CN117279943A - Methods, systems, and kits for treating inflammatory diseases by targeting TL1A - Google Patents

Abstract

Methods, systems, and kits are provided for selecting subjects for treatment with inhibitors of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression based on the presence of one or more genotypes associated with a positive therapeutic response to the TL1A inhibitor. Methods, systems, and kits for detecting one or more genotypes described herein are also provided.

Description

Methods, systems, and kits for treating inflammatory diseases by targeting TL1A

Cross reference

The present application claims the benefit of U.S. provisional application No. 63/113,657 filed 11/13/2020, U.S. provisional application No. 63/136,153 filed 1/2021, U.S. provisional application No. 63/147,165 filed 2/2021, U.S. provisional application No. 63/181,074 filed 4/20228, U.S. provisional application No. 63/226,032 filed 7/2021, each of which is incorporated by reference in its entirety.

Sequence listing

The present application contains a sequence listing, which is submitted electronically in ASCII format and hereby incorporated by reference in its entirety. The ASCII copy created at month 11 and 10 of 2021 is named 56884-782_601_sl.txt and is 14,800,566 bytes in size.

Background

Inflammatory, fibrotic and fibrotic diseases pose a significant health burden worldwide due to the large number of affected individuals and the pathogenesis and different clinical manifestations of heterogeneous diseases. One such disease is Inflammatory Bowel Disease (IBD), which has two common forms, crohn's Disease (CD) and Ulcerative Colitis (UC). IBD is a chronic, recurrent inflammatory disorder of the gastrointestinal tract. The incidence of IBD is high, affecting nearly three million people in the united states alone.

Few treatment options are available for patients with inflammatory, fibrotic and fibrotic diseases. Existing anti-inflammatory therapies such as steroids and Tumor Necrosis Factor (TNF) inhibitors are commonly used as first line therapies for the treatment of IBD. Unfortunately, a large number of patients experience either an inadequate or a loss of response to existing anti-inflammatory therapies, particularly TNF inhibitors. When patients are treated with ineffective anti-inflammatory therapies, the disease worsens. Surgery in the form of a structural angioplasty (intestinal remodeling) or resection (intestinal resection) is the only treatment option for patients who do not respond to first-line therapy. Surgical treatments for IBD are invasive, estimated to pose post-operative risks such as anastomotic leakage, infection, and bleeding to one third of patients undergoing surgery.

The pathogenesis of inflammatory, fibrotic and fibrotic diseases (such as IBD) is thought to involve uncontrolled immune responses that may be triggered by certain environmental factors in genetically susceptible individuals. The heterogeneity of disease pathogenesis and clinical course of disease and the different responses to treatment and their associated side effects suggests that personalized medical approaches to treat these diseases are the best therapeutic strategies. However, there are few personalized therapies available to patients. Thus, there is a need to identify targeted therapies for the treatment of inflammatory, fibrostenotic and fibrotic diseases and their sub-clinical phenotypes, and even more to develop reliable methods for identifying patients who are likely to respond to any given therapy based on their genotypes. The desired method will also identify undiagnosed subjects at risk of developing disease for whom preventive interventions can be prescribed to reduce the increasing health burden.

Disclosure of Invention

The genotypes described herein are associated with increased levels of TNFSF15 (TL 1A) protein expression in a sample obtained from a subject or patient as compared to a reference level of TNFSF15 (TL 1A) protein expression (e.g., from a normal individual). The genotypes disclosed herein are located at genes or loci that are directly or indirectly involved in TL1A mediated or T cell dependent inflammatory pathways. In addition, some genotypes provided herein are also clearly associated with Inflammatory Bowel Disease (IBD), such as Crohn's Disease (CD). Genotypes can be used to select patients or subjects for treatment with inhibitors of TL1A activity or expression. The patient may be diagnosed with IBD, CD, or both. The subject may be suspected of having IBD, CD, or both.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with the inhibitor of TL1A activity or expression that has a positive predictive value or specificity of at least about 51%, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that competes for binding to human TL1A with a reference antibody comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15. In some embodiments of the present invention, in some embodiments, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that competes for binding to human TL1A with a reference antibody comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with the inhibitor of TL1A activity or expression that has a positive predictive value or specificity of at least about 51%, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to human TL1A, comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15. In some embodiments of the present invention, in some embodiments, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to human TL1A, comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ id no:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ id no:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with the inhibitor of TL1A activity or expression having at least about 51% of a positive predictive value or specificity, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide that binds to SEQ ID NO:101-135 or 310-302, and a heavy chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NO:201-206 or 303, and a light chain variable domain of an amino acid sequence that is at least about 90% identical. In some embodiments of the present invention, in some embodiments, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 of at least 0.85, or a combination thereof. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:101-135 or 310-302, at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201-206 or 303, at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide sequence as set forth in SEQ ID NO:101-135 or 310-302, and a heavy chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NO:201-206 or 303, and a light chain variable domain of an amino acid sequence that is at least about 90% identical. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with the inhibitor of TL1A activity or expression that has a positive predictive value or specificity of at least about 51%, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising: (a) A heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework; and (b) a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein said heavy chain variable framework region and said light chain variable framework region comprise less than about 14 amino acid modifications in total compared to said human IGHV1-46 x 02 framework and said human IGKV3-20 framework. In some embodiments of the present invention, in some embodiments, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A, comprising: (a) A heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework; and (b) a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein said heavy chain variable framework region and said light chain variable framework region comprise less than about 14 amino acid modifications in total compared to said human IGHV1-46 x 02 framework and said human IGKV3-20 framework. In some embodiments, the amino acid modifications of less than 14 amino acid modifications comprise: (a) The amino acid modification is located at position 47 in the heavy chain variable region, and the amino acid at position 47 is R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (b) The amino acid modification is located at position 45 in the heavy chain variable region, and the amino acid at position 45 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (c) The amino acid modification is located at position 55 in the heavy chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; (d) The amino acid modification is located at position 78 in the heavy chain variable region, and the amino acid at position 78 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y; (e) The amino acid modification is located at position 80 in the heavy chain variable region, and the amino acid at position 80 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; (f) The amino acid modification is located at position 82 in the heavy chain variable region, and the amino acid at position 82 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (g) The amino acid modification is at position 89 in the heavy chain variable region, and the amino acid at position 89 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y; or (h) the amino acid modification is at position 91 in the heavy chain variable region, and the amino acid at position 91 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; or a combination of two or more modifications selected from (a) to (h). In some embodiments, the amino acid modifications of less than 14 amino acid modifications comprise: a47R, R45K, M55I, V A, M80I, R82T, V3589A, M91L in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid modifications of less than 14 amino acid modifications comprise: (a) Modification at amino acid position 54 in the light chain variable region; and/or (b) a modification at amino acid position 55 in the light chain variable region; numbered according to Aho or Kabat. In some embodiments, the amino acid modifications of less than 14 amino acid modifications comprise: (a) The amino acid modification is at position 54 of the light chain variable region, and the amino acid at position 54 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V; and/or (b) the amino acid modification is located at position 55 of the light chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid modifications of less than 14 amino acid modifications comprise L54P and/or L55W in the light chain variable region according to the Aho or Kabat numbering. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with the inhibitor of TL1A activity or expression that has a positive predictive value or specificity of at least about 51%, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO:301X1 VQLVQGGAEVEKKGGASVKVACUSCHAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] Rx5TX6TXDSTX8Ye9 ELSSLRSEDTAVYCAR [ HCDR3] WGQGTTVTVSS, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with the inhibitor of TL1A activity or expression that has a positive predictive value or specificity of at least about 51%, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO:302x1 vqlvqsgaevkkpgasvkvscskas [ hcdr1] wvx2qx3pgqglewx4g [ hcdr2] rx5tx6tx7 dtstx 8yx9 elsslrsettavyc [ hcdr3] wgqgttvss, and a light chain variable region comprising SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments of the present invention, in some embodiments, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO:301X1 VQLVQGGAEVEKKGGASVKVACUSCHAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] Rx5TX6TXDSTX8Ye9 ELSSLRSEDTAVYCAR [ HCDR3] WGQGTTVTVSS, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In some aspects, disclosed herein is a method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms include rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268 rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof, and wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises: a heavy chain variable region comprising SEQ ID NO:302x1 vqlvqsgaevkkpgasvkvscskas [ hcdr1] wvx2qx3pgqglewx4g [ hcdr2] rx5tx6tx7 dtstx 8yx9 elsslrsettavyc [ hcdr3] wgqgttvss, and a light chain variable region comprising SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments: (A) X1 is Q or E; (B)

X2 is R or K (C) X3 is A or R; (D) X4 is M or I; (E) X5 is V or A; (F) X6 is M or I; (G) X7 is R or T; (H) X8 is V or A; (I)

X9 is M or L (J) X10 is L or P; (K) X11 is L or W; or (L)

X1-X11 are any combination of (a) through (k). In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:1, as set forth by SEQ ID NO:2-5, a heavy chain CDR2 as set forth by any one of SEQ ID NOs: 6-9, a heavy chain CDR3 as set forth by any one of SEQ ID NOs: 10, as set forth by SEQ ID NO:11 and a light chain CDR2 as set forth by SEQ ID NO:12-15, and a light chain CDR3 as set forth in any one of claims 12-15. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:304, a heavy chain Framework (FR) 1 as set forth by SEQ ID NO:305 or SEQ ID NO:313, a heavy chain FR2 as represented by SEQ ID NO: 306. 307, 314 or 315, as represented by any one of SEQ ID NOs: 308, as represented by SEQ ID NO:309, the light chain FR1 as represented by SEQ ID NO:310, a light chain FR2 as represented by SEQ ID NO:311 or the light chain FR3 as represented by SEQ ID NO:312, or a combination thereof. In some embodiments, the antibody or antigen binding fragment comprises a human IgG1 Fc region comprising (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) 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) D or P, (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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L E, G a and P331S, (bbb) L234A, L, (82348 237A, P) 238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L a and P, (ddd) G236R and L328R, (eee) G237A, (fff 241A, (ggg) V234A and P329G, (y) L234F, L a and P331S, (zz) L234G 35A, (zz) and (G) N) 35A, (can be selected from any of (mm) and (mm) or (mm) N (mm) and (mm) 330A (mm) or (mm) 330G (mm). In some embodiments, the antibody or antigen binding fragment comprises a human IgG4 Fc region. In some embodiments, the antibody or antigen binding fragment comprises an Fc region comprising an amino acid sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, the antibody of the antigen binding fragment comprises a crystallizable fragment (Fc) region comprising reduced antibody dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and/or reduced Complement Dependent Cytotoxicity (CDC) as compared to human IgG1. In some embodiments, the Fc comprises a polypeptide comprising SEQ ID NO:320, human IgG1. In some embodiments, the ADCC function comprising the Fc region of reduced ADCC is reduced by at least about 50% compared to human IgG1. In some embodiments, the CDC function of the Fc region comprising reduced CDC is reduced by at least about 50% as compared to human IgG1. In some embodiments, the Fc comprises (i) a human IgG4 Fc region, or (ii) a human IgG4 Fc region comprising: (a) S228P, (b) S228P and L235E, or (c) S228P, F234A and L235A, numbered according to Kabat. In some embodiments, the Fc comprises a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. In some embodiments, the Fc comprises a human IgG1 having a substitution 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, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T and 440V, numbered according to Kabat. In some embodiments, the Fc comprises a nucleotide sequence that hybridizes to SEQ ID N0:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, the Fc comprises SEQ ID No:401-413 or with any one of SEQ ID nos: 401-413, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, the antibody or antigen binding fragment comprises a heavy chain comprising the amino acid sequence of SEQ ID No:501-513 or with any one of SEQ ID nos: 501-513, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In some embodiments, the antibody or antigen binding fragment comprises a light chain comprising SEQ ID N0:514 or any one of SEQ ID NO:514 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, the at least three polymorphisms are predicted to have a positive predictive value of at least about 51% and a specific positive therapeutic response. In some embodiments, the positive predictive value is greater than or equal to about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%. In some embodiments, the positive predictive value is between about 60% -100%, 65% -95%, 70% -90%, 75% -85% and 70% -80%. In some embodiments, the specificity is greater than or equal to about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%. In some embodiments, the specificity is between about 60% -100%, 65% -95%, 70% -90%, 75% -85% and 70% -80%. In some embodiments, the at least three polymorphisms include: rs6478109, rs56124762 and rs1892231. In some embodiments, the at least three polymorphisms include: rs6478109, rs56124762 and rs16901748. In some embodiments, the at least three polymorphisms include: rs6478109, rs1892231 and rs16901748. In some embodiments, the at least three polymorphisms include: rs56124762, rs1892231 and rs16901748. In some embodiments, the at least three polymorphisms include: rs6478109, rs2070558 and rs1892231. In some embodiments, the at least three polymorphisms include: rs6478109, rs2070558 and rs16901748. In some embodiments, the at least three polymorphisms include: rs6478109, rs1892231 and rs16901748. In some embodiments, the at least three polymorphisms include: rs2070558, rs1892231 and rs16901748. In some embodiments, the at least three polymorphisms include: rs6478109, rs2070561 and rs1892231. In some embodiments, the at least three polymorphisms include: rs6478109, rs2070561 and rs16901748. In some embodiments, the at least three polymorphisms include: rs6478109, rs1892231 and rs16901748. In some embodiments, the at least three polymorphisms include: rs2070561, rs1892231 and rs16901748. In some embodiments, the at least three polymorphisms include: rs6478109, rs7935393 and rs1892231. In some embodiments, the at least three polymorphisms include: rs6478109, rs7935393 and rs9806914. In some embodiments, the at least three polymorphisms include: rs6478109, rs7935393 and rs7278257. In some embodiments, the at least three polymorphisms include: rs6478109, rs7935393 and rs2070557. In some embodiments, the at least three polymorphisms include: rs6478109, rs1892231 and rs9806914. In some embodiments, the at least three polymorphisms include: rs6478109, rs1892231 and rs7278257. In some embodiments, the at least three polymorphisms include: rs6478109, rs1892231 and rs2070557. In some embodiments, the at least three polymorphisms include: rs6478109, rs9806914 and rs7278257. In some embodiments, the at least three polymorphisms include: rs6478109, rs9806914 and rs2070557. In some embodiments, the at least three polymorphisms include: rs6478109, rs7278257 and rs2070557. In some embodiments, the at least three polymorphisms include: rs7935393, rs1892231 and rs9806914. In some embodiments, the at least three polymorphisms include: rs7935393, rs1892231 and rs7278257. In some embodiments, the at least three polymorphisms include: rs7935393, rs1892231 and rs2070557. In some embodiments, the at least three polymorphisms include: rs7935393, rs9806914 and rs7278257. In some embodiments, the at least three polymorphisms include: rs7935393, rs9806914 and rs2070557. In some embodiments, the at least three polymorphisms include: rs7935393, rs7278257 and rs2070557. In some embodiments, the at least three polymorphisms include: rs1892231, rs9806914 and rs7278257. In some embodiments, the at least three polymorphisms include: rs1892231, rs9806914 and rs2070557. In some embodiments, the at least three polymorphisms include: rs1892231, rs7278257 and rs2070557. In some embodiments, the at least three polymorphisms include: rs9806914, rs7278257 and rs2070557. In some embodiments, the at least three polymorphisms include: rs6478109, rs56124762 and rs1892231. In some embodiments, the at least three polymorphisms further include a fourth polymorphism, the fourth polymorphism includes rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs 5268, rs7935393, rs12934476, rs12457255, and the like rs12457255, or rs12457255, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms in the sample are detected by performing an assay on the sample configured to detect a nucleotide sequence corresponding to SEQ ID NO:2001-20041 or 20057-20059, and the presence of at least three nucleotides of nucleic acid position 501 within at least three of them. In some embodiments, the inflammatory, fibrotic, or fibrotic disease or condition includes inflammatory bowel disease, crohn's disease, obstructive crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, pulmonary fibrosis, scleroderma, or primary sclerosing cholangitis. In some embodiments, the crohn's disease is ileal crohn's disease, ileal colon crohn's disease, or colon crohn's disease. In some embodiments, the pulmonary fibrosis comprises idiopathic pulmonary fibrosis. In some embodiments, the subject has or is at risk of developing a standard therapy including glucocorticoid, anti-TNF therapy, anti-a 4-b7 therapy, anti-IL 12p40 therapy, or a combination thereof. In some embodiments, the method further comprises determining whether the subject with an inflammatory, fibrotic, or fibrotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression based at least in part on the at least three polymorphisms detected in the sample. In some embodiments, the method further comprises obtaining or has obtained the sample from the subject. In some embodiments, the at least three polymorphisms are detected using assays that include quantitative polymerase chain reaction (qPCR), nucleic acid sequencing reaction, or genotyping array. In some embodiments, the at least three polymorphisms include three polymorphisms (3-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include four polymorphisms (4-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include five polymorphisms (5-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include six polymorphisms (6-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include seven polymorphisms (7-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include eight polymorphisms from one or more 8-SNP models provided in table 25. In some embodiments, the at least three polymorphisms include nine polymorphisms (9-SNP models) selected from table 1. In some embodiments, the at least three polymorphisms include ten polymorphisms (10-SNP models) selected from table 1.

In other embodiments, the at least three polymorphisms are at least eight polymorphisms. In some embodiments, at least eight polymorphisms are provided in the 8-SNP model in Table 25.

Other aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, wherein only illustrative embodiments of the disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments and its several details are capable of modification in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

Incorporated by reference

All publications, patents and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. When publications and patents or patent applications incorporated by reference contradict the present disclosure contained in this specification, this specification is intended to replace and/or take precedence over any such contradictory material.

Drawings

The novel features believed characteristic of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings thereof (also referred to herein as "Figure/fig").

Fig. 1 illustrates a workflow for processing a biological sample obtained from a subject to inform selection of a therapeutic agent for treating a disease or condition of the subject, according to an embodiment of the present disclosure.

Fig. 2 illustrates a computer-implemented workflow for generating an electronic report including a TNFSF15 profile of a subject to a user (such as a doctor) based on analysis of genotype data from the subject, according to an embodiment of the present disclosure.

FIG. 3 illustrates a computer system programmed or otherwise configured to implement the methods provided herein.

Fig. 4 illustrates a computer-implemented workflow for generating TNFSF15 profiles in accordance with an embodiment of the present disclosure.

Fig. 5A-5C illustrate cluster analysis within our TL1A companion diagnostic (CDx) dataset according to some embodiments herein. Fig. 5A shows cluster 1 from the TL1A CDx dataset, fig. 5B shows cluster 2, and fig. 5C shows cluster 3.

Fig. 6 shows that 3 clusters from fig. 5A-5C shrink into 2 clusters (high TL1A expression clusters are shown on the left) and (low TL1A expression clusters are shown on the right).

Fig. 7A-7C show chromatograms of analytical size exclusion chromatography of anti-TL 1A antibodies. Fig. 7A shows chromatograms of analytical size exclusion chromatography of antibodies a193, a194, and a 195. Fig. 7B shows chromatograms of analytical size exclusion chromatography of antibodies a196, a197, and a 198. Fig. 7C shows chromatograms of analytical size exclusion chromatography of antibodies a199, a200, and a 201.

Figures 8A-8B depict the inhibition of interferon gamma in human blood by anti-TL 1A antibodies. Fig. 8A depicts the inhibition of interferon gamma in human blood by anti-TL 1A antibodies a219 and a 213. Fig. 8B depicts inhibition of interferon gamma in human blood by anti-TL 1A antibody a 212.

FIGS. 9A-9C depict PLS models demonstrating the effect of pH and protein concentration on viscosity. Fig. 9A shows PLS plots, fig. 9B shows a model of predicted viscosity versus anti-TL 1A antibody concentration (in mg/mL), and fig. 9C shows a model of estimated viscosity versus actual viscosity. The viscosity unit is mPa-s.

FIG. 10 illustrates TL1A CDx performance statistics determined for TL1A ex-vivo production according to some embodiments.

FIGS. 11A-11B show exemplary clinical trial studies of the anti-TL 1A antibodies disclosed herein. Fig. 11A depicts a study protocol for induction period for phase 2 clinical trials of a219 in UC according to some embodiments herein. Fig. 11B depicts a study protocol of open-label extension phase for a phase 2 clinical trial of a219 in UC according to some embodiments herein.

Detailed Description

Provided herein are methods, systems, and kits for treating a subject who may be suitable for treatment with an inhibitor of tumor necrosis factor (ligand) superfamily member 15 (TL 1A) activity or expression, provided that the subject is a carrier of a genotype. The subject may be a patient who may be diagnosed with an inflammatory disease, a fibrotic disease, or a fibrotic disease such as Inflammatory Bowel Disease (IBD) or Crohn's Disease (CD). The subject may not be a patient, but may be suspected of having an inflammatory disease, a fibrotic disease, or a fibrotic disease. In some cases, the genotype can be used to treat an inflammatory fibrostenosis or fibrotic disease or condition, such as that mediated by TL 1A. In some embodiments, the subject is treated by administering to the subject an inhibitor of TL1A activity or expression (e.g., an anti-TL 1A antibody), provided that the genotype is detected. In some cases, it is desirable to identify the subject as suitable for treatment with an inhibitor of activity or expression in order to administer the inhibitor to the subject.

Referring to fig. 1, in some embodiments, the methods, systems, and kits of the present disclosure involve the steps of: providing an oral swab sample 101 from a subject, optionally purifying DNA from the sample by processing the sample 102, determining the optionally processed sample to detect genotypes 103 of at least three loci in the sample, processing the genotypes to generate a TNFSF15 profile 104, and treating the subject with an anti-TL 1A antibody or antibody fragment disclosed herein based on the TNFSF15 profile to treat a disease or condition 105 of the subject.

Suitable genotyping devices (e.g., array, sequencing) are used to detect genotypes described herein. In some cases, the sample is obtained indirectly or directly from the subject or patient. In some cases, the sample may be obtained from a subject. In other cases, the sample may be obtained by a medical staff member, such as a nurse or doctor. The sample may be derived from virtually any biological fluid or tissue containing genetic information, such as blood.

The subject disclosed herein can be a mammal, such as a mouse, rat, guinea pig, rabbit, non-human primate, or livestock. In some cases, the subject is a human. In some cases, the subject suffers from symptoms associated with the diseases or conditions disclosed herein (e.g., abdominal pain, cramps, diarrhea, rectal bleeding, fever, weight loss, fatigue, loss of appetite, dehydration, and malnutrition, anemia, or ulcers).

In some embodiments, the subject is susceptible to or suffering from thiopurine toxicity or a disease caused by thiopurine toxicity (such as pancreatitis or leukopenia). The subject may experience or be suspected of experiencing no response or a loss of response to standard therapy (e.g., anti-tnfα therapy, anti-a 4-b7 therapy (vedolizumab)), anti-IL 12p40 therapy (Wu Sinu mab), thalidomide (Thalidomide), or cytotoxin).

The disease or condition disclosed herein may be an inflammatory disease, a fibrotic disease, or a fibrotic disease. In some cases, the disease or condition is a TL1A mediated disease or condition. The term "TL1A mediated disease or condition" refers to a disease or condition pathology or pathogenesis driven at least in part by TL1A signaling. In some cases, the disease or condition is an immune-mediated disease or condition, such as those mediated by TL 1A.

In some embodiments, the disease or condition is an inflammatory disease or disorder mediated at least in part by TL1A signaling. Non-limiting examples of inflammatory diseases include allergies, ankylosing spondylitis, asthma, atopic dermatitis, autoimmune diseases or disorders, cancer, celiac disease, chronic Obstructive Pulmonary Disease (COPD), chronic peptic ulcers, cystic fibrosis, diabetes (e.g., type 1 and type 2 diabetes), glomerulonephritis, gout, hepatitis (e.g., active hepatitis), immune-mediated diseases or disorders, inflammatory Bowel Diseases (IBD) such as crohn's disease and ulcerative colitis, myositis, osteoarthritis, pelvic Inflammatory Disease (PID), multiple sclerosis, aging neurodegenerative diseases, periodontal disease (e.g., periodontitis), reperfusion injury graft rejection, psoriasis, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), rheumatic diseases, scleroderma, sinusitis, tuberculosis.

In some embodiments, the disease or condition is an autoimmune disease mediated at least in part by TL1A signaling. Non-limiting examples of autoimmune diseases or conditions include achalasia of the cardiac, addison's disease, adult stell's disease, agaropectinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM/anti-TBM nephritis, anti-phospholipid syndrome, autoimmune angioedema, autoimmune familial autonomic nerve abnormalities, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune Inner Ear Disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria,Axonal and neuronal neuropathy (AMAN), bal disease (Bal disease), behcet's disease, benign mucosal pemphigoid, bullous pemphigoid, cassman's disease (Castleman disease, CD), celiac disease, chagas disease, chronic Inflammatory Demyelinating Polyneuropathy (CIDP), chronic Recurrent Multifocal Osteomyelitis (CRMO), chegregarian-Strauss Syndrome (Churg-Strauss Syndrome, CSS) or Eosinophilic Granulomatosis (EGPA), cicatricial pemphigoid, ke Genzeng Syndrome (Cogan's Syndrome), collectin disease, congenital heart block, coxsackie viral myocarditis (Coxsackie myocarditis), CREST Syndrome, crohn's disease, dermatitis herpetiformis, dermatomyositis, devic's disease (neuromyelitis optica), discoid lupus, telesler's Syndrome (Dresser's Syndrome), endometriosis, eosinophilic esophagitis (EoE), eosinophilic fasciitis, erythema nodosum, primary mixed cryoglobulinemia, evans Syndrome, fibromyalgia, fibroalveolitis, giant cell arteritis (temporal arteritis), giant cell myocarditis, glomerulonephritis, goodpasture's Syndrome, granulomatous polyangiitis, graves 'disease, guillain-Barre Syndrome, hashimoto's thyroiditis, hemolytic anemia, henoch-Schonlein purpura (Henoch-Schonlein purpura, HSP), herpes gestation or gestational Pemphigoid (PG), suppurative sweat gland (HS) (abnormal acne), hypogammaglobemia, igA nephropathy, igG 4-related sclerotic disease, immune Thrombocytopenic Purpura (ITP), inclusion Body Myositis (IBM), interstitial Cystitis (IC), juvenile arthritis, juvenile diabetes (type 1 diabetes), juvenile Myositis (JM), kawasaki disease (Kawasaki disease), lanbert-Eaton syndrome (Lambert-Eaton syndrome), white blood cell disruption vasculitis, lichen planus, lichen sclerosus, linear conjunctivitis, igA disease (LAD), lupus, chronic lyme disease (Lyme disease chronic), meniere's disease (Meniere's disease), microscopic Polyangiitis (MPA), mixed Connective Tissue Disease (MCTD), mo Lunshi (Mon's), 62-Haeman's ulcer (Mubber-62-Mubber's disease) rmann disease), multifocal Motor Neuropathy (MMN) or MMNCB, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neonatal lupus, neuromyelitis optica, neutropenia, ocular cicatricial pemphigoid, optic neuritis, recurrent rheumatism (PR), PANDAS, paraneoplastic Cerebellar Degeneration (PCD), paroxysmal sleep hemoglobinuria (PNH), pari-Long Beige syndrome (Parry Romberg syndrome), ciliary body flattening (peripheral uveitis), pasen-turner syndrome (Parsonage-turner syndrome), pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious Anemia (PA), POEMS syndrome, polyarteritis nodosa type I, type II, type III polyadenopathy, polymyalgia rheumatica, polymyositis, post myocardial infarction syndrome, post pericardial opening syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red blood cell aplasia (PRCA), pyoderma gangrenosum, raynaud's phenomenon, reactive arthritis, reflex sympathetic dystrophia, recurrent polychondritis, restless Leg Syndrome (RLS), retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, schmidt syndrome (Schmidt syndrome), scleritis, scleroderma, sjogren syndrome syndrome), sperm and testis autoimmunity, stiff Person Syndrome (SPS), subacute Bacterial Endocarditis (SBE), sulsak's syndrome (Susac's syndrome), sympathogenic Ophthalmitis (SO), takayasu's artertitis, temporal arteritis/giant cell arteritis, thrombocytopenic purpura (TTP), tolossa-hunter syndrome (THS), transverse myelitis, type 1 diabetes, ulcerative Colitis (UC), undifferentiated connective tissue Disease (uccd), uveitis, vasculitis, vitiligo and wogolgi-salix-mata Tian Bing (Vogt-koyanag-Harada Disease).

In some embodiments, the disease or condition is a cancer mediated at least in part by TL1A signaling. Non-limiting examples of cancers include adenoid cystic carcinoma, adrenal carcinoma, amyloidosis, anal carcinoma, ataxia-telangiectasia, atypical nevus Syndrome, basal cell carcinoma, cholangiocarcinoma, bert Huo Gedu Syndrome (Birt Hogg Dube Syndrome), bladder cancer, bone cancer, brain tumor, breast cancer, male breast cancer, carcinoid tumor, cervical cancer, colorectal cancer, ductal carcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumor (GIST), HER2 positive breast cancer, islet cell tumor, juvenile polyposis Syndrome, renal cancer, laryngeal cancer, leukemia-acute lymphoblastic leukemia, acute Lymphoblastic Leukemia (ALL), acute myelogenous leukemia AML, adult leukemia, pediatric leukemia, chronic Lymphoblastic Leukemia (CLL) Chronic Myelogenous Leukemia (CML), liver cancer, lobular cancer, lung cancer, small Cell Lung Cancer (SCLC), non-small cell lung cancer (NSCLC), hodgkin's, non-Hodgkin's Lymphoma (Lymphoma-Non-Hodgkin's), glioblastoma, melanoma, meningioma, multiple myeloma, myelodysplastic Syndrome (MDS), nasopharyngeal carcinoma, neuroendocrine tumor, oral cancer, osteosarcoma, ovarian cancer, pancreatic neuroendocrine tumor, parathyroid cancer, penile cancer, peritoneal cancer, bois-yeger Syndrome (Peutz-Jeghers synomes), pituitary tumor, polycythemia vera, prostate cancer, renal cell carcinoma, retinoblastoma, salivary gland carcinoma, sarcoma, kaposi's Sarcoma (sarcomas-Kaposi), pancreatic cancer, pancreatic neuroendocrine tumor, and malignant tumor, skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymoma, thyroid cancer, uterine (endometrial) cancer, vaginal cancer, and Wilms' Tumor.

In some embodiments, the disease or condition is an inflammatory bowel disease, such as Crohn's Disease (CD) or Ulcerative Colitis (UC). The subject may have a fibrotic, fibrostenotic or fibrotic disease alone or in combination with an inflammatory disease. In some cases, the CD is a severe CD. Severe CD may be caused by inflammation leading to scar tissue formation (fibrostenosis) and/or swelling of the intestinal wall. In some cases, severe CD is characterized by the presence of fibrosis and/or inflammatory stenosis. Stenosis can be determined by Computed Tomography (CTE) and magnetic resonance imaging (MRE) small intestine imaging. The characteristics of the disease or condition may be refractory, which in some cases means that the disease is resistant to standard treatment (e.g., anti-tnfa therapy). Non-limiting examples of standard therapies include glucocorticoids, anti-TNF therapies, anti-a 4-b7 therapies (vedelizumab), anti-IL 12p40 therapies (Wu Sinu mab), thalidomide, and cytotoxins.

Genotype of the type

Disclosed herein are genotypes that can be detected in a sample obtained from a subject by analyzing genetic material in the sample. In some cases, the subject may be a human. In some embodiments, the genetic material is obtained from a subject having a disease or condition disclosed herein. In some cases, the genetic material is obtained from blood, serum, plasma, sweat, hair, tears, urine, and other techniques known to those skilled in the art. In some cases, the genetic material is obtained from a biopsy, e.g., from the intestinal tract of a subject.

The genotypes of the present disclosure comprise genetic material which is deoxyribonucleic acid (DNA). In some cases, the genotype comprises a denatured DNA molecule or fragment thereof. In some cases, the genotype comprises DNA selected from the group consisting of: genomic DNA, viral DNA, mitochondrial DNA, plasmid DNA, amplified DNA, circular DNA, circulating DNA, cell-free DNA, or exosome DNA. In some cases, the DNA is single-stranded DNA (ssDNA), double-stranded DNA, denatured double-stranded DNA, synthetic DNA, and combinations thereof. The circular DNA may be cleaved or fragmented.

The genotypes disclosed herein comprise at least one polymorphism at a gene or locus described herein. In some cases, the gene or locus is selected from the group consisting of: tumor necrosis factor (ligand) superfamily member 15 (TNFSF 15), the THADA-arm-and-band repeats (THADA) contained, the H2-containing pleckstrin homology MyTH4 and FERM domains (PLEKHH 2), XK-related 6 (XKR), myotube protein-related protein 9 (MTMR 9), ETS protooncogene 1, transcription factor (ETS 1), 16A-containing C-lectin domain (CLEC 16A), cytokine signaling inhibitor 1 (SOCS 1), protein tyrosine phosphatase type 2 non-receptor (PTPN 2), inducible T-cell co-stimulatory factor ligand (ICOSLG), two-sided Kinase (Janus Kinase) 2 (JAK 2), catenin delta 2 (CTNND 2), G-protein signaling 7 (RGS 7), RNA binding Fox-1 homolog 1 (RBFOX 1), RNA binding motif protein 17 (RBM 17), fructose-2-phosphate kinase/fructose-2, 6-bisphosphate enzyme 3 (PFKFB 3), extracellular NOX disulfide-thiol exchanger 1 (ENOX 1), 122-containing coiled coil domain (CCDC 122), telomere elongation helicase 1 regulator (RTEL 1), TNF receptor superfamily member 6B (TNFRSF 6B), GLIS family zinc finger 3 (GLIS 3), solute carrier family 1 member 1 (SLC 1 A1), IKAROS family zinc finger 2 (IKZF 2), fatty acyl CoA reductase 1 (FAR 1), reactive 1 (SPON 1), plexin A2 (PLXNA 2), MIR205 host genes (MIR 205 HG), 16A-containing C-type lectin domain (CLEC 16A), PR/SET domain 14 (dm), autocorrelation 5 (ATG 5) and prostaglandin 4 (pre receptor 4). In some cases, the gene or locus comprises a gene or locus provided in table 1. In some cases, the genotypes disclosed herein are haplotypes. In some cases, the genotype includes a particular polymorphism, a polymorphism in Linkage Disequilibrium (LD) therewith, or a combination thereof. In some cases, the LD consists of at least or about 0.70, 0.75, 0.80, 0.85, 0.90, or 1.0 r ² And (3) limiting. Genotypes disclosed herein may comprise at least or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more polymorphisms. In a preferred embodiment, the genotypes disclosed herein comprise a combination of 3 polymorphisms, such as those provided in table 1.

The polymorphism described herein may be a single nucleotide polymorphism, or an insertion deletion (indel) (insertion/deletion). In some cases, the polymorphism is an insertion or deletion (e.g., indel) of at least one nucleobase. In some cases, a genotype may comprise Copy Number Variation (CNV), which is a variation in the number of nucleic acid sequences between individuals in a given population. In some cases, a CNV comprises at least or about two, three, four, five, six, seven, eight, nine, ten, twenty, thirty, forty, or fifty nucleic acid molecules. In some cases, the genotype is heterozygous. In some cases, the genotype is homozygous.

In the following embodiments, disclosed herein are genotypes disclosed herein:

1. a genotype comprising at least one polymorphism at a gene or locus.

2. The genotype of embodiment 1, comprising the polymorphisms provided in table 1.

3. The genotype as described in embodiments 1-2, which is heterozygous.

4. The genotype as described in embodiments 1-2, which is homozygous.

5. The genotype of embodiments 1-4, wherein the genotype comprises at least two polymorphisms.

6. The genotype of embodiments 1-4, wherein the genotype comprises at least three polymorphisms.

7. The genotype of embodiments 1-4, wherein the genotype comprises at least four polymorphisms.

8. The genotype of embodiments 1-4, wherein the genotype comprises at least five polymorphisms.

9. The genotype of embodiments 1-4, wherein the genotype comprises at least six polymorphisms.

10. The genotype of embodiments 1-4, wherein the genotype comprises at least seven polymorphisms.

11. The genotype of embodiments 1-4, wherein the genotype comprises at least eight polymorphisms.

12. The genotype of embodiment 1, comprising polymorphisms in linkage disequilibrium with the polymorphisms provided in table 1.

13. The genotype of embodiment 0, wherein LD is defined by: (i) A D 'value of at least about 0.70, or (ii) a D' value of 0 and r ² A value of at least about 0.70.

14. The genotype of embodiment 0, wherein LD is defined by: (i) A D 'value of at least about 0.80, or (ii) a D' value of 0 and r ² A value of at least about 0.80.

15. The genotype of embodiment 0, wherein LD is defined by: (i) A D 'value of at least about 0.90, or (ii) a D' value of 0 And r is ² A value of at least about 0.90.

16. The genotype of embodiment 0, wherein LD is defined by: (i) A D 'value of at least about 0.95, or (ii) a D' value of 0 and r ² A value of at least about 0.95.

17. The genotype of embodiments 1-0, wherein the gene or locus is selected from the group consisting of: tumor necrosis factor (ligand) superfamily member 15 (TNFSF 15), the THADA-arm-and-group repeats (THADA) contained, the H2-containing pleckstrin homology MyTH4 and FERM domains (PLEKHH 2), XK-related 6 (XKR), myotube protein-related protein 9 (MTMR 9), ETS protooncogene 1, transcription factor (ETS 1), 16A-containing C-type lectin domain (CLEC 16A), cytokine signaling inhibitor 1 (SOCS 1), protein tyrosine phosphatase type 2 non-receptor (PTPN 2), inducible T-cell co-stimulatory factor ligand (ICOSLG), two-sided kinase 2 (JAK 2), catenin delta 2 (CTNND 2), regulator of G-protein signaling 7 (RGS 7) RNA binding Fox-1 homolog 1 (RBFOX 1), RNA binding motif protein 17 (RBM 17), fructose-2-phosphate kinase/fructose-2, 6-bisphosphatase 3 (PFKFB 3), extracellular NOX disulfide-thiol exchanger 1 (ENOX 1), 122-containing coiled-coil domain (CCDC 122), telomere-elongating helicase 1 modulator (RTEL 1), TNF receptor superfamily member 6B (TNFRSF 6B), GLIS family zinc finger 3 (GLIS 3), solute carrier family 1 member 1 (SLC 1A 1), IKAROS family zinc finger 2 (IKZF 2), fatty acyl CoA reductase 1 (FAR 1), reactin 1 (SPON 1), plexin A2 (PLXNA 2), MIR205 host gene (MIR 205 HG), TNF receptor superfamily member 6B (TNFRSF 6B), 16A-containing C-type lectin domain (CLEC 16A), PR/SET domain 14 (PRDM), autophagy-related 5 (ATG 5) and prostaglandin E receptor 4 (PTGER 4).

18. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of:

(1)rs16901748、rs7759385、sr4246905；

(2)rs16901748、rs7759385、rs7935393；

(3)rs16901748、rs7759385、rs1892231；

(4)rs16901748、rs7759385、rs12934476；

(5)rs16901748、rs7759385、rs9806914；

(6)rs16901748、rs7759385、rs2297437；

(7)rs16901748、rs7759385、rs2070557；

(8)rs16901748、rs7759385、rs7278257；

(9)rs16901748、rs7759385、rs11221332；

(10)rs16901748、rs7759385、rs41309367；

(11)rs16901748、rs7759385、rs6478109；

(12)rs16901748、rs4246905、rs7935393；

(13)rs16901748、rs4246905、rs1892231；

(14)rs16901748、rs4246905、rs12934476；

(15)rs16901748、rs4246905、rs9806914；

(16)rs16901748、rs4246905、rs2297437；

(17)rs16901748、rs4246905、rs2070557；

(18)rs16901748、rs4246905、rs7278257；

(19)rs16901748、rs4246905、rs11221332；

(20)rs16901748、rs4246905、rs41309367；

(21)rs16901748、rs4246905、rs6478109；

(22)rs16901748、rs7935393、rs1892231；

(23)rs16901748、rs7935393、rs12934476；

(24)rs16901748、rs7935393、rs9806914；

(25)rs16901748、rs7935393、rs2297437；

(26)rs16901748、rs7935393、rs2070557；

(27)rs16901748、rs7935393、rs7278257；

(28)rs16901748、rs7935393、rs11221332；

(29)rs16901748、rs7935393、rs41309367；

(30)rs16901748、rs7935393、rs6478109；

(31)rs16901748、rs1892231、rs12934476；

(32)rs16901748、rs1892231、rs9806914；

(33)rs16901748、rs1892231、rs2297437；

(34)rs16901748、rs1892231、rs2070557；

(35)rs16901748、rs1892231、rs7278257；

(36)rs16901748、rs1892231、rs11221332；

(37)rs16901748、rs1892231、rs41309367；

(38)rs16901748、rs1892231、rs6478109；

(39)rs16901748、rs12934476、rs9806914；

(40)rs16901748、rs12934476、rs2297437；

(41)rs16901748、rs12934476、rs2070557；

(42)rs16901748、rs12934476、rs7278257；

(43)rs16901748、rs12934476、rs11221332；

(44)rs16901748、rs12934476、rs41309367；

(45)rs16901748、rs12934476、rs6478109；

(46)rs16901748、rs9806914、rs2297437；

(47)rs16901748、rs9806914、rs2070557；

(48)rs16901748、rs9806914、rs7278257；

(49)rs16901748、rs9806914、rs11221332；

(50)rs16901748、rs9806914、rs41309367；

(51)rs16901748、rs9806914、rs6478109；

(52)rs16901748、rs2297437、rs2070557；

(53)rs16901748、rs2297437、rs7278257；

(54)rs16901748、rs2297437、rs11221332；

(55)rs16901748、rs2297437、rs41309367；

(56)rs16901748、rs2297437、rs6478109；

(57)rs16901748、rs2070557、rs7278257；

(58)rs16901748、rs2070557、rs11221332；

(59)rs16901748、rs2070557、rs41309367；

(60)rs16901748、rs2070557、rs6478109；

(61)rs16901748、rs7278257、rs11221332；

(62)rs16901748、rs7278257、rs41309367；

(63)rs16901748、rs7278257、rs6478109；

(64)rs16901748、rs11221332、rs41309367；

(65)rs16901748、rs11221332、rs6478109；

(66)rs16901748、rs41309367、rs6478109；

(67)rs7759385、rs4246905、rs7935393；

(68)rs7759385、rs4246905、rs1892231；

(69)rs7759385、rs4246905、rs12934476；

(70)rs7759385、rs4246905、rs9806914；

(71)rs7759385、rs4246905、rs2297437；

(72)rs7759385、rs4246905、rs2070557；

(73)rs7759385、rs4246905、rs7278257；

(74)rs7759385、rs4246905、rs11221332；

(75)rs7759385、rs4246905、rs41309367；

(76)rs7759385、rs4246905、rs6478109；

(77)rs7759385、rs7935393、rs1892231；

(78)rs7759385、rs7935393、rs12934476；

(79)rs7759385、rs7935393、rs9806914；

(80)rs7759385、rs7935393、rs2297437；

(81)rs7759385、rs7935393、rs2070557；

(82)rs7759385、rs7935393、rs7278257；

(83)rs7759385、rs7935393、rs11221332；

(84)rs7759385、rs7935393、rs41309367；

(85)rs7759385、rs7935393、rs6478109；

(86)rs7759385、rs1892231、rs12934476；

(87)rs7759385、rs1892231、rs9806914；

(88)rs7759385、rs1892231、rs2297437；

(89)rs7759385、rs1892231、rs2070557；

(90)rs7759385、rs1892231、rs7278257；

(91)rs7759385、rs1892231、rs11221332；

(92)rs7759385、rs1892231、rs41309367；

(93)rs7759385、rs1892231、rs6478109；

(94)rs7759385、rs12934476、rs9806914；

(95)rs7759385、rs12934476、rs2297437；

(96)rs7759385、rs12934476、rs2070557；

(97)rs7759385、rs12934476、rs7278257；

(98)rs7759385、rs12934476、rs11221332；

(99)rs7759385、rs12934476、rs41309367；

(100)rs7759385、rs12934476、rs6478109；

(101)rs7759385、rs9806914、rs2297437；

(102)rs7759385、rs9806914、rs2070557；

(103)rs7759385、rs9806914、rs7278257；

(104)rs7759385、rs9806914、rs11221332；

(105)rs7759385、rs9806914、rs41309367；

(106)rs7759385、rs9806914、rs6478109；

(107)rs7759385、rs2297437、rs2070557；

(108)rs7759385、rs2297437、rs7278257；

(109)rs7759385、rs2297437、rs11221332；

(110)rs7759385、rs2297437、rs41309367；

(111)rs7759385、rs2297437、rs6478109；

(112)rs7759385、rs2070557、rs7278257；

(113)rs7759385、rs2070557、rs11221332；

(114)rs7759385、rs2070557、rs41309367；

(115)rs7759385、rs2070557、rs6478109；

(116)rs7759385、rs7278257、rs11221332；

(117)rs7759385、rs7278257、rs41309367；

(118)rs7759385、rs7278257、rs6478109；

(119)rs7759385、rs11221332、rs41309367；

(120)rs7759385、rs11221332、rs6478109；

(121)rs7759385、rs41309367、rs6478109；

(122)rs4246905、rs7935393、rs1892231；

(123)rs4246905、rs7935393、rs12934476；

(124)rs4246905、rs7935393、rs9806914；

(125)rs4246905、rs7935393、rs2297437；

(126)rs4246905、rs7935393、rs2070557；

(127)rs4246905、rs7935393、rs7278257；

(128)rs4246905、rs7935393、rs11221332；

(129)rs4246905、rs7935393、rs41309367；

(130)rs4246905、rs7935393、rs6478109；

(131)rs4246905、rs1892231、rs12934476；

(132)rs4246905、rs1892231、rs9806914；

(133)rs4246905、rs1892231、rs2297437；

(134)rs4246905、rs1892231、rs2070557；

(135)rs4246905、rs1892231、rs7278257；

(136)rs4246905、rs1892231、rs11221332；

(137)rs4246905、rs1892231、rs41309367；

(138)rs4246905、rs1892231、rs6478109；

(139)rs4246905、rs12934476、rs9806914；

(140)rs4246905、rs12934476、rs2297437；

(141)rs4246905、rs12934476、rs2070557；

(142)rs4246905、rs12934476、rs7278257；

(143)rs4246905、rs12934476、rs11221332；

(144)rs4246905、rs12934476、rs41309367；

(145)rs4246905、rs12934476、rs6478109；

(146)rs4246905、rs9806914、rs2297437；

(147)rs4246905、rs9806914、rs2070557；

(148)rs4246905、rs9806914、rs7278257；

(149)rs4246905、rs9806914、rs11221332；

(150)rs4246905、rs9806914、rs41309367；

(151)rs4246905、rs9806914、rs6478109；

(152)rs4246905、rs2297437、rs2070557；

(153)rs4246905、rs2297437、rs7278257；

(154)rs4246905、rs2297437、rs11221332；

(155)rs4246905、rs2297437、rs41309367；

(156)rs4246905、rs2297437、rs6478109；

(157)rs4246905、rs2070557、rs7278257；

(158)rs4246905、rs2070557、rs11221332；

(159)rs4246905、rs2070557、rs41309367；

(160)rs4246905、rs2070557、rs6478109；

(161)rs4246905、rs7278257、rs11221332；

(162)rs4246905、rs7278257、rs41309367；

(163)rs4246905、rs7278257、rs6478109；

(164)rs4246905、rs11221332、rs41309367；

(165)rs4246905、rs11221332、rs6478109；

(166)rs4246905、rs41309367、rs6478109；

(167)rs7935393、rs1892231、rs12934476；

(168)rs7935393、rs1892231、rs9806914；

(169)rs7935393、rs1892231、rs2297437；

(170)rs7935393、rs1892231、rs2070557；

(171)rs7935393、rs1892231、rs7278257；

(172)rs7935393、rs1892231、rs11221332；

(173)rs7935393、rs1892231、rs41309367；

(174)rs7935393、rs1892231、rs6478109；

(175)rs7935393、rs12934476、rs9806914；

(176)rs7935393、rs12934476、rs2297437；

(177)rs7935393、rs12934476、rs2070557；

(178)rs7935393、rs12934476、rs7278257；

(179)rs7935393、rs12934476、rs11221332；

(180)rs7935393、rs12934476、rs41309367；

(181)rs7935393、rs12934476、rs6478109；

(182)rs7935393、rs9806914、rs2297437；

(183)rs7935393、rs9806914、rs2070557；

(184)rs7935393、rs9806914、rs7278257；

(185)rs7935393、rs9806914、rs11221332；

(186)rs7935393、rs9806914、rs41309367；

(187)rs7935393、rs9806914、rs6478109；

(188)rs7935393、rs2297437、rs2070557；

(189)rs7935393、rs2297437、rs7278257；

(190)rs7935393、rs2297437、rs11221332；

(191)rs7935393、rs2297437、rs41309367；

(192)rs7935393、rs2297437、rs6478109；

(193)rs7935393、rs2070557、rs7278257；

(194)rs7935393、rs2070557、rs11221332；

(195)rs7935393、rs2070557、rs41309367；

(196)rs7935393、rs2070557、rs6478109；

(197)rs7935393、rs7278257、rs11221332；

(198)rs7935393、rs7278257、rs41309367；

(199)rs7935393、rs7278257、rs6478109；

(200)rs7935393、rs11221332、rs4130936；7

(201)rs7935393、rs11221332、rs6478109；

(202)rs7935393、rs41309367、rs6478109；

(203)rs1892231、rs12934476、rs9806914；

(204)rs1892231、rs12934476、rs2297437；

(205)rs1892231、rs12934476、rs2070557；

(206)rs1892231、rs12934476、rs7278257；

(207)rs1892231、rs12934476、rs11221332；

(208)rs1892231、rs12934476、rs41309367；

(209)rs1892231、rs12934476、rs6478109；

(210)rs1892231、rs9806914、rs2297437；

(211)rs1892231、rs9806914、rs2070557；

(212)rs1892231、rs9806914、rs7278257；

(213)rs1892231、rs9806914、rs11221332；

(214)rs1892231、rs9806914、rs41309367；

(215)rs1892231、rs9806914、rs6478109；

(216)rs1892231、rs2297437、rs2070557；

(217)rs1892231、rs2297437、rs7278257；

(218)rs1892231、rs2297437、rs11221332；

(219)rs1892231、rs2297437、rs41309367；

(220)rs1892231、rs2297437、rs6478109；

(221)rs1892231、rs2070557、rs7278257；

(222)rs1892231、rs2070557、rs11221332；

(223)rs1892231、rs2070557、rs41309367；

(224)rs1892231、rs2070557、rs6478109；

(225)rs1892231、rs7278257、rs11221332；

(226)rs1892231、rs7278257、rs41309367；

(227)rs1892231、rs7278257、rs6478109；

(228)rs1892231、rs11221332、rs41309367；

(229)rs1892231、rs11221332、rs6478109；

(230)rs1892231、rs41309367、rs6478109；

(231)rs12934476、rs9806914、rs2297437；

(232)rs12934476、rs9806914、rs2070557；

(233)rs12934476、rs9806914、rs7278257；

(234)rs12934476、rs9806914、rs11221332；

(235)rs12934476、rs9806914、rs41309367；

(236)rs12934476、rs9806914、rs6478109；

(237)rs12934476、rs2297437、rs2070557；

(238)rs12934476、rs2297437、rs7278257；

(239)rs12934476、rs2297437、rs11221332；

(240)rs12934476、rs2297437、rs41309367；

(241)rs12934476、rs2297437、rs6478109；

(242)rs12934476、rs2070557、rs7278257；

(243)rs12934476、rs2070557、rs11221332；

(244)rs12934476、rs2070557、rs41309367；

(245)rs12934476、rs2070557、rs6478109；

(246)rs12934476、rs7278257、rs11221332；

(247)rs12934476、rs7278257、rs41309367；

(248)rs12934476、rs7278257、rs6478109；

(249)rs12934476、rs11221332、rs41309367；

(250)rs12934476、rs11221332、rs6478109；

(251)rs12934476、rs41309367、rs6478109；

(252)rs9806914、rs2297437、rs2070557；

(253)rs9806914、rs2297437、rs7278257；

(254)rs9806914、rs2297437、rs11221332；

(255)rs9806914、rs2297437、rs41309367；

(256)rs9806914、rs2297437、rs6478109；

(257)rs9806914、rs2070557、rs7278257；

(258)rs9806914、rs2070557、rs11221332；

(259)rs9806914、rs2070557、rs41309367；

(260)rs9806914、rs2070557、rs6478109；

(261)rs9806914、rs7278257、rs11221332；

(262)rs9806914、rs7278257、rs41309367；

(263)rs9806914、rs7278257、rs6478109；

(264)rs9806914、rs11221332、rs41309367；

(265)rs9806914、rs11221332、rs6478109；

(266)rs9806914、rs41309367、rs6478109；

(267)rs2297437、rs2070557、rs7278257；

(268)rs2297437、rs2070557、rs11221332；

(269)rs2297437、rs2070557、rs41309367；

(270)rs2297437、rs2070557、rs6478109；

(271)rs2297437、rs7278257、rs11221332；

(272)rs2297437、rs7278257、rs41309367；

(273)rs2297437、rs7278257、rs6478109；

(274)rs2297437、rs11221332、rs41309367；

(275)rs2297437、rs11221332、rs6478109；

(276)rs2297437、rs41309367、rs6478109；

(277)rs2070557、rs7278257、rs11221332；

(278)rs2070557、rs7278257、rs41309367；

(279)rs2070557、rs7278257、rs6478109；

(280)rs2070557、rs11221332、rs41309367；

(281)rs2070557、rs11221332、rs6478109；

(282)rs2070557、rs41309367、rs6478109；

(283)rs7278257、rs11221332、rs41309367；

(284)rs7278257、rs11221332、rs6478109；

(285) rs7278257, rs41309367, rs6478109; or (b)

(286)rs11221332、rs41309367、rs6478109。

19. The genotype of embodiment 0 wherein rs7278257 is replaced with rs 56124762.

20. The genotype of embodiment 0 wherein rs7278257 is replaced with rs 2070558.

21. The genotype of embodiment 0 wherein rs7278257 is replaced with rs 2070561.

22. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, imm_11_127948309, and rs1892231.

23. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, imm_11_127948309, and rs9806914.

24. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, imm_11_127948309, and imm_21_44478192.

25. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, imm_11_127948309, and imm_21_44479552.

26. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, rs1892231, and rs9806914.

27. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, rs1892231, and imm_21_44478192.

28. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, rs1892231, and imm_21_44479552.

29. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, rs9806914, and imm_21_44478192.

30. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, rs9806914, and imm_21_44479552.

31. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_9_116608587, imm_21_44478192, and imm_21_44479552.

32. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_11_127948309, rs1892231 and rs9806914.

33. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_11_127948309, rs1892231 and imm_21_44478192.

34. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_11_127948309, rs1892231 and imm_21_44479552.

35. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_11_127948309, rs9806914 and imm_21_44478192.

36. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_11_127948309, rs9806914 and imm_21_44479552.

37. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: imm_11_127948309, imm_21_44478192, and imm_21_44479552.

38. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs1892231, rs9806914 and imm_21_44478192.

39. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs1892231, rs9806914 and imm_21_44479552.

40. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs1892231, imm_21_44478192 and imm_21_44479552.

41. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs9806914, imm_21_44478192 and imm_21_44479552.

42. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs56124762 and rs1892231.

43. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs56124762 and rs16901748.

44. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs1892231 and rs16901748.

45. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs56124762, rs1892231 and rs16901748.

46. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs2070558 and rs1892231.

47. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs2070558 and rs16901748.

48. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs1892231 and rs16901748.

49. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs2070558, rs1892231 and rs16901748.

50. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs2070561 and rs1892231.

51. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs2070561 and rs16901748.

52. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs6478109, rs1892231 and rs16901748.

53. The genotype of embodiments 0-0, wherein the genotype comprises at least two polymorphisms selected from the group consisting of: rs2070561, rs1892231 and rs16901748.

