Anti-TL1a antibody or antigen-binding fragment thereof and use thereof

Abstract

The present invention relates to an anti-TL1A antibody or an antigen-binding fragment thereof and the use thereof. The anti-TL1A antibody or the antigen-binding fragment thereof comprises complementarity determining regions HCDR1, HCDR2 and HCDR3 of a heavy chain variable region and / or complementarity determining regions LCDR1, LCDR2 and LCDR3 of a light chain variable region. The anti-TL1A antibody or the antigen-binding fragment thereof can block, inhibit or reduce the activity of TL1A regulation, and can specifically bind to TL1A, so as to prevent and / or treat TL1A-mediated related diseases or disorders.

Description

Anti-TL1A antibodies or antigen-binding fragments thereof and applications thereof Technical Field

[0001] The present application relates to the field of biomedicine technology, and specifically to an anti-TL1A antibody or an antigen-binding fragment thereof and applications thereof. Background Art

[0002] Proteins structurally related to tumor necrosis factor (TNF) are collectively referred to as the TNF superfamily. Tumor necrosis factor (TNF)-like ligand 1A (TL1A) is a member of the TNF family of cytokines, also known as TNFSF15. TL1A is the only known ligand for its receptor, death receptor 3 (DR3), also known as TNFRSF25. TL1A expression on antigen-presenting cells (monocytes, macrophages, dendritic cells) and DR3 expression on effector cells (T cells, NK and NKT cells) are highly dependent on proinflammatory conditions. In vivo and in vitro evidence demonstrates a costimulatory role for the TL1A / DR3 pathway in enhancing T cell and effector cell function, inflammatory cell expansion, and cytokine secretion. Furthermore, this pathway has been implicated in the regulation of pathogenic Th1, Th2, and Th17 T-helper cell responses and NK and NK-T cell responses in immune-mediated diseases.

[0003] Currently, studies on mice deficient in the DR3 or TL1A genes or treated with anti-TL1A antibodies have confirmed the role of this pathway in a variety of autoimmune disease models, such as inflammatory bowel disease (IBD), asthma, multiple sclerosis, and arthritis. IBD refers to a series of intestinal disorders that lead to inflammatory conditions in the gastrointestinal tract. Severe forms of IBD may be characterized by intestinal fibrosis, which is the accumulation of scar tissue in the intestinal wall. The main types of IBD are ulcerative colitis (UC) and Crohn's disease (CD). UC and CD are both chronic, relapsing, remitting inflammatory conditions of the gastrointestinal tract that most often begin during adolescence and young adulthood. UC involves the mucosal layer of the large intestine, and symptoms include abdominal pain and diarrhea, often accompanied by blood and mucus. CD may affect the entire thickness of the intestinal wall and all parts of the GI tract from mouth to anus. CD symptoms include abdominal pain, diarrhea, and other more subtle symptoms, such as weight loss, nutritional deficiencies, and fever.

[0004] There are a limited number of treatments available for patients with IBD. In addition, a significant proportion of patients lack or lose response to existing anti-inflammatory therapies. When patients receive such ineffective anti-inflammatory treatments, the disease worsens. Currently, the treatment for patients who do not respond to first-line treatment is surgery, either strictureplasty (reshaping of the intestine) or resection (removal of the intestine). Surgical treatment for IBD is invasive, and an estimated one-third of patients who undergo surgery will experience postoperative risks such as anastomotic leaks, infection, and bleeding.

[0005] The pathogenesis of IBD is thought to involve an uncontrolled immune response that may be triggered by certain environmental factors in a genetically susceptible host. The heterogeneity in disease pathogenesis and clinical course, combined with the varying responses to treatment and associated side effects, suggests that targeted therapeutic approaches to treat these diseases are an ideal therapeutic strategy. However, few targeted therapies are available for patients with IBD, particularly those who may not respond to existing IBD therapies.

[0006] Therefore, the development of novel therapeutics for IBD, as well as for the treatment of other TL1A-mediated diseases and conditions, remains an unmet clinical need. Summary of the Invention

[0007] In response to the prior art, the present application provides an anti-TL1A antibody or an antigen-binding fragment thereof and its use. The anti-TL1A antibody or its antigen-binding fragment comprises the complementarity determining regions HCDR1, HCDR2, HCDR3 of the heavy chain variable region and / or the complementarity determining regions LCDR1, LCDR2, LCDR3 of the light chain variable region; the anti-TL1A antibody or its antigen-binding fragment can block, inhibit or reduce the activity regulated by TL1A, can specifically bind to TL1A, and prevent and / or treat related diseases or conditions mediated by TL1A.

[0008] In a first aspect, the present application provides an anti-TL1A antibody or an antigen-binding fragment thereof, comprising:

[0009] (a) a heavy chain variable region comprising the following complementarity determining regions:

[0010] a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46;

[0011] a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47;

[0012] a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48;

[0013] (b) a light chain variable region comprising the following complementarity determining regions:

[0014] LCDR1 comprising the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49, and that functions identically or similarly to the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49;

[0015] LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50;

[0016] LCDR3 comprising the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, and functions the same or similar to the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51.

[0017] The substitution, deletion or addition of one or more amino acids described herein is the substitution, deletion or addition of 1 or 2 amino acids. In some embodiments, the substitution, deletion or addition of one or more amino acids is a conservative modification.

[0018] In some embodiments, the amino acids that differ in the amino acid sequences having at least 80% identity or having one or more amino acid substitutions, deletions, or additions compared to the amino acid sequences set forth in SEQ ID NOs: 1-3, 7-9, 13-15, 19-21, 25-26, 28-30, 34-36, 40-42, and 46-48 are primarily or entirely located in the FR region of the heavy chain variable region. In some embodiments, the amino acids that differ in the amino acid sequences having at least 80% identity or having one or more amino acid substitutions, deletions, or additions compared to the amino acid sequences set forth in SEQ ID NOs: 4-6, 10-12, 16-18, 22-24, 27, 31-33, 37-39, 43-45, and 49-51 are primarily or entirely located in the FR region of the light chain variable region.

[0019] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0020] (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2, and 3, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5, and 6, respectively;

[0021] (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8, and 9, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11, and 12, respectively;

[0022] (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14, and 15, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17, and 18, respectively;

[0023] (4) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 19, 20, and 21, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 22, 23, and 24, respectively;

[0024] (5) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 25, 20, and 26, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 22, 23, and 27, respectively;

[0025] (6) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 28, 29, and 30, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 31, 32, and 33, respectively;

[0026] (7) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 34, 35, and 36, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 37, 38, and 39, respectively;

[0027] (8) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 40, 41, and 42, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 43, 44, and 45, respectively; or

[0028] (9) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 46, 47 and 48, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 49, 50 and 51, respectively.

[0029] In a preferred embodiment, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0030] (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2, and 3, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5, and 6, respectively;

[0031] (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12, respectively; or

[0032] (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14 and 15, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17 and 18, respectively.

[0033] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof is selected from 16H6, 12B3, 56C8, 5C6, 28G7, 70A3, 51G9, 69B1, 13B8, and humanized antibodies thereof (e.g., 16H6-H1L1, 16H6-H1L2, 16H6-H1L3, 16H6-H1L4, 16H6-H2L1, 16H6-H2L2, 16H6 -H2L3, 16H6-H2L4, 16H6-H3L1, 16H6-H3L2, 16H6-H3L3, 16H6-H3L4, 16H6-H4L1, 16H6-H 4L2, 16H6-H4L3, 16H6-H4L4, 12B3-H1L1, 12B3-H1L2, 12B3-H1L4, 12B3-H1L5, 12B3-H1L6 , 12B3-H1L8, 12B3-H2L1, 12B3-H2L2, 12B3-H2L4, 12B3-H2L5, 12B3-H3L1, 12B3-H3L2, 1 2B3-H3L4, 12B3-H3L5, 12B3-H3L6, 12B3-H3L8, 12B3-H4L1, 12B3-H4L2, 12B3-H4L4, 12B3 -H4L5, 12B3-H4L6, 12B3-H4L8, 12B3-H6L1, 12B3-H6L4, 12B3-H6L6, 12B3-H6L8, 12B3-H7L1, 12B3-H7L4, 12B3-H7L6, 12B3-H7L8, 12B3-H8L1, 12B3-H8L6, 12B3-H8L8) or an antigen-binding fragment thereof.

[0034] In some embodiments, the antibody is a mouse antibody, a monkey antibody, a rabbit antibody, a chimeric antibody, a humanized antibody, or a fully human antibody.

[0035] In some embodiments, the antibody is a murine antibody.

[0036] In some embodiments, the antibody is a chimeric antibody comprising an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the extracellular antigen-binding domain comprises the anti-TL1A antibody or an antigen-binding fragment thereof described herein.

[0037] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof is selected from at least one of a monoclonal antibody, a polyclonal antibody, a neutralizing antibody, an antagonistic antibody, an anti-idiotypic antibody, a fucosylated antibody, a monospecific antibody, a multispecific antibody, a nanobody, a Fab fragment, a Fab' fragment, a F(ab')2 fragment, a Fd fragment, a Fv fragment, a dAb fragment, an isolated CDR region, and a scFv; the anti-TL1A antibody is preferably a monoclonal antibody or a multispecific antibody, preferably, the multispecific antibody is a bispecific antibody, a trispecific antibody, or a tetraspecific antibody; or preferably, the multispecific antibody further comprises at least one second antibody having a second binding specificity for a second target.

[0038] In some embodiments, the antibody is a monoclonal antibody.

[0039] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof further comprises a heavy chain constant region and / or a light chain constant region.

[0040] Preferably, the heavy chain constant region is the heavy chain constant region of IgG, IgA, IgM, IgE or IgD or a variant thereof; the heavy chain constant region is preferably the heavy chain constant region of IgG (e.g., human IgG) or a variant thereof, such as the constant region of IgG1, IgG2, IgG3 or IgG4 or a variant thereof; the heavy chain constant region is more preferably the heavy chain constant region of human IgG1 or a variant thereof, such as the heavy chain constant region of human IgG1 or a variant thereof.

[0041] Preferably, the light chain constant region is the constant region of a human kappa chain or lambda chain, or a variant thereof.

[0042] In some embodiments, the heavy chain constant region comprises a full-length heavy chain constant region or a fragment thereof, and the fragment can be selected from a CH1 region, a CH2 region, an Fc region, or a CH3 region.

