the TL1A-mediated related diseases include inflammatory or immune diseases.

[0321] According to embodiments of the present application, the TL1A-mediated related diseases include allergy, asthma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, fibrosis-related diseases, systemic lupus erythematosus (SLE), psoriasis, type 1 diabetes, and transplant rejection.

[0322] According to embodiments of the present application, the inflammatory or immune diseases include Crohn's disease, ulcerative colitis, medically refractory ulcerative colitis (MR-UC), intestinal fibrosis, pulmonary fibrosis, and liver fibrosis.

[0323] Method

[0324] In the tenth aspect of the present application, the present application provides a method for detecting TL1A. According to an embodiment of the present application, the method includes: contacting a sample to be detected with the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, the conjugate described in the sixth aspect, or the reagent or kit described in the seventh aspect to form an immune complex. As known before, the aforementioned anti-TL1A antibody or its antigen-binding fragment, conjugate, reagent or kit all have TL1A-binding affinity. Therefore, the above anti-TL1A antibody or its antigen-binding fragment, conjugate, reagent or kit can effectively detect TL1A, especially for in vitro detection (such as detection for non-disease diagnosis and treatment purposes), and has advantages such as high detection accuracy.

[0325] According to an embodiment of the present application, based on the signal of the immune complex, it is determined whether the sample to be detected contains TL1A or cells expressing TL1A, or the content of TL1A or cells expressing TL1A in the sample to be detected.

[0326] According to an embodiment of the present application, the signal of the immune complex is detected by at least one of the methods of ELISA, WB, and IHC.

[0327] According to an embodiment of the present application, the immune complex further includes a secondary antibody that binds to the anti-TL1A antibody or its antigen-binding fragment.

[0328] According to an embodiment of the present application, the signal includes a fluorescence signal.

[0329] In the eleventh aspect of the present application, the present application provides a method for preventing and / or treating diseases related to TL1A-mediated. According to an embodiment of the present application, the method includes: administering to a subject a pharmaceutically acceptable amount of the anti-TL1A antibody or its antigen-binding fragment described in the first aspect or the second aspect, or the pharmaceutical composition described in the eighth aspect. The method of the present application can effectively prevent and / or treat diseases related to TL1A-mediated.

[0330] The effective amount of the anti-TL1A antibody or its antigen-binding fragment and the pharmaceutical composition described in the present application may vary with the mode of administration and the severity of the disease to be treated, etc. The selection of the preferred effective amount can be determined by those of ordinary skill in the art according to various factors (such as through clinical trials). The factors include but are not limited to: the pharmacokinetic parameters of the active ingredient, such as bioavailability, metabolism, half-life, etc.; the severity of the disease to be treated by the patient, the patient's weight, the patient's immune status, the route of administration, etc. For example, due to the urgency of the treatment condition, several separate doses may be administered daily, or the dose may be proportionally reduced.

[0331] The anti-TL1A antibody or antigen-binding fragment thereof, and the pharmaceutical composition of the present application can be incorporated into pharmaceuticals suitable for parenteral administration (such as intravenous, subcutaneous, intraperitoneal, intramuscular). These pharmaceuticals can be prepared in various forms. For example, liquid, semi-solid and solid dosage forms, etc., including but not limited to liquid solutions (such as injection solutions and infusion solutions) or lyophilized powders. Typical pharmaceuticals are in the form of injection solutions or infusion solutions. The aforementioned anti-TL1A antibody or antigen-binding fragment thereof, and the pharmaceutical composition can be administered by intravenous infusion or injection or intramuscular or subcutaneous injection.

[0332] As used herein, the term "subject" refers to a vertebrate, preferably a mammal, most preferably a human. Mammals include but are not limited to mice, apes, humans, domestic animals, game animals and pets. Also included are tissues, cells and progeny of biological entities obtained in vivo or cultured in vitro.

[0333] According to an embodiment of the present application, the administration route of the method is subcutaneous injection or intravenous injection.

[0334] According to an embodiment of the present application, the TL1A-mediated related diseases include inflammatory or immune diseases.

[0335] According to an embodiment of the present application, the TL1A-mediated related diseases include allergy, asthma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, fibrosis-related diseases, systemic lupus erythematosus (SLE), psoriasis, type 1 diabetes and transplant rejection.

[0336] According to an embodiment of the present application, the inflammatory or immune diseases include Crohn's disease, ulcerative colitis, medically refractory ulcerative colitis (MR-UC), intestinal fibrosis, pulmonary fibrosis, liver fibrosis.

[0337] The solution of the present application will be explained below in conjunction with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present application and should not be regarded as limiting the scope of the present application. For those without specific technical or conditions noted in the embodiments, the techniques or conditions described in the literature in the art or according to the product instructions are followed. Those reagents or instruments without the manufacturer noted are all conventional products that can be obtained through commercial purchase.

[0338] Example 1: Screening of monoclonal antibodies against TL1A

[0339] Balb / c mice were immunized multiple times with soluble recombinant human TL1A protein (Kaisi, FSF-HM415). The antigen protein was mixed with an immune adjuvant to form an immunogen reagent, which was then subcutaneously injected through the back of the mice. In the first round of immunization, each mouse was immunized with a solution of 50 μg of human TL1A protein emulsified with complete Freund's adjuvant (Sigma, F5881) at a volume ratio of 1:1. In each subsequent booster immunization, each mouse was boosted with a solution of 50 μg of human TL1A protein emulsified with incomplete Freund's adjuvant (Sigma, F5506) at a volume ratio of 1:1. The interval between each booster immunization was at least 2-3 weeks. Three days before cell fusion, the last booster immunization was performed at a dose of 50 μg of human TL1A protein per mouse.