54. The genotype of embodiment 0, wherein the genotype comprises eight polymorphisms selected from the group consisting of:

(1)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs2297437

(2)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs1326860

(3)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs12457255

(4)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs2815844

(5)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs10974900

(6)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs2409750

(7)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs1541020

(8)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs4942248

(9)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs9806914、rs7759385

(10)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs1326860

(11)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs12457255

(12)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs2815844

(13)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs10974900

(14)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs2409750

(15)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs1541020

(16)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs4942248

(17)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2297437、rs7759385

(18)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs12457255

(19)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs2815844

(20)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs10974900

(21)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs2409750

(22)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs1541020

(23)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs4942248

(24)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1326860、rs7759385

(25)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs12457255、rs2815844

(26)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs12457255、rs10974900

(27)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs12457255、rs2409750

(28)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs12457255、rs1541020

(29)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs12457255、rs4942248

(30)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs12457255、rs7759385

(31)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2815844、rs10974900

(32)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2815844、rs2409750

(33)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2815844、rs1541020

(34)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2815844、rs4942248

(35)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2815844、rs7759385

(36)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs10974900、rs2409750

(37)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs10974900、rs1541020

(38)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs10974900、rs4942248

(39)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs10974900、rs7759385

(40)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2409750、rs1541020

(41)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2409750、rs4942248

(42)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs2409750、rs7759385

(43)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1541020、rs4942248

(44)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs1541020、rs7759385

(45)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs7935393、rs4942248、rs7759385

(46)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs1326860

(47)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs12457255

(48)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs2815844

(49)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs10974900

(50)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs2409750

(51)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs1541020

(52)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs4942248

(53)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2297437、rs7759385

(54)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs12457255

(55)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs2815844

(56)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs10974900

(57)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs2409750

(58)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs1541020

(59)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs4942248

(60)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1326860、rs7759385

(61)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs12457255、rs2815844

(62)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs12457255、rs10974900

(63)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs12457255、rs2409750

(64)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs12457255、rs1541020

(65)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs12457255、rs4942248

(66)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs12457255、rs7759385

(67)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2815844、rs10974900

(68)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2815844、rs2409750

(69)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2815844、rs1541020

(70)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2815844、rs4942248

(71)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2815844、rs7759385

(72)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs10974900、rs2409750

(73)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs10974900、rs1541020

(74)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs10974900、rs4942248

(75)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs10974900、rs7759385

(76)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2409750、rs1541020

(77)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2409750、rs4942248

(78)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs2409750、rs7759385

(79)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1541020、rs4942248

(80)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs1541020、rs7759385

(81)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs9806914、rs4942248、rs7759385

(82)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs12457255

(83)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs2815844

(84)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs10974900

(85)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs2409750

(86)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs1541020

(87)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs4942248

(88)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs1326860、rs7759385

(89)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs12457255、rs2815844

(90)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs12457255、rs10974900

(91)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs12457255、rs2409750

(92)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs12457255、rs1541020

(93)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs12457255、rs4942248

(94)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs12457255、rs7759385

(95)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs2815844、rs10974900

(96)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs2815844、rs2409750

(97)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs2815844、rs1541020

(98)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs2815844、rs4942248

(99)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs2815844、rs7759385

(100)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs10974900、rs2409750

(101)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs10974900、rs1541020

(102)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs2297437、rs10974900、rs4942248

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(111)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs12457255、rs10974900

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(113)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs12457255、rs1541020

(114)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs12457255、rs4942248

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(117)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs2815844、rs2409750

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(119)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs2815844、rs4942248

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(123)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs10974900、rs4942248

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(126)rs6478109、rs56124762、rs1892231、rs16901748、rs12934476、rs1326860、rs2409750、rs4942248

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(199)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs9806914、rs1541020、rs4942248

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(206)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs1326860、rs1541020

(207)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs1326860、rs4942248

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(213)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs12457255、rs4942248

(214)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs12457255、rs7759385

(215)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs2815844、rs10974900

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(217)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs2815844、rs1541020

(218)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs2815844、rs4942248

(219)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2297437、rs2815844、rs7759385

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(234)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs12457255、rs4942248

(235)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs12457255、rs7759385

(236)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs2815844、rs10974900

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(238)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs2815844、rs1541020

(239)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs2815844、rs4942248

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(241)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs10974900、rs2409750

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(243)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs10974900、rs4942248

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(247)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs2409750、rs7759385

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(249)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs1326860、rs1541020、rs7759385

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(251)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs2815844、rs10974900

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(253)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs2815844、rs1541020

(254)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs2815844、rs4942248

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(256)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs10974900、rs2409750

(257)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs10974900、rs1541020

(258)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs10974900、rs4942248

(259)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs12457255、rs10974900、rs7759385

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(269)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2815844、rs10974900、rs7759385

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(271)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2815844、rs2409750、rs4942248

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(273)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2815844、rs1541020、rs4942248

(274)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2815844、rs1541020、rs7759385

(275)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs2815844、rs4942248、rs7759385

(276)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs10974900、rs2409750、rs1541020

(277)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs10974900、rs2409750、rs4942248

(278)rs6478109、rs56124762、rs1892231、rs16901748、rs7935393、rs10974900、rs2409750、rs7759385

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(374)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs1326860、rs12457255、rs4942248

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(391)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs2815844、rs10974900

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(393)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs2815844、rs1541020

(394)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs2815844、rs4942248

(395)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs2815844、rs7759385

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(398)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs10974900、rs4942248

(399)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs10974900、rs7759385

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(404)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs12457255、rs1541020、rs7759385

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(411)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs2815844、rs2409750、rs4942248

(412)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs2815844、rs2409750、rs7759385

(413)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs2815844、rs1541020、rs4942248

(414)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs2815844、rs1541020、rs7759385

(415)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs2815844、rs4942248、rs7759385

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(417)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs10974900、rs2409750、rs4942248

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(419)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs10974900、rs1541020、rs4942248

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(421)rs6478109、rs56124762、rs1892231、rs16901748、rs2297437、rs10974900、rs4942248、rs7759385

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(427)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs2815844、rs2409750

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(429)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs2815844、rs4942248

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(433)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs10974900、rs4942248

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(435)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs2409750、rs1541020

(436)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs2409750、rs4942248

(437)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs2409750、rs7759385

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(439)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs12457255、rs1541020、rs7759385

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(441)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs10974900、rs2409750

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(443)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs10974900、rs4942248

(444)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs10974900、rs7759385

(445)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs2409750、rs1541020

(446)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs2409750、rs4942248

(447)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs2409750、rs7759385

(448)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs1541020、rs4942248

(449)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs1541020、rs7759385

(450)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2815844、rs4942248、rs7759385

(451)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs10974900、rs2409750、rs1541020

(452)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs10974900、rs2409750、rs4942248

(453)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs10974900、rs2409750、rs7759385

(454)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs10974900、rs1541020、rs4942248

(455)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs10974900、rs1541020、rs7759385

(456)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs10974900、rs4942248、rs7759385

(457)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2409750、rs1541020、rs4942248

(458)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2409750、rs1541020、rs7759385

(459)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs2409750、rs4942248、rs7759385

(460)rs6478109、rs56124762、rs1892231、rs16901748、rs1326860、rs1541020、rs4942248、rs7759385

(461)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs10974900、rs2409750

(462)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs10974900、rs1541020

(463)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs10974900、rs4942248

(464)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs10974900、rs7759385

(465)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs2409750、rs1541020

(466)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs2409750、rs4942248

(467)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs2409750、rs7759385

(468)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs1541020、rs4942248

(469)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs1541020、rs7759385

(470)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2815844、rs4942248、rs7759385

(471)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs10974900、rs2409750、rs1541020

(472)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs10974900、rs2409750、rs4942248

(473)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs10974900、rs2409750、rs7759385

(474)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs10974900、rs1541020、rs4942248

(475)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs10974900、rs1541020、rs7759385

(476)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs10974900、rs4942248、rs7759385

(477)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2409750、rs1541020、rs4942248

(478)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2409750、rs1541020、rs7759385

(479)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs2409750、rs4942248、rs7759385

(480)rs6478109、rs56124762、rs1892231、rs16901748、rs12457255、rs1541020、rs4942248、rs7759385

(481)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs10974900、rs2409750、rs1541020

(482)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs10974900、rs2409750、rs4942248

(483)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs10974900、rs2409750、rs7759385

(484)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs10974900、rs1541020、rs4942248

(485)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs10974900、rs1541020、rs7759385

(486)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs10974900、rs4942248、rs7759385

(487)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs2409750、rs1541020、rs4942248

(488)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs2409750、rs1541020、rs7759385

(489)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs2409750、rs4942248、rs7759385

(490)rs6478109、rs56124762、rs1892231、rs16901748、rs2815844、rs1541020、rs4942248、rs7759385

(491)rs6478109、rs56124762、rs1892231、rs16901748、rs10974900、rs2409750、rs1541020、rs4942248

(492)rs6478109、rs56124762、rs1892231、rs16901748、rs10974900、rs2409750、rs1541020、rs7759385

(493)rs6478109、rs56124762、rs1892231、rs16901748、rs10974900、rs2409750、rs4942248、rs7759385

(494)rs6478109、rs56124762、rs1892231、rs16901748、rs10974900、rs1541020、rs4942248、rs7759385

(495)rs6478109、rs56124762、rs1892231、rs16901748、rs2409750、rs1541020、rs4942248、rs7759385

55. the genotype of embodiments 1-0, wherein the genotype comprises the minor alleles provided for at least one polymorphism in table 1.

56. The genotype of embodiments 1-0, wherein the genotype comprises the major alleles provided for at least one polymorphism in table 1.

57. The genotype of embodiments 1-0, wherein the presence of the genotype predicts a positive therapeutic response to treatment with an inhibitor of TL1A expression activity that has a positive predictive value of at least about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

58. The genotype of embodiments 1-0, wherein the presence of the genotype predicts a positive therapeutic response that is at least about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% specific for treatment with an inhibitor of TL1A expression activity.

Aspects disclosed herein provide genotypes associated with, and thus indicative of, a subject suffering from or susceptible to developing a particular disease or condition or subclinical phenotype thereof. Furthermore, the genotypes disclosed herein are associated with an increase in TNFSF15 (TL 1A) expression or activity. Thus, the genotype indicates that the subject will have a positive therapeutic response to an inhibitor of TL1A activity or expression. Table 1 provides exemplary polymorphisms associated with and thus predictive of positive therapeutic responses to inhibitors of TNFSF15 (TL 1A) expression or activity. The term "positive therapeutic response" refers to the reduction or elimination of at least one symptom of a disease or condition (e.g., crohn's disease) following induction of therapy (e.g., anti-TL 1A antibodies).

The present disclosure provides a model comprising 3 polymorphisms (e.g., a "3-SNP model"), which when detected in a sample obtained from a subject, indicates a positive therapeutic response in the subject to treatment, such as treatment with an inhibitor of TL1A activity or expression. Non-limiting examples of the models described herein include model a (rs 6478109, rs7278257, and rs 1892231); model B (rs 6478109, rs2070557, and rs 9806914); model C (rs 6478109, rs7935393, and rs 1892231); model D (rs 6478109, rs7935393, and rs 9806914); model E (rs 6478109, rs9806914, and rs 16901748); model F (rs 6478109, rs16901748, and rs 2297437); model G (rs 6478109, rs1892231, and rs 16901748); model H (rs 6478109, rs2070557, and rs 7935393); model I (rs 6478109, rs7278257, and rs 7935393); model J (rs 6478109, rs9806914, and rs 1892231); and model K (rs 6478109, rs7278257, and rs 16901748).

Therapeutic method

Disclosed herein are methods of treating a disease or condition or symptoms of a disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of one or more therapeutic agents. In some embodiments, one or more therapeutic agents are administered to a subject alone (e.g., independent therapy). In some embodiments, one or more therapeutic agents are administered in combination with an additional agent. In some embodiments, the therapeutic agent is a first line therapy of a disease or condition. In some embodiments, the therapeutic agent is a two-wire, three-wire, or four-wire therapy of a disease or condition. In some embodiments, the therapeutic agent comprises an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression.

Various embodiments provide methods of treating Inflammatory Bowel Disease (IBD) comprising administering to a subject in need thereof an anti-TL 1A antibody described herein. In some embodiments, the subject comprises one or more risk genotypes. In some embodiments, the IBD is a severe form of IBD.

In various embodiments, provided herein are methods of treating Inflammatory Bowel Disease (IBD) in a subject in need thereof, comprising: administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment that specifically binds TL 1A. In some embodiments, the anti-TL 1A antibody comprises antibody a. In some embodiments, the anti-TL 1A antibody comprises antibody B. In some embodiments, the anti-TL 1A antibody comprises antibody C. In some embodiments, the anti-TL 1A antibody comprises antibody D. In some embodiments, the anti-TL 1A antibody comprises antibody E. In some embodiments, the anti-TL 1A antibody comprises antibody F. In some embodiments, the anti-TL 1A antibody comprises antibody G. In some embodiments, the anti-TL 1A antibody comprises antibody I. In some embodiments, the anti-TL 1A antibody comprises antibody H. In some embodiments, the anti-TL 1A antibody comprises antibody A2. In some embodiments, the anti-TL 1A antibody comprises antibody B2. In some embodiments, the anti-TL 1A antibody comprises antibody C2. In some embodiments, the anti-TL 1A antibody comprises antibody D2. In some embodiments, the anti-TL 1A antibody comprises antibody E2. In some embodiments, the anti-TL 1A antibody comprises antibody F2. In some embodiments, the anti-TL 1A antibody comprises antibody G2. In some embodiments, the anti-TL 1A antibody comprises antibody I2. In some embodiments, the anti-TL 1A antibody comprises antibody H2. In certain embodiments, the anti-TL 1A antibody comprises any one of the antibodies of table 10. In some embodiments, the anti-TL 1A antibody comprises antibody a217. In some embodiments, the anti-TL 1A antibody comprises antibody a220. In some embodiments, the anti-TL 1A antibody comprises antibody a223. In some embodiments, the anti-TL 1A antibody comprises antibody a219. In some embodiments, the anti-TL 1A antibody comprises antibody a221. In some embodiments, the anti-TL 1A antibody comprises antibody a200. In some embodiments, the anti-TL 1A antibody comprises antibody a213. In some embodiments, the anti-TL 1A antibody comprises antibody a212. In some embodiments, the anti-TL 1A antibody comprises antibody a107. In some embodiments, the anti-TL 1A antibody comprises antibody a205. In some embodiments, the anti-TL 1A antibody comprises antibody a211. In some embodiments, the anti-TL 1A antibody comprises antibody a199. In some embodiments, the anti-TL 1A antibody comprises antibody a15. In some embodiments, the anti-TL 1A antibody comprises antibody a30. In some embodiments, the anti-TL 1A antibody comprises antibody a100. In some embodiments, the anti-TL 1A antibody comprises antibody a181. In some embodiments, the anti-TL 1A antibody comprises antibody a129. In some embodiments, the anti-TL 1A antibody comprises antibody a214. In some embodiments, the anti-TL 1A antibody comprises antibody a216. In some embodiments, the anti-TL 1A antibody comprises antibody a122. In some embodiments, the anti-TL 1A antibody comprises antibody a222. In some embodiments, the anti-TL 1A antibody comprises antibody a188. In some embodiments, the anti-TL 1A antibody comprises antibody a203. In some embodiments, the anti-TL 1A antibody comprises antibody a147. In some embodiments, the anti-TL 1A antibody comprises antibody a127. In some embodiments, the anti-TL 1A antibody comprises antibody a126. In some embodiments, the anti-TL 1A antibody comprises antibody a160. In some embodiments, the anti-TL 1A antibody comprises antibody a157. In some embodiments, the anti-TL 1A antibody comprises antibody a159. In some embodiments, the anti-TL 1A antibody comprises antibody a218. In some embodiments, the anti-TL 1A antibody comprises antibody a158. In some embodiments, the anti-TL 1A antibody comprises antibody a125. In some embodiments, the anti-TL 1A antibody comprises antibody a103. In some embodiments, the anti-TL 1A antibody comprises antibody a64. In some embodiments, the anti-TL 1A antibody comprises antibody a67. In some embodiments, the anti-TL 1A antibody comprises antibody a138. In some embodiments, the anti-TL 1A antibody comprises antibody a68. In some embodiments, the anti-TL 1A antibody comprises antibody a94. In some embodiments, the anti-TL 1A antibody comprises antibody a110. In some embodiments, the anti-TL 1A antibody comprises antibody a197. In some embodiments, the anti-TL 1A antibody comprises antibody a112. In some embodiments, the anti-TL 1A antibody comprises antibody a169. In some embodiments, the anti-TL 1A antibody comprises antibody a173. In some embodiments, the anti-TL 1A antibody comprises antibody a179. In some embodiments, the anti-TL 1A antibody comprises antibody a148. In some embodiments, the anti-TL 1A antibody comprises antibody a115. In some embodiments, the anti-TL 1A antibody comprises antibody a149. In some embodiments, the anti-TL 1A antibody comprises antibody a134. In some embodiments, the anti-TL 1A antibody comprises antibody a113. In some embodiments, the anti-TL 1A antibody comprises antibody a151. In some embodiments, the anti-TL 1A antibody comprises antibody a96. In some embodiments, the anti-TL 1A antibody comprises antibody a132. In some embodiments, the anti-TL 1A antibody comprises antibody a196. In some embodiments, the anti-TL 1A antibody comprises antibody a172. In some embodiments, the anti-TL 1A antibody comprises antibody a75. In some embodiments, the anti-TL 1A antibody comprises antibody a174. In some embodiments, the anti-TL 1A antibody comprises antibody a109. In some embodiments, the anti-TL 1A antibody comprises antibody a198. In some embodiments, the anti-TL 1A antibody comprises antibody a170. In certain embodiments, the anti-TL 1A antibody comprises any one of the antibodies of tables 20-21. In some embodiments, the anti-TL 1A antibody comprises antibody clone 34. In some embodiments, the anti-TL 1A antibody comprises antibody 5C3D11. In some embodiments, the anti-TL 1A antibody comprises antibody 9E12E5. In some embodiments, the anti-TL 1A antibody comprises antibody AS12824. In some embodiments, the anti-TL 1A antibody comprises antibody AS12823. In some embodiments, the anti-TL 1A antibody comprises antibody AS12819. In some embodiments, the anti-TL 1A antibody comprises antibody AS12816. In some embodiments, the anti-TL 1A antibody comprises antibody AS12825. In some embodiments, the anti-TL 1A antibody comprises antibody 12835. In some embodiments, the anti-TL 1A antibody comprises antibody 18-7S 93E. In some embodiments, the anti-TL 1A antibody comprises antibody 18-7. In some embodiments, the anti-TL 1A antibody comprises antibody 18-7S 92D. In some embodiments, the anti-TL 1A antibody comprises antibody 18-7S 92H. In some embodiments, the anti-TL 1A antibody comprises antibody 18-7S 92N. In some embodiments, the anti-TL 1A antibody comprises antibody 18-7S 92Q. In some embodiments, the anti-TL 1A antibody comprises an antibody 18-7 CDRV. In some embodiments, the anti-TL 1A antibody comprises antibody 21-3. In some embodiments, the anti-TL 1A antibody comprises antibody 21-3V102K. In some embodiments, the anti-TL 1A antibody comprises antibody 21-3V 102M. In some embodiments, the anti-TL 1A antibody comprises antibody 21-3V 102Q. In some embodiments, the anti-TL 1A antibody comprises antibody 21-3V 102W. In some embodiments, the anti-TL 1A antibody comprises an antibody 21-3CDRV. In some embodiments, the anti-TL 1A antibody comprises an antibody 21-3CDRV. In some embodiments, the anti-TL 1A antibody comprises antibody clone 2. In some embodiments, the anti-TL 1A antibody comprises antibody clone 52. In some embodiments, the anti-TL 1A antibody comprises antibody clone 46. In some embodiments, the anti-TL 1A antibody comprises antibody clone 47. In some embodiments, the anti-TL 1A antibody comprises antibody clone 14. In some embodiments, the anti-TL 1A antibody comprises antibody clone 16L. In some embodiments, the anti-TL 1A antibody comprises antibody clone 17L. In some embodiments, the anti-TL 1A antibody comprises antibody clone 17L-1. In some embodiments, the anti-TL 1A antibody comprises antibody clone 23. In some embodiments, the anti-TL 1A antibody comprises antibody clone 53. In some embodiments, the anti-TL 1A antibody comprises antibody clone E1. In some embodiments, the anti-TL 1A antibody comprises antibody clone 3-17L V-A. In some embodiments, the anti-TL 1A antibody comprises antibody clone 3-17L. In some embodiments, the anti-TL 1A antibody comprises the antibody clone L8mod. In some embodiments, the anti-TL 1A antibody comprises antibody clone X-V. In some embodiments, the anti-TL 1A antibody comprises antibody clone X. In some embodiments, the anti-TL 1A antibody comprises antibody clone XL3-6. In some embodiments, the anti-TL 1A antibody comprises antibody clone XL3-10. In some embodiments, the anti-TL 1A antibody comprises antibody clone XL3-15. In some embodiments, the anti-TL 1A antibody comprises antibody clone L3-13. In some embodiments, the anti-TL 1A antibody comprises antibody clone H3-1. In some embodiments, the anti-TL 1A antibody comprises antibody clone H2-2. In some embodiments, the anti-TL 1A antibody comprises antibody clone H2-5. In some embodiments, the anti-TL 1A antibody comprises antibody M1. In some embodiments, the anti-TL 1A antibody comprises antibody M2. In some embodiments, the anti-TL 1A antibody comprises antibody M3. In some embodiments, the anti-TL 1A antibody comprises antibody M4. In some embodiments, the anti-TL 1A antibody comprises antibody M5. In some embodiments, the anti-TL 1A antibody comprises antibody M6. In some embodiments, the anti-TL 1A antibody comprises antibody M7. In some embodiments, the anti-TL 1A antibody comprises antibody M8. In some embodiments, the anti-TL 1A antibody comprises antibody M9. In some embodiments, the anti-TL 1A antibody comprises antibody M10. In some embodiments, the anti-TL 1A antibody comprises antibody M11. In some embodiments, the anti-TL 1A antibody comprises antibody M12.

The methods disclosed herein provide methods of treating Inflammatory Bowel Disease (IBD) in a subject by administering to the subject an anti-TL 1A antibody described herein. In various embodiments, the IBD is Crohn's Disease (CD) or Ulcerative Colitis (UC). In some embodiments, the IBD is a severe form of IBD. In some embodiments, the IBD is a moderate to severe form of IBD. In some embodiments, the IBD is a moderate form of IBD. In various other embodiments, the subject is determined to have increased TL1A expression. In some embodiments, administration of a therapeutically effective amount of an anti-TL 1A antibody results in a reduction in TL1A in the subject being treated.

Detection method

The methods disclosed herein for detecting a genotype in a sample from a subject include analyzing genetic material in the sample to detect at least one of the presence, absence, and amount of a nucleic acid sequence that encompasses the genotype of interest, and administering an anti-TL 1A antibody or antigen-binding fragment disclosed herein. In some embodiments, the sample is assayed to measure the presence, absence, or quantity of at least three polymorphisms. In some embodiments, the sample is assayed to measure the presence, absence, or number of at least four polymorphisms. In some embodiments, the sample is assayed to measure the presence, absence, or number of at least five polymorphisms. In some embodiments, the sample is assayed to measure the presence, absence, or quantity of at least six polymorphisms. In some embodiments, the sample is assayed to measure the presence, absence, or number of at least seven polymorphisms. In some embodiments, the sample is assayed to measure the presence, absence, or number of at least eight polymorphisms. In some embodiments, at least three genotypes are detected using the methods described herein. In some embodiments, at least eight genotypes are detected using the methods described herein.

In some cases, the nucleic acid sequence comprises DNA. In some cases, the nucleic acid sequence comprises a denatured DNA molecule or fragment thereof. In some cases, the nucleic acid sequence comprises DNA selected from the group consisting of: genomic DNA, viral DNA, mitochondrial DNA, plasmid DNA, amplified DNA, circular DNA, circulating DNA, cell-free DNA, or exosome DNA. In some cases, the DNA is single-stranded DNA (ssDNA), double-stranded DNA, denatured double-stranded DNA, synthetic DNA, and combinations thereof. The circular DNA may be cleaved or fragmented. In some cases, the nucleic acid sequence comprises RNA. In some cases, the nucleic acid sequence comprises fragmented RNA. In some cases, the nucleic acid sequence comprises a partially degraded RNA. In some cases, the nucleic acid sequence comprises a microrna or a portion thereof. In some cases, the nucleic acid sequence comprises an RNA molecule or a fragmented RNA molecule (RNA fragment) selected from the group consisting of: micrornas (mirnas), pre-mirnas, pri-miRNA, mRNA, pre-mrnas, viral RNAs, viroid RNAs, circular RNAs (circrnas), ribosomal RNAs (rrnas), transfer RNAs (trnas), pre-trnas, long non-coding RNAs (lncrnas), micrornas (snrnas), circulating RNAs, cell-free RNAs, exosome RNAs, vector-expressed RNAs, RNA transcripts, synthetic RNAs, and combinations thereof.

Nucleic acid-based detection techniques useful in the methods herein include quantitative polymerase chain reaction (qPCR), gel electrophoresis, immunochemistry, in situ hybridization such as Fluorescence In Situ Hybridization (FISH), cytochemistry, and next generation sequencing. In some embodiments, the method involves TaqMan ^TM qPCR, which involves a nucleic acid amplification reaction with a specific primer pair, and hybridization of the amplified nucleic acid with a hydrolyzable probe specific for the target nucleic acid.

In some cases, the methods involve hybridization and/or amplification assays, including, but not limited to, southern or Northern analysis, polymerase chain reaction analysis, and probe arrays. Non-limiting amplification reactions include, but are not limited to, qPCR, autonomous sequence replication, transcription amplification systems, Q-beta replicase, rolling circle replication, or any other nucleic acid amplification known in the art. As discussed, references herein to qPCR include the use of TaqMan ^TM The method. Additional exemplary hybridization assays include the use of nucleic acid probes conjugated or otherwise immobilized on beads, multiwell plates, or other substrates, wherein the nucleic acid probes are configured to hybridize to target nucleic acid sequences of the genotypes provided herein. One non-limiting method is at animal chem.2013, 2, 5; 85 (3): 1932-9.

In some embodiments, detecting the presence or absence of a genotype comprises sequencing genetic material from a subject. Sequencing may be performed using any suitable sequencing technique, including, but not limited to, single Molecule Real Time (SMRT) sequencing, poony sequencing, ligation sequencing, reversible terminator sequencing, proton detection sequencing, ion semiconductor sequencing, nanopore sequencing, electronic sequencing, pyrosequencing, maxam-Gilbert sequencing, chain termination (e.g., sanger) sequencing, +s sequencing, binding sequencing (e.g., transient binding), or synthetic sequencing. Sequencing methods also include next generation sequencing, for example, modern sequencing techniques such as Illumina sequencing (e.g., solexa), roche 454 sequencing, ion torrent sequencing, transient binding sequencing, and SOLiD sequencing. In some cases, the next generation sequencing involves a high throughput sequencing method. Additional sequencing methods available to those skilled in the art may also be employed.

In some cases, the number of nucleotides sequenced is at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, 150, 200, 300, 400, 500, 2000, 4000, 6000, 8000, 10000, 20000, 50000, 100000, or more than 100000 nucleotides. In some cases, the number of nucleotides sequenced is in the range of about 1 to about 100000 nucleotides, about 1 to about 10000 nucleotides, about 1 to about 1000 nucleotides, about 1 to about 500 nucleotides, about 1 to about 300 nucleotides, about 1 to about 200 nucleotides, about 1 to about 100 nucleotides, about 5 to about 100000 nucleotides, about 5 to about 10000 nucleotides, about 5 to about 1000 nucleotides, about 5 to about 500 nucleotides, about 5 to about 300 nucleotides, about 5 to about 200 nucleotides, about 5 to about 100 nucleotides, about 10 to about 100000 nucleotides, about 10 to about 10000 nucleotides, about 10 to about 1000 nucleotides, about 10 to about 500 nucleotides, about 10 to about 300 nucleotides, about 10 to about 200 nucleotides, about 10 to about 100 nucleotides, about 20 to about 100000 nucleotides, about 20 to about 10000 nucleotides, about 20 to about 1000 nucleotides, about 20 to about 20 nucleotides, about 20 to about 200 nucleotides, about 30 to about 30 nucleotides, about 50 to about 30 nucleotides, about 30 to about 50 nucleotides, about 50 to about 30 nucleotides, or about 50 to about 100 nucleotides.

Exemplary probes comprise SEQ ID NOs: a nucleic acid sequence of at least 10 contiguous nucleic acids provided by any one of 2001-2048 or 2057-2059, including a nucleobase indicated with a non-nucleobase letter (e.g., R, N, S) or its inverse. In some cases, probes can be used to detect the polymorphisms provided in table 1, wherein the probes comprise the nucleic acid sequence of at least 10 consecutive nucleic acids provided in the corresponding SEQ ID NOs, or the reverse complement thereof, the 10 consecutive nucleic acids comprising the "risk allele" or the reverse complement thereof at the nuclear position indicated with non-nucleobase letters also provided in table 1. In some embodiments, the probe hybridizes to SEQ ID NO: any of 2001-2048 or 2057-2059, or a complement thereof, has at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity. In some cases, forward and reverse primers are used to amplify a target nucleic acid sequence. The forward and reverse primers may comprise sequences flanking the sequences provided in table 1 corresponding to SEQ ID NOs: 2001-2048 or 2057-2059, or a reverse complement thereof.

Examples of molecules for use as probes include, but are not limited to, RNA and DNA. In some embodiments, the term "probe" with respect to a nucleic acid refers to any molecule capable of selectively binding to a particular intended target nucleic acid sequence. In some cases, the probes are specifically designed to be labeled, for example, with a radiolabel, a fluorescent label, an enzyme, a chemiluminescent label, a colorimetric label, or other labels or tags known in the art. In some cases, the fluorescent label comprises a fluorophore. In some cases, the fluorophore is an aromatic or heteroaromatic compound. In some cases, the fluorophore is pyrene, anthracene, naphthalene, acridine, stilbene, benzoxazole, indole, benzindole, oxazole, thiazole, benzothiazole, cyanine, carbocyanine, salicylate, anthranilate, xanthene dye, coumarin. Exemplary xanthene dyes include, for example, fluorescein and rhodamine (rhodomine) dyes. Fluorescein and rhodamine dyes include, but are not limited to, 6-carboxyfluorescein (FAM), 2'7' -dimethoxy-4 '5' -dichloro-6-carboxyfluorescein (JOE), tetrachlorofluorescein (TET), 6-carboxyrhodamine (R6G), N; n' -tetramethyl-6-carboxyrhodamine (TAMRA), 6-carboxy-X-Rhodamine (ROX). Suitable fluorescent probes also include naphthylamine dyes having an amino group in the alpha or beta position. For example, naphthylamino compounds include 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalenesulfonate, and 2-p-toluidinyl-6-naphthalenesulfonate, 5- (2' -aminoethyl) aminonaphthalene-1-sulfonic acid (EDANS). Exemplary coumarins include, for example, 3-phenyl-7-isocyanatocoumarin; acridines such as 9-isothiocyanacridine and acridine orange; n- (p- (2-benzoxazolyl) phenyl) maleimide; cyanines, such as indodicarbonyl cyanine 3 (Cy 3), indodicarbonyl cyanine 5 (Cy 5), indodicarbonyl cyanine 5.5 (Cy 5.5), 3- (-carboxy-pentyl) -3 '-ethyl-5, 5' -dimethyloxacarbocyanine (CyA); 1H,5H,11H, 15H-xanthene [2,3,4-ij:5,6,7-i 'j' ] biquinolin-18-ium, 9- [2 (or 4) - [ [ [6- [2, 5-dioxo-1-pyrrolidinyl) oxy ] -6-oxohexyl ] amino ] sulfonyl ] -4 (or 2) -sulfophenyl ] -2,3,6,7, 12, 13, 16, 17-octahydro-inner salt (TR or texas red); or BODIPYTM dye. In some cases, the probe comprises FAM as a dye label.

In some cases, the primers and/or probes described herein for detecting a target nucleic acid are used in an amplification reaction. In some cases, the amplification reaction is qPCR. Exemplary qPCR is with TaqMan ^TM The method of measurement. Non-limiting examples of primer pairs that can be used to detect one or more polymorphisms described herein are provided in table 2 below.

TABLE 2 exemplary primer sequences

"Wt_Probe_Hex" and "Mut_Probe_FAM" mean "wild-type Probe labeled with HEX reporter dye" and "mutant Probe labeled with FAM reporter dye", respectively. "+" represents LNA base (locked nucleotide), which is an analogue modified at 2'-O, 4' -C and forms a bridge. This bridge results in limited base pairing, providing room for Tm adjustment between probes as desired. Thus, +A, +T, +C or +G represents A, T, G or C bases added to the modified backbone.

In some cases, qPCR involves the use of intercalating dyes. Examples of intercalating dyes include SYBR Green I, SYBR Green II, SYBR gold, ethidium bromide, methylene Blue, pyronine Y, DAPI, acridine orange, blue View or phycoerythrin. In some cases, the intercalating dye is SYBR.

In some cases, the number of amplification cycles used to detect a target nucleic acid in an amplification assay is from about 5 to about 30 cycles. In some cases, the number of amplification cycles used to detect the target nucleic acid is at least about 5 cycles. In some cases, the number of amplification cycles for detecting a target nucleic acid is up to about 30 cycles. In some cases, the number of amplification cycles for detecting a target nucleic acid is about 5 to about 10, about 5 to about 15, about 5 to about 20, about 5 to about 25, about 5 to about 30, about 10 to about 15, about 10 to about 20, about 10 to about 25, about 10 to about 30, about 15 to about 20, about 15 to about 25, about 15 to about 30, about 20 to about 25, about 20 to about 30, or about 25 to about 30 cycles.

In one aspect, methods provided herein for determining the presence, absence, and/or quantity of a nucleic acid sequence from a particular genotype include amplification reactions, such as qPCR. In one exemplary method, genetic material is obtained from a sample of a subject, such as a blood or serum sample. In certain embodiments of extracting nucleic acids, any technique that does not interfere with subsequent analysis is used to extract the nucleic acids. In certain embodiments, the technique utilizes alcohol precipitation using ethanol, methanol, or isopropanol. In certain embodiments, the technique uses phenol, chloroform, or any combination thereof. In certain embodiments, the technology uses cesium chloride. In certain embodiments, the technique uses sodium, potassium or ammonium acetate or any other salt commonly used to precipitate DNA. In certain embodiments, the technology utilizes column or resin based nucleic acid purification protocols, such as those commonly available commercially, one non-limiting example being the geneleute bacterial genomic DNA kit available from Sigma Aldrich. In certain embodiments, after extraction, the nucleic acid is stored in water, tris buffer or Tris-EDTA buffer, and then subjected to subsequent analysis. In one exemplary embodiment, the nucleic acid material is extracted in water. In some cases, the extraction does not include nucleic acid purification.

In an exemplary qPCR assay, a nucleic acid sample is combined with primers and probes specific for target nucleic acids that may or may not be present in the sample, and a DNA polymerase. The amplification reaction is performed with a thermal cycler that heats and cools the sample for nucleic acid amplification and irradiates the sample at a specific wavelength to excite fluorophores on the probes and detect the emitted fluorescence. For TaqMan ^TM In the method, the probe may be a hydrolyzable probe comprising a fluorophore and a quencher, which is hydrolyzed by a DNA polymerase upon hybridization with the target nucleic acid. In some cases, the presence of a target nucleic acid is determined when the number of amplification cycles to reach the threshold is less than 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, or 20 cycles.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:2001, the non-reference allele at core position 501 of SEQ ID NO: 2001. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO: 2001. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 2001 are sufficient to detect the polymorphism at rs 11897732.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 2002 is SEQ ID NO:2002, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele of SEQ ID NO:2002, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 2002 are sufficient to detect the polymorphism at rs 6740739.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 2003 of SEQ ID NO:2003, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "C" allele at core position 501 within 2003 has the sequence of SEQ ID NO:2003, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "C" allele at core position 501 within 2003 are sufficient to detect a polymorphism at rs 17796285.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 2004 of SEQ ID NO:2004, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "C" or "a" allele of SEQ ID NO:2004, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "a" allele at core position 501 within 2004 are sufficient to detect the polymorphism at rs 7935393.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: SEQ ID NO:2005, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele at core position 501 within 2005 of SEQ ID NO:2005, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 2005 are sufficient to detect a polymorphism at rs 12934476.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 2006 of SEQ ID NO:2006 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "C" allele at core position 501 within 2006 of SEQ ID NO:2006 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "C" allele at core position 501 within 2006 are sufficient to detect a polymorphism at rs 12457255.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:2007 of the non-reference allele at core position 501: 2007, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:2007 the "a" or "T" allele at core position 501, SEQ ID NO:2007, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "T" allele at nuclear position 501 within 2007 are sufficient to detect a polymorphism at rs 2070557.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 2008 of SEQ ID NO:2008, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele of SEQ ID NO:2008, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at nuclear position 501 within 2008 are sufficient to detect a polymorphism at rs 4246905.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: SEQ ID NO:2009, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 2009 is set forth in SEQ ID NO:2009, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at nuclear position 501 within 2009 are sufficient to detect a polymorphism at rs 10974900.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: SEQ ID NO:2010 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: SEQ ID NO:2010 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "a" allele at core position 501 within 2010 are sufficient to detect a polymorphism at rs 12434976.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20011 has the sequence of SEQ ID NO:20011 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "C" allele at core position 501 within 20011 has the sequence of SEQ ID NO:20011 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "C" allele at core position 501 within 20011 are sufficient to detect the polymorphism at rs 16901748.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20012 of SEQ ID NO:20012 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20012 has the sequence of SEQ ID NO:20012 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20012 are sufficient to detect the polymorphism at rs 2815844.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20013 SEQ ID NO:20013, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20013, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 2013 are sufficient to detect the polymorphism at rs 889702.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20014 SEQ ID NO:20014 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "C" or "a" allele at core position 501 within 20014 has the sequence of SEQ ID NO:20014 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "a" allele at core position 501 within 20014 are sufficient to detect the polymorphism at rs 2409750.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:20015, the non-reference allele at core position 501, SEQ ID NO:20015 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20015 has the sequence of SEQ ID NO:20015 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 2015 are sufficient to detect the polymorphism at rs 1541020.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20016 SEQ ID NO:20016 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "T" or "a" allele of SEQ ID NO:20016 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "T" or "a" allele at core position 501 within 20016 are sufficient to detect the polymorphism at rs 4942248.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20017 of SEQ ID NO:20017 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20017 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20017 are sufficient to detect a polymorphism at rs 12934476.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20018 SEQ ID NO:20018 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "C" allele at core position 501 within 20018 has the sequence of SEQ ID NO:20018 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "C" allele at core position 501 within 20018 are sufficient to detect the polymorphism at rs 12457255.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20019 of SEQ ID NO:20019 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20019 has the sequence of SEQ ID NO:20019 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20019 are sufficient to detect the polymorphism at rs 2297437.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20020 of SEQ ID NO:20020 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20020 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20020 are sufficient to detect a polymorphism at rs 41309367.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20021 of SEQ ID NO:20021 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 2021 is represented by SEQ ID NO:20021 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20021 are sufficient to detect the polymorphism at rs 10733509.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20022 is SEQ ID NO:20022 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20022 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20022 are sufficient to detect a polymorphism at rs 10750376.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20023 of SEQ ID NO:20023 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20023 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20023 are sufficient to detect a polymorphism at rs 10932456.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20024 of SEQ ID NO:20024, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20024 has the sequence of SEQ ID NO:20024, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20024 are sufficient to detect a polymorphism at rs 1326860.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele at core position 501 within 20025 has the sequence of SEQ ID NO:20025 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20025 are sufficient to detect the polymorphism at rs 1528663.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20026 is SEQ ID NO:20026 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "C" or "a" allele of SEQ ID NO:20026 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "a" allele at core position 501 within 20026 are sufficient to detect the polymorphism at rs 1892231.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20027 of SEQ ID NO:20027 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20027 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20027 are sufficient to detect the polymorphism at rs 951279.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20028 has the sequence of SEQ ID NO:20028 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20028 has the sequence of SEQ ID NO:20028 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20028 are sufficient to detect the polymorphism at rs 9806914.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20029 of SEQ ID NO:20029 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "C" or "a" allele of SEQ ID NO:20029 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "a" allele at core position 501 within 20029 are sufficient to detect the polymorphism at rs 7935393.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20030 has the sequence of SEQ ID NO:20030 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "C" allele of SEQ ID NO:20030 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "C" allele at core position 501 within 20030 are sufficient to detect the polymorphism at rs 1690492.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20031 has the sequence of SEQ ID NO:20031 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele of SEQ ID NO:20031 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20031 are sufficient to detect a polymorphism at rs 420726.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20032 has the sequence of SEQ ID NO:20032 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "T" or "a" allele of SEQ ID NO:20032 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "T" or "a" allele at core position 501 within 20032 are sufficient to detect a polymorphism at rs 7759385.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20033 of SEQ ID NO:20033 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20033 has the sequence of SEQ ID NO:20033 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20033 are sufficient to detect the polymorphism at rs 10974900.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20034 has the sequence of SEQ ID NO:20034, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20034 has the sequence of SEQ ID NO:20034, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20034 are sufficient to detect the polymorphism at rs 1326860.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 2035 of SEQ ID NO:20035, at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "C" or "G" allele of SEQ ID NO:20035, at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "G" allele at core position 501 within 20035 are sufficient to detect the polymorphism at rs 2548147.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20036 SEQ ID NO:20036 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20036 has the sequence of SEQ ID NO:20036 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20036 are sufficient to detect the polymorphism at rs 2815844.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:20037, the non-reference allele at core position 501, SEQ ID NO:20037 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "G" or "a" allele at core position 501 within 20037 has the sequence of SEQ ID NO:20037 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "G" or "a" allele at core position 501 within 20037 are sufficient to detect the polymorphism at rs 889702.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20038 of SEQ ID NO:20038 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20038 has the sequence of SEQ ID NO:20038 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20038 are sufficient to detect the polymorphism at rs 9806914.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20039 of SEQ ID NO:20039 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele of SEQ ID NO:20039 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20039 are sufficient to detect the polymorphism at rs 6478109.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20040 of SEQ ID NO:20040 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "C" or "G" allele at core position 501 within 20040 has the sequence of SEQ ID NO:20040 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "C" or "G" allele at core position 501 within 2040 are sufficient to detect a polymorphism at rs 7278257.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20041 of SEQ ID NO:20041 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele of SEQ ID NO:20041 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20041 are sufficient to detect the polymorphism at rs 11221332.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the non-reference allele at core position 501 within 20057 of SEQ ID NO:20057 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele of SEQ ID NO:20057 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20057 are sufficient to detect the polymorphism at rs 56124762.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:20058, the non-reference allele at core position 501, SEQ ID NO:20058 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "a" or "G" allele at core position 501 within 20058 has the sequence of SEQ ID NO:20058 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "a" or "G" allele at core position 501 within 20058 are sufficient to detect the polymorphism at rs 2070558.

In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO:20059, the non-reference allele at core position 501, SEQ ID NO:20059 of at least 10 consecutive nucleic acid molecules. In some embodiments, the target nucleic acid is a nucleic acid comprising SEQ ID NO: the "T" or "C" allele at core position 501 within 20059 has the sequence of SEQ ID NO:20059 of at least 10 consecutive nucleic acid molecules. In some embodiments, a nucleic acid comprising SEQ ID NO: at least 10 consecutive nucleic acid molecules of the "T" or "C" allele at core position 501 within 20059 are sufficient to detect the polymorphism at rs 2070561.

In some embodiments, a target nucleic acid (e.g., polymorphism) is detected using the methods disclosed herein. In some embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 target nucleic acids are detected. In some embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 target nucleic acids are detected in a single multiplex assay. In some embodiments, when 4 target nucleic acids are detected in a sample from a subject, 4 unique 3-polymorphism combinations are measured. In one non-limiting example, a sample (e.g., blood or plasma) obtained from a subject is contacted with 4 primer pairs, each primer pair adapted to amplify rs6487109, rs56124762, rs1892231, and rs16901748, respectively. Positive, negative or indeterminate TNFSF15 profiles may depend at least in part on which 3-polymorphism combination is detected in the sample, and/or whether the genotype of the polymorphism is heterozygous or homozygous. In this example, determining 4 polymorphisms means that a total of 4 unique 3-polymorphisms, rs6478109, rs56124762, rs1892231, can be detected in the patient sample; rs6478109, rs56124762, rs16901748; rs6478109, rs1892231, rs16901748; and rs56124762, rs1892231, rs16901748. Each polymorphism detected may be heterozygous or homozygous.

In some aspects, disclosed herein are methods of sample preparation, the methods comprising: (a) Extracting a plurality of nucleic acids from a sample disclosed herein that has been obtained from a subject; and (b) enriching the target nucleic acid from a plurality of nucleic acids comprising one or more polymorphisms disclosed herein, wherein the enriching is performed by: (i) Contacting a fluid reaction formulation comprising a synthetic oligonucleotide molecule with a sample; (ii) Hybridizing a synthetic oligonucleotide molecule to a target nucleic acid molecule; and (iii) amplifying the target nucleic acid molecule, thereby enriching the target nucleic acid molecule in the fluidic reaction formulation. In some embodiments, the method further comprises detecting the target nucleic acid molecule enriched in (b). In some embodiments, the target nucleic acid comprises a TNFSF15 locus. In some embodiments, the one or more polymorphisms include the polymorphisms provided in table 1. In some embodiments, the one or more polymorphisms comprise a combination of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more polymorphisms provided in table 1. In some embodiments, the synthetic oligonucleotide comprises a primer sequence. In some embodiments, the synthetic oligonucleotide comprises a detectable probe.

To practice the methods and systems provided herein, genetic material may be extracted from a sample (e.g., a blood or serum sample) obtained from a subject. In certain embodiments of extracting nucleic acids, any technique that does not interfere with subsequent analysis is used to extract the nucleic acids. In certain embodiments, the technique utilizes alcohol precipitation using ethanol, methanol, or isopropanol. In certain embodiments, the technique uses phenol, chloroform, or any combination thereof. In certain embodiments, the technology uses cesium chloride. In certain embodiments, the technique uses sodium, potassium or ammonium acetate or any other salt commonly used to precipitate DNA. In certain embodiments, the technology utilizes column or resin based nucleic acid purification protocols, such as those commonly available commercially, one non-limiting example being the geneleute bacterial genomic DNA kit available from Sigma Aldrich. In certain embodiments, after extraction, the nucleic acid is stored in water, tris buffer or Tris-EDTA buffer, and then subjected to subsequent analysis. In one exemplary embodiment, the nucleic acid material is extracted in water. In some cases, the extraction does not include nucleic acid purification. In certain embodiments, RNA may be extracted from cells using RNA extraction techniques, including, for example, using phenol/guanidine isothiocyanate extraction (RNAzol B; biogenesis), RNeasy RNA preparation kit (Qiagen) or PAXgene (PreAnalytix, switzerland).

In some embodiments, a method of detecting the presence, absence, or level of a target protein (e.g., biomarker) in a sample obtained from a subject involves detecting protein activity or expression. In some embodiments, the target protein is TL1A, or a binding partner of TL1A, such as death domain receptor 3 (DcR 3). The target protein may be detected by using an antibody-based assay in which antibodies specific for the target protein are utilized. In some embodiments, antibody-based detection methods utilize antibodies that bind to any region of the target protein. Exemplary analytical methods include performing an enzyme-linked immunosorbent assay (ELISA). The ELISA assay may be a sandwich ELISA or a direct ELISA. Another exemplary assay includes single molecule arrays, such as Simoa. Other exemplary detection methods include immunohistochemistry and lateral flow assays. Other exemplary methods of detecting a target protein include, but are not limited to, gel electrophoresis, capillary electrophoresis, high Performance Liquid Chromatography (HPLC), thin Layer Chromatography (TLC), super-diffusion chromatography, and the like, or various immunological methods such as fluid or gel precipitation reactions, immunodiffusion (single or double), immunoelectrophoresis, radioimmunoassay (RIA), immunofluorescent assay, and western blot. In some embodiments, the antibody or antibody fragment is used in a method such as western blot or immunofluorescence techniques to detect the expressed protein. Antibodies or proteins may be immobilized on a solid support for use in western blotting and immunofluorescence techniques. Suitable solid supports or carriers include any support capable of binding an antigen or antibody. Exemplary supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylase, natural and modified celluloses, polyacrylamides, gabbros, and magnetite.

In some cases, the target protein may be detected by detecting binding between the target protein and a binding partner of the target protein. Non-limiting examples of binding partners for TL1A include DcR3 and tumor necrosis factor receptor superfamily member 25 (TNR 25). Exemplary assays for protein-protein binding include in vivo or in vitro or ex vivo assays. In some cases, the analytical method includes assays such as the following: co-immunoprecipitation (co-IP), pulldown, cross-linked protein interaction analysis, labeled transfer protein interaction analysis, or remote western blot analysis, FRET-based assays, including, for example, FRET-FLIM, yeast two-hybrid assays, biFC, or split luciferase assays.

Disclosed herein are methods of detecting the presence or level of one or more serological markers in a sample obtained from a subject. In some embodiments, the one or more serological markers include an anti-saccharomyces cerevisiae (Saccharomyces cerevisiae) antibody (ASCA), an anti-neutrophil cytoplasmic antibody (ANCA), an anti-escherichia coli (e.coli) outer membrane porin C antibody (anti-OmpC), an anti-chitin antibody, a pANCA antibody, an anti-I2 antibody, and an anti-Cbir 1 flagellin antibody. In some embodiments, the antibody comprises immunoglobulin a (IgA), immunoglobulin G (IgG), immunoglobulin E (IgE), or immunoglobulin M (IgM), immunoglobulin D (IgD), or a combination thereof. Any suitable method for detecting a target protein or biomarker disclosed herein may be used to detect the presence, absence, or level of a serological marker. In some embodiments, the presence or level of one or more serological markers is detected using an enzyme-linked immunosorbent assay (ELISA), single molecule array (Simoa), immunohistochemistry, internal Transcribed Spacer (ITS) sequencing, or any combination thereof. In some embodiments, the ELISA is a fixed leukocyte ELISA. In some embodiments, the ELISA is a fixed neutrophil ELISA. Fixed leukocyte or neutrophil ELISA can be used to detect certain serological markers, such as those described in Saxon et al A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease, j. 2;202-210 (month 8 1990). In some embodiments, ELISA Units (EUs) are used to measure positives (e.g., seropositives) of the presence or level of a serological marker, reflecting a percentage of a standard or reference value. In some embodiments, the criteria include pooled sera obtained from a well-characterized patient population (e.g., diagnosed with the same disease or condition that the subject has or is suspected of having), which patient population is reported to be seropositive for the serological marker of interest. In some embodiments, the control or reference value comprises 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100EU. In some cases, for example, landers C J, cohavy O, misra R. Et al, selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto-and microbial agents, geometry (2002) 123: the method reported in 689-699 calculates a quartile sum score.

Therapeutic agent

Antibodies to

In one aspect, provided herein are antibodies and antigen binding fragments. In some embodiments, the antibody comprises an antigen binding fragment, which refers to an antibody portion having the epitope variable region of the antibody. Examples of antigen binding fragments include, but are not limited to, fab ', F (ab') ₂ And Fv fragments, linear antibodies, single chain antibodies, and multispecific antibodies formed from antibody fragments. In some embodiments, an antibody refers to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or a combination of the foregoing, through at least one antigen recognition site within the variable region of the immunoglobulin molecule. In some embodiments, antibodies include intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, fab ', F (ab') ₂ And Fv fragments), single chain Fv (scFv) mutants, CDR-grafted antibodies, multispecific antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins comprising an epitope of an antibody, and any other modified immunoglobulin molecule comprising an antigen recognition site, so long as the antibody exhibits the desired biological activity. Antibodies can have any of five main classes of immunoglobulins based on the identity of the heavy chain constant domains of the antibodies, called α, δ, epsilon, γ, and μ, respectively: igA, igD, igE, igG and IgM, or subclasses (isotypes) thereof (e.g., igG1, igG2, igG3, igG4, igA1, and IgA 2). Immunoglobulins of different classes have different and well known properties Subunit structures and three-dimensional configurations of (a). The antibodies may be naked or conjugated to other molecules such as toxins, radioisotopes.

In some embodiments, humanized antibodies refer to a form of a non-human (e.g., murine) antibody having a particular immunoglobulin chain, chimeric immunoglobulin, or fragment thereof that contains minimal non-human (e.g., murine) sequences. In one non-limiting example, the humanized antibody comprises less than about 40% non-human sequences in the variable region. In some cases, the humanized antibody comprises less than about 20% non-human sequences in the full length antibody sequence. In another non-limiting example, the humanized antibody comprises less than about 20% non-human sequences in the framework regions of each of the heavy and light chain variable regions. For example, a humanized antibody comprises less than about 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% non-human sequence in the framework regions of each of the heavy and light chain variable regions. As another example, a humanized antibody comprises about or less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequences in the framework regions of each of the heavy and light chain variable regions. In some cases, the humanized antibody is a human immunoglobulin in which residues from a Complementarity Determining Region (CDR) are replaced with residues from a CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) having the desired specificity, affinity, and capacity. These humanized antibodies may contain one or more non-human species mutations, for example, the heavy chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 non-human species mutations in the framework regions, and the light chain comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 non-human species mutations in the framework regions. The humanized heavy chain variable domain may comprise IGHV1-46 x 02 frameworks with no amino acid mutations or with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid mutations. The humanized light chain variable domain may comprise an IGKV3-20 framework having no amino acid mutation or having less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutation.

In some embodiments, chimeric antibodies refer to antibodies in which the sequence of an immunoglobulin molecule is derived from two or more species. As a non-limiting example, the variable regions of both the light and heavy chains correspond to the variable regions of antibodies derived from one mammalian species (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and ability, while the constant regions are homologous to sequences in antibodies derived from another species (typically human) to avoid eliciting an immune response in that species.

In certain aspects, described herein are antibodies that specifically bind to TL1A (Entrez Gene:9966; uniProtKB: O95150). In some embodiments, the antibody specifically binds to soluble TL1A. In some embodiments, the antibody specifically binds to membrane-bound TL1A. In some embodiments, an anti-TL 1A antibody is provided having a heavy chain comprising four Heavy Chain Framework Regions (HCFR) and three heavy chain complementarity determining regions (HCDR): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3 and HCFR4; and a light chain comprising four Light Chain Framework Regions (LCFR) and three light chain complementarity determining regions (LCDR): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3 and LCFR4. anti-TL 1A antibodies can comprise any of the regions provided herein, e.g., in table 15-table 21, examples, and sequences.

Exemplary anti-TL 1A CDR

In certain embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1 or 601-722. In certain embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO: HCDR2 as shown in any one of 2-5 or 723-787. In certain embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO: HCDR3 as shown in any one of 6-9 or 788-842. In certain embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO: LCDR1 as shown in any one of 10 or 843-865. In certain embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO: LCDR2 as shown in any one of 11 or 866-885. In certain embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO: LCDR3 as shown in any one of 12-15 or 886-1101.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:1 or 601-708, HCDR1 comprising any one of SEQ ID NOs: 2-5 or 723-774, HCDR2 comprising any one of SEQ ID NOs: 6-9 or 788-828, HCDR3 comprising any one of SEQ ID NOs: 10 or 843-852, LCDR1 comprising any one of SEQ ID NOs: 11 or 866-873 and an LCDR2 comprising any one of SEQ ID NOs: LCDR3 of any of 12-15 or 886-1089.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:709, HCDR1 comprising SEQ ID NO:775, HCDR2 comprising SEQ ID NO:829 HCDR3 comprising SEQ ID NO:853 LCDR1 comprising SEQ ID NO:874 and LCDR2 comprising SEQ ID NO:1090 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:710, HCDR1 comprising SEQ ID NO:776, HCDR2 comprising SEQ ID NO:830, HCDR3 comprising SEQ ID NO:854, LCDR1 comprising SEQ ID NO:875 and LCDR2 comprising SEQ ID NO:1091 LCDR3. In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:711 or 712, HCDR1 comprising SEQ ID NO:777 or 778, HCDR2 comprising SEQ ID NO:831 or 832, HCDR3 comprising SEQ ID NO:855, LCDR1 comprising SEQ ID NO:876 and LCDR2 comprising SEQ ID NO:1092 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:713 HCDR1 comprising SEQ ID NO:779, HCDR2 comprising SEQ ID NO:833, HCDR3 comprising SEQ ID NO:856, LCDR1 comprising SEQ ID NO:877 and LCDR2 comprising SEQ ID NO:1093 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:714, HCDR1 comprising SEQ ID NO:780, HCDR2 comprising SEQ ID NO:834 HCDR3 comprising SEQ ID NO:857 LCDR1 comprising SEQ ID NO:878 and LCDR2 comprising SEQ ID NO:1094 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:715 or 716, HCDR1 comprising SEQ ID NO:781, HCDR2 comprising SEQ ID NO:835 or 836, HCDR3 comprising SEQ ID NO:858 or 859, LCDR1 comprising SEQ ID NO:879 and LCDR2 comprising SEQ ID NO:1095 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:717, HCDR1 comprising SEQ ID NO:782, HCDR2 comprising SEQ ID NO:837, HCDR3 comprising SEQ ID NO:860, LCDR1 comprising SEQ ID NO:880 and LCDR2 comprising SEQ ID NO:1096 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:718, HCDR1 comprising SEQ ID NO:783 HCDR2 comprising SEQ ID NO:838 HCDR3 comprising SEQ ID NO:861, LCDR1 comprising SEQ ID NO:881 and LCDR2 comprising SEQ ID NO:1097 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:719, HCDR1 comprising SEQ ID NO:784 HCDR2 comprising SEQ ID NO:839, HCDR3 comprising SEQ ID NO:862 LCDR1, comprising SEQ ID NO:882 LCDR2 and a nucleic acid sequence comprising SEQ ID NO:1098 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:720, HCDR1 comprising SEQ ID NO:785 HCDR2 comprising SEQ ID NO:840, HCDR3 comprising SEQ ID NO:863, LCDR1 comprising SEQ ID NO:883 and LCDR2 comprising SEQ ID NO:1099 LCDR3.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:721 HCDR1 comprising SEQ ID NO:786 HCDR2 comprising SEQ ID NO:841, HCDR3 comprising SEQ ID NO:864, LCDR1 comprising SEQ ID NO:884 and LCDR2 comprising SEQ ID NO: LCDR3 of 1100.

In one aspect, provided herein is an anti-TL 1A antibody having a sequence comprising SEQ ID NO:722, HCDR1 comprising SEQ ID NO:787 HCDR2 comprising SEQ ID NO:842, HCDR3 comprising SEQ ID NO:865, LCDR1 comprising SEQ ID NO:885 and LCDR2 comprising SEQ ID NO: LCDR3 of 1101.

