Anti-TL1A antibody composition and skin treatment method

Abstract

Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of skin diseases and / or conditions, including, among others, hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, and alopecia areata.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 485,815, filed February 17, 2023.

[0002] Reference to an electronically submitted sequence listing This application contains a Sequence Listing that has been submitted electronically in XML format, which is incorporated by reference in its entirety. The XML file, created on February 2, 2024, is named 25814-WO-PCT_SL.xml and is 380,462 bytes in size. [Background technology]

[0003] TL1A is a cytokine secreted by antigen-presenting cells, T cells, and endothelial cells. TL1A signals through death receptor 3 (DR3), a TNF family receptor found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphoid cells (ILCs), fibroblasts, and epithelial cells, and potently drives Th1, Th2, Th9, and Th17 responses. Furthermore, it is induced in antigen-presenting cells by toll-like receptor (TLR) ligands and FcR crosslinking, and in T cells by T cell receptor (TCR) stimulation. TL1A has been shown to be upregulated in the mucosa and serum of patients with inflammatory bowel disease. In dextran sulfate sodium (DSS) and adoptive transfer mouse models, antibodies against TL1A reduced inflammation and reversed fibrosis, even when treatment was administered late in the disease course, after inflammation and fibrosis had been established. Summary of the Invention

[0004] The present disclosure provides tumor necrosis factor ligand 1A (TL1A)-binding antibodies and antigen-binding fragments thereof, and compositions thereof, for the treatment of inflammation and / or fibrosis, including diseases or conditions present in a subject's skin, and / or systemic sclerosis. In various aspects, the antibodies and antigen-binding fragments thereof described herein possess characteristics useful for therapeutic applications, such as low immunogenicity, and / or characteristics that facilitate production of the antibody or antigen-binding fragment thereof, such as a high percentage of monomeric fraction as measured by size exclusion chromatography and / or high expression. In further aspects, the antibodies and antigen-binding fragments thereof described herein possess characteristics useful for subcutaneous administration, such as low viscosity at high antibody or antigen-binding fragment concentrations. Further aspects of the antibodies and antigen-binding fragments and their formulations may include high solubility, low sub-visible particles, low opalescence, no visible particles, and any combination thereof.

[0005] In one aspect, provided herein is a method of treating inflammation in a subject in need thereof, comprising administering to the subject an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody) or an antigen-binding fragment thereof. In some embodiments, the subject has inflammation in the skin. Further provided is a method of treating fibrosis in a subject in need thereof, comprising administering to the subject an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody) or an antigen-binding fragment thereof. In some embodiments, the subject has fibrosis in the skin. Further provided is a method of treating a skin disease and / or condition in a subject in need thereof, comprising administering to the subject an antibody that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody) or an antigen-binding fragment thereof.

[0006] In some embodiments, the subject has a chronic skin disorder. In some embodiments, the subject has systemic sclerosis. In some embodiments, the subject with systemic sclerosis has skin symptoms of systemic sclerosis. In some embodiments, the subject with systemic sclerosis has systemic sclerosis-associated interstitial lung disease. In some embodiments, the subject has scleroderma. In some embodiments, the subject has psoriasis. In some embodiments, the subject has lupus. In some embodiments, the subject has eczema. In some embodiments, the subject has dermatomyositis. In some embodiments, the subject has systemic sclerosis or scleroderma, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof. In some embodiments, the subject has hidradenitis suppurativa. In some embodiments, the subject has atopic dermatitis. In some embodiments, the subject has vitiligo. In some embodiments, the subject has alopecia areata. In some embodiments, the subject has alopecia areata. In some embodiments, the inflammation in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata. In some embodiments, the fibrosis in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata. In some embodiments, the skin disease and / or condition in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

[0007] In one aspect, provided herein is a method of treating hidradenitis suppurativa in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A. In one aspect, provided herein is a method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A. In a further aspect, provided herein is a method of treating psoriasis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A. In yet another aspect, provided herein is a method of treating vitiligo in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A. In another aspect, provided herein is a method of treating alopecia areata in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A.

[0008] In some embodiments, the anti-TL1A antibody or antigen-binding fragment is administered in a pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises an anti-TL1A antibody or antigen-binding fragment at a concentration greater than about 150 mg / mL. In some embodiments, the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, or 200 mg / mL. In some embodiments, the concentration is about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, or 225 mg / mL. In some embodiments, the concentration is between about 150 mg / mL and about 250 mg / mL. In some embodiments, the concentration is between about 175 mg / mL and about 225 mg / mL. In one aspect, provided herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody) at a concentration greater than about 50 mg / mL. In some embodiments, the concentration is greater than about 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, or 145 mg / mL. In certain embodiments, the concentration is greater than about 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, or 145 mg / mL. In some embodiments, the pharmaceutical composition is administered subcutaneously. In some embodiments, about 150 mg to about 500 mg of the anti-TL1A antibody or antigen-binding fragment is present in the composition. In some embodiments, the composition has a total volume of about 2 mL or less. In some embodiments, the composition has a total volume of about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 mL or less. In some embodiments, the pharmaceutical composition comprises a therapeutically effective dose of an anti-TL1A antibody or antigen-binding fragment.In some embodiments, the composition comprises about 9.0, 8.9, 8.8, 8.7, 8.6, 8.5, 8.4, 8.3, 8.2, 8.1, 8.0, 7.9, 7.8, 7.7, 7.6, 7.5, 7.4, 7.3, 7.2, 7.1, 7.0, 6.9, 6.8, 6.7, 6.6, 6.5, 6.4, 6.3, 6.2, 6.1, 6.0, 5.9, 5.8, 5.7, 5.6, 5.5, 5.4, 5.3, 5.2, 5.1, 5.0, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 ...1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4. In some embodiments, the compositions have a total volume of about 0.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, or 0.8 mL or less. In some embodiments, the compositions have a total volume of about 0.5 mL to about 1.5 mL. In some embodiments, the compositions herein have a total volume of about 0.5 mL to about 2.5 mL. In some embodiments, the compositions herein have a total volume of about 0.5 mL to about 3.5 mL. In some embodiments, the compositions herein have a total volume of about 0.5 mL to about 4.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 1.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 2.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 3.5 mL. In some embodiments, the compositions herein have a total volume of about 1 mL to about 4.5 mL. In some embodiments, the compositions herein have a viscosity of less than about 20 cP. In some embodiments, the compositions have a viscosity of less than about 15 cP. In some embodiments, the compositions have a viscosity of less than about 10 cP. In some embodiments, the compositions have a viscosity of less than about 9, 8, 7, 6, or 5 cP. In some embodiments, the compositions have a viscosity of about 1 cP to about 7 cP, about 1 cP to about 2 cP, or about 10 cP to about 20 cP. In some embodiments, the compositions have a viscosity of about 1 cP to about 10 cP. In some embodiments, the compositions have a viscosity of about 1 cP to about 15 cP. In some embodiments, the composition has a viscosity of about 1 cP to about 20 cP.In some embodiments, the pharmaceutical composition has an aggregate percentage of anti-TL1A antibodies or antigen-binding fragments of less than about 5% of the total anti-TL1A antibodies or antigen-binding fragments in the composition, as measured by size exclusion chromatography. In some embodiments, the aggregation is less than about 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5%. In some embodiments, the composition comprises a surfactant. In some embodiments, the surfactant comprises a non-ionic surfactant. In some embodiments, the non-ionic surfactant comprises polysorbate-20. In some embodiments, the surfactant is present at a concentration of about 0.005% to about 0.05% of the composition. In some embodiments, the surfactant is present at a concentration of about 0.01% to about 0.02% of the composition. In some embodiments, the surfactant is present at a concentration of about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, about 0.015%, about 0.016%, about 0.017%, about 0.018%, about 0.019%, about 0.02%, about 0.021%, about 0.022%, about 0.023%, about 0.024%, about 0.025%, about 0.026%, about 0.027%, about 0.028%, about 0.029%, or about 0.03% (v / v) of the composition. In some embodiments, the composition comprises a salt. In some embodiments, the salt comprises sodium chloride, glycine, lysine hydrochloride, arginine hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof. In some embodiments, the salt comprises sodium chloride. In some embodiments, the salt comprises lysine-HCl. In some embodiments, the salt is present in the composition at a concentration of about 10 mM to about 100 mM. In some embodiments, the salt is present in the composition at a concentration of about 25 mM. In some embodiments, the salt is present in the composition at a concentration of about 40 mM. In some embodiments, the composition comprises a stabilizer. In some embodiments, the stabilizer comprises a sugar, a polyol, an amino acid, or a polymer, a cyclodextrin (e.g., HP-b-CD), or a combination thereof. In some embodiments, the stabilizer comprises a sugar.In some embodiments, the sugar comprises sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof. In some embodiments, the sugar comprises sucrose. In some embodiments, the amino acid comprises glycine. In some embodiments, the stabilizer is present in the composition at a concentration of about 50 mM to about 300 mM. In some embodiments, the stabilizer is present at a concentration of about 200 mM to about 280 mM. In some embodiments, the stabilizer is present at a concentration of about 220 to about 240 mM. In certain embodiments, the stabilizer is present at a concentration of about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 210 mM, about 220 mM, about 230 mM, about 240 mM, or about 250 mM. In some embodiments, the stabilizer comprises sucrose and glycine. In certain embodiments, sucrose is present at a concentration of about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 210 mM, about 220 mM, about 230 mM, about 240 mM, or about 250 mM. In some embodiments, glycine is present at a concentration of about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 105 mM, about 110 mM, about 115 mM, or about 120 mM. In some embodiments, the composition comprises a buffering agent. In some embodiments, the buffering agent comprises acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, tris(tris(hydroxymethyl)aminomethane), or diethanolamine, or a combination thereof. In some embodiments, the buffering agent comprises acetate. In some embodiments, the buffering agent comprises phosphate. In some embodiments, the buffering agent is present in the composition at a concentration of about 10 mM to about 50 mM. In some embodiments, the composition comprises about 20 mM buffer. In some embodiments, the composition has a pH of about 4.5 to about 8.0. In some embodiments, the composition has a pH of about 4.5 to about 7.5. In some embodiments, the composition has a pH of about 6 to about 7.In some embodiments, the composition has a pH of about 6.5, in some embodiments, the composition has a pH of about 5 to about 5.5, in some embodiments, the composition has a pH of about 5.3.

[0009] In some embodiments, the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a first dose of up to about 1000 mg. In some embodiments, the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a first dose of about 150 mg to about 1000 mg. In some embodiments, the first dose is about 500 mg to about 1000 mg. In some embodiments, the first dose is about 500 mg or about 800 mg. In some embodiments, the first dose is administered to the subject at a first time point and the second dose is administered to the subject at a second time point. In some embodiments, the second time point is 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 31 days after the first time point. In some embodiments, the second time point is about 1, 2, 3, or 4 weeks after the first time point. In some embodiments, the second dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the second dose comprises about 150 mg to about 1000 mg. In some embodiments, the second dose comprises about 150 mg to about 600 mg. In some embodiments, a third dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at the third time point. In some embodiments, the third time point is 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 31 days after the second time point. In some embodiments, the third time point is about 1, 2, 3, or 4 weeks after the second time point. In some embodiments, the third dose comprises up to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the third dose comprises about 150 mg to about 1000 mg. In some embodiments, the third dose comprises about 150 mg to about 600 mg. In some embodiments, a fourth dose of an anti-TL1A antibody or antigen-binding fragment is administered to the subject at the fourth time point. In some embodiments, the fourth time point is 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 31 days after the third time point.In some embodiments, the fourth time point is about 1, 2, 3, or 4 weeks after the third time point. In some embodiments, the fourth dose comprises up to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the fourth dose comprises about 150 mg to about 1000 mg. In some embodiments, the fourth dose comprises about 150 mg to about 600 mg. In some embodiments, a fifth dose of an anti-TL1A antibody or antigen-binding fragment is administered to the subject at the fifth time point. In some embodiments, the fifth time point is 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 31 days after the fourth time point. In some embodiments, the fifth time point is about 1, 2, 3, or 4 weeks after the fourth time point. In some embodiments, the fifth dose comprises up to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the fifth dose comprises about 150 mg to about 1000 mg. In some embodiments, the fifth dose comprises about 150 mg to about 600 mg. In some embodiments, a sixth dose of an anti-TL1A antibody or antigen-binding fragment is administered to the subject at the sixth time point. In some embodiments, the sixth time point is 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 31 days after the fifth time point. In some embodiments, the sixth time point is about 1, 2, 3, or 4 weeks after the fifth time point. In some embodiments, the sixth dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the sixth dose comprises about 150 mg to about 1000 mg. In some embodiments, the sixth dose comprises about 150 mg to about 600 mg.