[0340] When the antibody titer specific for TL1A in the mouse serum reached a certain level, the spleen cells of the mice were taken out and fused with a myeloma cell line to obtain hybridoma cells; after multiple rounds of screening and subcloning of the hybridoma cells, several hybridoma cells expressing monoclonal antibody molecules against TL1A protein were isolated. The amino acid sequences encoding the variable domains of the antibody molecules were obtained using conventional hybridoma sequencing methods. The variable region sequences and CDR sequences of each monoclonal antibody are shown in Table 1.

[0341] Table 1: Serial numbers of variable region amino acids of anti-TL1A monoclonal antibodies

[0342] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 C2C1L 1 2 43 44 45 46 47 48 C5A8A 3 4 49 50 51 52 53 54 C19E5B 5 6 43 55 56 57 58 59

[0343] Example 2: Recombinant expression of TL1A monoclonal antibody

[0344] 1. Connect the light chain variable region sequence and heavy chain variable region sequence of each hybridoma clone (see Table 1) to the light chain constant region of human IgK (the amino acid sequence is shown in SEQ ID NO: 71) or the heavy chain constant region sequence of human IgG1 (the amino acid sequence is shown in SEQ ID NO: 70) respectively. After codon optimization of the spliced amino acid sequence, obtain the corresponding nucleotide sequence, and then synthesize the heavy and light chain nucleotide sequences of each clone into the expression plasmid pcDNA3.4 respectively, amplify and extract the plasmid; after filtering the expression plasmid through a 0.22 μm filter membrane, mix it with CHO cells and electroporation solution, add it into a 1 ml electroporation tube, and after electroporation, divide the cells in the electroporation tube into a shaking flask containing 20 ml of culture medium prepared in advance, and incubate statically for 40 min. After the incubation, place the shaking flask in an incubator at 37 °C, 270 rpm, and 8% CO2 for culture. After 24 h, add feeding / sodium butyrate / penicillin-streptomycin, and continue to culture for 3 - 6 days, then collect the cell supernatant; add the cell supernatant into a Protein A affinity chromatography column, wash the chromatography column with 20 mL of PBS buffer, then add 5 mL of sodium acetate buffer (pH 3.4) to elute the chromatography column, collect the eluate into a dialysis bag, and dialyze it into PBS buffer to obtain the target product, the recombinant monoclonal antibody against human TL1A, namely antibody C2C1L, C5A8A, C19E5B.

[0345] 2. For the preparation methods of the control antibodies RVT-3101 (the amino acid sequence of the heavy chain variable region sequence is shown in SEQ ID NO: 80, and the amino acid sequence of the light chain variable region sequence is shown in SEQ ID NO: 81), PRA023 (the amino acid sequence of the heavy chain variable region sequence is shown in SEQ ID NO: 82, and the amino acid sequence of the light chain variable region sequence is shown in SEQ ID NO: 83), and TEV-48574 (the amino acid sequence of the heavy chain variable region sequence is shown in SEQ ID NO: 84, and the amino acid sequence of the light chain variable region sequence is shown in SEQ ID NO: 85) in the subsequent examples, refer to step 1 of this example.

[0346] Example 3: Detection of the affinity of anti-TL1A monoclonal antibodies by BLI

[0347] Use Sartorius R8 to detect the affinity of different anti-human TL1A recombinant monoclonal antibodies:

[0348] First, place the AHC2 sensor in 1x Kinetic buffer (1x KB) for pre-wetting for more than 10 minutes. Dilute the concentrations of different monoclonal antibody samples against human TL1A (antibodies C2C1L, C5A8A, C19E5B) to 10 μg / mL with 1xKB. Then, dilute human TL1A protein (Abnova, catalog number FSF-HM415) to the corresponding molar concentrations (100 nmol / L, 50 nmol / L, 25 nmol / L, 12.5 nmol / L, 6.25 nmol / L, 3.125 nmol / L, 1.5625 nmol / L, 0 nmol / L) with 1x KB. Prepare 10 mM glycine for sensor regeneration. Transfer the above-prepared solutions to a 96-well plate, and set the detection program according to the cycle sequence of baseline1 (equilibration), Loading (antibody binding), baseline2 (equilibration), Association (antigen binding), Dissociation (antigen dissociation), Regeneration (regeneration), and Neutralization (neutralization), so that each antibody can bind to human TL1A antigen at different concentrations. Finally, analyze the data using Octet Analysis Studio 12.2 software, and obtain the specific affinity data of each antibody for human TL1A protein by fitting the binding and dissociation curves; the smaller the KD value, the stronger the binding activity. The specific data is shown in Table 2.

[0349] Table 2: Affinity (BLI) of different monoclonal antibodies against human TL1A for human TL1A protein

[0350] Sample KD (M) ka (1 / Ms) kdis (1 / s) C2C1L 1.018E-12 3.063E05 3.119E-07 C5A8A 3.767E-11 1.299E06 4.895E-05 C19E5B 1.465E-10 1.086E06 1.591E-04

[0351] Example 4: Study on the activity of anti-TL1A monoclonal antibody blocking the activation of transcription factor NFκB by TL1A

[0352] Use human TL1A to stimulate the NFκB-Luc-TF-1 cell line, and simultaneously add anti-TL1A antibody to block the activation of transcription factor NFκB by TL1A, and detect the expression of luciferase to judge the activity of anti-TL1A antibody blocking the activation of transcription factor NFκB by TL1A.