[0043] As non-limiting examples, the anti-TL1A antibody or antigen-binding fragment thereof has one or more of the following properties:

[0044] (1) Ability to bind to human TL1A;

[0045] (2) capable of binding to non-human mammalian TL1A, such as mouse, rabbit, cat, dog, or pig TL1A, preferably capable of binding to mouse TL1A;

[0046] (3) capable of binding to non-human primate TL1A, preferably, capable of binding to cynomolgus monkey TL1A;

[0047] (4) cross-reacting with human, non-human mammalian, and non-human primate TL1A, preferably, cross-reacting with human, mouse, and cynomolgus monkey TL1A;

[0048] (5) having an affinity for a human homolog of TL1A that is lower than the affinity for human TL1A, and the human homolog of TL1A is selected from TNFSF6, TNFSF10, TNFSF14, TNF-β, TNF-α, lymphotoxin α2-β1, and lymphotoxin α1-β2;

[0049] (6) blocking, inhibiting or reducing the interaction between TL1A and receptor DR3 (TNFRSF25);

[0050] (7) blocking, inhibiting, or reducing the signaling pathway triggered by TL1A;

[0051] (8) blocking, inhibiting, or reducing TL1A-regulated activity;

[0052] (9) Block, inhibit or reduce TL1A-mediated cellular responses; such as lymphocyte proliferation, cytokine expression or lymphocyte survival.

[0053] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof has a blocking effect on TL1A-induced caspase activity in TF-1 cells.

[0054] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof can cross-bind to human, cynomolgus monkey, mouse, or rat TL1A.

[0055] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof can specifically bind to human, mouse, rat, or cynomolgus monkey TL1A.

[0056] The second aspect of the present application provides a nucleic acid molecule encoding the anti-TL1A antibody or antigen-binding fragment thereof according to the first aspect.

[0057] The third aspect of the present application provides a recombinant vector comprising the nucleic acid molecule described in the first aspect.

[0058] The fourth aspect of the present application provides a host cell comprising the nucleic acid molecule described in the second aspect or the recombinant vector described in the third aspect.

[0059] A fifth aspect of the present application provides a method for preparing an anti-TL1A antibody or antigen-binding fragment thereof, comprising culturing the host cell described in the fourth aspect. The method may further comprise isolating and / or purifying the antibody or fragment thereof from the cell culture after the expression or culturing step, for example, by purification using a Protein A affinity column.

[0060] In some embodiments, the host cell is a prokaryotic cell. In other embodiments, the host cell is a eukaryotic cell.

[0061] In some embodiments, the host cell is selected from yeast cells, mammalian cells, or other cells suitable for preparing antibodies or antigen-binding fragments thereof, or moieties thereof. Mammalian cells are, for example, Chinese hamster ovary cells (CHO), human kidney epithelial cell lines 293 cells, or 293T cells. In some embodiments, the host cell is a recombinant CHO cell. In some embodiments, the method further comprises isolating and purifying the expression product of the host cell, for example, by purification using a Protein A affinity column.

[0062] In a sixth aspect, the present application provides the anti-TL1A antibody or antigen-binding fragment thereof according to the first aspect, the nucleic acid molecule according to the second aspect, the recombinant vector according to the third aspect, and the host cell according to the fourth aspect for preventing and / or treating diseases or conditions mediated by TL1A.

[0063] In some embodiments, the present application relates to the use of the anti-TL1A antibody or antigen-binding fragment thereof of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect in the preparation of a medicament for preventing and / or treating a disease or condition mediated by TL1A. Alternatively, the present application relates to a method for preventing and / or treating a disease or condition mediated by TL1A, comprising administering to a subject in need thereof the anti-TL1A antibody or antigen-binding fragment thereof of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect. Alternatively, the present application relates to the anti-TL1A antibody or antigen-binding fragment thereof of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect for preventing and / or treating a disease or condition mediated by TL1A.

[0064] In some embodiments, the disease or condition is prevented, alleviated, ameliorated or inhibited by eliminating, inhibiting or reducing TL1A activity.

[0065] In some embodiments, the disease or disorder is an immune-related or inflammatory disease.

[0066] In some embodiments, the disease or condition is selected from at least one of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), systemic sclerosis-associated interstitial lung disease, idiopathic pulmonary fibrosis, viral-induced pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), allergic lung inflammation, neurodegenerative diseases, cancer, diabetes, arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, transplant rejection, graft-versus-host disease (GVHD), spondyloarthropathies, primary sclerosing cholangitis, primary biliary cirrhosis, atherosclerosis, bladder syndrome, interstitial cystitis, urinary intestinal dysfunction, sepsis, uveitis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus, cutaneous lupus erythematosus, autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjögren's syndrome, scleroderma, and vasculitis.

[0067] In the present application, the inflammatory bowel disease includes Crohn's disease and ulcerative colitis.

[0068] In some embodiments, the disease or disorder is inflammatory bowel disease.

[0069] In a seventh aspect, the present application provides a kit for detecting TL1A, comprising the anti-TL1A antibody or antigen-binding fragment thereof according to the first aspect and the nucleic acid molecule according to the second aspect.

[0070] Beneficial effects of this application:

[0071] The anti-TL1A antibodies or antigen-binding fragments thereof disclosed herein have high affinity for TL1A and high biological activity, effectively blocking, inhibiting, or reducing the interaction between TL1A and its receptor, DR3. These antibodies or antigen-binding fragments can block, inhibit, or reduce TL1A-regulated activities and have a blocking effect on TL1A-induced caspase activity in TF-1 cells.

[0072] The anti-TL1A antibody or antigen-binding fragment thereof of the present application can cross-bind to TL1A of humans, non-human primates (such as cynomolgus macaques), and non-human mammals (such as mice and rats), and can specifically bind to TL1A, specifically, can specifically bind to TL1A of humans, non-human primates (such as cynomolgus macaques), and non-human mammals (such as mice and rats), and has good stability.

[0073] The anti-TL1A antibody or antigen-binding fragment thereof of the present application strongly binds to both human TL1A monomers and polymers (eg, trimers). BRIEF DESCRIPTION OF THE DRAWINGS

[0074] FIG1 is a graph showing the reporter gene signal results induced by TL1A in Example 1.

[0075] FIG2 is a graph showing the reporter gene activity detection results of the positive control antibody 1D1 in Example 1.

[0076] FIG3-1 is a graph showing the activity detection results of the chimeric antibody 5C6 reporter gene assay in Example 4.

[0077] Figure 3-2 shows the activity detection results of the chimeric antibodies 28G7 and 16H6 reporter gene method in Example 4.

[0078] Figure 3-3 shows the activity detection results of the chimeric antibodies 51G9, 69B1, 12B3 and 56C8 using the reporter gene method in Example 4.

[0079] Figures 3-4 are graphs showing the activity detection results of the chimeric antibodies 13B8 and 70A3 reporter gene assay in Example 4.

[0080] FIG4-1 is a graph showing the activity detection results of the chimeric antibody 5C6 using the caspase method in Example 5.

[0081] Figure 4-2 shows the activity detection results of the chimeric antibodies 28G7 and 16H6 using the caspase method in Example 5.

[0082] FIG4-3 is a graph showing the activity detection results of the chimeric antibodies 51G9 and 69B1 using the caspase method in Example 5.

[0083] Figure 4-4 shows the activity detection results of the chimeric antibodies 12B3 and 56C8 using the caspase method in Example 5.

[0084] Figures 4-5 are graphs showing the activity detection results of the chimeric antibody 13B8 in Example 5 using the caspase method.

[0085] Figures 4-6 are graphs showing the activity detection results of the chimeric antibody 70A3 of Example 5 using the caspase method.

[0086] FIG5-1 is a graph showing the binding activity test results of the chimeric antibodies 16H6, 12B3 and 56C8 of Example 6 with the human TL1A monomer.

[0087] FIG5-2 is a graph showing the binding activity test results of chimeric antibodies 69B1 and 13B8 of Example 6 with human TL1A monomer.

[0088] Figure 6-1 is a graph showing the binding activity test results of the chimeric antibodies 16H6, 12B3 and 56C8 of Example 6 with the human TL1A trimer.

[0089] Figure 6-2 is a graph showing the binding activity test results of chimeric antibodies 69B1 and 13B8 in Example 6 with human TL1A trimer.

[0090] FIG7-1 is a graph showing the activity detection results of the humanized antibodies 16H6-H1L1, 16H6-H1L2, 16H6-H1L3 and 16H6-H1L4 in Example 8 using the human TL1A trimer reporter gene assay.

[0091] Figure 7-2 shows the activity detection results of the humanized antibodies 16H6-H2L1, 16H6-H2L2, 16H6-H2L3 and 16H6-H2L4 in Example 8 using the human TL1A trimer reporter gene assay.

[0092] Figure 7-3 shows the activity detection results of the humanized antibodies 16H6-H3L1, 16H6-H3L2, 16H6-H3L3 and 16H6-H3L4 in Example 8 using the human TL1A trimer reporter gene assay.

[0093] Figure 7-4 shows the activity detection results of the humanized antibodies 16H6-H4L1, 16H6-H4L2, 16H6-H4L3 and 16H6-H4L4 in Example 8 using the human TL1A trimer reporter gene assay.

[0094] Figure 7-5 shows the activity detection results of the humanized antibodies 12B3-H1L1, 12B3-H1L2, 12B3-H1L4 and 12B3-H1L5 in Example 8 using the human TL1A trimer reporter gene method.

[0095] Figure 7-6 shows the activity detection results of the humanized antibodies 12B3-H2L1, 12B3-H2L2, 12B3-H2L4 and 12B3-H2L5 in Example 8 using the human TL1A trimer reporter gene method.

[0096] Figure 7-7 shows the activity detection results of the humanized antibodies 12B3-H3L1, 12B3-H3L2, 12B3-H3L4 and 12B3-H3L5 in Example 8 using the human TL1A trimer reporter gene assay.

[0097] Figures 7-8 are graphs showing the activity detection results of the humanized antibodies 12B3-H4L1, 12B3-H4L2, 12B3-H4L4 and 12B3-H4L5 in Example 8 using the human TL1A trimer reporter gene assay.

[0098] Figures 7-9 are graphs showing the activity detection results of the humanized antibodies 12B3-H1L6, 12B3-H6L1 and 12B3-H6L6 in Example 8 using the human TL1A trimer reporter gene assay.

[0099] Figures 7-10 are graphs showing the activity detection results of the humanized antibodies 12B3-H1L8, 12B3-H6L4 and 12B3-H6L8 in Example 8 using the human TL1A trimer reporter gene assay.

[0100] Figures 7-11 are graphs showing the activity detection results of the humanized antibodies 12B3-H3L6, 12B3-H7L1 and 12B3-H7L6 in Example 8 using the human TL1A trimer reporter gene assay.

[0101] Figures 7-12 are graphs showing the activity detection results of the humanized antibodies 12B3-H3L8, 12B3-H7L4 and 12B3-H7L8 in Example 8 using the human TL1A trimer reporter gene assay.

[0102] Figures 7-13 are graphs showing the activity detection results of the humanized antibodies 12B3-H4L6, 12B3-H8L1 and 12B3-H8L6 in Example 8 using the human TL1A trimer reporter gene assay.

[0103] Figures 7-14 are graphs showing the activity detection results of the humanized antibodies 12B3-H4L8 and 12B3-H8L8 in Example 8 using the human TL1A trimer reporter gene assay.