[0010] In some embodiments, additional doses of the anti-TL1A antibody or antigen-binding fragment are administered to the subject at one or more additional time points. In some embodiments, the one or more additional time points include about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 additional time points. In some embodiments, the composition is administered to the subject at about 12 additional time points. In some embodiments, each additional time point is independently 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 31 days after the previous time point. In some embodiments, each additional time point is independently about 1, 2, 3, or 4 weeks after the previous time point. In some embodiments, at least one of the additional time points is about 2 weeks after the previous time point. In some embodiments, the additional dose comprises up to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the additional dose comprises about 150 mg to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the additional dose is about 175 mg to about 300 mg of an anti-TL1A antibody or antigen-binding fragment.

[0011] In one aspect, provided herein is an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A ("TL1A", and such an antibody or antigen-binding fragment thereof, "anti-TL1A antibody or antigen-binding fragment"), wherein the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A.

[0012] In some embodiments, the antibody or antigen-binding fragment blocks the interaction of TL1A with death receptor 3 ("DR3"). In some embodiments, the dissociation equilibrium constant (K D-monomer The binding affinity of an antibody or antigen-binding fragment to monomeric TL1A, as measured by the dissociation equilibrium constant (K D-trimer ) corresponds to the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A. In some embodiments, K D-monomer But, K D-trimerIn some embodiments, K is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times of D-monomer is 0.06 nM or less. D-trimer is less than 0.06 nM.

[0013] In one aspect, provided herein is a method of neutralizing monomeric and trimeric TL1A in a subject with skin inflammation and / or skin fibrosis, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A, and the antibody or antigen-binding fragment blocks the interaction of TL1A with DR3, such that the concentration of TL1A in diseased tissue of the subject is reduced to below the concentration of TL1A in the corresponding tissue of a control subject without skin inflammation and / or skin fibrosis, and the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues with skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of skin inflammation and / or skin fibrosis. In some embodiments, the subject has one or more inflammatory conditions selected from the group consisting of chronic skin disorders, systemic sclerosis, psoriasis, lupus, eczema, and dermatomyositis. In some embodiments, the subject has systemic sclerosis, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof. In some embodiments, the subject has hidradenitis suppurativa. In some embodiments, the subject has atopic dermatitis. In some embodiments, the subject has vitiligo. In some embodiments, the subject has alopecia areata. In some embodiments, the subject has alopecia areata. In some embodiments, the skin inflammation and / or skin fibrosis is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata. In some embodiments, the skin inflammation and / or skin fibrosis is hidradenitis suppurativa. In some embodiments, the skin inflammation and / or skin fibrosis is atopic dermatitis. In some embodiments, the skin inflammation and / or skin fibrosis is psoriasis. In some embodiments, the skin inflammation and / or skin fibrosis is vitiligo. In some embodiments, the skin inflammation and / or skin fibrosis is alopecia areata.

[0014] In one aspect, provided herein is a method for reducing the concentration of TL1A in diseased tissue of a subject with skin inflammation and / or skin fibrosis, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment, thereby reducing the concentration of TL1A in the subject's diseased tissue to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues with skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of skin disease and / or skin fibrosis.

[0015] In one aspect, provided herein is a method of treating skin inflammation and / or skin fibrosis in a subject in need thereof, comprising: (a) administering to the subject an anti-TL1A antibody or antigen-binding fragment, wherein the anti-TL1A antibody or antigen-binding fragment is administered at an effective dose such that the concentration of TL1A in the subject's diseased tissue after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis, and the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of skin inflammation and / or skin fibrosis.

[0016] In one aspect, provided herein is a method of treating skin inflammation and / or skin fibrosis in a subject in need thereof, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment; and (b) reducing the concentration of TL1A in the subject's diseased tissue to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of skin inflammation and / or skin fibrosis.

[0017] In some embodiments, the effective dose includes an induction regimen.

[0018] In some embodiments, the method further comprises (c) maintaining TL1A in the diseased tissue of the subject at a concentration that is less than the concentration of TL1A in the corresponding tissue of the control subject.

[0019] In some embodiments, TL1A in the subject's diseased tissue is maintained with a maintenance regimen of an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the induction regimen and the maintenance regimen are the same. In some embodiments, the induction regimen and the maintenance regimen are different. In some embodiments, the maintenance regimen is administered after the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A during the induction regimen compared to corresponding tissue in a control subject. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to corresponding tissue in a control subject within 1, 2, 3, 4, 5, or 6 weeks of starting the induction regimen. In some embodiments, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to corresponding tissue in a control subject.

[0020] In some embodiments, the induction regimen comprises a single administration of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody or antigen-binding fragment is administered at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

[0021] In some embodiments, the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the induction regimen comprises: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 100 mg / dose at week 2, 100 mg / dose at week 6, and 100 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; or (v) 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10.

[0022] In some embodiments, the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose. In some embodiments, the induction regimen comprises administration once every 2, 4, 6, or 8 weeks. In some embodiments, the induction regimen involves administration once every 2 or 4 weeks for the first two doses, then once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

[0023] In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than corresponding tissue in a control subject. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than corresponding tissue in a control subject during a maintenance regimen. In some embodiments, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than corresponding tissue in a control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks or more of the start of a maintenance regimen.

[0024] In some embodiments, the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments, the maintenance regimen includes (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks. g / dose, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0025] In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose. In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks. In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every 4 weeks. In some embodiments, the maintenance regimen comprises administration of an anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every 4 weeks. In some embodiments, the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

[0026] In some embodiments, the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A, and the antibody or antigen-binding fragment blocks TL1A binding to DR3. In some embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the subject's blood is occupied by the anti-TL1A antibody or antigen-binding fragment. In some embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the subject's blood is occupied by anti-TL1A antibodies or antigen-binding fragments.

[0027] In some embodiments, the dissociation equilibrium constant (K D-monomer The binding affinity of an antibody or antigen-binding fragment to monomeric TL1A, as measured by the dissociation equilibrium constant (K D-trimer ) corresponds to the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A. In some embodiments, K D-monomer But, K D-trimerIn some embodiments, K is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times of D-monomer is 0.06 nM or less. D-trimer is less than 0.06 nM.

[0028] In some embodiments, the subject has one or more conditions of skin inflammation and / or skin fibrosis selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0029] In some embodiments, the subject has systemic sclerosis, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

[0030] In some embodiments, the subject has hidradenitis suppurativa.

[0031] In some embodiments, the subject has atopic dermatitis.

[0032] In some embodiments, the subject has vitiligo.

[0033] In some embodiments, the subject has alopecia areata.

[0034] In some embodiments, the subject has alopecia areata.

[0035] In some embodiments of the methods provided herein, the skin inflammation and / or skin fibrosis is hidradenitis suppurativa. In some embodiments, the skin inflammation and / or skin fibrosis is atopic dermatitis. In some embodiments, the skin inflammation and / or skin fibrosis is psoriasis. In some embodiments, the skin inflammation and / or skin fibrosis is vitiligo. In some embodiments, the skin inflammation and / or skin fibrosis is alopecia areata. In some embodiments, the skin inflammation and / or skin fibrosis is selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, a chronic skin disorder, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0036] In some embodiments of the methods provided herein, the skin inflammation and / or skin fibrosis is skin inflammation. In some embodiments, the skin inflammation is hidradenitis suppurativa. In some embodiments, the skin inflammation is atopic dermatitis. In some embodiments, the skin inflammation is psoriasis. In some embodiments, the skin inflammation is vitiligo. In some embodiments, the skin inflammation is alopecia areata. In some embodiments, the skin inflammation is selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, a chronic skin disorder, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0037] In some embodiments of the methods provided herein, the skin inflammation and / or skin fibrosis is skin inflammation. In some embodiments, the skin inflammation is hidradenitis suppurativa. In some embodiments, the skin inflammation is atopic dermatitis. In some embodiments, the skin inflammation is psoriasis. In some embodiments, the skin inflammation is vitiligo. In some embodiments, the skin inflammation is alopecia areata. In some embodiments, the skin inflammation is selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, a chronic skin disorder, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0038] In some embodiments of the methods provided herein, the skin inflammation and / or skin fibrosis is skin fibrosis. In some embodiments, the skin fibrosis is hidradenitis suppurativa. In some embodiments, the skin fibrosis is atopic dermatitis. In some embodiments, the skin fibrosis is psoriasis. In some embodiments, the skin fibrosis is vitiligo. In some embodiments, the skin fibrosis is alopecia areata. In some embodiments, the skin fibrosis is selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, a chronic skin disorder, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0039] In some embodiments, the effective dose or induction regimen is determined by a dose determination method, the dose determination method comprising: (i) receiving parameters of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (ii) integrating the parameters received in (i) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or population pharmacokinetic (popPK) model; and (iii) determining an effective dose or induction regimen such that the concentration of TL1A in the diseased tissue of the subject after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis. In some embodiments, the parameter for TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200-fold or more overproduction compared to TL1A production in normal reference tissue.

[0040] In some embodiments, the maintenance regimen is determined by a dose determination method, the dose determination method comprising: (i) receiving a parameter of TL1A overproduction in the diseased tissue compared to TL1A production in a normal reference tissue; (ii) integrating the parameter received in (i) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or a population pharmacokinetic (popPK) model; and (iii) determining a maintenance regimen such that the concentration of TL1A in the diseased tissue of the subject after step (c) is less than the concentration of TL1A in the corresponding tissue of a control subject without skin inflammation and / or skin fibrosis. In some embodiments, the parameter of TL1A overproduction is 10-, 15-, 20-, 25-, 30-, 35-, 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-, 80-, 85-, 90-, 95-, 100-, or more-fold overproduction compared to TL1A production in the normal reference tissue.

[0041] In some embodiments, step (i) of the dose determination method comprises measuring the association rate of the antibody to TL1A (k on-mAb ), the dissociation rate of the antibody from TL1A (k off-mAb ), the synthesis rate of TL1A in normal tissues (k syn-normal ), the synthesis rate of TL1A in diseased tissue (k syn-disease ), and / or the degradation rate of TL1A (k deg-total-TL1A In some embodiments, the association rate of the antibody to TL1A (k on-mAb ) is the association rate of the antibody to monomeric TL1A (k on-monomer ) and the association rate of the antibody to trimeric TL1A (k on-trimer ), and the dissociation rate of the antibody from TL1A (k off-mAb ) is the dissociation rate of the antibody from monomeric TL1A (k off-monomer ) and the dissociation rate of the antibody from trimeric TL1A (k off-trimer ) and / or the degradation rate of TL1A (k deg-total-TL1A ) is the degradation rate of monomeric TL1A (k deg-TL1A-monomer ) and the degradation rate of trimeric TL1A (k deg-TL1A-trimer ) is included.

[0042] In some embodiments, step (i) of the dose determination method comprises measuring the association rate of the antibody to the FcRn receptor (k on-mAb-FcRn ), the dissociation rate of antibody from FcRn (k off-mAb-FcRn ), and the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn In some embodiments, the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ) is the association rate (k on-(mAb-monoTL1A)-FcRn ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k on-(mAb-triTL1A)-FcRn ) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is the dissociation rate of the antibody-monomer-TL1A complex from FcRn (k off-(mAb-monoTL1A)-FcRn ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k off-(mAb-triTL1A)-FcRn ) is included.