[0353] First, plate the NFκB-Luc-TF-1 cells at a cell density of 8*10 5cells / ml, inoculate 50 μl per well; then prepare and serially dilute the antibodies (antibodies C2C1L, C5A8A, C19E5B, control antibody RVT-3101 (the amino acid sequence of the heavy chain variable region sequence is shown in SEQ ID NO:80, and the amino acid sequence of the light chain variable region sequence is shown in SEQ ID NO:81) or PRA023 (the amino acid sequence of the heavy chain variable region sequence is shown in SEQ ID NO:82, and the amino acid sequence of the light chain variable region sequence is shown in SEQ ID NO:83)) with a 200 ng / ml human TL1A protein solution. The initial concentration of the antibody in the first well is 25 nM, and it is serially diluted 3-fold, with a total of 9 concentrations. Incubate in a 37 °C cell culture incubator for 4 hours. Detect luciferase in the supernatant using the one lite luciferase detection kit (Vazyme, DD1203-01). Use the software GraphPad Prism 8.0 for data processing and graph analysis. Through four-parameter non-linear fitting, obtain binding curves and parameters such as IC 50 value and other parameters; the smaller the IC 50 value, the stronger the blocking activity. The results are shown in Table 3 and Figure 1 .

[0354] The heavy chain variable region sequence of RVT-3101 is:

[0355] QVQLVQSGAEVKKPGASVKVSCKASGYDFTYYGISWVRQAPGQGLEWMGWISTYNGNTHYAR MLQGRVTMTTDTSTRTAYMELRSLRSDDTAVYYCARENYYGSGAYRGGMDVWGQGTTVTVSS (SEQ ID NO:80);

[0356] The light chain variable region sequence of RVT-3101 is:

[0357] EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPWTFGQGTKVEIK (SEQ ID NO:81).

[0358] The heavy chain variable region sequence of PRA023 is:

[0359] QVQLVQSGAEVKKPGASVKVSCKASGFDIQDTYMHWVKQRPGQGLEWMGRIDPASGHTKYDPKFQVRVTITRDTSTSTVYLELSSLRSEDTAVYYCARSGGLPDVWGQGTTVTVSS(SEQ ID NO:82);

[0360] The variable region sequence of PRA023 light chain is:

[0361] EIVLTQSPGTLSLSPGERATLSCRASSSVSYMYWYQQKPGQAPRPLIYATSNLASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQWEGNPRTFGGGTKLEIK(SEQ ID NO:83).

[0362] Table 3: Ability of different anti-TL1A monoclonal antibodies to block the TL1A-activated NFκB signaling pathway

[0363] Antibody Name RVT-3101 PRA023 C2C1L C5A8A C19E5B <![CDATA[IC 50 (nM)]]> 0.37 1.68 1.20 0.65 1.07

[0364] Example 5: Virtual affinity maturation of anti-TL1A monoclonal antibody

[0365] 1. Based on antibody C5A8A, use Discovery studio software to model the amino acid sequence of the variable region of the anti-TL1A monoclonal antibody. Use the antibody model and the crystal structure of human TL1A protein numbered 2RE9 in PDB as ligand and receptor respectively for molecular docking simulation to obtain a series of docking conformations; judge and screen the rationality of different docking conformations, select the conformations that match the experimental results, analyze the specific amino acid sites on the antibody that interact with the antigen for amino acid scanning mutations, and select the mutation with the largest binding free energy for recombinant expression to obtain the mutant antibody variants (i.e., antibodies PO16-C5AA and PO16-C5AE). The variable region sequences and CDR sequences of each antibody are shown in Table 4-1.

[0366] Table 4-1: Serial numbers of variable region amino acids of anti-TL1A humanized antibodies

[0367] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 PO16-C5AA 7 8 60 50 51 52 53 54 PO16-C5AE 15 16 61 50 51 52 53 54

[0368] 2. Based on antibody C5A8A and antibody PO16-C5AA, use Discovery studio software to mutate the amino acid sequence of the framework region of the anti-TL1A monoclonal antibody to obtain the mutant antibody variants (i.e., antibodies PO16-C5AB, PO16-C5AC, and PO16-C5AD). The variable region sequences and CDR sequences of each antibody are shown in Table 4-2.

[0369] Table 4-2: Serial numbers of variable region amino acids of anti-TL1A humanized antibody

[0370] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 PO16-C5AB 9 10 49 50 51 52 53 54 PO16-C5AC 11 12 60 50 51 52 53 54 PO16-C5AD 13 14 60 50 51 52 53 54

[0371] Example 6: Phage affinity maturation of anti-TL1A monoclonal antibody

[0372] Based on antibody C5A8A, Kabat annotation was performed on the heavy chain variable region of the anti-TL1A monoclonal antibody. Saturation mutagenesis libraries were constructed for heavy chain CDRH1, heavy chain CDRH2, and CDRH3 respectively, and the mutant libraries were packaged and expressed using M13K07 helper phage (NEB, N0315S); after blocking the two libraries respectively, biotinylated TL1A antigen was used for four rounds of screening. The antigen usage amount in the first round of panning was 200 ng, in the second round was 20 ng, in the third round was 1 ng, and in the fourth round was 0.1 ng. Binding was carried out at room temperature or overnight at 4°C; each time after the phage bound to the antigen, it was washed 15 times with PBST*NaCl and then 2 times with PBS to wash away non-specifically bound phages. Then, 500 μl of 100 mM Glycine-HCl (pH 2.2) was added to each library, and it was eluted by rotation at room temperature for 10 minutes. Then, 22 μL of 2 M TRIS-HCl (pH 9.1) was immediately added to elute and neutralize the phages specifically bound to the TL1A protein; finally, through sequencing, clones with aggregation were recombinantly expressed as whole antibodies in eukaryotes; Table 5 lists the variable region sequences and CDR sequences of the enriched monoclonal mutant clones obtained by screening.