In certain embodiments, the anti-TL 1A antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 selected from table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody B as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody C as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody D as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody E as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody F as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises CDRs listed in antibody G as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises CDRs listed in antibody H as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody A2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody B2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody C2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody D2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody E2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody F2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises CDRs listed in antibody G2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises CDRs listed in antibody H2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody I as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody I2 as shown in table 20. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M1 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M2 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M3 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M4 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M5 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M6 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M7 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M8 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M9 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M10 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M11 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M12 as shown in table 15. In certain embodiments, the anti-TL 1A antibody comprises P HCDR1 (any of SEQ ID NOS: 1 or 601-708), P HCDR2 (any of SEQ ID NOS: 2-5 or 723-774), P HCDR3 (any of SEQ ID NOS: 6-9 or 788-828), P LCDR1 (any of SEQ ID NOS: 10 or 843-852), P LCDR2 (any of SEQ ID NOS: 11 or 866-873), and P LCDR3 (any of SEQ ID NOS: 12-15 or 886-1089) as shown in Table 15.

In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in any one of the antibodies of table 10. In certain embodiments, the anti-TL 1A antibody comprises CDRs listed in any one of the heavy chain variable regions in table 16. In certain embodiments, the anti-TL 1A antibody comprises CDRs listed in any one of the light chain variable regions in table 17. CDRs can be defined by the Aho or Kabat, chothia or IMGT methods. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 217. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 220. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 223. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 219. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 221. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 200. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 213. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 212. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 107. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 205. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 211. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 199. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 15. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 30. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 100. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 181. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 129. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 214. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 216. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 122. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 222. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 188. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 203. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 147. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 127. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 126. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 160. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 157. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 159. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 218. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 158. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 125. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 103. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 64. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 67. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 138. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 68. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 94. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 110. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 197. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 112. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 169. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 173. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 179. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 148. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 115. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 149. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 134. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 113. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 151. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 96. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 132. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 196. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 172. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 75. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 174. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 109. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 198. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody a 170. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M1. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M2. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M3. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M4. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M5. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M6. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M7. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M8. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M9. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M10. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M11. In certain embodiments, the anti-TL 1A antibody comprises the CDRs listed in antibody M12.

Exemplary TL1A resistant frame region

Tables 16-18 and 21 provide exemplary frameworks and variable region sequences. In some embodiments, the anti-TL 1A antibody comprises HC FR1 of Table 19 (SEQ ID NO: 304), HC FR2 of Table 19 (any of SEQ ID NO:305, 313, 1317), HC FR3 of Table 19 (any of SEQ ID NO:306, 307, 314, 315, 1318-1323), HC FR4 of Table 19 (SEQ ID NO: 308), LC FRI of Table 19 (SEQ ID NO: 309), LC FR2 of Table 19 (SEQ ID NO:310 or 1324), LC FR3 of Table 19 (SEQ ID NO: 311), and LC FR4 of Table 19 (SEQ ID NO: 312).

In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence comprising SEQ ID NO:301 (X1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQG TTVTVSS). In some cases, X1 is Q. In some cases, x1=e. In some cases, x2=r. In some cases, x2=k. In some cases, x3=a. In some cases, x3=r. In some cases, x4=m. In some cases, x4=i. In some cases, x5=v. In some cases, x5=a. In some cases, x6=m. In some cases, x6=i. In some cases, x7=r. In some cases, x7=t. In some cases, x8=v. In some cases, x8=a. In some cases, x9=m. In some cases, x9=l. In some embodiments, X1 is located at position 1 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X2 is located at position 45 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X3 is located at position 47 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X4 is located at position 55 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X5 is located at position 78 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X6 is located at position 80 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X7 is located at position 82 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X8 is located at position 89 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X9 is located at position 91 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering.

In one aspect, provided herein is a first embodiment of an anti-TL 1A antibody comprising a heavy chain framework comprising IGHV1-46 x 02 or a variant thereof, wherein said variant comprises about 1 to about 9 amino acid substitutions, or about 1 to about 20 amino acid substitutions, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions compared to the IGHV1-46 x 02 framework. Additional embodiments include: (2) The anti-TL 1A of embodiment (1), wherein said heavy chain framework comprises the amino acid sequence of SEQ ID NO:301. (3) anti-TL 1A as described in embodiment 2, wherein x1=q. (4) anti-TL 1A as described in embodiment 2, wherein x1=e. (5) The anti-TL 1A of any one of embodiments 2 to 4, wherein x2=r. (6) The anti-TL 1A of any one of embodiments 2 to 4, wherein x2=k. (7) The anti-TL 1A of any one of embodiments 2 to 6, wherein x3=a. (8) The anti-TL 1A of any one of embodiments 2 to 6, wherein x3=r. (9) The anti-TL 1A of any one of embodiments 2 to 8, wherein x4=m. (10) The anti-TL 1A of any one of embodiments 2 to 8, wherein x4=i. (11) The anti-TL 1A of any one of embodiments 2 to 10, wherein x5=v. (12) The anti-TL 1A of any one of embodiments 2 to 10, wherein x5=a. (13) The anti-TL 1A of any one of embodiments 2 to 12, wherein x6=m. (14) The anti-TL 1A of any one of embodiments 2 to 12, wherein x6=i. (15) The anti-TL 1A of any one of embodiments 2 to 14, wherein x7=r. (16) The anti-TL 1A of any one of embodiments 2 to 14, wherein x7=t. (17) The anti-TL 1A of any one of embodiments 2 to 16, wherein x8=v. (18) The anti-TL 1A of any one of embodiments 2 to 16, wherein x8=a. (19) The anti-TL 1A of any one of embodiments 2 to 18, wherein x9=m. (20) The anti-TL 1A of any one of embodiments 2 to 4, wherein x9=l. (21) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody a. (22) The anti-TL 1A of any one of embodiments 1 to 20, comprising an antibody B. (23) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody C. (24) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody D. (25) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody E. (26) The anti-TL 1A of any one of embodiments 1 to 20, comprising an antibody F. (27) The anti-TL 1A of any one of embodiments 1 to 20, comprising an antibody G or I. (28) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody H. (29) The anti-TL 1A of any one of embodiments 1 to 28, comprising a human IgG1Fc region comprising: (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) 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) G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G a and P331S, (bbb) L234A, L235 82348 237A, (bbb) 238S, H S and P331S (IgG 1 σ268), (ccc) L234A, L a and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hh) D a, (iii) D and N297A, (jj a and N) j) N and (k) 265A, (karn) and (G331A) (or any combination (mm) 331A) - (G) 331A (mm) 331S (G) or (mm) 331A). As used herein, any group, such as a combination of (a) to (uu), includes at least about two or more items from the group, e.g., any combination of groups (a) to (uu) includes 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, and up to 47 or members of all groups. (30) The anti-TL 1A of any one of embodiments 1 to 28, comprising (i) a human IgG4 Fc region, or (ii) a human IgG4 Fc region comprising: (a) S228P, (b) S228P and L235E, or (c) S228P, F234A and L235A, numbered according to Kabat. (31) The anti-TL 1A of any one of embodiments 1 to 28, comprising a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. (32) The anti-TL 1A of any one of embodiments 1 to 31, comprising an amino acid sequence comprising SEQ ID NO: 320-362. (33) The anti-TL 1A of any one of embodiments 1 to 32, comprising an amino acid sequence comprising SEQ ID NO: 319. (34) The anti-TL 1A of any one of embodiments 1 to 33, comprising a light chain framework comprising IGKV3-20 x 01 or a variant thereof, wherein said variant comprises about 1 to about 2 substitutions, or about 1 to about 20 amino acid substitutions, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions in the framework. (35) The anti-TL 1A antibody of embodiment 34, wherein X10 is L. (36) The anti-TL 1A antibody of embodiment 34, wherein X10 is P. (37) The anti-TL 1A antibody of any one of embodiments 34 to 36, wherein X11 is L. (38) The anti-TL 1A antibody of any one of embodiments 34 to 36, wherein X11 is W.

In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence comprising SEQ ID NO:302 (X1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS). In some cases, X1 is Q. In some cases, x1=e. In some cases, x2=r. In some cases, x2=k. In some cases, x3=a. In some cases, x3=r. In some cases, x4=m. In some cases, x4=i. In some cases, x5=v. In some cases, x5=a. In some cases, x6=m. In some cases, x6=i. In some cases, x7=r. In some cases, x7=t. In some cases, x8=v. In some cases, x8=a. In some cases, x9=m. In some cases, x9=l. In some embodiments, X1 is located at position 1 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X2 is located at position 45 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X3 is located at position 47 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X4 is located at position 55 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X5 is located at position 78 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X6 is located at position 80 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X7 is located at position 82 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X8 is located at position 89 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering. In some embodiments, X9 is located at position 91 of IGHV 1-46X 02, as determined by the Aho or Kabat numbering.

In one aspect, provided herein is another first embodiment of an anti-TL 1A antibody comprising a heavy chain framework comprising IGHV1-46 x 02 or a variant thereof, wherein said variant comprises about 1 to about 9 amino acid substitutions, or about 1 to about 20 amino acid substitutions, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions compared to the IGHV1-46 x 02 framework. Additional embodiments include: (2) The anti-TL 1A of embodiment (1), wherein said heavy chain framework comprises the amino acid sequence of SEQ ID NO:302. (3) anti-TL 1A as described in embodiment 2, wherein x1=q. (4) anti-TL 1A as described in embodiment 2, wherein x1=e. (5) The anti-TL 1A of any one of embodiments 2 to 4, wherein x2=r. (6) The anti-TL 1A of any one of embodiments 2 to 4, wherein x2=k. (7) The anti-TL 1A of any one of embodiments 2 to 6, wherein x3=a. (8) The anti-TL 1A of any one of embodiments 2 to 6, wherein x3=r. (9) The anti-TL 1A of any one of embodiments 2 to 8, wherein x4=m. (10) The anti-TL 1A of any one of embodiments 2 to 8, wherein x4=i. (11) The anti-TL 1A of any one of embodiments 2 to 10, wherein x5=v. (12) The anti-TL 1A of any one of embodiments 2 to 10, wherein x5=a. (13) The anti-TL 1A of any one of embodiments 2 to 12, wherein x6=m. (14) The anti-TL 1A of any one of embodiments 2 to 12, wherein x6=i. (15) The anti-TL 1A of any one of embodiments 2 to 14, wherein x7=r. (16) The anti-TL 1A of any one of embodiments 2 to 14, wherein x7=t. (17) The anti-TL 1A of any one of embodiments 2 to 16, wherein x8=v. (18) The anti-TL 1A of any one of embodiments 2 to 16, wherein x8=a. (19) The anti-TL 1A of any one of embodiments 2 to 18, wherein x9=m. (20) The anti-TL 1A of any one of embodiments 2 to 4, wherein x9=l. (21) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody a. (22) The anti-TL 1A of any one of embodiments 1 to 20, comprising an antibody B. (23) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody C. (24) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody D. (25) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody E. (26) The anti-TL 1A of any one of embodiments 1 to 20, comprising an antibody F. (27) The anti-TL 1A of any one of embodiments 1 to 20, comprising an antibody G or I. (28) The anti-TL 1A of any one of embodiments 1 to 20, comprising antibody H. (29) The anti-TL 1A of any one of embodiments 1 to 28, comprising a human IgG1Fc region comprising: (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) 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) G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G a and P331S, (bbb) L234A, L235 82348 237A, (bbb) 238S, H S and P331S (IgG 1 σ268), (ccc) L234A, L a and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hh) D a, (iii) D and N297A, (jj a and N) j) N and (k) 265A, (karn) and (G331A) (or any combination (mm) 331A) - (G) 331A (mm) 331S (G) or (mm) 331A). (30) The anti-TL 1A of any one of embodiments 1 to 28, comprising (i) a human IgG4 Fc region, or (ii) a human IgG4 Fc region comprising: (a) S228P and L235E, or (b) S228P, F234A and L235A, numbered according to Kabat. (31) The anti-TL 1A of any one of embodiments 1 to 28, comprising a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. (32) The anti-TL 1A of any one of embodiments 1 to 31, comprising an amino acid sequence comprising SEQ ID NO: 320-362. (33) The anti-TL 1A of any one of embodiments 1 to 32, comprising an amino acid sequence comprising SEQ ID NO: 319. (34) The anti-TL 1A of any one of embodiments 1 to 33, comprising a light chain framework comprising IGKV3-20 x 01 or a variant thereof, wherein said variant comprises about 1 to about 2 substitutions, or about 1 to about 20 amino acid substitutions, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions in the framework. (35) The anti-TL 1A antibody of embodiment 34, wherein X10 is L. (36) The anti-TL 1A antibody of embodiment 34, wherein XI0 is P. (37) The anti-TL 1A antibody of any one of embodiments 34 to 36, wherein X11 is L. (38) The anti-TL 1A antibody of any one of embodiments 34 to 36, wherein X11 is W.

In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK). In some cases, X10 is L. In some cases, X10 is P. In some cases, X11 is L. In some cases, X11 is W. In some embodiments, X10 is located at position 54 of IGKV 3-20X 01, as determined by the Aho or Kabat numbering. In some embodiments, X11 is located at position 55 of IGKV 3-20X 01, as determined by the Aho or Kabat numbering.

In some embodiments, the anti-TL 1A antibody comprises a heavy chain framework comprising IGHV1-46 x 02. In some embodiments, the anti-TL 1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46 x 02 that hybridizes to SEQ ID NO:316 comprises about 1 to about 20 amino acid substitutions. In some embodiments, the anti-TL 1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46 x 02 that hybridizes to SEQ ID NO:316 comprises about 1 to about 9 amino acid substitutions. In some embodiments, the anti-TL 1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46 x 02 that hybridizes to SEQ ID NO:316 comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the frame. In some cases, the heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises R45K, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises a47R, as determined by the Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises M55I, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises V78A, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises M80I, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises R82T, as determined by the Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises V89A, as determined by Aho or Kabat numbering. In some cases, the heavy chain framework substitution comprises M91L, as determined by Aho or Kabat numbering.

In some embodiments, the anti-TL 1A antibody comprises a light chain framework comprising IGKV3-20 x 01. In some embodiments, the anti-TL 1A antibody comprises a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 1 to about 20 amino acid substitutions. In some embodiments, the anti-TL 1A antibody comprises a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 1 amino acid substitution. In some embodiments, the anti-TL 1A antibody comprises a light chain framework comprising a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 2 amino acid substitutions. In some embodiments, the anti-TL 1A antibody comprises a light chain framework comprising a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions in the frame. In some cases, the light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some cases, the light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:304, and a heavy chain FR1. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:305, heavy chain FR2. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:313, and a heavy chain FR2. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1317, and a heavy chain FR2. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:306, and heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:307, heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:314, and a heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:315, heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1318, heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1319, heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1320, a heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1321 and a heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1322, heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1323, and a heavy chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:308, and a heavy chain FR4. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:309, light chain FR1. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:310, and a light chain FR2 indicated. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1324, and a light chain FR2. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:311, light chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:1325, light chain FR3. In some embodiments, the anti-TL 1A antibody comprises an amino acid sequence as set forth in SEQ ID NO:312, and a light chain FR4.

In certain embodiments, the anti-TL 1A antibody comprises a framework region listed in any one of the antibodies of table 1, wherein the framework region is defined by the Aho or Kabat, chothia or IMGT method. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 217. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 220. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 223. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 219. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 221. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 200. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 213. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 212. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 107. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 205. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 211. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 199. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 15. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 30. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 100. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 181. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 129. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 214. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 216. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 122. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 222. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 188. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 203. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 147. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 127. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 126. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 160. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 157. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 159. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 218. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 158. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 125. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 103. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 64. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 67. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 138. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 68. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 94. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 110. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 197. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 112. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 169. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 173. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 179. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 148. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 115. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 149. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 134. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 113. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 151. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 96. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 132. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 196. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 172. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 75. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 174. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 109. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 198. In certain embodiments, the anti-TL 1A antibody comprises the framework regions listed in antibody a 170.

In certain embodiments, the anti-TL 1A antibody comprises a heavy chain framework region set forth in any one of the antibodies of table 16, and a light chain framework region set forth in any one of the antibodies of table 17, wherein the framework regions are defined by the Aho or Kabat, chothia or IMGT methods.

Exemplary anti-TL 1A variable region

In one aspect, provided herein is an anti-TL 1A antibody comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:101-135 of at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:201-206 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.

Also provided herein is a first embodiment of an anti-TL 1A antibody comprising a heavy chain variable region and a light chain variable region. Additional non-limiting embodiments include: (embodiment 2) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:101. (embodiment 3) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:101 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. (embodiment 4) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:101 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 5) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:102. (embodiment 6) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:102 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 7) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:102 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 8) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:103. (embodiment 9) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:103 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 10) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:103 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 11) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104. (embodiment 12) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:104 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 13) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:104 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 14) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:105. (embodiment 15) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:105 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 16) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:105 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 17) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:106. (embodiment 18) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:106 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 19) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:106 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 20) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:107. (embodiment 21) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:107 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 22) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:107 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 23) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:108. (embodiment 24) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:108 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 25) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:108 have about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 26) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:109. (embodiment 27) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:109 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 28) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:109 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 29) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:110. (embodiment 30) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:110 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 31) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:110 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 32) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:111. (embodiment 33) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:111 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 34) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:111 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 35) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:112. (embodiment 36) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:112 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 37) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:112 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 38) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:113. (embodiment 39) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:113 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 40) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:113 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 41) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:114. (embodiment 42) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:114 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 43) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:114 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 44) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:115. (embodiment 45) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:115 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 46) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:115 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 47) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:116. (embodiment 48) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:116 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 49) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:116 have about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 50) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:117. (embodiment 51) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:117 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 52) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:117 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 53) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:118. (embodiment 54) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:118 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 55) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:118 have about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 56) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:119. (embodiment 57) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:119, at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 58) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:119 to a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 59) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:120. (embodiment 60) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:120 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 61) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:120 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to the sequence.

(embodiment 62) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:121. (embodiment 63) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:121 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 64) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:121 has a sequence of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 65) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:122. (embodiment 66) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:122 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 67) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:122 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 68) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:123. (embodiment 69) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:123 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 70) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:123 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 71) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:124. (embodiment 72) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:124 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 73) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:124 having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 74) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:125. (embodiment 75) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:125 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 76) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:125 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 77) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:126. (embodiment 78) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:126 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 79) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:126 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 80) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:127. (embodiment 81) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:127 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 82) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:127 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 83) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:128. (embodiment 84) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:128 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 85) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:128 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 86) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:129. (embodiment 87) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:129, at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 88) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:129 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 89) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:130. (embodiment 90) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:130 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 91) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:130 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 92) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:131. (embodiment 93) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:131 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 94) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:131 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 95) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:132. (embodiment 96) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:132 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 97) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:132 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 98) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:133. (embodiment 99) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:133 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 100) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:133 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to the sequence. (embodiment 101) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:134. (embodiment 102) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:134 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 103) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:134 having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 104) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:135. (embodiment 105) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:135 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 106) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:135 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 107) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:201. (embodiment 108) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 109) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:201 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 110) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:202. (embodiment 111) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 112) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:202 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 113) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:203. (embodiment 114) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:203 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 115) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:203 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 116) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:204. (embodiment 117) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 118) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:204 have about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 119) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:205. (embodiment 120) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 121) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:205 have about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions. (embodiment 122) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:206. (embodiment 123) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:206 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 124) the anti-TL 1A antibody of any one of embodiments 1 to 106, wherein said light chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:206 has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions.

(embodiment 125) the anti-TL 1A antibody as described in embodiment 1, comprising a217. (embodiment 126) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:101 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 127) the anti-TL 1A antibody of embodiment 1, comprising a220. (embodiment 128) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:102, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 129) the anti-TL 1A antibody of embodiment 1, comprising a223. (embodiment 130) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:103, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 131) the anti-TL 1A antibody of embodiment 1, comprising a219. (embodiment 132) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:104, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 133) an anti-TL 1A antibody as described in embodiment 1, comprising a221. (embodiment 134) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:105 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 135) an anti-TL 1A antibody as described in embodiment 1, comprising a200. (embodiment 136) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:103, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 137) an anti-TL 1A antibody as described in embodiment 1, comprising a213. (embodiment 138) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:106 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 139) the anti-TL 1A antibody as described in embodiment 1, comprising a212. (embodiment 140) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:107 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 141) an anti-TL 1A antibody as described in embodiment 1, comprising a107. (embodiment 142) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:108 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 143) an anti-TL 1A antibody as described in embodiment 1, comprising a205. (embodiment 144) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:109, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 145) an anti-TL 1A antibody as described in embodiment 1, comprising a211. (embodiment 146) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:108 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 147) the anti-TL 1A antibody of embodiment 1, comprising a199. (embodiment 148) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:109, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 149) the anti-TL 1A antibody as described in embodiment 1, comprising a15. (embodiment 150) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:108 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:203 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 151) an anti-TL 1A antibody as described in embodiment 1, comprising a30. (embodiment 152) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:108 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 153) the anti-TL 1A antibody of embodiment 1, comprising a100. (embodiment 154) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:107 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 155) an anti-TL 1A antibody as described in embodiment 1, comprising a181. (embodiment 156) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:107 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 157) the anti-TL 1A antibody of embodiment 1, comprising a129. (embodiment 158) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:110, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 159) the anti-TL 1A antibody of embodiment 1, comprising a214. (embodiment 160) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:111 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 161) the anti-TL 1A antibody of embodiment 1, comprising a216. (embodiment 162) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:112, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 163) an anti-TL 1A antibody as described in embodiment 1, comprising a122. (embodiment 164) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:113, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 165) the anti-TL 1A antibody of embodiment 1, comprising a222. (embodiment 166) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:114, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 167) an anti-TL 1A antibody as described in embodiment 1, comprising a188. (embodiment 168) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:115, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 169) an anti-TL 1A antibody as described in embodiment 1, comprising a203. (embodiment 170) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:116 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 171) an anti-TL 1A antibody as described in embodiment 1, comprising a147. (embodiment 172) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:117 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence that is identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 173) the anti-TL 1A antibody of embodiment 1, comprising a127. (embodiment 174) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:118, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 175) the anti-TL 1A antibody as described in embodiment 1, comprising a126. (embodiment 176) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:114, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 177) the anti-TL 1A antibody as described in embodiment 1, comprising a160. (embodiment 178) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:102, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 179) an anti-TL 1A antibody as described in embodiment 1, comprising a157. (embodiment 180) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:104, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 181) an anti-TL 1A antibody as described in embodiment 1, comprising a159. (embodiment 182) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:119, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 183) an anti-TL 1A antibody as described in embodiment 1, comprising a218. (embodiment 184) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:119, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 185) an anti-TL 1A antibody as described in embodiment 1, comprising a158. (embodiment 186) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:101 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 187) the anti-TL 1A antibody as described in embodiment 1, comprising a125. (embodiment 188) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:105 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 189) an anti-TL 1A antibody as described in embodiment 1, comprising a103. (embodiment 190) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:120, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 191) the anti-TL 1A antibody as described in embodiment 1, comprising a64. (embodiment 192) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:121, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 193) the anti-TL 1A antibody as described in embodiment 1, comprising a67. (embodiment 194) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:122, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 195) an anti-TL 1A antibody as described in embodiment 1, comprising a138. (embodiment 196) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:122, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:204 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 197) an anti-TL 1A antibody as described in embodiment 1, comprising a68. (embodiment 198) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:123, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 199) the anti-TL 1A antibody as described in embodiment 1, comprising a94. (embodiment 200) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:124, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:202 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 201) an anti-TL 1A antibody as described in embodiment 1, comprising a110. (embodiment 202) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:125 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 203) the anti-TL 1A antibody as described in embodiment 1, comprising a197. (embodiment 204) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:116 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 205) an anti-TL 1A antibody as described in embodiment 1, comprising a112. (embodiment 206) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:117 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence that is identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 207) an anti-TL 1A antibody as described in embodiment 1, comprising a169. (embodiment 208) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:126, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 209) the anti-TL 1A antibody of embodiment 1, comprising a173. (embodiment 210) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:127 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 211) an anti-TL 1A antibody as described in embodiment 1, comprising a179. (embodiment 212) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:127 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 213) an anti-TL 1A antibody as described in embodiment 1, comprising a148. (embodiment 214) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:121, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 215) the anti-TL 1A antibody of embodiment 1, comprising a115. (embodiment 216) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:122, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 217) the anti-TL 1A antibody of embodiment 1, comprising a149. (embodiment 218) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:122, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 219) an anti-TL 1A antibody as described in embodiment 1, comprising a134. (embodiment 220) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:122, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:206 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 221) the anti-TL 1A antibody as described in embodiment 1, comprising a113. (embodiment 222) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:124, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 223) the anti-TL 1A antibody of embodiment 1, comprising a151. (embodiment 224) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:124, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 is at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 225) the anti-TL 1A antibody of embodiment 1, comprising a96. (embodiment 226) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:128 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 227) the anti-TL 1A antibody of embodiment 1, comprising a132. (embodiment 228) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:128 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:206 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 229) an anti-TL 1A antibody as described in embodiment 1 comprising a196. (embodiment 230) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:129, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 231) an anti-TL 1A antibody as described in embodiment 1, comprising a172. (embodiment 232) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:130, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 233) an anti-TL 1A antibody as described in embodiment 1, comprising a75. (embodiment 234) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:131 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical.

(embodiment 235) an anti-TL 1A antibody as described in embodiment 1, comprising a174. (embodiment 236) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:132, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 237) the anti-TL 1A antibody as described in embodiment 1, comprising a109. (embodiment 238) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:133, and the light chain variable region comprises a sequence at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 239) an anti-TL 1A antibody as described in embodiment 1, comprising a198. (embodiment 240) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence that hybridizes to SEQ ID NO:134 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 241) an anti-TL 1A antibody as described in embodiment 1, comprising a170. (embodiment 242) the anti-TL 1A antibody of embodiment 1, wherein said heavy chain variable region comprises an amino acid sequence which hybridizes to SEQ ID NO:135 at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical, and the light chain variable region comprises a sequence identical to SEQ ID NO:205 are at least about 90%, 95%, 96%, 97%, 98%, 99% or 100% identical. (embodiment 243) the anti-TL 1A antibody as described in embodiment 1, comprising a500. (embodiment 244) an anti-TL 1A antibody as described in embodiment 1, comprising a501.

(embodiment 245) the anti-TL 1A of any one of embodiments 1 to 244, comprising a human IgG1 Fc region comprising: (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) 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) G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G a and P331S, (bbb) L234A, L235 82348 237A, (bbb) 238S, H S and P331S (IgG 1 σ268), (ccc) L234A, L a and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hh) D a, (iii) D and N297A, (jj a and N) j) N and (k) 265A, (karn) and (G331A) (or any combination (mm) 331A) - (G) 331A (mm) 331S (G) or (mm) 331A). (embodiment 246) the anti-TL 1A of any one of embodiments 1 to 244, comprising (i) a human IgG4 Fc region, or (ii) a human IgG4 Fc region comprising: (a) S228P and L235E, or (b) S228P, F234A and L235A, numbered according to Kabat. (embodiment 247) the anti-TL 1A of any one of embodiments 1 to 244, comprising a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. (embodiment 248) the anti-TL 1A of any one of embodiments 1 to 247, comprising an amino acid sequence comprising SEQ ID NO: 320-362. (embodiment 249) the anti-TL 1A of any one of embodiments 1 to 248, comprising an amino acid sequence comprising SEQ ID NO: 319.

(embodiment 250) the anti-TL 1A of any one of embodiments 1 to 249, comprising at least about 80% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 251) the anti-TL 1A of any one of embodiments 1 to 250, comprising at least about 81%, at least about 82%, at least about 83% or at least about 84% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 252) the anti-TL 1A of any one of embodiments 1 to 251, comprising at least about 85% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 253) the anti-TL 1A of any one of embodiments 1 to 252, comprising at least about 86%, at least about 87%, at least about 88%, or at least about 89% monomeric moieties as determined by the size exclusion chromatography methods described herein. (embodiment 254) the anti-TL 1A of any one of embodiments 1 to 253, comprising at least about 90% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 255) the anti-TL 1A of any one of embodiments 1 to 254, comprising at least about 91%, at least about 92%, at least about 93% or at least about 94% monomeric moieties as determined by the size exclusion chromatography methods described herein. (embodiment 256) the anti-TL 1A of any one of embodiments 1 to 255, comprising at least about 95% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 257) the anti-TL 1A of any one of embodiments 1 to 256, comprising at least about 96%, at least about 97%, at least about 98% or at least about 99% monomeric moieties as determined by the size exclusion chromatography methods described herein.

(embodiment 258) the anti-TL 1A of any one of embodiments 1 to 257, comprising an expression of at least about 2 μg/mL, as determined by the methods disclosed herein. (embodiment 259) the anti-TL 1A of any one of embodiments 1 to 258, comprising expression of about 2 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. (embodiment 260) the anti-TL 1A of any one of embodiments 1 to 259, comprising expression of about 5 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. (embodiment 261) the anti-TL 1A of any one of embodiments 1 to 260, comprising expression of about 10 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. (embodiment 262) the anti-TL 1A of any one of embodiments 1 to 261, comprising expression of at least about 5 μg/mL as determined by the methods disclosed herein. (embodiment 263) the anti-TL 1A of any one of embodiments 1 to 262, comprising an expression of at least about 10 μg/mL as determined by the methods disclosed herein. (embodiment 264) the anti-TL 1A of any one of embodiments 1 to 263, comprising an expression of at least about 15 μg/mL as determined by the methods disclosed herein. (embodiment 265) the anti-TL 1A of any one of embodiments 1 to 264, comprising an expression of at least about 20 μg/mL as determined by the methods disclosed herein.

In one aspect, provided herein is an anti-TL 1A antibody comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1200-1263 of at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1264-1300, 1304-1316 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.

In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:136 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 34). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1200 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:12646 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (5C 3D 11). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1201 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1265 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (9E 12E 5). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1202 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:208 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (AS 12824). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1266 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (AS 12823). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1204 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1267 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (AS 12819). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1205 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1268 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (AS 12816). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1206 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1269 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (AS 12825). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1207 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1270 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (12835). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7S 93E). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1272 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7S 92D). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1273 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7S 92H). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1274 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7S 92N). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7S 92Q). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1208 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1276 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (18-7 CDRv). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1209 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1210 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3V 102K). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1211 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3V 102M). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1212 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3V 102Q). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1213 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3V 102W). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1214 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3 CDRv). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1215 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1271 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (21-3 CDRv). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1216 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 2). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1216 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1277 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 52). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1217 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 46). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1218 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 47). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1219 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 14). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1220 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 16L). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1221 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 17L). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1222 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 17L-1). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1223 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 23). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1224 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:202 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 53). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1224 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1277 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone E1). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1225 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 3-17L V-A). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1226 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1275 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone 3-17L). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1227 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone L8 mod). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1209 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone L8). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1228 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone X-V). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1229 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone X). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1229 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1278 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone XL 3-6). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1229 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1279 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone XL 3-10). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1229 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:207 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone XL 3-15). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1229 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:204 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone L3-13). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1230 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone H3-1). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1231 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone H2-2). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1232 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:203 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (clone H2-5). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1233 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1280 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M1). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1234 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1281 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M2). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1235 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1282 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M3). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1235 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1283 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M3). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1237 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical in amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1284 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M4). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1238 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1285 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M5). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1239-1242 by at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO: any of 1286-1293 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M6). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1243-1247 of at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical; and a light chain variable region that hybridizes to SEQ ID NO:1294-1297 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M7). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1248-1259 by at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1298-1312 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M8). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1260 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1313 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M9). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1261 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1314 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M10). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1262 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1315 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M11). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1263 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:1316 is at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical (M12). In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:301 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:303 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:302 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:303 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1301 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:303 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In one aspect, an anti-TL 1A antibody is provided comprising a heavy chain variable region comprising an amino acid sequence that hybridizes to SEQ ID NO:1302 at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequence; and a light chain variable region that hybridizes to SEQ ID NO:303 are at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.

Exemplary anti-TL 1A constant region

In some embodiments, one or more amino acid modifications may be introduced to the crystallizable fragment (Fc) region of a human or humanized antibody, thereby producing an Fc region variant. The Fc region may comprise a C-terminal region of an immunoglobulin heavy chain comprising a hinge region, a CH2 domain, a CH3 domain, or any combination thereof. As used herein, fc regions include native sequence Fc regions and variant Fc regions. The Fc region variant may comprise a human Fc region sequence (e.g., a human IgG1, igG2, igG3, or IgG4 Fc region) comprising amino acid modifications (e.g., substitutions, additions, or deletions) at one or more amino acid positions. In one exemplary embodiment, the Fc region comprises SEQ ID NO:320-362, 401-413, 501-515.

In some embodiments, the antibodies of the disclosure have reduced effector function compared to human IgG. Effector function refers to a biological event resulting from the interaction of an antibody Fc region with an Fc receptor or ligand. Non-limiting effector functions include C1q binding, complement Dependent Cytotoxicity (CDC), fc receptor binding, antibody dependent cell-mediated cytotoxicity (ADCC), antibody Dependent Cell Phagocytosis (ADCP), cytokine secretion, immune complex-mediated antigen uptake by antigen presenting cells, down-regulation of cell surface receptors (e.g., B cell receptors), and B cell activation. In some cases, antibody-dependent cell-mediated cytotoxicity (ADCC) refers to a cell-mediated reaction in which nonspecific cytotoxic cells expressing Fc receptors (e.g., natural killer cells, neutrophils, macrophages) recognize bound antibody on a target cell, which subsequently causes lysis of the target cell. In some cases, complement Dependent Cytotoxicity (CDC) refers to lysis of target cells in the presence of complement, where the complement pathway is initiated by the binding of C1q to antibodies that bind to the target.

Some Fc regions naturally lack effector function, and some Fc regions may contain mutations that reduce effector function. For example, igG4 has low ADCC and CDC activity, and IgG2 has low ADCC activity.

The present disclosure provides antibodies comprising an Fc region characterized by exhibiting at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70% or more reduced ADCC as compared to an antibody comprising a non-variant Fc region (i.e., an antibody having the same sequence identity but having a substitution that reduces ADCC, such as human IgG1, SEQ ID NO: 320). The present disclosure provides antibodies comprising an Fc region characterized by exhibiting at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70% or more reduced CDC as compared to an antibody comprising a non-variant Fc region (i.e., an antibody having the same sequence identity but having a substitution that reduces CDC, such as human IgG1, SEQ ID NO: 320). In certain embodiments, the antibodies of the disclosure have reduced effector function compared to human IgG 1. Measurement of effector function may be performed as described in example 3.

Non-limiting examples of Fc mutations in IgG1 that can reduce ADCC and/or CDC include substitutions at one or more of the following positions: 231, 232, 234, 235, 236, 237, 238, 239, 264, 265, 267, 269, 270, 297, 299, 318, 320, 322, 325, 327, 328, 329, 330 and 331 in IgG1, wherein the numbering system of the constant regions is that of the EU index as set forth by Kabat. In certain embodiments, the antibodies of the disclosure have reduced effector function compared to human IgG 1.

In some embodiments, the antibody comprises an IgG1Fc region comprising an N297A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an N297Q substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an N297D substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a D265A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an S228P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an L235A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an L237A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an L234A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an E233P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an L234V substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a C236 deletion according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a P238A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an a327Q substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a P329A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a P329G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an L235E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a P331S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising an L234F substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 235G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 235Q substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 235R substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 235S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 236F substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 236R substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 237E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 237K substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 237N substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 237R substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238H substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238I substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 238V substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238W substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 238Y substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 248A substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254D substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254H substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254I substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254N substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254Q substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254T substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 254V substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 255N substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 256H substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 256K substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 256R substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 256V substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 264S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 265H substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 265K substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 265S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 265Y substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 267G substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 267H substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 267I substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 267K substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 268K substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 269N substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 269Q substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 270A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 270G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 270M substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 270N substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 271T substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 272N substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 279F substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 279K substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 279L substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 292E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 292F substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 292G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 292I substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 293S substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 301W substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 304E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 311E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 311G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 311S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 316F substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 327T substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 328V substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 329Y substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 330R substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 339E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 339L substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 343I substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 343V substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 373A substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 373G substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 373S substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 376E substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 376W substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising 376Y substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 380D substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 382D substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 382P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 385P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 424H substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 424M substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 424V substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 434I substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 438G substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 439E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 439H substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 439Q substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440A substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440D substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440E substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440F substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440M substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440T Fc region substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1Fc region comprising a 440V substitution according to the Kabat numbering system.

In some embodiments, the antibody comprises an Fc region selected from the representative sequences disclosed in table 3 or table 20. In some embodiments, the antibody comprises an IgG1 Fc region comprising E233P according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising S228P and L235E. In some embodiments, the antibody comprises an IgG1 Fc region comprising L235E according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A and L235A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235A and G237A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235A, P329G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234F, L235E and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235E and G237A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235E, G237A and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region (IgG 1 sigma) comprising L234A, L235A, G237A, P238S, H268A, A S and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising L234A, L235A and P329A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising G236R and L328R according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising G237A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising F241A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising V264A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D265A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D265A and N297A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D265A and N297G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising D270A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297D according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising N297Q according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P329A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P329G according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P329R according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising a330L according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P331A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG1 Fc region comprising P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region. In some embodiments, the antibody comprises an IgG4 Fc region. In some embodiments, the antibody comprises an IgG4 Fc region comprising S228P according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising S228P, F234A and L235A according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2-IgG4 cross-subclass (IgG 2/G4) Fc region. In some embodiments, the antibody comprises an IgG2-IgG3 cross subclass Fc region. In some embodiments, the antibody comprises an IgG2 Fc region comprising H268Q, V309L, A S and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising V234A, G237A, P238S, H268A, V309L, A330S and P331S according to the Kabat numbering system. In some embodiments, the antibody comprises an Fc region comprising high mannose glycosylation.

In some embodiments, the antibody comprises an IgG4 Fc region comprising an S228P substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising an a330S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG4 Fc region comprising a P331S substitution according to the Kabat numbering system.

In some embodiments, the antibody comprises an IgG2 Fc region comprising an a330S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising a P331S substitution according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising 234A substitutions according to the Kabat numbering system. In some embodiments, the antibody comprises an IgG2 Fc region comprising a 237A substitution according to the Kabat numbering system.

In certain embodiments, the anti-TL 1A antibodies described herein comprise an Fc region comprising a sequence from table 19. In certain embodiments, an anti-TL 1A described herein comprises an Fc region as shown in table 3.

TABLE 3 exemplary Fc mutations

In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:320 or with SEQ ID NO:320 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:321 or with SEQ ID NO:321, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:322 or with SEQ ID NO:322 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:323 or with SEQ ID NO:323 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:324 or with SEQ ID NO:324 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:325 or with SEQ ID NO:325 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:326 or with SEQ ID NO:326 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:327 or to SEQ ID NO:327 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:328 or with SEQ ID NO:328 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:329 or to SEQ ID NO:329 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:330 or with SEQ ID NO:330 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:331 or with SEQ ID NO:331 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical sequence. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:332 or with SEQ ID NO:332, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:333 or with SEQ ID NO:333 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:334 or with SEQ ID NO:334 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:335 or to SEQ ID NO:335 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:336 or with SEQ ID NO:336 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:337 or to SEQ ID NO:337 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:338 or with SEQ ID NO:338 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:339 or with SEQ ID NO:339 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:340 or with SEQ ID NO:340 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:341 or with SEQ ID NO:341 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:342 or with SEQ ID NO:342 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:343 or with SEQ ID NO:343 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:344 or with SEQ ID NO:344 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:345 or to SEQ ID NO:345 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical sequence. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:346 or with SEQ ID NO:346 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:347 or with SEQ ID NO:347 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:348 or with SEQ ID NO:348 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:349 or with SEQ ID NO:349 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:350 or with SEQ ID NO:350 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:351 or a sequence corresponding to SEQ ID NO:351 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:352 or with SEQ ID NO:352 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical sequence. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:353 or to SEQ ID NO:353 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:354 or with SEQ ID NO:354 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:355 or a sequence identical to SEQ ID NO:355 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical sequence. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:356 or with SEQ ID NO:356 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:357 or with SEQ ID NO:357 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:358 or with SEQ ID NO:358, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:359 or with SEQ ID NO:359, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:360 or with SEQ ID NO:360 of at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical sequence. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:361 or with SEQ ID NO:361 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:362 or with SEQ ID NO:362 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical.

In some embodiments, the antibodies of the present disclosure are variants with some, but not all, effector functions, which makes the antibodies candidates for use where in vivo antibody half-life is important, but some effector functions (such as complement and ADCC) are unnecessary or detrimental.

In vitro and/or in vivo cytotoxicity assays may be performed to confirm reduction/depletion of CDC and/or ADCC activity. For example, an Fc receptor (FcR) binding assay may be performed to ensure that the antibody lacks fcγr binding (and thus may lack ADCC activity), but retains FcRn binding capacity. Measurement of effector function may be performed as described in example 3.

In some embodiments, antibodies are tested for binding to fcγ receptor and complement C1q by ELISA. In some embodiments, the ability of an antibody to activate primary human immune cells in vitro is tested, for example, by assessing the ability of the antibody to induce expression of an activation marker.

In some embodiments, the assessment of ADCC activity of an anti-TL 1A antibody comprises adding the antibody to a combination of target cells and immune effector cells that can be activated by antigen-antibody complexes that result in cell lysis of the target cells. Cell lysis can be detected by releasing a label (e.g., a radioactive substrate, fluorescent dye, or native intracellular protein) from the lysed cells. Useful effector cells for such assays include Peripheral Blood Mononuclear Cells (PBMC) and Natural Killer (NK) cells. Specific examples of in vitro ADCC assays are described in Wisecarver et al, 198579:277-282; bruggemann et al, 1987,J Exp Med 166:1351-1361; wilkinson et al, 2001,J Immunol Methods 258:183-191; patel et al, 1995J Immunol Methods 184: 29-38. Alternatively, or in addition, the treatment may be in vivo, for example, in a treatment system such as Clynes et al, 1998, pnas USA 95: the ADCC activity of the antibody of interest was evaluated in an animal model as disclosed in 652-656.

In some embodiments, antibodies comprising an Fc region herein exhibit reduced ADCC activity compared to an unmodified antibody (e.g., an antibody with human IgG 1). In some embodiments, the antibodies herein exhibit ADCC activity that is at least 2-fold, or at least 3-fold, or at least 5-fold, or at least 10-fold, or at least 50-fold, or at least 100-fold lower than that of the unmodified antibody. In some embodiments, the antibodies herein exhibit at least 10%, or at least 20%, or at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90%, or at least 100%, or at least 200%, or at least 300%, or at least 400%, or at least 500% reduced ADCC activity relative to the unmodified antibody. In certain embodiments, the antibodies herein have no detectable ADCC activity. In certain embodiments, the decrease and/or attenuation of ADCC activity may be due to a decrease in affinity of the antibodies of the invention for Fc ligands and/or receptors.

In some embodiments, the assessment of complement activation (CDC assay) may be as in Gazzano-Santoro et al, 1996, J.Immunol. Methods,202:163, as described in detail below.

In some embodiments, an antibody comprising an Fc region described herein exhibits reduced affinity for C1q relative to an unmodified antibody (e.g., human IgG 1). In some embodiments, the antibodies herein exhibit at least 2-fold, or at least 3-fold, or at least 5-fold, or at least 7-fold, or at least 10-fold, or at least 20-fold, or at least 30-fold, or at least 40-fold, or at least 50-fold, or at least 60-fold, or at least 70-fold, or at least 80-fold, or at least 90-fold, or at least 100-fold, or at least 200-fold lower affinity for the C1q receptor than the unmodified antibody. In some embodiments, the antibodies herein exhibit an affinity for C1q that is at least 90%, at least 80%, at least 70%, at least 60%, at least 50%, at least 40%, at least 30%, at least 20%, at least 10%, or at least 5% lower than that of the unmodified antibody. In some embodiments, the antibodies herein exhibit an affinity for C1q of between about 100nM to about 100 μm, or about 100nM to about 10 μm, or about 100nM to about 1 μm, or about 1nM to about 100 μm, or about 10nM to about 100 μm, or about 1 μm to about 100 μm, or about 10 μm to about 100 μm. In certain embodiments, the antibodies herein exhibit an affinity for C1q of greater than 1 μΜ, greater than 5 μΜ, greater than 10 μΜ, greater than 25 μΜ, greater than 50 μΜ or greater than 100 μΜ.

In some embodiments, antibodies comprising an Fc region described herein exhibit reduced CDC activity compared to an unmodified antibody (e.g., human IgG 1). In some embodiments, an antibody herein exhibits CDC activity that is at least 2-fold, or at least 3-fold, or at least 5-fold, or at least 10-fold, or at least 50-fold, or at least 100-fold less than an unmodified antibody. In some embodiments, an antibody herein exhibits CDC activity that is reduced by at least 10%, or at least 20%, or at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90%, or at least 100%, or at least 200%, or at least 300%, or at least 400%, or at least 500% relative to an unmodified antibody. In certain embodiments, the antibodies herein do not exhibit detectable CDC activity. In some embodiments, the decrease and/or attenuation of CDC activity may be due to a decrease in affinity of an antibody of the invention for an Fc ligand and/or receptor.

Accordingly, further provided and described herein are anti-TL 1A antibodies comprising a variant (e.g., carrying a mutation) Fc region that reduces the cytotoxic response (e.g., ADCC or CDC) elicited by the anti-TL 1A antibodies. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:401 or with SEQ ID NO:401 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:402 or with SEQ ID NO:402 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:403 or with SEQ ID NO:403 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:404 or with SEQ ID NO:404 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:405 or with SEQ ID NO:405 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:406 or with SEQ ID NO:406 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:407 or with SEQ ID NO:407 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:408 or with SEQ ID NO:408 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:409 or with SEQ ID NO:409 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:410 or with SEQ ID NO:410 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:411 or with SEQ ID NO:411 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:412 or with SEQ ID NO:412 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, an anti-TL 1A antibody described herein comprises an Fc region comprising the amino acid sequence of SEQ ID NO:413 or with SEQ ID NO:413 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical.

As another example, in certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:501 or with SEQ ID NO:501 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:502 or with SEQ ID NO:502 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:503 or a sequence corresponding to SEQ ID NO:503 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:504 or with SEQ ID NO:504 are at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:505 or with SEQ ID NO:505 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:506 or with SEQ ID NO:506 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:507 or with SEQ ID NO:507 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:508 or with SEQ ID NO:508 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:509 or with SEQ ID NO:509 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:510 or with SEQ ID NO:510 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:511 or a sequence identical to SEQ ID NO:511 is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:512 or with SEQ ID NO:512 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical sequence. In certain embodiments, an anti-TL 1A antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:513 or with SEQ ID NO:513 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, the heavy chain is paired with a light chain comprising the amino acid sequence of SEQ ID NO:514 or with SEQ ID NO:514 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In certain embodiments, the heavy chain hybridizes to SEQ ID NO:514 or light chain variable region of SEQ ID NO:514, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In certain embodiments, the heavy chain hybridizes to SEQ ID NO:514 or light chain variable region of SEQ ID NO:515, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical.

In some embodiments, an anti-TL 1A described herein comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO:319 or with SEQ ID NO:319 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical.

Other non-limiting exemplary anti-TL 1A antibodies

In one aspect, provided herein is a first embodiment of an anti-TL 1A antibody comprising: heavy chains comprising HCDR1, HCDR2 and HCDR3, and light chains comprising LCDR1, LCDR2 and LCDR3. Additional non-limiting embodiments include: (embodiment 2) an anti-TL 1A antibody as described in embodiment 1 comprising an amino acid sequence comprising SEQ ID NO: HCDR1 of 1. (embodiment 3) the anti-TL 1A antibody as described in embodiment 1 or embodiment 2, comprising an amino acid sequence comprising SEQ ID NO: HCDR2 of 2. (embodiment 4) the anti-TL 1A antibody as described in embodiment 1 or embodiment 2, comprising an amino acid sequence comprising SEQ ID NO: HCDR2 of 3. (embodiment 5) the anti-TL 1A antibody as described in embodiment 1 or embodiment 2, comprising an amino acid sequence comprising SEQ ID NO: HCDR2 of 4. (embodiment 6) the anti-TL 1A antibody as described in embodiment 1 or embodiment 2, comprising an amino acid sequence comprising SEQ ID NO: HCDR2 of 5. (embodiment 7) the anti-TL 1A antibody of any one of embodiments 1 to 6, comprising an amino acid sequence comprising SEQ ID NO: HCDR3 of 6. (embodiment 8) the anti-TL 1A antibody of any one of embodiments 1 to 6, comprising an amino acid sequence comprising SEQ ID NO: HCDR3 of 7. (embodiment 9) the anti-TL 1A antibody of any one of embodiments 1 to 6, comprising an amino acid sequence comprising SEQ ID NO: HCDR3 of 8. (embodiment 10) the anti-TL 1A antibody of any one of embodiments 1 to 6, comprising an amino acid sequence comprising SEQ ID NO: HCDR3 of 9. (embodiment 11) the anti-TL 1A antibody of any one of embodiments 1 to 10, comprising an amino acid sequence comprising SEQ ID NO: LCDR1 of 10. (embodiment 12) the anti-TL 1A antibody of any one of embodiments 1 to 11, comprising an amino acid sequence comprising SEQ ID NO: LCDR2 of 11. (embodiment 13) the anti-TL 1A antibody of any one of embodiments 1 to 12, comprising an amino acid sequence comprising SEQ ID NO: LCDR3 of 12. (embodiment 14) the anti-TL 1A antibody of any one of embodiments 1 to 12, comprising an amino acid sequence comprising SEQ ID NO: LCDR3 of 13. (embodiment 15) the anti-TL 1A antibody of any one of embodiments 1 to 12, comprising an amino acid sequence comprising SEQ ID NO: LCDR3 of 14 or 15.

(embodiment 16) the anti-TL 1A antibody of any one of embodiments 1 to 15, comprising a heavy chain framework comprising IGHV1-46 x 02. (embodiment 17) the anti-TL 1A antibody of any one of embodiments 1 to 15, comprising a heavy chain framework comprising a variant of IGHV1-46 x 02 which hybridizes to SEQ ID NO:316 comprises about 1 to about 20 amino acid substitutions. (embodiment 18) the anti-TL 1A antibody of any one of embodiments 1 to 15, comprising a heavy chain framework comprising a variant of IGHV1-46 x 02 which hybridizes to SEQ ID NO:316 comprises about 1 to about 9 amino acid substitutions. (embodiment 19) the anti-TL 1A antibody of any one of embodiments 1 to 15, comprising a heavy chain framework comprising a variant of IGHV1-46 x 02 which hybridizes to SEQ ID NO:316 comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the frame. (embodiment 20) the anti-TL 1A antibody of any one of embodiments 17 to 19, wherein said heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. (embodiment 21) the anti-TL 1A antibody of any one of embodiments 17 to 20, wherein said heavy chain framework substitution comprises R45K, as determined by Aho or Kabat numbering. (embodiment 22) the anti-TL 1A antibody of any one of embodiments 17 to 21, wherein said heavy chain framework substitution comprises a47R, as determined by Aho or Kabat numbering. (embodiment 23) the anti-TL 1A antibody of any one of embodiments 17 to 22, wherein said heavy chain framework substitution comprises M55I as determined by Aho or Kabat numbering. (embodiment 24) the anti-TL 1A antibody of any one of embodiments 17 to 23, wherein said heavy chain framework substitution comprises V78A, as determined by Aho or Kabat numbering. (embodiment 25) the anti-TL 1A antibody of any one of embodiments 17 to 24, wherein said heavy chain framework substitution comprises M80I, as determined by Aho or Kabat numbering. (embodiment 26) the anti-TL 1A antibody of any one of embodiments 17 to 25, wherein said heavy chain framework substitution comprises R82T, as determined by Aho or Kabat numbering. (embodiment 27) the anti-TL 1A antibody of any one of embodiments 17 to 26, wherein said heavy chain framework substitution comprises V89A, as determined by Aho or Kabat numbering. (embodiment 28) the anti-TL 1A antibody of any one of embodiments 17 to 27, wherein said heavy chain framework substitution comprises M91L, as determined by Aho or Kabat numbering.

(embodiment 29) the anti-TL 1A antibody of any one of embodiments 1 to 15, comprising an amino acid sequence comprising SEQ ID NO: 301. (embodiment 30) the anti-TL 1A antibody of embodiment 29, wherein X1 is Q. (embodiment 31) the anti-TL 1A of embodiment 29, wherein x1=e. (embodiment 32) the anti-TL 1A of any one of embodiments 29 to 31, wherein x2=r. (embodiment 33) the anti-TL 1A of any one of embodiments 29 to 31, wherein x2=k. (embodiment 34) the anti-TL 1A of any one of embodiments 29 to 33, wherein x3=a. (embodiment 35) the anti-TL 1A of any one of embodiments 29 to 33, wherein x3=r. (embodiment 36) the anti-TL 1A of any one of embodiments 29 to 35, wherein x4=m. (embodiment 37) the anti-TL 1A of any one of embodiments 29 to 35, wherein x4=i. (embodiment 38) the anti-TL 1A of any one of embodiments 29 to 37, wherein x5=v. (embodiment 39) the anti-TL 1A of any one of embodiments 29 to 37, wherein x5=a. (embodiment 40) the anti-TL 1A of any one of embodiments 29 to 39, wherein x6=m. (embodiment 41) the anti-TL 1A of any one of embodiments 29 to 39, wherein x6=i. (embodiment 42) the anti-TL 1A of any one of embodiments 29 to 41, wherein x7=r. (embodiment 43) the anti-TL 1A of any one of embodiments 29 to 41, wherein x7=t. (embodiment 44) the anti-TL 1A of any one of embodiments 29 to 43, wherein x8=v. (embodiment 45) the anti-TL 1A of any one of embodiments 29 to 43, wherein x8=a. (embodiment 46) the anti-TL 1A of any one of embodiments 29 to 45, wherein x9=m. (embodiment 47) the anti-TL 1A of any one of embodiments 29 to 45, wherein x9=l.

(embodiment 48) the anti-TL 1A antibody of any one of embodiments 1 to 15, comprising an amino acid sequence comprising SEQ ID NO: 302. (embodiment 49) the anti-TL 1A antibody of embodiment 48, wherein X1 is Q. (embodiment 50) the anti-TL 1A of embodiment 48, wherein x1=e. (embodiment 51) the anti-TL 1A of any one of embodiments 48 to 50, wherein x2=r. (embodiment 52) the anti-TL 1A of any one of embodiments 48 to 50, wherein x2=k. (embodiment 53) the anti-TL 1A of any one of embodiments 48 to 52, wherein x3=a. (embodiment 54) the anti-TL 1A of any one of embodiments 48 to 52, wherein x3=r. (embodiment 55) the anti-TL 1A of any one of embodiments 48 to 54, wherein x4=m. (embodiment 56) the anti-TL 1A of any one of embodiments 48 to 54, wherein x4=i. (embodiment 57) the anti-TL 1A of any one of embodiments 48 to 56, wherein x5=v. (embodiment 58) the anti-TL 1A of any one of embodiments 48 to 56, wherein x5=a. (embodiment 59) the anti-TL 1A of any one of embodiments 48 to 58, wherein x6=m. (embodiment 60) the anti-TL 1A of any one of embodiments 48 to 58, wherein x6=i. (embodiment 61) the anti-TL 1A of any one of embodiments 48 to 60, wherein x7=r. (embodiment 62) the anti-TL 1A of any one of embodiments 48 to 60, wherein x7=t. (embodiment 63) the anti-TL 1A of any one of embodiments 48 to 62, wherein x8=v. (embodiment 64) the anti-TL 1A of any one of embodiments 48 to 62, wherein x8=a. (embodiment 65) the anti-TL 1A of any one of embodiments 48 to 64, wherein x9=m. (embodiment 66) the anti-TL 1A of any one of embodiments 48 to 64, wherein x9=l.

(embodiment 67) the anti-TL 1A antibody of any one of embodiments 1 to 66, comprising a light chain framework comprising IGKV3-20 x 01. (embodiment 68) the anti-TL 1A antibody of any one of embodiments 1 to 66, comprising a light chain framework comprising a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 1 to about 20 amino acid substitutions. (embodiment 69) the anti-TL 1A antibody of any one of embodiments 1 to 66, comprising a light chain framework comprising a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 1 amino acid substitution. (embodiment 70) the anti-TL 1A antibody of any one of embodiments 1 to 66, comprising a light chain framework comprising a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 2 amino acid substitutions. (embodiment 71) the anti-TL 1A antibody of any one of embodiments 1 to 66, comprising a light chain framework comprising a variant of IGKV3-20 x 01 that hybridizes to SEQ ID NO:317 comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions in the frame. (embodiment 72) the anti-TL 1A antibody of any one of embodiments 69 to 71, wherein said light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. (embodiment 73) the anti-TL 1A antibody of any one of embodiments 69 to 72, wherein said light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

(embodiment 74) the anti-TL 1A antibody of any one of embodiments 1 to 66, comprising a light chain framework comprising the amino acid sequence of SEQ ID NO:303. (embodiment 75) the anti-TL 1A antibody of embodiment 74, wherein X10 is L. (embodiment 76) the anti-TL 1A antibody of embodiment 74, wherein X10 is P. (embodiment 77) the anti-TL 1A antibody of any one of embodiments 74 to 76, wherein X11 is L. (embodiment 78) the anti-TL 1A antibody of any one of embodiments 74 to 76, wherein X11 is W.