[0043] In some embodiments, step (i) of the dose determination method comprises measuring the clearance rate of antibody-bound FcRn receptor (k deg-mAb-FcRn In some embodiments, the clearance rate (k) of the antibody-bound FcRn receptor is measured. deg-mAb-FcRn ) is the clearance rate (k deg-(mAb-monoTL1A)-FcRn ) and the clearance rate (k deg-(mAb-triTL1A)-FcRn In some embodiments, the method for determining the dose comprises: (1) k on-monomer and k on-trimer are the same or different, (2)k off-monomer and k off-trimer are the same or different, (3)k deg-monomer and k deg-trimer are the same or different, (4)k on-(mAb-monoTL1A)-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (5)k on-mAb-FcRn and k on-(mAb-monoTL1A)-FcRnare the same or different, (6)k on-mAb-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (7)k off-(mAb-monoTL1A)-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (8)k off-mAb-FcRn and k off-(mAb-monoTL1A)-FcRn are the same or different, (9)k off-mAb-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (10)k deg-(mAb-monoTL1A)-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (11)k deg-mAb-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (12)k deg-mAb-FcRn and k deg-(mAb-monoTL1A)-FcRn are the same or different, and are any combination of (13)(1) to (12). In some embodiments, in the dosage determination method, k syn-disease But, k syn-normal In some embodiments, step (i) of the dose determination method comprises measuring the rate of TL1A trimerization (k on-TL1A-monomer-to-trimer ) and / or the rate of TL1A monomerization (k off-TL1A-trimer-to-monomer ).

[0044] In one aspect, provided herein is a method for determining an effective dose regimen for administering an anti-TL1A antibody to a subject with skin inflammation and / or skin fibrosis, the method comprising: (a) receiving parameters of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (b) integrating the parameters received in (a) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model; and (c) determining an effective dose regimen of the anti-TL1A antibody in the PBPK model from (b), such that after administration of the effective dose regimen, the concentration of TL1A in the diseased tissue of the subject with skin inflammation and / or skin fibrosis is less than the concentration of TL1A in the corresponding tissue of a control subject without lung inflammation, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues with skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of skin inflammation and / or skin fibrosis.

[0045] In one aspect, provided herein is a method for determining an effective dose regimen for administering an anti-TL1A antibody to a subject with skin inflammation and / or skin fibrosis, the method comprising: (a) receiving parameters of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (b) integrating the parameters received in (a) into a population pharmacokinetic (popPK) model; and (c) determining an effective dose regimen of the anti-TL1A antibody in the popPK model from (b) such that after administration of the effective dose regimen, the concentration of TL1A in the diseased tissue of the subject with skin inflammation and / or skin fibrosis is less than the concentration of TL1A in the corresponding tissue of a control subject without skin inflammation and / or skin fibrosis, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues with skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of skin inflammation and / or skin fibrosis.

[0046] In some embodiments of the dose-determining method, the parameter of TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200-fold or more overproduction compared to TL1A production in a normal reference tissue. In some embodiments of the dose-determining method, step (a) comprises measuring the association rate of the antibody to TL1A (k on-mAb ), the dissociation rate of the antibody from TL1A (k off-mAb ), the synthesis rate of TL1A in normal tissues (k syn-normal ), the synthesis rate of TL1A in diseased tissue (k syn-disease ), and / or the degradation rate of TL1A (k deg-total-TL1A ).

[0047] In some embodiments of the dose determination method, the association rate of the antibody to TL1A (k on-mAb ) is the association rate of the antibody to monomeric TL1A (k on-monomer ) and the association rate of the antibody to trimeric TL1A (k on-trimer ), and the dissociation rate of the antibody from TL1A (k off-mAb ) is the dissociation rate of the antibody from monomeric TL1A (k off-monomer ) and the dissociation rate of the antibody from trimeric TL1A (k off-trimer ) and / or the degradation rate of TL1A (k deg-total-TL1A ) is the degradation rate of monomeric TL1A (k deg-TL1A-monomer ) and the degradation rate of trimeric TL1A (k deg-TL1A-trimer In some embodiments of the dose determination method, step (a) comprises determining the association rate of the antibody to the FcRn receptor (k on-mAb-FcRn ), the dissociation rate of antibody from FcRn (k off-mAb-FcRn ), and the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is received.

[0048] In some embodiments of the dose determination method, the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn) is the association rate (k on-(mAb-monoTL1A)-FcRn ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k on-(mAb-triTL1A)-FcRn ) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is the dissociation rate of the antibody-monomer-TL1A complex from FcRn (k off-(mAb-monoTL1A)-FcRn ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k off-(mAb-triTL1A)-FcRn ) is included.

[0049] In some embodiments of the dose determination method, step (a) comprises determining the clearance rate of antibody-bound FcRn receptor (k deg-mAb-FcRn In some embodiments of the method for determining the dose, the clearance rate of the antibody-bound FcRn receptor (k deg-mAb-FcRn ) is the clearance rate (k deg-(mAb-monoTL1A)-FcRn ) and the clearance rate (k deg-(mAb-triTL1A)-FcRn ) further included.

[0050] In some embodiments of the dose-determining method, the subject has one or more inflammatory conditions selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, a chronic skin disorder, systemic sclerosis, lupus, eczema, and dermatomyositis. In some embodiments of the dose-determining method, the subject has hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

[0051] In some embodiments of the dosage determination method, the dosage determination method comprises: (1) k on-monomer and k on-trimer are the same or different, (2)k off-monomer and k off-trimer are the same or different, (3)k deg-monomer and k deg-trimer are the same or different, (4)kon-(mAb-monoTL1A)-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (5)k on-mAb-FcRn and k on-(mAb-monoTL1A)-FcRn are the same or different, (6)k on-mAb-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (7)k off-(mAb-monoTL1A)-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (8)k off-mAb-FcRn and k off-(mAb-monoTL1A)-FcRn are the same or different, (9)k off-mAb-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (10)k deg-(mAb-monoTL1A)-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (11)k deg-mAb-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (12)k deg-mAb-FcRn and k deg-(mAb-monoTL1A)-FcRn are the same or different, or any combination of (13)(1) to (12).

[0052] In some embodiments of the dosage method, the dosage method further comprises: syn-disease But, k syn-normal up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 times or more.

[0053] In some embodiments of the dose-determining method, the effective dose regimen comprises an induction regimen of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose-determining method, the effective dose regimen comprises a maintenance regimen of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose-determining method, the induction regimen and the maintenance regimen are the same. In some embodiments of the dose-determining method, the induction regimen and the maintenance regimen are different. In some embodiments of the dose-determining method, the maintenance regimen is administered after the induction regimen.

[0054] In some embodiments of the dose-determining method, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A during the induction regimen compared to corresponding tissue in a control subject. In some embodiments of the dose-determining method, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A within 1, 2, 3, 4, 5, or 6 weeks of the start of the induction regimen compared to corresponding tissue in a control subject. In some embodiments of the dose-determining method, the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to corresponding tissue in a control subject. In some embodiments of the dose-determining method, the induction regimen comprises a single administration of an anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dosing method, the anti-TL1A antibody or antigen-binding fragment is administered at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

[0055] In some embodiments of the dose-determining method, the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose-determining method, the induction regimen comprises: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; or (v) 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10.

[0056] In some embodiments of the dosage method, the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose. In some embodiments of the dosage method, the induction regimen comprises administration once every 2, 4, 6, or 8 weeks. In some embodiments of the dosing method, the induction regimen includes administration once every 2 or 4 weeks for the first two doses, then once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

[0057] In some embodiments of the dosage-determining method, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than the corresponding tissue in the control subject. In some embodiments of the dosage-determining method, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A than the corresponding tissue in the control subject during the maintenance regimen. In some embodiments of the dose determination method, the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times or more TL1A compared to the corresponding tissue in a control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks or more of the initiation of the maintenance regimen.

[0058] In some embodiments of the dosing method, the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment. In some embodiments of the dose determination method, the maintenance regimen is (i) 500 mg / dose every 2 weeks, (ii) 400 mg / dose every 2 weeks, (iii) 300 mg / dose every 2 weeks, (iv) 250 mg / dose every 2 weeks, (v) 200 mg / dose every 2 weeks, (vi) 150 mg / dose every 2 weeks, (vii) 100 mg / dose every 2 weeks, (viii) 50 mg / dose every 2 weeks, (ix) 500 mg / dose every 4 weeks, (x) 400 mg / dose every 4 weeks, (xi) 300 mg / dose every 4 weeks, (xii) 250 mg / dose every 4 weeks, (xiii) 200 mg / dose every 4 weeks, (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 50 mg / dose every 6 ... (xxiii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks, (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks, (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks, (xxvi) 400 mg / dose every 8 weeks, (xxvii) 300 mg / dose every 8 weeks, (xxviii) 250 mg / dose every 8 weeks, (xxix) 200 mg / dose every 8 weeks, (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks.

[0059] In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose. In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks. In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every 4 weeks. In some embodiments of the dose-determining method, the maintenance regimen comprises administering the anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every 4 weeks. In some embodiments of the dosing method, the maintenance regimen continues for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

[0060] In some embodiments of the dose determination method, an effective dose regimen maintains the concentration of TL1A in the subject's diseased tissue below the concentration of TL1A in the corresponding tissue of a control subject without skin inflammation and / or skin fibrosis for at least 4 weeks, 8 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 2 years, and longer.

[0061] In some embodiments of the dose determination method, step (a) comprises measuring the rate of TL1A trimerization (k on-TL1A-monomer-to-trimer ) and / or the rate of TL1A monomerization (k off-TL1A-trimer-to-monomer ).

[0062] In some embodiments of the methods provided herein, including the methods of use / treatment and dosing methods provided herein, the concentration of TL1A is the concentration of free TL1A.

[0063] In some embodiments, the anti-TL1A antibody comprises a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 2-5, and an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 6-9; and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 10, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 11, and an LCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 12-15. In some examples, the anti-TL1A antibody comprises the CDRs of antibody J in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody J2 in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody K in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody M in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody N in Table 10.

[0064] In some embodiments, the anti-TL1A antibody comprises a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*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 collectively comprise no amino acid modifications or collectively comprise fewer than nine amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

[0065] In some embodiments, the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220. In some examples, the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 420, and a light chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 430. In some examples, the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 421, and a light chain variable domain comprising an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 431. In some examples, the anti-TL1A antibody comprises a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 423, and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 433. In some examples, the anti-TL1A antibody comprises a heavy chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 424 and a light chain at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 434.

[0066] In some embodiments, the anti-TL1A antibody is SEQ ID NO: 301 a heavy chain variable region comprising: X1VQLVQSGAEVKKPGASVKVSCKAS [HCDR1] WVX2QX3PGQGLEWX4G [HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [HCDR3] WGQGTTVTVSS; and and a light chain variable region comprising: EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1 to 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; HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 1; HCDR2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 2 to 5; HCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 6 to 9; LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 10; LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 11; and LCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 12 or 13. In some examples, the anti-TL1A antibody comprises the CDRs of antibody J in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody J2 in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody K in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody M in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody N in Table 10.

[0067] In some embodiments, the anti-TL1A antibody comprises a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 401, 407, 413, or 450, an HCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 402, 408, 414, or 451, and an HCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 403, 409, 415, or 452; and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 404, 410, 416, or 453, an LCDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 405, 411, 417, or 454, and an LCDR3 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 406, 412, 418, or 455.

[0068] In some embodiments, the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 420-427, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 430-437.

[0069] Additional numbered embodiments are provided in the following paragraphs of this section.

[0070] Embodiment 1. An antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment) for use in treating inflammation in a subject in need thereof.

[0071] Embodiment 2. The anti-TL1A antibody or antigen-binding fragment for use according to embodiment 1, wherein the subject has inflammation in the skin.