[0373] Table 5: Serial numbers of variable region amino acids of anti-TL1A humanized antibody

[0374] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 C5T5 17 18 49 50 62 52 53 54 C5T15 19 20 49 50 63 52 53 54 C5T18 21 22 49 50 64 52 53 54 C5T20 23 24 49 50 65 52 53 54 C5T28 25 26 49 50 66 52 53 54 C5T35 27 28 49 50 67 52 53 54

[0375] Example 7: Detection of the affinity of anti-human TL1A humanized antibody for human TL1A protein using SPR

[0376] The affinity of different anti-human TL1A humanized antibodies was detected using Biacore T200:

[0377] First, the anti-human Fc antibody was immobilized on a CM5 chip (Cytiva, BR100530). Then, different anti-human TL1A humanized antibody samples (i.e., antibody C5A8A, PO16-C5AA, PO16-C5AB, PO16-C5AC, PO16-C5AD, PO16-C5AE, C5T5, C5T15, C5T18, C5T20, C5T28, C5T35) were diluted to a concentration of 2 μg / mL with 1X HBS-EP+ buffer, and 10 mM glycine (pH 1.5) was prepared for chip regeneration. The contact time between different antibodies and the chip immobilized with the anti-human Fc antibody was adjusted to make the response value of antibody binding to the chip reach 100 RU. After binding, the human TL1A protein (KaiKa, catalog number FSF-HM415) was diluted with 1X HBS-EP+ buffer, starting at a concentration of 100 nM, and gradient-diluted at a 3-fold concentration gradient for a total of 8 concentrations. The detection was performed in the cycle order of Capture (binding different anti-TL1A monoclonal antibodies to be tested), Contact (binding different concentrations of human TL1A protein), Dissociation (dissociating the protein), and Regeneration. After the program finished running, the data was analyzed using the Biacore T200 Evaluation Software, and the specific affinity data of each antibody for the human TL1A protein was obtained by fitting the binding and dissociation curves. The smaller the KD value, the stronger the binding activity. The results are shown in Table 6.

[0378] Table 6: Affinity (SPR) of different anti-human TL1A humanized antibodies for human TL1A protein

[0379] Sample KD (M) ka (1 / Ms) kdis (1 / s) C5A8A 4.17E-09 7.68E+05 3.20E-03 PO16-C5AA 2.27E-09 4.73E+05 1.07E-03 PO16-C5AC 2.97E-10 1.28E+06 3.80E-04 PO16-C5AE 5.11E-09 5.81E+05 2.97E-03 C5T5 1.00E-08 4.25E+05 4.27E-03 C5T15 7.11E-09 3.05E+05 2.17E-03 C5T18 8.43E-09 4.76E+05 4.01E-03 C5T20 4.18E-09 4.62E+05 1.93E-03 C5T28 1.35E-08 3.68E+05 4.98E-03 C5T35 2.95E-09 3.88E+05 1.14E-03

[0380] Example 8: Recombinant expression of variant antibodies combining mutation sites of antibodies with different affinity maturation sources and their SPR detection

[0381] 1. Source and sequence analysis were performed on the molecules with improved affinity verified in Example 7. Clones with non-overlapping mutation sites relative to the CDR of the parental antibody were selected and combined for recombinant expression. The variable region sequences and CDR sequences of the recombinant variants are shown in Table 7-1.

[0382] Table 7-1: Serial numbers of variable region amino acids of anti-TL1A humanized antibodies

[0383] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 C5033307 31 32 60 50 68 52 53 54 C503H6M 33 34 60 50 69 52 53 54 C503H4 35 36 60 50 65 52 53 54

[0384] 2. Based on the antibodies PO16-C5AA, C5033307, and C503H6M, the amino acid sequences of the framework regions of the anti-TL1A monoclonal antibodies were mutated using Discovery studio software to obtain mutant antibody variants (i.e., antibodies C50301, C503013307, and C50301H6M). The variable region sequences and CDR sequences of each antibody are shown in Table 7-2.

[0385] Table 7-2: Serial numbers of variable region amino acids of anti-TL1A humanized antibodies

[0386] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 C50301 29 30 60 50 51 52 53 54 C503013307 39 40 60 50 68 52 53 54 C50301H6M 37 38 60 50 69 52 53 54

[0387] 3. The affinities of the anti-TL1A antibodies obtained by combining the mutation sites from different affinity maturations in Steps 1 and 2 of this example for human TL1A protein were detected by SPR, and the results are shown in Table 8.

[0388] Table 8: Affinities of different anti-human TL1A monoclonal antibody affinity combined mutant variants for human TL1A protein (SPR)

[0389] Sample KD (M) ka (1 / Ms) kdis (1 / s) C503H6M 4.67E-11 2.45E+06 1.14E-04 C50301H6M 7.37E-11 2.03E+06 1.50E-04 C503H4 3.38E-10 9.06E+05 3.06E-04 C50301 2.71E-10 1.93E+06 5.23E-04 C503013307 1.19E-09 4.51E+05 5.34E-04 C5033307 2.51E-09 3.17E+05 7.97E-04

[0390] Example 9: Humanization of affinity matured combined antibodies and their SPR detection

[0391] Humanization modification was performed on the affinity matured combined variants:

[0392] First, the antibody was modeled using Discovery studio. A human antibody close to the murine antibody sequence was selected for CDR transplantation, and back mutations were made to the key amino acids responsible for structural stability in the murine antibody model. This application exemplarily shows the antibody HC503H6M after humanization modification based on the antibody C503H6M. The variable region sequence and CDR sequence of the antibody HC503H6M are shown in Table 9. By SPR detection, the affinity results of the antibody HC503H6M, as well as the control antibodies TEV-48574 (the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO:84, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:85) and PRA023, are shown in Table 10.