(embodiment 79) the anti-TL 1A of any one of embodiments 1-78 comprising a human IgG1Fc region comprising (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) 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) D or 382P, (nn) 385P, (op) 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G a and P331S, (bbb) L234A, L235 82348 237A, P S, H268 56330S and P331S (IgG 1), (σccc) L A, L a and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) 241A, (xx) F241A, (xx) L234V 234A and P329G, (y) L234E and G237A, (aaa) L234G 35A, (aaa) N) L234G 35 b, (taa, (taaa) 35 b) 35A, (bbb) N (b) 35G 35A, (b) and P331A, (G) N) 35G (G331A, (G) 35G) and (b) 35G 330S (b) and P331A, (G1) V) (or (G1). (embodiment 80) the anti-TL 1A of any one of embodiments 1 to 78, comprising (i) a human IgG4 Fc region, or (ii) a human IgG4 Fc region comprising: (a) S228P and L235E, or (b) S228P, F234A and L235A, numbered according to Kabat. (embodiment 81) the anti-TL 1A of any one of embodiments 1 to 78, comprising a human IgG2 Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or an IgG2 (IgG 2 ≡ ≡ζ ≡ (embodiment 82)) comprising V234A, G237A, P238S, H268 32309L, A330S, P S anti-TL 1A of any one of embodiments 1-81 comprising a heavy chain Fc region (embodiment 83) comprising any one of SEQ ID NOs 320-362 comprising a light chain constant region comprising SEQ ID NO 319.

(embodiment 84) the anti-TL 1A antibody of any one of embodiments 1 to 83, comprising at least about 80% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 85) the anti-TL 1A antibody of any one of embodiments 1 to 84, comprising at least about 81%, at least about 82%, at least about 83% or at least about 84% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 86) the anti-TL 1A antibody of any one of embodiments 1 to 85, comprising at least about 85% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 87) the anti-TL 1A antibody of any one of embodiments 1 to 86, comprising at least about 86%, at least about 87%, at least about 88%, or at least about 89% monomeric moiety as determined by the size exclusion chromatography method described herein. (embodiment 88) the anti-TL 1A antibody of any one of embodiments 1 to 87, comprising at least about 90% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 89) the anti-TL 1A antibody of any one of embodiments 1 to 88, comprising at least about 91%, at least about 92%, at least about 93% or at least about 94% monomeric moieties as determined by the size exclusion chromatography methods described herein. (embodiment 90) the anti-TL 1A antibody of any one of embodiments 1 to 89, comprising at least about 95% monomeric moieties as determined by the size exclusion chromatography method described herein. (embodiment 91) the anti-TL 1A antibody of any one of embodiments 1 to 90, comprising at least about 96%, at least about 97%, at least about 98% or at least about 99% monomeric moieties as determined by the size exclusion chromatography method described herein.

(embodiment 92) the anti-TL 1A antibody of any one of embodiments 1 to 91, comprising expression of at least about 2 μg/mL as determined by the methods disclosed herein. (embodiment 93) the anti-TL 1A antibody of any one of embodiments 1 to 92, comprising expression of about 2 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. (embodiment 94) the anti-TL 1A antibody of any one of embodiments 1 to 93, comprising expression of about 5 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. (embodiment 95) the anti-TL 1A antibody of any one of embodiments 1 to 94, comprising expression of about 10 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. (embodiment 96) the anti-TL 1A antibody of any one of embodiments 1 to 95, comprising expression of at least about 5 μg/mL as determined by the methods disclosed herein. (embodiment 97) the anti-TL 1A antibody of any one of embodiments 1 to 96, comprising expression of at least about 10 μg/mL as determined by the methods disclosed herein. (embodiment 98) the anti-TL 1A antibody of any one of embodiments 1 to 97, comprising expression of at least about 15 μg/mL as determined by the methods disclosed herein. (embodiment 99) the anti-TL 1A antibody of any one of embodiments 1 to 98, comprising expression of at least about 20 μg/mL as determined by the methods disclosed herein. (embodiment 100) the anti-TL 1A antibody of any one of embodiments 1 to 91, comprising expression of about 2 μg/mL to about 50 μg/mL, about 2 μg/mL to about 40 μg/mL, about 2 μg/mL to about 30 μg/mL, about 2 μg/mL to about 20 μg/mL, about 5 μg/mL to about 50 μg/mL, about 5 μg/mL to about 40 μg/mL, about 5 μg/mL to about 30 μg/mL, about 10 μg/mL to about 50 μg/mL, about 10 μg/mL to about 40 μg/mL, or about 10 μg/mL to about 30 μg/mL, as determined by the methods disclosed herein. (embodiment 101) the anti-TL 1A antibody of any one of embodiments 1 to 91, comprising an expression of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 μg/mL as determined by the methods disclosed herein.

In some embodiments, the anti-TL 1A antibody comprises antibody a. As used herein, antibody a comprises the CDRs of antibody a in table 20. In some cases, antibody a comprises a polypeptide comprising SEQ ID NO:301 (embodiment X1VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody a comprises a polypeptide comprising SEQ ID NO:303 (embodiment EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody a comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody a comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody a comprises a constant region comprising reduced ADCC and/or CDC as compared to IgG 1. For example, antibody A comprises a human IgG1 Fc region comprising (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) 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, (ij) 373A, 373G or 373S, (kk) 376E, 376W or 376Y, (ll) 424D, (mm) D or P, (nn) 385P, (oo) H 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some cases, antibody a comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody a comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody a comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody a comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody a is expressed by FreeStyle 293-F (e.g., thermoFisher Scientific #r79007) cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody A is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody A is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL. In some cases, the viscosity of antibody a is less than about 30mPa-s. In some cases, the viscosity of antibody a is about 4mPa-s to about 30mPa-s, or about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30mPa-s. In some cases, antibody A is formulated in a solution having a viscosity of less than about 30mPa-s at a concentration of about 10mg/ml to about 170 mg/ml. In some cases, the pH of the formulation is from about 5 to about 7.5.

In some embodiments, the anti-TL 1A antibody comprises antibody B. As used herein, antibody B comprises the CDRs of antibody B in table 20. In some cases, antibody B comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQG TTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody B comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody B comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody B comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody B comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody B comprises a human IgG1 Fc region comprising (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) 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) 424D, (mm) D, or P, (nn) 385P, (oo) 301H, 376E, or 339L, (ll) 380D, or (mm) D or P 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody B comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody B is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody B is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody B is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody C. As used herein, antibody C comprises the CDRs of antibody C in table 20. In some cases, antibody C comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody C comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody C comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody C comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody C comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody C comprises a human IgG1 Fc region comprising (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) 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) 424D, (mm) D, or P, (nn) 385P, (oo) 301H, 376E, or 339L, (ll) 380D, or (mm) D or P 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some cases, antibody C comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody C comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody C is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody C is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody C is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody D. As used herein, antibody D comprises the CDRs of antibody D in table 20. In some cases, antibody D comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody D comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody D comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody D comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody D comprises a constant region with reduced ADCC and/or CDC compared to IgG 1. For example, antibody D comprises a human IgG1 Fc region comprising (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) 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) 424D, (mm) D, or P, (nn) 385P, (oo) 301H, 376E, or 339L, (ll) 380D, or (mm) D or P 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody D comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody D is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody D is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody D is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody E. As used herein, antibody E comprises the CDRs of antibody E in table 20. In some cases, antibody E comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody E comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody E comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody E comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody E comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody E comprises a human IgG1 Fc region comprising (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) 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) 424D, (mm) D, or P, (nn) 385P, (oo) 301H, 376E, or 339L, (ll) 380D, or (mm) D or P 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody E comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody E is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody E is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody E is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody F. As used herein, antibody F comprises the CDRs of antibody F in table 20. In some cases, antibody F comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody F comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody F comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody F comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody F comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody F comprises a human IgG1 Fc region comprising (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) 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) 424D, (mm) D, or P, (nn) 385P, (oo) 301H, 376E, or 339L, (ll) 380D, or (mm) D or P 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody F comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody F is expressed by FreeStyle293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody F is expressed by FreeStyle293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody F is expressed by FreeStyle293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody G. As used herein, antibody G comprises the CDRs of antibody G in table 20. In some cases, antibody G comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody G comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody G comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody G comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody G comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody G comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody G comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody G comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody G is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody G is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody G is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody H. As used herein, antibody H comprises the CDRs of antibody H in table 20. In some cases, antibody H comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQG TTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody H comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody H comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody H comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody H comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody H comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody H comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody H comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody H is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody H is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody H is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody I. As used herein, antibody I comprises the CDRs of antibody I in table 20. In some cases, antibody I comprises a polypeptide comprising SEQ ID NO:301 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody I comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody I comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody I comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody I comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody I comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody I comprises an amino acid sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody I comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody I is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody I is expressed by FreeStyle 293-F cells at an expression level of between about 2 μg/mL to about 60 μg/mL. In some cases, antibody I is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody A2. As used herein, antibody A2 comprises the CDRs of antibody A2 in table 20. In some cases, antibody A2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody A2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody A2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody A2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody A2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody A2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody A2 comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody A2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody A2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody A2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody A2 is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody B2. As used herein, antibody B2 comprises the CDRs of antibody B2 in table 20. In some cases, antibody B2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody B2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, antibody B2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody B2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody B2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody B2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody B2 comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody B2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody B2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody B2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody B2 is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody C2. As used herein, antibody C2 comprises the CDRs of antibody C2 in table 20. In some cases, antibody C2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody C2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody C2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody C2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody C2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody C2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody C2 comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody C2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody C2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody C2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody C2 is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody D2. As used herein, antibody D2 comprises the CDRs of antibody D2 in table 20. In some cases, antibody D2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody D2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody D2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody D2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody D2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody D2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody D2 comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody D2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody D2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody D2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody D2 is expressed by FreeStyle 293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody E2. As used herein, antibody E2 comprises the CDRs of antibody E2 in table 20. In some cases, antibody E2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody E2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody E2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody E2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody E2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody E2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody E2 comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody E2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody E2 is expressed by FreeStyle293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody E2 is expressed by FreeStyle293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody E2 is expressed by FreeStyle293-F cells at an expression level of between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody F2. As used herein, antibody F2 comprises the CDRs of antibody F2 in table 20. In some cases, antibody F2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody F2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody F2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody F2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody F2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody F2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody F2 comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody F2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody F2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody F2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody F2 is expressed by FreeStyle 293-F cells at an expression level between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody G2. As used herein, antibody G2 comprises the CDRs of antibody G2 in table 20. In some cases, antibody G2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody G2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody G2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody G2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody G2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody G2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody G2 comprises a sequence identical to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody G2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody G2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody G2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody G2 is expressed by FreeStyle 293-F cells at an expression level between about 10 μg/mL to about 60 μg/mL.

In some embodiments, the anti-TL 1A antibody comprises antibody H2. As used herein, antibody H2 comprises the CDRs of antibody H2 in table 20. In some cases, antibody H2 comprises a polypeptide comprising SEQ ID NO:302 (x1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), wherein x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, and x9=m or L. In some cases, antibody H2 comprises a polypeptide comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] wyqkpgqaprx 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein x10=l or P and x11=l or W. In some cases, the antibody H2 comprises a heavy chain variable region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, wherein the modified human IGHV1-46 x 02 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, antibody H2 comprises a light chain variable region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework, wherein the modified human IGKV3-20 framework has less than or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid substitutions in the framework. In some cases, the antibody H2 comprises a constant region with reduced ADCC and/or CDC as compared to IgG 1. For example, antibody H2 comprises a human IgG1Fc region comprising (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) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:320 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:321 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:322 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:323 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:324 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:325 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:326 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:327 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:328 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:329 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:330 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:331 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:332 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:333 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:334 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:335 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:336 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:337 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:338 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:339 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:340 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:341 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:342 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:343 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:344 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:345 have a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:346 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:347 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:348 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:349 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:350 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:351 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:352 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:353 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:354 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:355 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:356 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:357 has a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:358 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:359 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:360 have a constant region of at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:361 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical. In some cases, antibody H2 comprises a sequence that hybridizes to SEQ ID NO:362 has a constant region that is at least about 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some cases, antibody H2 comprises at least about 80%, 81%, 82%, 83%, 84%, 85%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties as measured by the size exclusion method described in example 2. In some cases, antibody H2 is expressed by FreeStyle 293-F cells at an expression level of about or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5, 57, 58, 59, or 60 μg/mL as determined by the method described in example 2. In some cases, antibody H2 is expressed by FreeStyle 293-F cells at an expression level between about 2 μg/mL to about 60 μg/mL. In some cases, antibody H2 is expressed by FreeStyle 293-F cells at an expression level between about 10 μg/mL to about 60 μg/mL.

The TL1A antibodies described herein bind to specific regions or epitopes of human TL1A that are demonstrated herein to be useful in inhibiting interferon gamma secretion by T lymphocytes. Various embodiments provide anti-TL 1A antibodies that bind to the same regions of a TL1A protein or portion thereof as reference antibodies, such as anti-TL 1A antibodies described herein. In some embodiments, the reference antibody comprises antibody A, B, C, D, E, F, G, H, A, B2, C2, D2, E2, F2, G2, or H2, or a combination thereof. In some embodiments, provided herein are anti-TL 1A antibodies that specifically bind to the same region of TL1A as a reference antibody comprising a sequence that is identical to SEQ ID NO:104, and comprises a heavy chain sequence that is at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical. In some embodiments, provided herein are anti-TL 1A antibodies that specifically bind to the same region of TL1A as a reference antibody comprising a sequence that is identical to SEQ ID NO:107, and comprises a heavy chain sequence that is at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:201 at least about 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.

Non-limiting methods are provided for determining whether an anti-TL 1A antibody (i.e., a test antibody) binds to the same region of a TL1A protein or portion thereof as an antibody described herein. One exemplary embodiment includes a competition assay. For example, the method includes determining whether the test antibody competes with binding between the reference antibody and the TL1A protein or portion thereof, or determining whether the reference antibody competes with binding between the test antibody and the TL1A protein or portion thereof. An exemplary method includes using surface plasmon resonance to assess whether an anti-TL 1A antibody can compete with binding between TL1A and another anti-TL 1A antibody. In some cases, surface plasmon resonance is used for competition assays. Non-limiting methods are described in the examples.

In certain embodiments, disclosed herein are antibodies that compete with the antibodies described herein for binding to TL 1A. In certain embodiments, disclosed herein are antibodies that bind to discrete epitopes that overlap with epitopes of TL1A bound by antibodies described herein. In certain embodiments, disclosed herein are antibodies that bind to a polypeptide comprising SEQ ID NO:104 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:201 or a fragment thereof binds to the same epitope of TL1A, overlaps with an epitope of TL1A by one or more amino acid residues, or competes for binding to an epitope of TL 1A. In certain embodiments, disclosed herein are antibodies that bind to a polypeptide comprising SEQ ID NO:107 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:201 or a fragment thereof binds to the same epitope of TL1A, overlaps with an epitope of TL1A by one or more amino acid residues, or competes for binding to an epitope of TL 1A.

Additional antibody embodiments

In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region comprise less than 9 amino acid modifications in total compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework. In some embodiments, the amino acid modification comprises: (a) a modification at amino acid position 47 in the heavy chain variable region; (b) a modification at amino acid position 45 in the heavy chain variable region; (c) a modification at amino acid position 55 in the heavy chain variable region; (d) a modification at amino acid position 78 in the heavy chain variable region; (e) a modification at amino acid position 80 in the heavy chain variable region; (f) a modification at amino acid position 82 in the heavy chain variable region; (g) a modification at amino acid position 89 in the heavy chain variable region; or (h) a modification at amino acid position 91 in the heavy chain variable region; numbering according to Aho or Kabat; or a combination of two or more modifications selected from (a) to (h). In some embodiments, (a) the amino acid modification is located at position 47 in the heavy chain variable region, and the amino acid at position 47 is R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (b) The amino acid modification is at position 45 in the heavy chain variable region, and the amino acid at position 45 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (c) The amino acid modification is located at position 55 in the heavy chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; (d) The amino acid modification is located at position 78 in the heavy chain variable region, and the amino acid at position 78 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y; (e) The amino acid modification is located at position 80 in the heavy chain variable region, and the amino acid at position 80 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; (f) Amino acid modification is located at position 82 in the heavy chain variable region, and the amino acid at position 82 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (g) The amino acid modification is at position 89 in the heavy chain variable region, and the amino acid at position 89 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y; or (h) the amino acid modification is at position 91 in the heavy chain variable region, and the amino acid at position 91 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; or a combination of two or more modifications selected from (a) to (h). In some embodiments, the amino acid modification comprises one or more of the following: a47R, R45K, M55I, V A, M80I, R82T, V3589A, M91L in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid modification comprises: (a) a modification at amino acid position 54 in the light chain variable region; and/or (b) a modification at amino acid position 55 in the light chain variable region; numbered according to Aho or Kabat. In some embodiments, (a) the amino acid modification is at position 54 of the light chain variable region, and the amino acid at position 54 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V; and/or (b) the amino acid modification is at position 55 of the light chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid modification comprises L54P and/or L55W in the light chain variable region according to the Aho or Kabat numbering. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:1, as set forth by SEQ ID NO:2-5, a heavy chain CDR2 as set forth by any one of SEQ ID NOs: 6-9, a heavy chain CDR3 as set forth by any one of SEQ ID NOs: 10, as set forth by SEQ ID NO:11 and a light chain CDR2 as set forth by SEQ ID NO:12-15, and a light chain CDR3 as set forth in any one of claims 12-15. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:1, as set forth by SEQ ID NO:2, as set forth by SEQ ID NO:6, a heavy chain CDR3 as set forth by SEQ ID NO:10, as set forth by SEQ ID NO:11 and a light chain CDR2 as set forth by SEQ ID NO:12, and a light chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:304, a heavy chain Framework (FR) 1 as set forth by SEQ ID NO:305 or SEQ ID NO:313, a heavy chain FR2 as represented by SEQ ID NO: 306. 307, 314 or 315, as represented by any one of SEQ ID NOs: 308, as represented by SEQ ID NO:309, the light chain FR1 as represented by SEQ ID NO:310, a light chain FR2 as represented by SEQ ID NO:311 or the light chain FR3 as represented by SEQ ID NO:312, or a combination thereof. In some embodiments, the antibody or antigen binding fragment comprises a human IgG1Fc region comprising (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) 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) D or P, (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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L E, G a and P331S, (bbb) L234A, L, (82348 237A, P) 238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L a and P, (ddd) G236R and L328R, (eee) G237A, (fff 241A, (ggg) V234A and P329G, (y) L234F, L a and P331S, (zz) L234G 35A, (zz) and (G) N) 35A, (can be selected from any of (mm) and (mm) or (mm) N (mm) and (mm) 330A (mm) or (mm) 330G (mm). In some embodiments, the antibody or antigen binding fragment comprises a human IgG4Fc region. In some embodiments, the antibody or antigen binding fragment comprises an Fc region comprising an amino acid sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, the antibody or antigen binding fragment comprises at least about 80% monomeric moieties, as determined by size exclusion chromatography. In some embodiments, the antibody or antigen binding fragment expresses at least about 20ug/mL total antibody, optionally about 20ug/mL and 70ug/mL total antibody.

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide that binds to SEQ ID NO:104, and a heavy chain variable domain comprising an amino acid sequence at least 96% identical to SEQ ID NO:201, a light chain variable domain of an amino acid sequence that is at least 97% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least 97% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least 98% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least 99% identical. In some embodiments, the heavy chain variable domain comprises SEQ ID NO:104. in some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 is at least 98% identical. In some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 is at least about 99% identical. In some embodiments, the light chain variable domain comprises SEQ ID NO:201.

in another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide that binds to SEQ ID NO:101-135, and a heavy chain variable domain comprising an amino acid sequence at least about 99% identical to any one of SEQ ID NOs: 201-206, a light chain variable domain of an amino acid sequence that is at least about 99% identical.

In some embodiments, an antibody or antigen binding fragment described herein comprises a human IgG1Fc region comprising (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) 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) D or P, (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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L E, G a and P331S, (bbb) L234A, L, (82348 237A, P) 238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L a and P, (ddd) G236R and L328R, (eee) G237A, (fff 241A, (ggg) V234A and P329G, (y) L234F, L a and P331S, (zz) L234G 35A, (zz) and (G) N) 35A, (can be selected from any of (mm) and (mm) or (mm) N (mm) and (mm) 330A (mm) or (mm) 330G (mm). In some embodiments, an antibody or antigen binding fragment described herein comprises a human IgG4Fc region. In some embodiments, an antibody or antigen binding fragment described herein comprises an Fc region comprising an amino acid sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, an antibody or antigen binding fragment described herein comprises at least about 80% monomeric moieties as determined by size exclusion chromatography. In some embodiments, the antibodies or antigen binding fragments described herein express at least about 20ug/mL total antibody, optionally about 20ug/mL and 70ug/mL total antibody.

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15; and a crystallizable fragment (Fc) region comprising reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and/or reduced complement-dependent cytotoxicity (CDC) as compared to human IgG 1. In some embodiments, human IgG1 comprises SEQ ID NO:320. in some embodiments, the ADCC function comprising the Fc region of reduced ADCC is reduced by at least about 50% compared to human IgG 1. In some embodiments, the CDC function of the Fc region comprising reduced CDC is reduced by at least about 50% as compared to human IgG 1. In some embodiments, the Fc region comprises a human IgG1 comprising (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) 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) 424D, (mm) D, or P, (nn) 385P, (oo) 301H, 376E, or 339L, (ll) 380D, or (mm) D or P 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L35237A and P331S, (bbb) L234A, L235 82348 237A, P S, H268A, A S and P331S (IgG 1 sigma), (ccc) L234A, L235A and P329A, (ddd) G236R and L328R, (eee) G237A, (F) F241A, (ggg) V264A, (hfiii) D) 265A and N297A, (E) N) G297A, (N) G331S, (mm) G331S, (b) N) G331A, (mm) G (G) or (mm) 331A (mm) G (mm) or (pp). In some embodiments, the antibody or antigen binding fragment comprises (i) a human IgG4Fc region, or (ii) a human IgG4Fc region comprising: (a) S228P, (b) S228P and L235E, or (c) S228P, F234A and L235A, numbered according to Kabat. In some embodiments, the antibody or antigen binding fragment comprises a human IgG2Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. In some embodiments, the Fc region comprises a human IgG1 having a substitution 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, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T and 440V, numbered according to Kabat. In some embodiments, the antibody or antigen binding fragment comprises a sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, HCDR1 comprises SEQ ID NO:1, hcdr2 comprises SEQ ID NO:2-5, HCDR3 comprises SEQ ID NO:6-9, LCDR1 comprises SEQ ID NO:10, lcdr2 comprises SEQ ID NO:11, and LCDR3 comprises SEQ ID NO: 12-15. In some embodiments, the Fc region comprises SEQ ID No:401-413 or with any one of SEQ ID nos: 401-413, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, the heavy chain comprises SEQ ID No:501-513 or with any one of SEQ ID nos: 501-513, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical. In some embodiments, the light chain comprises SEQ ID NO:514 or any one of SEQ ID NO:514 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, HCDR2 comprises SEQ ID NO:2, hcdr3 comprises SEQ ID NO:6, and LCDR3 comprises SEQ ID NO:12, and wherein the Fc region comprises SEQ ID No:401-413 or with any one of SEQ ID nos: 401-413, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical. In some embodiments, the antibody or antigen binding fragment comprises at least about 80% monomeric moieties, as determined by size exclusion chromatography. In some embodiments, the antibody or antigen binding fragment expresses at least about 20ug/mL total antibody, optionally about 20ug/mL and 70ug/mL total antibody.

Also provided are methods of treating a fibrosis or an inflammatory condition, disease, or disorder in the gut in a subject in need thereof, the method comprising administering to the subject an antibody or antigen-binding fragment of any of the antibodies or antigen-binding fragments disclosed herein. In some embodiments, the subject has fibrosis. In some embodiments, the subject has an inflammatory condition, disease, or disorder of the gut. In some embodiments, the inflammatory condition, disease, or disorder of the gut includes Inflammatory Bowel Disease (IBD). In some embodiments, the IBD comprises crohn's disease. In some embodiments, the IBD comprises ulcerative colitis.

In some embodiments, the antibody or antigen-binding fragment described herein is present in the liquid composition at a concentration of 10mg/ml to 170mg/ml of antibody or antigen-binding fragment. In some embodiments, the concentration of the antibody or antigen binding fragment thereof is from 10mg/ml to 170mg/ml. In some embodiments, the viscosity is about 4 to about 30mPa-s (mPa-s). In some embodiments, the viscosity is from about 4 to about 10mPa-s (mPa-s).

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region together comprise less than about 14 amino acid modifications as compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework. In some embodiments, the heavy chain variable framework region and the light chain variable framework region comprise a total of 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 amino acid modifications, or no amino acid modifications, as compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework. In some embodiments, the amino acid modification comprises a modification at amino acid position 1 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 1 comprises A, R, N, D, C, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 1 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 1 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 1 comprises E. In some embodiments, the amino acid modification comprises a modification at amino acid position 45 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 45 comprises A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 45 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 45 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 45 comprises K. In some embodiments, the amino acid modification comprises a modification at amino acid position 47 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 47 comprises R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 47 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 47 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 47 comprises R. In some embodiments, the amino acid modification comprises a modification at amino acid position 55 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 55 comprises A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 55 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 55 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 55 comprises I. In some embodiments, the amino acid modification comprises a modification at amino acid position 78 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 78 comprises A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y. In some embodiments, the amino acid at position 78 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 78 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 78 comprises a. In some embodiments, the amino acid modification comprises a modification at amino acid position 80 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 80 comprises A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 80 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 80 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 80 comprises I. In some embodiments, the amino acid modification comprises a modification at amino acid position 82 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 82 comprises A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 82 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 82 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 82 comprises T. In some embodiments, the amino acid modification comprises a modification at amino acid position 89 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 89 comprises A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y. In some embodiments, the amino acid at position 89 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 89 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 89 comprises a. In some embodiments, the amino acid modification comprises a modification at amino acid position 91 in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 91 comprises A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 91 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 91 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 91 comprises L.

In some embodiments, the amino acid modification comprises one or more of the following: Q1E, R45K, A47R, M I, V78A, M80I, R82T, V89A, M91L in the heavy chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid modification comprises Q1E. In some embodiments, the amino acid modification comprises R45K. In some embodiments, the amino acid modification comprises a47R. In some embodiments, the amino acid modification comprises M55I. In some embodiments, the amino acid modification comprises V78A. In some embodiments, the amino acid modification comprises M80I. In some embodiments, the amino acid modification comprises R82T. In some embodiments, the amino acid modification comprises V89A. In some embodiments, the amino acid modification comprises M91L.

In some embodiments, the amino acid modification comprises a modification at amino acid position 54 in the light chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 54 comprises A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 54 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 54 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 54 comprises P. In some embodiments, the amino acid modification comprises a modification at amino acid position 55 in the light chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid at position 55 comprises A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V. In some embodiments, the amino acid at position 55 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, the amino acid at position 55 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, the amino acid at position 55 comprises W.

In some embodiments, the amino acid modification comprises L54P and/or L55W in the light chain variable region, numbered according to Aho or Kabat. In some embodiments, the amino acid modification comprises L54P. In some embodiments, the amino acid modification comprises L55W.

In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:1, and a heavy chain CDR1. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:2, and a heavy chain CDR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:3, and a heavy chain CDR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:4, and a heavy chain CDR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:5, and a heavy chain CDR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:6, and a heavy chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:7, and a heavy chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:8, and a heavy chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:9, and a heavy chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:10, and a light chain CDR1. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:11, and a light chain CDR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:12, and a light chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:13, and a light chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:14, and a light chain CDR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:15, and a light chain CDR3.

In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:304, and a heavy chain FR1. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:305, heavy chain FR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:313, and a heavy chain FR2. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:306, and heavy chain FR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:307, heavy chain FR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:314, and a heavy chain FR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:315, heavy chain FR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:308, and a heavy chain FR4. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:309, light chain FR1. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:310, and a light chain FR2 indicated. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:311, light chain FR3. In some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:312, and a light chain FR4.

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising: (a) a heavy chain variable region comprising SEQ ID NO:301 (X1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [ HCDR3] WGQGTTVTVSS), and (b) a light chain variable region comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V.

In some embodiments, X1 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X1 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X2 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X2 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X3 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X3 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X4 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X4 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X5 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X5 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X6 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X6 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X7 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X7 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X8 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X8 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X9 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X9 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X10 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X10 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X11 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X11 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid.

In some embodiments, x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, x9=m or L, x10=l or P, and x11=l or W. In some embodiments, x1=q. In some embodiments, x1=e. In some embodiments, x2=r. In some embodiments, x2=k. In some embodiments, x3=a. In some embodiments, x3=r. In some embodiments, x4=m. In some embodiments, x4=i. In some embodiments, x5=v. In some embodiments, x5=a. In some embodiments, x6=m. In some embodiments, x6=i. In some embodiments, x7=r. In some embodiments, x7=t. In some embodiments, x8=v. In some embodiments, x8=a. In some embodiments, x9=m. In some embodiments, x9=l. In some embodiments, x10=l. In some embodiments, x10=p. In some embodiments, x11=l. In some embodiments, x11=w.

In some embodiments, HCDR1 comprises SEQ ID NO:1. in some embodiments, HCDR2 comprises SEQ ID NO:2. in some embodiments, HCDR2 comprises SEQ ID NO:3. in some embodiments, HCDR2 comprises SEQ ID NO:4. in some embodiments, HCDR2 comprises SEQ ID NO:5. in some embodiments, HCDR3 comprises SEQ ID NO:6. in some embodiments, HCDR3 comprises SEQ ID NO:7. in some embodiments, HCDR3 comprises SEQ ID NO:8. in some embodiments, HCDR3 comprises SEQ ID NO:9. in some embodiments, LCDR1 comprises SEQ ID NO:10. in some embodiments, LCDR2 comprises SEQ ID NO:11. in some embodiments, LCDR3 comprises SEQ ID NO:12. in some embodiments, LCDR3 comprises SEQ ID NO:13. in some embodiments, LCDR3 comprises SEQ ID NO:14. in some embodiments, the antibody or antigen binding fragment comprises a sequence as set forth in SEQ ID NO:15, and a light chain CDR3.

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising: (a) a heavy chain variable region comprising SEQ ID NO:302 (X1 VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS), and (b) a light chain variable region comprising SEQ ID NO:303 (EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK), wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V.

In some embodiments, X1 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X1 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X2 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X2 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X3 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X3 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X4 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X4 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X5 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X5 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X6 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X6 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X7 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X7 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X8 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X8 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X9 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X9 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X10 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X10 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid. In some embodiments, X11 comprises a hydrophobic amino acid, a hydrophilic amino acid, or an amphiphilic amino acid. In some embodiments, X11 comprises an aliphatic amino acid, an aromatic amino acid, an acidic amino acid, a basic amino acid, a hydroxyl amino acid, a sulfur-containing amino acid, or an amide amino acid.

In some embodiments, x1=q or E, x2=r or K, x3=a or R, x4=m or I, x5=v or a, x6=m or I, x7=r or T, x8=v or a, x9=m or L, x10=l or P, and x11=l or W. In some embodiments, x1=q. In some embodiments, x1=e. In some embodiments, x2=r. In some embodiments, x2=k. In some embodiments, x3=a. In some embodiments, x3=r. In some embodiments, x4=m. In some embodiments, x4=i. In some embodiments, x5=v. In some embodiments, x5=a. In some embodiments, x6=m. In some embodiments, x6=i. In some embodiments, x7=r. In some embodiments, x7=t. In some embodiments, x8=v. In some embodiments, x8=a. In some embodiments, x9=m. In some embodiments, x9=l. In some embodiments, x10=l. In some embodiments, x10=p. In some embodiments, x11=l. In some embodiments, x11=w.

In some embodiments, HCDR1 comprises SEQ ID NO:1. in some embodiments, HCDR2 comprises SEQ ID NO:2. in some embodiments, HCDR2 comprises SEQ ID NO:3. in some embodiments, HCDR2 comprises SEQ ID NO:4. in some embodiments, HCDR2 comprises SEQ ID NO:5. in some embodiments, HCDR3 comprises SEQ ID NO:6. in some embodiments, HCDR3 comprises SEQ ID NO:7. in some embodiments, HCDR3 comprises SEQ ID NO:8. in some embodiments, HCDR3 comprises SEQ ID NO:9. in some embodiments, LCDR1 comprises SEQ ID NO:10. in some embodiments, LCDR2 comprises SEQ ID NO:11. in some embodiments, LCDR3 comprises SEQ ID NO:12. in some embodiments, LCDR3 comprises SEQ ID NO:13. in some embodiments, LCDR3 comprises SEQ ID NO:14. in some embodiments, LCDR3 comprises SEQ ID NO:15.

Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide that hybridizes to SEQ ID NO:104, and a heavy chain variable domain comprising an amino acid sequence at least about 96% identical to SEQ ID NO:201, a light chain variable domain of an amino acid sequence that is at least about 97% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least about 97% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least about 98% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, and an amino acid sequence that is at least about 99% identical. In some embodiments, the heavy chain variable domain comprises SEQ ID NO:104. in some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 are at least about 98% identical. In some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 is at least about 99% identical. In some embodiments, the light chain variable domain comprises SEQ ID NO:201.

also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide that hybridizes to SEQ ID NO:107 and a heavy chain variable domain comprising an amino acid sequence at least about 99% identical to SEQ ID NO:201, a light chain variable domain of an amino acid sequence that is at least about 97% identical. In some embodiments, the heavy chain variable domain comprises SEQ ID NO:107. in some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 are at least about 98% identical. In some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 is at least about 99% identical. In some embodiments, the light chain variable domain comprises SEQ ID NO:201.

Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:101 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:102 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:103 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:104 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:105 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:103 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:106 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:107 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:108 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:109 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:108 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:109 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:108 and a heavy chain variable domain comprising SEQ ID NO: 203. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:108 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:107 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:107 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:110 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:111 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:112 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:113 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:114 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:115 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:116 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:117 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:118 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:114 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:102 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:104 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:119 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:119 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:101 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:105 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:120 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:121 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:122 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:122 and a heavy chain variable domain comprising SEQ ID NO:204, and a light chain variable domain of 204. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:123 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:124 and a heavy chain variable domain comprising SEQ ID NO: 202. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:125 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:116 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:117 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:126 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:127 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:127 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:121 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:122 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:122 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:122 and a heavy chain variable domain comprising SEQ ID NO: 206. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:124 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:124 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:128 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:128 and a heavy chain variable domain comprising SEQ ID NO: 206. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:129 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:130 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:131 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:132 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:133 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:134 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:135 and a heavy chain variable domain comprising SEQ ID NO: 205. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:132 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:126 and a heavy chain variable domain comprising SEQ ID NO: 201. Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence comprising SEQ ID NO:130 and a heavy chain variable domain comprising SEQ ID NO: 201.

Also provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A), comprising a polypeptide comprising SEQ ID No:501-513 and a heavy chain comprising any one of SEQ ID nos: 514.

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15; and a crystallizable fragment (Fc) region comprising reduced antibody-dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and/or reduced complement-dependent cytotoxicity (CDC) as compared to human IgG 1. In some embodiments, human IgG1 comprises SEQ ID NO:320. in some embodiments, the ADCC function comprising the Fc region of reduced ADCC is reduced by at least about 50% compared to human IgG 1. In some embodiments, CDC function of the Fc region comprising reduced ADCC is reduced by at least about 50% compared to human IgG 1. In some embodiments, the Fc region comprises a human IgG1 comprising (a) 297A, 297Q 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, (K) 331S, (1) 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 V, (pp) 434I, (qq) 438G, (rr) 439E, 439H or 439Q, (ss) 440A, 440D, 440E, 440F, 440M, 440T or 440V, (tt) E233P, (uu) L235E, (V) L234A and L235A, (ww) L234A, L A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235E, G237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some embodiments, the antibody of the antigen binding fragment comprises (i) a human IgG4Fc region, or (ii) a human IgG4Fc region comprising: (a) S228P and L235E, or (b) S228P, F234A and L235A, numbered according to Kabat. In some embodiments, the antibody of the antigen binding fragment comprises a human IgG2Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. In some embodiments, the antibody of the antigen binding fragment comprises a human Fc region comprising high mannose glycosylation. In some embodiments, the Fc region comprises a human IgG1 having a substitution selected from the group consisting of: 297A, 297Q, 297D, 279F, 279K, 279L, 228P, 235A, 235E, 235G, 235Q, 235R, 235S, 237A, 237E, 237K, 237N, 237R, 268K, 269N, 269Q, 270A, 270G, 270M, 270N, 424H, 424M and 424V, numbered according to Kabat. In some embodiments, the Fc region comprises a human IgG1 having a substitution selected from the group consisting of: 271T, 272N, 292E, 292F, 292G, 292I, 293S, 301W, 304E, 311G, 311S, 255N, 256H, 256K, 256R, 256V, 316F, 328V, 330R, 339E, 339L, 343I, 343V, 373A, 373G, 373S, 376E, 376W, 376Y, 380D, 382P, 385P, 234A, 234V, 234F, 233P, 328A, 327Q, and 327T, numbered according to Kabat. In some embodiments, the Fc region comprises a human IgG1 having a substitution 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, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T and 440V, numbered according to Kabat. In some embodiments, the antibody or antigen binding fragment comprises a sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, HCDR1 comprises SEQ ID NO:1. in some embodiments, HCDR2 comprises SEQ ID NO:2. in some embodiments, HCDR2 comprises SEQ ID NO:3. in some embodiments, HCDR2 comprises SEQ ID NO:4. in some embodiments, HCDR2 comprises SEQ ID NO:5. in some embodiments, HCDR3 comprises SEQ ID NO:6. in some embodiments, HCDR3 comprises SEQ ID NO:7. in some embodiments, HCDR3 comprises SEQ ID NO:8. in some embodiments, HCDR3 comprises SEQ ID NO:9. in some embodiments, LCDR1 comprises SEQ ID NO:10. in some embodiments, LCDR2 comprises SEQ ID NO:11. in some embodiments, LCDR3 comprises SEQ ID NO:12. in some embodiments, LCDR3 comprises SEQ ID NO:13. in some embodiments, LCDR3 comprises SEQ ID NO:14. in some embodiments, LCDR3 comprises SEQ ID NO:15.

In another aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to TL1A, comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15. In some embodiments, the heavy chain variable region comprises a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework. In some embodiments, the light chain variable framework region comprises a human IGKV3-20 framework or a modified human IGKV3-20 framework. In some embodiments, the heavy chain variable region comprises one or more of the following amino acids: 1E, 45K, 47R, 55I, 78A, 80I, 82T, 89A, 91L, numbered according to Aho or Kabat. In some embodiments, the heavy chain variable region comprises 1E. In some embodiments, the heavy chain variable region comprises 45K. In some embodiments, the heavy chain variable region comprises 47R. In some embodiments, the heavy chain variable region comprises 55I. In some embodiments, the heavy chain variable region comprises 78A. In some embodiments, the heavy chain variable region comprises 80I. In some embodiments, the heavy chain variable region comprises 82T. In some embodiments, the heavy chain variable region comprises 89A. In some embodiments, the heavy chain variable region comprises 91L. In some embodiments, the light chain variable region comprises one or more of the following amino acids: 54P and 55W, numbered according to Aho or Kabat. In some embodiments, the light chain variable region comprises 54P. In some embodiments, the light chain variable region comprises 55W. In some embodiments, HCDR2 comprises SEQ ID NO:2. in some embodiments, HCDR2 comprises SEQ ID NO:3. in some embodiments, HCDR2 comprises SEQ ID NO:4. in some embodiments, HCDR2 comprises SEQ ID NO:5. in some embodiments, HCDR3 comprises SEQ ID NO:6. in some embodiments, HCDR3 comprises SEQ ID NO:7. in some embodiments, HCDR3 comprises SEQ ID NO:8. in some embodiments, HCDR3 comprises SEQ ID NO:9. in some embodiments, LCDR3 comprises SEQ ID NO:12. in some embodiments, LCDR3 comprises SEQ ID NO:13. in some embodiments, LCDR3 comprises SEQ ID NO:14. in some embodiments, LCDR3 comprises SEQ ID NO:15.

In some embodiments, an antibody or antigen binding fragment described herein comprises a human IgG1Fc region comprising (a) 297A, 297Q or 297D, (b) 279F, 279K or 279L, (c) 228P, (D) 235A, 235E, 235G, 235Q, 235E, 237K, 237N or 237R, (F) 234A, 234V or 234F, (G) 233P, (H) 328A, (I) 327Q or 327T, (j) 329A, 329G, 329Y, (K) 331S, (L) 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) D or P, (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, (V) L234A and L235A, (WW) L234A, L235A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L235E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235 35237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some embodiments, an antibody of an antigen binding fragment herein comprises (i) a human IgG4Fc region, or (ii) a human IgG4Fc region comprising: (a) S228P and L235E, or (b) S228P, F234A and L235A, numbered according to Kabat. In some embodiments, an antibody of an antigen binding fragment herein comprises a human IgG2Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S. In some embodiments, an antibody of an antigen binding fragment herein comprises a human Fc region comprising high mannose glycosylation. In some embodiments, any of the antibodies or antigen binding fragments described herein comprise a human IgG4Fc region.

In some embodiments, an antibody or antigen binding fragment described herein comprises a human IgG1 having a substitution selected from the group consisting of: 297A, 297Q, 297D, 279F, 279K, 279L, 228P, 235A, 235E, 235G, 235Q, 235R, 235S, 237A, 237E, 237K, 237N, 237R, 268K, 269N, 269Q, 270A, 270G, 270M, 270N, 424H, 424M and 424V, numbered according to Kabat. In some embodiments, an antibody or antigen binding fragment described herein comprises a human IgG1 having a substitution selected from the group consisting of: 271T, 272N, 292E, 292F, 292G, 292I, 293S, 301W, 304E, 311G, 311S, 255N, 256H, 256K, 256R, 256V, 316F, 328V, 330R, 339E, 339L, 343I, 343V, 373A, 373G, 373S, 376E, 376W, 376Y, 380D, 382P, 385P, 234A, 234V, 234F, 233P, 328A, 327Q, and 327T, numbered according to Kabat. In some embodiments, an antibody or antigen binding fragment described herein comprises a human IgG1 having a substitution 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, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T and 440V, numbered according to Kabat.

In some embodiments, an antibody or antigen binding fragment described herein comprises an Fc region comprising an amino acid sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence.

In some embodiments, an antibody or antigen binding fragment described herein comprises at least about 80% monomeric moieties as determined by size exclusion chromatography. In some embodiments, an antibody or antigen binding fragment described herein comprises at least about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% monomeric moieties. In some embodiments, size exclusion chromatography comprises injecting purified antibodies or antigen binding fragments onto a size exclusion column, wherein the antibodies or antigen binding fragments are purified by protein a. In some embodiments, the antibody or antigen binding fragment is purified as described in example 2. In some embodiments, the antibody or antigen binding fragment is expressed under the conditions described in example 2. In some embodiments, the inner diameter of the size exclusion chromatography column is 4.6mm. In some embodiments, the size exclusion chromatography column has a length of 150mm. In some embodiments, the size exclusion chromatography column has a pore size of In some embodiments, the size exclusion chromatography column has a particle size of 1.7 microns. In some embodiments, the size exclusion chromatography column is an ACQUITY UPLC BEH200SEC column. In some embodiments, the antibody or antigen binding fragment is injected in a total volume of 15 μl. In some embodiments, the antibody or antigen binding fragment is injected at a concentration of about 0.1 μg/μl to about 1.0 μg/μl. In some embodiments, size exclusion chromatography is performed on a Shimadzu UPLC instrument. In some embodiments, size exclusion chromatography is performed at a flow rate of 0.2 mL/min. In some embodimentsSize exclusion chromatography was performed at a column oven temperature of 30 ℃. In some embodiments, the percentage of monomer is calculated using Shimadzu software. In some embodiments, size exclusion chromatography is performed as described in example 2.

In some embodiments, an antibody or antigen binding fragment described herein expresses at least about 20ug/ml total antibody. In some embodiments, the antibodies or antigen binding fragments described herein express about 20ug/mL to 70ug/mL total antibody. In some embodiments, the antibody or antigen binding fragment is expressed in FreeStyle 293-F cells. In some embodiments, the antibody or antigen binding fragment is expressed as described in example 2. In some embodiments, enzyme-linked immunosorbent assay (ELISA) is used to quantify the level of antibody or antigen binding fragment expression. In some embodiments, the ELISA comprises coating the surface of a substrate with a capture antibody that binds to a human or humanized antibody, applying an antibody or antigen binding fragment to the substrate, and applying a second antibody that binds to a human or humanized antibody to the substrate. In some embodiments, the capture antibody comprises an anti-kappa antibody. In some embodiments, the second antibody comprises an anti-Fc antibody. In some embodiments, ELISA is performed as described in example 2.

Also provided herein are methods of treating Inflammatory Bowel Disease (IBD) in a subject in need thereof, comprising administering to the subject an antibody or antigen binding fragment described herein. In some embodiments, the IBD comprises crohn's disease. In some embodiments, the IBD comprises ulcerative colitis.

Also provided are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide identical to SEQ ID NO:104, and a heavy chain variable domain comprising an amino acid sequence at least 96% identical to SEQ ID NO:201, a light chain variable domain of an amino acid sequence that is at least 97% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least 97% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least 98% identical. In some embodiments, the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:104, at least 99% identical. In some embodiments, the heavy chain variable domain comprises SEQ ID NO:104. in some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 is at least 98% identical. In some embodiments, the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201 is at least about 99% identical. In some embodiments, the light chain variable domain comprises SEQ ID NO:201.

Also provided are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (TL 1A) comprising a polypeptide identical to SEQ ID NO:101-135, and a heavy chain variable domain comprising an amino acid sequence at least about 99% identical to any one of SEQ ID NOs: 201-206, a light chain variable domain of an amino acid sequence that is at least about 99% identical. Tables 16 and 17 list exemplary variable region amino acid sequences of anti-TL 1A antibodies.

Also provided are antibodies or antigen binding fragments as described herein, further comprising a human IgG1Fc region comprising (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) 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) D or P, (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, (V) L234A and L235A, (WW) L234A, L235A and G237A, (xx) L234A, L A and P329G, (yy) L234F, L235E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L235 35237A and P331S, (bbb) L234A, L235A, G237A, P238S, H268 56330S and P331S (IgG 1 sigma), (ccc) L234A, L A and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (ggg) V264A, (hhh) D265A, (iii) D265A and N297A, (jjjj) D265A and N297G, (kkk) D270A, (lll) A330L, (mmm) P331A or P331S, or (nnn) (a) - (uu) in any combination, numbered according to Kabat. In some embodiments, the antibody comprises a human IgG4Fc region. In some embodiments, the antibody Fc region comprises an amino acid sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence. In some embodiments, the antibody comprises at least about 80% monomeric moieties, as determined by size exclusion chromatography. In some embodiments, the antibodies are expressed in an amount of at least about 20ug/mL total antibody, optionally about 20ug/mL and 70ug/mL total antibody.

Antibody Properties

In various embodiments, the anti-TL 1A antibodies are antagonists of TL1A receptors, such as, but not limited to DR3 and TR6/DcR3. In certain embodiments, the antibody inhibits one or more activities of a bound TL1A receptor by at least about 10%, at least about 20%, at least about 30%, at least about 50%, at least about 75%, at least about 90%, or about 100%. In certain embodiments, the antibody inhibits TL1A activation as measured by release of interferon gamma in human blood. In certain embodiments, the antibodies are in an IC of between about 1 nanomolar and about 30 picomolar ₅₀ Inhibiting release of interferon gamma in human blood. In certain embodiments, the antibodies are between about 500 picomoles and about 30 picomoles of IC ₅₀ Inhibiting release of interferon gamma in human blood. In certain embodiments, the antibodies are between about 200 picomoles and about 30 picomoles of IC ₅₀ Inhibiting release of interferon gamma in human blood. In certain embodiments, the antibodies are raised to an IC of less than or equal to about 200 picomoles ₅₀ Inhibiting release of interferon gamma in human blood. In certain embodiments, the antibodies are raised against less than or equal to about 100 picomoles of IC ₅₀ Inhibiting release of interferon gamma in human blood.

In various embodiments, an anti-TL 1A antibody provided herein has a binding affinity for human TL1A of less than about 1E ^-7 、1E ^-8 、1E ^-9 Or 1E ^-10 Kd. In some cases, the binding affinity is about 1E ^-9 To about 1E ^-10 Kd. In some embodiments, an anti-TL 1A antibody provided herein has a binding affinity for murine TL1A and/or rat TL1A of less than about 1E ^-7 、1E ^-8 、1E ^-9 、1E ^-10 Or 1E ^-11 Kd. Methods for determining binding affinity are illustrated herein, including in example 2.

In various embodiments, an anti-TL 1A antibody provided herein comprises at least about 80% monomeric moieties after expression and purification as described in example 2 or elsewhere herein. In various embodiments, an anti-TL 1A antibody provided herein comprises at least about 85% monomeric moieties after expression and purification as described in example 2 or elsewhere herein. In various embodiments, an anti-TL 1A antibody provided herein comprises at least about 90% monomeric moieties after expression and purification as described in example 2 or elsewhere herein. In various embodiments, an anti-TL 1A antibody provided herein comprises at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% monomeric moieties after expression and purification as described in example 2 or elsewhere herein.

In various embodiments, the anti-TL 1A antibodies provided herein have an expression of at least about 2 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of about 2 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of about 5 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of about 10 μg/mL to about 60 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of at least about 5 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of at least about 10 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of at least about 15 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of at least about 20 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody expresses about 2 μg/mL to about 50 μg/mL, about 2 μg/mL to about 40 μg/mL, about 2 μg/mL to about 30 μg/mL, about 2 μg/mL to about 20 μg/mL, about 5 μg/mL to about 50 μg/mL, about 5 μg/mL to about 40 μg/mL, about 5 μg/mL to about 30 μg/mL, about 10 μg/mL to about 50 μg/mL, about 10 μg/mL to about 40 μg/mL, or about 10 μg/mL to about 30 μg/mL as determined by the methods disclosed herein. In some embodiments, the anti-TL 1A antibody has an expression of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 μg/mL as determined by the methods disclosed herein. The methods disclosed herein include those described in example 2.

In various embodiments, the anti-TL 1A antibodies provided herein are humanized and have less than about 20% non-human sequences in the framework regions of each of the heavy and light chain variable regions. For example, a humanized antibody comprises less than about 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% non-human sequence in the framework regions of each of the heavy and light chain variable regions. As another example, a humanized antibody comprises about or less than about 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human sequences in the framework regions of each of the heavy and light chain variable regions. The humanized heavy chain variable domain may comprise an IGHV1-46 x 02 framework with no non-human mutations or with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 non-human mutations. The humanized light chain variable domain may comprise an IGKV3-20 framework having no non-human mutation or less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 non-human mutation.

Measurement

An exemplary screening paradigm for identifying antibody variants that express well in mammalian cells and retain TL1A binding activity while minimizing the propensity of the antibodies to aggregate includes a five-step process. The screening was performed as detailed in the examples. Briefly, (1) the variants were cloned and transiently expressed as intact Ig in 293 cells using small-scale (3 ml,6 well plates) transfection, (2) the expression levels of the antibodies were assessed in the culture supernatants using antibody quantitative ELISA 96-120 hours post-transfection, (3) the binding of the supernatant antibody variants to human TL1A was assessed by ELISA, (4) the antibodies were purified using protein a in a single step, and (5) the material was analyzed by analytical SEC to assess monomer/aggregate content. This method enables the identification of variants that are well expressed, retain binding to TL1A and exhibit high monomer content.

Also provided herein are methods of analyzing antibody solubility based on the percentage of monomeric moieties. For example, as described in example 2.

Also provided herein are assays for quantifying antibody expression. For example, as described in example 2.

Also provided herein are assays for quantifying the immunogenicity of antibodies.

Specific binding of an antibody described herein can be determined by any method known in the art. Immunoassays that can be used include, but are not limited to, competitive and non-competitive assay systems using techniques such as: BIAcore analysis, FACS analysis, immunofluorescence, immunocytochemistry, western blotting, radioimmunoassay, ELISA, "sandwich" immunoassays, immunoprecipitation assays, precipitation reactions, gel diffusion precipitant reactions, immunodiffusion assays, agglutination assays, complement fixation assays, immunoradioassays, fluorescent immunoassays, and protein a immunoassays. Such assays are provided, for example, in Ausubel et al, volume 1994,Current Protocols in Molecular Biology, volume 1, john Wiley & Sons, inc., new York.

Additional therapeutic agents

The therapeutic agent may be used alone or in combination with another therapeutic agent. The therapeutic agents may be administered together or sequentially. The combination therapy may be administered within the same day, or may be administered one or more days, weeks, months or years apart. In some cases, a therapeutic agent provided herein is administered if the subject is determined to be non-responsive to first line therapy (e.g., TNF inhibitor). Such determinations may be made by monitoring treatment with first line therapy and disease states and/or making diagnostic determinations that the subject is not responsive to first line therapy.

In some embodiments, the additional therapeutic agent comprises an anti-TNF therapy, such as an anti-tnfα therapy. In some embodiments, the additional therapeutic agent comprises a two-wire therapy to anti-TNF therapy. In some embodiments, the additional therapeutic agent comprises an immunosuppressant, or a class of drugs that inhibit or reduce the intensity of the immune system. In some embodiments, the immunosuppressant is an antibody. Non-limiting examples of immunosuppressive therapeutic agents include(Wu Sinu mab), azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate, cyclosporin A. (CsA).

In some embodiments, the additional therapeutic agent comprises a selective anti-inflammatory agent, or a class of agents that specifically target a pro-inflammatory molecule in vivo. In some embodiments, the anti-inflammatory agent comprises an antibody. In some embodiments, the anti-inflammatory agent comprises a small molecule. Non-limiting examples of anti-inflammatory agents include ENTTYVIO (vedelizumab), corticosteroids, aminosalicylates, mesalazine (mesalamine), balsalazide (Colazal), and olsalazine (Dipentum).

Method for producing antibodies

In various embodiments, monoclonal antibodies are prepared using methods known in the art, such as, but not limited to, the hybridoma method, in which a host animal is immunized to elicit lymphocytes that produce antibodies that will specifically bind to the immunizing antigen (Kohler and Milstein (1975) Nature 256:495). Hybridomas produce monoclonal antibodies specific for the selected antigen. When transmitted in vitro or in vivo, monoclonal antibodies are purified from the culture medium or ascites fluid by techniques known in the art.

In some embodiments, monoclonal antibodies are prepared using recombinant DNA methods. Polynucleotides encoding monoclonal antibodies are isolated from mature B cells or hybridoma cells. The isolated polynucleotides encoding the heavy and light chains are then cloned into suitable expression vectors that produce monoclonal antibodies when transfected into host cells, e.g., E.coli (E.coli) cells, simian COS cells, chinese Hamster Ovary (CHO) cells, or myeloma cells. Polynucleotides encoding monoclonal antibodies can be further modified in a number of different ways using recombinant DNA techniques to produce surrogate antibodies.

In various embodiments, chimeric antibodies can be produced, i.e., molecules in which different portions are derived from different animal species, such as those having variable regions derived from murine monoclonal antibodies and human immunoglobulin constant regions (e.g., humanized antibodies).

In some embodiments, the anti-TL 1A monoclonal antibody is a humanized antibody to reduce antigenicity and HAMA (human anti-mouse antibody) response when administered to a human subject. Various techniques known in the art may be used to prepare the humanized antibodies. For example, antibodies are humanized by: (1) Determining the nucleotide and predicted amino acid sequences of the starting antibody light and heavy chain variable domains; (2) Humanized antibodies are designed, e.g., to determine which antibody framework regions to use during the humanization process; (3) actual humanization methods/techniques; and (4) transfection and expression of humanized antibodies. In various embodiments, the humanized antibodies may be further optimized to reduce potential immunogenicity while maintaining functional activity for use in therapy in humans.

Humanized antibodies can also be prepared in transgenic mice containing human immunoglobulin loci that are capable of producing a complete repertoire of human antibodies upon immunization in the absence of endogenous immunoglobulin production. Humanized antibodies can also be obtained by genetic engineering methods that are capable of producing affinity matured human-like polyclonal antibodies in large animals.

Fully humanized antibodies can be generated by first designing variable region amino acid sequences that contain non-human, e.g., rodent-derived CDRs embedded within a framework sequence of human origin. The non-human CDRs provide the desired specificity. Thus, in some cases, these residues are included in the design of the substantially unchanged, reconstructed variable region. In some cases, modification should therefore be limited to the minimum of and closely observe changes in the specificity and affinity of an antibody. On the other hand, the theoretical framework residues may be derived from any human variable region. Human framework sequences that are also suitable for producing the recombinant variable regions and for maintaining the affinity of the antibody should be selected in order to produce a recombinant antibody that exhibits acceptable or even improved affinity. The human framework may be of germline origin, or may be derived from non-germline (e.g., mutated or affinity matured) sequences. Genetic engineering techniques well known to those skilled in the art, such as, but not limited to, phage display of human antibody libraries, transgenic mice, human-human hybridomas, hybrid-hybridomas, B cell immortalization and cloning, single cell RT-PCR or HuRAb techniques, can be used to produce humanized antibodies having hybrid DNA sequences containing human frameworks and non-human CDRs.