[0104] Figure 8-1 shows the results of the caspase activity assay of the humanized antibodies 12B3-H1L8, 12B3-H7L1, 12B3-H8L1 and 12B3-H8L8 in Example 9 against human TL1A trimer.

[0105] Figure 8-2 shows the results of the caspase activity assay of the humanized antibodies 16H6-H3L1 and 16H6-H4L3 in Example 9 against human TL1A trimer.

[0106] Figure 8-3 shows the results of the caspase activity assay of the humanized antibody 16H6-H3L3 in Example 9 against human TL1A trimer.

[0107] Figure 8-4 shows the results of the caspase activity assay of the humanized antibody 16H6-H4L1 in Example 9 against human TL1A trimer.

[0108] Figure 9-1 is a graph showing the activity detection results of the humanized antibodies 16H6-H4L1, 16H6-H4L3 and 12B3-H8L1 in Example 10 against human TL1A trimer cytokine assay.

[0109] Figure 9-2 shows the activity test results of the humanized antibodies 12B3-H8L8 and 12B3-H7L1 in Example 10 against human TL1A trimer cytokine assay.

[0110] Figure 10-1 is a graph showing the DAI score results of the humanized antibodies 16H6-H4L1 and 16H6-H4L3 in Example 11 in a rat model.

[0111] FIG10-2 is a graph showing the colon weight / length / body weight ratios of the humanized antibodies 16H6-H4L1 and 16H6-H4L3 in Example 11 in a rat model.

[0112] Figure 10-3 shows the results of colon gross scoring of the humanized antibodies 16H6-H4L1 and 16H6-H4L3 in Example 11 in a rat model.

[0113] Figure 10-4 is a graph showing the results of colon pathology scoring of the humanized antibodies 16H6-H4L1 and 16H6-H4L3 in Example 11 in a rat model. DETAILED DESCRIPTION

[0114] In order to make the present application easier to understand, the present application will be described in detail below with reference to embodiments. These embodiments are merely illustrative and do not limit the scope of application of the present application.

[0115] Unless otherwise defined, the various technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. See, for example, Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, NY 1994); Sambrook et al., Molecular Cloning, A Laboratory Manual, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989); Davis et al., Basic Methods in Molecular Biology, Elsevier Science Publishing Inc., New York, USA (2012); Abbas et al., Cellular and Molecular Immunology, Elsevier Science Health Science div (2009); He Wei et al., Medical Immunology (2nd ed.), People's Medical Publishing House, 2010.

[0116] Unless otherwise indicated, the terms "comprise, comprise, and comprising" or their equivalents (contain, contains, containing, include, includes, including) used herein are open-ended expressions and mean that in addition to the listed elements, components, and steps, other unspecified elements, components, and steps may also be included.

[0117] Unless otherwise indicated, the term "optional" or "optionally" used herein means that the object or event it modifies exists or does not exist, or occurs or does not occur. Unless the context clearly indicates otherwise, the word "or" herein is intended to include "and".

[0118] As used herein, "about" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within one or more standard deviations, as practiced in the art. Alternatively, "about" can mean a range of up to 20% (i.e., ±20%), for example, a fluctuation within ±10%, ±5%, ±2%, ±1%, or ±0.5% of the specific value given. Furthermore, particularly with respect to biological systems or methods, the term can mean up to an order of magnitude or up to five times a value. When a specific value is given in the application or claims, unless otherwise indicated, "about" should be understood to mean within an acceptable error range for that specific value. Throughout this document, unless otherwise indicated, the value of each measured value, step parameter, or condition is modified by the word "about."

[0119] Herein, singular terms encompass plural referents and vice versa unless the context clearly dictates otherwise.

[0120] Unless otherwise indicated, the term "treat" as used herein means that after administration, a disease or its related symptoms can be inhibited, contained, alleviated, improved, slowed down, relieved or eliminated, the progression of a disease or its related symptoms can be delayed, postponed, slowed down, suspended or terminated, or the recurrence of a disease or its related symptoms can be prevented, controlled or reduced. For the prevention and treatment of a disease, a therapeutically effective amount or a prophylactically effective amount can be determined by a clinician through conventional methods or experience based on the individual condition of the subject, the severity of the disease, sex, age, weight, mode of administration, etc.

[0121] Unless otherwise indicated, the term "subject" as used herein encompasses any vertebrate, e.g., mammals, such as humans, non-human primates, sheep, dogs, cats, horses, cows, chickens, pigs, mice, etc. Preferably, the subject in the present application is a human.

[0122] The term "antibody" refers to a polypeptide that is encoded by an immunoglobulin gene and that is capable of binding to an antigen. The term "complementarity determining region" may refer to the portion of the variable region of an antibody that confers antigen binding specificity, and may refer to an amino acid sequence found in the hypervariable region of the heavy or light chain of an immunoglobulin. The heavy chain may include three complementary determining regions (CDRs) (HCDR1, HCDR2, and HCDR3; and the light chain may include three complementary determining regions (CDRs) (LCDR1, LCDR2, and LCDR3). The CDRs may provide contact residues that play an important role in the binding of an antibody to its antigen or antigenic epitope.

[0123] The term "humanized antibody" refers to a non-human antibody that has been genetically engineered and whose amino acid sequence has been modified to increase homology with the sequence of a human antibody. Generally speaking, all or part of the CDR region of a humanized antibody comes from a non-human antibody (donor antibody), and all or part of the non-CDR region (e.g., variable region FR and / or constant region) comes from a human immunoglobulin (recipient antibody). Humanized antibodies generally retain or partially retain the expected properties of the donor antibody, including but not limited to antigen specificity, affinity, reactivity, ability to increase immune cell activity, ability to enhance immune response, etc.

[0124] The term "chimeric antibody" refers to an antibody whose variable region sequence is derived from one species and whose constant region sequence is derived from another species, for example, an antibody formed by fusing the variable region of a mouse antibody with the constant region of a human antibody.

[0125] In this context, the percent identity (degree of homology) between sequences can be determined by comparing two sequences, for example, using freely available computer programs commonly used for this purpose on the World Wide Web (e.g. www.ncbi.nlm.nih.gov), such as BLASTp or BLASTn with default settings.

[0126] In some embodiments, the present application provides an anti-TL1A antibody or an antigen-binding fragment thereof, comprising:

[0127] (a) a heavy chain variable region comprising the following complementarity determining regions:

[0128] a HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46;

[0129] a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47;

[0130] a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48;

[0131] (b) a light chain variable region comprising the following complementarity determining regions:

[0132] LCDR1 comprising the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49, and that functions identically or similarly to the amino acid sequence of SEQ ID NO:4, 10, 16, 22, 31, 37, 43 or 49;

[0133] LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, and that functions identically or similarly to the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50;

[0134] LCDR3 comprising the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, or an amino acid sequence obtained by substitution, deletion or addition of one or more amino acids to the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, and functions the same or similar to the amino acid sequence of SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51.

[0135] The scope of the above-mentioned CDR has been defined according to the ImMunoGenTics (IMGT) numbering rules, but those skilled in the art will understand that CDR sequences numbered according to any one or more of the AbM numbering rules, Kabat numbering rules, Chothia numbering rules and Contact numbering rules (based on analysis of available complex crystal structures) also fall within the scope of protection of this application.

[0136] The substitution, deletion, or addition of one or more amino acids described herein is the substitution, deletion, or addition of one or two amino acids. In some embodiments, the substitution, deletion, or addition of one or more amino acids is a conservative modification. In some embodiments, compared to the amino acid sequences set forth in SEQ ID NOs: 1-3, 7-9, 13-15, 19-21, 25-26, 28-30, 34-36, 40-42, and 46-48, the amino acids that differ in the amino acid sequences having at least 80% identity or having one or more amino acid substitutions, deletions, or additions are primarily or entirely located in the FR region of the heavy chain variable region. In some embodiments, compared to the amino acid sequences set forth in SEQ ID NOs: 4-6, 10-12, 16-18, 22-24, 27, 31-33, 37-39, 43-45, and 49-51, the amino acids that differ in the amino acid sequences having at least 80% identity or having one or more amino acid substitutions, deletions, or additions are primarily or entirely located in the FR region of the light chain variable region.

[0137] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0138] (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2, and 3, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5, and 6, respectively;

[0139] (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8, and 9, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11, and 12, respectively;

[0140] (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14, and 15, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17, and 18, respectively;

[0141] (4) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 19, 20, and 21, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 22, 23, and 24, respectively;

[0142] (5) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 25, 20, and 26, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 22, 23, and 27, respectively;

[0143] (6) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 28, 29, and 30, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 31, 32, and 33, respectively;

[0144] (7) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 34, 35, and 36, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 37, 38, and 39, respectively;

[0145] (8) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 40, 41, and 42, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 43, 44, and 45, respectively; or

[0146] (9) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 46, 47 and 48, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 49, 50 and 51, respectively.

[0147] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0148] (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2, and 3, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5, and 6, respectively;

[0149] (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8, and 9, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11, and 12, respectively;

[0150] (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14, and 15, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17, and 18, respectively;

[0151] (4) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 40, 41 and 42, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 43, 44 and 45, respectively; or

[0152] (5) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 46, 47 and 48, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 49, 50 and 51, respectively.

[0153] In a preferred embodiment, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0154] (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2, and 3, respectively, and the LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5, and 6, respectively;

[0155] (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12, respectively; or

[0156] (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14 and 15, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17 and 18, respectively.

[0157] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0158] (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2 and 3, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5 and 6, respectively; or

[0159] (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9, respectively, and the LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12, respectively.

[0160] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises: a heavy chain variable region comprising an amino acid sequence selected from any one of SEQ ID NOs: 61, 54, 59, 60, 62, 69, 70, 71, 72, 73, and 74, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto; and

[0161] A light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 55, 56, 57, 58, 63, 64, 65, 66, 67, and 68, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto.

[0162] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0163] (1) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0164] (2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0165] (3) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:56;

[0166] (4) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:57;

[0167] (5) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:58;

[0168] (6) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0169] (7) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:56;

[0170] (8) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:57;

[0171] (9) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:58;

[0172] (10) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:60 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:55;

[0173] (11) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:60 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:56;

[0174] (12) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:60 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:57;

[0175] (13) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:60 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:58;

[0176] (14) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:56;

[0177] (15) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:57;

[0178] (16) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:58;

[0179] (17) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:63;

[0180] (18) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:64 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:64;

[0181] (19) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:65 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:65;

[0182] (20) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:66 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:66;

[0183] (21) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:67 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:67;

[0184] (22) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:68;

[0185] (23) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:69, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:63;

[0186] (24) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:69, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:64 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:64;

[0187] (25) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:69, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:65 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:65;

[0188] (26) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:69 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:69, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:66 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:66;

[0189] (27) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:63;

[0190] (28) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:64 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:64;

[0191] (29) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:65 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:65;

[0192] (30) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:66 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:66;

[0193] (31) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:67 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:67;

[0194] (32) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:70, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:68;

[0195] (33) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:63;

[0196] (34) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:64 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:64;

[0197] (35) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:65 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:65;

[0198] (36) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:66 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:66;

[0199] (37) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:67 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:67;

[0200] (38) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:71, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:68;

[0201] (39) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 63;

[0202] (40) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 65;

[0203] (41) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67;

[0204] (42) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 72, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68;

[0205] (43) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 63;

[0206] (44) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 65;

[0207] (45) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67;

[0208] (46) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68;

[0209] (47) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 63;

[0210] (48) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 67; or

[0211] (49) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68.