[0393] The heavy chain variable region sequence of TEV-48574 is:

[0394] QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWLNPNSGYTGYAQKFQGRVTMTADRSTSTAYMELSSLRSEDTAVYYCAREVPETAAFEYWGQGTLVTVSS(SEQ ID NO:84);

[0395] The variable region sequence of the light chain of TEV-48574 is:

[0396] QSVLTQPPSVSGAPGQRVTISCTSSSSDIGAGLGVHWYQQLPGTAPKLLIEGYYNRPSGVPDRFSGSKSGTSASLTITGLLPEDEGDYYCQSWDGTLSALFGGGTKLTVL(SEQ ID NO:85).

[0397] Table 9: Serial numbers of amino acids in the variable regions of antibody HC503H6M

[0398] Antibody Name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 HC503H6M 41 42 60 50 69 52 53 54

[0399] Table 10: Results of affinity detection of antibody HC503H6M against human TL1A protein (SPR)

[0400] Sample KD (M) ka (1 / Ms) kdis (1 / s) HC503H6M 5.11E-11 1.46E+06 7.47E-05 PRA023 9.64E-10 4.99E+05 4.82E-04 TEV-48574 5.70E-11 1.49E+06 8.51E-05

[0401] Example 10: Detecting the activity of an anti-TL1A humanized antibody in blocking the activation of transcription factor NFκB by TL1A

[0402] Using human TL1A to stimulate the DR3-NFKB-Luc-Jurkat cell line, and adding different anti-TL1A humanized antibodies simultaneously to block the activation of transcription factor NFκB by TL1A, and detecting the expression of luciferase to determine the activity of the anti-TL1A humanized antibody in blocking the activation of transcription factor NFκB by TL1A.

[0403] First, plate the DR3-NFKB-Luc-Jurkat cells at a cell density of 4*10 5cells / ml, 50 μl was inoculated in each well; then 200 ng / ml human TL1A protein solution was used to prepare and graded dilution antibodies (the antibodies obtained in Examples 5, 6, and 9, and the control antibody RVT-3101), the antibody concentration in the first well was 10 nM, 5-fold graded dilution, a total of 9 concentrations, incubated at 37°C cell culture incubator for 3 hours, and the luciferase in the supernatant was detected using the one lite luciferase detection kit (Vazyme, DD1203-01), and the software GraphPad Prism 8.0 was used for data processing and graphical analysis, and the binding curve and IC were obtained by four-parameter nonlinear fitting. 50 Parameters such as value; IC 50 The smaller the value, the stronger the blocking activity. The results show that each antibody has the ability to block the activation of NFκB signaling pathway by human TL1A protein. The results of antibody HC503H6M shown in this application are specifically shown in Table 6 and Figure 2 .

[0404] Table 6: Ability of different anti-TL1A humanized antibodies to block the activation of NFκB signaling pathway by human TL1A protein

[0405] Antibody Name RVT-3101 HC503H6M <![CDATA[IC 50 (nM)]]> 0.0372 0.0238

[0406] Example 11: Study on the hydrophilicity of anti-TL1A monoclonal antibody

[0407] The anti-TL1A monoclonal antibodies (the antibodies obtained in Examples 5, 6 and 9) were diluted with mobile phase A (1.8 M ammonium sulfate + 0.1 M sodium dihydrogen phosphate solution, pH 6.5) to a final test solution containing 1.0 M ammonium sulfate, with mobile phase A (1.8 M ammonium sulfate + 0.1 M sodium dihydrogen phosphate solution, pH 6.5) and mobile phase B (0.1 M sodium dihydrogen phosphate solution, pH 6.5) as mobile phases, chromatographic column (manufacturer: Saifen Technology, model: Protemix HIC Butyl-NP5 4.6*10mm, 5μm), wavelength 214nm, flow rate 1.0mL / min, injection volume 5μg, column temperature 25°C, sample chamber temperature 8°C. The gradient elution method is 0-5min, 44% B; 5-15min, 44% B→100% B; 15-20min, 100% B; 20.1-25min, 44% B. The elution is performed, and the hydrophilicity of the target protein is determined by comparing the retention time of the target protein peak; the shorter the peak time, the stronger the hydrophilicity, and the more hydrophilic the protein, the better the solubility. The present application exemplifies the results of the antibody HC503H6M, see Table 12.

[0408] Table 12: Hydrophilicity of anti-TL1A monoclonal antibodies

[0409] Sample Elution Time (min) HC503H6M 1.014 RVT-3101 7.563

[0410] Example 12: Solubility Study of Anti-TL1A Monoclonal Antibody

[0411] Perform a rapid concentration test on the anti-TL1A monoclonal antibody to detect its solubility:

[0412] First, change the solution of 50 mg of the sample to be tested (each antibody obtained in Examples 5, 6, and 9, and the control antibody RVT-3101) to 20 mM His-HCl solvent, and then transfer it to an ultrafiltration concentration tube for centrifugation multiple times. Take samples each time for dilution and concentration detection. Each antibody has good solubility. This example exemplarily shows the solubility of some samples. For example, Figure 3 As shown, after concentrating the sample to be tested 3 times, the concentration of antibody HC503H6M reaches 149.0 mg / ml.