In certain embodiments, the anti-TL 1A antibody is a human antibody. Human antibodies can be prepared directly using a variety of techniques known in the art. Immortalized human B lymphocytes may be produced by in vitro immunization or isolated from an immunized individual producing antibodies to the target antigen.

Chimeric, humanized and human antibodies may be produced by recombinant expression. Recombinant polynucleotide constructs typically include expression control sequences, including naturally-associated or heterologous promoter regions, operably linked to the coding sequence of the antibody chain. In certain embodiments, it may be desirable to produce amino acid sequence variants of these humanized antibodies, particularly where such variants improve the binding affinity or other biological properties of the antibody.

In certain embodiments, the antibody fragments are used to treat and/or ameliorate IBD. Various techniques for producing antibody fragments are known. Typically, these fragments are obtained by proteolytic digestion of the intact antibody (e.g., morimoto et al, 1993,Journal of Biochemical and Biophysical Methods 24:107-117; brennan et al, 1985, science,229: 81). Fab, fv and scFv antibody fragments can all be expressed in and secreted from e.coli or other host cells, thus allowing the production of large amounts of these fragments. Other techniques for generating antibody fragments will be apparent to those skilled in the art.

In accordance with the present disclosure, the techniques may be adapted to produce single chain antibodies specific for TL1A. Furthermore, the methods may be adapted for constructing Fab expression libraries to allow for the rapid and efficient identification of monoclonal Fab fragments, or derivatives, fragments, analogs, or homologs thereof, having the desired specificity for TL1A. Antibody fragments may be produced by techniques in the art including, but not limited to: (a) F (ab') 2 fragments produced by pepsin digestion of antibody molecules; (b) A Fab fragment produced by reducing the disulfide bonds of a F (ab') 2 fragment, (c) a Fab fragment produced by treating an antibody molecule with papain and a reducing agent, and (d) an Fv fragment.

Also provided herein are modified antibodies comprising any type of variable region that provides binding of the antibody to TL1A. Those of skill in the art will appreciate that modified antibodies can include antibodies (e.g., full length antibodies or immunoreactive fragments thereof) in which at least a portion of one or more constant region domains have been deleted or otherwise altered to provide desired biochemical characteristics, such as reduced TL1A. In certain embodiments, the variable regions in both the heavy and light chains are altered by at least partial substitution of one or more CDRs and, if desired, partial framework region substitutions and sequence alterations. In some embodiments, the substituted CDRs may be derived from antibodies of the same class, subclass, from different classes of antibodies, e.g., from different species and/or combinations thereof. In some embodiments, the constant region of the modified antibody will comprise a human constant region. Modifications to constant regions compatible with the present disclosure include additions, deletions, or substitutions of one or more amino acids in one or more domains.

In various embodiments, expression of an antibody or antigen binding fragment thereof as described herein may occur in a prokaryotic cell or eukaryotic cell. Suitable hosts include bacterial or eukaryotic hosts, including yeast, insect, fungal, avian and mammalian cells, in vivo or in situ, or host cells of mammalian, insect, avian or yeast origin. The mammalian cells or tissues may be of human, primate, hamster, rabbit, rodent, cow, pig, sheep, horse, goat, dog or cat origin, but any other mammalian cell may be used. In other embodiments, an antibody or antigen fragment thereof as described herein may be transfected into a host.

In some embodiments, the expression vector is transfected into a recipient cell line for the production of the chimeric, humanized or composite human antibodies described herein. In various embodiments, mammalian cells may be used as hosts for the production of antibody proteins, which may include, but are not limited to, fibroblasts-derived cells, such as Vero (ATCC CRL 81) or CHO-K1 (ATCC CRL 61) cells, heLa cells, and L cells. Exemplary eukaryotic cells that may be used to express the polypeptide include, but are not limited to, COS cells, including COS 7 cells; 293 cells, including 293-6E cells; CHO cells, including CHO-S and DG44 cells; PER.C6 ^TM Cells (Crucell); and NSO cells. In some embodiments, the particular eukaryotic host cell is selected based on its ability to make the desired post-translational modification of the heavy and/or light chain.

Many suitable host cell lines capable of secreting intact heterologous proteins have been developed in the art and include, but are not limited to, CHO cell lines, various COS cell lines, heLa cells, L cells and multiple myeloma cell lines.

Expression vectors carrying chimeric, humanized or composite human antibody constructs, antibodies or antigen binding fragments thereof as described herein may be introduced into suitable host cells by any of a variety of suitable means, depending on the type of cellular host, including, but not limited to, transformation, transfection, lipofection, conjugation, electroporation, direct microinjection, and microprojectile bombardment as known to one of ordinary skill in the art. Expression vectors for these cells may include expression control sequences such as replication origin sites, promoters, enhancers and necessary processing information sites such as ribosome binding sites, RNA splice sites, polyadenylation sites and transcription terminator sequences.

In various embodiments, yeast may also be used as a host for producing the antibody molecules or peptides described herein. In various other embodiments, bacterial strains may also be used as hosts for the production of antibody molecules or peptides described herein. Examples of bacterial strains include, but are not limited to, E.coli, bacillus species, E.coli, and various Pseudomonas species.

In some embodiments, one or more antibodies or antigen binding fragments thereof as described herein may be produced in vivo in an animal that has been engineered (transgenic) or transfected with one or more nucleic acid molecules encoding the polypeptides according to any suitable method. To produce a transgenic animal, the transgene may be microinjected into a fertilized oocyte, or the transgene may be incorporated into the genome of an embryonic stem cell, and the nucleus of such cell transferred into an enucleated oocyte. Once expressed, the antibodies can be purified according to standard procedures in the art, including HPLC purification, column chromatography, gel electrophoresis, and the like (see generally, scens, protein Purification (Springer-Verlag, N.Y., 1982)).

Once expressed in the host, the intact antibodies, antibody fragments (e.g., individual light and heavy chains), or other immunoglobulin forms of the present disclosure may be recovered and purified by known techniques, such as immunoabsorbent or immunoaffinity chromatography, chromatographic methods such as HPLC (high performance liquid chromatography), ammonium sulfate precipitation, gel electrophoresis, or any combination of these methods. See generally, scenes, PROTEIN purif (spring-Verlag, NY, 1982). Substantially pure immunoglobulins of at least about 90% to 95% homogeneity are advantageous, as are those immunoglobulins having 98% to 99% or more homogeneity, in particular for pharmaceutical use. Once partially purified or purified to homogeneity as desired, the humanized or composite human antibodies can be used therapeutically or for developing and performing assay procedures, immunofluorescent staining, and the like. See generally Immunol. Meth. Volumes I and II (Lefkovits and Pernis, et al, acad.Acad.Press, NY,1979 and 1981).

Various embodiments provide genetic constructs comprising nucleic acids encoding anti-TL 1A antibodies or fragments provided herein. The genetic construct of the antibody may be in the form of an expression cassette, which may be suitable for expression of the encoded anti-TL 1A antibody or fragment. The gene construct may be introduced into a host cell with or without incorporation into a vector. For example, the genetic construct may be incorporated into a liposome or viral particle. Alternatively, the purified nucleic acid molecule may be inserted directly into a host cell by methods known in the art. The gene construct may be introduced directly into the cells of the host subject by transfection, infection, electroporation, cell fusion, protoplast fusion, microinjection or ballistic bombardment.

Various embodiments provide recombinant vectors comprising the genetic constructs of the antibodies provided herein. The recombinant vector may be a plasmid, cosmid or phage. The recombinant vector may include other functional elements; for example, a suitable promoter for promoting gene expression.

Various embodiments provide host cells comprising the genetic constructs and/or recombinant vectors described herein.

Various host systems are also advantageously used for expression of recombinant proteins. Examples of suitable mammalian host cell lines include the COS-7 line of monkey kidney cells, and other cell lines capable of expressing suitable vectors, including, for example, L cell, C127, 3T3, chinese Hamster Ovary (CHO), heLa, and BHK cell lines. Mammalian expression vectors may contain non-transcribed elements such as an origin of replication, suitable promoters and enhancers linked to the gene to be expressed, and other 5 'or 3' flanking non-transcribed sequences, and 5 'or 3' non-translated sequences such as necessary ribosome binding sites, polyadenylation sites, splice donor and acceptor sites, and transcription termination sequences.

The protein produced by the transformed host may be purified according to any suitable method. Such standard methods include chromatography (e.g., ion exchange chromatography, affinity chromatography, and fractionation column chromatography), centrifugation, differential dissolution, or any other standard technique for protein purification. Affinity tags such as hexahistidine (SEQ ID NO: 1303), maltose binding domain, influenza envelope sequences, and glutathione-S-transferase may be attached to the protein to allow easy purification by a suitable affinity column. The isolated proteins may also be physically characterized using techniques such as proteolysis, nuclear magnetic resonance, and x-ray crystallography. Recombinant proteins produced in bacterial culture can be isolated.

One of skill in the art will recognize that individual substitutions, deletions, or additions to a nucleic acid, peptide, polypeptide, or protein sequence that alter a single amino acid or a small portion of an amino acid in the encoded sequence are "conservatively modified variants" where the alteration results in the substitution of an amino acid with a chemically similar amino acid and retains the ability to specifically bind to the target antigen. Such conservatively modified variants are additionally polymorphic variants, interspecies homologs, and alleles consistent with the present disclosure.

A given amino acid may be substituted with residues having similar physiochemical characteristics, e.g., one aliphatic residue with another aliphatic residue (such as He, val, leu or Ala with each other), or one polar residue with another polar residue (such as between Lys and Arg; between Glu and Asp; or between gin and Asn). Other such conservative substitutions, for example substitutions of the entire region with similar hydrophobic character, are well known. Polypeptides comprising conservative amino acid substitutions may be tested in any of the assays described herein to confirm retention of a desired activity, such as antigen binding activity and specificity of a native or reference polypeptide.

Specific conservative substitutions include, for example; substitution of Ala to Gly or Ser; arg is substituted by Lys; asn is substituted with Gin or His; asp is substituted with Glu; cys is substituted by Ser; gin is substituted with Asn; glu is substituted with Asp; gly is substituted to Ala or Pro; his is substituted by Asn or Gin; lie is substituted with Leu or Val; leu is substituted with lie or Val; lys is replaced by Arg, gin or Glu; met is replaced by Leu, tyr or lie; phe is replaced by Met, leu or Tyr; substitution of Ser for Thr; thr is substituted by Ser; trp is substituted with Tyr; tyr is substituted with Trp; and/or Phe is replaced with Val, lie or Leu.

In some embodiments, an antibody and/or antigen binding fragment thereof described herein may be a variant of a sequence described herein, e.g., a conservatively substituted variant of an antibody polypeptide. In some embodiments, the variant is a conservatively modified variant. A variant may refer to a polypeptide that is substantially homologous to a native or reference polypeptide, but differs in amino acid sequence from the native or reference polypeptide by one or more deletions, insertions or substitutions. DNA sequences encoding variant polypeptides encompass sequences that contain one or more nucleotide additions, deletions, or substitutions when compared to the native or reference DNA sequence, but encode variant proteins or fragments thereof that retain the activity of the relevant target polypeptide, e.g., antigen-specific binding activity.

Alterations of the natural amino acid sequence may be accomplished by any of a number of techniques known to those skilled in the art. Mutations may be introduced at specific loci or by oligonucleotide-directed site-specific mutagenesis procedures. Techniques for making such changes are well-defined and include, for example, those disclosed by: walder et al (Gene 42:133, 1986); bauer et al (Gene 37:73, 1985); craik (BioTechniques, month 1, 1985, 12-19); smith et al (Genetic Engineering: principles and Methods, plenum Press, 1981).

Nucleic acid molecules encoding amino acid sequence variants of antibodies are prepared by a variety of methods known in the art. These methods include, but are not limited to, preparation by oligonucleotide-mediated (or site-directed) mutagenesis, PCR mutagenesis, and cassette mutagenesis of variant or non-variant forms of the early preparation of antibodies. Nucleic acid sequences encoding at least one antibody, moiety or polypeptide as described herein may be recombined with vector DNA according to conventional techniques, including but not limited to blunt-ended or staggered-ended termini for ligation and restriction enzyme digestion. Techniques for such manipulation are disclosed, for example, by Maniatis et al, molecular Cloning, lab.Manual (Cold Spring Harbor Lab.Press, NY,1982 and 1989), and can be used to construct nucleic acid sequences encoding monoclonal antibody molecules or antigen binding regions.

In some embodiments, the vector comprises a nucleic acid encoding an antibody or antigen binding fragment thereof as described herein. In some aspects described herein, a nucleic acid sequence encoding an antibody or antigen binding fragment thereof as described herein, or any module thereof, is operably linked to a vector. As used herein, the term "vector" refers to a nucleic acid construct designed for delivery to a host cell or for transfer between different host cells. As used herein, a vector may be viral or non-viral. The term "vector" encompasses any genetic element that is capable of replication when combined with an appropriate control element and that can transfer a gene sequence to a cell. Vectors may include, but are not limited to, cloning vectors, expression vectors, plasmids, phages, transposons, cosmids, chromosomes, viruses, virions, and the like.

As used herein, the term "expression vector" refers to a vector that directs the expression of RNA or a polypeptide from a sequence of a transcriptional regulatory sequence linked to the vector. The term "expression" refers to cellular processes involving the production of RNA and proteins and, where appropriate, the partitioning of proteins, including, but not limited to, for example, transcription, transcriptional processing, translation, and protein folding, modification, and processing. "expression product" includes RNA transcribed from a gene, and a polypeptide obtained by translating mRNA transcribed from a gene. The term "gene" means a nucleic acid sequence that, when operably linked to appropriate regulatory sequences, transcribes (DNA) into RNA in vitro or in vivo. Genes may or may not include regions preceding and following the coding region, such as 5' untranslated (5 ' utr) or "leader" sequences and 3' utr or "trailer" sequences, as well as intervening sequences (introns) between individual coding segments (exons).

As used herein, the term "viral vector" refers to a nucleic acid vector construct comprising at least one viral-derived element and having the ability to be packaged into viral vector particles. The viral vector may contain a nucleic acid encoding an antibody or antigen binding portion thereof as described herein in place of the non-essential viral genes. The vector and/or particle may be used for the purpose of transferring any nucleic acid into a cell in vitro or in vivo. Various forms of viral vectors are known in the art.

By "recombinant vector" is meant that the vector comprises a heterologous nucleic acid sequence or "transgene" capable of expression in vivo.

Pharmaceutical compositions, administration and dosage

The provided anti-TL 1A antibodies can be used in a variety of applications, including but not limited to therapeutic treatment methods, such as the treatment of IBD. The method of use may be in vitro, ex vivo or in vivo. In certain embodiments, the anti-TL 1A antibody is an antagonist of a TL1A receptor.

In certain embodiments, the disease treated with an anti-TL 1A antibody or TL1A receptor antagonist is IBD, CD, UC and/or MR-UC.

In various embodiments, the pharmaceutical composition is formulated for delivery by any route of administration. The "route of administration" may refer to any route of administration known in the art including, but not limited to, aerosol, nasal, oral, transmucosal, transdermal, or parenteral.

The pharmaceutical composition may also contain any pharmaceutically acceptable carrier. By "pharmaceutically acceptable carrier" is meant a pharmaceutically acceptable material, composition or vehicle that is involved in carrying or transporting a compound of interest from one tissue, organ or portion of the body to another tissue, organ or portion of the body. For example, the carrier may be a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, or a combination thereof. Each component of the carrier must be "pharmaceutically acceptable" in that it must be compatible with the other ingredients of the formulation. It must also be suitable for contact with any tissue or organ with which it may be in contact, meaning that it must not carry the risk of toxicity, irritation, allergic response, immunogenicity, or any other complication beyond its therapeutic benefit.

In various embodiments, pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of an anti-TL 1A antibody are provided. By "pharmaceutically acceptable excipient" is meant an excipient that can be used to prepare generally safe, non-toxic and desirable pharmaceutical compositions and includes excipients that are acceptable for veterinary as well as human pharmaceutical use. The active ingredient may be admixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient and in amounts suitable for use in the therapeutic methods described herein. Such excipients may be solid, liquid, semi-solid, or gaseous in the case of aerosol compositions. Suitable excipients are, for example, starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, water, saline, dextrose, propylene glycol, glycerol, ethanol, mannitol, polysorbate and the like and combinations thereof. In addition, the compositions may contain minor amounts of auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, and the like, which enhance or maintain the effectiveness of the active ingredient, if desired. The therapeutic compositions as described herein may include pharmaceutically acceptable salts. Pharmaceutically acceptable salts include acid addition salts formed with inorganic acids (e.g., hydrochloric acid or phosphoric acid), organic acids (e.g., acetic acid, tartaric acid, or mandelic acid), salts formed with inorganic bases (e.g., sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, or ferric hydroxide), and salts formed with organic bases (e.g., isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine (procaine), and the like). The liquid composition may contain aqueous and non-aqueous liquid phases, for example glycerol, vegetable oils such as cottonseed oil, and aqueous oil emulsions. Physiologically tolerable carriers are well known in the art. The amount of active agent (i.e., antibody or fragment thereof) used that will be effective in treating a particular disorder or condition will depend on the nature of the disorder or condition and can be determined by one of skill in the art using standard clinical techniques.

The pharmaceutical composition may be delivered in a therapeutically effective amount. The precise therapeutically effective amount is the amount of the composition that will produce the most effective result in terms of therapeutic efficacy in a given subject. The amount will vary depending on a variety of factors including, but not limited to, the characteristics of the therapeutic compound (including activity, pharmacokinetics, pharmacodynamics, and bioavailability), the physiological condition of the subject (including age, sex, disease type and stage, general physical condition, responsiveness to a given dose, and drug type), the nature of one or more pharmaceutically acceptable carriers in the formulation, and the route of administration. Those skilled in the clinical and pharmacological arts will be able to determine a therapeutically effective amount by routine experimentation, for example, by monitoring the subject's response to administration of a compound and adjusting the dosage accordingly. For additional guidance, see Remington: the Science and Practice of Pharmacy (Gennaro, 20 th edition, williams & Wilkins Pa., USA) (2000).

For the treatment of diseases, the appropriate dosage of the antibody depends on the type of disease to be treated, the severity and course of the disease, the responsiveness of the disease, the administration of the antibody for therapeutic or prophylactic purposes, past therapies and the clinical history of the patient. The dose may also be adjusted by the individual physician and left to the treating physician in the event of any complications. The optimum dosage, method of administration and repetition rate can be determined by the administering physician. TL1A antibodies may be administered once or in a series of treatments lasting from days to months, or until a cure is achieved or a reduction in the disease state is achieved (e.g., treatment or amelioration of IBD). The duration of treatment depends on the clinical progress of the subject and the responsiveness to the therapy. In certain embodiments, the dose is from 0.01 μg to 100mg per kilogram body weight and may be administered one or more times per day, once per week, once per month, or once per year.

Antibody therapeutics suitable for injection and/or administration are important to achieve the full therapeutic potential of mabs (monoclonal antibodies, e.g., anti-TL 1A monoclonal antibodies). However, administration is generally limited by volume. This in turn demonstrates the importance of developing high concentration mAb formulations greater than (e.g., in some cases) 100 mg/ml. Problems associated with mAb opening, including high solution viscosity and opalescence, are often encountered during development of high concentrations (e.g., greater than 100 mg/ml). Viscosity and opalescence both widely affect mAb development, affecting manufacturability, stability, and delivery. High solution viscosity (e.g., greater than 30 mPa-s) results in backpressure that limits ultrafiltration/diafiltration during mAb concentration unit operation. Similarly, viscous mAb solutions also result in interference with injection forces or the generation of incompatible injection forces when administered by injection, including by a patient friendly auto-injector. In fact, the solution viscosity may be a determinant of the maximum possible mAb dose achieved by injection. Solution opalescence in therapeutic mabs can also be problematic, as opalescence can indicate a tendency for liquid-liquid phase separation, precipitation, or aggregation.

The anti-TL 1A antibodies provided herein exhibit advantageous viscosity and aggregation properties at high antibody concentrations (e.g., greater than 100mg/mL or greater than 150 mg/mL). Notably, the anti-TL 1A antibodies provided herein are characterized by low viscosity (e.g., less than 10 mPa-s) and low aggregation (e.g., less than 5% high molecular weight species) at high concentrations (fig. 7A-7C).

For example, for a case wherein HCDR1 comprises SEQ ID NO: 1. HCDR2 comprises SEQ ID NO: 2. HCDR3 comprises SEQ ID NO: 6. LCDR1 comprises SEQ ID NO: 10. LCDR2 comprises SEQ ID NO:11 and LCDR3 comprises SEQ ID NO:12, or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104 and the light chain variable region comprises SEQ ID NO:201, in some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than about 30, 20, 15, or 10mPa-s at a concentration of greater than about 100mg/mL, e.g., up to about 170mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than about 30, 20, 15, or 10mPa-s at a concentration of greater than at least about 100 mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than about 30, 20, 15, or 10mPa-s at a concentration of up to about 170mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than about 30, 20, 15, or 10mPa-s at a concentration of about 100mg/mL to about 125mg/mL, about 100mg/mL to about 150mg/mL, about 100mg/mL to about 160mg/mL, about 100mg/mL to about 170mg/mL, about 125mg/mL to about 150mg/mL, about 125mg/mL to about 160mg/mL, about 125mg/mL to about 170mg/mL, about 150mg/mL to about 170mg/mL, or about 160mg/mL to about 170mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than about 30, 20, 15 or 10mPa-s at a concentration of about or greater than about 100mg/mL, about 125mg/mL, about 150mg/mL, about 160mg/mL or about 170mg/mL. In some embodiments, less than about 10 mPas comprises about 4 to about 10 mPas, about 4 to about 9 mPas, about 4 to about 8 mPas, about 4 to about 7 mPas, about 4 to about 6 mPas, about 4 to about 5 mPas, about 5 to about 10 mPas, about 5 to about 9 mPas, about 5 to about 8 mPas, about 5 to about 7 mPas, about 5 to about 6 mPas, about 6 to about 10 mPas, about 6 to about 9 mPas, about 6 to about 8 mPas or about 6 to about 7 mPas. In some embodiments, greater than about 100, 125, 150, or 160mg/ml is up to about 170mg/ml.

Further, for example, for a case wherein HCDR1 comprises SEQ ID NO: 1. HCDR2 comprises SEQ ID NO: 2. HCDR3 comprises SEQ ID NO: 6. LCDR1 comprises SEQ ID NO: 10. LCDR2 comprises SEQ ID NO:11 and LCDR3 comprises SEQ ID NO:12, or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104 and the light chain variable region comprises SEQ ID NO:201, in some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of greater than about 100mg/mL to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of greater than at least about 100 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of up to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of about 100mg/mL to about 125mg/mL, about 100mg/mL to about 150mg/mL, about 100mg/mL to about 160mg/mL, about 100mg/mL to about 170mg/mL, about 125mg/mL to about 150mg/mL, about 125mg/mL to about 160mg/mL, about 125mg/mL to about 170mg/mL, about 150mg/mL to about 160mg/mL, about 150mg/mL to about 170mg/mL, or about 160mg/mL to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of at or greater than about 100mg/mL, about 125mg/mL, about 150mg/mL, about 160mg/mL, or about 170 mg/mL.

By way of further example, for a polypeptide wherein HCDR1 comprises SEQ ID NO: 1. HCDR2 comprises SEQ ID NO: 2. HCDR3 comprises SEQ ID NO: 6. LCDR1 comprises SEQ ID NO: 10. LCDR2 comprises SEQ ID NO:11 and LCDR3 comprises SEQ ID NO:12, or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104 and the light chain variable region comprises SEQ ID NO:201, in some embodiments, an anti-T1 LA antibody at a concentration of about 150mg/mL to about or greater than about 170mg/mL is characterized by a viscosity of less than about 10mPa-s to about 30 mPa-s. In some embodiments, an anti-T1 LA antibody at a concentration of about 150mg/mL to about or greater than about 170mg/mL is characterized by a viscosity of less than about 30 mPa-s. In some embodiments of the present invention, in some embodiments, an anti-T1 LA antibody at a concentration of about 150mg/mL to about or greater than about 170mg/mL is characterized by less than about 5mPa-s to about 10mPa-s, about 5mPa-s to about 15mPa-s, about 5mPa-s to about 20mPa-s, about 5mPa-s to about 30mPa-s, about 10mPa-s to about 15mPa-s, about 10mPa-s to about 20mPa-s, about 10mPa-s to about 30mPa-s, about 15mPa-s to about 20mPa-s, about 15mPa-s to about 30mPa-s, about 20mPa-s to about 30mPa-s about 5 to about 9 mPas, about 4 to about 10 mPas, about 4 to about 9 mPas, about 4 to about 8 mPas, about 4 to about 7 mPas, about 4 to about 6 mPas, about 4 to about 5 mPas, about 5 to about 10 mPas, about 5 to about 9 mPas, about 5 to about 8 mPas, about 5 to about 7 mPas, about 5 to about 6 mPas, about 6 to about 10 mPas, about 6 to about 9 mPas, about 6 to about 8 mPas or about 6 to about 7 mPas. In some embodiments, an anti-T1 LA antibody at a concentration of about 150mg/mL to about or greater than about 170mg/mL is characterized by a viscosity of less than about 5 mPas, about 10 mPas, about 15 mPas, about 20 mPas, or about 30 mPas. In some embodiments, less than about 5, 10, 15, 20, or 30 mPas is at least about 1 mPas.

Further, for example, for a case wherein HCDR1 comprises SEQ ID NO: 1. HCDR2 comprises SEQ ID NO: 2. HCDR3 comprises SEQ ID NO: 6. LCDR1 comprises SEQ ID NO: 10. LCDR2 comprises SEQ ID NO:11 and LCDR3 comprises SEQ ID NO:12, or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104 and the light chain variable region comprises SEQ ID NO:201, in some embodiments, an anti-TL 1A antibody at a concentration of greater than 150mg/mL is characterized by a turbidity of less than about 5 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU). In some embodiments, an anti-TLIA antibody at a concentration greater than 150mg/mL is characterized by a turbidity of less than at least about 5 Nephelometric Turbidity Units (NTUs). In some embodiments, an anti-TL 1A antibody at a concentration greater than 150mg/mL is characterized by a turbidity of less than at most about 15 Nephelometric Turbidity Units (NTU). In some embodiments, an anti-TL 1A antibody having a concentration of greater than 150mg/mL is characterized by less than about 5 Nephelometric Turbidity Units (NTU) to about 7.5 Nephelometric Turbidity Units (NTU), about 5 Nephelometric Turbidity Units (NTU) to about 10 Nephelometric Turbidity Units (NTU), about 5 Nephelometric Turbidity Units (NTU) to about 12.5 Nephelometric Turbidity Units (NTU), about 5 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU) to about 10 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU) to about 12.5 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU), about 10 Nephelometric Turbidity Units (NTU) to about 12.5 Nephelometric Turbidity Units (NTU), about 10 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU), or about 15 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU). In some embodiments, an anti-TL 1A antibody at a concentration greater than 150mg/mL is characterized by a turbidity of less than about 5 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU), about 10 Nephelometric Turbidity Units (NTU), about 12.5 Nephelometric Turbidity Units (NTU), or about 15 Nephelometric Turbidity Units (NTU).

The anti-TL 1A antibodies described herein also exhibit advantageous aggregation properties. For those wherein HCDR1 comprises SEQ ID NO: 1. HCDR2 comprises SEQ ID NO: 2. HCDR3 comprises SEQ ID NO: 6. LCDR1 comprises SEQ ID NO: 10. LCDR2 comprises SEQ ID NO:11 and LCDR3 comprises SEQ ID NO:12, or wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:104 and the light chain variable region comprises SEQ ID NO:201, in some embodiments, the anti-TL 1A antibody composition is characterized by a percentage of high molecular weight species (e.g., species having a molecular weight greater than the molecular weight of the monomer) of less than 10% when at a concentration of greater than about 100mg/mL to about greater than 170 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of greater than at least about 100 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of up to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight mass percentage of less than 10% when at a concentration of about 100mg/mL to about 125mg/mL, about 100mg/mL to about 150mg/mL, about 100mg/mL to about 160mg/mL, about 100mg/mL to about 170mg/mL, about 125mg/mL to about 150mg/mL, about 125mg/mL to about 160mg/mL, about 125mg/mL to about 170mg/mL, about 150mg/mL to about 160mg/mL, about 150mg/mL to about 170mg/mL, or about 160mg/mL to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of about or greater than about 100mg/mL, about 125mg/mL, about 150mg/mL, about 160mg/mL, or about 170 mg/mL. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration greater than 150mg/mL is characterized by a high molecular weight substance of less than about 5% to about 15%. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration greater than 150mg/mL is characterized by a high molecular weight substance of less than at most about 15%. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration of greater than 150mg/mL is characterized by a high molecular weight substance of less than about 5% to about 7.5%, about 5% to about 10%, about 5% to about 15%, about 5% to about 17.5%, about 5% to about 20%, about 5% to about 25%, about 7.5% to about 10%, about 7.5% to about 15%, about 7.5% to about 17.5%, about 7.5% to about 20%, about 7.5% to about 25%, about 10% to about 15%, about 10% to about 17.5%, about 10% to about 20%, about 10% to about 25%, about 15% to about 17.5%, about 15% to about 20%, about 15% to about 25%, about 17.5% to about 20%, about 17.5% to about 25%, or about 20% to about 25%. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration greater than 150mg/mL is characterized by a high molecular weight substance of less than about 5%, about 7.5%, about 10%, about 15%, about 17.5%, about 20% or about 25%.

By way of further example, for antibodies or antigen binding fragments comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region comprise less than 9 amino acid modifications in total compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework, in some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than 10mPa-s at a concentration of greater than about 100mg/mL to about greater than 170 mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than 10mPa-s at a concentration greater than at least about 100 mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than 10mPa-s at a concentration of greater than at most about 170 mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than 10mPa-s at a concentration of greater than about 100mg/mL to about 125mg/mL, about 100mg/mL to about 150mg/mL, about 100mg/mL to about 160mg/mL, about 100mg/mL to about 170mg/mL, about 125mg/mL to about 150mg/mL, about 125mg/mL to about 160mg/mL, about 125mg/mL to about 170mg/mL, about 150mg/mL to about 160mg/mL, about 150mg/mL to about 170mg/mL, or about 160mg/mL to about 170 mg/mL. In some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than 10mPa-s at a concentration of greater than about 100mg/mL, about 125mg/mL, about 150mg/mL, about 160mg/mL, or about 170 mg/mL.

Further, for example, for an antibody or antigen binding fragment comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region comprise less than 9 amino acid modifications in total compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework, in some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTUs) when at a concentration of greater than about 100mg/mL to about greater than 170 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of greater than at least about 100 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of greater than up to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of greater than about 100mg/mL to about 125mg/mL, about 100mg/mL to about 150mg/mL, about 100mg/mL to about 160mg/mL, about 100mg/mL to about 170mg/mL, about 125mg/mL to about 150mg/mL, about 125mg/mL to about 160mg/mL, about 125mg/mL to about 170mg/mL, about 150mg/mL to about 160mg/mL, about 150mg/mL to about 170mg/mL, or about 160mg/mL to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody is characterized by a turbidity of less than 12 Nephelometric Turbidity Units (NTU) when at a concentration of greater than about 100mg/mL, about 125mg/mL, about 150mg/mL, about 160mg/mL, or about 170 mg/mL.

Furthermore, for antibodies or antigen binding fragments comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region comprise less than 9 amino acid modifications in total compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework, in some embodiments, the anti-T1 LA antibody is characterized by a viscosity of less than about 10mPa-s to about 30mPa-s at a concentration of greater than 150mg/mL to greater than about 170 mg/mL. In some embodiments, an anti-T1 LA antibody at a concentration of greater than 150mg/mL to greater than about 170mg/mL is characterized by a viscosity of less than at most about 30 mPa-s. In some embodiments, an anti-T1 LA antibody at a concentration of greater than 150mg/mL to greater than about 170mg/mL is characterized by a viscosity of less than about 5mPa-s to about 10mPa-s, about 5mPa-s to about 15mPa-s, about 5mPa-s to about 20mPa-s, about 5mPa-s to about 30mPa-s, about 10mPa-s to about 15mPa-s, about 10mPa-s to about 20mPa-s, about 10mPa-s to about 30mPa-s, about 15mPa-s to about 20mPa-s, about 15mPa-s to about 30mPa-s, or about 20mPa-s to about 30 mPa-s. In some embodiments, an anti-T1 LA antibody at a concentration of greater than 150mg/mL to greater than about 170mg/mL is characterized by a viscosity of less than about 5 mPas, about 10 mPas, about 15 mPas, about 20 mPas, or about 30 mPas.

Further, for example, for an antibody or antigen binding fragment comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region comprise less than 9 amino acid modifications in total compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework, and in some embodiments, an anti-TL 1A antibody at a concentration of greater than 150mg/mL is characterized by a turbidity of less than about 5 Nephelometric Turbidity Units (NTUs) to about 15 Nephelometric Turbidity Units (NTUs). In some embodiments, an anti-TL 1A antibody at a concentration greater than 150mg/mL is characterized by a turbidity of less than at least about 5 Nephelometric Turbidity Units (NTU). In some embodiments, an anti-TL 1A antibody at a concentration greater than 150mg/mL is characterized by a turbidity of less than at most about 15 Nephelometric Turbidity Units (NTU). In some embodiments, an anti-TL 1A antibody having a concentration of greater than 150mg/mL is characterized by less than about 5 Nephelometric Turbidity Units (NTU) to about 7.5 Nephelometric Turbidity Units (NTU), about 5 Nephelometric Turbidity Units (NTU) to about 10 Nephelometric Turbidity Units (NTU), about 5 Nephelometric Turbidity Units (NTU) to about 12.5 Nephelometric Turbidity Units (NTU), about 5 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU) to about 10 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU) to about 12.5 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU), about 10 Nephelometric Turbidity Units (NTU) to about 12.5 Nephelometric Turbidity Units (NTU), about 10 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU), or about 15 Nephelometric Turbidity Units (NTU) to about 15 Nephelometric Turbidity Units (NTU). In some embodiments, an anti-TL 1A antibody at a concentration greater than 150mg/mL is characterized by a turbidity of less than about 5 Nephelometric Turbidity Units (NTU), about 7.5 Nephelometric Turbidity Units (NTU), about 10 Nephelometric Turbidity Units (NTU), about 12.5 Nephelometric Turbidity Units (NTU), or about 15 Nephelometric Turbidity Units (NTU).

The anti-TL 1A antibodies described herein also exhibit advantageous aggregation properties. For antibodies or antigen binding fragments comprising: a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein the heavy chain variable framework region and the light chain variable framework region together comprise less than 9 amino acid modifications as compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework, in some embodiments, the anti-TL 1A antibody composition is characterized by a percentage of high molecular weight species (e.g., species having a molecular weight greater than that of the monomer) of less than 10% when at a concentration of greater than about 100mg/mL to about greater than 170 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of greater than at least about 100 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of greater than up to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of greater than about 100mg/mL to about 125mg/mL, about 100mg/mL to about 150mg/mL, about 100mg/mL to about 160mg/mL, about 100mg/mL to about 170mg/mL, about 125mg/mL to about 150mg/mL, about 125mg/mL to about 160mg/mL, about 125mg/mL to about 170mg/mL, about 150mg/mL to about 160mg/mL, about 150mg/mL to about 170mg/mL, or about 160mg/mL to about 170 mg/mL. In some embodiments, the anti-TL 1A antibody composition is characterized by a high molecular weight substance percentage of less than 10% when at a concentration of greater than about 100mg/mL, about 125mg/mL, about 150mg/mL, about 160mg/mL, or about 170 mg/mL. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration greater than 150mg/mL is characterized by a high molecular weight substance of less than about 5% to about 15%. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration greater than 150mg/mL is characterized by a high molecular weight substance of less than at most about 15%. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration of greater than 150mg/mL is characterized by a high molecular weight substance of less than about 5% to about 7.5%, about 5% to about 10%, about 5% to about 15%, about 5% to about 17.5%, about 5% to about 20%, about 5% to about 25%, about 7.5% to about 10%, about 7.5% to about 15%, about 7.5% to about 17.5%, about 7.5% to about 20%, about 7.5% to about 25%, about 10% to about 15%, about 10% to about 17.5%, about 10% to about 20%, about 10% to about 25%, about 15% to about 17.5%, about 15% to about 20%, about 15% to about 25%, about 17.5% to about 20%, about 17.5% to about 25%, or about 20% to about 25%. In some embodiments, an anti-TL 1A antibody composition with an antibody concentration greater than 150mg/mL is characterized by a high molecular weight substance of less than about 5%, about 7.5%, about 10%, about 15%, about 17.5%, about 20% or about 25%.

Dosage and route of administration

Generally, the methods disclosed herein comprise administering the therapeutic agent by oral administration. However, in some cases, the method includes administering the therapeutic agent by intraperitoneal injection. In some cases, the method includes administering the therapeutic agent in the form of an anal suppository. In some cases, the method comprises administering the therapeutic agent by intravenous ("i.v.") administration. It is envisioned that one may also administer the therapeutic agents disclosed herein by other routes, such as subcutaneous injection, intramuscular injection, intradermal injection, transdermal administration by transdermal injection, intranasal administration, intralymphatic injection, intragastric administration by rectal administration, or any other suitable enteral administration. In some embodiments, a local delivery route closer to the site of injury or inflammation is preferred over a systemic route. The route, dosage, point of time and duration of administration of the therapeutic agent may be adjusted. In some embodiments, the therapeutic agent is administered before or after the onset of either or both acute and chronic symptoms of the disease or condition.

The effective dosages and dosages of therapeutic agents to prevent or treat the diseases or conditions disclosed herein are defined by the observed beneficial response associated with the disease or condition or symptoms of the disease or condition. Beneficial reactions include preventing, alleviating, preventing, or curing a disease or condition, or symptoms of the disease or condition (e.g., reducing diarrhea, rectal bleeding, weight loss, and size or number of intestinal lesions or strictures, reducing fibrosis or fibrosis, reducing fibroplasia, reducing inflammation). In some embodiments, the beneficial response can be measured by detecting a measurable improvement in the presence, level, or activity of a biomarker in the subject, a transcriptome risk profile, or an intestinal microbiome. As used herein, "ameliorating" refers to a transition in presence, level, or activity to that observed in a normal individual (e.g., an individual not suffering from a disease or condition). In cases where the therapeutic agent is not therapeutically effective or does not provide sufficient relief from the disease or condition or symptoms of the disease or condition, then the dosage and/or route of administration may be altered or additional agents may be administered to the subject with the therapeutic agent. In some embodiments, when the patient begins the regimen of therapeutic agent, the patient also stops (e.g., steps down the dose) the second therapeutic regimen.

Suitable dosages and dosages to be administered to a subject are determined by factors including, but not limited to: specific therapeutic agents, disease conditions and severity thereof, characteristics (e.g., body weight, sex, age) of the subject in need of treatment; and may be decided according to a specific case surrounding a case including, for example, the following: the particular agent administered, the route of administration, the condition being treated, and the subject or host being treated. However, in general, the dosage for adult treatment is usually in the range of 0.01mg to 5000mg per day. In one aspect, the dosage for adult treatment is from about 1mg to about 1000mg per day. In one embodiment, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously (or over a short period of time) or at appropriate intervals, for example two, three, four or more sub-doses per day. Non-limiting examples of effective dosages for oral delivery of therapeutic agents include between about 0.1mg and about 100mg per kilogram of body weight per day, and preferably between about 0.5mg and about 50mg per kilogram of body weight per day. In other cases, an effective amount of the active agent is delivered orally at a dose of about 1mg and about 10mg per kilogram of body weight per day. Non-limiting examples of effective dosages of the therapeutic agent administered intravenously include at a rate of between about 0.01 to 100 picomoles per kilogram of body weight per minute. In some embodiments, the daily dose or amount of active agent in the dosage form is below or above the ranges described herein, based on a number of variables regarding the individual treatment regimen. In various embodiments, the daily dose and unit dose vary according to a number of variables including, but not limited to, the activity of the therapeutic agent used, the disease or condition to be treated, the mode of administration, the needs of the individual subject, the severity of the disease or condition being treated, and the discretion of the physician.

In some embodiments, the therapeutic agent is administered once per hour, every 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, or 5 years or 10 years. The effective dosage range can be adjusted based on the subject's response to treatment. Some routes of administration will require a higher concentration of the effective amount of therapeutic agent than other routes.

In certain embodiments, wherein the patient's condition is not improved at the discretion of the physician, administration of the therapeutic agent is administered chronically, that is, for an extended period of time, including throughout the patient's life, in order to improve or otherwise control or limit the symptoms of the patient's disease or condition. In certain embodiments, wherein the patient's condition does improve, the dose of the therapeutic agent administered may be temporarily reduced or temporarily stopped for a certain period of time (i.e., a "drug holiday"). In specific embodiments, the length of the drug holiday is between 2 days and 1 year, including (by way of example only) 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, or more than 28 days. Dose reduction during drug holidays (by way of example only) is 10% -100%, including (by way of example only) 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% and 100%. In certain embodiments, the dose of the administered drug may be temporarily reduced or temporarily stopped for a certain period of time (i.e., a "drug transfer"). In specific embodiments, the length of drug transfer is between 2 days and 1 year, including (by way of example only) 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, or more than 28 days. Dose reduction during drug transfer (by way of example only) is 10% -100%, including (by way of example only) 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% and 100%. After a suitable period of time, the normal dosing regimen is optionally restored.

In some embodiments, once the patient's condition has improved, a maintenance dose is administered as necessary. Subsequently, in specific embodiments, the dosage or frequency of administration, or both, is reduced according to symptoms to a level that maintains an improved disease, disorder, or condition. However, in certain embodiments, the patient requires long-term intermittent treatment to prevent any recurrence of symptoms.

Toxicity and therapeutic efficacy of such treatment regimens are determined by standard pharmaceutical procedures in cell cultures or experimental animals, including but not limited to determination of LD50 and ED 50. The dose ratio between toxic and therapeutic effects is the therapeutic index and is expressed as the ratio between LD50 and ED 50. In certain embodiments, the data obtained from cell culture assays and animal studies are used in formulating a therapeutically effective daily dosage range and/or a therapeutically effective unit dosage for use in mammals, including humans. In some embodiments, the daily dose of a therapeutic agent described herein is in a range that includes circulating concentrations of ED50 with minimal toxicity. In certain embodiments, the daily dose range and/or unit dose varies within this range depending on the dosage form used and the route of administration used.

Numbered embodiments

In certain embodiments, described herein are methods for assessing the effect of a treatment described herein. In some cases, the treatment comprises administering an inhibitor of TL1A activity or expression and optionally one or more additional therapeutic agents. In some cases, treatment is monitored by assessing the amount of TL1A in the subject before and/or after administration of the therapeutic agent.

1. A method of inhibiting or reducing TL1A activity or expression in a subject having or suspected of having at least one of an inflammatory, fibrotic, and fibrotic disease or condition, the method comprising:

a) Identifying the subject as a carrier of a genotype comprising the polymorphisms provided in table 1 or table 4 or polymorphisms in Linkage Disequilibrium (LD) state therewith; and

b) Administering to the subject a therapeutically effective amount of an anti-TL 1A antibody from table 16-table 17 or table 20, thereby inhibiting or reducing TL1A activity or expression in the subject.

2. The method of embodiment 1, provided that the inflammatory, fibrostenotic, and fibrotic disease or condition comprises crohn's disease, scleroderma, or pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis).

3. The method of embodiment 2, provided that the crohn's disease comprises ileal crohn's disease, ileal colon crohn's disease, or colon crohn's disease.

4. The method of embodiment 1, with the proviso that the inflammatory disease comprises Ulcerative Colitis (UC).

5. The method of embodiment 4, provided that the UC is medically refractory UC.

6. The method of any one of embodiments 1-5, wherein identifying the subject as a carrier of genotype of step (a) comprises:

a) Allowing a sample comprising genetic material from the subject to bind to a nucleic acid sequence comprising a nucleic acid sequence set forth in SEQ ID NO: contact of nucleic acid sequences hybridized with at least 10 consecutive nucleobases of a risk allele at nuclear position 501 within any one of 2001-2048 or 2057-2059; and

b) Detecting binding between said nucleic acid sequence and at least 10 consecutive nucleobases comprising said at-risk allele.

7. The method of embodiment 6, provided that the standard hybridization conditions include a binding temperature between about 35 ℃ and about 65 ℃.

8. The method of embodiment 6 or embodiment 7, provided that the standard hybridization conditions are performed with a TaqMan master mix solution.

9. The method of any one of embodiments 6 to 8, provided that the nucleic acid sequence is conjugated to a detectable molecule.

10. The method of embodiment 9, provided that the detectable molecule comprises a fluorophore.

11. The method of any one of embodiments 6 to 10, provided that the nucleic acid sequence is conjugated to a quencher.

12. The method of any one of embodiments 6-11, provided that the sample comprising genetic material from the subject is amplified genetic material obtained from a nucleic acid amplification assay.

13. The method of embodiment 12, provided that the nucleic acid amplification assay comprises a nucleic acid amplification assay comprising a nucleic acid sequence set forth in SEQ ID NO:2001-2048 or 2057-2059, comprising a first primer and a second primer, a pair of primers of at least 15 consecutive nucleobases of the at-risk allele at nuclear position 501 within any of the primers to amplify DNA from the subject.

14. The method of embodiment 12, provided that the first primer comprises a nucleotide sequence that hybridizes to a nucleotide sequence set forth in SEQ ID NO:2001-2048 or 2057-2059, and said second primer comprises a nucleic acid sequence complementary to at least 15 consecutive nucleobases upstream of said at-risk allele at nucleobase 501 within any one of SEQ ID NOs: 2001-2048 or 2057-2059, at least 15 consecutive nucleobases downstream of said at-risk allele at nucleobase 501.

15. The method of any one of embodiments 1-14, provided that the subject has been determined to be a carrier of the genotype by a method comprising DNA sequencing.

16. The method of any one of embodiments 1-15, provided that the subject further comprises a level of soluble TL1A that is greater than a control level derived from a non-diseased individual or a non-diseased individual population.

17. The method of any one of embodiments 1-16, provided that the genotype of the subject is homozygous.

18. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least two polymorphisms provided in table 1 or table 4.

19. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least three polymorphisms provided in table 1 or table 4.

20. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least four polymorphisms provided in table 1 or table 4.

21. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least five polymorphisms provided in table 1 or table 4.

22. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least six polymorphisms provided in table 1 or table 4.

23. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least seven polymorphisms provided in table 1 or table 4.

24. The method of any one of embodiments 1 to 17, wherein the genotype comprises at least eight polymorphisms provided in table 1 or table 4.

25. The method of any one of embodiments 1 to 24, wherein the genotype comprises polymorphisms selected from the group consisting of: rs11897732 (SEQ ID NO: 2001), an "A" allele at rs6740739 (SEQ ID NO: 2002), an "A" allele at rs17796285 (SEQ ID NO: 2003), an "A" allele at rs7935393 (SEQ ID NO: 2004), an "G" allele at rs12934476 (SEQ ID NO: 2005), an "A" allele at rs12457255 (SEQ ID NO: 2006), an "A" allele at rs2070557 (SEQ ID NO: 2007), an "A" allele at rs4246905 (SEQ ID NO: 2008), an "A" allele at rs10974900 (SEQ ID NO: 2009), an "C" allele at rs12434976 (SEQ ID NO: 2010), an "A" allele at rs16901748 (SEQ ID NO: 20011), an "A" allele at rs 74 2815844 (SEQ ID NO: 20012), an "A" allele at rs12457255 (SEQ ID NO: 2006), an "A" allele at rs 5235 (SEQ ID NO: 2007), an "allele at rs 5232 (SEQ ID NO: 2007), an" allele at rs 20018 "20054 a" allele at rs10974900 (SEQ ID NO: 2009), an "allele at rs 20037A" of rs 20019, an "allele at rs 20037 (SEQ ID NO: 2009), an" allele at rs 20037A (SEQ ID NO: 2009), the "G" allele at rs10932456 (SEQ ID NO: 20023), the "A" allele at rs1326860 (SEQ ID NO: 20024), the "G" allele at rs1528663 (SEQ ID NO: 20025), the "C" allele at rs1892231 (SEQ ID NO: 20026), the "A" allele at rs951279 (SEQ ID NO: 20027), the "A" allele at rs9806914 (SEQ ID NO: 20028), the "G" allele at rs7935393 (SEQ ID NO: 20029), the "A" allele at rs1690492 (SEQ ID NO: 20030), the "T" allele at rs420726 (SEQ ID NO: 20031), the "A" allele at rs7759385 (SEQ ID NO: 20032), the "A" allele at rs1326860 (SEQ ID NO: 20034), the "A" allele at rs 4632 (SEQ ID NO: 20028), the "allele at rs 5233 (SEQ ID NO: 20035), the" G "allele at rs1690492 (SEQ ID NO: 20030), the" T "allele at rs420726 (SEQ ID NO: 20032), the" allele at rs7759385 (SEQ ID NO: 20032), the "A" allele at rs 300, the "allele (SEQ ID NO: 200) and the" A "allele (SEQ ID NO: 200) alleles at rs 37, the" A "allele (SEQ ID NO: 200) and the" allele (SEQ ID NO: 35, and the "allele) alleles at rs 300, and the" A "allele (SEQ ID NO: 200) The "G" allele at rs2070558 (SEQ ID NO: 20058) and the "T" allele at rs2070561 (SEQ ID NO: 20059).

26. The method of embodiments 1-25, wherein the inhibitor of TL1A activity or expression is an anti-TL 1A antibody.

27. The method of embodiment 26, wherein the anti-TL 1A antibody is selected from table 20.

28. The method of embodiment 26, wherein the anti-TL 1A antibody comprises the amino acid sequences provided in tables 16-17.

29. The method of embodiment 26, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody selected from table 20.

30. The method of embodiment 26, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody comprising the amino acid sequences provided in tables 16-17.

31. The method of embodiments 26-30, wherein the anti-TL 1A antibody is a neutralizing TL1A antibody.

32. The method of embodiments 26-31, wherein the anti-TL 1A antibody is an antagonist of TL 1A.

33. A method of treating an inflammatory, fibrotic, and fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, provided that the presence of a genotype is detected in a sample obtained from the subject.

34. A method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising:

a) Analyzing a sample obtained from a subject to detect the presence or absence of a genotype;

b) Detecting the presence of the genotype in the sample obtained from the subject;

c) Administering to the subject a therapeutically effective amount of a TL1A antibody or antigen binding fragment from table 16-table 17 or table 21.

35. The method of embodiments 33-34, provided that the inflammatory, fibrostenotic, or fibrotic disease or condition comprises crohn's disease, scleroderma, or pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis).

36. The method of embodiment 35, provided that the crohn's disease comprises ileal crohn's disease, ileal colonic crohn's disease, or colonic crohn's disease.

37. The method of embodiments 33-34, provided that the inflammatory disease is Ulcerative Colitis (UC).

38. The method of embodiment 37, provided that the UC is medically refractory UC.

39. The method of any one of embodiments 33 to 38, wherein the presence of the genotype is detected in the sample obtained from the subject by:

a) Allowing the sample comprising genetic material from the subject to bind to a nucleic acid comprising a nucleic acid sequence set forth in SEQ ID NO: contact of nucleic acid sequences hybridized with at least 10 consecutive nucleobases of a risk allele at nuclear position 501 within any one of 2001-2048 or 2057-2059; and

b) Detecting binding between said nucleic acid sequence and at least 10 consecutive nucleobases comprising said at-risk allele.

40. The method of embodiment 39, provided that the standard hybridization conditions include a binding temperature between about 35 ℃ and about 65 ℃.

41. The method of embodiment 39 or embodiment 40, provided that the standard hybridization conditions are performed with a TaqMan master mix solution.

42. The method of any one of embodiments 39 to 37, provided that the nucleic acid sequence is conjugated to a detectable molecule.

43. The method of embodiment 42, provided that the detectable molecule comprises a fluorophore.

44. The method of any one of embodiments 39 to 43, provided that the nucleic acid sequence is conjugated to a quencher.

45. The method of any one of embodiments 39-44, provided that the sample comprising genetic material from the subject is amplified genetic material obtained from a nucleic acid amplification assay.

46. The method of embodiment 45, provided that the nucleic acid amplification assay comprises a nucleic acid amplification assay capable of amplifying a nucleic acid sequence comprising a nucleic acid sequence set forth in SEQ ID NO:2001-2048 or 2057-2059, comprising a first primer and a second primer, a pair of primers of at least 15 consecutive nucleobases of the at-risk allele at nuclear position 501 within any of the primers to amplify DNA from the subject.

47. The method of embodiment 46, provided that the first primer comprises a nucleotide sequence that hybridizes to a nucleotide sequence set forth in SEQ ID NO:2001-2048 or 2057-2059, and said second primer comprises a nucleic acid sequence complementary to at least 15 consecutive nucleobases upstream of said at-risk allele at nucleobase 501 within any one of SEQ ID NOs: 2001-2048 or 2057-2059, at least 15 consecutive nucleobases downstream of said at-risk allele at nucleobase 501.

48. The method of any one of embodiments 34-47, detecting the presence of the genotype in the sample obtained from the subject by a method comprising DNA sequencing.

49. The method of any one of embodiments 34-48, provided that the subject further comprises a level of soluble TL1A that is greater than a control level derived from a non-diseased individual or a non-diseased individual population.

50. The method of any one of embodiments 34-49, provided that the genotype of the subject is homozygous.

51. The method of any one of embodiments 34 to 50, wherein the genotype comprises at least two polymorphisms provided in table 1 or table 4.

52. The method of any one of embodiments 34 to 51, wherein the genotype comprises at least three polymorphisms provided in table 1 or table 4.

53. The method of any one of embodiments 34 to 52, wherein the genotype comprises at least four polymorphisms provided in table 1 or table 4.

54. The method of any one of embodiments 34 to 53, wherein the genotype comprises at least five polymorphisms provided in table 1 or table 4.

55. The method of any one of embodiments 34 to 54, wherein the genotype comprises at least six polymorphisms provided in table 1 or table 4.

56. The method of any one of embodiments 34 to 55, wherein the genotype comprises at least seven polymorphisms provided in table 1 or table 4.

57. The method of any one of embodiments 34 to 56, wherein the genotype comprises at least eight polymorphisms provided in table 1 or table 4.

58. The method of any one of embodiments 34 to 57, wherein the genotype comprises polymorphisms selected from the group consisting of: rs11897732 (SEQ ID NO: 2001), an "A" allele at rs6740739 (SEQ ID NO: 2002), an "A" allele at rs17796285 (SEQ ID NO: 2003), an "A" allele at rs7935393 (SEQ ID NO: 2004), an "G" allele at rs12934476 (SEQ ID NO: 2005), an "A" allele at rs12457255 (SEQ ID NO: 2006), an "A" allele at rs2070557 (SEQ ID NO: 2007), an "A" allele at rs4246905 (SEQ ID NO: 2008), an "A" allele at rs10974900 (SEQ ID NO: 2009), an "C" allele at rs12434976 (SEQ ID NO: 2010), an "A" allele at rs16901748 (SEQ ID NO: 20011), an "A" allele at rs 74 2815844 (SEQ ID NO: 20012), an "A" allele at rs12457255 (SEQ ID NO: 2006), an "A" allele at rs 5235 (SEQ ID NO: 2007), an "allele at rs 5232 (SEQ ID NO: 2007), an" allele at rs 20018 "20054 a" allele at rs10974900 (SEQ ID NO: 2009), an "allele at rs 20037A" of rs 20019, an "allele at rs 20037 (SEQ ID NO: 2009), an" allele at rs 20037A (SEQ ID NO: 2009), the "G" allele at rs10932456 (SEQ ID NO: 20023), the "A" allele at rs1326860 (SEQ ID NO: 20024), the "G" allele at rs1528663 (SEQ ID NO: 20025), the "C" allele at rs1892231 (SEQ ID NO: 20026), the "A" allele at rs951279 (SEQ ID NO: 2027), the "A" allele at rs9806914 (SEQ ID NO: 20028), the "G" allele at rs7935393 (SEQ ID NO: 20029), the "A" allele at rs1690492 (SEQ ID NO: 20030), the "T" allele at rs420726 (SEQ ID NO: 20031), the "A" allele at rs7759385 (SEQ ID NO: 20032), the "A" allele at rs1326860 (SEQ ID NO: 20034), the "A" allele at rs 4632 (SEQ ID NO: 20028), the "allele at rs 5240 (SEQ ID NO: 20035), the" G "allele at rs420726 (SEQ ID NO: 20031), the" T "allele at rs7759385 (SEQ ID NO: 20032), the" allele at rs 5233 "," A "allele (SEQ ID NO: 20035), the" allele (SEQ ID NO: 200) and the "allele" A "allele (SEQ ID NO: 300, the" allele "30) at rs 20035 (SEQ ID NO: 35), the" allele "A" allele (SEQ ID NO: 200) The "G" allele at rs2070558 (SEQ ID NO: 20058) and the "T" allele at rs2070561 (SEQ ID NO: 20059).