[0212] In some embodiments, the amino acids that differ in an amino acid sequence with at least 80% identity compared to the amino acid sequence set forth in any one of SEQ ID NOs: 61, 54, 59, 60, 62, 69, 70, 71, 72, 73, and 74 or SEQ ID NOs: 55, 56, 57, 58, 63, 64, 65, 66, 67, and 68 are primarily or entirely located in the FR regions.

[0213] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0214] (1) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0215] (2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0216] (3) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:56;

[0217] (4) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:57;

[0218] (5) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:54, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:58;

[0219] (6) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0220] (7) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:56;

[0221] (8) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:57;

[0222] (9) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:59, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:59, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:58;

[0223] (10) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:60 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:55;

[0224] (11) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:60 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:60, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:57;

[0225] (12) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:56;

[0226] (13) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:57;

[0227] (14) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:58;

[0228] (15) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:62 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:62, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:68;

[0229] (16) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 73, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 63;

[0230] (17) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 63; or

[0231] (18) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 68.

[0232] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0233] (1) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:55;

[0234] (2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:56 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:56;

[0235] (3) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:57 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:57;

[0236] (4) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:61 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:61, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:58 or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:58;

[0237] (5) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:73, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:73, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:63, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:63;

[0238] (6) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:74, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:63, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids set forth in SEQ ID NO:63; or

[0239] (7) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:74, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids of SEQ ID NO:74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:68, or a sequence of amino acids that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence of amino acids of SEQ ID NO:68.

[0240] In some embodiments, the antibody is a mouse antibody, a monkey antibody, a rabbit antibody, a chimeric antibody, a humanized antibody, or a fully human antibody.

[0241] In some embodiments, the antibody is a murine antibody.

[0242] In some embodiments, the antibody is a chimeric antibody comprising an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the extracellular antigen-binding domain comprises the anti-TL1A antibody or an antigen-binding fragment thereof described herein.

[0243] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof is selected from at least one of a monoclonal antibody, a polyclonal antibody, a neutralizing antibody, an antagonistic antibody, an anti-idiotypic antibody, a fucosylated antibody, a monospecific antibody, a multispecific antibody, a nanobody, a Fab fragment, a Fab' fragment, a F(ab')2 fragment, a Fd fragment, a Fv fragment, a dAb fragment, an isolated CDR region, and a scFv; the anti-TL1A antibody is preferably a monoclonal antibody or a multispecific antibody, preferably, the multispecific antibody is a bispecific antibody, a trispecific antibody, or a tetraspecific antibody; or preferably, the multispecific antibody further comprises at least one second antibody having a second binding specificity for a second target.

[0244] In some embodiments, the antibody is a monoclonal antibody.

[0245] In the present application, the antibodies can be monovalent, bivalent or multivalent, that is, the antibodies can bind to one, two or more antigen molecules at a time. An antibody "monovalently" binds to a specific protein, that is, one molecule of the antibody binds only to one molecule of the protein, but the antibody can also bind to different proteins. When an antibody binds only to each molecule of two different proteins, the antibody is "monovalently" bound to each protein, and the antibody is "bispecific" and "monovalently" binds to each of the two different proteins. An antibody can be "monomeric", that is, it comprises a single polypeptide chain. An antibody can comprise multiple polypeptide chains ("multimeric") or can comprise two ("dimeric"), three ("trimeric") or four ("tetrameric") polypeptide chains. If the antibody is multimeric, the antibody can be a homomultimer, that is, the antibody comprises more than one molecule of only one polypeptide chain, including homodimers, homotrimers or homotetramers. Alternatively, the multimeric antibody may be a heteromultimer, ie, the antibody comprises more than one different polypeptide chain, including heterodimers, heterotrimers, or heterotetramers.

[0246] In the present application, conservative modifications can also be made to the anti-TL1A antibody or antigen-binding fragment thereof. Conservative modifications refer to amino acid modifications that do not significantly affect or change the binding properties of the antibody. For example, conservative amino acid substitutions can be made by replacing an amino acid of the same type (having similar chemical properties or functions). As an example, amino acids can be divided into the following categories based on their side chain properties: (1) non-polar amino acids: Ala (A), Val (V), Leu (L), Ile (I), Pro (P), Phe (F), Trp (W), Met (M); (2) uncharged polar amino acids: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N), Gln (Q); (3) acidic amino acids: Asp (D), Glu (E); (4) basic amino acids: Lys (K), Arg (R), His (H). Alternatively, amino acids can be divided into the following categories based on common side chain properties: (1) hydrophobic amino acids: Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic amino acids: Cys, Ser, Thr, Asn, Gln; (3) acidic amino acids: Asp, Glu; (4) basic amino acids: His, Lys, Arg; (5) amino acids that affect chain orientation: Gly, Pro; (6) aromatic amino acids: Trp, Tyr, Phe.

[0247] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof further comprises a heavy chain constant region and / or a light chain constant region.

[0248] Preferably, the heavy chain constant region is the heavy chain constant region of IgG, IgA, IgM, IgE or IgD or a variant thereof; the heavy chain constant region is preferably the heavy chain constant region of IgG (e.g., human IgG) or a variant thereof, such as the constant region of IgG1, IgG2, IgG3 or IgG4 (e.g., human IgG1, IgG2, IgG3 or IgG4) or a variant thereof; the heavy chain constant region is more preferably the heavy chain constant region of human IgG1 or a variant thereof, such as the heavy chain constant region of human IgG1 or a variant thereof.

[0249] Preferably, the light chain constant region is a constant region of a human kappa chain or lambda chain or a variant thereof, preferably a constant region of a human kappa chain. In some embodiments, the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 76, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0250] In some embodiments, the heavy chain constant region comprises a full-length heavy chain constant region or a fragment thereof, and the fragment can be selected from a CH1 region, a CH2 region, an Fc region, or a CH3 region.

[0251] In some embodiments, the Fc region comprises an Fc region of human IgG1, preferably, the Fc region of human IgG1 may further comprise any one or more of the following mutations: (a) 297A, 297Q, 297G or 297D, (b) 279F, 279K or 279L, (c) 228P, (d) 235A, 235E, 235G, 235Q, 235R or 235S, (e) 237A, 237E, 237K, 237N or 237R, (f) 234A, 234V or 234F, (g) 233P, (h) 328A, (i) 327Q or 327T, (j) 329A, 329G, 329Y or 329R, (k) 331S, (l) 332E, 332E, 332Y or 332R 236F or 236R, (m) 238A, 238E, 238G, 238H, 238I, 238V, 238W or 238Y, (n) 248A, (o) 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T or 254V, (p) 255N, ( q)256H, 256K, 256R, or 256V, (r)264S, (s)265H, 265K, 265S, 265Y, or 265A, (t)267G, 267H, 267I, or 267K, (u)268K, (v)269N or 269Q, (w)270A, 270G, 270M, or 270N , (x) 271T, (y) 272N, (z) 292E, 292F, 292G or 292I, (aa) 293S, (bb) 301W, (cc) 304E, (dd) 311E, 311G or 311S, (ee) 316F, (ff) 328V, (gg) 330R, (hh) 339E or 339L, (ii) 343I or 343V, (jj) 373A, 373G or 373S, (kk) 376E, 376W or 376Y, (ll) 380D, (mm) 382D or 382P, (nn) 385P, (oo) 424H, 424M or 424V, (pp) 434I, (qq) 438G 、(rr)439E、439H or 439Q、(ss)440A、440D、440E、440F、440M、440T or 440V、(tt)E233P、(uu)L235E、(vv)L234A and L235A、(ww)L234A、L235A and G237A、(xx)L234A、L235A and P329G、(yy)L234F、L235E and P331S、(zz)L234A、L235E and G237A、(aaa)L234A、L235E、G237A and P331S(bbb)L234A、L235A、G237A、P238S、H268A、A330S and P331S (IgG1σ), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or any combination of (nnn) (a)–(uu), according to Kabat numbering.

[0252] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a human IgG4 Fc region, or (ii) a human IgG4 Fc region comprising any one or more mutations selected from (a) S228P, (b) S228P and L235E, or (c) S228P, F234A, and L235A, according to Kabat numbering.

[0253] In some embodiments, the antibody or antigen-binding fragment comprises a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; an IgG2 Fc region comprising any one or more mutations of H268Q, V309L, A330S, P331S (IgG2m4); or an IgG2 Fc region comprising any one or more mutations of V234A, G237A, P238S, H268A, V309L, A330S, P331S (IgG2σ).

[0254] In some embodiments, the Fc region comprises a human IgG1 Fc region. Preferably, the human IgG1 Fc region may further have a member selected from the group consisting of 329A, 329G, 329Y, 331S, 236F, 236R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, 254 Any one or more substitution mutations of 440V, 440D, 440E, 440F, 440M, 440T, and 440V, numbered according to Kabat.

[0255] In some embodiments, the heavy chain constant region is the heavy chain constant region of human IgG1 or a variant thereof (e.g., having L234A / L235A / G237A mutation (referred to as "AAA mutation"), LALA mutation (L234A / L235A), LALA-PG mutation (L234A / L235A / P329G), YTE mutation, LS mutation). In some embodiments, the heavy chain constant region comprises the amino acid sequence shown in SEQ ID NO: 77 or 75, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto.

[0256] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain, wherein:

[0257] The heavy chain comprises: a heavy chain variable region comprising an amino acid sequence selected from any one of SEQ ID NOs: 61, 54, 59, 60, 62, 69, 70, 71, 72, 73 and 74, or an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, and a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NOs: the amino acid sequence of NO:75, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto;

[0258] The light chain comprises: a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 55, 56, 57, 58, 63, 64, 65, 66, 67, and 68, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto; and a light chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 55, 56, 57, 58, 63, 64, 65, 66, 67, and 68, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical thereto. The amino acid sequence shown in NO:76, or an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto.

[0259] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain, wherein:

[0260] The heavy chain comprises a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence set forth in any one of SEQ ID NOs: 78, 81 and 83; and

[0261] The light chain comprises a sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence set forth in any one of SEQ ID NOs: 79, 80, 82 and 84.

[0262] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof comprises:

[0263] (1) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 78, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto, and

[0264] a light chain comprising the amino acid sequence set forth in SEQ ID NO: 79, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto;

[0265] (2) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 78, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto, and

[0266] a light chain comprising the amino acid sequence set forth in SEQ ID NO: 80, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto;

[0267] (3) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 81, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto, and

[0268] a light chain comprising the amino acid sequence set forth in SEQ ID NO: 82, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto;

[0269] (4) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 83, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto, and

[0270] a light chain comprising the amino acid sequence set forth in SEQ ID NO: 82, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto;

[0271] (5) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 81, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto, and

[0272] A light chain comprising the amino acid sequence set forth in SEQ ID NO: 84, or an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical thereto.