[0413] Example 13: Detect the Ability of Anti-TL1A Monoclonal Antibody to Block the Co-Stimulation of Human TL1A and IL12 / 18 on Human PBMC to Produce IFN-γ

[0414] Use human TL1A (KaiKa, FSF-HM415) and IL12 / 18 (Acro, IL2-H4210 / IL8-H5113) to co-stimulate human PBMC (MaiShun, PB050C), and at the same time add different anti-TL1A antibodies or their variants (each antibody obtained in Examples 5, 6, and 9, and the control antibodies TEV-48574, RVT-3101, and PRA023) to block the production of IFN-γ. Detect the ability of different antibodies to block the production of IFN-γ by Human IFN-γ ELISA Kit (Elabscience, E-EL-H0108).

[0415] First, resuscitate the cryopreserved PMBC, and the cell density is 1.05*10 6cells / ml, add human IL-12 at a final concentration of 2 ng / ml, human IL-18 at 100 μg / ml and human TL1A protein at a final concentration of 100 ng / ml to the cells. Add 190 μl of the above suspension to each well, and then add 10 μl of anti-TL1A antibodies at different concentrations (the antibodies obtained in Example 5, Example 6, and Example 9, as well as the control antibodies TEV-48574, RVT-3101, and PRA023), so that the final concentration of the antibody in each well decreases 3-fold from an initial concentration of 200 nM to 0.09 nM. There are a total of 8 inhibitory concentrations for each antibody. Finally, calculate the IFN-γ concentration in each well according to the standard curve of the kit, and use the software GraphPad Prism 8.0 for data processing and plotting analysis. Through four-parameter nonlinear fitting, obtain the binding curve and IC 50 values and other parameters; the smaller the IC 50 value, the stronger the blocking activity. It was found that the antibodies of the present application can all block the coordinated stimulation of human TL1A and IL12 / 18 on human PBMC to produce IFN-γ. The results of some exemplary antibodies of the present application are shown in Table 13 and Figure 4 .

[0416] Table 13: The ability of each antibody to block the coordinated stimulation of TL1A and IL12 / 18 on human PBMC to produce IFN-γ

[0417] Antibody Name TEV-48574 RVT-3101 HC503H6M PRA023 <![CDATA[IC 50 (nM)]]> 0.5319 0.8909 1.448 1.908

[0418] In the description of this specification, the descriptions with reference to terms such as "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0419] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present application. Those of ordinary skill in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present application.

Claims

1. An anti-TL1A antibody or an antigen-binding fragment thereof, characterized in that, It includes HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3; The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by any one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by any one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42; Optionally, the HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:1; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:2; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:3; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:4; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:5; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:6; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:7; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:8; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:9; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:10; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:10; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:12; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:13; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:14; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:15; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:16; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO:17; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO:18; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 19; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 20; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 21; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 22; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 23; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 24; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 25; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 26; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 27; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 28; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 29; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 30; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 31; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 32; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 33; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 34; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 35; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 36; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 37; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 38; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 39; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 40; or The HCDR1, HCDR2, and HCDR3 are amino acid sequences identical to the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region defined by SEQ ID NO: 41; the LCDR1, LCDR2, and LCDR3 are amino acid sequences identical to the LCDR1, LCDR2, and LCDR3 of the light chain variable region defined by SEQ ID NO: 42; Optionally, the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are defined by the Kabat, Chothia, AbM, Contact, or IMGT system.

2. An anti-TL1A antibody or an antigen-binding fragment thereof, characterized in that, Comprising HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3; HCDR1: X1YX2MH, wherein X1 is S, G, R or V, and X2 is I or T; HCDR2: X3X4NPYX5X6X7TX8YX9X 10 KFKG, wherein X3 is Y or L, X4 is V or I, X5 is N or S, X6 is D or G, X7 is V or G, X8 is N, T or K, X9 is I or N, X 10 is E or Q; HCDR3: X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 Y, wherein, X 11 is Y, V or H, X 12 is Y, Q or R, X 13 is Y or L, X 14 is G or R, X 15 is N, Y, H, A, R, E, M or P, X 16 is P, D, V, L or S, X 17 is G or W, X 18 is F, L, M or Y, X 19 is A or D; LCDR1: X 20 ASX 21 X 22 VX 23 X 24 X 25 X 26 X 27 , where X 20 is K or S, X 21 is Q or S, X 22 is D or S, X 23 is G, T or S, X 24 is T, Y or A, X 25 is M or A, X 26 is V or H, X 27 is A or empty; LCDR2: X 28 X 29 X 30 X 31 X 32 X 33 X 34 , where X 28 is W or D, X 29 is T or A, X 30 is S or A, X 31 is T or K, X 32 is R or L, X 33 is H or A, X 34 is T or S; LCDR3: QQX 35 SSX 36 PX 37 T, where X 35 is Y, W or H, X 36 is Y, D or S, X 37 is Y or W; Optionally, in the HCDR1, X1 is G, R or V, and X2 is T; or X1 is S and X2 is I; Optionally, in the HCDR2, X3 is L, X4 is I, X5 is S, X6 is G, X7 is V, X8 is T, X9 is N, X 10 is Q; or X3 is Y, X4 is V or I, X5 is N, X6 is D, X7 is G, X8 is N or K, X9 is I, X 10 is E; Optionally, in said HCDR3, X 11 is V, X 12 is Q or R, X 13 is Y or L, X 14 is R, X 15 is Y, A, R, E, M or P, X 16 is D, V, L or S, X 17 is G, X 18 is L, M or Y, X 19 is A or D; or X 11 is Y or H, X 12 is Y, X 13 is Y or L, X 14 is G, X 15 is N or H, X 16 is P, X 17 is W, X 18 is F, X 19 is A; Optionally, in the LCDR1, X 20 is S, X 21 is S, X 22 is S, X 23 is T, X 24 is Y, X 25 is M, X 26 is H, X 27 is empty; or X 20 is K, X 21 is Q, X 22 is D, X 23 is G or S, X 24 is T or A, X 25 is A, X 26 is V, X 27 is A; Optionally, in the LCDR2, X 28 is D, X 29 is T, X 30 is S, X 31 is K, X 32 is L, X 33 is A, X 34 is S; or X 28 is W, X 29 is T or A, X 30 is S or A, X 31 is T, X 32 is R, X 33 is H, X 34 is T; Optionally, in the LCDR3, X 35 is W, X 36 is D, X 37 is Y; or X 35 is Y or H, X 36 is Y or S, X 37 is Y or W; Optionally, HCDR1: X1YTMH, wherein X1 is G, R or V; HCDR2: LINPYSGVTTYNQKFKG; HCDR3: VX 12 X 13 RX 15 X 16 GX 18 X 19 Y, wherein, X 12 is Q or R, X 13 is Y or L, X 15 is Y, A, R, E, M or P, X 16 is D, V, L or S, X 18 is L, M or Y, X 19 is A or D; LCDR1: SASSSVTYMH; LCDR2: DTSKLAS; LCDR3: QQWSSDPYT.