59. The method of embodiments 34-58, wherein the inhibitor of TL1A activity or expression is an anti-TL 1A antibody.

60. The method of embodiment 59, wherein the anti-TL 1A antibody is selected from table 20.

61. The method of embodiment 59, wherein the anti-TL 1A antibody comprises the amino acid sequences provided in tables 16-17.

62. The method of embodiment 59, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody selected from table 20.

63. The method of embodiment 59, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody comprising the amino acid sequences provided in tables 16-17.

64. The method of embodiments 59-643, wherein said anti-TL 1A antibody is a neutralizing TL1A antibody.

65. The method of embodiments 59-64, wherein the anti-TL 1A antibody is an antagonist of TL 1A.

66. A method of characterizing at least one of an inflammatory, fibrotic, and fibrotic disease or condition in a subject, the method comprising assaying genetic material from the subject to identify the presence or absence of a genotype comprising a polymorphism provided in table 1 or table 4.

67. The method of embodiment 66, further comprising assigning a prognosis that is more favorable for treatment with an inhibitor of TL1A activity or expression when said genotype is present.

68. The method of embodiment 66, further comprising assigning a prognosis that is less favorable to inhibitors of TL1A activity or expression when the genotype is not present.

69. The method of embodiment 66, further comprising, when said genotype is present, prescribing that said subject be treated with an inhibitor of TL1A activity or expression.

70. The method of embodiment 66, further comprising, when said genotype is present, instructing said subject to use an inhibitor of TL1A activity or expression.

71. The method of embodiment 66, further comprising administering to said subject an inhibitor of anti-CD 30 ligand activity or expression when said genotype is present.

72. The method of any one of embodiments 67-71, provided that the inhibitor of TL1A activity or expression is an anti-TL 1A antibody or antigen binding fragment thereof.

73. The method of any one of embodiments 67 to 72, provided that the determining comprises amplifying from the genetic material comprising a primer set comprising a first primer and a second primer, the genetic material comprising a primer set comprising a nucleotide sequence set forth in SEQ ID NO: at least 15 consecutive nucleobases of the risk allele at nuclear position 501 within any one of 2001-2048 or 2057-2059.

74. The method of any one of embodiment 73, provided that the first primer comprises a nucleotide sequence that hybridizes to a nucleotide sequence set forth in SEQ ID NO:2001-2048 or 2057-2059, and said second primer comprises a nucleic acid sequence complementary to at least 15 consecutive nucleobases upstream of said at-risk allele at nucleobase 501 within any one of SEQ ID NOs: 2001-2048 or 2057-2059, at least 15 consecutive nucleobases downstream of said at-risk allele at nucleobase 501.

75. The method of any one of embodiments 66 to 74, provided that the determining comprises contacting a nucleic acid comprising SEQ ID NO:2001-2048 or 2057-2059.

76. The method of embodiment 75, provided that the nucleic acid sequence is conjugated to a detectable molecule.

77. The method of embodiment 76, provided that the detectable molecule comprises a fluorophore.

78. The method of any one of embodiments 75 to 77, provided that the nucleic acid sequence is conjugated to a quencher.

79. The method of any one of embodiments 66 to 78, provided that the determining comprises DNA sequencing.

80. The method of any one of embodiments 66-79, further comprising measuring the level of TL1A in the subject.

81. The method of any one of embodiments 66-80, provided that the genotype of the subject is homozygous.

82. The method of embodiments 66-81, wherein the genotype comprises at least two polymorphisms provided in table 1 or table 4.

83. The method of any one of embodiments 66 to 82, wherein the genotype comprises at least three polymorphisms provided in table 1 or table 4.

84. The method of any one of embodiments 66 to 83, wherein the genotype comprises at least one polymorphism that comprises a non-reference allele.

85. The method of any one of embodiments 66-84, further comprising characterizing at least one of the inflammatory, fibrotic, and fibrotic diseases or conditions as Crohn's Disease (CD), provided that the genotype is present.

86. The method of embodiment 85, provided that the CD comprises ileum, ileum colon or colon CD.

87. The method of any one of embodiments 66-86, further comprising characterizing at least one of the inflammatory, fibrotic, and fibrotic diseases or conditions as Ulcerative Colitis (UC), provided that the genotype is present.

88. The method of embodiment 87, provided that the fibrotic disease is medically refractory UC.

89. The method of embodiment 72, wherein the anti-TL 1A antibody is selected from table 20.

90. The method of embodiment 72, wherein the anti-TL 1A antibody comprises the amino acid sequences provided in tables 16-17.

91. The method of embodiment 72, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody selected from table 20.

92. The method of embodiment 72, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody comprising the amino acid sequences provided in tables 16-17.

93. The method of embodiments 89-92, wherein the anti-TL 1A antibody is a neutralizing TL1A antibody.

94. The method of embodiments 89-93, wherein the anti-TL 1A antibody is an antagonist of TL 1A.

95. A method for detecting a genotype of interest in a subject having at least one of an inflammatory, fibrotic, and fibrotic disease or condition, the method comprising:

(a) Contacting genetic material from the subject with a composition sufficiently complementary to and capable of crossing the genotype of interest, the composition comprising:

(i) A detectably labeled oligonucleotide probe comprising the sequence of SEQ ID NO: at least 10 consecutive nucleobases provided by any one of 2001-2048 or 2057-2059,

(ii) A detectably labeled oligonucleotide probe comprising the sequence of SEQ ID NO: at least 10 consecutive nucleobases provided by any one of 2001-2048 or 2057-2059,

(iii) A detectably labeled oligonucleotide probe comprising the sequence of SEQ ID NO: at least 10 consecutive nucleobases provided by any one of 2001-2048 or 2057-2059,

(iv) A detectably labeled oligonucleotide probe comprising a nucleic acid sequence differing by up to three nucleobases from a probe selected from the group consisting of (i) - (iii), provided that said detectably labeled oligonucleotide probe of (iv) hybridizes to said genotype of interest,

(v) A detectably labeled oligonucleotide probe comprising a nucleic acid sequence complementary to a probe selected from the group consisting of (i) - (iv), or

(vi) A combination of probes selected from the group consisting of (i) - (v),

wherein the detectably labeled oligonucleotide probes of (i), (ii) and (iii) are different,

(b) Detecting the presence or absence of hybridization of the genetic material to the composition using the detectably labeled probe, whereby hybridization of the genetic material to the composition is indicative of the presence of the genotype of interest in the subject.

96. The method of embodiment 95, provided that the presence of the genotype of interest indicates that the subject comprises elevated levels of TL1A.

97. The method of embodiment 95 or embodiment 96, provided that the inflammatory, fibrostenotic, or fibrotic disease or condition comprises Crohn's Disease (CD), scleroderma, or pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis).

98. The method of embodiment 97, provided that the CD comprises ileum, ileum colon or colon CD.

99. The method of embodiment 99 or 92, with the proviso that the inflammatory disease is Ulcerative Colitis (UC).

100. A method of treating at least one of an inflammatory disease, a fibrotic disease in a subject according to any one of embodiments 95 to 99, the method comprising:

a) Administering to a subject as in any one of embodiments 95-89 a therapeutically effective amount of an inhibitor of TL1A activity or expression, provided that the subject comprises the genotype of interest.

101. The method of embodiment 100, with the proviso that the inhibitor of TL1A activity comprises an anti-TL 1A ligand antibody or an antigen binding fragment thereof.

102. A composition comprising SEQ ID NO:2001-2048 or 2057-2059, or a complement thereof, wherein said contiguous nucleobase residues comprises at least 10 but less than 50 contiguous nucleobase residues of any one of SEQ ID NOs: 2001-2048 or 2057-2059, and wherein the contiguous nucleobase residue is linked to a detectable molecule.

103. The composition of embodiment 102, provided that the detectable molecule is a fluorophore.

104. The composition of embodiments 102-103, wherein the contiguous nucleobase residues comprise the amino acid sequence of SEQ ID NO:2001-2048 or 2057-2059.

105. The composition of embodiments 102-104, wherein the contiguous nucleobase residues comprise the amino acid sequence of SEQ ID NO: a nucleobase at position 501 of any one of 2060-2108 or 364141-364142.

106. The composition of embodiments 102-105, provided that the contiguous nucleobase residues are linked to a quencher.

107. A kit comprising the composition of any one of embodiments 102 to 106, and a nucleic acid capable of amplifying SEQ ID NO:2001-2048 or 2057-2059, said at least 15 consecutive nucleic acid molecules comprising a primer pair of at least 15 consecutive nucleic acid molecules comprising a sequence set forth in any one of SEQ ID NOs: 2001-2048 or 2057-2059.

108. A method comprising contacting DNA from a subject with the composition of any one of embodiments 102-106 or the kit of any one of embodiments 107 under conditions configured to hybridize the composition to the DNA if the DNA comprises a sequence complementary to the composition.

109. A method comprising treating the subject of embodiment 108 with an inhibitor of TL1A activity or expression, provided that the DNA from the subject comprises a sequence complementary to the composition.

110. The method of embodiment 109, with the proviso that the inhibitor of TL1A comprises an anti-TL 1A antibody or an antigen binding fragment thereof.

111. A method of identifying a risk of developing a TL1A mediated disease or condition comprising at least one of an inflammatory, fibrotic, and fibrotic disease or condition in a subject, the method comprising:

a) Assaying a sample obtained from the subject to identify the presence of a genotype comprising the polymorphism provided in table 1 or table 4 or a polymorphism in Linkage Disequilibrium (LD) state therewith; and

b) Identifying a risk of developing at least one of an inflammatory, fibrotic, and fibrotic disease or condition in the subject, provided that the presence of the genotype is identified in step (a).

112. A method of selecting a subject for treatment, the method comprising:

a) Assaying a sample obtained from the subject to identify the presence of a genotype comprising the polymorphism provided in table 1 or table 4 or a polymorphism in Linkage Disequilibrium (LD) state therewith; and

b) Selecting the subject for treatment with an inhibitor of TL1A activity or expression, provided that the presence of the genotype is identified in step (a).

113. The method of any one of embodiments 111 to 112, provided that the genotype of the subject is homozygous.

114. The method of any one of embodiments 111 to 113, wherein the genotype comprises at least two polymorphisms provided in table 1 or table 4.

115. The method of any one of embodiments 111 to 114, wherein the genotype comprises at least three polymorphisms provided in table 1 or table 4.

116. The method of any one of embodiments 111 to 115, wherein the genotype comprises at least four polymorphisms provided in table 1 or table 4.

117. The method of any one of embodiments 111 to 116, wherein the genotype comprises at least five polymorphisms provided in table 1 or table 4.

118. The method of any one of embodiments 111 to 117, wherein the genotype comprises at least six polymorphisms provided in table 1 or table 4.

119. The method of any one of embodiments 111 to 118, wherein the genotype comprises at least seven polymorphisms provided in table 1 or table 4.

120. The method of any one of embodiments 111 to 119, wherein the genotype comprises at least eight polymorphisms provided in table 1 or table 4.

121. The method of any one of embodiments 111 to 1220, wherein the genotype comprises at least one polymorphism that comprises a non-reference allele.

122. The method of embodiments 111-121, further comprising treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression.

123. The method of embodiment 122, wherein the inhibitor of TL1A activity or expression is an anti-TL 1A antibody.

124. The method of embodiment 123, wherein the anti-TL 1A antibody is selected from table 20.

125. The method of embodiment 123, wherein the anti-TL 1A antibody comprises the amino acid sequences provided in tables 16-17.

126. The method of embodiment 123, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody selected from table 20.

127. The method of embodiment 123, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody comprising the amino acid sequences provided in tables 16-17.

128. The method of embodiments 123-128, wherein the anti-TL 1A antibody is a neutralizing TL1A antibody.

129. The method of embodiments 123-129, wherein the anti-TL 1A antibody is an antagonist of TL 1A.

130. The method of embodiments 33-65 or 111-121, further comprising administering a therapeutically effective amount of an additional therapeutic agent.

131. The method of embodiment 130, wherein the additional therapeutic agent is a modulator of receptor-interacting serine/threonine kinase 2 (RIPK 2).

132. The method of embodiment 130, wherein the additional therapeutic agent is a modulator of G protein-coupled receptor 35 (GPR 35).

133. The method of embodiment 130, wherein the additional therapeutic agent is a modulator of a CD30 ligand (CD 30L).

134. The method of any one of embodiments 1-134, further comprising predicting a positive therapeutic response in a subject to treatment with an inhibitor of the TL1A activity or expression having a positive predictive value of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

135. The method of any one of embodiments 1-135, further comprising predicting a positive therapeutic response in a subject to treatment with an inhibitor of the TL1A activity or expression having at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% specificity.

136. A method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression, provided that at least three polymorphisms including: rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof; wherein the inhibitor of TL1A activity is an antibody or antigen binding fragment as described herein.

137. The method of embodiment 136, wherein the at least three polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a positive predictive value of at least about 70%.

138. The method of embodiment 136, wherein the at least three polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a specificity of at least about 70%.

139. The method of embodiment 136, wherein the at least three polymorphisms comprise:

(a) rs6478109, rs56124762 and rs1892231;

(b) rs6478109, rs56124762 and rs16901748;

(c) rs6478109, rs1892231 and rs16901748;

(d) rs56124762, rs1892231 and rs16901748;

(e) rs6478109, rs2070558 and rs1892231;

(f) rs6478109, rs2070558 and rs16901748;

(g) rs6478109, rs1892231 and rs16901748;

(h) rs2070558, rs1892231 and rs16901748;

(i) rs6478109, rs2070561 and rs1892231;

(j) rs6478109, rs2070561 and rs16901748;

(k) rs6478109, rs1892231 and rs16901748;

(l) rs2070561, rs1892231 and rs16901748;

(m) rs6478109, rs7935393, and rs1892231;

(n) rs6478109, rs7935393, and rs9806914;

(o) rs6478109, rs7935393, and rs7278257;

(p) rs6478109, rs7935393, and rs2070557;

(q) rs6478109, rs1892231, and rs9806914;

(r) rs6478109, rs1892231, and rs7278257;

(s) rs6478109, rs1892231, and rs2070557;

(t) rs6478109, rs9806914, and rs7278257;

(u) rs6478109, rs9806914, and rs2070557;

(v) rs6478109, rs7278257 and rs2070557;

(w) rs7935393, rs1892231, and rs9806914;

(x) rs7935393, rs1892231 and rs7278257;

(y) rs7935393, rs1892231, and rs2070557;

(z) rs7935393, rs9806914, and rs7278257;

(aa) rs7935393, rs9806914 and rs2070557;

(bb) rs7935393, rs7278257, and rs2070557;

(cc) rs1892231, rs9806914, and rs7278257;

(dd) rs1892231, rs9806914 and rs2070557;

(ee) rs1892231, rs7278257, and rs2070557; or (b)

(ff) rs9806914, rs7278257 and rs2070557.

140. The method of embodiment 136, wherein the at least three polymorphisms further comprise a fourth polymorphism comprising a polymorphism of rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or 11221332, or a substitution polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof.

141. The method of embodiment 136, wherein the at least three polymorphisms in the sample are detected by performing an assay on the sample, the assay configured to detect a nucleotide sequence corresponding to SEQ ID NO:2001-2041 or 2057-2059.

142. The method of embodiment 136, wherein the at least eight polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a positive predictive value of at least about 70%.

143. The method of embodiment 136, wherein the at least eight polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a specificity of at least about 70%.

144. The method of embodiment 136, wherein the at least eight polymorphisms comprise a collection of polymorphisms selected from table 25.

145. The method of embodiment 1, wherein the inflammatory, fibrotic, or fibrotic disease or condition comprises inflammatory bowel disease, crohn's disease, obstructive crohn's disease, ulcerative colitis, intestinal fibrosis, rheumatoid arthritis, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), scleroderma, or primary sclerosing cholangitis.

146. The method of embodiment 145, wherein the crohn's disease is ileal crohn's disease, ileal colonic crohn's disease, or colonic crohn's disease.

147. The method of embodiment 136, wherein the subject has or is at risk of developing a non-response or a loss of response to standard therapy comprising a glucocorticoid, an anti-TNF therapy, an anti-a 4-b7 therapy, an anti-IL 12p40 therapy, or a combination thereof.

148. The method of embodiment 136, wherein the inhibitor of TL1A is an anti-TL 1A antibody or antigen binding fragment.

149. A method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising:

(a) Determining whether the subject suffering from an inflammatory, fibrotic or fibrotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by:

(i) Obtaining or having obtained a sample from the subject; and

(ii) Subjecting the sample to an assay suitable for detecting at least three polymorphisms, including polymorphisms of rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or a polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof; and

(b) Treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of the TL1A activity or expression;

wherein the inhibitor of TL1A activity or expression is an anti-TL 1A antibody or antigen as described herein.

150. The method of embodiment 149, wherein the at least three polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a positive predictive value of at least about 70%.

151. The method of embodiment 149, wherein the at least three polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a specificity of at least about 70%.

152. A method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising:

(c) Determining whether the subject suffering from an inflammatory, fibrotic or fibrotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by:

(iii) Obtaining or having obtained a sample from the subject; and

(iv) Subjecting the sample to an assay suitable for detecting at least eight polymorphisms, including polymorphisms of rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or a polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof; and

(d) Treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of the TL1A activity or expression;

wherein the inhibitor of TL1A activity or expression is an anti-TL 1A antibody or antigen as described herein.

153. The method of embodiment 152, wherein the at least eight polymorphisms predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a positive predictive value of at least about 70%.

154. The method of embodiment 152, wherein the at least eight polymorphisms predict a positive therapeutic response in the subject with at least about 70% specificity for treatment with an inhibitor of the TL1A activity or expression.

155. The method of embodiment 136, wherein the inflammatory, fibrotic, or fibrotic disease or condition comprises inflammatory bowel disease, crohn's disease, obstructive crohn's disease, ulcerative colitis, intestinal fibrosis, rheumatoid arthritis, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), scleroderma, or primary sclerosing cholangitis.

156. The method of embodiment 156, wherein the crohn's disease is ileal crohn's disease, ileal colonic crohn's disease, or colonic crohn's disease.

157. The method of embodiment 149, wherein the inhibitor wherein the TL1A activity or expression is an anti-TL 1A antibody or antigen binding fragment.

158. The method of embodiment 149, wherein the at least three polymorphisms comprise:

(a) rs6478109, rs56124762 and rs1892231;

(b) rs6478109, rs56124762 and rs16901748;

(c) rs6478109, rs1892231 and rs16901748;

(d) rs56124762, rs1892231 and rs16901748;

(e) rs6478109, rs2070558 and rs1892231;

(f) rs6478109, rs2070558 and rs16901748;

(g) rs6478109, rs1892231 and rs16901748;

(h) rs2070558, rs1892231 and rs16901748;

(i) rs6478109, rs2070561 and rs1892231;

(j) rs6478109, rs2070561 and rs16901748;

(k) rs6478109, rs1892231 and rs16901748;

(l) rs2070561, rs1892231 and rs16901748;

(m) rs6478109, rs7935393, and rs1892231;

(n) rs6478109, rs7935393, and rs9806914;

(o) rs6478109, rs7935393, and rs7278257;

(p) rs6478109, rs7935393, and rs2070557;

(q) rs6478109, rs1892231, and rs9806914;

(r) rs6478109, rs1892231, and rs7278257;

(s) rs6478109, rs1892231, and rs2070557;

(t) rs6478109, rs9806914, and rs7278257;

(u) rs6478109, rs9806914, and rs2070557;

(v) rs6478109, rs7278257 and rs2070557;

(w) rs7935393, rs1892231, and rs9806914;

(x) rs7935393, rs1892231 and rs7278257;

(y) rs7935393, rs1892231, and rs2070557;

(z) rs7935393, rs9806914, and rs7278257;

(aa) rs7935393, rs9806914 and rs2070557;

(bb) rs7935393, rs7278257, and rs2070557;

(cc) rs1892231, rs9806914, and rs7278257;

(dd) rs1892231, rs9806914 and rs2070557;

(ee) rs1892231, rs7278257, and rs2070557; or (b)

(ff) rs9806914, rs7278257 and rs2070557.

159. The method of embodiment 136, wherein the at least three polymorphisms further comprise a fourth polymorphism comprising a polymorphism of rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or 11221332, or a substitution polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85, or a combination thereof.

160. The method of embodiment 136, wherein the subject is at risk of developing a non-response or a loss of response to standard therapy comprising a glucocorticoid, an anti-TNF therapy, an anti-a 4-b7 therapy, an anti-IL 12p40 therapy, or a combination thereof.

161. A method of treating an inflammatory, fibrotic, or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, wherein the subject expresses at least three polymorphisms including rs16901748, rs6478109, rs56124762, or a surrogate polymorphism in linkage disequilibrium therewith, as determined by R2 being at least 0.85;

wherein the inhibitor of TL1A expression activity is an anti-TL 1A antibody or antigen binding fragment as described herein.

162. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide, wherein the antibody or antigen binding fragment comprises:

a) A heavy chain comprising heavy chain complementarity determining region 1 (HCDR 1), heavy chain complementarity determining region 2 (HCDR 2), and heavy chain complementarity determining region 3 (HCDR 3), wherein the HCDR1 comprises SEQ ID NO:601 a first amino acid sequence of dtemh; the HCDR2 comprises SEQ ID NO:768, a second amino acid sequence of PASGH; and the HCDR3 comprises SEQ ID NO:805 to a third amino acid sequence of SGGLPD; and

b) A light chain comprising light chain complementarity determining region 1 (LCDR 1), light chain complementarity determining region 2 (LCDR 2), and light chain complementarity determining region 3 (LCDR 3), wherein the LCDR1 comprises SEQ ID NO:851, a fourth amino acid sequence of ASSSVSYMY; the LCDR2 comprises SEQ ID NO:11, a fifth amino acid sequence of attnlas; and said LCDR3 comprises SEQ ID NO:921, a sixth amino acid sequence of GNPRT.

163. The method of embodiment 163, with the proviso that the antibody or antigen binding fragment is a chimeric antibody, CDR-grafted antibody, humanized antibody, fab ', F (ab') 2, fv, disulfide-linked Fv, scFv, single domain antibody, diabody, multispecific antibody, dual specific antibody, anti-idiotype antibody, bispecific antibody, or a combination thereof.

164. The method of embodiment 163, provided that the antibody or antigen binding fragment is a humanized antibody.

165. The method of embodiment 163, wherein the antibody or antigen-binding fragment of embodiment 141 is administered with a pharmaceutically acceptable carrier.

166. The method of embodiment 163, provided that the antibody or antigen-binding fragment is immunoglobulin G (IgG).

167. The method of embodiment 165, provided that the IgG comprises IgG1.

168. The method of embodiment 164, provided that the IgG comprises IgG2.

169. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen-binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide, wherein the antibody or antigen-binding fragment comprises an antibody or antigen-binding fragment thereof that binds to TL1A comprising a polypeptide as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3002 and 3006; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3013.

170. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least eight polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen-binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide, wherein the antibody or antigen-binding fragment comprises an antibody or antigen-binding fragment thereof that binds to TL1A comprising a polypeptide as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3002 and 3006; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3013.

171. The method of embodiment 170 or 171, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:3204.

172. a method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

Wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3005 and 3008; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3012.

173. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least eight polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3005 and 3008; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3012.

174. The method of embodiment 173 or 174, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:3202.

175. the method of any one of embodiments 173 to 175, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3121.

176. the method of any one of embodiments 173 to 175, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3122.

177. the method of any one of embodiments 173 to 175, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3123.

178. the method of any one of embodiments 173 to 175, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3124.

179. the method of embodiment 173 or 174, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:3205.

180. the method of embodiment 173 or embodiment 174, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3122.

181. the method of embodiment 173 or embodiment 174, wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3124.

182. a method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

Wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3005 and 3008; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3013.

183. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least eight polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3005 and 3008; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3013.

184. The method of embodiment 183 or 184, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3122.

185. the method of embodiment 183 or embodiment 184, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:3204.

186. the method of embodiment 183 or embodiment 184, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:3206.

187. a method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3003 and 3008; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3013.

188. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least eight polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression having at least about 51% positive predictive value or specificity, and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 3001. the heavy chain variable region of the Complementarity Determining Regions (CDRs) shown in 3003 and 3008; and a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 3010. 3011 and 3013.

189. The method of embodiment 188 or 189, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3128.

190. the method of embodiment 188 or 189, wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:3206.

191. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject, said at least three polymorphisms predicting a positive therapeutic response in the subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and wherein said inhibitor of TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide, said antibody or antigen binding fragment comprising a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein said heavy chain variable framework region and said light chain variable framework region comprise less than about 14 amino acid modifications in total compared to said human IGHV1-46 x 02 framework and said human IGKV3-20 framework.

192. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

Wherein at least eight polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of the TL1A activity or expression of at least about 51% and wherein the inhibitor of the TL1A activity or expression comprises an antibody or antigen binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL 1A) polypeptide comprising a heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework, and a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein said heavy chain variable framework region and said light chain variable framework region comprise less than about 14 amino acid modifications in total compared to said human IGHV1-46 x 02 framework and said human IGKV3-20 framework.

193. The method of embodiment 193 or 194, wherein the heavy chain variable framework region and the light chain variable framework region comprise a total of 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 amino acid modifications, or no amino acid modifications as compared to the human IGHV1-46 x 02 framework and the human IGKV3-20 framework.

194. The method of any one of embodiments 170-193, wherein the antibody is humanized.

195. The method of any one of embodiments 170-194, wherein the antibody comprises a human IgG1 crystallizable fragment (Fc) region.

196. The method of any one of embodiments 170-194, wherein the antibody comprises a human IgG4 crystallizable fragment (Fc) region.

197. The method of embodiments 170-197, wherein the disease or condition comprises inflammatory bowel disease.

198. The method of embodiments 170-198, wherein the disease or condition comprises crohn's disease.

199. The method of embodiments 170-199, wherein the disease or condition comprises ulcerative colitis.

200. The method of any one of embodiments 170-200, further comprising predicting a positive therapeutic response in the subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

201. The method of any one of embodiments 169-201, further comprising predicting a positive therapeutic response in a subject to treatment with an inhibitor of said TL1A activity or expression having at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% specificity.

202. The method of any one of embodiments 162-201, an inflammatory, fibrotic, or fibrotic disease or condition comprising inflammatory bowel disease, crohn's disease, obstructive crohn's disease, ulcerative colitis, intestinal fibrosis, rheumatoid arthritis, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), scleroderma, or primary sclerosing cholangitis.

In some embodiments, the at least three polymorphisms are eight polymorphisms. Paragraph [045], embodiment 54 (495 combinations) provides a non-limiting example of eight polymorphic combinations.

Kit for detecting a substance in a sample

Kits for treating IBD (e.g., CD, UC, and/or mrUC) are also provided. The kit comprises an antibody described herein that can be used to perform the methods described herein. Kits may be used to practice the methods of the invention for providing treatment to IBD, CD, UC and/or mrUC patients by administration of an anti-TL 1A antibody. A kit is a collection of materials or components comprising at least one composition of the invention. Thus, in some embodiments, the kit contains a composition comprising an anti-TL 1A antibody for use in treating IBD, CD, UC and/or MR-UC as described above. In other embodiments, the kit contains all components necessary and/or sufficient for performing a detection assay on TL1A, including all controls, instructions for performing the assay, and any necessary software for analyzing and presenting the results.

The exact nature of the components configured in the kit of the invention depends on its intended purpose. For example, some embodiments are configured for the purpose of treating IBD, CD, UC and/or MR-UC. In one embodiment, the kit is configured, inter alia, for the purpose of treating a mammalian subject. In another embodiment, the kit is configured, inter alia, for the purpose of treating a human subject. In other embodiments, the kit is configured for veterinary use, treating subjects such as, but not limited to, farm animals, livestock, and laboratory animals.

Instructions for use may be included in the kit. "instructions for use" generally include a tangible representation describing the techniques employed in using the components of the kit to achieve a desired result, such as therapeutic or relief IBD, CD, UC and/or MR-UC. Optionally, the kit also contains other useful components, such as diluents, buffers, pharmaceutically acceptable carriers, syringes, catheters, applicators, pipetting or measuring tools, bandage materials or other useful appliances as will be readily recognized by those skilled in the art.

The materials or components assembled in the kit may be provided to a physician, stored in any convenient and suitable manner that preserves their operability and utility. For example, the components may be in dissolved, dehydrated or lyophilized form; they may be provided at room temperature, refrigerated or frozen temperatures. The components are typically contained in a suitable packaging material. As used herein, the phrase "packaging material" refers to one or more physical structures for containing the contents of a kit (such as the present compositions, etc.). The packaging material is constructed by well known methods, preferably providing a sterile, contaminant-free environment. The packaging materials employed in the kit are those commonly used in gene expression assays and therapeutic applications. As used herein, the term "package" refers to a suitable solid matrix or material, such as glass, plastic, paper, foil, etc., capable of containing the individual kit components. Thus, for example, the package may be a glass vial or a prefilled syringe for containing a suitable amount of a composition of the invention containing an anti-TL 1A antibody and/or primers and probes for TL 1A. The packaging material typically has an external label that indicates the contents and/or purpose of the kit and/or its components.

Disclosed herein are kits useful for detecting genotypes and/or biomarkers disclosed herein. In some embodiments, the kits disclosed herein can be used to diagnose and/or treat a disease or condition in a subject; or selecting a patient for treatment and/or monitoring the treatment disclosed herein. In some embodiments, the kit comprises a composition described herein useful for performing the methods described herein. The kit comprises a collection of materials or components comprising at least one composition. Thus, in some embodiments, the kit contains a composition comprising a pharmaceutical composition for treating IBD. In other embodiments, the kit contains all components necessary and/or sufficient to perform an assay for detecting and measuring IBD markers, including all controls, instructions for performing the assay, and any necessary software for analyzing and presenting the results.

In some cases, the kits described herein comprise components for detecting the presence, absence, and/or amount of target nucleic acids and/or proteins described herein. In some embodiments, the kit further comprises components for detecting the presence, absence, and/or amount of a serological marker described herein. In some embodiments, the kit comprises a composition described herein (e.g., primer, probe, antibody). The present disclosure provides kits suitable for assays such as enzyme-linked immunosorbent assays (ELISA), single molecule arrays (Simoa), PCR, and qPCR. The exact nature of the components configured in the kit depends on its intended purpose.

In some embodiments, the kits described herein are configured for the purpose of treating and/or characterizing a disease or condition (e.g., crohn's disease, pulmonary fibrosis, scleroderma, ulcerative colitis) or a subclinical phenotype thereof (e.g., a stenosis, a penetration, or a stenosis and penetration disease phenotype) in a subject. In some embodiments, the kits described herein are configured for the purpose of identifying a subject suitable for treatment with an inhibitor of TL1A activity or expression (e.g., an anti-TL 1A antibody). In some embodiments, the kit is configured, inter alia, for the purpose of treating a mammalian subject. In some embodiments, the kit is configured, inter alia, for the purpose of treating a human subject. In other embodiments, the kit is configured for veterinary use, treating subjects such as, but not limited to, farm animals, livestock, and laboratory animals. In some embodiments, the kit is configured to select a subject for a therapeutic agent (such as those disclosed herein). In some embodiments, the kit is configured to select a subject for treatment with a therapeutic agent disclosed herein. An exemplary therapeutic agent is an anti-TL 1A antibody.

Instructions for use may be included in the kit. Optionally, the kit also contains other useful components, such as diluents, buffers, pharmaceutically acceptable carriers, syringes, catheters, applicators, pipetting or measuring tools, bandaging materials or other useful tools. The materials or components assembled in the kit may be provided to a physician, stored in any convenient and suitable manner that preserves their operability and utility. For example, the components may be in dissolved, dehydrated or lyophilized form; they may be provided at room temperature, refrigerated or frozen temperatures. The components are typically contained in a suitable packaging material. As used herein, the phrase "packaging material" refers to one or more physical structures for containing the contents of a kit (such as a composition, etc.). The packaging material is constructed by well known methods, preferably providing a sterile, contaminant-free environment. The packaging materials employed in the kit are those commonly used in gene expression assays and therapeutic applications. As used herein, the term "package" refers to a suitable solid matrix or material, such as glass, plastic, paper, foil, etc., capable of containing the individual kit components. Thus, for example, the package may be a glass vial or a prefilled syringe for containing an appropriate amount of the pharmaceutical composition. The packaging material has an external label indicating the contents and purpose of the kit and/or its components.

System and method for controlling a system

Disclosed herein are systems for treating a subject with an inhibitor of TL1A activity or expression (e.g., an anti-TL 1A antibody), wherein at least three polymorphisms are detected in a sample obtained from the subject that predict a positive therapeutic response in the subject to treatment with an inhibitor of TL1A activity or expression having a positive predictive value or specificity of at least about 51%. In some embodiments, the systems described herein include kits and compositions for detecting the genotypes described herein in a biological sample of a subject. The system may include a computer system for implementing one or more methods of the present disclosure, such as receiving genotype data 201 of a subject, entering the genotype data into an algorithm to generate a TNFSF15 profile 202, and generating a report 203 including the TNFSF15 profile of the subject, and displaying the report 204 to a user on a graphical user interface, as shown in FIG. 2. As used herein, a "TNFSF15 profile" refers to a profile of one or more genotypes described herein of a subject detected in a biological sample obtained from the subject. In some embodiments, the TNFSF15 profile comprises a positive, negative, or indeterminate result (e.g., a therapeutic response to treatment with an inhibitor of TL1A activity or expression).

Computer system

Fig. 3 shows a computer system 301 programmed or otherwise configured to generate a TNFSF15 profile of a subject in need thereof. Computer system 301 may adjust various aspects of the present disclosure that generate TNFSF15 profiles (e.g., receive genotype data, generate reports with TNFSF15 profiles of biological samples, and display the reports to a user), for example, by including permissions or encryption of genotype data and/or TNFSF15 profiles of the subject to ensure patient privacy.

The computer system 301 may be the user's electronic device or a computer system that is remotely located relative to the electronic device. The electronic device may be a mobile electronic device, such as a mobile electronic device belonging to a doctor.

Computer system 301 includes a central processing unit (CPU, also referred to herein as a "processor" and a "computer processor") 305, which may be a single-core or multi-core processor, or multiple processors for parallel processing. Computer system 301 also includes memory or memory location 310 (e.g., random access memory, read only memory, flash memory), electronic storage unit 315 (e.g., hard disk), communication interface 320 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 325 such as cache, other memory, data storage, and/or electronic display adapter. The memory 310, the storage unit 315, the interface 320, and the peripheral device 325 communicate with the CPU 305 through a communication bus (solid line) such as a motherboard. The storage unit 315 may be a data storage unit (or data repository) for storing data. Computer system 301 may be operably coupled to a computer network ("network") 330 by way of a communication interface 320. The network 330 may be the internet, i.e., the internet and/or an extranet, or an intranet and/or an extranet in communication with the internet. In some cases, network 330 is a telecommunications and/or data network. Network 330 may include one or more computer servers that may implement distributed computing, such as cloud computing. In some cases, network 330 may implement a peer-to-peer network with the aid of computer system 301 that may enable devices coupled to computer system 301 to appear as clients or servers.

The CPU 305 may execute a series of machine readable instructions that may be embodied in a program or software. The instructions may be stored in a memory location, such as memory 310. The instructions may be directed to the CPU 305, which may then program or otherwise configure the CPU 305 to implement the methods of the present disclosure. Examples of operations performed by the CPU 305 may include fetch, decode, execute, and write back.

The CPU 305 may be part of a circuit such as an integrated circuit. One or more other components of system 301 may be included in the circuit. In some cases, the circuit is an Application Specific Integrated Circuit (ASIC).

The storage unit 315 may store files such as drivers, libraries, and saved programs. The storage unit 315 may store user data such as user preferences and user programs. In some cases, computer system 301 may include one or more additional data storage units external to computer system 301, such as on a remote server in communication with computer system 301 via an intranet or the Internet.

Computer system 301 may communicate with one or more remote computer systems over network 330. For example, computer system 301 may communicate with a user's remote computer system. Examples of remote computer systems include personal computers (e.g., portable PCs), tablet or tablet PCs (e.g., iPad、/>Galaxy Tab), phone, smart phone (e.g.)>iPhone, android-enabled device, +.>) Or a personal digital assistant. A user may access computer system 301 through network 330.

The methods as described herein may be implemented by means of machine (e.g., computer processor) executable code stored on an electronic storage location of computer system 301, such as on memory 310 or electronic storage unit 315. The machine executable code or machine readable code may be provided in the form of software. During use, code may be executed by processor 305. In some cases, code may be retrieved from the memory unit 315 and stored on the memory 310 for ready access by the processor 305. In some cases, electronic storage unit 315 may be eliminated and machine executable instructions stored on memory 310.

The code may be precompiled and configured for use with a machine having a processor adapted to execute the code, or may be compiled during runtime. The code may be provided in a programming language that is selectable to enable execution of the code in a precompiled or just compiled manner.

Aspects of the systems and methods provided herein, such as computer system 301, may be embodied in programming. Aspects of the technology may be considered to be "an article" or "an article of manufacture" that is typically in the form of machine (or processor) executable code and/or associated data carried or embodied in a type of machine-readable medium. The machine executable code may be stored on an electronic storage unit such as a memory (e.g., read only memory, random access memory, flash memory) or a hard disk. The "storage" media may include any or all of the tangible memory of a computer, processor, etc., or related modules thereof, such as various semiconductor memories, tape drives, disk drives, etc., which may provide non-transitory storage for software programming at any time. All or part of the software may sometimes communicate over the internet or various other telecommunications networks. Such communication may enable, for example, loading of software from one computer or processor into another computer or processor, such as from a management server or host computer into a computer platform of an application server. Thus, another type of medium that can carry software elements includes optical, electrical, and electromagnetic waves, such as those used through physical interfaces between local devices, through wired and optical landline networks, and through various air links. Physical elements carrying such waves, such as wired or wireless links, optical links, etc., may also be considered as media carrying software. As used herein, unless limited to a non-transitory, tangible "storage" medium, terms, such as computer or machine "readable medium," refer to any medium that participates in providing instructions to a processor for execution.

Thus, a machine-readable medium, such as computer-executable code, may take many forms, including but not limited to, tangible storage media, carrier wave media, or physical transmission media. Nonvolatile storage media includes, for example, optical or magnetic disks, any storage devices, such as any computers, such as may be used to implement the databases shown in the figures. Volatile storage media include dynamic memory, such as the main memory of a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier wave transmission media can take the form of electrical or electromagnetic signals, or acoustic or light waves, such as those generated during Radio Frequency (RF) and Infrared (IR) data communications. Thus, common forms of computer-readable media include, for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD, or DVD-ROM, any other optical medium, punch card reels (punch cards paper tape), any other physical storage medium with patterns of holes, RAM, ROM, PROM and EPROM, FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, a cable or link transporting such a carrier wave, or any other medium from which a computer can read programming code and/or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

Computer system 301 may include or be in communication with an electronic display 335 that includes a User Interface (UI) 340 for providing, for example, a report including a TNFSF15 profile of a subject or other relevant clinical information for the purpose of informing a subject of a series of therapeutic agents (e.g., anti-TL 1A antibodies) treating a disease or condition described herein. Examples of UIs include, but are not limited to, graphical User Interfaces (GUIs) and web-based user interfaces.

The methods and systems of the present disclosure may be implemented by means of one or more algorithms. The algorithm, when executed by the central processing unit 305, may be implemented by means of software. The algorithm may, for example, perform: (a) receiving genotype data of a subject 401, (b) determining whether genotypes of at least three polymorphisms are heterozygous or homozygous 402, (c) generating a result using predetermined parameters 403, and (d) displaying the result 404 to a user (e.g., a doctor) on a user interface of an electronic device, as shown in fig. 4. In some embodiments, the result is positive, negative, or indeterminate. In some embodiments, the predetermined parameter is a genotype combination known to predict a therapeutic response to treatment, such as treatment with an inhibitor of TL1A activity or expression.

Web application program

In some embodiments, the computer system includes software for a web application. Those skilled in the art will recognize in light of the disclosure provided herein that web applications may utilize one or more software frameworks and one or more database systems. For example, web applications build on a software framework, such asNET or Ruby on Rails (RoR). In some cases, web applications utilize one or more database systems, including relational, non-relational, feature-oriented, associative, and XML database systems, as non-limiting examples. Suitable relational database systems include, as non-limiting examples +.>SQL server, mySQL ^TM And->Those skilled in the art will also recognize that web applications may be written in one or more versions of one or more languages. In some embodiments, the web application is written in one or more markup languages, presentation definition languages, client-side scripting languages, server-side coding languages, database query languages, or combinations thereof. In some embodiments, web applications are written in a markup language such as hypertext markup language (HTML), extensible hypertext markup language (XHTML), or extensible markup language (XML), to some extent. In some embodiments, the web application is written in a representation definition language such as Cascading Style Sheets (CSS) to some extent. In some embodiments, the web application is in part described in terms of applications such as Asynchronous Javascript and XML (AJAX), for example >Actionscript, javascript orIs written in a client scripting language. In some embodiments, the web application is implemented to some extent with a web application such as an Active Server Page (ASP), or +>Perl、Java ^TM Java Server Pages (JSP), hypertext preprocessor (PHP), python ^TM 、Ruby、Tcl、Smalltalk、/>Or a server-side encoding language of Groovy. In some embodiments, web applications are written in a database query language, such as Structured Query Language (SQL), to some extent. The web application may integrate an enterprise server product, such as +.>Lotus/>The web application may include a media player element. The media player element may utilize one or more of a number of suitable multimedia technologies including, as non-limiting examples +.> HTML 5、Java ^TM And->

Mobile application program

In some embodiments, the computer system includes software for a mobile application. The mobile digital processing device may be provided with a mobile application when it is manufactured. The mobile application may be provided to the mobile digital processing device through a computer network as described herein.

Mobile applications are created by techniques known to those skilled in the art using hardware, language, and development environments known in the art. Those skilled in the art will recognize that mobile applications may be written in several languages. Suitable programming languages include, by way of non-limiting example, C, C ++, C#, featureive-C, java ^TM 、Javascript、Pascal、Feature Pascal、Python ^TM Ruby, VB.NET, WML and XHTML/HTML with or without CSS, or combinations thereof.

Suitable mobile application development environments are available from several sources. As non-limiting examples, commercially available development environments include AirplaySDK, alcheMo,Celsius, bedrock Flash Lite NET Compact Framework Rhomobile and WorkLight Mobile Platform. As non-limiting examples, other development environments are available for free, including but not limited to Lazarus, mobiFlex, moSync and Phonegap. Further, as a non-limiting example, mobile device manufacturers distribute software development kits, including iPhone and IPad (iOS) SDKs, android ^TM SDK、/>SDK、BREW SDK、/>OS SDK, symbian SDK, webOS SDK and +.>Mobile SDK。

Those skilled in the art will recognize that several commercial forums may be used for distribution of mobile applications, including, as non-limiting examplesApp Store、Android ^TM Market、/>App World, app Store for Palm device, app catalyst for webOS, +.f. for mobile device>Marketplace, for ∈>Ovi Store of the device,/->Apps and->DSi Shop。

Standalone applications

In some embodiments, the computer system includes a software independent application, which is a program that can run as a stand-alone computer process, without being attached to an existing process, such as a plug-in. Those skilled in the art will recognize that standalone applications are sometimes compiled. In some cases, a compiler is a computer program that converts source code written in a programming language into binary feature code, such as assembly language or machine code. Suitable compiled programming languages include, by way of non-limiting example, C, C ++, featureive-C, COBOL, delphi, eiffel, java ^TM 、Lisp、Python ^TM Visual Basic and VB.NET or combinations thereof. Typically, the compilation may be at least partially performed to create an executable program. In some cases, the computer program includes one or more executable compiled applications.

Web browser plug-in

In some embodiments, the computer system includes software that includes a web browser plug-in. In some cases, a plug-in is one or more software components that add specific functionality to a larger software application at the time of computation. A manufacturer of a software application may support plug-ins to enable third party developers to create the ability to extend the application, to support easy addition of new features, and to reduce the size of the application. When supported, the plug-in is able to customize the functionality of the software application. For example, plug-ins are commonly used in web browsers to play video, generate interactivity, scan for viruses, and display specific file types. Those skilled in the art will be familiar with several web browser plug-ins, includingPlayer、 And->The toolbar may include one or more web browser extensions, add-ons, or add-ons. The toolbar may include one or more browser bars, tool bands, or desktop areas.

In view of the disclosure provided herein, those skilled in the art will recognize that several plug-in frameworks are available that enable plug-ins to be developed in a variety of programming languages, including, as non-limiting examples, C++, delphi, java ^TM 、PHP、Python ^TM And VB. NET or combinations thereof.

In some embodiments, a Web browser (also referred to as an internet browser) is a software application designed for use with a network-connected digital processing device for retrieving, presenting, and traversing information resources on the world wide Web. Suitable web browsers include, by way of non-limiting exampleInternetChrome、/>OperaAnd KDE Konqueror. In some cases, the web browser is a mobile web browser. Mobile web browsers (also known as mini-browsers, and wireless browsers) may be designed for mobile digital processing devices including, by way of non-limiting example, handheld computers, tablet computers, netbook computers, notebook computers, smartphones, music players, personal Digital Assistants (PDAs), and handheld video gaming systems. Suitable mobile web browsers include, as non-limiting examples +.>Browser, RIM->A browser, Blazer、/>Browser, mobile device-directed Internet/>Mobile、/>Basic Web、/>Browser, opera->Mobile and->PSP ^TM And (5) a browser.

Software module

The media, methods, and systems disclosed herein include one or more software, server, and database modules, or uses thereof. In view of the disclosure provided herein, software modules may be created by techniques known to those skilled in the art using machines, software, and languages known in the art. The software modules disclosed herein may be implemented in a variety of ways. In some embodiments, the software modules include files, code segments, programming features, programming structures, or combinations thereof. A software module may include multiple files, multiple code segments, multiple programming features, multiple programming structures, or a combination thereof. By way of non-limiting example, the one or more software modules include a web application, a mobile application, and/or a standalone application. The software modules may be in a computer program or application. A software module may be in more than one computer program or application. The software modules may be hosted on one machine. A software module may be hosted on more than one machine. The software module may be hosted on a cloud computing platform. The software modules may be hosted on one or more machines at a location. A software module may be hosted on one or more machines in more than one location.

Database for storing data

The media, methods, and systems disclosed herein include one or more databases or uses thereof. In view of the disclosure provided herein, those skilled in the art will recognize that many databases are suitable for storing and retrieving geological profiles, operator activities, departments of interest, and/or contact information of the privilege owners. Suitable databases include, by way of non-limiting example, relational databases, non-relational databases, feature-oriented databases, feature databases, entity-relational model databases, associative databases, and XML databases. In some embodiments, the database is internet-based. In some embodiments, the database is web-based. In some embodiments, the database is cloud computing based. The database may be based on one or more local computer storage devices.

Data transmission

The subject matter described herein, including methods for generating TNFSF15 profiles, is configured to be performed in one or more facilities at one or more locations. The facility location is not limited by country and includes any country or region. In some cases, one or more steps are performed in a different country than another step of the method. In some cases, the one or more steps for obtaining the sample are performed in a different country than the one or more steps for detecting the presence or absence of the genotype in the biological sample. In some embodiments, one or more method steps involving a computer system are performed in a different country than another step of the methods provided herein. In some embodiments, the data processing and analysis is performed in a different country or location than one or more steps of the methods described herein. In some embodiments, one or more articles, products, or data are transferred from one or more facilities to one or more different facilities for analysis or further analysis. Articles of manufacture include, but are not limited to, one or more components obtained from a subject, such as processed cellular material. Processed cellular material includes, but is not limited to, cDNA reverse transcribed from RNA, amplified cDNA, sequenced DNA, isolated and/or purified RNA, isolated and/or purified DNA, and isolated and/or purified polypeptides. Data includes, but is not limited to, information about subject stratification and any data generated by the methods disclosed herein. In some embodiments of the methods and systems described herein, the analysis is performed and the subsequent data transmission step will convey or transmit the results of the analysis.

In some embodiments, any steps of any methods described herein are performed by a software program or module on a computer. In further or other embodiments, transferring data from any step of any of the methods described herein to and from facilities located within the same or different countries includes analyzing in one facility at a particular location and shipping the data to another location or directly to individuals in the same or different countries. In further or other embodiments, the data from any step of any of the methods described herein is transferred to and/or received from a facility located within the same or different country, including data input performed in one facility in a particular location, such as analysis of genetic or processed cellular material, and corresponding data transmitted to another location or directly to an individual in the same or different location or country, such as data related to diagnosis, prognosis, responsiveness to therapy (e.g., anti-TL 1A in further or other embodiments), and the like.

Business method using computer

The methods described herein may utilize one or more computers. The computer may be used to manage customer and biological sample information such as sample or customer tracking, database management, analysis of molecular profiling data, analysis of cytological data, storage of data, billing, marketing, reporting of results, storage of results, or combinations thereof. The computer may include a monitor or other user interface for displaying data, results, billing information, marketing information (e.g., demographics), customer information, or sample information. The computer may also include means for data or information input. The computer may include a processing unit and a fixed or removable medium or combination thereof. A computer may be accessed by a user physically near the computer, for example, through a keyboard and/or mouse, or by a user who does not have to access the physical computer through a communication medium such as a modem, internet connection, telephone connection, or wired or wireless communication signal carrier. In some cases, the computer may be connected to a server or other communication device for relaying information from the user to the computer or from the computer to the user. In some cases, a user may store data or information obtained from a computer on a medium, such as a removable medium, through a communication medium. It is contemplated that data related to the method may be transmitted over such a network or connection for receipt and/or review by a party. The recipient may be, but is not limited to, an individual, a health care provider (e.g., doctor), or a health care manager. In one embodiment, the computer readable medium includes a medium suitable for transmitting the results of an analysis of a biological sample, such as an exosome biological feature. The medium may include results regarding extracellular body biological characteristics of the subject, wherein such results are obtained using the methods described herein.

The entity obtaining the report with TNFSF15 profile may input biological sample information into a database for the purpose of one or more of: inventory tracking, measurement tracking, order tracking, customer management, customer service, billing, and sales. Sample information may include, but is not limited to: customer name, unique customer identification, a medical professional associated with the customer, one or more indicated assays, assay results, sufficiency status, indicated sufficiency test, medical history of the individual, preliminary diagnosis, suspected diagnosis, sample history, insurance provider, medical provider, third party test center, or any information suitable for storage in a database. Sample history may include, but is not limited to: sample age, sample type, collection method, storage method, or transportation method.

The database may be accessed by a customer, medical professional, insurance provider, or other third party. Database access may take the form of electronic communications, such as computers or telephones. The database may be accessed by an intermediary, such as a customer service representative, a business representative, a consultant, a stand-alone test center, or a medical professional. The availability or extent of database access or sample information (such as assay results) may vary upon payment of the product and service fees offered or to be offered. The extent of database access or sample information may be limited to compliance with generally accepted or legitimate patient or customer confidentiality requirements.

System embodiments

Exemplary embodiments include:

1. a computer system for evaluating a sample from a subject, the system comprising:

a) A central computing environment;

b) An input device operably connected to the central computing environment, wherein the input device is configured to receive the presence or absence of a genotype associated with a disease state in the sample;

c) An algorithm executed by the central computing environment, wherein the algorithm is configured to use the presence or absence of the genotype to classify the sample as at least one of: (i) A disease or normal sample, and (ii) is responsive or non-responsive to anti-TL 1A therapy; and

d) An output device operatively connected to the central computing environment, wherein the output device is configured to provide information regarding classification of a user.

2. The computer system of embodiment 1, wherein the disease condition comprises at least one of an inflammatory, a fibrotic, and a fibrotic disease or condition.

3. The computer system of embodiment 1 or embodiment 2, wherein the disease condition is a TL1A mediated disease condition selected from the group consisting of: inflammatory Bowel Disease (IBD), crohn's Disease (CD), obstructive CD, ulcerative Colitis (UC), intestinal fibrosis, rheumatoid arthritis and primary sclerosing cholangitis.

4. The computer system of any preceding embodiment, wherein the sample comprises whole blood, plasma, serum, or tissue.

5. The computer system of any preceding embodiment, wherein the genotype comprises at least one polymorphism selected from table 1 or table 4, polymorphisms in Linkage Disequilibrium (LD) therewith, and any combination thereof.

6. The computer system of any preceding embodiment, wherein the genotype comprises at least one polymorphism that comprises a non-reference allele.

7. The computer system of any preceding embodiment, wherein the genotype comprises at least two polymorphisms provided in table 1 or table 4.

8. The computer system of any preceding embodiment, wherein the genotype comprises at least three polymorphisms provided in table 1 or table 4.

9. The computer system of any preceding embodiment, wherein the genotype comprises at least four polymorphisms provided in table 1 or table 4.

10. The computer system of any preceding embodiment, wherein the genotype comprises at least five polymorphisms provided in table 1 or table 4.

11. The computer system of any preceding embodiment, wherein the genotype comprises at least six polymorphisms provided in table 1 or table 4.

12. The computer system of any preceding embodiment, wherein the genotype comprises at least seven polymorphisms provided in table 1 or table 4.

13. The computer system of any preceding embodiment, wherein the genotype comprises at least eight polymorphisms provided in table 1 or table 4.

14. The computer system of any preceding embodiment, further comprising that the genotype is homozygous.

15. The computer system of embodiments 5 through 13 wherein the LD is formed from at least 0.80, 0.85, 0.90, 0.95, or 1.0 r ² The values define.

16. The computer system of any preceding embodiment, wherein the genotype is associated with a subject's risk of having or of developing a disease state in accordance with up to about 1.0 x 10 ^-6 About 1.0 x 10 ^-7 About 1.0 x 10 ^-8 About 1.0 x 10 ^-9 About 1.0 x 10 ^-10 About 1.0 x 10 ^-20 About 1.0 x 10 ^-30 About 1.0 x 10 ^-40 About 1.0 x 10 ^-50 About 1.0 x 10 ^-60 About 1.0 x 10 ^-70 About 1.0 x 10 ^-80 About 1.0 x 10 ^-90 Or about 1.0 x 10 ^-100 P value of (c).

17. A computer system as in any preceding embodiment, wherein the output device provides a report summarizing the information about the classification.

18. The computer system of any preceding embodiment, wherein the report comprises a suggestion for treatment of the disease condition.

19. The computer system of embodiment 18, wherein the treatment comprises administration of an inhibitor of TL1A activity or expression.

20. The computer system of embodiment 19, wherein the inhibitor of TL1A activity or expression comprises an antibody or antigen binding fragment, peptide or small molecule.

21. The computer system of any preceding embodiment, wherein the genotype is determined with an assay comprising Polymerase Chain Reaction (PCR), quantitative reverse transcription PCR (qPCR), automated sequencing, genotype array, or a combination thereof.

22. Use of a composition comprising one or more binding agents for generating a report classifying a sample from a subject as at least one of: (i) A disease or non-disease condition and (ii) reacting or not reacting against TL1A therapy, wherein the one or more binding agents specifically bind to the at-risk allele provided in table 1 corresponding to the polymorphism provided in table 1, their complements, the polymorphism in linkage disequilibrium therewith, and any combination thereof.

23. The use of embodiment 22, wherein generating the report further comprises:

a) Providing the sample from the subject;

b) Assaying the sample from the subject to detect the presence of a polymorphism provided in table 1;

c) Generating the report based on the results of step (b); and

d) Based on the results of step (b), determining whether the subject has exhibited or is likely to exhibit a positive therapeutic response to treatment with an inhibitor of TL1A activity or expression.

24. The use of embodiment 22 or 23, wherein the disease condition comprises at least one of an inflammatory, fibrostenotic, and fibrotic disease or condition.

25. The use according to embodiments 22 to 24, wherein the disease condition is a TL1A mediated disease condition selected from the group consisting of: inflammatory Bowel Disease (IBD), crohn's Disease (CD), obstructive CD, ulcerative Colitis (UC), intestinal fibrosis, scleroderma, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis), and primary sclerosing cholangitis.

26. The use according to any one of embodiments 22 to 25, wherein the sample comprises whole blood, plasma, serum or tissue.

27. The use of embodiment 23, wherein assaying the sample from the subject of step (b) to detect the presence of a risk allele corresponding to a polymorphism provided in table 1 comprises:

a) Allowing the sample to bind specifically to a nucleic acid comprising SEQ ID NO: one or more binding agent contacts of at least 10 consecutive nucleobases of a risk allele provided in any one of 2001-2041 or 2057-2059; and

b) Determining whether the sample specifically binds to the one or more binding agents, wherein binding of the sample to the one or more binding agents is indicative of the presence of the polymorphism in the subject.

28. The use of embodiment 23, wherein the assaying of the sample from the subject of step (b) to detect the presence of a risk allele corresponding to a polymorphism provided in table 1 comprises sequencing the sample.

29. The use of embodiment 23, wherein the assaying of the sample from the subject of step (b) to detect the presence of the one or more polymorphisms comprises quantifying the amount of DNA comprising the at-risk allele.

30. The use of embodiment 29, wherein the quantification comprises PCR.

31. The use of embodiment 30, wherein the PCR comprises real-time PCR.

32. The use of embodiment 29, wherein said quantifying comprises hybridization.

33. A composition comprising one or more binding agents that specifically bind to a risk allele corresponding to a polymorphism provided in table 1, wherein the one or more binding agents are selected to classify a sample as at least one of: (i) A disease or non-disease or disease condition and (ii) is responsive or non-responsive to anti-TL 1A therapy.