[0072] Embodiment 3. An antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment) for use in treating fibrosis in a subject in need thereof.

[0073] Embodiment 4. The anti-TL1A antibody or antigen-binding fragment for use according to embodiment 3, wherein the subject has fibrosis in the skin.

[0074] Embodiment 5. An antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment) for use in treating a skin disease and / or condition in a subject in need thereof.

[0075] Embodiment 6. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 5, wherein the subject has a chronic skin disorder.

[0076] Embodiment 7. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has systemic sclerosis.

[0077] Embodiment 8. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has psoriasis.

[0078] Embodiment 9. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has lupus.

[0079] Embodiment 10. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has eczema.

[0080] Embodiment 11. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has dermatomyositis.

[0081] Embodiment 12. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has systemic sclerosis or scleroderma, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

[0082] Embodiment 13. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has hidradenitis suppurativa.

[0083] Embodiment 14. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has atopic dermatitis.

[0084] Embodiment 15. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has vitiligo.

[0085] Embodiment 16. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the subject has alopecia areata.

[0086] Embodiment 17. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 6, wherein the inflammation in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

[0087] Embodiment 18. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 3 to 4 and 6, wherein the fibrosis in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

[0088] Embodiment 19. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 5 to 6, wherein the disease and / or condition of the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

[0089] Embodiment 20. A method of treating hidradenitis suppurativa in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

[0090] Embodiment 21. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

[0091] Embodiment 22. A method of treating psoriasis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

[0092] Embodiment 23. A method of treating vitiligo in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

[0093] Embodiment 24. A method of treating alopecia areata in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

[0094] Embodiment 25. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 24, wherein the anti-TL1A antibody or antigen-binding fragment is administered in a pharmaceutical composition.

[0095] Embodiment 26. The anti-TL1A antibody or antigen-binding fragment for use according to embodiment 26, wherein the pharmaceutical composition comprises the anti-TL1A antibody or antigen-binding fragment at a concentration of greater than about 150 mg / mL.

[0096] Embodiment 27. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 26, wherein the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, or 250 mg / mL.

[0097] Embodiment 28. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 26, wherein the concentration is about 150 mg / mL to about 250 mg / mL.

[0098] Embodiment 29. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 26, wherein the concentration is about 175 mg / mL to about 225 mg / mL.

[0099] Embodiment 30. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 29, wherein the pharmaceutical composition is administered subcutaneously.

[0100] Embodiment 31. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 30, wherein about 150 mg to about 500 mg of the anti-TL1A antibody or antigen-binding fragment is present in the composition.

[0101] Embodiment 32. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 31, wherein the composition has a total volume of about 2 mL or less.

[0102] Embodiment 33. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 32, wherein the pharmaceutical composition comprises a therapeutically effective amount of the anti-TL1A antibody or antigen-binding fragment.

[0103] Embodiment 34. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 33, wherein the composition has a total volume of about 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, or 0.8 mL or less.

[0104] Embodiment 35. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 34, wherein the composition has a total volume of about 0.5 mL to about 1.5 mL.

[0105] Embodiment 36. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 35, wherein the composition has a viscosity of less than about 20 cP.

[0106] Embodiment 37. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 36, wherein the composition has a viscosity of less than about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or 5 cP.

[0107] Embodiment 38. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 37, wherein the composition has a viscosity of about 1 cP to about 20 cP.

[0108] Embodiment 39. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 38, wherein the pharmaceutical composition has an aggregation rate of anti-TL1A antibodies or antigen-binding fragments of less than about 5% of the total anti-TL1A antibodies or antigen-binding fragments in the composition as measured by size exclusion chromatography.

[0109] Embodiment 40. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 39, wherein the aggregation is less than about 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5%.

[0110] Embodiment 41. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 39, wherein the composition comprises a surfactant.

[0111] Embodiment 42. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 41, wherein the surfactant comprises a non-ionic surfactant.

[0112] Embodiment 43. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 42, wherein the non-ionic surfactant comprises polysorbate-20.

[0113] Embodiment 44. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 41 to 43, wherein the surfactant is present at a concentration of about 0.005% to about 0.05% of the composition.

[0114] Embodiment 45. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 44, wherein the surfactant is present at a concentration of about 0.01% to about 0.02% of the composition.

[0115] Embodiment 46. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 45, wherein the composition comprises a salt.

[0116] Embodiment 47. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 46, wherein the salt comprises sodium chloride, glycine, lysine hydrochloride, arginine hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof.

[0117] Embodiment 48. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 47, wherein the salt comprises sodium chloride.

[0118] Embodiment 49. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 47, wherein the salt comprises lysine-HCl.

[0119] Embodiment 50. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 46 to 49, wherein the salt is present in the composition at a concentration of about 10 mM to about 100 mM.

[0120] Embodiment 51. The anti-TL1A antibody or antigen-binding fragment for use according to embodiment 50, wherein the salt is present in the composition at a concentration of about 25 mM.

[0121] Embodiment 52. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 50, wherein the salt is present in the composition at a concentration of about 40 mM.

[0122] Embodiment 53. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 52, wherein the composition comprises a stabilizer.

[0123] Embodiment 54. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 53, wherein the stabilizer comprises a sugar, a polyol, an amino acid, or a polymer, a cyclodextrin (e.g., HP-b-CD), or a combination thereof.

[0124] Embodiment 55. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 54, wherein the stabilizer comprises the sugar.

[0125] Embodiment 56. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 55, wherein the sugar comprises sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof.

[0126] Embodiment 57. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 56, wherein the sugar comprises sucrose.

[0127] Embodiment 58. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 53 to 57, wherein the stabilizer is present in the composition at a concentration of about 50 mM to about 300 mM.

[0128] Embodiment 59. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 58, wherein the stabilizer is present at a concentration of about 200 mM to about 280 mM.

[0129] Embodiment 60. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 59, wherein the stabilizer is present at a concentration of about 220 to about 240 mM.

[0130] Embodiment 61. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 60, wherein the composition comprises a buffer.

[0131] Embodiment 62. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 61, wherein the buffer comprises acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, tris(tris(hydroxymethyl)aminomethane), or diethanolamine, or a combination thereof.

[0132] Embodiment 63. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 62, wherein the buffer comprises an acetate buffer.

[0133] Embodiment 64. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 61 to 63, wherein the buffering agent is present in the composition at a concentration of about 10 mM to about 50 mM.

[0134] Embodiment 65. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 64, wherein the composition comprises about 20 mM buffer.

[0135] Embodiment 66. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 25 to 65, wherein the composition has a pH of about 4.5 to about 8.0.

[0136] Embodiment 67. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 66, wherein the composition has a pH of about 4.5 to about 7.5.

[0137] Embodiment 68. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 67, wherein the composition has a pH of about 5 to about 5.5.

[0138] Embodiment 69. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 68, wherein the composition has a pH of about 5.3.

[0139] Embodiment 70. The anti-TL1A antibody or antigen-binding fragment for use according to any one of embodiments 1 to 69, wherein the anti-TL1A antibody or antigen-binding fragment is administered to the subject in a first dose of up to about 1000 mg.

[0140] Embodiment 71. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 69, wherein the anti-TL1A antibody or antigen-binding fragment is administered to the subject in a first dose of about 150 mg to about 1000 mg.

[0141] Embodiment 72. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 71, wherein the first dose is about 500 mg to about 1000 mg.

[0142] Embodiment 73. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 72, wherein the first dose is about 500 mg or about 800 mg.

[0143] Embodiment 74. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 70 to 73, wherein the first dose is administered to the subject at a first time point and the second dose is administered to the subject at a second time point.

[0144] Embodiment 75. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 74, wherein the second time point is 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 31 days after the first time point.

[0145] Embodiment 76. The anti-TL1A antibody or antigen-binding fragment for use according to embodiment 74, wherein the second time point is about 1, 2, 3, or 4 weeks after the first time point.

[0146] Embodiment 77. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 74 to 76, wherein the second dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0147] Embodiment 78. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 74 to 76, wherein the second dose comprises from about 150 mg to about 1000 mg.

[0148] Embodiment 79. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 78, wherein the second dose comprises about 150 mg to about 600 mg.

[0149] Embodiment 80. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 74 to 79, wherein a third dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a third time point.

[0150] Embodiment 81. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 80, wherein the third time point is 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 31 days after the second time point.

[0151] Embodiment 82. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 80, wherein the third time point is about 1, 2, 3, or 4 weeks after the second time point.

[0152] Embodiment 83. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 80 to 82, wherein the third dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0153] Embodiment 84. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 80 to 82, wherein the third dose comprises from about 150 mg to about 1000 mg.

[0154] Embodiment 85. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 84, wherein the third dose comprises about 150 mg to about 600 mg.

[0155] Embodiment 86. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 80 to 85, wherein a fourth dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a fourth time point.

[0156] Embodiment 87. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 86, wherein the fourth time point is 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 31 days after the third time point.

[0157] Embodiment 88. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 86, wherein the fourth time point is about 1, 2, 3, or 4 weeks after the third time point.

[0158] Embodiment 89. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 86 to 88, wherein the fourth dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0159] Embodiment 90. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 86 to 88, wherein the fourth dose comprises from about 150 mg to about 1000 mg.

[0160] Embodiment 91. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 90, wherein the fourth dose comprises from about 150 mg to about 600 mg.

[0161] Embodiment 92. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 86 to 91, wherein a fifth dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a fifth time point.

[0162] Embodiment 93. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 92, wherein the fifth time point is 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 31 days after the fourth time point.

[0163] Embodiment 94. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 92, wherein the fifth time point is about 1, 2, 3, or 4 weeks after the fourth time point.

[0164] Embodiment 95. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 92 to 94, wherein the fifth dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0165] Embodiment 96. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 92 to 94, wherein the fifth dose comprises from about 150 mg to about 1000 mg.

[0166] Embodiment 97. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 96, wherein the fifth dose comprises about 150 mg to about 600 mg.

[0167] Embodiment 98. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 92 to 97, wherein a sixth dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a sixth time point.

[0168] Embodiment 99. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 98, wherein the sixth time point is 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 31 days after the fifth time point.

[0169] Embodiment 100. The anti-TL1A antibody or antigen-binding fragment for use according to embodiment 98, wherein the sixth time point is about 1, 2, 3, or 4 weeks after the fifth time point.

[0170] Embodiment 101. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 98 to 100, wherein the sixth dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0171] Embodiment 102. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 98 to 100, wherein the sixth dose comprises from about 150 mg to about 1000 mg.

[0172] Embodiment 103. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 102, wherein the sixth dose comprises from about 150 mg to about 600 mg.

[0173] Embodiment 104. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 70 to 103, wherein additional doses of the anti-TL1A antibody or antigen-binding fragment are administered to the subject at each of one or more additional time points.

[0174] Embodiment 105. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 104, wherein the one or more additional time points comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 additional time points.

[0175] Embodiment 106. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 104, wherein the composition is administered to the subject at about 12 additional time points.

[0176] Embodiment 107. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 104 to 106, wherein each additional time point is independently 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 31 days after the previous time point.

[0177] Embodiment 108. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 104 to 106, wherein each additional time point is independently about 1, 2, 3, or 4 weeks after the previous time point.

[0178] Embodiment 109. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 108, wherein at least one of the additional time points is about 2 weeks after the previous time point.

[0179] Embodiment 110. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 104 to 109, wherein the additional dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0180] Embodiment 111. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 104 to 109, wherein the additional dose comprises about 150 mg to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

[0181] Embodiment 112. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 111, wherein the additional dose is about 175 mg to about 300 mg of the anti-TL1A antibody or antigen-binding fragment.