[0273] In some embodiments, the amino acids that differ in the amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity compared to the amino acid sequence set forth in any one of SEQ ID NOs: 78-84 are all present in the FR regions or the constant region.

[0274] As non-limiting examples, the anti-TL1A antibody or antigen-binding fragment thereof has one or more of the following properties:

[0275] (1) Ability to bind to human TL1A;

[0276] (2) capable of binding to non-human mammalian TL1A, such as mouse, rabbit, cat, dog, or pig TL1A, preferably capable of binding to mouse TL1A;

[0277] (3) capable of binding to non-human primate TL1A, preferably, capable of binding to cynomolgus monkey TL1A;

[0278] (4) cross-reacting with human, non-human mammalian, and non-human primate TL1A, preferably, cross-reacting with human, mouse, and cynomolgus monkey TL1A;

[0279] (5) having an affinity for a human homolog of TL1A that is lower than the affinity for human TL1A, and the human homolog of TL1A is selected from TNFSF6, TNFSF10, TNFSF14, TNF-β, TNF-α, lymphotoxin α2-β1, and lymphotoxin α1-β2;

[0280] (6) blocking, inhibiting or reducing the interaction between TL1A and receptor DR3 (TNFRSF25);

[0281] (7) blocking, inhibiting, or reducing the signaling pathway triggered by TL1A;

[0282] (8) blocking, inhibiting, or reducing TL1A-regulated activity;

[0283] (9) Block, inhibit or reduce TL1A-mediated cellular responses; such as lymphocyte proliferation, cytokine expression or lymphocyte survival.

[0284] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof has a blocking effect on TL1A-induced caspase activity in TF-1 cells.

[0285] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof can cross-bind to human, cynomolgus monkey, mouse, or rat TL1A.

[0286] In some embodiments, the anti-TL1A antibody or antigen-binding fragment thereof can specifically bind to human, mouse, rat, or cynomolgus monkey TL1A.

[0287] In some embodiments of the present application, a nucleic acid molecule is provided, wherein the nucleic acid molecule encodes the above-mentioned anti-TL1A antibody or antigen-binding fragment thereof.

[0288] In some embodiments of the present application, a recombinant vector is provided, comprising the above-mentioned nucleic acid molecule.

[0289] The term "vector" refers to a tool for expressing a target gene in a host cell, such as a plasmid vector, a cosmid vector, and a viral vector such as a phage vector, a lentiviral vector, an adenoviral vector, a retroviral vector, and an adeno-associated viral vector. Recombinant vectors can be constructed by or by manipulating plasmids (e.g., pSC101, pGV1106, pACYC177, ColE1, pKT230, pME290, pBR322, pUC8 / 9, pUC6, pBD9, pHC79, pIJ61, pLAFR1, pHV14, pGEX series, pET series, pUC19, etc.), phages (e.g., λgt4λB, λ-Charon, λΔz1, M13, etc.), or viral vectors (e.g., SV40, etc.), which are commonly used in the art.

[0290] In a recombinant vector, a nucleic acid molecule can be operably linked to a promoter. The term "operably linked" is intended to refer to a functional connection between a target nucleotide sequence and an expression control sequence (e.g., a promoter sequence). When "operably linked," a regulatory element can control the transcription and / or translation of the target polynucleotide.

[0291] Recombinant vectors can generally be constructed as cloning vectors or expression vectors. For recombinant expression vectors, vectors commonly available in the relevant art for expressing foreign proteins in plants, animals, or microbial cells can be used. Various methods well known in the art can be used to construct recombinant vectors.

[0292] In order to use in a host such as a prokaryotic or eukaryotic cell, a recombinant vector can be constructed accordingly. For example, when constructing a vector as an expression vector for a prokaryotic host, the vector generally includes a strong promoter for transcription (e.g., pLλ promoter, CMV promoter, trp promoter, lac promoter, tac promoter, T7 promoter, etc.), a ribosome binding site for initiating translation, and a transcription / translation termination sequence. On the other hand, expression vectors for eukaryotic hosts include replication origins that can be operated in eukaryotic cells, such as f1 replication origin, SV40 replication origin, pMB1 replication origin, adenovirus replication origin, AAV replication origin, and BBV replication origin, but are not limited thereto. In addition, expression vectors generally include promoters derived from mammalian cell genomes (e.g., metallothionein promoters) or promoters derived from mammalian viruses (e.g., adenovirus late promoter, vaccinia virus 7.5K promoter, SV40 promoter, cytomegalovirus promoter, tk promoter of HSV, etc.), and a polyadenylation sequence as a transcription termination sequence. Recombinant cells can be prepared by introducing the recombinant vector into a suitable host cell. Any host cell known in the art can be used in the present disclosure, as long as it allows the recombinant vector to be continuously cloned and expressed in a stable manner. Examples of prokaryotic host cells that can be used in the present disclosure can be selected from Escherichia coli (E. coli) such as E. coli JM109, E. coli BL21, E. coli RR1, E. coli LE392, E. coli B, E. coli X1776, E. coli W3110, Bacillus species such as Bacillus subtilis and Bacillus thuringiensis, and Enterobacteriaceae strains, such as Salmonella typhimurium, Serratia marcescens and various Pseudomonas species. The eukaryotic host cell that can be used for conversion can be selected from, but is not limited to, yeast saccharomyces cerevisiae (Saccharomyces cerevisiae), insect cell and zooblast, for example Sp2 / 0, CHO (Chinese hamster ovary) K1, CHO DG44, CHO S, CHO DXB11, CHO GS-KO, PER.C6, W138, BHK, COS-7, 293, HepG2, Huh7, 3T3, RIN, MDCK etc.Can use method well-known in the relevant art that nucleic acid molecule or the recombinant vector carrying nucleic acid molecule are introduced (transfection) into host cell.For example, when host cell is prokaryotic cell, can use CaCl Or electroporation method carries out this transfection.For eukaryotic host cell, can use, but is not limited to microinjection, calcium phosphate precipitation, electroporation, liposome-mediated transfection or particle bombardment realize gene introduction.

[0293] In order to select transformed host cells, the phenotype associated with the selection marker can be utilized according to methods well known in the art. For example, when the selection marker is a gene that confers resistance to certain antibiotics, the host cells can be grown in culture medium in the presence of antibiotics to select target transformants.

[0294] In some embodiments of the present application, a host cell is provided, comprising the aforementioned nucleic acid molecule or the aforementioned recombinant vector.

[0295] In some embodiments of the present application, a method for preparing an anti-TL1A antibody or antigen-binding fragment thereof is provided, comprising culturing the host cells described above. The method may further comprise isolating and / or purifying the antibody or fragment thereof from the cell culture after the expression or culturing step, for example, by purification using a Protein A affinity column.

[0296] In some embodiments, the host cell is a prokaryotic cell. In other embodiments, the host cell is a eukaryotic cell.

[0297] In some embodiments, the host cell is selected from yeast cells, mammalian cells, or other cells suitable for preparing antibodies or antigen-binding fragments thereof, or moieties thereof. Mammalian cells are, for example, Chinese hamster ovary cells (CHO), human kidney epithelial cell lines 293 cells, or 293T cells. In some embodiments, the host cell is a recombinant CHO cell. In some embodiments, the method further comprises isolating and purifying the expression product of the host cell, for example, by purification using a Protein A affinity column.

[0298] In a sixth aspect, the present application provides the anti-TL1A antibody or antigen-binding fragment thereof according to the first aspect, the nucleic acid molecule according to the second aspect, the recombinant vector according to the third aspect, and the host cell according to the fourth aspect for preventing and / or treating diseases or conditions mediated by TL1A.

[0299] In some embodiments, the present application relates to the use of the anti-TL1A antibody or antigen-binding fragment thereof of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect in the preparation of a medicament for preventing and / or treating a disease or condition mediated by TL1A. Alternatively, the present application relates to a method for preventing and / or treating a disease or condition mediated by TL1A, comprising administering to a subject in need thereof the anti-TL1A antibody or antigen-binding fragment thereof of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect. Alternatively, the present application relates to the anti-TL1A antibody or antigen-binding fragment thereof of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect for preventing and / or treating a disease or condition mediated by TL1A.

[0300] In some embodiments, the disease or condition is prevented, alleviated, ameliorated or inhibited by eliminating, inhibiting or reducing TL1A activity.

[0301] In some embodiments, the disease or disorder is an immune-related or inflammatory disease.

[0302] In some embodiments, the disease or condition is selected from at least one of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), systemic sclerosis-associated interstitial lung disease, idiopathic pulmonary fibrosis, viral-induced pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), allergic lung inflammation, neurodegenerative diseases, cancer, diabetes, arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, transplant rejection, graft-versus-host disease (GVHD), spondyloarthropathies, primary sclerosing cholangitis, primary biliary cirrhosis, atherosclerosis, bladder syndrome, interstitial cystitis, urinary intestinal dysfunction, sepsis, uveitis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus, cutaneous lupus erythematosus, autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjögren's syndrome, scleroderma, and vasculitis.

[0303] In the present application, the inflammatory bowel disease includes Crohn's disease and ulcerative colitis.

[0304] In some embodiments, the disease or disorder is inflammatory bowel disease.

[0305] In a seventh aspect, the present application provides a kit for detecting TL1A, comprising the anti-TL1A antibody or antigen-binding fragment thereof according to the first aspect and the nucleic acid molecule according to the second aspect.

[0306] The dosage and administration frequency of the anti-TL1A antibodies or antigen-binding fragments thereof described herein can be determined by a clinician based on factors such as the age, weight, sex, general condition, and severity of the disease of the subject; they can be administered by any conventional route known in the art, such as parenteral, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal, epidural, and intrasternal administration.

[0307] Example

[0308] The solution of the present application will be further described below with reference to embodiments. However, those skilled in the art will appreciate that the scope of protection of the present application is not limited to these embodiments.

[0309] Unless otherwise specified, the reagents, materials, or instruments involved in the following examples are commercially available.

[0310] Example 1: Construction of reporter gene cell lines for functional activity evaluation

[0311] Pfizer's anti-TL1A antibody 1D1 was used as a positive control antibody. The amino acid sequence of 1D1 was from patent WO2021260577 (the heavy chain sequence and light chain sequence of 1D1 are shown in SEQ NO ID: 52 and 53, respectively).

[0312] The light and heavy chain genes of 1D1 were synthesized and subcloned into the pcDNA3.4 expression vector, respectively. CHO-K1 cells were transfected using BIOHUB 78PEI transfection reagent (purchased from Shanghai Qifa). After incubation at 37°C and 5% CO2, the cell culture was collected, centrifuged, and purified using a Protein A affinity column.