3. The anti-TL1A antibody or antigen-binding fragment thereof according to claim 1 or 2, characterized in that, The anti-TL1A antibody or antigen-binding fragment thereof comprises: an HCDR1 having the amino acid sequence shown in SEQ ID NO: 43, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 44, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 45, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 46, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 47, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 48; or an HCDR1 having the amino acid sequence shown in SEQ ID NO: 49, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 51, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or an HCDR1 having the amino acid sequence shown in SEQ ID NO: 43, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 55, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 56, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 57, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 58, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 59; or an HCDR1 having the amino acid sequence shown in SEQ ID NO: 60, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 51, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or an HCDR1 having the amino acid sequence shown in SEQ ID NO: 61, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 51, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO: 49, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 62, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO: 49, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 63, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO: 49, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 64, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO: 49, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 65, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO: 49, an HCDR2 having the amino acid sequence shown in SEQ ID NO: 50, an HCDR3 having the amino acid sequence shown in SEQ ID NO: 66, and an LCDR1 having the amino acid sequence shown in SEQ ID NO: 52, an LCDR2 having the amino acid sequence shown in SEQ ID NO: 53, an LCDR3 having the amino acid sequence shown in SEQ ID NO: 54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO:49, an HCDR2 having the amino acid sequence shown in SEQ ID NO:50, an HCDR3 having the amino acid sequence shown in SEQ ID NO:67, and an LCDR1 having the amino acid sequence shown in SEQ ID NO:52, an LCDR2 having the amino acid sequence shown in SEQ ID NO:53, an LCDR3 having the amino acid sequence shown in SEQ ID NO:54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO:60, an HCDR2 having the amino acid sequence shown in SEQ ID NO:50, an HCDR3 having the amino acid sequence shown in SEQ ID NO:68, and an LCDR1 having the amino acid sequence shown in SEQ ID NO:52, an LCDR2 having the amino acid sequence shown in SEQ ID NO:53, an LCDR3 having the amino acid sequence shown in SEQ ID NO:54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO:60, an HCDR2 having the amino acid sequence shown in SEQ ID NO:50, an HCDR3 having the amino acid sequence shown in SEQ ID NO:69, and an LCDR1 having the amino acid sequence shown in SEQ ID NO:52, an LCDR2 having the amino acid sequence shown in SEQ ID NO:53, an LCDR3 having the amino acid sequence shown in SEQ ID NO:54; or An HCDR1 having the amino acid sequence shown in SEQ ID NO:60, an HCDR2 having the amino acid sequence shown in SEQ ID NO:50, an HCDR3 having the amino acid sequence shown in SEQ ID NO:65, and an LCDR1 having the amino acid sequence shown in SEQ ID NO:52, an LCDR2 having the amino acid sequence shown in SEQ ID NO:53, an LCDR3 having the amino acid sequence shown in SEQ ID NO:54; Optionally, the anti-TL1A antibody or its antigen-binding fragment comprises a heavy chain framework region and / or a light chain framework region; Optionally, at least a portion of the heavy chain framework region and / or the light chain framework region is derived from at least one of a murine antibody, a primate antibody, a bovine antibody, a horse antibody, a dairy cow antibody, a porcine antibody, a sheep antibody, a goat antibody, a dog antibody, a cat antibody, a rabbit antibody, a camel antibody, a donkey antibody, a deer antibody, a mink antibody, a chicken antibody, a duck antibody, a goose antibody, a turkey antibody, a fighting chicken antibody or a mutant thereof; Optionally, at least a portion of the heavy chain framework region and / or the light chain framework region is derived from at least one of a rabbit antibody or a mutant thereof, a murine antibody or a mutant thereof, and a human antibody or a mutant thereof; Optionally, the anti-TL1A antibody or antigen-binding fragment thereof comprises: a heavy chain variable region as shown by the amino acid sequence of any one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41; and a light chain variable region as shown by the amino acid sequence of any one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42; Optionally, the anti-TL1A antibody or antigen-binding fragment thereof comprises: a heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:1, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:2; or a heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:3, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:4; or a heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:5, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:6; or a heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:7, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:8; or a heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:9, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:10; or a heavy chain variable region as shown by the amino acid sequence of SEQ ID NO:11, and a light chain variable region as shown by the amino acid sequence of SEQ ID NO:12; The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:13, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:14; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:15, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:16; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:17, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:18; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:19, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:20; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:21, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:22; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:23, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:24; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:25, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:26; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:27, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:28; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:29, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:30; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:31, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:32; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:33, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:34; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:35, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:36; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:37, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:38; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:39, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:40; or The heavy chain variable region as shown in the amino acid sequence of SEQ ID NO:41, and the light chain variable region as shown in the amino acid sequence of SEQ ID NO:

42.