[0182] Embodiment 113. An anti-TL1A antibody or antigen-binding fragment for use in neutralizing monomeric and trimeric TL1A in a subject with skin inflammation and / or skin fibrosis, wherein the anti-TL1A antibody or antigen-binding fragment is formulated in an effective amount for administration to the subject; the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A; the antibody or antigen-binding fragment blocks the interaction between TL1A and DR3; the concentration of TL1A in the diseased tissue of the subject is reduced to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; An anti-TL1A antibody or antigen-binding fragment for use, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

[0183] Embodiment 114. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 113, wherein the subject has one or more inflammatory conditions selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0184] Embodiment 115. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 113 or 114, wherein the subject has hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

[0185] Embodiment 116. An anti-TL1A antibody or antigen-binding fragment for use in reducing the concentration of TL1A in diseased tissue of a subject with skin inflammation and / or skin fibrosis, comprising: the anti-TL1A antibody or antigen-binding fragment is formulated in an effective dose for administration to the subject to reduce the concentration of TL1A in the diseased tissue of the subject to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; An anti-TL1A antibody or antigen-binding fragment for use, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

[0186] Embodiment 117. An anti-TL1A antibody or antigen-binding fragment for use in treating skin inflammation and / or skin fibrosis in a subject in need thereof, comprising: the anti-TL1A antibody or antigen-binding fragment is administered at an effective dose such that the concentration of TL1A in the diseased tissue of the subject after administration is less than the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; An anti-TL1A antibody or antigen-binding fragment for use, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

[0187] Embodiment 118. An anti-TL1A antibody or antigen-binding fragment for use in treating skin inflammation and / or skin fibrosis in a subject in need thereof, wherein the anti-TL1A antibody or antigen-binding fragment is: (a) administering to said subject an effective dose; (b) reducing the concentration of TL1A in diseased tissue of the subject to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; An anti-TL1A antibody or antigen-binding fragment for use, wherein the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

[0188] Embodiment 119. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 113 to 118, wherein the effective dose comprises an induction regimen.

[0189] Embodiment 120. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 113 to 119, wherein the anti-TL1A antibody or antigen-binding fragment is also used to maintain a concentration of TL1A in the diseased tissue of the subject that is lower than the concentration of TL1A in the corresponding tissue of the control subject.

[0190] Embodiment 121. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 120, wherein the TL1A in the diseased tissue of the subject is maintained with a maintenance regimen of the anti-TL1A antibody or antigen-binding fragment.

[0191] Embodiment 122. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 121, wherein the induction regimen and the maintenance regimen are the same.

[0192] Embodiment 123. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 121, wherein the induction regimen and the maintenance regimen are different.

[0193] Embodiment 124. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 123, wherein the maintenance regimen is administered after the induction regimen.

[0194] Embodiment 125. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 124, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A during the induction regimen compared to the corresponding tissue in the control subject.

[0195] Embodiment 126. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 124, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of initiating the induction regimen.

[0196] Embodiment 127. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 124, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to the corresponding tissue in the control subject.

[0197] Embodiment 128. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 119 to 127, wherein the induction regimen comprises a single administration of the anti-TL1A antibody or antigen-binding fragment.

[0198] Embodiment 129. The anti-TL1A antibody or antigen-binding fragment is administered in a dose of 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, or 950 mg / dose. 129. The anti-TL1A antibody or antigen-binding fragment for use of embodiment 128, wherein the antibody or antigen-binding fragment is administered in an amount of 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

[0199] Embodiment 130. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 119 to 127, wherein the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment.

[0200] Embodiment 131. The induction regimen comprises: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 500 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10, or (v) 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10 131. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 119 to 127 and 130, comprising administration of:

[0201] Embodiment 132. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 119 to 127 and 130, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

[0202] Embodiment 133. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 119 to 127, 130, and 132, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

[0203] Embodiment 134. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 119 to 127, 130, and 132, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first two doses, followed by administration once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

[0204] Embodiment 135. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 120 to 134, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A compared to the corresponding tissue in the control subject.

[0205] Embodiment 136. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 120 to 131, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50 times more TL1A during the maintenance regimen compared to the corresponding tissue in the control subject.

[0206] Embodiment 137. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 120 to 131, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks or more from the start of the maintenance regimen.

[0207] Embodiment 138. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 137, wherein the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment.

[0208] Embodiment 139. The maintenance regimen comprises: (i) 500 mg / dose every 2 weeks; (ii) 400 mg / dose every 2 weeks; (iii) 300 mg / dose every 2 weeks; (iv) 250 mg / dose every 2 weeks; (v) 200 mg / dose every 2 weeks; (vi) 150 mg / dose every 2 weeks; (vii) 100 mg / dose every 2 weeks; (viii) 50 mg / dose every 2 weeks; (ix) 500 mg / dose every 4 weeks; (x) 400 mg / dose every 4 weeks (xi) 300 mg / dose every 4 weeks; (xii) 250 mg / dose every 4 weeks; (xiii) 200 mg / dose every 4 weeks; (xiv) 150 mg / dose every 4 weeks, (xv) 100 mg / dose every 4 weeks, (xvi) 50 mg / dose every 4 weeks, (xvii) 500 mg / dose every 6 weeks, (xviii) 400 mg / dose every 6 weeks, (xix) 300 mg / dose every 6 weeks (xx) 250 mg / dose every 6 weeks, (xxi) 200 mg / dose every 6 weeks (xxii) 150 mg / dose every 6 weeks, (xxiii) 100 mg / dose every 6 weeks, (xxiv) 50 mg / dose every 6 weeks, (xxv) 500 mg / dose every 8 weeks (xxvi) 400 mg / dose every 8 weeks (xxvii) 300 mg / dose every 8 weeks (xxviii) 250 mg / dose every 8 weeks (xxix) 200 mg / dose every 8 weeks (xxx) 150 mg / dose every 8 weeks, (xxxi) 100 mg / dose every 8 weeks, or (xxxii) 50 mg / dose every 8 weeks The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 138, comprising administering the anti-TL1A antibody or antigen-binding fragment in a patient receiving the ...

[0209] Embodiment 140. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 138, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

[0210] Embodiment 141. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 138 and 140, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

[0211] Embodiment 142. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 141, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every 4 weeks.

[0212] Embodiment 143. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 141, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every 4 weeks.

[0213] Embodiment 144. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 143, wherein the maintenance regimen lasts for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

[0214] Embodiment 145. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 116 to 144, wherein the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A, and the antibody or antigen-binding fragment blocks binding of TL1A to DR3.

[0215] Embodiment 146. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 113 to 145, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the subject's blood is occupied by the anti-TL1A antibody or antigen-binding fragment.

[0216] Embodiment 147. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 113 to 146, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the blood of the subject is occupied by the anti-TL1A antibody or antigen-binding fragment.

[0217] Embodiment 148. Dissociation equilibrium constant (K D-monomer The binding affinity of the antibody or antigen-binding fragment to monomeric TL1A, as measured by a dissociation equilibrium constant (K D-trimer 148. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 113 to 147, wherein the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A is measured by the following method:

[0218] Embodiment 149. The K D-monomer However, the above K D-trimer 149. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 148, wherein the antibody or antigen-binding fragment is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold of the total TL1A antibody or antigen-binding fragment.

[0219] Embodiment 150. The K D-monomer 150. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 148 or 149, wherein the IL-1A antibody or antigen-binding fragment has a IL-1A activity of 0.06 nM or less.

[0220] Embodiment 151. The K D-trimer The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 148 to 150, wherein the IL-1A antibody or antigen-binding fragment has a IL-1A activity of 0.06 nM or less.

[0221] Embodiment 152. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the subject has one or more conditions of skin inflammation and / or skin fibrosis selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0222] Embodiment 153. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 152, wherein the subject has systemic sclerosis, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

[0223] Embodiment 154. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 152, wherein the subject has hidradenitis suppurativa.

[0224] Embodiment 155. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 152, wherein the subject has atopic dermatitis.

[0225] Embodiment 156. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 152, wherein the subject has psoriasis.

[0226] Embodiment 157. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 152, wherein the subject has vitiligo.

[0227] Embodiment 158. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 152, wherein the subject has alopecia areata.

[0228] Embodiment 159. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the skin inflammation and / or skin fibrosis is hidradenitis suppurativa.

[0229] Embodiment 160. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the skin inflammation and / or skin fibrosis is atopic dermatitis.

[0230] Embodiment 161. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the skin inflammation and / or skin fibrosis is psoriasis.

[0231] Embodiment 162. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the skin inflammation and / or skin fibrosis is vitiligo.

[0232] Embodiment 163. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the skin inflammation and / or skin fibrosis is alopecia areata.

[0233] Embodiment 164. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 115 to 151, wherein the skin inflammation and / or skin fibrosis is selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

[0234] Embodiment 165. The effective dose or the induction regimen is determined by a dose-determining method, and the dose-determining method comprises: (i) receiving a parameter of TL1A overproduction in the diseased tissue compared to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (a) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or population pharmacokinetic (popPK) model; (iii) determining the effective dose or the induction regimen such that the concentration of TL1A in the diseased tissue of the subject after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject who does not have skin inflammation and / or skin fibrosis; The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 113 to 164, comprising:

[0235] Embodiment 166. An anti-TL1A antibody or antigen-binding fragment for use in embodiment 165, wherein the parameter of TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200-fold or more overproduction compared to TL1A production in the normal reference tissue.

[0236] Embodiment 167. The maintenance regimen is determined by a dose-determining method, and the dose-determining method comprises: (i) receiving a parameter of TL1A overproduction in the diseased tissue compared to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (i) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or population pharmacokinetic (popPK) model; (iii) determining the maintenance regimen such that the concentration of TL1A in the diseased tissue of the subject after step (c) is less than the concentration of TL1A in the corresponding tissue of a control subject who does not have skin inflammation and / or skin fibrosis; The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 121 to 166, comprising:

[0237] Embodiment 168. An anti-TL1A antibody or antigen-binding fragment for use in embodiment 167, wherein the parameter of TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100-fold or more overproduction compared to TL1A production in the normal reference tissue.

[0238] Embodiment 169. The step (i) of the dose determination method comprises determining the association rate of the antibody to TL1A (k on-mAb ), the dissociation rate of the antibody from TL1A (k off-mAb ), the synthesis rate of TL1A in normal tissues (k syn-normal ), the synthesis rate of TL1A in diseased tissue (ksyn-disease ), and / or the degradation rate of TL1A (k deg-total-TL1A The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 165 to 168, further comprising receiving

[0239] Embodiment 170. The association rate (k on-mAb ) is the association rate of the antibody to monomeric TL1A (k on-monomer ) and the association rate of the antibody to trimeric TL1A (k on-trimer ), and the dissociation rate of the antibody from TL1A (k off-mAb ) is the dissociation rate of the antibody from monomeric TL1A (k off-monomer ) and the dissociation rate of the antibody from trimeric TL1A (k off-trimer ) and / or the degradation rate of TL1A (k deg-total-TL1A ) is the degradation rate of monomeric TL1A (k deg-TL1A-monomer ) and the degradation rate of trimeric TL1A (k deg-TL1A-trimer 169. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 169, comprising:

[0240] Embodiment 171. The method for determining the dose in step (i) comprises determining the association rate of the antibody to the FcRn receptor (k on-mAb-FcRn ), the dissociation rate of the antibody from FcRn (k off-mAb-FcRn ), the association rate of the antibody-TL1A complex to the FcRn receptor (k on-(mAb-TL1A)-FcRn ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn 171. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 165 to 170, further comprising receiving

[0241] Embodiment 172. The association rate (k on-(mAb-TL1A)-FcRn ) is the association rate of the antibody-monomer-TL1A complex to the FcRn receptor (k on-(mAb-monoTL1A)-FcRn ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k on-(mAb-triTL1A)-FcRn) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k off-(mAb-TL1A)-FcRn ) is the dissociation rate (k off-(mAb-monoTL1A)-FcRn ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k off-(mAb-triTL1A)-FcRn 172. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 171, comprising:

[0242] Embodiment 173. The step (i) of the dose-determining method comprises determining the clearance rate (k deg-mAb-FcRn The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 165 to 172, further comprising receiving

[0243] Embodiment 174. The clearance rate (k deg-mAb-FcRn ) is the clearance rate (k deg-(mAb-monoTL1A)-FcRn ) and the clearance rate (k deg-(mAb-triTL1A)-FcRn 174. The anti-TL1A antibody or antigen-binding fragment for use in embodiment 173, comprising:

[0244] Embodiment 175. In the method for determining the dosage, (1)k on-monomer and k on-trimer are the same or different, (2)k off-monomer and k off-trimer are the same or different, (3)k deg-monomer and k deg-trimer are the same or different, (4)k on-(mAb-monoTL1A)-FcRn and k on-(mAb-triTL1A)-FcRn are the same or different, (5)k on-mAb-FcRn and k on-(mAb-monoTL1A)-FcRn are the same or different, (6)k on-mAb-FcRn and kon-(mAb-triTL1A)-FcRn are the same or different, (7)k off-(mAb-monoTL1A)-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (8)k off-mAb-FcRn and k off-(mAb-monoTL1A)-FcRn are the same or different, (9)k off-mAb-FcRn and k off-(mAb-triTL1A)-FcRn are the same or different, (10)k deg-(mAb-monoTL1A)-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (11)k deg-mAb-FcRn and k deg-(mAb-triTL1A)-FcRn are the same or different, (12)k deg-mAb-FcRn and k deg-(mAb-monoTL1A)-FcRn are the same or different, or (13) Any combination of (1) to (12). The anti-TL1A antibody or antigen-binding fragment for use according to any one of embodiments 169 to 174.