34. The composition of embodiment 33, wherein the one or more binding agents comprise an oligonucleotide.

35. The composition of embodiment 34, wherein the oligonucleotide comprises RNA or DNA.

36. The composition of embodiment 34, wherein the one or more binding agents comprise an aptamer, an antibody, a peptide nucleic acid, or a pyranosyl RNA.

37. A kit for detecting at least one of an inflammatory, fibrotic, and fibrotic disease or condition in a subject, the kit comprising:

a) Specific binding to SEQ ID NO: at least one binding agent of at least 10 consecutive nucleic acid molecules provided in any one of 2001-2041 or 2057-2059 or complements thereof, wherein the at least one binding agent is selected to detect at least one of: (i) A disease or non-disease condition and (ii) either responsive or non-responsive to anti-TL 1A therapy; and

b) A reagent for detecting binding of the at least one binding agent to a DNA sample from a subject.

38. The kit of embodiment 37, wherein the at least one binding agent comprises at least one oligonucleotide.

39. The kit of embodiment 37, wherein the at least one binding agent comprises at least one aptamer, antibody, peptide nucleic acid, or pyranosyl RNA.

40. The kit of embodiments 37-39, wherein the at least one binding agent is labeled with a detectable label.

41. The kit of embodiments 37-40, wherein the at least one binding agent is immobilized to a surface.

42. A system for generating a report classifying a sample as a disease or a non-disease of a disease condition, the system comprising:

a) A computer system that performs the following:

i. generating a molecular profile of the DNA sample based on the presence of at least one polymorphism or complement thereof; and

generating a report classifying the sample based on the molecular profile; and

b) And displaying a computer screen of the report.

43. The system of embodiment 42, wherein the presence of the at least one polymorphism is based on the results of the determination of the DNA sample, which results are entered into a database.

44. The system of embodiments 42-43 further comprising an input of the result.

45. The system of claims 42 to 44, wherein the at least one polymorphism is selected from Table 1.

46. The system of claims 42-45, wherein the at least one polymorphism comprises a non-reference allele.

47. The system of claim 46, wherein the at least one polymorphism is two polymorphisms.

48. The system of claim 46, wherein the at least one polymorphism is three polymorphisms.

49. Use of a composition comprising an inhibitor of TL1A for treating a subject, provided that the subject is a carrier of a genotype comprising the polymorphisms provided in table 1 or table 4.

50. The use of embodiment 49, wherein the inhibitor of TL1A activity or expression is an anti-TL 1A antibody.

51. The use of embodiment 50, wherein the anti-TL 1A antibody is selected from table 20.

52. The use of embodiment 50, wherein the anti-TL 1A antibody comprises the amino acid sequences provided in tables 16-17.

53. The use of embodiment 50, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody selected from table 20.

54. The use of embodiment 50, wherein the anti-TL 1A antibody binds to the same region of human TL1A as a reference antibody comprising the amino acid sequences provided in tables 16-17.

55. The use of embodiments 50-55, wherein the anti-TL 1A antibody is a neutralizing TL1A antibody.

56. The use of embodiments 50-55, wherein the anti-TL 1A antibody is an antagonist of TL 1A.

57. The use of embodiments 49-56, wherein the genotype comprises at least two polymorphisms provided in table 1 or table 4.

58. The use of embodiments 49-56, wherein the genotype comprises at least three polymorphisms provided in table 1 or table 4.

59. The use of embodiments 49-56, wherein the genotype comprises at least four polymorphisms provided in table 1 or table 4.

60. The use of embodiments 49-56, wherein the genotype comprises at least five polymorphisms provided in table 1 or table 4.

61. The use of embodiments 49-56, wherein the genotype comprises at least six polymorphisms provided in table 1 or table 4.

62. The use of embodiments 49-56, wherein the genotype comprises at least seven polymorphisms provided in table 1 or table 4.

63. The use of embodiments 49-56, wherein the genotype comprises at least eight polymorphisms provided in table 1 or table 4.

64. The method for use according to embodiments 49-63, wherein the genotype comprises at least one polymorphism that comprises a non-reference allele.

65. The computer system of embodiments 1-21, wherein the algorithm is configured to classify the sample as positive therapeutic response to the anti-TL 1A therapy with a positive predictive value of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%.

66. The computer system of embodiments 1-21, wherein the algorithm is configured to classify the sample as positive for the anti-TL 1A therapy with a specificity of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

67. The use of embodiments 22-32, wherein the report classifies the sample as positive therapeutic response to the anti-TL 1A therapy with a positive predictive value of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

68. The use as in embodiments 22-32, wherein the report classifies the sample as positive for the anti-TL 1A therapy with a specificity of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

69. The system of embodiments 72-78, wherein the report classifies the sample as positive for a therapeutic response to treatment with anti-TL 1A therapy based on the molecular profile with a positive predictive value of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

70. The system of embodiments 72-78, wherein the report classifies the sample as positive for a therapeutic response to treatment with anti-TL 1A therapy with a specificity of at least or about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% based on the molecular profile.

Definition of the definition

Unless defined otherwise, all technical, symbolic and other technical and scientific terms or terminology used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art to which claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ease of reference, and inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is commonly understood in the art.

Throughout this application, various embodiments may be presented in a range format. It should be understood that the description of the range format is merely for convenience and brevity and should not be interpreted as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all possible sub-ranges as well as individual values within the range. For example, descriptions of ranges such as 1 to 6 should be considered to have specifically disclosed sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numbers within the range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the range.

As used in the specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the term "sample" includes a plurality of samples, including mixtures thereof.

The terms "determining," "measuring," "evaluating," "determining," and "analyzing" are generally used interchangeably herein to refer to the form of measurement. The term includes determining whether an element is present (e.g., detecting). These terms may include quantitative, qualitative, or both quantitative and qualitative determinations. The evaluation may be relative or absolute. "detecting the presence of a thing" may include determining the amount of the presence of something in addition to determining the presence or absence of something according to the context.

The term "in vivo" is used to describe an event that occurs in a subject.

The term "ex vivo" is used to describe events that occur outside the body of a subject. No ex vivo assays were performed on subjects. Instead, it is performed on a sample that is isolated from the subject. An example of an ex vivo assay performed on a sample is an "in vitro" assay.

The term "in vitro" is used to describe an event that occurs in a container that is used to hold a laboratory reagent such that it is separated from the biological source from which the material was obtained. In vitro assays may encompass cell-based assays employing living or dead cells. In vitro assays may also encompass cell-free assays that do not employ intact cells.

As used herein, the term "about" a number refers to the number plus or minus 10% of the number. The term "about" a range means that the range minus 10% of its lowest value plus 10% of its maximum value. For example, an antibody variable region having about 80% identity to a reference variable region may have 72% to 88% identity to the reference variable region.

The terms "complementarity determining region" and "CDR," synonymous with "hypervariable region" or "HVR," are known in the art to refer to non-contiguous amino acid sequences within the variable region of an antibody that confer antigen specificity and/or binding affinity. Typically, three CDRs (CDR-H1, CDR-H2, CDR-H3) are present in each heavy chain variable region, and three CDRs (CDR-L1, CDR-L2, CDR-L3) are present in each light chain variable region. "framework region" and "FR" are known in the art to refer to the non-CDR portions of the variable regions of the heavy and light chains. Typically, four FRs (FR-H1, FR-H2, FR-H3 and FR-H4) are present in each full-length heavy chain variable region, and four FRs (FR-L1, FR-L2, FR-L3 and FR-L4) are present in each full-length light chain variable region. The exact amino acid sequence boundaries for a given CDR or FR can be readily determined using any of a number of well known schemes, including those described by the following documents: kabat et Al, (1991), "Sequences of Proteins of Immunological Interest", 5 th edition, public Health Service, national Institutes of Health, bethesda, MD ("Kabat" numbering scheme), al-Lazikani et Al, (1997) JMB 273, 927-948 ("Chothia" numbering scheme); macCallum et al, J.mol. Biol.262:732-745 (1996), "anti-body-antigen interactions: contact analysis and binding site topography ", j.mol. Biol.262, 732-745" ("Contact" numbering scheme); lefranc MP et al, "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains," Dev Comp Immunol, month 1 2003; 27 (1): 55-77 ("IMGT" numbering scheme); honeygger a and pluckthun a, "Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool, "J Mol Biol, month 6 and 8 of 2001; 309 (3): 657-70, ("Aho" numbering scheme); and Whitelegg NR and Rees AR, "WAM: an improved algorithm for modelling antibodies on the WEB, "Protein eng.12, 2000; 13 (12): 819-24 ("AbM" numbering scheme). In certain embodiments, the CDRs of an antibody described herein can be defined by a method selected from Kabat, chothia, IMGT, aho, abM or a combination thereof.

In some embodiments, an antibody that specifically binds to a protein indicates that the antibody reacts or associates with the protein more frequently, more rapidly, for a longer duration, with greater affinity, or some combination thereof, than an alternative substance (including an unrelated protein).

In some embodiments, the terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to a polymer of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The term also encompasses amino acid polymers that are modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as fusion with another polypeptide and/or conjugation, for example, with a labeling component. Also included within the definition are polypeptides, for example, that contain one or more amino acid analogs (e.g., unnatural amino acids, etc.), as well as other modifications known in the art.

In some embodiments, a protein (such as an antibody described herein) comprises hydrophobic amino acids. Non-limiting exemplary hydrophobic amino acids include glycine (Gly), proline (Pro), phenylalanine (Phe), alanine (Ala), isoleucine (Ile), leucine (Leu), and valine (Val). In some embodiments, a protein (such as an antibody described herein) comprises hydrophilic amino acids. Non-limiting exemplary hydrophilic amino acids include serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), cysteine (Cys), asparagine (Asn), glutamine (gin), arginine (Arg), and histidine (His). In some embodiments, a protein (such as an antibody described herein) comprises amphiphilic amino acids. Non-limiting exemplary amphiphilic amino acids include lysine (Lys), tryptophan (Trp), tyrosine (Tyr), and methionine (Met). In some embodiments, the protein (such as the antibodies described herein) comprises an aliphatic amino acid. Non-limiting exemplary aliphatic amino acids include alanine (Ala), isoleucine (Ile), leucine (Leu) and valine (Val). In some embodiments, a protein (such as an antibody described herein) comprises an aromatic amino acid. Non-limiting exemplary aromatic amino acids include phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). In some embodiments, a protein (such as an antibody described herein) comprises an acidic amino acid. Non-limiting exemplary acidic amino acids include aspartic acid (Asp) and glutamic acid (Glu). In some embodiments, a protein (such as an antibody described herein) comprises a basic amino acid. Non-limiting exemplary basic amino acids include arginine (Arg), histidine (His), and lysine (Lys). In some embodiments, a protein (such as an antibody described herein) comprises a hydroxy amino acid. Non-limiting exemplary hydroxy amino acids include serine (Ser) and threonine (Thr). In some embodiments, a protein (such as an antibody described herein) comprises a sulfur-containing amino acid. Non-limiting exemplary sulfur-containing amino acids include cysteine (Cys) and methionine (Met). In some embodiments, the protein (e.g., an antibody described herein) comprises an amide amino acid. Non-limiting exemplary amide amino acids include asparagine (Asn) and glutamine (Gln).

As used herein, the terms "homology", "homology" or "percent homology" when used herein to describe an amino acid sequence or nucleic acid sequence relative to a reference sequence, can be determined using the formula described by Karlin and Altschul (proc.Natl. Acad.Sci.USA 87:2264-2268, 1990, as modified in proc.Natl. Acad.Sci.USA 90:5873-5877, 1993). Such formulas are incorporated into the base partial alignment search tool (BLAST) program of Altschul et al (J Mol biol.1990, 10, 5; 215 (3): 403-10;Nucleic Acids Res.1997, 9, 1; 25 (17): 3389-402). By the date of filing of this application, the percent homology of a sequence can be determined using the latest version of BLAST. By the date of filing of this application, the percent identity of sequences can be determined using the latest version of BLAST.

As used herein, the term "percent identity (%)" or "percent sequence identity" with respect to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical to amino acid residues in the reference polypeptide sequence after aligning the sequences and introducing gaps (if necessary) to achieve the maximum percent sequence identity and not considering any conservative substitutions as part of the sequence identity. As used herein, the term "percent identity (%)" or "percent sequence identity" with respect to a reference nucleic acid sequence is the percentage of nucleotides in a candidate sequence that are identical to nucleotides in the reference nucleic acid sequence after aligning the sequences and introducing gaps (if necessary) to achieve the maximum percent sequence identity. Alignment for the purpose of determining percent sequence identity may be accomplished in a variety of ways known, for example using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Suitable parameters for aligning sequences can be determined, including the algorithms required to achieve maximum alignment over the full length of the sequences being compared. However, for purposes herein, the sequence comparison computer program ALIGN-2 was used to generate% amino acid sequence identity values. ALIGN-2 sequence comparison computer program was written by Genntech, inc. and the source code was already in the United states copyright office, washington D.C.,20559 for user documentation, which was registered under the United states copyright registry No. TXU 510087. ALIGN-2 programs are publicly available from Genentech, inc., south San Francisco, calif., or can be compiled from source code. The ALIGN-2 program should be compiled for use with the UNIX operating system, including the digital UNIX V4.0D. All sequence comparison parameters were set by the ALIGN-2 program and did not change.

In the case of amino acid sequence comparisons using ALIGN-2, the percent amino acid sequence identity for a given pair of amino acid sequences A, with or against a given amino acid sequence B (which may alternatively be expressed as a given amino acid sequence A having or comprising percent amino acid sequence identity to, with or against a given amino acid sequence B) is calculated as follows: 100 by a fraction X/Y, where X is the number of amino acid residues obtained by the sequence alignment program ALIGN-2 in identical matches in the alignment of the program of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that in the case where the length of amino acid sequence a is not equal to the length of amino acid sequence B, the% amino acid sequence identity of a to B will not be equal to the% amino acid sequence identity of B to a. All% amino acid sequence identity values used herein are obtained using the ALIGN-2 computer program as just described in the previous paragraph, unless specifically stated otherwise.

The term "increased" or "increase" generally means herein an increase in a statically significant amount. In some embodiments, the term "increased" or "increase" means an increase of at least 10% compared to a reference level, e.g., an increase of at least about 10%, at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including any increase between 100%, or 10% -100% compared to a reference level, standard, or control. Other examples of "increasing" include increasing by at least 2-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 1000-fold, or more than the reference level. The increase may be an absolute amount (e.g., protein expression level), or a rate of production (e.g., rate of protein expression between two time points).

The term "reduced" or "reduction" is generally used herein to mean a statistically significant amount of reduction. In some embodiments, "reduced" or "reduced" means reduced by at least 10% from a reference level, such as by at least about 20%, or by at least about 30%, or by at least about 40%, or by at least about 50%, or by at least about 60%, or by at least about 70%, or by at least about 80%, or by at least about 90% or up to and including 100% reduction (e.g., a level that is absent or undetectable from the reference level), or any reduction between 10% and 100% from the reference level. In the context of markers or symptoms, these terms mean a statistically significant reduction in such levels. The reduction may be, for example, at least 10%, at least 20%, at least 30%, at least 40% or more, and is preferably reduced to a level that is acceptable within normal ranges for individuals without the given disease.

In some embodiments, the term "individual" or "subject" is used interchangeably and refers to any animal that will be the recipient of a particular treatment, including, but not limited to, humans, non-human primates, rodents, and domestic and hunting animals. Primates include chimpanzees, cynomolgus monkeys, spider monkeys, and macaques, e.g., rhesus monkeys. Rodents include mice, rats, woodchuck, ferrets, rabbits, and hamsters. Domestic and hunting animals include cattle, horses, pigs, deer, bison, buffalo, feline species (e.g., domestic cats), canine species (e.g., dogs, foxes, wolves), avian species (e.g., chickens, emus, ostriches), and fish (e.g., trout, catfish, and salmon). In various embodiments, the subject may be a subject that has been previously diagnosed with or identified as suffering from or having a condition in need of treatment. In certain embodiments, the subject is a human. In various other embodiments, a subject previously diagnosed with or identified as suffering from or having a condition may or may not experience treatment for the condition. In further embodiments, the subject may also be a subject who has not been previously diagnosed as having a condition (i.e., a subject who exhibits one or more risk factors for the condition). A "subject in need of treatment for a particular condition" may be a subject suffering from, diagnosed with, or at risk of developing the condition. In some embodiments, the subject is a "patient" who has been diagnosed with a disease or condition described herein.

As used herein, the term "gene" refers to a nucleic acid fragment (also referred to as a "coding sequence" or "coding region") encoding a single protein or RNA, optionally together with associated regulatory regions such as promoters, operators, terminators, etc., which may be located upstream or downstream of the coding sequence. Reference herein to a "locus" is a specific location within a gene.

As disclosed herein, the term "genotype" refers to the chemical composition of polynucleotide sequences within an individual's genome. In some embodiments, the genotype comprises Single Nucleotide Polymorphisms (SNPs) or/and indels (insertions or deletions of nucleobases within a polynucleotide sequence). In some embodiments, the genotype of a particular SNP or indel is heterozygous. In some embodiments, the genotype of a particular SNP or indel is homozygous.

As used herein, "polymorphism" refers to a aberration (e.g., mutation) in a nucleic acid sequence or aberration (e.g., insertion/deletion) thereof, as compared to nucleic acid sequences in a reference population. In some embodiments, polymorphisms are common in a reference population. In some embodiments, the polymorphism is rare in the reference population. In some embodiments, the polymorphism is a single nucleotide polymorphism.

As disclosed herein, the term "single nucleotide polymorphism" or SNP refers to a variation of a single nucleotide within a polynucleotide sequence. The term should not be construed as limiting the frequency of SNPs in a given population. Variation of SNPs can take a number of different forms. The single form of a SNP is referred to as an "allele". SNPs may be monoallelic, biallelic, triallelic, or tetrallelic. SNPs may include "risk alleles", "protective alleles", or neither. By way of example, the reference polynucleotide sequence read 5 'to 3' is TTACG. The SNP at allele position 3 of (5 '-TTACG-3') comprises a substitution of the reference allele "A" for the non-reference allele "C". A "C" allele of a SNP is considered to be a "risk" allele if it is associated with an increased probability of developing a phenotypic trait. However, the same SNP may also comprise a substitution of the "a" allele at position 3 for the "T" allele. A T allele of a SNP is considered to be a "protective" allele if it is associated with a reduced probability of developing a phenotypic trait. SNPs can be observed in at least 1% of a given population. In some embodiments, SNPs are represented by an "rs" number, which refers to the accession number of a reference cluster of one or more submitted SNPs in the dbSNP bioinformatics database by the filing date of this patent application, and which is included within the sequence comprising the total number of nucleobases from 5 'to 3'. In some embodiments, a SNP may be further defined by the position of the SNP (nucleobase) within the dbSNP sequence, which position is always the 5' length of the reference sequence plus 1. In some embodiments, SNPs are defined as genomic positions and allelic changes in the reference genome (e.g., in reference human genome construction 37, chromosome 7 at positions 234, 123, 567 changes from the G allele to the a allele). In some embodiments, SNV is defined as the genomic position identified with brackets or "N" in the sequences disclosed herein.

As disclosed herein, the term "indel" refers to an insertion or deletion of a nucleobase within a polynucleotide sequence. Indels may be monoallelic, biallelic, triallelic, or tetrallelic. For a phenotypic trait, an indel may be "at risk", "protective", or neither. In some embodiments, indels are represented by an "rs" number, which refers to the accession number of the reference cluster of indels submitted by one or more of the dbSNP bioinformatics databases by the filing date of this patent application, and which is included within the sequence comprising the total number of nucleobases from 5 'to 3'. In some embodiments, indels can be further defined by the position of the indels/insertions within the dbSNP sequence, which position is always the 5' length of the reference sequence plus 1. In some embodiments, indels are defined as genomic positions and allelic variations in the reference genome. In some embodiments, indels are defined as genomic positions identified with brackets or "N" in the sequences disclosed herein.

As used herein, a "haplotype" encompasses a set of one or more genotypes that are intended to be inherited together in a reference population. In some embodiments, a haplotype comprises a particular polymorphism or another polymorphism in Linkage Disequilibrium (LD) with it.

As used herein, "linkage disequilibrium" or "LD" refers to a non-random association of alleles or indels of different loci in a given population. LD may be defined by a D' value corresponding to the difference between the observed allele or indel frequency and the expected allele or indel frequency in the population (d=pab-PaPb), which is scaled by the theoretical maximum value of D. LD can be determined by the frequency units corresponding to the observed risk in the population and the expected windR of difference between risk frequency units ² The value is defined (d=pab-PaPb), which is scaled by the single frequency of the different loci. In some embodiments, D' comprises at least 0.20. In some embodiments, r ² Including at least 0.70.

In some embodiments, "polynucleotide" or "nucleic acid" as used interchangeably herein refers to a polymer of nucleotides of any length, and includes DNA and RNA. The nucleotide may be a deoxyribonucleotide, a ribonucleotide, a modified nucleotide or base and/or analogue thereof, or any substrate that can be incorporated into a polymer by a DNA or RNA polymerase. Polynucleotides may include modified nucleotides such as, but not limited to, methylated nucleotides and their analogs or non-nucleotide components. The nucleotide structure may be modified before or after assembly of the polymer. The polynucleotide may be further modified after polymerization, such as by binding to a labeling component.

As used herein, the term "medically refractory" or "refractory" refers to treatment that does not induce remission of a disease. In some embodiments, the disease comprises an inflammatory disease as disclosed herein. Non-limiting examples of refractory inflammatory diseases include refractory crohn's disease and refractory ulcerative colitis (e.g., mrUC). Non-limiting examples of standard therapies include glucocorticoids, anti-TNF therapies, anti-a 4-b7 therapies (vedelizumab), anti-IL 12p40 therapies (Wu Sinu mab), thalidomide, and cytotoxins.

As used herein, the term "treatment" refers to the alleviation or elimination of a disorder, disease or condition; or one or more symptoms associated with the disorder, disease, or condition; or to alleviate or eradicate the etiology of the disorder, disease or condition itself. Desirable therapeutic effects may include, but are not limited to, preventing occurrence or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of a disease, preventing metastasis, reducing the rate of disease progression, improving or alleviating a disease condition, and alleviating or improving prognosis.

The term "therapeutically effective amount" refers to an amount of a compound or therapy that, when administered, is sufficient to prevent the development or to some extent ameliorate one or more symptoms of a disorder, disease or disease condition; or an amount of a compound sufficient to elicit the biological or medical response of a cell, tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or clinician. In some cases, a therapeutically effective amount of the drug reduces the severity of the symptoms of the disease or disorder. In some cases, the disease or disorder includes Inflammatory Bowel Disease (IBD), crohn's Disease (CD), or Ulcerative Colitis (UC). In some cases, the IBD, CD, and/or UC is a severe or medically refractory form of IBD, CD, and/or UC. Non-limiting examples of symptoms of IBD, CD, and/or UC include, but are not limited to, diarrhea, fever, fatigue, abdominal pain, abdominal cramps, inflammation, ulcers, nausea, vomiting, bleeding, hematochezia, loss of appetite, and weight loss.

The terms "pharmaceutically acceptable carrier", "pharmaceutically acceptable excipient", "physiologically acceptable carrier" or "physiologically acceptable excipient" refer to a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. The component may be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients of the pharmaceutical formulation. It may also be suitable for contact with tissues or organs of humans and animals without undue toxicity, irritation, allergic response, immunogenicity, or other problems or complications commensurate with a reasonable benefit/risk ratio. See Remington: the Science and Practice of Pharmacy, 21 st edition; lippincott Williams & Wilkins: philiadelphia, PA,2005; handbook of Pharmaceutical Excipients, 5 th edition; rowe et al, the Pharmaceutical Press and the American Pharmaceutical Association:2005, a step of detecting a defect; and Handbook ofPharmaceutical Additives, 3 rd edition; ash and Ash, gower Publishing Company:2007; pharmaceutical Preformulation and Formulation, gibson, CRC Press LLC: boca Raton, FL, 2004).

The term "pharmaceutical composition" refers to a mixture of a compound disclosed herein with other chemical components such as diluents or carriers. The pharmaceutical compositions may facilitate administration of the compounds to an organism. There are a variety of techniques in the art for administering compounds including, but not limited to, oral, injection, aerosol, parenteral and topical administration.

As used herein, the term "inflammatory bowel disease" or "IBD" refers to a gastrointestinal disorder of the gastrointestinal tract. Non-limiting examples of IBD include Crohn's Disease (CD), ulcerative Colitis (UC), indeterminate Colitis (IC), microscopic colitis, diversion colitis, behcet's disease, and other indeterminate forms of IBD. In some cases, IBD includes fibrosis, fibrostenosis, stenosis and/or penetrating disease, obstructive or refractory disease (e.g., mrUC, refractory CD), perianal CD, or other complex forms of IBD.

Non-limiting examples of "samples" include any material from which nucleic acids and/or proteins may be obtained. This includes, by way of non-limiting example, whole blood, peripheral blood, plasma, serum, saliva, mucus, urine, semen, lymph, fecal extracts, cheek swabs, cells, or other bodily fluids or tissues, including but not limited to tissues obtained by surgical biopsy or surgical excision. In various embodiments, the sample comprises tissue from the large intestine and/or small intestine. In various embodiments, the large intestine sample comprises cecum, colon (ascending colon, transverse colon, descending colon, and sigmoid colon), rectum, and/or anal canal. In some embodiments, the small intestine sample comprises the duodenum, jejunum, and/or ileum. Alternatively, the sample may be obtained from a primary patient-derived cell line, or an archived patient sample in the form of a preserved sample, or a freshly frozen sample.

The term "biomarker" comprises a measurable substance in a subject whose presence, level, or activity is indicative of a phenomenon (e.g., phenotypic expression or activity; a disease, condition, subclinical phenotype of a disease or condition, infection; or environmental stimulus). In some embodiments, the biomarker comprises a gene, a gene expression product (e.g., RNA or protein), or a cell type (e.g., immune cell).

As used herein, the term "serological marker" refers to a class of biomarkers representing an antigen response in a subject that can be detected in the serum of the subject. In some embodiments, the serology comprises antibodies against different fungal antigens. Non-limiting examples of serological markers include anti-Saccharomyces cerevisiae antibody (ASCA), anti-neutrophil cytoplasmic antibody (ANCA), E.coli outer membrane porin C (OmpC), anti-limiting malassezia antibody (anti-Malassezia restricta antibody), anti-malassezia thickii antibody (anti-Malassezia pachydermatis antibody), anti-malassezia furfur antibody (anti-Malassezia furfur antibody), anti-malassezia globosa antibody (anti-Malassezia globasa antibody), anti-cladosporium album antibody (anti-Cladosporium albicans antibody), anti-laminarin antibody (ALCA), anti-chitin antibody, pANCA antibody, anti-I2 antibody, and anti-Cbir 1 flagellin antibody.

The term "microbiome" and variations thereof as used herein describe populations and interactions of bacteria, fungi, protozoa, and viruses that are localized to the gastrointestinal tract of a subject. A subject with IBD may have a microbiome present, absent, excessive, reduced, or a combination thereof, as compared to a healthy subject.

As used herein, the term "non-responsive" or "lost response" refers to a phenomenon in a subject or patient that does not respond to induction of standard therapy (e.g., anti-TNF therapy) or experiences a lost response to standard therapy following successful induction of therapy. Induction of standard therapy may include 1, 2, 3, 4, or 5 doses of therapy. The "successful induction" of a therapy may be the initial therapeutic response or benefit provided by the therapy. The loss of response may be characterized by a recurrence of symptoms consistent with onset following successful induction of therapy.

The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

Examples

The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.

Example 1: overview of genotypic identification

Through whole genome association studies (GWAS) (e.g., cases and controls), it has been determined that tumor necrosis factor (ligand) superfamily member 15 (TNFSF 15) is significantly associated with Inflammatory Bowel Disease (IBD), including Crohn's Disease (CD). In addition, elevated levels of TL1A (e.g., RNA and protein) are associated with IBD, including CD. Thus, therapeutic strategies targeting TNFSF15 (TL 1A) expression or activity offer promising approaches for the treatment of IBD. Disclosed herein are the identification, and thus prediction, of polymorphisms associated with increased TNFSF15 (TL 1A) expression in patients with IBD (including CD) using machine learning methods.

A Polygenic Risk Score (PRS) suitable for identifying individuals at increased risk of TNFSF15 (TL 1A) was applied to a CD patient group enrolled in the celars-Sinai medical center. Machine learning algorithms (e.g., XGBoost) are used to identify combinations of polymorphisms associated with increased TNFSF15 (TL 1A) expression or activity. The resulting 41 polymorphisms and possible polymorphism combinations have the best prediction accuracy in training multiple iterations of a machine learning algorithm that is capable of analyzing a large number of combinations of polymorphic interactions (e.g., including nonlinear interactions) in an efficient manner that is not possible with the traditional GWAS method. The resulting polymorphisms can be used to select subjects that may or may not be diagnosed with IBD that may exhibit a therapeutic response to TNFSF15 (TL 1A) -targeted therapeutic agents (e.g., neutralizing anti-TL 1A antibodies).

Example 2: TNFSF15PRS calculation

A multi-gene risk score (PRS) based on polymorphisms within multiple genes of interest (e.g., involving TL 1A-mediated inflammatory pathways) and its associated weights in each respective reference population are calculated. PRS is referred to herein as "TNFSF15PRS". Polymorphisms are selected from a plurality of GWAS based on a defined distance from transcription start and stop sites (e.g., 250 kilobases upstream and downstream) of the gene of interest. Each GWAS is used to define individual weights that contribute polymorphisms to the total score. The GWAS used include, but are not limited to, jostins et al 2012.Nature 491:119-124, liu et al, 2015.Nat Genet.47:979-986, ellingaus et al, 2016.Nat Genet.48:510-518, huang et al, 2017.Nat Genet.49:256-261, and de Lange et al, 2017.Nat Genet.48:256-261.

To confirm the relatedness of the inclusion of polymorphisms within TNFSF15 PRS, the polymorphisms were cross checked by: (i) Evidence of cis QTL, wherein SNPs are directly related to target gene expression in tissue, and (ii) sensitivity analysis, wherein selected polymorphisms are removed from TNFSF15 PRS and regression analysis is performed for disease susceptibility and subclinical phenotype, thereby highlighting relevant polymorphisms at risk for disease. In some cases, the polymorphism is subjected to a sensitivity analysis, while in other cases, the polymorphism is not subjected to a sensitivity analysis. For example, in some cases, only those polymorphisms associated with the path TNFSF15 PRS that are suspected (e.g., no eQTL or multiple genes within a locus) are subjected to sensitivity analysis.

Patients with Crohn's Disease (CD) were recruited. The diagnosis of each patient is based on standard endoscopy, histology and radiological features. Blood samples were collected from the patient at the time of enrollment. All samples collected were genotyped using an Immune Chip (ICHIP) according to the manufacturer's protocol.

TNFSF15 PRS was calculated for caucasian patients within the Cedars-Sinai CD group from example 1 based on the defined set of polymorphisms selected in example 2 (which are provided in Table 4). Exemplary calculations of TNFSF15 PRS are summarized in Li et al, 2018.Inflamm Bowel Dis.12;24 (11): 2413-2422. TNFSF15 PRS was calculated as the weighted sum of the number of risk alleles (0, 1 or 2) carried by each patient (in the Cedars-Sinai CD group) at each locus of the genes described in this example 2 divided by the total number of genetic variants used in the model. The same calculation is performed for each individual belonging to the reference group, resulting in a range of raw scores (observation range). The resulting TNFSF15 PRS was generated by comparing the scores of each patient to the observed range in the reference group.

Example 3: XGBoost machine learning algorithm trained on binary classifier based on TNFSF15 polygenic risk score

A binary classifier for the XGBoost machine learning platform for CD samples was created based on the distribution of TNFSF15 PRS scores (calculated in example 2) in the CD group. In this example, if its TNFSF15 PRS.ltoreq.TNFSF 15 PRS CD distribution is 25%, patient samples from the CD group are classified as 0. Patient samples were classified as 1 if their TNFSF15 PRS.gtoreq.75% of TNFSF15 PRS CD distribution.

Once the initial classifier for the TNFSF15 SNP is established, the XGBoost algorithm is optimized for the polymorphism and implemented to produce an initial list of candidate polymorphisms. XGBoost is rooted in a gradient-enhanced decision tree that incorporates complex nonlinear feature interactions in a predictive model in a non-additive form as compared to the lasso and ridge regression methods. Exemplary optimizations and practices are provided in Behravan et al Sci Rep.2018;8: 13149. A total of ten iterations of 5-fold cross-validation were used to obtain an initial list of candidate polymorphisms. These polymorphisms were further filtered/optimized using an adaptive iterative search procedure as outlined in behrav et al, along with a Support Vector Machine (SVM), resulting in a final SNP list with high prediction accuracy (> 90%) for the TNFSF15 PRS binary classifier.

Example 4: XGBoost machine learning algorithm trained on binary classifier based on TNFSF15 protein expression

Patients with Crohn's Disease (CD) were recruited. The diagnosis of each patient is based on standard endoscopy, histology and radiological features. A blood sample is collected from a patient. All patients were genotyped by Illumina immune array or Polymerase Chain Reaction (PCR) under standard hybridization conditions. Peripheral Blood Mononuclear Cells (PBMCs) are isolated from a blood sample. PMBC was stimulated in vitro with immune complexes. Supernatants were collected from unstimulated and stimulated samples at 6, 18, 24, and 72 hours. Soluble TL1A proteins in the supernatants were quantified at all time points using plate-based ELISA and monoclonal antibodies.

The binary classifier for the XGBoost machine learning platform for the samples was obtained using TL1A protein expression levels at 6 hours. The classifier at 6 hours reflects the absolute level of TL1A protein expression at this time point. Based on TNFSF15 protein expression in 6, 18, 24 and 72 hour time points, additional binary classifiers were derived using the clustering results of the samples (k=2 and k=3 groups). The classifier at the time point (e.g., 6, 18, 24, and 72) combination reflects the rate of TL1A production between time points. Clustering was performed using TMixClust Bioconductor suite software as described in golombeanu et al ("Clustering time series gene expression data with TMixClust 2018"). A set of predicted SNPs is obtained from each of the three XGBoost analyses of the three classifiers. The polymorphisms identified herein were compared to the list of polymorphisms generated in example 3 to identify those that only overlapped between the two assays.

The overlap determination of SNPs was performed on the gene annotation (refGene annotation) of the produced SNPs, rather than on the actual ICHIP or dbSNP reference sequence recognition numbers. Only polymorphisms with Minor Allele Frequencies (MAF) 0.1 or more and beta coefficients (from Support Vector Machine (SVM) runs) absolute value 0.1 or more were retained. This resulted in 129 polymorphisms being left for further analysis. The 9 polymorphisms used in TNFF15PRS (Table 4) were also added to the SNP list, yielding a total of 138 SNPs.

Example 5: implementation of shopping basket analysis for determining CD-associated nonlinear polymorphism combining rules

To further screen for SNPs that are not closely related to clinical phenotypes, shopping basket analysis methods were used to determine the combination rules for polymorphisms associated with the clinical phenotype of Crohn's Disease (CD). Exemplary shopping basket analyses are described in Breuer et al Int J Bipolar dis.2018; 6:24 A) is provided. An initial dataset was obtained from 1,803 CD groups of the celars-Sinai medical center for CD localization and CD characterization. Using the genotypes of the 138 SNPs previously generated (example 4), the RUDI (Rule Discoverer) program (dominant minor model) in Breuer et al was also described for the 1,803 CD group runs. This analysis produced 57 rules with significant relevance to the clinical phenotype of crohn's disease. The clinical phenotypes used in this analysis were CD position (ileum, colon and ileum colon), CD characteristics (non-stenotic/non-penetrating, stenotic and endopenetrating, and isolated endopenetrating), and the presence of perianal disease. 57 correlation rules consisted of only 89/138 of the input polymorphisms from example 4. Therefore, only these 89 polymorphisms were considered for further evaluation.

Finally, for this 89 polymorphism list, support Vector Machine (SVM) analysis based on the 3 binary classifiers described in example 3 and example 4 was reapplied. Only maintaining XGBoost model (and corresponding polymorphism) with prediction precision not less than 0.70. And furthermore, only polymorphisms from these models having SVM coefficients.gtoreq.0.25 or SVM coefficients.ltoreq.0.25 remain. These filters were applied, yielding a total of 41 polymorphisms when all 3 classifiers were analyzed. These polymorphisms and reference alleles are provided in table 1. The nucleic acid sequence comprising the polymorphism is set forth in SEQ ID NO:1-41 or 57-59, and the location of the polymorphism within the nucleic acid sequence is indicated with a non-nucleobase letter (e.g., V, R, S, etc.). The sequence provided is from construct 151.

The polymorphisms identified in the assays provided in the examples above can be used to predict positive therapeutic response to inhibitors of TL1A activity or expression alone (e.g., anti-TL 1A antibodies) or in combination (e.g., 2, 3, 4, 5, 6, 7, etc.) in a subject or patient. The polymorphisms described herein can be used in diagnostic or prognostic tests to identify subjects suitable for treatment with inhibitors of TL1A activity or expression, thereby treating a disease or condition described herein in a subject. In some cases, the diagnosis is a companion diagnostic test, such as TL1A companion diagnostic test ("TL 1A CDx").

In one non-limiting example, any combination of three polymorphisms (each selected from table 1) can be used to predict a positive therapeutic response to an inhibitor of TL1A activity or expression. An exemplary three polymorphism combination includes: imm_9_116608587, imm_11_127948309, and rs1892231; imm_9_116608587, imm_11_127948309, and rs9806914; imm_9_116608587, imm_11_127948309, and imm_21_44478192; imm_9_116608587, imm_11_127948309, and imm_21_44479552; imm_9_116608587, rs1892231, and rs9806914; imm_9_116608587, rs1892231, and imm_21_44478192; imm_9_116608587, rs1892231, and imm_21_44479552; imm_9_116608587, rs9806914, and imm_21_44478192; imm_9_116608587, rs9806914, and imm_21_44479552; imm_9_116608587, imm_21_44478192, and imm_21_44479552; imm_11_127948309, rs1892231 and rs9806914; imm_11_127948309, rs1892231, and imm_21_44478192; imm_11_127948309, rs1892231, and imm_21_44479552; imm_11_127948309, rs9806914, and imm_21_44478192; imm_11_127948309, rs9806914, and imm_21_44479552; imm_11_127948309, imm_21_44478192, and imm_21_44479552; rs1892231, rs9806914 and imm_21_44478192; rs1892231, rs9806914 and imm_21_44479552; rs1892231, imm_21_44478192 and imm_21_44479552; and rs9806914, imm_21_44478192, and imm_21_44479552.

Table 5 provides a table with the location of each polymorphism provided in table 1 within the human genome according to grch38.p13 primary assembly. The nucleic acid sequences flanking each polymorphism with the relevant SEQ ID NO are identified.

TABLE 5 primary GRCh38.p13 assembly position of polymorphism

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Example 6 verification of 3-SNP model for TL1A companion diagnosis

Machine learning workflow identified several SNP model combinations for developing TL1A companion diagnostics (TL 1A CDx). Previous analysis has identified a 3-SNP combinatorial model consisting of variants associated with TNFSF15 (rs 6478109), ICOSLG (rs 7278257, rs 2070557), ETS1 (rs 7935393) and RBFOX1 (rs 9806914) genes, variant rs 1892231. These SNP models were identified via the celars Sinai crohn's disease group. To verify these findings, the external group of patients with Crohn's disease was identified and genotyped. Genotype and TL1A protein expression were obtained from the non-Cedars group in order to validate the 3-SNP model. A total of 712 crohn's disease individuals were genotyped, while 114 subsets of 712 samples were used to obtain TL1A protein expression via PBMC assays.

Genotyping and deduction of groups

Initial data mining analysis was performed on the Cedars Sinai group using the genotype of the ICHIP (immune chip) platform from Illumina. The validation group was genotyped using GSA platform (24 v 2.0) with a substantial improvement of Illumina over the immune chip platform. Most of the SNPs identified in the model were not present on the GSA platform. Thus, deduction of GSA genotype data was started to obtain a larger set of genotyped SNPs, so that SNP models could be validated. Genotype deduction refers to predicting genotypes that are not directly measured on a given platform. Significant improvements in the different methods and algorithms have been developed for implementing genotype deductions. The quality of genotype deductions was verified by genotyping random samples from 120 patients in our validation set for a small set of deducting SNPs. Cohen's kappa statistics were used to evaluate the overall agreement between the deduced genotype and the measured genotype.

The validation group genotyping results were downloaded from Illumina and converted to PED format (via Illumina's genome studio bench) so that they were further processed using PLINK software (v 1.9). Genotyping data was subjected to the QC procedure to observe factors such as heterozygosity, SNP deletions, MAF distribution, and correlation of samples to determine the preparation genotype data for the ancestors. Once the genotyping data was QC, the blend and ancestral PCA plots were used to determine which samples were European (EUR) ancestors to continue the deduction. For deduction, ancestors need to be considered, since the deduction algorithm uses a genotype reference map based on ancestors. For our deduction, the european reference panel was selected: hrc.r1.1 is the reference panel. All qc'd EUR ancestral genotyping samples were submitted to the Michigan deduction server for genotyping deduction. The resulting deduced genotypes were downloaded and further processed for model validation.

To continue analysis of the 3-SNP model verified derived genotypes, a random selection of 120 samples from the first 470 samples was sent to Illumina for genotyping to compare the derived genotypes with the actual laboratory genotype results. The deduced genotypes were assessed by looking at the consistent level of SNPs: rs6478109, rs2070557, rs1892231, rs7935393.

SNP rs6478109 is already on the GSA platform and is used as a "control" to determine that the assay is actually working properly. The level of agreement (based on Cohen's kappa) was high (based on the table below) and therefore it was decided to continue further analysis using the deduced genotype data.

TABLE 6 consistent levels based on Cohen's kappa

Assessment and validation of 3-SNP models

Next, the initial 3-SNP model was evaluated using the validation set. Similar to the analysis of the Cedars group TL1A protein expression data, TL1A expression from the validation group (PBMC-based assay) was clustered using TL1A measurements at time points 0, 3, 6, 24 and 72 hours. The clusters identify 3 clusters within the dataset, which are provided in fig. 5A-5C. Fig. 5A shows cluster 1, fig. 5B shows cluster 2, and fig. 5C shows cluster 3.

The 3 clusters are folded into 2 clusters (high-expression clusters) and (low-expression clusters), which are shown in fig. 6. The above clusters are folded into two clusters because there is a large overlap between cluster 3 above (fig. 5C) and cluster 1 (fig. 6, left). For cluster 1 (fig. 5A) and cluster 2 (fig. 5B) (based on 3 clusters) and cluster 2 (fig. 6, right), the same level of overlap was seen.

Derived genotype data from the validation set was integrated with TL1A protein expression data to determine which models were validated in the external validation set. This was done by observing the results of the TL1A CDx 3-SNP model. The 3-SNP model in the case of validation set and TL1A expression clusters was evaluated. "positive" genotype hits are determined based on the relevance of a particular genotype and its ability to correlate with higher expression TL1A clusters. Without being bound by any particular theory, high TL1A clusters (e.g., TL1A high expression in CD patients, relative to baseline TL1A expression in normal individuals) are directly correlated with positive therapeutic responsiveness to inhibitors of TL1A activity or expression; whereas low TL1A clusters (e.g., low TL1A expression in CD patients, relative to baseline TL1A expression in normal individuals) are directly related to an inhibitor of TL1A activity or expression anergy.

Calculation of Positive Predictive Value (PPV) and calculation of specificity of 3-SNP model. Each model consisted of 3 unique SNPs based on the identified SNPs in our training set analysis (TNFSF 15 (rs 6478109), ICOSLG (rs 7278257, rs 2070557), ETS1 (rs 7935393) and RBFOX1 (rs 9806914) genes, as well as variant rs 1892231). The PPV and specificity of model A-C are provided in Table 7. As shown in table 7, model a can be used to predict positive therapeutic response to treatment with inhibitors of TL1A activity or expression with a PPV of at least or about 0.797 and a specificity of at least or about 0816 (when considering both the combined training and validation sets). Model a was further explored because it had better performance than models B and C (when considering both the training set and the validation set).

TABLE 7 exemplary 3-SNP models A-C

Other previously identified 3-SNP models were further evaluated because of the fact that only model a showed strong agreement of positive hit genotypes in the training and validation sets. These additional SNP models (model D-K) consist of 3-SNP combinations of the following SNPs: rs6478109, rs7935393, rs9806914, rs16901748, rs2070557, rs7278257, rs2297437, rs1892231, as shown in table 8.

TABLE 8.3 SNP model D-K

PPV and specificity of each model were assessed in the case of positive and negative hits and their correlation with high and lower TL1A clusters, as described previously. After evaluating the models in both the training and validation sets, an additional model (model K) was evaluated, which contained SNP, rs16901748 (CTNND 2), which was not used in our previous model (based on the initial training set).

ICOSLG replaces SNP selection

In view of the SNP locations within the genome, determining one of the ICOSLG SNPs (rs 7278257) is challenging for the genotype. Thus, candidates for rs7278257 were identified instead of SNPs. Replacement SNPs were identified via LDLink. A list of potential replacement SNPs for rs7278257 is shown in table 9 below.

TABLE 9 substitution of SNP for use in verification

Next, relevant inflammatory bowel disease-related clinical correlations within the Cedars R/Shiny database of SNPs provided in table 9 were analyzed. According to the above SNPs, the following SNPs have relevant clinical relevance (examples include critical phenotypes: CD and control, IBD and control, L1B2a+B2b and B1): rs2070561, rs56124762, rs2070558, rs11558819.CD and control refer to cases of crohn's disease relative to control cases (individuals without crohn's disease); IBD and control refer to inflammatory bowel disease cases relative to control cases (individuals without IBD); l1 refers to the ileum; b2a+b2b refers to stenosis and penetration disorders; b1 refers to non-stenotic and non-penetrating diseases.

TL1A companion diagnosis described herein was validated in two independent CD and UC patient groups (CDx), the results of which are summarized in fig. 10. TL1A CDx captured about 32% of the IBD population and a Positive Predictive Value (PPV) of 86% was predicted as to whether CD or UC subjects were positive for TL1A therapeutic response ("CDx +"). Overall, the probability that TL1A CDx recognizes patients with a tendency to increase TL1A expression ("high producers") is about 4.6 times greater than IBD patients with a tendency to decrease TL1A expression ("low producers"). TL1A CDx predicts that up to 42% of IBD patients have increased TL1A expression in two separate CD patient groups.

Example 7 verification in Japanese group

An external group of Crohn's disease patients from Japanese ancestors was identified and genotyped. Genotype and TL1A protein expression were obtained from the second Japanese group in order to verify the 3-SNP model. A total of 800 crohn's disease individuals were genotyped while TL1A protein expression was obtained via PBMC assays using 100 subsets of 800 samples.

The initial 3-SNP model was evaluated using the Japanese validation group. Similar to the analysis of the validation set in example 6, TL1A expression (based on PBMC assays) from the validation set was clustered using TL1A measurements at time points 0, 3, 6, 24 and 72 hours. The clusters identify at least 2 clusters in the dataset: (i) high expression clusters and (ii) low expression clusters.

Derived genotype data from the Japanese validation set was integrated with TL1A protein expression data to determine which models were validated in the Japanese validation set. This was done by observing the results of the TL1A CDx 3-SNP model. The 3-SNP model in the case of Japanese validation set and TL1A expression cluster was evaluated. "positive" genotype hits are determined based on the relevance of a particular genotype and its ability to correlate with higher expression TL1A clusters. Calculation of PPV and specificity of 3-SNP model. Each model consisted of 3 unique SNPs based on the identified SNPs in the training set analysis (TNFSF 15 (rs 6478109), ICOSLG (rs 7278257, rs 2070557), ETS1 (rs 7935393) and RBFOX1 (rs 9806914) genes, as well as variants rs 1892231). The 3-SNP models shown in tables 7 and 8 were explored in this verification. The expected PPV and SPEC values in the Japanese validation set of models A-K are the same as those reported in tables 7 and op. Without being bound by any particular theory, validation of the 3-SNP model for TL1A CDx was expected in all ancestral populations.

Candidates for any of the SNPs provided in table 7 or table 8 may be identified instead of SNPs. The reference population using the japan ancestor was identified via LDLink instead of SNP. The relevant inflammatory bowel disease-related clinical relevance within the Cedars R/Shiny database in Japanese groups replacing SNPs was further analyzed, e.g., CD versus control, IBD versus control, L1B2a+B2b versus B1).

Example 8: design of humanized anti-TL 1A antibodies

Two different strategies were employed to identify humanized variants that were fully expressed in mammalian cells, retained TL1A binding and displayed high monomer content.

The first strategy utilized a previous humanized variant called ASX, which showed high monomer content (98%) and was fully expressed (30 μg/mL in small scale transient culture) as a template for additional mutagenesis. However, ASX contains a large number of murine framework residues, eight heavy chain residues and 7 light chain residues, which can pose an immunogenicity risk. ASX heavy and light chain templates are used to systematically mutate murine framework residues to human residues corresponding to the most closely related human germline frameworks. The goal of this strategy is to reduce the total number of murine framework residues while preserving the favorable expression and solubility characteristics of ASX. Since ASX contains 15 murine framework residues, there are 2≡15 (32,768) different variants that can be made and tested (limiting each position to either murine or human residues).

The second strategy utilized a previous humanized variant called c34, which was fully expressed (17 μg/mL in small-scale transient culture) and contained CDRs optimized for binding within the framework of a fully human germline, as a template for additional mutagenesis. Large scale expression of c34 unexpectedly resulted in suboptimal monomer content (55-60%). c34 heavy and light chain templates were used to systematically mutate certain framework residues to murine residues corresponding to the original murine antibody framework. The goal of this strategy is to improve the solubility (monomer content) of c34 by introducing as few murine framework residues as possible (minimizing the potential risk of immunogenicity) while preserving the favorable expression profile of c 34.

For both strategies, the initial approach is to scan the different framework residues (one at a time) and express and characterize the variants. Thus, human framework residues were introduced into variant ASX at a point different from c34, and conversely, murine framework mutations were introduced into variant c34 at a point different from ASX. Initial scans identified certain framework and CDR residues that had minimal impact on the features displayed by the template antibody, while other mutations had more significant impact, which was advantageous in some cases and disadvantageous in other cases. The information obtained from the position scan is then used in an iterative and combined manner to identify a plurality of variants having advantageous features. Importantly, by applying stepwise, iterative and combinatorial methods, advantageous variants were identified without the necessity of expressing and characterizing 32,768 different variants.

In some cases, mutations of the first residue of the heavy chain from glutamine to aspartic acid or glutamic acid are evaluated alone or in combination with other mutations.

Furthermore, for both strategies, some CDR residues were also mutated to determine the effect on expression and solubility. For example, a limited number of mutations in HCDR2, HCDR3 and LCDR3 are detected. Similar to the approach used in the framework case, mutations are primarily limited to original murine CDR residues or mutations previously identified as enhancing binding affinity.

Finally, for both strategies, a "substitution (shuffle)" of the heavy and light chains was used. Specifically, certain human light chains containing small amounts of murine framework residues and having a beneficial effect on the expression of antibodies with higher monomer content were identified early in the process and paired with various engineered heavy chains to accelerate the process of identifying suitable variants.

TABLE 10 sequences of certain engineered anti-TL 1A antibodies

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As used herein, reference to a (number) refers to an antibody of the table. For example, a15 as used herein refers to a15 in table 10.

Example 9: production and characterization of humanized anti-tl 1a antibodies

Humanized anti-TL 1A antibodies designed in example 1 were prepared and characterized.

Cloning of humanized antibodies

DNA encoding the leader sequence of the humanized variant of interest and the heavy and light chain variable regions were cloned into pFuse1-hIgG1-Fc1 (invitrogen) and pFuse2-CLig-hk (invitogen), respectively. Two different humanized heavy chain templates, designated ASX-HC and c34-HC, and four different humanized light chain templates, designated ASX-LC, cH3-1, c34-LC, cXL3-13-LC and cXL3-15-LC, were cloned.

To introduce mutations into the templates, the QuickChange site-directed mutagenesis kit (Agilent, catalog number 200518) was used according to the manufacturer's instructions. Briefly, miniprep double-stranded plasmid DNA, two synthetic oligonucleotide primers containing the desired mutation, and,DNA polymerase and temperature cycler to carry out mutagenesis. After temperature cycling, the product was treated with Dpn I. The nicked vector DNA containing the mutation of interest is used to transform bacteria. Colonies were then picked and the DNA sequenced to confirm mutagenesis and subsequently used to transfect mammalian FreeStyle 293-F cells.

Antibody expression

Small scale (3 mL,6 well) expression of the variants in FreeStyle 293-F cells was performed as follows. Cells were passaged one or two days prior to transfection such that the density would be > 1 x 10 on the day of transfection ⁶ Individual cells/ml. Typically, this means passaging at 6-7X 105 cells/ml the previous day or 4X 105 cells/ml the previous two days. Transfection was only performed at > 90% cell viability. On the day of transfection, the Opti-MEM medium was warmed to 37 ℃ and the cells were resuspended to 1.1 x 106 cells/mL, using 3.3 x 106 cells per 3mL of transfection. A total of 3ug DNA was used per transfection. Briefly, the transfection used heavy and light chain plasmids with a 1:3 ratio of heavy to light chain. For 3mL transfection, 4uL of 293fectin was added to 96uL of Opti-MEM, combined with 100uL of DNA mix and incubated for 20-30 min at 25 ℃. Subsequently, the mixture was added dropwise to 2.8mL of cells, and the plate was transferred to an incubator and placed on a rotating platform at 175rpm for up to 120 hours. After 96-120 hours, the transfected cells and supernatant were collected by centrifugation at 1200rpm for 5 minutes. The supernatant was transferred to a clean tube and centrifuged again at 3900rpm for 10 minutes to remove any remaining cell debris. The supernatant was filtered through a 0.45mm PES syringe filter and stored at 4℃until the next step.

Quantification of antibody expression

Antibody expression was quantified by ELISA. Briefly, corning Costar 3366 96 Kong Yuande high binding plates were coated overnight at 4deg.C with 50mL of anti-kappa (2. Mu.g/mL) containing PBS. Plates were washed 3 times with PBS-0.05% Tween 20 (PBS-T) and blocked with 100. Mu.L of 1% BSA/PBS for 1 hour at 25 ℃. The blocking was removed and culture supernatants diluted 5-fold were added and serially diluted 2-fold on plates. Each plate also contained IgG standards that were serially diluted 3-fold starting at 1 ug/mL. Samples were incubated at 25℃for 1 hour, plates were washed three times with PBS-T, and 50uL of secondary anti-Fc HRP (Southern Biotech # 2048-05) diluted 1:4000 in BSA/PBS was added at 25℃for 1 hour. Plates were washed three times with PBS-T and developed up to 15 minutes after addition of 50. Mu. L Ultra TMB ELISA substrate (Thermo # 34028). By adding 50. Mu.L of 2N H ₂ SO ₄ The reaction was terminated and a450nm was measured. The expression levels of antibodies obtained from 3mL scale transfection are shown in table 11.

TABLE 11 expression, binding and analytical SEC characterization of anti-TL 1A antibodies (ND, undetermined)

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Antibodies that bind to human TL1A

The ELISA was used for the detection of human TL1A (Fitzgerald #)30R-AT 070) bound antibodies. Briefly, corning Costar 3366 96 Kong Yuande high binding plates were coated overnight at 4deg.C with 50. Mu.L of PBS containing TL1A (1. Mu.g/mL). Plates were washed 3 times with PBS-0.05% Tween 20 (PBS-T) and blocked with 100. Mu.L of 1% BSA/PBS for 1 hour at 25 ℃. The blocking was removed and culture supernatants diluted 5-fold were added and serially diluted 2-fold on plates. Samples were incubated at 25℃for 1 hour, plates were washed three times with PBS-T, and 50. Mu.L of secondary anti-FcHRP diluted 1:4000 in BSA/PBS was added at 25℃for 1 hour. Plates were washed three times with PBS-T and developed up to 15 minutes after addition of 50. Mu. LULTRATMB ELISA substrate. By adding 50. Mu.L of 2N H ₂ SO ₄ The reaction was terminated and a450nm was measured. The antibody affinities as determined by ELISA titration against human TL1A using the unpurified culture supernatants are shown in table 11.

Purification of antibodies

Antibodies were purified from culture supernatants in a single step using Dynabeads protein a (ThermoFisher Scientific, catalog number 10002D). First, culture supernatants were concentrated using an Amicon Ultra-4 centrifugal filtration device (30,000MWCO;Millipore Sigma, cat# C7719) according to the manufacturer's instructions. Dynabeads were resuspended by gentle vortexing and 100uL was transferred to an Eppendorf tube (Eppendorf tube). The beads were fixed using a magnet, the storage buffer was removed, and the beads were washed with 0.5mL of 20mM sodium phosphate, 150mM NaCl (pH 7.4) (EB, equilibration buffer). A total of up to 24ug IgG from culture supernatant was added to the beads and gently mixed until the beads were resuspended. Antibody supernatants were diluted with EB, if necessary. The tube was placed laterally on a shaking table and mixed at 500rpm for 10 minutes at 25 ℃. Subsequently, the beads were collected at the bottom of the tube using 10,000rpm microcentrifugation for 30 seconds. The beads were fixed using a magnet and the supernatant removed. The beads were washed once with 0.5mL of 20mM sodium phosphate, 500mM NaCl (pH 7.4), followed by another wash with 50mM sodium phosphate (pH 6.0). The beads were collected at the bottom of the tube using 10,000rpm microcentrifugation for 30 seconds. Purified antibodies were eluted from the beads by gentle mixing at 25℃for 2 min using 20uL of 50mM sodium acetate (pH 3.5). The beads were fixed using a magnet and the eluate was transferred to a new tube containing 1.1ul 1m Tris (pH 8.5) to neutralize the pH of the sample. The sample was then centrifuged at 10,000rpm for 2 minutes and transferred to a new tube to ensure removal of residual Dynabeads. The concentration of the purified samples was determined at 280nm for a 1% igg solution using a DeNovix DS-11 spectrophotometer/fluorometer, buffer blank and a mass extinction coefficient of 13.70.