[0313] TF-1 cells in the logarithmic growth phase were seeded in 6-well plates at 1.5E5 cells / 3mL and infected with the PCDH-NFκB-Luc-CMV-EGFP-Hygro lentivirus (MOI = 20). Stable transfections were screened with 500 μg / mL Hygromycin B to obtain the TF-1-NFκB-Luc reporter gene cell line. The activation of this reporter gene cell line by human TL1A was verified using the following steps.

[0314] (1) Take TF-1-NFκB-Luc reporter gene cells in the logarithmic growth phase, wash them twice with RPMI 1640 + 10% FBS medium, adjust the cell density to 4E5 / mL, and aspirate 10 μL of cell suspension into a 384-well white plate, with 4E3 cells per well.

[0315] (2) Human TL1A trimer protein (purchased from Kaixia) was diluted 5-fold in RPMI 1640 + 10% FBS medium starting from the highest concentration of 200 μg / mL, and 10 gradients were continuously diluted. 10 μL of the diluted gradient concentration protein was added to the above-mentioned 384-well white plate, with two replicate wells for each concentration gradient. The final concentration of TL1A trimer in each well was 200 μg / mL, 40 μg / mL, 8 μg / mL, 1.6 μg / mL, 0.32 μg / mL, 0.064 μg / mL, 0.0128 μg / mL, 0.00256 μg / mL, 0.000512 μg / mL, and 0.000102 μg / mL.

[0316] (3) The culture medium was supplemented to make the reaction system 40 μL / well, and the plate was placed at 37° C. and 5% CO 2 for 18 h.

[0317] (4) After the culture is completed, Bio Lite TM The plate was equilibrated to room temperature for 30 min, and 20 μL of Bio Lite was added to each well. TM Luciferase fluorescence was measured using a BMG PLOARstar Omega multi-functional microplate reader using the detection reagent (purchased from Norvegian). The data are shown in Figure 1 (TL1A-induced reporter gene signal results), indicating that the reporter gene cell line can be activated in a dose-dependent manner by human TL1A trimer.

[0318] The blocking effect of the positive control antibody 1D1 on human TL1A-induced signaling was verified by the following steps.

[0319] (1) The positive control antibody 1D1 was diluted 1.25-fold in a gradient starting from the highest concentration of 6 μg / mL using RPMI 1640 + 10% FBS medium, and 10 gradients were continuously diluted. 20 μL of the diluted concentration gradient antibody was added to a 384-well white plate, with two replicates for each concentration gradient, so that the antibody concentrations in the 384-well white plate were 8 μg / mL, 6.4 μg / mL, 5.12 μg / mL, 4.096 μg / mL, 3.277 μg / mL, 2.621 μg / mL, 2.097 μg / mL, 1.678 μg / mL, 1.342 μg / mL, and 1.074 μg / mL, and then 10 μL of 2 μg / mL human TL1A trimer protein (purchased from Kaixia) was added to each corresponding well to a final concentration of 0.5 μg / mL. Incubate at 37°C, 5% CO2 for 1 hour.

[0320] (2) TF-1-NFκB-Luc cells in the logarithmic growth phase were washed twice with RPMI 1640 + 10% FBS medium. The cell density was adjusted to 4E5 / mL with RPMI 1640 + 10% FBS medium. 10 μL of the cell suspension was added to the 384-well white plate described above, with 4E3 cells per well. The cells were cultured at 37°C and 5% CO2 for 18 h.

[0321] (3) After the culture is completed, Bio Lite TM The plate was equilibrated to room temperature for 30 min, and 20 μL of Bio Lite was added to each well. TM Luciferase fluorescence was measured using a BMG PLOARstar Omega multi-function microplate reader using the detection reagent (purchased from Novagen). The data are shown in Figure 2 (reporter gene activity assay results for positive control antibody 1D1), demonstrating that positive control antibody 1D1 can dose-dependently block TL1A-induced reporter gene signaling. This functional assay system can be used to evaluate the activity of candidate antibodies.

[0322] Example 2: Hybridoma Screening

[0323] Ten Balb / c and ten CD1 mice (SPF grade) were immunized three times, 14 days apart. The first immunization was performed with 50 μg of human TL1A (purchased from Klebsiella pneumoniae) emulsified in Freund's adjuvant and injected subcutaneously at multiple sites. The second and third immunizations were performed with 25 μg of human TL1A and 25 μg of mouse TL1A (both purchased from Klebsiella pneumoniae) emulsified in Freund's adjuvant and injected subcutaneously at multiple sites. Mice with high titer were subjected to a surge immunization. Three days later, the mice were sacrificed by cervical dislocation. Spleens were aseptically harvested, and single-cell suspensions of B cells were prepared. These suspensions were mixed with SP2 / 0 myeloma cells at a 2:1 ratio and fused using a BTX cell electrofusion instrument. Following electrofusion, all cells were immediately suspended in DMEM supplemented with 20% FBS and HAT and seeded into 96-well plates. Approximately 10 days after fusion, the cells were switched to HT medium and cultured for two days. The supernatant was then assayed for specific antibodies.

[0324] 100 μL of culture supernatant was removed from each well of a 96-well plate, and fresh DMEM medium containing HT was added to each well. The supernatant was assayed for binding to human TL1A (purchased from Kaixia), mouse TL1A (purchased from Kaixia), rat TL1A (purchased from Sino Biological), and cynomolgus macaque TL1A (purchased from Kaixia) using ELISA (HRP Anti-Mouse IgG H&L purchased from BioAolong, TMB colorimetric solution purchased from Huzhou Yingchuang). Clones that cross-bind to human, cynomolgus macaque, mouse, and rat TL1A were selected. Two rounds of subcloning were performed to obtain monoclonal antibodies that secrete antibodies that specifically bind to human, mouse, rat, and cynomolgus macaque TL1A.

[0325] The monoclonal hybridomas obtained from the two rounds of subcloning screening were expanded and cultured, and the mouse antibodies were then purified by protein A column affinity chromatography. The purified mouse antibodies and the positive control antibody 1D1 were assayed by the reporter gene assay according to the steps described in Example 1. Nine mouse antibodies with activities superior to or equivalent to the positive control antibody 1D1 were selected and subjected to hybridoma sequencing to obtain the light and heavy chain variable region amino acid sequences.

[0326] Example 3: Construction and expression of chimeric antibodies

[0327] Based on the amino acid sequences of the light and heavy chain variable regions of 9 mouse antibodies obtained by sequencing, the light and heavy chain variable region genes were synthesized. The heavy chain variable region gene was subcloned into the pcDNA3.4-hIgG1 expression vector. Its heavy chain constant region was eliminated by L234A / L235A / G237A mutation to eliminate the effector function. The light chain variable region gene was subcloned into the pcDNA3.4-hIgKc expression vector to obtain the heavy chain expression vector and the light chain expression vector. After the constructed vector was verified by sequencing, it was transiently expressed in CHO-K1 cells. 120μg BIOHUB 78PEI transfection reagent (purchased from Shanghai Qifa) was added to 1.5mL OPM-Trans CHO transfection medium (purchased from Aopuma), mixed thoroughly, and then added to 1.5mL OPM-Trans CHO transfection medium containing 30μg of the expression vector. After thorough mixing, it was allowed to stand at room temperature for 20 minutes. The complex was then added to 30 mL of CHO-K1 cells at a density of 4E6 / mL, gently shaken to mix thoroughly, and cultured at 37°C, 5% CO2, and 100 rpm. The temperature was lowered to 32°C on the first day after transfection, and 2.5% OPM-CHO ProFeed medium (purchased from OPM) was added on days 1, 3, 5, and 7. The cells were cultured until day 8, and the culture supernatant was collected by centrifugation. The chimeric antibody was purified by affinity chromatography on a protein A column. Table 1 shows the CDR sequences of the chimeric antibody.

[0328] Table 1 Chimeric antibody CDR sequences

[0329] Example 4: Detection of chimeric antibody activity by reporter gene method

[0330] The reporter gene assay was used to detect the activity of nine chimeric antibodies and the positive control antibody 1D1 according to the steps described in Example 1. Table 2 and Figures 3-1 to 3-4 (Chimeric Antibody Reporter Gene Assay Activity Result Graphs) show the results of the reporter gene assay. It can be seen that both the chimeric antibodies and the positive control antibody can dose-dependently block the fluorescence signal of the TL1A-induced reporter gene cell line. From the curves and IC 50 From the results, we can see that the activities of chimeric antibodies 12B3 and 16H6 were significantly better than the positive control antibody 1D1, and the activities of the other chimeric antibodies were comparable to that of 1D1.

[0331] Table 2 Activity detection results of chimeric antibody reporter gene method

[0332] Example 5: Detection of chimeric antibody activity by caspase assay

[0333] The activities of nine chimeric antibodies and the positive control antibody 1D1 were detected using a caspase assay according to the following steps to evaluate the blocking effect of the candidate antibodies on caspase activity in TF-1 cells induced by TL1A and Cycloheximide.

[0334] (1) Cycloheximide (purchased from MCE) was diluted to 10 μg / mL with RPMI 1640 + 10% FBS medium and added to each well of a 384-well white plate at 10 μL.

[0335] (2) TL1A trimer (purchased from Kaixia) was diluted to 200 ng / mL with RPMI 1640 + 10% FBS medium and added to the above-mentioned 384-well white plate at 10 μL per well.

[0336] (3) The positive control antibody 1D1 and the nine chimeric antibodies were diluted 1.6-fold starting from the highest concentration of 6.4 μg / mL in RPMI 1640 + 10% FBS medium. The dilutions were repeated 10 times, with the antibody concentrations being 6.4 μg / mL, 4 μg / mL, 2.5 μg / mL, 1.562 μg / mL, 0.976 μg / mL, 0.610 μg / mL, 0.381 μg / mL, 0.238 μg / mL, 0.149 μg / mL, and 0.0931 μg / mL, respectively. 10 μL of each diluted antibody was added to the above-mentioned 384-well white plate, with two replicates for each concentration gradient. The 384-well plate was incubated at 37°C, 5% CO2 for 1 hour.

[0337] (2) TF-1 cells in the logarithmic growth phase were washed twice with RPMI 1640 + 10% FBS medium. The cell density was adjusted to 6E5 / mL with RPMI 1640 + 10% FBS medium. 10 μL of the cell suspension was added to the 384-well white plate described above, with 6E3 cells per well. The cells were cultured at 37°C and 5% CO2 for 18 h.

[0338] (3) After the incubation, Caspase-Glo 3 / 7 Reagent (purchased from Promega) and the plate were equilibrated to room temperature, 40 μL of Caspase-Glo 3 / 7 Reagent was added to each well, and the reaction was carried out at room temperature for 1 hour.

[0339] (4) Use BMG PLOARstar Omega multifunctional microplate reader to read the luciferase fluorescence value.