[0245] Embodiment 176. In the method for determining the dosage, k syn-disease But, k syn-normal 176. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 165 to 175, wherein the antibody or antigen-binding fragment is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200-fold or more.

[0246] Embodiment 177. The dose determination method in step (i) comprises determining the rate of TL1A trimerization (k on-TL1A-monomer-to-trimer ) and / or the rate of TL1A monomerization (k off-TL1A-trimer-to-monomer 177. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 165 to 176, further comprising receiving

[0247] Embodiment 179. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 114 to 177, wherein the concentration of TL1A is the concentration of free TL1A.

[0248] Embodiment 180. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 179, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising HCDR1 having the amino acid sequence described by SEQ ID NO: 1, HCDR2 having the amino acid sequence described by any one of SEQ ID NOs: 2 to 5, and HCDR3 having the amino acid sequence described by any one of SEQ ID NOs: 6 to 9, and a light chain variable region comprising LCDR1 having the amino acid sequence described by SEQ ID NO: 10, LCDR2 having the amino acid sequence described by SEQ ID NO: 11, and LCDR3 having the amino acid sequence described by any one of SEQ ID NOs: 12 to 15.

[0249] Embodiment 181. The anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 180, wherein the anti-TL1A antibody comprises a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*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 collectively comprise fewer than 9 amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

[0250] Embodiment 182. An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 181, wherein the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101 to 169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201 to 220.

[0251] Embodiment 183. The anti-TL1A antibody is selected from the group consisting of SEQ ID NO: 301 a heavy chain variable region comprising: X1VQLVQSGAEVKKPGASVKVSCKAS [HCDR1] WVX2QX3PGQGLEWX4G [HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [HCDR3] WGQGTTVTVSS; and and a light chain variable region comprising: EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK, wherein each of X1 through 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; HCDR1 comprises the amino acid sequence set forth by SEQ ID NO: 1; and HCDR2 comprises An anti-TL1A antibody or antigen-binding fragment for use in any one of embodiments 1 to 182, wherein the anti-TL1A antibody or antigen-binding fragment comprises an amino acid sequence described by any one of SEQ ID NOs: 2 to 5, HCDR3 comprises an amino acid sequence described by any one of SEQ ID NOs: 6 to 9, LCDR1 comprises an amino acid sequence described by SEQ ID NO: 10, LCDR2 comprises an amino acid sequence described by SEQ ID NO: 11, and LCDR3 comprises an amino acid sequence described by any one of SEQ ID NOs: 12 or 13.

[0252] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0253] Exemplary embodiments are illustrated in the referenced drawings. It is intended that the embodiments and figures disclosed herein be considered illustrative and not restrictive. [Brief explanation of the drawings]