Size exclusion chromatography

Antibodies were analyzed by Size Exclusion Chromatography (SEC) to determine the percent monomer and identify any large molecular weight aggregated contaminant species. The water SEC column was used on a Shimadzu UPLC instrument at a flow rate of 0.2mL/min and a column box temperature of 30 ℃ (Acquity UPLC BEH SEC,1.7 μm,4.6 x 150 mm) to analyze the total volume 15. Mu.E of protein A purified antibodies at a concentration of 0.1-1. Mu.g/. Mu.L. Standard PBS was used as the mobile phase and absorbance at 280nm was used to monitor protein elution. For some of the tested antibody clones demonstrating asymmetric elution profiles, PBS buffer pH 6.0 supplemented with 350mM NaCl was used to reduce non-specific interactions with the column matrix. The Shimadzu software was used to calculate the main peak (monomer) percent value. Representative sample curves are shown in fig. 7A-7C. The monomer content of the purified antibody variants is shown in table 11.

Example 10: disabling effector functions

In some cases, it may be beneficial to reduce the potential effector functions of the antibody. Various strategies have been described to attenuate effector function, including point mutations that eliminate fcγr and C1q binding, cross subclass Fc designs that eliminate fcγr and C1q binding, and glycoengineering that eliminates fcγr and C1q binding. Representative embodiments are highlighted in table 12.

TABLE 12 representative methods of disabling effector functions

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To express antibodies with eliminated effector functions, the light chain variable regions of the antibodies disclosed in example 2 and table 10 were cloned with kappa light chain constant regions, while the heavy chain variable regions were cloned with modified IgG1 heavy chain backbones, or modified IgG2 backbones, or modified IgG4 backbones, or unmodified IgG2 or IgG4 backbones (such as those disclosed in table 3 or elsewhere).

The effect of various Fc engineering methods on CDC activity can be assessed using C1q binding and C3 immobilization assays. Purified antibodies were diluted in PBS and serial dilutions were inoculated onto microtiter plates at 4 ℃ for 12-18h. Plates were blocked with 5% gelatin/PBS containing 1% (v/v) Tween-20 for 1h at 25 ℃. Subsequently, plates were incubated with PBS containing 10% (v/v) human serum, and C1q binding was detected using a 1:500 dilution of HRP conjugated rabbit anti-C1 q (Bioss Inc.) in PBS containing 1% (v/v) Tween-20. To test C3 immobilization, a 1:1000 dilution of rabbit anti-C3 (abcam) was used followed by a 1:2000 dilution of HRP conjugated chicken anti-rabbit IgG (abcam). Plates were developed as described for the antibody quantitation in example 1. EC50 values were calculated by fitting data to a log (agonist) and response-variable slope (four parameter) model using GraphPad Prism (Sunnyvale, CA).

Furthermore, variants can be characterized for binding of isolated C1 q. The MaxiSorp 384-well plates (Thermo scientific, nunc) were coated with antibodies serially diluted in 50mM carbonate buffer (pH 9.6) (coating buffer) at 4 ℃ for 12-18h. Plates were washed with Phosphate Buffered Saline (PBS) containing 0.05% polysorbate 20 (pH 7.4) and blocked with PBS (pH 7.4) containing 0.5% bsa, 0.05% polysorbate 20, 15ppm proclin, and 10% blocker casein (ThermoScientific). After incubation for 1 hour at 25 ℃, the plates were washed. The same buffer containing human C1q (Quidel, san Diego, calif.) was added and incubated for 1.5 hours. Bound C1q was detected by: 20ng/mL biotinylated mouse anti-mouse C1q (Hycult biotech; cross-reactive with human C1 q) was added for 1.5 hours followed by horseradish peroxidase (HRP) -conjugated streptavidin (GE Healthcare Life Sciences) for 1 hour. To check coating efficiency, some coated wells received buffer only in the first two incubation steps and goat anti-human Fab' 2-HRP when wells used to measure C1q binding received streptavidin-HRP. After each incubation step the plates were washed. Peroxidase activity was detected with the substrate 3,3 ', 5' -Tetramethylbenzidine (TMB) (Kirkegaard & Perry Laboratories). The reaction was quenched with 1M phosphoric acid and absorbance was measured at 450 nm. Dose-response binding curves were fitted with a four-parameter model and EC50 values were calculated using GraphPad Prism (Sunnyvale, CA).

The effect of various Fc engineering methods on ADCC activity was assessed using a soluble fcγr receptor binding ELISA. Soluble human fcyri, fcyriib, and fcyriii (assessing binding affinity to F158 and V158 polymorphic forms of fcyriii) are expressed as recombinant fusion proteins with Gly-His 6-glutathione-S-transferase (GST) at the C-terminus of the extracellular domain of the receptor. MaxiSorp 384-well plates were coated with a coating buffer containing 1. Mu.g/ml human FcγR. Plates were washed and blocked with PBS containing 0.5% BSA, 15ppm Proclin (pH 7.4). After 1 hour incubation, the plates were washed and 3-fold serial dilutions of antibodies in PBS (pH 7.4) containing 0.5% bsa, 0.05% polysorbate 20, 15ppm Proclin were added to the plates and incubated for 2 hours. Immune complexes are formed using anti-human antibodies for enhanced binding sensitivity due to avidity. Bound antibodies were detected with HRP conjugated goat anti-human kappa (Southern Biotech) using Ultra TMB substrate as described in example 1. The reaction was terminated as described above and the plates were read. A GraphPad Prism (Sunnyvale, CA) four-parameter curve fitting program was used to fit the dose-dependent binding curve of wild-type antibodies (without Fc modification). The relative affinity of the variant relative to the wild type was estimated by dividing by the equivalent ng/ml wild type concentration at the appropriate concentration.

In addition, variants were tested directly in Fc effector bioassays (Promega) as directed by the manufacturer. These assays include fcyriia-H ADCP bioassays (Promega catalog No. G9901), ADCC reporter bioassays, fcyriiia F variants (Promega catalog No. G9798), ADCC reporter bioassays, fcyriiia V variants (Promega catalog No. G7015). Variants in monomeric Ig form and in small Immune Complex (IC) form were tested, using anti-huig antibodies to form small ICs.

Europium-based ADCC assays were performed. Briefly, peripheral Blood Lymphocytes (PBLs) were isolated by Ficoll Paque Plus gradient centrifugation. PBLs were collected, washed with RPMI1640, 10% fcs, and resuspended in cell culture medium. Dilution of cells to 2.5X10 ⁶ Individual cells/ml. Target cells were labeled with BADTA (2, 2 ': 6', 2 '-terpyridine-6, 6' -acetoxymethyl diformate): cells were harvested by addition of aconase (Ackutase) (Millipore), washed once and diluted to 1X10 ⁶ Individual cells/ml. Next, every 1×10 ⁶ 2.5uL BADTA was added to each cell and incubated at 37℃and 5% CO ₂ Incubate for 35 minutes. After labelling, the cells were diluted with 10ml of medium, centrifuged at 200Xg for 10 min and the supernatant was aspirated. This procedure was repeated 3 times with medium/2 mM probenecid and the samples were diluted to 1X10 ⁵ Individual cells/ml were centrifuged at 300xg for 5 min, the supernatant was removed and 50uL was pipetted into wells intended for background control. The final ratio of effector (PBL) to target cells was 25:1.

The control group included: (1) background: 50uL aliquots, diluted with 100uL medium, (2) spontaneous lysis: 50uL of labelled target cell suspension plus 100uL of medium, incubated for 2 hours at 37 ℃, (3) maximum lysis: 50uL of labeled target cell suspension per well was incubated with 100uL Triton X-100 (0.5% in PBS) for 2 hours at 37 ℃, (4) no antibody containing lysis control: 50uL of labelled target cell suspension per well and 50uL of medium plus 50uL of effector cells, incubated for 2 hours at 37 ℃, (5) lysis control without effector cells: 50uL of labelled target cell suspension per well; 50uL of medium plus the highest concentration of antibody used was added and incubated for 2 hours at 37 ℃.

At the end of the incubation period, 96-well plates were centrifuged at 100 rpm. 20uL of each supernatant was transferred to OptiPlate HTRF-96 (Packard) and 200uL of europium solution was added and incubated for 15 minutes on a shaker. Fluorescence was measured as time resolved fluorescence and spontaneous and specific release was calculated.

CDC measurement was performed. Briefly, target cells were washed and diluted to 1x10 ⁵ Each cell/ml, and 100uL (10 ⁴ Individual cells) were added to 96-well flat bottom microtiter plates. A titration curve for the test antibody was formed using serial dilutions starting at 1 ug/mL. Antibodies were added to the plates, gently mixed, then at 37 ℃/5% co ₂ The cells were placed in an incubator for 30 minutes. Next, 25uL of freshly dissolved young rabbit complement (Cedarlane CL3441,1ml freeze-dried, freshly diluted in 4ml double distilled water) was added, gently mixed, and the plates were incubated for 30 min in 37 ℃/5% co2 incubator. After the incubation period, 50uL of supernatant was removed and 100uL Cell Titer Glo reagent (Promega corp.) was added to the remaining 100uL of supernatant. The plate was placed on an orbital shaker for 2 minutes, 100uL per well was transferred to a black luminescence microtiter plate (Costar), and luminescence measured.

The control group included: (1) Medium control (target cells plus 50uL Medium), (2) maximum lysis control (target cells plus 50uL 0.5%Triton X-100), (3) complement control (target cells plus 25uL Medium plus 25uL complement).

Example 11: characterization of potency and species selectivity in whole blood assays

The relative efficacy of a set of candidate antibodies was first assessed by determining inhibition of interferon gamma release in human blood using antibodies of 1 and 10 nM. All antibodies showed potent activity, with a219 appearing to be one of the most potent candidates (table 13).

Table 13.

Cloning	Inhibition at 1nM Ig%	Inhibition at 10nM Ig%
			A147	51.3	72.4
A212	46.8	71.2
			A213	48.6	69.8
A217	46.0	72.2
			A219	59.8	75.2
A220	36.9	63.2

Next, three variants were characterized for inhibition of interferon gamma release in human blood using a variety of human blood donors and testing antibodies over a wider concentration range (0.01-100 nM). Representative inhibition curves for variants a212, a213 and a219 are shown in fig. 8. The average IC50 values of inhibition of interferon gamma release from various human donors by these variants and the control antibody designated 1D1 are shown in table 14.

Table 14.

Cloning	Average value of	SD
			A212	51.3	72.4
A213	46.8	71.2
			A219	48.6	69.8
1D1	46.0	72.2

Example 12: in vivo evaluation of anti-Tl 1a efficacy

Efficacy of anti-TL 1A antibodies in animal models of colitis was performed. anti-TL 1A antibodies in acute colitis induced by intrarectal administration of di-or trinitrobenzene sulphonic acid (D/TNBS) or oxazolone and by administration of DSS-containing drinking water or transfer of CD45RB ^hi The test was performed in rodent models of T cell induced chronic colitis. DNBS and oxazolone induce local ulcers and inflammation. DSS administration induces stable general inflammation of the gut characterized by erosive lesions and inflammatory infiltrates. Symptoms of all these models generally include diarrhea, occult blood, weight loss, and occasional rectal prolapse. In a prophylactic model, antibody treatment induces binding at the beginning of administration Enteritis compounds begin at the time of their onset. In the therapeutic model, antibody treatment was started a few days after induction was started. The effect of treatment on body weight, stool consistency and occult blood was determined as a microscopic effect on epithelial integrity and degree of inflammatory infiltration. Daily clinical scores were based on fecal consistency and the presence of occult blood, yielding a Disease Activity Index (DAI) score.

Example 13: phase I clinical trial

Phase 1 clinical trials were conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of anti-TL 1A antibodies from table 20 to subjects with Crohn's Disease (CD).

Single increment dose (SAD) group: subjects in each group (subjects grouped based on the presence of genotypes comprising at least one, preferably three, polymorphisms selected from table 1, and subjects in the absence of genotypes) receive a single dose of antibody or placebo. Exemplary doses are 1, 3, 10, 30, 100, 300, 600, and 800mg of antibody. Safety monitoring and PK assessment are performed over a predetermined period of time. Based on the evaluation of PK data, and if antibody tolerance is considered good, dose escalation is performed in the same group or another group of healthy subjects. Dose escalation is continued until a maximum dose is reached unless a predetermined maximum exposure or intolerable side effects become apparent.

Multiple Ascending Dose (MAD) group: subjects in each group (subjects grouped based on the same criteria as described above) received multiple doses of antibody or placebo. Dosage levels and dosing intervals are selected as those that are predicted to be safe based on the SAD data. Dose levels and dosing frequency are selected to achieve therapeutic drug levels that maintain steady state for days in the systemic circulation to allow for monitoring of appropriate safety parameters. Samples were collected and analyzed to determine PK profile.

Inclusion criteria: healthy subjects with no fertility potential between 18 and 55 years of age. Health is defined as the absence of clinically relevant abnormalities identified by detailed medical history, comprehensive physical examination (including blood pressure and pulse rate measurements, 12-lead ECG and clinical laboratory testing). Female subjects without fertility potential must meet at least one of the following criteria: (1) reaching a postmenopausal state, defined as: stopping normal menstruation without alternative pathological or physiological causes for at least 12 consecutive months; and serum Follicle Stimulating Hormone (FSH) levels are within laboratory reference ranges for postmenopausal women; (2) Hysterectomy and/or bilateral ovariectomy have been performed as noted; (3) ovarian failure has been confirmed medically. All other female subjects (including fallopian tube ligated females and females without recorded hysterectomy, bilateral ovariectomy and/or ovarian failure) will be considered to have fertility potential. Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and total body weight > 50kg (110 lbs). Evidence of personal signed and dated informed consent documents indicates that the subject (or legal representative) has informed all relevant aspects of the study.

Two groups of CD patients were selected: patients with genotypes as described herein and patients without genotypes. For example, genotypes may include rs6478109, rs56124762, and rs1892231; rs6478109, rs56124762 and rs16901748; rs6478109, rs1892231 and rs16901748; rs56124762, rs1892231 and rs16901748; rs6478109, rs2070558 and rs1892231; rs6478109, rs2070558 and rs16901748; rs6478109, rs1892231 and rs16901748; rs2070558, rs1892231 and rs16901748; rs6478109, rs2070561 and rs1892231; rs6478109, rs2070561 and rs16901748; rs6478109, rs1892231 and rs16901748; rs2070561, rs1892231 and rs16901748; rs6478109, rs7935393 and rs1892231; rs6478109, rs7935393 and rs9806914; rs6478109, rs7935393 and rs7278257; rs6478109, rs7935393 and rs2070557; rs6478109, rs1892231 and rs9806914; rs6478109, rs1892231 and rs7278257; rs6478109, rs1892231 and rs2070557; rs6478109, rs9806914 and rs7278257; rs6478109, rs9806914 and rs2070557; rs6478109, rs7278257 and rs2070557; rs7935393, rs1892231 and rs9806914; rs7935393, rs1892231 and rs7278257; rs7935393, rs1892231 and rs2070557; rs7935393, rs9806914 and rs7278257; rs7935393, rs9806914 and rs2070557; rs7935393, rs7278257 and rs2070557; rs1892231, rs9806914 and rs7278257; rs1892231, rs9806914 and rs2070557; rs1892231, rs7278257 and rs2070557; or rs9806914, rs7278257 and rs2070557.

Exclusion criteria: clinically significant evidence or history of hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, liver, psychiatric, neurological or allergic diseases (including drug allergies but excluding untreated, asymptomatic seasonal allergies upon administration). Subjects with a history of positive results or current positive results for any of the following serological tests: hepatitis b surface antigen (HBsAg), hepatitis b core antibody (HBcAb), anti-hepatitis c antibody (HCV Ab) or Human Immunodeficiency Virus (HIV). A subject having a history of allergic (allergy/anaphyllac) response to a therapeutic agent. Treatment with the drug of interest occurs within 30 days (or longer as determined by local requirements) or 5 half-lives or 180 days (for biological agents) prior to the first dose of drug of interest. Pregnant women; female for lactation; and females with fertility potential.

Main outcome measurement: incidence of dose limiting or intolerance treatment-related Adverse Events (AEs) [ time frame: 12 weeks ]. AE (TEAE) occurring in treatment and incidence, severity and causality of withdrawal due to adverse events occurring in treatment [ time frame: 12 weeks ]. Incidence and extent of abnormal laboratory findings [ time frame: 12 weeks ]. Abnormal and clinically relevant changes in vital sign, blood Pressure (BP) and Electrocardiogram (ECG) parameters [ time frame: 12 weeks ].

Secondary outcome measure: single increment dose: maximum plasma concentration (Cmax) observed [ time frame: 12 weeks ]. Single increment dose: time to maximum plasma concentration observed (Tmax) [ time range: 12 weeks ]. Single increment dose: area under the plasma concentration-time curve (AUC 14 days) from time zero to 14 days [ time range: 12 weeks ]. Single increment dose: area under plasma concentration-time curve (AUCinf) [ time range ] extrapolated from time zero to an infinitely long time: 12 weeks ]. Single increment dose: area under plasma concentration-time curve (AUClast) [ time range ] from time zero to time of last quantifiable concentration: 12 weeks ]. Single increment dose: dose normalized maximum plasma concentration (Cmax [ dn ]) [ time frame: 12 weeks ]. Single increment dose: area under dose normalized plasma concentration-time curve (AUCinf [ dn ]) [ time range ] extrapolated from time zero to an infinitely long time: 12 weeks ]. Single increment dose: dose normalized plasma concentration versus time curve area under time (AUClast [ dn ]) [ time range) from time zero to time of last quantifiable concentration: 12 weeks ]. Single increment dose: plasma decay half-life (t 1/2) [ time frame: 12 weeks ]. Plasma decay half-life is the time measured by a half-decrease in plasma concentration. Single increment dose: average residence time (MRT) [ time range: 12 weeks ]. Single increment dose: steady state volume of distribution (Vss) [ time range: 6 weeks ]. The distribution volume is defined as the theoretical volume in which the total amount of drug will need to be evenly distributed to produce the desired blood concentration of the drug. The steady state volume of distribution (Vss) is the apparent volume of distribution at steady state. Single increment dose: systemic Clearance (CL) [ time frame: 6]. CL is a quantitative measure of the rate at which drug substances are cleared from the body.

Multiple incremental dose first dose: maximum plasma concentration (Cmax) observed [ time frame: 12 weeks ]. Multiple incremental dose first dose: time to maximum plasma concentration observed (Tmax) [ time range: 12 weeks ]. Multiple incremental dose first dose: from time zero to time τ, the area under the plasma concentration-time curve (aucτ) for the dosing interval (where τ=2 weeks) [ time range: 12 weeks ]. Multiple incremental dose first dose: dose normalized maximum plasma concentration (Cmax [ dn ]) [ time frame: 12 weeks ]. Multiple incremental dose first dose: from time zero to time τ, dose normalized plasma concentration versus time area under the curve (aucτdn) for dosing interval (where τ=2 weeks) time range: 12 weeks ]. Plasma decay half-life (t 1/2) [ time frame: 12 weeks ]. Plasma decay half-life is the time measured by a half-decrease in plasma concentration. Multiple incremental dose first dose: average residence time (MRT) [ time range: 12 weeks ]. Apparent volume of distribution (Vz/F) [ time range: 12 weeks ]. The distribution volume is defined as the theoretical volume in which the total amount of drug will need to be evenly distributed to produce the desired plasma concentration of drug. The apparent volume of distribution (Vz/F) after oral dosing is affected by the absorption fraction. Multiple incremental dose first dose: steady state volume of distribution (Vss) [ time range: 12 weeks ]. The distribution volume is defined as the theoretical volume in which the total amount of drug will need to be evenly distributed to produce the desired blood concentration of the drug. The steady state volume of distribution (Vss) is the apparent volume of distribution at steady state. Multiple incremental dose first dose: apparent oral clearance (CL/F) [ time frame: 12 weeks ]. Clearance of a drug is a measure of the rate at which the drug is metabolized or eliminated by normal biological processes. The clearance obtained after oral dosing (apparent oral clearance) is affected by the fraction of the dose absorbed. Clearance was estimated by population Pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which drug substances are cleared from the blood. Multiple incremental dose first dose: systemic Clearance (CL) [ time frame: 12 weeks ]. CL is a quantitative measure of the rate at which drug substances are cleared from the body.

Multiple incremental doses multiple doses: maximum plasma concentration (Cmax) observed [ time frame: 12 weeks ]. Multiple incremental doses multiple doses: time to maximum plasma concentration observed (Tmax) [ time range: 12 weeks ]. Multiple incremental doses multiple doses: from time zero to time τ, the area under the plasma concentration-time curve (aucτ) for the dosing interval (where τ=2 weeks) [ time range: 12 weeks ]. Multiple incremental doses multiple doses: dose normalized maximum plasma concentration (Cmax [ dn ]) [ time frame: 12 weeks ]. Multiple incremental doses multiple doses: from time zero to time τ, dose normalized plasma concentration versus time area under the curve (aucτdn) for dosing interval (where τ=2 weeks) time range: 12 weeks ]. Multiple incremental doses multiple doses: plasma decay half-life (t 1/2) [ time frame: 12 weeks ]. Plasma decay half-life is the time measured by a half-decrease in plasma concentration. Multiple incremental doses multiple doses: apparent volume of distribution (Vz/F) [ time range: 12 weeks ]. The distribution volume is defined as the theoretical volume in which the total amount of drug will need to be evenly distributed to produce the desired plasma concentration of drug. The apparent volume of distribution (Vz/F) after oral dosing is affected by the absorption fraction. Multiple incremental doses multiple doses: steady state volume of distribution (Vss) [ time range: 12 weeks ]. The distribution volume is defined as the theoretical volume in which the total amount of drug will need to be evenly distributed to produce the desired blood concentration of the drug. The steady state volume of distribution (Vss) is the apparent volume of distribution at steady state.

Multiple incremental doses multiple doses: apparent oral clearance (CL/F) [ time frame: 12 weeks ]. Clearance of a drug is a measure of the rate at which the drug is metabolized or eliminated by normal biological processes. The clearance obtained after oral dosing (apparent oral clearance) is affected by the fraction of the dose absorbed. Clearance was estimated by population Pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which drug substances are cleared from the blood. Multiple incremental doses multiple doses: systemic Clearance (CL) [ time frame: 12 weeks ]. CL is a quantitative measure of the rate at which drug substances are cleared from the body. Multiple incremental doses multiple doses: minimum plasma trough concentration (Cmin) observed [ time frame: 12 weeks ]. Multiple incremental doses multiple doses: steady state average concentration (Cav) [ time frame: 12 weeks ]. Multiple incremental doses multiple doses: observed cumulative ratio (Rac) [ time frame: 12 weeks ]. Multiple incremental doses multiple doses: peak to valley ripple (PTF) [ time range: 12 weeks ]. Multiple increment dose-add-on parameters: estimated bioavailability (F) for subcutaneous administration at the corresponding intravenous dose [ time range: 12 weeks ]. Immunogenicity of both single and multiple escalated doses: development of anti-drug antibodies (ADA) [ time frame: 12 weeks ].

Example 14: phase 1B clinical trial

Phase 1b open-label clinical trials were conducted to assess the efficacy of anti-TL 1A antibodies on subjects with CD.

Group: antibodies were administered to 10 positive patients containing at least one, but preferably three, genotypes of the polymorphisms provided in table 1. Antibodies were administered to 10 negative patients of genotype. The patient is monitored in real time. Center-ready endoscopy and biopsy were used, with the reader being unaware of the treatment time points and endpoints.

For example, genotypes may include rs6478109, rs56124762, and rs1892231; rs6478109, rs56124762 and rs16901748; rs6478109, rs1892231 and rs16901748; rs56124762, rs1892231 and rs16901748; rs6478109, rs2070558 and rs1892231; rs6478109, rs2070558 and rs16901748; rs6478109, rs1892231 and rs16901748; rs2070558, rs1892231 and rs16901748; rs6478109, rs2070561 and rs1892231; rs6478109, rs2070561 and rs16901748; rs6478109, rs1892231 and rs16901748; rs2070561, rs1892231 and rs16901748; rs6478109, rs7935393 and rs1892231; rs6478109, rs7935393 and rs9806914; rs6478109, rs7935393 and rs7278257; rs6478109, rs7935393 and rs2070557; rs6478109, rs1892231 and rs9806914; rs6478109, rs1892231 and rs7278257; rs6478109, rs1892231 and rs2070557; rs6478109, rs9806914 and rs7278257; rs6478109, rs9806914 and rs2070557; rs6478109, rs7278257 and rs2070557; rs7935393, rs1892231 and rs9806914; rs7935393, rs1892231 and rs7278257; rs7935393, rs1892231 and rs2070557; rs7935393, rs9806914 and rs7278257; rs7935393, rs9806914 and rs2070557; rs7935393, rs7278257 and rs2070557; rs1892231, rs9806914 and rs7278257; rs1892231, rs9806914 and rs2070557; rs1892231, rs7278257 and rs2070557; or rs9806914, rs7278257 and rs2070557.

Inclusion criteria: two groups of patients were selected: subjects with genotypes as described herein and patients without genotypes.

Main outcome measurement: simple endoscopic scoring for crohn's disease (seccd), crohn's Disease Activity Index (CDAI), and Patient Report Outcome (PRO). If the risk positive group showed a 50% decrease from baseline, a phase 2a clinical trial was performed.

Inclusion criteria: PRO entry criteria: abdominal pain scores 2 or higher and/or stool frequency scores 4 or higher. The main results were a pain core of 0 or 1 and a stool frequency score of 3 or less with no deterioration from baseline. Endoscopic access criteria: if colon is involved, the SESCD ileum is only entered at scores of 4 and 6. The primary endoscopy results were 40-50% delta of the average SESCD.

Example 15: phase 2A clinical trial

Phase 2a clinical trials were conducted to assess the efficacy of anti-TL 1A antibodies in patients with CD. Optionally, the patient is positive for genotypes comprising at least one, but preferably three, polymorphisms provided in table 1.

Group: 40 patients in each group (antibody group and placebo group) were treated with either antibody or placebo for 12 weeks. An interim analysis was performed after treatment of 20 patients from each group at the highest dose to find 40-50% delta between placebo and treatment groups in the primary results (50% reduction in SESCD, CDAI and PRO from baseline).

Main outcome measurement: simple endoscopic scoring for crohn's disease (seccd), crohn's Disease Activity Index (CDAI), and Patient Report Outcome (PRO).

Inclusion criteria: PRO entry criteria: abdominal pain scores 2 or higher and/or stool frequency scores 4 or higher. The main results were a pain core of 0 or 1 and a stool frequency score of 3 or less with no deterioration from baseline. Endoscopic access criteria: if colon is involved, the SESCD ileum is only entered at scores of 4 and 6. The primary endoscopy results were 40-50% delta of the average SESCD.

Example 16: treating Crohn's Disease (CD) in a subject

The CD of the subject is treated by first determining the genotype of the subject. Optionally, the subject is unresponsive to induction of certain therapies, such as anti-TNF, steroids, or immunomodulators, or is lost or is susceptible to such therapies after a period of time. A whole blood sample is obtained from a subject. Samples obtained from the subject are assayed to detect the presence of genotypes comprising at least one, but preferably three or four, of the polymorphisms provided in table 1.

By Illumina ImmunoArray or Polymerase Chain Reaction (PCR), three polymorphisms including the following are detected in a sample under standard hybridization conditions: rs6478109, rs56124762 and rs1892231; rs6478109, rs56124762 and rs16901748; rs6478109, rs1892231 and rs16901748; rs56124762, rs1892231 and rs16901748; rs6478109, rs2070558 and rs1892231; rs6478109, rs2070558 and rs16901748; rs6478109, rs1892231 and rs16901748; rs2070558, rs1892231 and rs16901748; rs6478109, rs2070561 and rs1892231; rs6478109, rs2070561 and rs16901748; rs6478109, rs1892231 and rs16901748; rs2070561, rs1892231 and rs16901748; rs6478109, rs7935393 and rs1892231; rs6478109, rs7935393 and rs980691 4, a step of; rs6478109, rs7935393 and rs7278257; rs6478109, rs7935393 and rs2070557; rs6478109, rs1892231 and rs9806914; rs6478109, rs1892231 and rs7278257; rs6478109, rs1892231 and rs2070557; rs6478109, rs9806914 and rs7278257; rs6478109, rs9806914 and rs2070557; rs6478109, rs7278257 and rs2070557; rs7935393, rs1892231 and rs9806914; rs7935393, rs1892231 and rs7278257; rs7935393, rs1892231 and rs2070557; rs7935393, rs9806914 and rs7278257; rs7935393, rs9806914 and rs2070557; rs7935393, rs7278257 and rs2070557; rs1892231, rs9806914 and rs7278257; rs1892231, rs9806914 and rs2070557; rs1892231, rs7278257 and rs2070557; or rs9806914, rs7278257 and rs2070557, or any of the foregoing combinations in which one polymorphism is replaced with a replacement polymorphism. Using a D' 1 value of at least 0.8 or r of at least 0.85 ² Linkage disequilibrium identification of values replaces polymorphisms. In some cases, alternative polymorphisms are additionally selected based on independent correlations between polymorphisms and related clinical phenotypes of CD (e.g., stenosis and penetration disease). In this embodiment, one or more primer pairs and/or nucleic acid probes described herein are used, comprising a primer capable of hybridizing to SEQ ID NO:2001-2041 or 2057-2059 or a reverse complement thereof.

Generating a TNFSF15 profile associated with the presence of positive, negative, or indeterminate results of a positive predictive value of at least or about 70% and a specific response to treatment with an inhibitor of TL1A activity or expression.

The TNFSF15 profile of the subject was positive. Based on the TNFSF15 profile of CD patients, the physician determines that the subject is suitable for treatment with inhibitors of TL1A activity or expression. A therapeutically effective amount of an inhibitor of TL1A activity or expression is administered to a subject having a positive TNFSF15 profile. Inhibitors of TL1A activity or expression may comprise anti-TL 1A antibodies. The anti-TL 1A antibodies may be the antibodies listed in table 20. The anti-TL 1A antibody may be a neutralizing anti-TL 1A antibody.

TABLE 15 CDR amino acid sequences

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TABLE 16 heavy chain variable region (VH) amino acid sequence

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TABLE 17 light chain variable region (VL) amino acid sequences

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TABLE 18A additional sequences

Table 18B: additional sequences

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TABLE 19 Fc and constant regions

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TABLE 20 selected antibodies

TABLE 21 selected antibody-variable regions

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Example 17: design of humanized anti-TL 1A antibodies with reduced cell-mediated cytotoxicity.

As provided and described herein, fc variants (e.g., SEQ ID nos: 401-413) were designed to attenuate effector function and then tested for the following capabilities: (i) efficient purification/manufacture (table 22), (ii) reduced antibody-dependent cell-mediated cytotoxicity (ADCC), and (iii) reduced complement-dependent cytotoxicity. The test article tested comprises heavy chain SEQ ID No:501-513 comprising the amino acid sequence comprising SEQ ID No: 401-413. The heavy chain used is identical to a heavy chain comprising SEQ ID NO: 514. ELISA titration curves and EC50 against recombinant TL1A antigen were generated ("EC 50", table 23). Interestingly, the Fc mutation did affect the purity of the selected mutation/Fc variant as measured by monomer content (table 22, wild-type IgG1 control).

Reduction of CDC Activity

The CDC activity of the test preparations was evaluated on HEK293 target cells expressing TL1A compared to a negative control human IgG4 isotype control. Rituxan (Rituxan) (anti-CD 20) was used as a positive technical control on Raji cells expressing CD 20. All test preparations were used at a final maximum concentration of 10 μg/mL, followed by five-fold dilution series (7 spots total) and no treatment control, in triplicate. Cells were incubated with the test preparation at 37℃for 15 minutes and then treated with human complement at a final concentration of 25% at 37℃and 5% CO2 for 3 hours. After incubation, cells were washed and resuspended in propidium iodide (p.i.) at a final concentration of 5 μg/mL prior to flow cytometry analysis. All cells were detected by flow cytometry during sample collection. The data are plotted on an XY graph, plotted against the log of the percentage of p.i. positive cells versus concentration, and fitted to a nonlinear regression curve. Cytotoxicity in the presence of all test preparations was not different from cytotoxicity in the presence of isotype control (table 23). CDC bioactivity was observed on Raji target cells treated with rituximab.

Reduction of CDC Activity

Antibody-dependent cell-mediated cytotoxicity (ADCC) reporter assays were performed on HEK293 TL1A cells to characterize the test preparations and IgG4 isotype controls. The reporter cell line engineered to express human Fc-gamma-RIIIaV 158 (high affinity) is used as an effector cell.

Prometheus test preparations were evaluated at the highest concentration of 10ug/mL (log dilution of 7 points total, and no test preparation control). Treatment conditions were tested in triplicate and effector and target cells were co-cultured at 37 ℃ and 5% co2 for 6 hours. Raji target cells were used as positive controls, with rituximab at the highest concentration of 10ug/mL, 7-point log dilution series, and no-treatment controls. Test article 502 treatment resulted in a dose-dependent increase in luciferase reporter activity, while 5044 treatment resulted in an increase in reporter activity at the highest test concentration. The remaining test preparations did not induce reporter activity (table 23).

Table 22.

Table 23.

Example 18: biophysical Properties of anti-Tl 1a antibodies at high concentrations

Data on the properties of a219 anti-TL 1A antibodies in solution were analyzed together using a chemometric method called Partial Least Squares (PLS). Detailed descriptions of PLS modeling have been published in the following documents, for example: katz, m.h. multitariate Analysis: a Practice Guide for clinical, cambridge University Press, new York, pages 158-162 (1999); stahle, l., wold, k., multivariate data analysis and experimental design in biomedical research. Prog. Med. Chem.1988, 25:291-338; wold S.PLS-regression: a basic tools of chemometrics, chemom. Intel. Lab. Syst.2001, 58:109-130; and Martens, h.; martens, M.multitariate Analysis of Quality: an induction, wiley and Sons, chichester, UK (2001).

Fig. 9A-9C show viscosity as a function of antibody concentration and pH. The antibody concentration is in the range of greater than about 125mg/mL to greater than about 170 mg/mL. The pH is in the range of less than 5.0 to about 7.5. The concentration dependence is evident, which has a very low viscosity (e.g. as indicated by a viscosity of less than 5mPa-s or 7 mPa-s). m-VROC with A10 chip using Rheosense ^TM A viscometer measures the viscosity. The shear rate employed was about 1820s-1. The viscometer uses a ThermoCube thermoelectric cooler for temperature control and a Hamilton 100 μl syringe (81060) to deliver the sample. The accuracy of the instrument was verified and measured at 25 ℃ using pure isopropanol. Furthermore, the percentage increase in HMW fraction as measured by size exclusion chromatography is in the range of 0% to 1.3% increase over the concentration range tested. HMW as used herein refers to a high molecular weight antibody fraction, e.g., aggregated protein, and it excludes monomeric antibodies.

The foregoing description of various embodiments known to the applicant at the time of filing the application has been presented and is intended for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and many modifications and variations are possible in light of the above teaching. The embodiments described are for explanation of the principles and practical applications and to enable others skilled in the art to utilize the various embodiments and with various modifications as are suited to the particular use contemplated. Therefore, it is intended that the disclosure not be limited to the particular embodiments disclosed.

TABLE 24 additional sequences

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Example 19: verification of 8-SNP model for TL1A companion diagnosis

Machine learning workflow identified several SNP model combinations for developing TL1A companion diagnostics (TL 1A CDx). Previous analysis has identified a 3-SNP combinatorial model consisting of variants associated with TNFSF15 (rs 6478109), ICOSLG (rs 7278257, rs 2070557), ETS1 (rs 7935393) and RBFOX1 (rs 9806914) genes, variant rs 1892231. Next, the 8-SNP model was studied to identify new combinations with improved Positive Predictive Value (PPV) and Negative Predictive Value (NPV).

The 8-SNP model was identified using the method described above via the Hidersianecrohn's Disease group (Cedars Sinai Crohn's Disease method). These additional SNP Models (models_1-model_495) consist of the 8-SNP combination of the following SNPs: TNFSF15 (rs 6478109), ICOSLG (rs 56124762), ETS1 (rs 7935393), RBFOX1 (rs 9806914), C14orf177 (rs 1892231), CTNND2 (rs 16901748), CLEC16A (rs 12934476), RTEL1-TNFRSF6B (rs 2297437), (LINC 01031) rs1326860, PTPN2 (rs 12457255), RGS7 (rs 2815844), JAK2 (rs 10974900), XKR6 (rs 2409750), RBM17 (rs 1541020), ENOX1 (rs 4942248) and PRDM1 (rs 7759385). Table 25 provides 8-SNP model combinations according to embodiments disclosed herein.

TABLE 25.8 SNP model

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Example 20: SNP genotyping assay

This assay was used to identify 8 SNPs in the 8SNP model of example 19. DNA from a sample derived from a subject is combined with primers, PCR reagents, wild-type probes, and mutant probes specific for each SNP. The wild type probe was marked at the 5 'end with a Hex and at the 3' end with a quencher dye. Mutant probes were labeled at the 5 'end with FAM and at the 3' end with quencher.

For each SNP to be tested, 4 standard reactions were performed: template-free, homozygous wild-type, heterozygous and homozygous mutant forms. Standard reactions used templates containing G blocks (gblock) that contained all 8 WT or mutant SNP sequences. For the heterozygous standard reaction, the template contains a WT G block and a mutant G block.

Samples were run in duplicate. Reactions were run and analyzed using quantsudiodx software to detect the genotype of each sample. For each SNP and sample tested, the genotype was identified as homozygous wild type, heterozygous or homozygous mutant.

Example 22: phase 2, multicentric, double blind, placebo-controlled study of CDx with treatment with anti-TL 1A antibodies in subjects with moderate to severe active ulcerative colitis was assessed.

To verify the efficacy of CDx treatment with anti-TL 1A antibodies in Ulcerative Colitis (UC), a phase 2 clinical trial was performed. The detailed design of the clinical trial protocol is provided in the protocol summary of table 26 below and shown in fig. 11A-11B.

TABLE 26 scheme overview

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While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (89)

1. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from said subject, said at least three polymorphisms predicting a positive therapeutic response in said subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and

Wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that competes for binding to human TL1A with a reference antibody comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15.

2. The method of claim 1, wherein the at least three polymorphisms comprise rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or alternative polymorphisms in an unbalanced state therewith, such as by R ² As determined for at least 0.85Or a combination thereof.

3. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms comprising rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257 or rs11221332, or alternative polymorphisms in linkage disequilibrium therewith, such as by R ² As determined by at least 0.85, or a combination thereof, and

Wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that competes for binding to human TL1A with a reference antibody comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15.

4. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from said subject, said at least three polymorphisms predicting a positive therapeutic response in said subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and

Wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to TL1A comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15.

5. The method of claim 4, wherein the at least three polymorphisms comprise rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or alternative polymorphisms in unbalanced state therewith, such as by R ² As determined by at least 0.85, or a combination thereof.

6. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms comprising rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257 or rs11221332, or alternative polymorphisms in linkage disequilibrium therewith, such as by R ² As determined by at least 0.85, or a combination thereof, and

Wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to TL1A comprising a heavy chain variable region comprising: (a) HCDR1 comprising an amino acid sequence consisting of SEQ ID NO:1, and a polypeptide sequence shown in the specification; (b) HCDR2 comprising an amino acid sequence consisting of SEQ ID NO:2-5, and a polypeptide comprising an amino acid sequence as set forth in any one of figures 2-5; and (c) HCDR3 comprising an amino acid sequence consisting of SEQ ID NO: 6-9; and a light chain variable region comprising: (d) LCDR1 comprising an amino acid sequence represented by SEQ ID NO:10, and a polypeptide comprising the amino acid sequence shown in seq id no; (e) LCDR2 comprising an amino acid sequence represented by SEQ ID NO:11, and a polypeptide comprising the amino acid sequence shown in seq id no; and (f) LCDR3 comprising an amino acid sequence represented by SEQ ID NO: 12-15.

7. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from said subject, said at least three polymorphisms predicting a positive therapeutic response in said subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and

Wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence that binds to SEQ ID NO:101-135 or 310-302, and a heavy chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NO:201-206 or 303, and a light chain variable domain of an amino acid sequence that is at least about 90% identical.

8. The method of claim 7, wherein the at least three polymorphisms comprise rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or alternative polymorphisms in unbalanced state therewith, such as by R ² As determined by at least 0.85, or a combination thereof.

9. The method of any one of claims 1 to 8, wherein the heavy chain variable domain comprises a sequence that hybridizes to SEQ ID NO:101-135 or 310-302, at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.

10. The method of any one of claims 1 to 8, wherein the light chain variable domain comprises a sequence that hybridizes to SEQ ID NO:201-206 or 303, at least about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.

11. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms comprising rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257 or rs11221332, or alternative polymorphisms in linkage disequilibrium therewith, such as by R ² As determined by at least 0.85, or a combination thereof, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (TL 1A) comprising an amino acid sequence that binds to SEQ ID NO:101-135 or 310-302, and a heavy chain variable domain comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NO:201-206 or 303, and a light chain variable domain of an amino acid sequence that is at least about 90% identical.

12. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from said subject, said at least three polymorphisms predicting a positive therapeutic response in said subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A, comprising: (a) A heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework; and (b) a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein said heavy chain variable framework region and said light chain variable framework region comprise less than about 14 amino acid modifications in total compared to said human IGHV1-46 x 02 framework and said human IGKV3-20 framework.

13. The method of claim 12, wherein the at least three polymorphisms comprise rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or alternative polymorphisms in an unbalanced state therewith, such as by R ² As determined by at least 0.85, or a combination thereof.

14. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from the subject, the at least three polymorphisms comprising rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750 Rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257 or rs11221332, or alternative polymorphisms in linkage disequilibrium therewith, e.g. by R ² As determined by at least 0.85, or a combination thereof, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A, comprising: (a) A heavy chain variable framework region comprising a human IGHV1-46 x 02 framework or a modified human IGHV1-46 x 02 framework; and (b) a light chain variable framework region comprising a human IGKV3-20 framework or a modified human IGKV3-20 framework; wherein said heavy chain variable framework region and said light chain variable framework region comprise less than about 14 amino acid modifications in total compared to said human IGHV1-46 x 02 framework and said human IGKV3-20 framework.

15. The method of any one of claims 12 to 14, wherein the amino acid modifications of less than 14 amino acid modifications comprise: (a) The amino acid modification is located at position 47 in the heavy chain variable region, and the amino acid at position 47 is R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (b) The amino acid modification is located at position 45 in the heavy chain variable region, and the amino acid at position 45 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (c) The amino acid modification is located at position 55 in the heavy chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; (d) The amino acid modification is located at position 78 in the heavy chain variable region, and the amino acid at position 78 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y; (e) The amino acid modification is located at position 80 in the heavy chain variable region, and the amino acid at position 80 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; (f) The amino acid modification is located at position 82 in the heavy chain variable region, and the amino acid at position 82 is A, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V; (g) The amino acid modification is at position 89 in the heavy chain variable region, and the amino acid at position 89 is A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W or Y; or (h) the amino acid modification is at position 91 in the heavy chain variable region, and the amino acid at position 91 is A, R, N, D, C, Q, E, G, H, I, L, K, F, P, S, T, W, Y or V; or a combination of two or more modifications selected from (a) to (h).

16. The method of claim 15, wherein the amino acid modifications of less than 14 amino acid modifications comprise: a47R, R45K, M55I, V A, M80I, R82T, V3589A, M91L in the heavy chain variable region, numbered according to Aho or Kabat.

17. The method of claim 15, wherein the amino acid modifications of less than 14 amino acid modifications comprise: (a) Modification at amino acid position 54 in the light chain variable region; and/or (b) a modification at amino acid position 55 in the light chain variable region; numbered according to Aho or Kabat.

18. The method of any one of claims 12 to 14, wherein the amino acid modifications of less than 14 amino acid modifications comprise: (a) The amino acid modification is at position 54 of the light chain variable region, and the amino acid at position 54 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V; and/or (b) the amino acid modification is located at position 55 of the light chain variable region, and the amino acid at position 55 is A, R, N, D, C, Q, E, G, H, I, K, M, F, P, S, T, W, Y or V.

19. The method of claim 18, wherein the amino acid modification of less than 14 amino acid modifications comprises L54P and/or L55W in the light chain variable region, numbered according to Aho or Kabat.

20. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from said subject, said at least three polymorphisms predicting a positive therapeutic response in said subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises:

a heavy chain variable region comprising SEQ ID NO:301X1 VQLVQSGAEVKKGASVKVAKVSKAS [ HCDR1] WVX 2X 3PGQGLEWX4G [ HCDR2] Rx5TX6TX7 DTSTX8 YX9 ELSSLRSEDTAVTYCARYYCAR [ HCDR3] WGQGTTVSS, and

a light chain variable region comprising SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V.

21. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms are detected in a sample obtained from said subject, said at least three polymorphisms predicting a positive therapeutic response in said subject to treatment with an inhibitor of said TL1A activity or expression having a positive predictive value or specificity of at least about 51%, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises:

a heavy chain variable region comprising SEQ ID NO:302

X1VQLVQSGAEVKKPGASVKVSCKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC [ HCDR3] WGQGTTVTVSS, and

a light chain variable region comprising SEQ ID NO:303

EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V.

22. The method of any one of claims 20 to 21, wherein the at least three polymorphisms comprise rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or alternative polymorphisms in an unbalanced state therewith, such as by R ² As determined by at least 0.85, or a combination thereof.

23. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

wherein at least three polymorphisms including rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs494 are detected in a sample obtained from the subject 2248. rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or alternative polymorphisms in linkage disequilibrium therewith, e.g., by R ² As determined by at least 0.85, or a combination thereof, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises:

a heavy chain variable region comprising SEQ ID NO:301X1 VQLVQSGAEVKKGASVKVAKVSKAS [ HCDR1] WVX 2X 3PGQGLEWX4G [ HCDR2] Rx5TX6TX7 DTSTX8 YX9 ELSSLRSEDTAVTYCARYYCAR [ HCDR3] WGQGTTVSS, and

a light chain variable region comprising SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V.

24. A method of treating an inflammatory, fibrotic or fibrotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL 1A) activity or expression,

Wherein at least three polymorphisms are detected in a sample obtained from the subject, including rs16901748, rs56124762, rs6478109, rs1892231, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257 or rs11221332, orAlternative polymorphisms in linkage disequilibrium therewith, e.g. by R ² As determined by at least 0.85, or a combination thereof, and

wherein the inhibitor of TL1A activity or expression is an antibody or antigen binding fragment thereof that binds to TL1A and comprises:

a heavy chain variable region comprising SEQ ID NO:302X1 VQLVQCGAEVEKKKGASVKVAKVSKAS [ HCDR1] WVX2QX3PGQGLEWX4G [ HCDR2] Rx5TX6TX7 DTSTX8 YX9 ELSSLRSEDTAVYC [ HCDR3] WGQGTTVSS, and

A light chain variable region comprising SEQ ID NO:303EIVLTQSPGTLSLSPGERATLSC [ LCDR1] WYQKPGQAPRX 10X11IY [ LCDR2] GIPDRFSGSGTDFTTYLCRRLEDEFAVYC [ LCDR3] FGGGTKLEIK, wherein each of X1-X11 is independently selected from A, R, N, D, C, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y or V.

25. The method of any one of claims 20 to 24, wherein:

(A) X1 is Q or E;

(B) X2 is R or K

(C) X3 is A or R;

(D) X4 is M or I;

(E) X5 is V or A;

(F) X6 is M or I;

(G) X7 is R or T;

(H) X8 is V or A;

(I) X9 is M or L

(J) X10 is L or P;

(K) X11 is L or W; or (b)

(L) X1-X11 is any combination of (a) through (k).

26. The method of any one of claims 20 to 24, wherein the antibody or antigen binding fragment comprises an amino acid sequence as set forth in SEQ ID NO:1, as set forth by SEQ ID NO:2-5, a heavy chain CDR2 as set forth by any one of SEQ ID NOs: 6-9, a heavy chain CDR3 as set forth by any one of SEQ ID NOs: 10, as set forth by SEQ ID NO:11 and a light chain CDR2 as set forth by SEQ ID NO:12-15, and a light chain CDR3 as set forth in any one of claims 12-15.

27. The method of any one of claims 20 to 24, wherein the antibody or antigen binding fragment comprises an amino acid sequence as set forth in SEQ ID NO:304, a heavy chain Framework (FR) 1 as set forth by SEQ ID NO:305 or SEQ ID NO:313, a heavy chain FR2 as represented by SEQ ID NO: 306. 307, 314 or 315, as represented by any one of SEQ ID NOs: 308, as represented by SEQ ID NO:309, the light chain FR1 as represented by SEQ ID NO:310, a light chain FR2 as represented by SEQ ID NO:311 or the light chain FR3 as represented by SEQ ID NO:312, or a combination thereof.

28. The method of any one of claims 1 to 27, wherein the antibody or antigen binding fragment comprises a human IgG1Fc region comprising (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) 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 L, (ii) 343I, 373, (jj) A, 267G, or 373, (kk) 376E, W, or 376, (ll) 376D, (ll) 382D, (382D, or 382I, (373D 382I, (nn) 385P, (op) 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, (V) L234A and L235A, (ww) L234A, L a and G237A, (xx) L234A, L a and P329G, (yy) L234F, L E and P331S, (zz) L234A, L E and G237A, (aaa) L234A, L E, G a and P331S, (bbb) L234A, L235A, G237A, P S, H268A, A S and P331S (IgG 1), (σccc) L A, L a and P329A, (ddd) G236R and L328R, (eee) G237A, (fff) F241A, (xx) L234G 235A and P329G, (y) L234E and P237A, (gaa) L234E and P35 b, (gaa) L234A, (aaa) L234N) 35 b and P35 b (G37A, (G35 b) N) and P35 b (G).

29. The method of any one of claims 1 to 27, wherein the antibody or antigen binding fragment comprises a human IgG4Fc region.

30. The method of any one of claims 1 to 27, wherein the antibody or antigen binding fragment comprises an Fc region comprising an amino acid sequence that hybridizes to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence.

31. The method of any one of claims 1 to 27, wherein the antibody of an antigen binding fragment comprises a crystallizable fragment (Fc) region comprising reduced antibody dependent cell-mediated cytotoxicity (ADCC) function as compared to human IgG1 and/or reduced Complement Dependent Cytotoxicity (CDC) as compared to human IgG1.

32. The method of any one of claims 1 to 27, wherein the Fc comprises a polypeptide comprising SEQ ID NO:320, human IgG1.

33. The method of any one of claims 1-27, wherein the ADCC function comprising a reduced ADCC Fc region is reduced by at least about 50% compared to human IgG1.

34. Wherein the CDC function of the Fc region comprising reduced CDC is reduced by at least about 50% as compared to human IgG1.

35. The method of any one of claims 1 to 27, wherein the Fc comprises (i) a human IgG4Fc region, or (ii) a human IgG4Fc region comprising: (a) S228P, (b) S228P and L235E, or (c) S228P, F234A and L235A, numbered according to Kabat.

36. The method of any one of claims 1 to 27, wherein the Fc comprises a human IgG2Fc region; an IgG2-IgG4 cross-subclass Fc region; an IgG2-IgG3 cross-subclass Fc region; igG2 (IgG 2m 4) comprising H268Q, V309L, A S, P331S; or IgG2 (lgg2σ) comprising V234A, G237A, P238S, H268A, V309L, A330S, P S.

37. The method of any one of claims 1 to 27, wherein the Fc comprises a human IgG1 having a substitution 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, 254V, 264S, 265H, 265K, 265S, 265Y, 265A, 267G, 267H, 267I, 267K, 434I, 438G, 439E, 439H, 439Q, 440A, 440D, 440E, 440F, 440M, 440T and 440V, numbered according to Kabat.

38. The method of any one of claims 1 to 27, wherein the Fc comprises a sequence identical to SEQ ID NO:320-362, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical sequence.

39. The method of any one of claims 1 to 27, wherein the Fc comprises SEQ ID No:401-413 or with any one of SEQ ID nos: 401-413, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical.

40. The method of any one of claims 1 to 27, wherein the antibody or antigen-binding fragment comprises a heavy chain comprising the amino acid sequence of SEQ ID No:501-513 or with any one of SEQ ID nos: 501-513, at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical.

41. The method of any one of claims 1 to 27, wherein the antibody or antigen-binding fragment comprises a light chain comprising the amino acid sequence of SEQ ID NO:514 or any one of SEQ ID NO:514 at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical.

42. The method of any one of claims 1 to 41, wherein the at least three polymorphisms are predicted to have a positive predictive value of at least about 51% and a specific positive therapeutic response.

43. The method of any one of claims 1 to 41, wherein the positive predictive value is greater than or equal to about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

44. The method of any one of claims 1-41, wherein the positive predictive value is between about 60% -100%, 65% -95%, 70% -90%, 75% -85% and 70% -80%.

45. The method of any one of claims 1 to 41, wherein the specificity is greater than or equal to about 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

46. The method of any one of claims 1-41, wherein the specificity is between about 60% -100%, 65% -95%, 70% -90%, 75% -85% and 70% -80%.

47. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs56124762 and rs1892231.

48. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs56124762 and rs16901748.

49. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs1892231 and rs16901748.

50. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs56124762, rs1892231 and rs16901748.

51. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs2070558 and rs1892231.

52. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs2070558 and rs16901748.

53. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs1892231 and rs16901748.

54. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs2070558, rs1892231 and rs16901748.

55. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs2070561 and rs1892231.

56. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs2070561 and rs16901748.

57. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs1892231 and rs16901748.

58. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs2070561, rs1892231 and rs16901748.

59. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs7935393 and rs1892231.

60. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs7935393 and rs9806914.

61. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs7935393 and rs7278257.

62. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs7935393 and rs2070557.

63. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs1892231 and rs9806914.

64. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs1892231 and rs7278257.

65. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs1892231 and rs2070557.

66. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs9806914 and rs7278257.

67. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs9806914 and rs2070557.

68. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs7278257 and rs2070557.

69. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs7935393, rs1892231 and rs9806914.

70. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs7935393, rs1892231 and rs7278257.

71. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs7935393, rs1892231 and rs2070557.

72. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs7935393, rs9806914 and rs7278257.

73. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs7935393, rs9806914 and rs2070557.

74. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs7935393, rs7278257 and rs2070557.

75. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs1892231, rs9806914 and rs7278257.

76. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs1892231, rs9806914 and rs2070557.

77. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs1892231, rs7278257 and rs2070557.

78. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs9806914, rs7278257 and rs2070557.

79. The method of any one of claims 1 to 41, wherein the at least three polymorphisms comprise: rs6478109, rs56124762 and rs1892231.

80. The method of any one of claims 1 to 79, wherein the at least three polymorphisms further comprise a fourth polymorphism comprising rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, 10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, 7278257, or rs11221332, or a surrogate thereof in linkage disequilibrium state, as determined by R2 of at least 0.85, or a combination thereof.

81. The method of any one of claims 1 to 80, wherein the at least three polymorphisms in the sample are detected by performing an assay on the sample, the assay configured to detect a nucleotide sequence corresponding to SEQ ID NO:2001-20041 or 20057-20059, and the presence of at least three nucleotides of nucleic acid position 501 within at least three of them.

82. The method of any one of claims 1-81, wherein the inflammatory, fibrotic, or fibrotic disease or condition comprises inflammatory bowel disease, crohn's disease, obstructive crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, pulmonary fibrosis, scleroderma, or primary sclerosing cholangitis.

83. The method of claim 82, wherein the Crohn's disease is ileal Crohn's disease, ileal colon Crohn's disease or colon Crohn's disease.

84. The method of claim 82, wherein the pulmonary fibrosis comprises idiopathic pulmonary fibrosis.

85. The method of any one of claims 1-83, wherein the subject has or is at risk of developing a standard therapy that does not respond or loses response to, including glucocorticoid, anti-TNF therapy, anti-a 4-b7 therapy, anti-IL 12p40 therapy, or a combination thereof.

86. The method of any one of claims 1-85, further comprising determining whether the subject with an inflammatory, fibrotic, or fibrotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression based at least in part on the at least three polymorphisms detected in the sample.

87. The method of any one of claims 1-86, further comprising obtaining or having obtained the sample from the subject.

88. The method of any one of claims 1 to 87, wherein the at least three polymorphisms are detected using an assay comprising quantitative polymerase chain reaction (qPCR), nucleic acid sequencing reaction, or genotyping array.

89. The method of any one of claims 1-88, wherein the at least three polymorphisms comprise:

(i) Three polymorphisms selected from table 1;

(ii) Four polymorphisms selected from table 1;

(iii) Five polymorphisms selected from table 1;

(iv) Six polymorphisms selected from table 1;

(v) Seven polymorphisms selected from table 1;

(vi) Eight polymorphisms from one or more 8-SNP models provided in Table 25

(vii) Nine polymorphisms selected from table 1; or (b)

(viii) Ten polymorphisms selected from table 1.