4. The anti-TL1A antibody or antigen-binding fragment thereof according to claim 1 or 2, characterized in that, Further comprising a heavy chain constant region and / or a light chain constant region; Optionally, at least a part of at least one of the heavy chain constant region and the light chain constant region is derived from at least one of a murine antibody, a primate antibody, a bovine antibody, a horse antibody, a dairy cow antibody, a pig antibody, a sheep antibody, a goat antibody, a dog antibody, a cat antibody, a rabbit antibody, a camel antibody, a donkey antibody, a deer antibody, a mink antibody, a chicken antibody, a duck antibody, a goose antibody, a turkey antibody, a fighting chicken antibody or a mutant thereof; Optionally, the heavy chain constant region comprises a heavy chain constant region selected from IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE or IgD; or the light chain constant region comprises a light chain constant region selected from kappa type or lambda type; Optionally, both the light chain constant region and the heavy chain constant region are derived from at least one of a rabbit antibody or a mutant thereof, a murine antibody or a mutant thereof and a human antibody or a mutant thereof; Optionally, the N-terminus of the heavy chain constant region is linked to the C-terminus of the heavy chain variable region; and / or the N-terminus of the light chain constant region is linked to the C-terminus of the light chain variable region; Optionally, the heavy chain constant region has an amino acid sequence as shown in SEQ ID NO:70; Optionally, the light chain constant region has an amino acid sequence as shown in SEQ ID NO:71; Optionally, the antibody comprises at least one selected from polyclonal antibody, full-length monoclonal antibody, Fab antibody, Fab' antibody, F(ab')2 antibody, Fv antibody, single-chain antibody, and minimum recognition unit; or the antigen-binding fragment comprises at least one selected from F(ab')2 fragment, Fab' fragment, Fab fragment, F(ab)2 fragment, Fv fragment, scFv fragment, scFv-Fc fusion protein, scFv-Fv fusion protein and minimum recognition unit.

5. A nucleic acid molecule, characterized in that, The nucleic acid molecule encodes the anti-TL1A antibody or its antigen-binding fragment according to any one of claims 1 to 4; Optionally, the nucleic acid molecule is DNA.

6. An expression vector, characterized in that, Carrying the nucleic acid molecule according to claim 5; Optionally, the expression vector comprises at least one selected from eukaryotic expression vectors or prokaryotic expression vectors.

7. A recombinant cell, characterized in that, Comprising: Carrying the nucleic acid molecule according to claim 5 or the expression vector according to claim 6; Or, Expressing the anti-TL1A antibody or its antigen-binding fragment according to any one of claims 1 to 4; Optionally, the recombinant cell is obtained by introducing the expression vector according to claim 6 into a host cell.

8. An conjugate, characterized in that, Containing: The anti-TL1A antibody or its antigen-binding fragment according to any one of claims 1 to 4; and A conjugate part, which is linked to the anti-TL1A antibody or its antigen-binding fragment; Optionally, the conjugate part is selected from at least one of a purification tag or label, a carrier, a drug, a toxin, a cytokine, a modifier; Optionally, the carrier is selected from at least one of magnetic microspheres, plastic microspheres, plastic particles, microtiter plates, glass, capillary tubes, nylon and nitrocellulose membranes; Optionally, the purification tag or label is selected from at least one of a protein tag, colloidal gold, a radioactive label, a luminescent substance, a colored substance, an enzyme, biotin / avidin and a spin label; Optionally, the purification tag or label is selected from at least one of a fluorescent label, a chromophore label, and an electron-dense label; Optionally, the protein tag includes at least one of a His tag, a Flag tag, a GST tag, an MBP tag, a SUMO tag, and a C-Myc tag.

9. A reagent or kit, characterized in that, Comprising: The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, or the conjugate according to claim 8.

10. A pharmaceutical composition, characterized in that, Comprising: The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, the nucleic acid molecule according to claim 5, the expression vector according to claim 6, the recombinant cell according to claim 7, or the conjugate according to claim 8; Optionally, further comprising a pharmaceutically acceptable excipient.

11. Use of the anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, the nucleic acid molecule according to claim 5, the expression vector according to claim 6, the recombinant cell according to claim 7, the conjugate according to claim 8, or the pharmaceutical composition according to claim 10 in the preparation of a multispecific antibody, a fusion protein, a drug, or a kit; Optionally, the drug is used for preventing and / or treating TL1A-mediated related diseases; Optionally, the TL1A-mediated related diseases include inflammatory or immune diseases; Optionally, the inflammatory or immune diseases include allergy, asthma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, fibrosis-related diseases, medically refractory ulcerative colitis, systemic lupus erythematosus, psoriasis, type 1 diabetes, and transplant rejection; Optionally, the inflammatory or immune diseases include Crohn's disease, ulcerative colitis, intestinal fibrosis, pulmonary fibrosis, and liver fibrosis; Optionally, the kit is used for detecting TL1A.

12. A method for detecting TL1A, characterized in that, Comprising: Contacting a sample to be detected with the anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, the conjugate according to claim 8, or the reagent or kit according to claim 9 to form an immune complex; Optionally, based on the signal of the immune complex, determining whether the sample to be detected contains TL1A or cells expressing TL1A, or determining the content of TL1A or cells expressing TL1A in the sample to be detected; Optionally, the signal of the immune complex is detected by at least one method of ELISA, WB, and IHC; Optionally, the signal includes a fluorescent signal.

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