[0254] [Figure 1A]Figure 1 shows chromatograms of analytical size exclusion chromatography of anti-TL1A antibodies. The large peak (main peak) corresponds to the monomer fraction. The percentage of the monomer sample is indicated for each antibody. Figure 1A shows chromatograms of antibodies A193, A194, and A195. Figure 1B shows chromatograms of antibodies A196, A197, and A198. Figure 1C shows chromatograms of antibodies A199, A200, and A201. [Figure 1B] Figure 1 shows chromatograms of analytical size exclusion chromatography of anti-TL1A antibodies. The large peak (main peak) corresponds to the monomer fraction. The percentage of the monomer sample is indicated for each antibody. Figure 1A shows chromatograms of antibodies A193, A194, and A195. Figure 1B shows chromatograms of antibodies A196, A197, and A198. Figure 1C shows chromatograms of antibodies A199, A200, and A201. [Figure 1C] Figure 1 shows chromatograms of analytical size exclusion chromatography of anti-TL1A antibodies. The large peak (main peak) corresponds to the monomer fraction. The percentage of the monomer sample is indicated for each antibody. Figure 1A shows chromatograms of antibodies A193, A194, and A195. Figure 1B shows chromatograms of antibodies A196, A197, and A198. Figure 1C shows chromatograms of antibodies A199, A200, and A201. [Figure 2] 1 shows the inhibition of interferon gamma in human blood by anti-TL1A antibody. [Figure 3A] 1 shows a comparison between predicted and measured viscosity. [Figure 3B] Figure 3B shows a PLS model demonstrating the effect of pH and protein concentration on viscosity. Figure 3B shows a PLS graph (the x-axis of the PLS graph is pH, the y-axis is protein concentration (mg / ml), and the z-axis is viscosity (mPa-s)), Figure 3C shows a model of predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration in mg / mL (x-axis), and Figure 3D shows a model of estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). [Figure 3C]Figure 3B shows a PLS model demonstrating the effect of pH and protein concentration on viscosity. Figure 3B shows a PLS graph (the x-axis of the PLS graph is pH, the y-axis is protein concentration (mg / ml), and the z-axis is viscosity (mPa-s)), Figure 3C shows a model of predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration in mg / mL (x-axis), and Figure 3D shows a model of estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). [Figure 3D] Figure 3B shows a PLS model demonstrating the effect of pH and protein concentration on viscosity. Figure 3B shows a PLS graph (the x-axis of the PLS graph is pH, the y-axis is protein concentration (mg / ml), and the z-axis is viscosity (mPa-s)), Figure 3C shows a model of predicted viscosity (y-axis, mPa-s) versus anti-TL1A antibody concentration in mg / mL (x-axis), and Figure 3D shows a model of estimated viscosity (y-axis, mPa-s) versus actual viscosity (x-axis, mPa-s). [Figure 3E] 1 shows the effect of pH versus acetate concentration on viscosity. [Figure 3F] 1 shows the effect of NaCl versus sucrose on viscosity. [Figure 3G] Figure 1 shows the effect of Arg-HCl vs. Lys-HCl on viscosity. Viscosity units are in mPa-s. Arrows point to the regions of highest viscosity. Stars correspond to the regions of lowest viscosity. [Figure 4A] 1 shows the PLS1 model for the effect on high molecular weight (HMW) aggregates. [Figure 4B] 1 shows the effect of pH versus acetate on aggregation. [Figure 4C] The effect of sucrose versus NaCl concentration is shown. [Figure 4D] 1 shows the effect of Arg-HCl versus Lys-HCl on aggregation. [Figure 4E] 1 shows the effect of sucrose concentration versus Lys-HCl concentration. [Figure 5A] Expected versus measured loss of main peak at 2 weeks and 25° C. is shown. [Figure 5B]1 shows the effect of pH and protein concentration on the loss of the main peak in the CEX profile. [Figure 5C] 1 shows the effect of pH and acetate concentration on the loss of the main peak in the CEX profile. [Figure 5D] 1 shows the effect of sucrose and NaCl concentrations on the loss of the main peak in the CEX profile. [Figure 5E] 1 shows the effect of Lys-HCl and sucrose concentrations on the loss of the main peak in the CEX profile. [Figure 6A] SEC shows loss of monomer upon agitation. [Figure 6B] SEC demonstrates loss of monomer upon freeze-thawing. [Figure 7A] Figure 1 shows that anti-TL1A antibodies bind to cynomolgus monkey and human TL1A, but not to mouse or rat TL1A. ELISAs for each protein were performed at least three times. Data from a representative experiment are shown and are the mean ± SD. Abbreviations: A = absorbance, Ab = antibody, Cyno = cynomolgus monkey, nm = nanometer, nM = nanomolar. [Figure 7B] Figure 1 shows the mean sTL1A levels that increased with increasing IV doses of anti-TL1A in cynomolgus monkeys, as measured by ELISA. Samples were assayed in triplicate on two separate occasions. Data presented are the mean TL1A concentrations ± SD for three animals per group. Samples collected from animals administered an isotype control antibody are indicated by circles, and samples collected from animals administered anti-TL1A are indicated by triangles and squares. Abbreviations: hr = hour, kg = kilogram, mg = milligram, mL = milliliter, ng = nanogram, TL1A = tumor necrosis factor-like cytokine 1A. [Figure 8] Figure 1 shows that TL1A drives inflammation and fibrosis through binding to DR3. [Figure 9-1]Figures 9A-9C show size-exclusion chromatography (SEC) profiles of recombinant human TL1A (rhTL1A). Briefly, rhTL1A was labeled with Alexa fluor 488 (AF488) and spiked into normal human serum (NHS). In Figure 9A, when injected alone, the rhTL1A SEC profile shows two peaks on SEC, representing the trimeric and monomeric forms of TL1A. In Figure 9B, preincubation of rhTL1A with a control reference antibody shifted the trimeric peak to the left, indicating greater complex formation between the reference antibody and trimeric rhTL1A. There was no shift in the monomeric peak, indicating that the reference antibody binds only to trimeric rhTL1A. In Figure 9C, preincubation of rhTL1A with A219 shifted both the trimeric and monomeric rhTL1A peaks, thus indicating that A219 binds to both the trimeric and monomeric forms of TL1A. [Figure 9-2] Figures 9A-9C show size-exclusion chromatography (SEC) profiles of recombinant human TL1A (rhTL1A). Briefly, rhTL1A was labeled with Alexa fluor 488 (AF488) and spiked into normal human serum (NHS). In Figure 9A, when injected alone, the rhTL1A SEC profile shows two peaks on SEC, representing the trimeric and monomeric forms of TL1A. In Figure 9B, preincubation of rhTL1A with a control reference antibody shifted the trimeric peak to the left, indicating greater complex formation between the reference antibody and trimeric rhTL1A. There was no shift in the monomeric peak, indicating that the reference antibody binds only to trimeric rhTL1A. In Figure 9C, preincubation of rhTL1A with A219 shifted both the trimeric and monomeric rhTL1A peaks, thus indicating that A219 binds to both the trimeric and monomeric forms of TL1A. [Figure 10A] A whole-body physiologically based pharmacokinetic (PBPK) model is shown. [Figure 10A-1] A whole-body physiologically based pharmacokinetic (PBPK) model is shown. [Figure 10B]FIG. 1 shows a tissue-level diagram of the integrated whole-body PBPK model used to characterize the PK of a monoclonal antibody (mAb), a ligand, and the complex between the mAb and the ligand. [Figure 10B-1] FIG. 1 shows a tissue-level diagram of the integrated whole-body PBPK model used to characterize the PK of a monoclonal antibody (mAb), a ligand, and the complex between the mAb and the ligand. [Figure 11A] A comparison of the mAb pharmacokinetics predicted by integrated whole-body PBPK (solid curve) and observed in healthy volunteers (various points with points from the same subject shown in the same format) is shown in each case after injection of A219 at the doses indicated. [Figure 11A-1] A comparison of the mAb pharmacokinetics predicted by integrated whole-body PBPK (solid curve) and observed in healthy volunteers (various points with points from the same subject shown in the same format) is shown in each case after injection of A219 at the doses indicated. [Figure 11B] A comparison of the TL1A concentrations predicted by integrated whole-body PBPK with those observed in healthy volunteers is shown in each case after injection of A219 at the doses indicated. [Figure 11B-1] A comparison of the TL1A concentrations predicted by integrated whole-body PBPK with those observed in healthy volunteers is shown in each case after injection of A219 at the doses indicated. [Figure 12A] Figure 12A shows the observed concentrations of TL1A in serum after injection of (i) the anti-TL1A antibody A219, which binds both TL1A monomer and trimer (shown in red, the top of the two curves, and the observed data points associated with those curves), and (ii) a control reference anti-TL1A antibody that binds only the TL1A trimer (shown in blue, the bottom of the two curves, and the observed data points associated with those curves). In Figure 12A, the solid curves represent predictions from the model, and the various dots represent observations from subjects injected with the indicated antibodies. [Figure 12B]Shown in each case at basal levels (without injection of any anti-TL1A antibody) are the predicted total TL1A concentrations (monomers and trimers, solid curves and observed data points associated with such curves), monomeric TL1A concentrations (fine dotted lines), and trimeric TL1A concentrations (coarse dotted lines). [Figure 12C] Serum TL1A concentrations in healthy volunteers (NHVs) and UC patients predicted by the whole-body PBPK model (solid line, upper line for UC patients, and lower line for NHVs) and observed (various points) are shown. [Figure 13A] The fit of the model is demonstrated. Figure 13A shows the observed concentrations of TL1A (dots) in the serum of NHVs after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX3 = 3 times every 2 weeks. Figure 13B shows the observed concentrations of TL1A (dots) in the serum of UC patients after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX7 = 7 times every 2 weeks. [Figure 13B] The fit of the model is demonstrated. Figure 13A shows the observed concentrations of TL1A (dots) in the serum of NHVs after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX3 = 3 times every 2 weeks. Figure 13B shows the observed concentrations of TL1A (dots) in the serum of UC patients after injection of an anti-TL1A antibody that binds only to the TL1A trimer, and the predictions of the model that fits the observations at the indicated doses (solid curves). Q2WX7 = 7 times every 2 weeks. [Figure 13C] The concentrations of TL1A in the intestine of NHVs (two solid black lines predicted from the model, the bottom line, and the observed data points associated with such lines) and in the intestine of UC patients (two solid red lines, the top line) are shown. [Figure 14A]Baseline concentrations of TL1A based on various parameters of TL1A production in the intestine (14A) and serum (14B) are shown. In Figures 14A-14B, 1x is baseline in NHVs, and 25x, 50x, 75x, and 100x represent various parameters of TL1A overproduction in the intestine. [Figure 14B] Baseline concentrations of TL1A based on various parameters of TL1A production in the intestine (14A) and serum (14B) are shown. In Figures 14A-14B, 1x is baseline in NHVs, and 25x, 50x, 75x, and 100x represent various parameters of TL1A overproduction in the intestine. [Figure 15A] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15B] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15C] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15D] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15E] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15F] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15G] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15H] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15I] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15J] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15K] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15L] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15M] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15N] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15O]1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15P] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15Q] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15R] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15S] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15T] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15U] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15V] 1 shows the concentration of free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under various dose regimens of the anti-TL1A antibody A219 as indicated. [Figure 15W]Figure 1 shows free soluble TL1A in tissues as determined by a whole-body PBPK model according to various parameters of TL1A overproduction under the indicated dose regimens of a reference anti-TL1A antibody. [Figure 15X] Figures 15W-15Z show a comparison of modeled free soluble TL1A concentrations in subjects treated with a reference anti-TL1A antibody (red, upper curve of the two curves) or A219 (green, lower curve of the two curves). In Figures 15W-15Z, the light chain sequence of the reference antibody is SEQ ID NO: 382, ​​the heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses the observed rapid equilibration between the monomeric and trimeric forms of TL1A with a continuous 60:40 ratio of monomer to trimer. The solid black lines in Figures 15A-15Z show TL1A concentrations in tissues of NHVs. Q2W = every 2 weeks. Q4W = every 4 weeks. SC = subcutaneous. LD = loading dose (first dose). 4W = week 4. D1 = day 1. W2, 6, 10 = weeks 2, 6, and 10. W2, 4, 6, 10 = weeks 2, 4, 6, and 10. EOW = every other week. W4, 8, 12 = weeks 4, 8, and 12. W2, 4, 8, 12 = weeks 2, 4, 8, and 12. sTL1A = soluble TL1A. [Figure 15Y] Figures 15W-15Z show a comparison of modeled free soluble TL1A concentrations in subjects treated with a reference anti-TL1A antibody (red, upper curve of the two curves) or A219 (green, lower curve of the two curves). In Figures 15W-15Z, the light chain sequence of the reference antibody is SEQ ID NO: 382, ​​the heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses the observed rapid equilibration between the monomeric and trimeric forms of TL1A with a continuous 60:40 ratio of monomer to trimer. The solid black lines in Figures 15A-15Z show TL1A concentrations in tissues of NHVs. Q2W = every 2 weeks. Q4W = every 4 weeks. SC = subcutaneous. LD = loading dose (first dose). 4W = week 4. D1 = day 1. W2, 6, 10 = weeks 2, 6, and 10. W2, 4, 6, 10 = weeks 2, 4, 6, and 10. EOW = every other week. W4, 8, 12 = weeks 4, 8, and 12. W2, 4, 8, 12 = weeks 2, 4, 8, and 12. sTL1A = soluble TL1A. [Figure 15Z]Figures 15W-15Z show a comparison of modeled free soluble TL1A concentrations in subjects treated with a reference anti-TL1A antibody (red, upper curve of the two curves) or A219 (green, lower curve of the two curves). In Figures 15W-15Z, the light chain sequence of the reference antibody is SEQ ID NO: 382, ​​the heavy chain sequence is SEQ ID NO: 383, and the whole-body PBPK model uses the observed rapid equilibration between the monomeric and trimeric forms of TL1A with a continuous 60:40 ratio of monomer to trimer. The solid black lines in Figures 15A-15Z show TL1A concentrations in tissues of NHVs. Q2W = every 2 weeks. Q4W = every 4 weeks. SC = subcutaneous. LD = loading dose (first dose). 