[0340] Table 3 and Figures 4-1 to 4-6 (chimeric antibody caspase activity assay results) show the caspase activity assay results. It can be seen that both the chimeric antibody of the present application and the positive control can dose-dependently block TL1A-induced caspase activation. From the curve and IC 50 From the above results, it can be seen that the activities of the chimeric antibodies 12B3, 56C8, and 16H6 of the present application are better than the positive control antibody 1D1, and the activities of the other chimeric antibodies are comparable to that of 1D1.

[0341] Table 3 Activity detection results of chimeric antibody caspase method

[0342] Example 6: Binding activity detection of chimeric antibodies

[0343] The binding of five preferred chimeric antibodies 16H6, 12B3, 56C8, 69B1, and 13B8, as well as the positive control antibody 1D1, to human TL1A monomers and trimers was detected by ELISA according to the following steps.

[0344] (1) Coating: Coat a 96-well plate with 1 μg / mL target protein (human TL1A monomer or trimer), 100 μL per well, incubate overnight at 4°C, and wash once with PBST.

[0345] (2) Blocking: Add PBST containing 2% BSA to each well for blocking at room temperature for 2 hours, and wash the plate once with PBST.

[0346] (3) Primary antibody incubation: The antibody to be tested was diluted 3.5-fold using PBST containing 0.5% BSA to a final concentration of 10, 2.86, 0.816, 0.233, 0.0666, 0.0190, 0.00544, 0.00155, 0.000444, 0.000127, and 0.0000363 μg / mL, respectively. The diluted antibody was added to the above 96-well plate at 100 μL / well, incubated at 37°C for 1 hour, and the plate was washed three times with PBST.

[0347] (4) Secondary antibody incubation: Secondary antibody Anti-human-Fc-IgG-HRP (purchased from Thermo) diluted 1:30,000 in PBST containing 0.5% BSA was added to the above 96-well plate, incubated at 37°C for 1 hour, and washed 5 times with PBST.

[0348] (5) Termination: TMB (purchased from Huzhou Shenke) was added to the above 96-well plate at 100 μL / well for color development at room temperature for 10 minutes, and then 50 μL / well of stop solution (1 M sulfuric acid) was added to terminate the reaction. The OD450 and OD630 data were read using a microplate reader.

[0349] Table 4, Figures 5-1 and 5-2 (charts showing the binding activity of chimeric antibodies to human TL1A monomers), and Figures 6-1 and 6-2 (charts showing the binding activity of chimeric antibodies to human TL1A trimers) show the binding of chimeric antibodies to human TL1A monomers and trimers. As can be seen, the chimeric antibodies of the present application strongly bind to both human TL1A monomers and trimers, with binding activity comparable to that of the positive control antibody 1D1.

[0350] Table 4 Binding activity of chimeric antibodies to human TL1A monomer and trimer

[0351] Example 7: Antibody Humanization

[0352] The preferred chimeric antibodies 16H6 and 12B3 were humanized. Humanization designs were based on the amino acid sequences of their murine heavy and light chains, retaining the CDR sequences of the original antibodies. Based on the results of germline alignment and antibody structure simulation, different humanized antibody templates were selected for the heavy and light chains, respectively. After humanization, the framework regions were backmutated to design candidate humanized antibody sequences. The heavy and light chains of the designed humanized antibodies were synthesized separately. The heavy chain gene was subcloned into the pcDNA3.4-hIgG1 expression vector. The heavy chain constant region was ablated by the L234A / L235A / G237A mutation to eliminate effector function. The light chain gene was subcloned into the pcDNA3.4-hIgKc expression vector. After sequencing verification, the constructed vectors were transiently expressed in CHO cells according to the method described in Example 3. The variable and constant region sequences of the humanized antibodies are shown in Table 5.

[0353] Table 5 Amino acid sequences of heavy and light chains of humanized antibodies

[0354] Example 8: Detection of humanized antibody activity by reporter gene method

[0355] The activity of the humanized antibodies against human TL1A trimer was tested using a reporter gene assay according to the steps described in Example 1. Table 6 and Figures 7-1 to 7-14 (Figures 7-1 to 7-14 (Figures 7-2 and 7-3) show the results of the humanized antibody activity assay against human TL1A trimer. It can be seen that the humanized antibodies of the present application can dose-dependently block the fluorescence signal of the reporter gene cell line induced by TL1A trimer. From the curves and IC values, it can be seen that the humanized antibodies of the present application can dose-dependently block the fluorescence signal of the reporter gene cell line induced by TL1A trimer. 50 From the above results, the activity of the humanized antibody of the present application is better than or comparable to that of the positive control antibody 1D1.

[0356] Table 6 Activity test results of humanized antibodies against human TL1A trimer reporter gene assay

[0357] Example 9: Detection of humanized antibody activity by caspase assay

[0358] The caspase assay was used to detect the activity of the humanized antibodies against human TL1A trimer according to the steps described in Example 5. Table 7 and Figures 8-1 to 8-4 (humanized antibody caspase assay results against human TL1A trimer) show the results of the caspase assay. It can be seen that the humanized antibodies of the present application can dose-dependently block TL1A trimer-induced caspase activation. From the curve and IC 50 From the above results, the activity of the humanized antibody of the present application is better than or comparable to that of the positive control antibody 1D1.

[0359] Table 7 Activity test results of humanized antibodies against human TL1A trimer caspase

[0360] Example 10: Detection of humanized antibody activity by cytokine method

[0361] The activity of the humanized antibody of the present application was detected by cytokine assay according to the following steps to evaluate the blocking effect of the candidate antibody on the release of IFN-γ from human primary PBMC cells induced by TL1A trimer, IL-12 and IL-18.

[0362] (1) Human IL-12 (purchased from Sino Biological) was diluted to 200 pg / mL in RPMI 1640 + 10% FBS medium and added to a 96-well transparent flat-bottom plate at 20 μL per well.

[0363] (2) Human IL-18 (purchased from Sino Biological) was diluted to 270 ng / mL using RPMI 1640 + 10% FBS medium and added to the above-mentioned 96-well transparent flat-bottom plate at 20 μL per well.

[0364] (3) Human TL1A trimer (purchased from Kaixia) was diluted to 250 ng / mL with RPMI 1640 + 10% FBS medium and added to the above-mentioned 96-well transparent flat-bottom plate at 20 μL per well.

[0365] (4) Frozen human PBMCs (purchased from Miaoshun Biotechnology) were rapidly thawed in a 37°C water bath, resuspended in 6 mL of RPMI 1640 + 10% FBS medium, and centrifuged at 400 g for 8 min. The supernatant was discarded, and the cell density was adjusted to 5E5 / mL with RPMI 1640 + 10% FBS. 20 μL of the cell suspension was pipetted into the 96-well transparent flat-bottom plate described above, with 1E4 cells per well. The 96-well transparent flat-bottom plate was incubated at 37°C, 5% CO2 for 1 h.

[0366] (5) The positive control antibody 1D1 and the humanized antibody were diluted two-fold starting from a maximum concentration of 2.5 μg / mL in RPMI 1640 + 10% FBS medium. Six dilutions were performed, with the antibody concentrations being 2.5 μg / mL, 1.25 μg / mL, 0.625 μg / mL, 0.312 μg / mL, 0.156 μg / mL, and 0.0780 μg / mL, respectively. 20 μL of each diluted antibody was added to a 96-well transparent flat-bottom plate, with four replicates for each concentration gradient. The plates were incubated at 37°C, 5% CO2 for 72 h.

[0367] (6) After the culture is complete, the plate is centrifuged, the culture supernatant is collected, and the culture supernatant is diluted to an appropriate multiple using RPMI 1640 + 10% FBS medium. Following the manufacturer's instructions, the human IFN-γ ELISA Kit (purchased from Lianke Bio) is used to measure the human IFN-γ content in the culture supernatant.

[0368] Table 8 and Figures 9-1 to 9-2 (activity test results of humanized antibodies against human TL1A trimer cytokine assay) show the activity test results of humanized antibodies against human TL1A trimer cytokine assay. It can be seen that the humanized antibodies of the present application can dose-dependently block the release of IFN-γ from human primary PBMC cells induced by TL1A trimer. Judging from the curve graph and IC50, the activity of the humanized antibodies of the present application is better than or equivalent to that of the positive control antibody 1D1.

[0369] Table 8 Activity test results of humanized antibodies against human TL1A trimer cytokine method

[0370] Example 11: In vivo efficacy of humanized antibodies in rats

[0371] The in vivo efficacy of the humanized antibodies 16H6-H4L1 and 16H6-H4L3 of the present application, as well as the positive control antibody 1D1, was evaluated in a rat colitis model. Forty Sprague-Dawley rats (half male and half female) were divided into five groups as shown in Table 9. An acute colitis model was established by intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in ethanol via catheter. A blank control group was given an equal volume of ethanol intrarectally. The drugs were administered once on the day of modeling (D0) and once three days after modeling (D3) according to the protocol shown in Table 9. The blank and model control groups were given an equal volume of normal saline. The 7th day after modeling (D7) was used as the endpoint of the experiment. During this period, the disease activity index (DAI) was scored daily based on body weight, stool characteristics, and stool blood. At the endpoint of the experiment (D7), the animals were killed and the colon was dissected and collected. The weight and length of the colon were measured, and the gross score of colon damage was performed by naked eye observation. The colon specimens were fixed with formalin, paraffin-sectioned, and the colon pathology score was performed by HE staining.

[0372] Figures 10-1 to 10-4 (in vivo efficacy results of humanized antibodies in rats) show the efficacy of humanized antibodies in TNBS-induced colitis in rats. It can be seen that compared with the model control group, the humanized antibodies 16H6-H4L1 and 16H6-H4L3 of the present application can significantly reduce the colon weight / length / body weight ratio and significantly improve the colon gross score. 16H6-H4L1 can also significantly improve the colon pathology score and is superior to the positive control antibody 1D1 (statistical analysis of inter-group differences was performed using the t-test. *: P < 0.05 compared with the model control; **: P < 0.01 compared with the model control; ***: P < 0.001 compared with the model control).

[0373] Table 9 In vivo efficacy study plan of humanized antibodies in rats

[0374] The sequences of the present application are listed in Table 10 below.

[0375] Table 10 Sequences of this application

[0376] For the purposes of description and disclosure, all patents, patent applications, and other publications are expressly incorporated herein by reference. These publications are provided solely because their disclosure predates the filing date of the present application. All statements regarding the dates of these documents or the representations of their contents are based on the information available to the applicant and do not constitute any admission as to the correctness of the dates of these documents or the contents of these documents. Furthermore, any citation of these publications herein does not constitute an admission that such publications become part of the common general knowledge in the art in any country.

[0377] Those skilled in the art will recognize that the scope of the present application is not limited to the various specific implementation modes and examples described above, but that various modifications, replacements, or recombinations can be made without departing from the spirit of the present application, which all fall within the scope of protection of the present application.

Claims

1. An anti-TL1A antibody or an antigen-binding fragment thereof, comprising: (a) A heavy chain variable region comprising the following complementarity-determining regions: HCDR1, which comprises the amino acid sequence shown in SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence shown in SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46 and having the same or similar function as the amino acid sequence shown in SEQ ID NO: 1, 7, 13, 19, 25, 28, 34, 40 or 46; HCDR2, which comprises the amino acid sequence shown in SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence shown in SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47 and having the same or similar function as the amino acid sequence shown in SEQ ID NO: 2, 8, 14, 20, 29, 35, 41 or 47; HCDR3, which comprises the amino acid sequence shown in SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence shown in SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48 and having the same or similar function as the amino acid sequence shown in SEQ ID NO: 3, 9, 15, 21, 26, 30, 36, 42 or 48; (b) A light chain variable region comprising the following complementarity-determining regions: LCDR1, which comprises the amino acid sequence shown in SEQ ID NO: 4, 10, 16, 22, 31, 37, 43 or 49, or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 4, 10, 16, 22, 31, 37, 43 or 49, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence shown in SEQ ID NO: 4, 10, 16, 22, 31, 37, 43 or 49 and having the same or similar function as the amino acid sequence shown in SEQ ID NO: 4, 10, 16, 22, 31, 37, 43 or 49; LCDR2, which comprises the amino acid sequence shown in SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence shown in SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50 and having the same or similar function as the amino acid sequence shown in SEQ ID NO: 5, 11, 17, 23, 32, 38, 44 or 50; LCDR3, which comprises the amino acid sequence shown in SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51, or an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence shown in SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51 and having the same or similar function as the amino acid sequence shown in SEQ ID NO: 6, 12, 18, 24, 27, 33, 39, 45 or 51.

2. The anti-TL1A antibody or anti-TL1A antibody or antigen-binding fragment thereof according to claim 1, comprising: (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2 and 3 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5 and 6 respectively; (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12 respectively; (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14 and 15 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17 and 18 respectively; (4) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 19, 20 and 21 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 22, 23 and 24 respectively; (5) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 25, 20 and 26 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 22, 23 and 27 respectively; (6) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 28, 29 and 30 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 31, 32 and 33 respectively; (7) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 34, 35 and 36 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 37, 38 and 39 respectively; (8) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 40, 41 and 42 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 43, 44 and 45 respectively; or (9) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 46, 47 and 48 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 49, 50 and 51 respectively; Preferably, the anti-TL1A antibody or its antigen-binding fragment comprises: (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2 and 3 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5 and 6 respectively; (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12 respectively; (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14 and 15 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17 and 18 respectively; (4) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 40, 41 and 42 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 43, 44 and 45 respectively; or (5) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 46, 47 and 48 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 49, 50 and 51 respectively; More preferably, the anti-TL1A antibody or its antigen-binding fragment comprises: (1) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 1, 2 and 3 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 4, 5 and 6 respectively; (2) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1, HCDR2 and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 7, 8 and 9 respectively, and LCDR1, LCDR2 and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 10, 11 and 12 respectively; or (3) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein HCDR1, HCDR2, and HCDR3 have the amino acid sequences shown in SEQ ID NOs: 13, 14, and 15, respectively, and LCDR1, LCDR2, and LCDR3 have the amino acid sequences shown in SEQ ID NOs: 16, 17, and 18, respectively.

3. The anti-TL1A antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein, The anti-TL1A antibody or antigen-binding fragment thereof comprises: (1) A heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 61 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 55 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 55; (2) A heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 55 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 55; (3) A heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 56 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 56; (4) A heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 57 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 57; (5) A heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 58 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 58; (6) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 59 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 59, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 55 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 55; (7) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 59 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 59, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 56 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 56; (8) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 59 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 59, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 57 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 57; (9) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 59 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 59, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 58 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 58; (10) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 60 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 55 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 55; (11) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 60 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 56 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 56; (12) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 60 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 57 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 57; (13) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 60 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 58 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 58; (14) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 61 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 56 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 56; (15) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 61 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 57 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 57; (16) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 61 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 58 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 58; (17) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (18) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 64 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 64; (19) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 65; (20) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 66 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 66; (21) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 67; (22) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 68; (23) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 69 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (24) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 69 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 64 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 64; (25) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 69 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 65; (26) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 69 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 66 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 66; (27) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (28) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 64 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 64; (29) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 65; (30) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 66 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 66; (31) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 67; (32) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 68; (33) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (34) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 64 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 64; (35) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 65; (36) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 66 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 66; (37) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 67; (38) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 68; (39) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 72 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (40) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 72 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 65; (41) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 72 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 67; (42) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 72 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 68; (43) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 73 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (44) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 73 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 65; (45) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 73 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 67; (46) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 73 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 68; (47) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 74 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 63; (48) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 74 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 67; or (49) Heavy chain variable region and light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 74 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 68 4. The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1-3, wherein, Compared with the amino acid sequence shown in any one of SEQ ID NOs: 61, 54, 59, 60, 62, 69, 70, 71, 72, 73, 74, 55, 56, 57, 58, 63, 64, 65, 66, 67 and 68, the different amino acids in the amino acid sequence having at least 80% identity are mainly or entirely located in the FR region.

5. The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1-4, wherein, The anti-TL1A antibody or its antigen-binding fragment further comprises a heavy chain constant region and / or a light chain constant region; Preferably, the heavy chain constant region is the heavy chain constant region of IgG, IgA, IgM, IgE or IgD or a variant thereof; the heavy chain constant region is preferably the heavy chain constant region of IgG or a variant thereof; the heavy chain constant region is more preferably the heavy chain constant region of human IgG1 or a variant thereof; Preferably, the light chain constant region is the constant region of human kappa chain or lambda chain or a variant thereof.

6. The anti-TL1A antibody or antigen-binding fragment thereof according to claim 5, wherein, The heavy chain constant region comprises a full-length heavy chain constant region or a fragment thereof, and the fragment can be selected from the CH1 region, CH2 region, CH3 region or Fc region.

7. The anti-TL1A antibody or antigen-binding fragment thereof according to claim 5, wherein, The Fc region is the human IgG1 Fc region. Preferably, the human IgG1 Fc region further has one or more mutations selected from the following: 329A, 329G, 329Y, 331S, 236F, 236R, 238A, 238E, 238G, 238H, 238I, 238V, 238W, 238Y, 248A, 254D, 254E, 254G, 254H, 254I, 254N, 254P, 254Q, 254T, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T and 440V, according to Kabat numbering.

8. The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 5-7, wherein, The heavy chain constant region comprises the amino acid sequence shown in SEQ ID NO: 77 or 75, or an amino acid sequence having at least 80% identity therewith; and / or The light chain constant region comprises the amino acid sequence shown in SEQ ID NO: 76 or an amino acid sequence having at least 80% identity thereto.

9. The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1-8, wherein, The anti-TL1A antibody or antigen-binding fragment thereof comprises: a heavy chain, the heavy chain comprising a heavy chain variable region and a heavy chain constant region, the heavy chain variable region comprising the amino acid sequence shown in any one of SEQ ID NOs: 61, 54, 59, 60, 62, 69, 70, 71, 72, 73 and 74 or an amino acid sequence having at least 80% identity thereto, and the heavy chain constant region comprising the amino acid sequence shown in SEQ ID NO: 75 or an amino acid sequence having at least 80% identity thereto; and a light chain, the light chain comprising: a light chain variable region, the light chain variable region comprising the amino acid sequence shown in any one of SEQ ID NOs: 55, 56, 57, 58, 63, 64, 65, 66, 67 and 68 or an amino acid sequence having at least 80% identity thereto, and a light chain constant region, the light chain constant region comprising the amino acid sequence shown in SEQ ID NO: 76 or an amino acid sequence having at least 80% identity thereto. Preferably, the anti-TL1A antibody or antigen-binding fragment thereof comprises: (1) a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 78 or an amino acid sequence having at least 80% identity thereto, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 80% identity thereto; (2) a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 78 or an amino acid sequence having at least 80% identity thereto, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 80 or an amino acid sequence having at least 80% identity thereto; (3) a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 81 or an amino acid sequence having at least 80% identity thereto, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 82 or an amino acid sequence having at least 80% identity thereto; (4) a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 83 or an amino acid sequence having at least 80% identity thereto, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 82 or an amino acid sequence having at least 80% identity thereto; (5) a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 81 or an amino acid sequence having at least 80% identity thereto, and a light chain comprising the amino acid sequence shown in SEQ ID NO: 84 or an amino acid sequence having at least 80% identity thereto.

10. The anti-TL1A antibody or antigen-binding fragment thereof according to any one of claims 1-9, wherein, The antibody is a murine antibody, a simian antibody, a rabbit antibody, a chimeric antibody, a humanized antibody, a fully human antibody; and / or The anti-TL1A antibody is selected from monoclonal antibodies, polyclonal antibodies, neutralizing antibodies, antagonistic antibodies, anti-idiotypic antibodies, aglycosylated antibodies, monospecific antibodies, multispecific antibodies or nanobodies, and the antigen-binding fragment is at least one selected from Fab fragment, Fab' fragment, F(ab')2 fragment, Fd fragment, Fv fragment, dAb fragment, isolated CDR region and scFv; and / or The anti-TL1A antibody is a monoclonal antibody or a multispecific antibody. Preferably, the multispecific antibody is a bispecific antibody, trispecific antibody or tetra-specific antibody.

11. A nucleic acid molecule encoding the anti-TL1A antibody or its antigen-binding fragment according to any one of claims 1-10.

12. A recombinant vector comprising the nucleic acid molecule according to claim 11.

13. A host cell comprising the nucleic acid molecule according to claim 11 or the recombinant vector according to claim 12.

14. The anti-TL1A antibody or its antigen-binding fragment according to any one of claims 1-10, the nucleic acid molecule according to claim 11, the recombinant vector according to claim 12, and the host cell according to claim 13 for preventing and / or treating TL1A-mediated related diseases or disorders; Preferably, the disease or disorder is prevented, alleviated, improved or inhibited by eliminating, inhibiting or reducing TL1A activity; Preferably, the disease is an immune-related or inflammatory disease; Preferably, the disease or disorder is selected from at least one of the following: inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), interstitial lung disease associated with systemic sclerosis, idiopathic pulmonary fibrosis, virus-induced pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), allergic pulmonary inflammation, neurodegenerative diseases, cancer, diabetes, arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, transplant rejection, graft-versus-host disease (GVHD), spondyloarthropathy, primary sclerosing cholangitis, primary biliary cirrhosis, atherosclerosis, bladder syndrome, interstitial cystitis, urointestinal dysfunction, sepsis, uveitis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus, cutaneous lupus erythematosus, autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjögren's syndrome, scleroderma and vasculitis; Preferably, the inflammatory bowel disease includes Crohn's disease and ulcerative colitis; More preferably, the disease or disorder is inflammatory bowel disease.

15. A kit for detecting TL1A, comprising the anti-TL1A antibody or its antigen-binding fragment according to any one of claims 1-10 and the nucleic acid molecule according to claim 11.

Images