4W = week 4. D1 = day 1. W2, 6, 10 = weeks 2, 6, and 10. W2, 4, 6, 10 = weeks 2, 4, 6, and 10. EOW = every other week. W4, 8, 12 = weeks 4, 8, and 12. W2, 4, 8, 12 = weeks 2, 4, 8, and 12. sTL1A = soluble TL1A. [Figure 16A] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16B] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16C] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16D] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16E] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16F] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16G] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 16H] Figure 1 shows the goodness of fit plot for A219 in the population PK model. [Figure 17A] A visual prediction check of the A219 concentrations predicted from the popPK model against the observed A219 concentrations is shown. [Figure 17B] The induction dose selected in the popPK model to rapidly achieve steady-state concentrations is shown. [Figure 18] Figure 1 shows the osmolality at 5°C measured for the stability of A219 samples in various formulations at TO, 3, and 6 months. [Figure 19] 1 shows the A219 protein concentration at 5° C. measured to assess the stability of A219 samples in various formulations at TO, 3, and 6 months. [Figure 20] 1 shows the pH at 5° C. measured to assess the stability A219 samples of various formulations at TO, 3, and 6 months. [Figure 21A] Figure 1 shows viscosity data at TO and 3M for formulations 1-5 at 25°C. [Figure 21B] Figure 1 shows viscosity data at TO and 3M for formulations 6-8 at 25°C. [Figure 22A] Figure 1 shows the monomer content of the formulations at 5°C as measured by SEC. [Figure 22B] Figure 1 shows the loss of monomer (main peak) per month of the formulations at 5°C as determined by SEC. [Figure 22C] Figure 1 shows the monomer content of the formulations at 25°C as measured by SEC. [Figure 22D] Figure 1 shows the loss of monomer (main peak) per month of the formulations at 5°C as determined by SEC. [Figure 23A] The relative area (%) of the main peak of the formulations at 5° C. as characterized by cation exchange chromatography is shown. [Figure 23B] Figure 1 shows the main peak (relative area (%) per month) of the formulation at 5°C as characterized by cation exchange chromatography. [Figure 23C] The relative area (%) of the main peak of the formulations at 25° C., characterized by cation exchange chromatography, is shown. [Figure 23D] The main peak (relative area (%) per month) of the formulation at 25° C. as characterized by cation exchange chromatography is shown. [Figure 24A] Predictions from a PLS model using monomer loss by SEC versus measurements are shown for samples stored at 25°C for 2 months as the endpoint. [Figure 24B] The effect of pH and protein is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored at 25° C. for 2 months. In Figure 24B, the sucrose concentration was fixed at 200 mM. [Figure 24C] The effect of pH and acetate is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored for 2 months at 25° C. In Figure 24C, the sucrose concentration was fixed at 200 mM. [Figure 24D] The effect of sucrose and lysine is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored at 25° C. for 2 months. In Figure 24D, the protein concentration was fixed at 150 mg / mL, pH at 5.5, and acetate at 20 mM. [Figure 24E] The effect of glycine and NaCl is shown by a PLS model using monomer loss by SEC as the endpoint for samples stored at 25°C for 2 months. In Figure 24E, the protein concentration was fixed at 150 mg / mL, pH at 5.5, and acetate at 20 mM. In Figures 18, 19, 20, 21A-21B, 22A-22D, 23A-23D, and 24A-24E, Formulations 1-8 (F01-F08, Forms 1-8, or simply 1-8) referenced therein are Formulations 1-8 described in Table 31 of Example 24. [Figure 25A] 1 shows the geometric mean serum A219 concentration-time profile (linear scale) following a single dose of A219 administered as an IV infusion (SAD study). [Figure 25B] 1 shows the geometric mean serum A219 concentration-time profiles (linear scale) after multiple doses of A219 Q2W administered as IV infusions on Day 29 (MAD study). Q2W = every 2 weeks. [Figure 26A] Geometric mean serum sTL1A concentrations versus nominal time (semi-log scale) following a single dose of A219 administered as an IV infusion (SAD study). [Figure 26B]Geometric mean serum sTL1A concentrations versus nominal time (semi-logarithmic scale) after multiple doses of A219 Q2W administered as an IV infusion (MAD study). [Figure 27A] Shown are central compartment total A219 concentrations (circulating) in SAD as predicted by the model (curves) and as determined in a phase I study (dots). [Figure 27B] Figure 1 shows total soluble TL1A (circulating) in the central compartment in SAD as predicted by the model (curve) and as determined in a phase I study. [Figure 27C] The central compartment total A219 concentration (in circulation) at the MAD is shown as predicted by the model (curve) and as determined in a phase I study (dots). [Figure 27D] Figure 1 shows the total soluble TL1A (circulating) in the central compartment at MAD as predicted by the model (curve) and as determined in a phase I study (dots). Predicted curve fitted to the measured data points. [Figure 27E] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 27F]Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 27G] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 27H] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 27I]Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 27J] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 27K] Model predictions and data for a control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) that binds only to the TL1A trimer are shown for (1) Phase I single ascending dose data (Figures 27E and 27F), (2) Phase I multiple ascending dose data (Figures 27G and 27H), and (3) Phase II data for PK and total sTL1A levels (Figures 27I and 27J). IBD-specific parameters were then calibrated to capture the free tissue TL1A levels in the intestine observed with the control reference antibody (light chain SEQ ID NO: 382 and heavy chain SEQ ID NO: 383) (Figure 27K). NR = non-responder, R = responder. [Figure 28A] 1 shows the dose of A219 determined from a validated model that can reduce the free TL1A concentration in diseased tissues of patients to below that of healthy subjects. [Figure 28B]Figure 1 shows the percent reduction of free TL1A in diseased tissue after administration of doses of A219 as determined from the model. IV_4x = 1000mg loading dose, 3x 500mg on days 14, 42, 70. SC administration 240mg Q1W or Q2W. [Figure 28C] Direct comparison in a validated model shows that anti-TL1A antibodies that bind to both TL1A monomers and trimers engage more (3.5-fold more) TL1A in the circulation than anti-TL1A antibodies that bind only to TL1A trimers. [Figure 28D] In a direct comparison in a validated model, anti-TL1A antibodies that bind to both TL1A monomers and trimers also resulted in a higher rate (approximately 100%) of TL1A reduction in diseased tissue when compared to anti-TL1A antibodies that only bind to TL1A trimers. [Figure 29A] A diagram of the popPK model is shown. [Figure 29B] 1 shows a comparison of A219 concentrations predicted from the popPK model and observed in a population of subjects from a Phase I clinical trial via a linear regression plot. [Figure 29C] 1 shows a comparison of predicted TL1A concentrations from the popPK model and observed TL1A concentrations in a population of subjects from a Phase I clinical trial via a linear regression plot. [Figure 29D] 1 shows a comparison of predicted A219 concentrations from the popPK model and observed A219 concentrations in a Phase I clinical trial subject population via a time series plot. [Figure 29E] 1 shows a comparison of predicted TL1A concentrations from the popPK model and observed TL1A concentrations in a Phase I clinical trial subject population via a time series plot. [Figure 30A]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30B]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30C]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30D]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30E]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30F]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30G]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 30H]Figures 30A and 30B show circulating A219 (30A) and TL1A (30B) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30C and 30D show circulating A219 (30C) and TL1A (30D) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 500 mg Q4W (10 doses) extension from week 12 to week 52. Figures 30E and 30F show circulating A219 (30E) and TL1A (30F) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 100 mg Q2W (20 doses) extension from week 12 to week 52. Figures 30G and 30H show A219 (30G) and TL1A (30H) concentrations using a dosing regimen of 500 mg Q2W (6 doses) induction through week 10 and 250 mg Q4W (10 doses) extension from week 12 to week 52. [Figure 31] A-B show gene expression levels of TNFSF15 (A) and TNFRSF25 (B) in hidradenitis suppurativa HS and healthy control skin. [Figure 32] A-C show gene set variation analysis (GSVA) ​​of the Th1, Th17, and Th2 pathways in lesional HS and healthy control skin, showing that Th1, Th17, and Th2 pathway genes are upregulated in lesional HS tissue compared to healthy control skin. Th = helper T cells. [Figure 33] A-B show GSVA of fibroblast-enriched fibrosis genes (Set 1.1) and fibrosis genes expressed by stromal and immune cells (Set 1.2) in lesional HS and healthy control skin, demonstrating that fibrosis genes are upregulated in lesional HS tissue compared to healthy control skin. [Figure 34]A-B show GSVA of TL1A-induced genes in IFNg-producing cells and Th17 T cells in lesional HS and healthy control skin, showing that TL1A-induced genes are upregulated in lesional HS tissue compared to healthy control skin. [Figure 35A] 1 shows upregulation of TNFSF15 regulator activity of target genes identified from the healthy skin gene regulatory network in lesional HS skin compared to control skin from healthy subjects. [Figure 35B] Figure 1 shows TNFSF15 as a top master regulator in differential master regulator analysis in the HS dataset. [Figure 36A] Figure 1 shows normalized gene expression levels of TNFRSF25 in single cells grouped by cell type in lesional HS skin (N=8) and controls (N=10) analyzed by single-cell RNAseq from Kim et al., demonstrating high expression levels of TNFRSF25 in HS tissues. [Figure 36B] Figure 1 shows TNFSF15 in single cells grouped by cell type in lesional HS skin (N=4) and lesional HS skin (N=3) control (N=1) analyzed by single-cell RNAseq from Gudjonsson et.al. and Mariottoni et.al., demonstrating that TNFSF15 was expressed by epithelial cells (keratinocytes), immune cells (myeloid cells), and smooth muscle cells in lesional HS tissue. [Figure 37A] Figures 37A-37E show the detection of TL1A transcripts in skin tissue from diseased HS (37A and 37B) and healthy controls (37C and 37D) by fluorescence in situ hybridization. Figure 37B shows the boxed area in Figure 37A at 60x magnification, and Figure 37D shows the boxed area in Figure 37C at 60x magnification. Figure 37E shows a negative control probe targeting the DapB gene from the soil bacterium Bacillus subtilis strain SMY. Magnification not shown. Blue = dapi, green = autofluorescence, red = TL1A probe. Representative n = 3. Scale bar = 20 μm. Figures 37A and 37C show autofluorescence, and Figures 37B and 37D show TL1A FISH. [Figure 37B] Figures 37A-37E show the detection of TL1A transcripts in skin tissue from diseased HS (37A and 37B) and healthy controls (37C and 37D) by fluorescence in situ hybridization. Figure 37B shows the boxed area in Figure 37A at 60x magnification, and Figure 37D shows the boxed area in Figure 37C at 60x magnification. Figure 37E shows a negative control probe targeting the DapB gene from the soil bacterium Bacillus subtilis strain SMY. Magnification not shown. Blue = dapi, green = autofluorescence, red = TL1A probe. Representative n = 3. Scale bar = 20 μm. Figures 37A and 37C show autofluorescence, and Figures 37B and 37D show TL1A FISH. [Figure 37C] Figures 37A-37E show the detection of TL1A transcripts in skin tissue from diseased HS (37A and 37B) and healthy controls (37C and 37D) by fluorescence in situ hybridization. Figure 37B shows the boxed area in Figure 37A at 60x magnification, and Figure 37D shows the boxed area in Figure 37C at 60x magnification. Figure 37E shows a negative control probe targeting the DapB gene from the soil bacterium Bacillus subtilis strain SMY. Magnification not shown. Blue = dapi, green = autofluorescence, red = TL1A probe. Representative n = 3. Scale bar = 20 μm. Figures 37A and 37C show autofluorescence, and Figures 37B and 37D show TL1A FISH. [Figure 37D] Figures 37A-37E show the detection of TL1A transcripts in skin tissue from diseased HS (37A and 37B) and healthy controls (37C and 37D) by fluorescence in situ hybridization. Figure 37B shows the boxed area in Figure 37A at 60x magnification, and Figure 37D shows the boxed area in Figure 37C at 60x magnification. Figure 37E shows a negative control probe targeting the DapB gene from the soil bacterium Bacillus subtilis strain SMY. Magnification not shown. Blue = dapi, green = autofluorescence, red = TL1A probe. Representative n = 3. Scale bar = 20 μm. Figures 37A and 37C show autofluorescence, and Figures 37B and 37D show TL1A FISH. [Figure 37E]Figures 37A-37E show the detection of TL1A transcripts in skin tissue from diseased HS (37A and 37B) and healthy controls (37C and 37D) by fluorescence in situ hybridization. Figure 37B shows the boxed area in Figure 37A at 60x magnification, and Figure 37D shows the boxed area in Figure 37C at 60x magnification. Figure 37E shows a negative control probe targeting the DapB gene from the soil bacterium Bacillus subtilis strain SMY. Magnification not shown. Blue = dapi, green = autofluorescence, red = TL1A probe. Representative n = 3. Scale bar = 20 μm. Figures 37A and 37C show autofluorescence, and Figures 37B and 37D show TL1A FISH. [Figure 38A] Figures 38A-38D show immunohistochemical detection of TL1A (Figures 38A and 38C) and DR3 protein (Figures 38B and 38D) in skin tissue from lesional HS (Figures 38A and 38B) or healthy controls (Figures 38C and 38D), showing strong expression in HS nodules and surrounding fistulas, with little or no staining in healthy controls. Figures 38A-38D show representative images of n=5. [Figure 38B] Figures 38A-38D show immunohistochemical detection of TL1A (Figures 38A and 38C) and DR3 protein (Figures 38B and 38D) in skin tissue from lesional HS (Figures 38A and 38B) or healthy controls (Figures 38C and 38D), showing strong expression in HS nodules and surrounding fistulas, with little or no staining in healthy controls. Figures 38A-38D show representative images of n=5. [Figure 38C] Figures 38A-38D show immunohistochemical detection of TL1A (Figures 38A and 38C) and DR3 protein (Figures 38B and 38D) in skin tissue from lesional HS (Figures 38A and 38B) or healthy controls (Figures 38C and 38D), showing strong expression in HS nodules and surrounding fistulas, with little or no staining in healthy controls. Figures 38A-38D show representative images of n=5. [Figure 38D]Figures 38A-38D show immunohistochemical detection of TL1A (Figures 38A and 38C) and DR3 protein (Figures 38B and 38D) in skin tissue from lesional HS (Figures 38A and 38B) or healthy controls (Figures 38C and 38D), showing strong expression in HS nodules and surrounding fistulas, with little or no staining in healthy controls. Figures 38A-38D show representative images of n=5. [Figure 39] Figures A-D show immunofluorescence detection of DR3 (red) and T cells (CD3, green) in acute HS lesion samples (A and B) and HS lesion fistula skin tissue (C and D). Figures A and C show low-magnification views of composite images of anti-DR3 (red), anti-CD3 (green), and dapi (blue). Figures B and D show individual channels (left and center panels of B and D) and composite views (right panels of B and D) of the enlarged squared areas of A and C. Figures A-D show colocalization of DR3 with CD3 (asterisk) and DR3 expression by non-T cells (CD3- cells). Figures A-D show representative images of n = 5. [Figure 40] Figure 1 shows soluble levels of IL6, IL1b, IL17A, IL17F, TL1a and TNFa in HS skin tissue lysates and healthy control lysates, as quantified by immunoassay (Meso Scale Discovery), demonstrating higher levels of TL1A in HS skin tissue compared to skin tissue from normal healthy volunteers (NHV). [Figure 41] A-B show gene set variation analysis (GSVA) ​​of TL1A-induced genes in Th17 T cells and TL1A-induced genes in IFNg-producing cells in lesional atopic dermatitis ("AD") skin and healthy control skin. Th = helper T cells. [Figure 42A] Figure 1 shows TNFSF15 regulator activity of target genes identified from the healthy skin gene regulatory network in lesional AD skin compared to control skin from healthy subjects. [Figure 42B] 1 shows TNFSF15 in differential master regulator analysis in AD compared to controls in transcriptome datasets. [Figure 43] Normalized gene expression levels of TNFRSF25 and percentage of TNFRSF25-expressing cells are shown in T / NKT clusters in lesional and non-lesional AD skin (N=5 patients) and healthy controls (N=7) analyzed from a single-cell RNAseq dataset (GSE147424). [Figure 44A] Figures 44A-44B show TL1A (44A) and DR3 (44B) proteins detected immunohistochemically in lesional AD skin tissue, demonstrating elevated TL1A expression and strong DR3 expression in nodules and peripheral fistulas in AD. Representative images of N=8 AD and N=5 healthy controls. [Figure 44B] Figures 44A-44B show TL1A (44A) and DR3 (44B) proteins detected immunohistochemically in lesional AD skin tissue, demonstrating elevated TL1A expression and strong DR3 expression in nodules and peripheral fistulas in AD. Representative images of N=8 AD and N=5 healthy controls. DETAILED DESCRIPTION OF THE INVENTION

[0255] TL1A is a cytokine secreted by antigen-presenting cells, T cells, and endothelial cells. TL1A signals through death receptor 3 (DR3), a TNF family receptor found primarily on T cells, natural killer (NK) and NK-T cells, innate lymphocytes (ILCs), fibroblasts, and epithelial cells, and potently drives Th1, Th2, Th9, and Th17 responses. Furthermore, it is induced in antigen-presenting cells by toll-like receptor (TLR) ligands and FcR crosslinking, and in T cells by T cell receptor (TCR) stimulation. Figure 8 demonstrates how TL1A binding to DR3 independently promotes inflammation and fibrosis. TL1A binding to DR3 on innate and T cells results in an early cytokine response (release of IL-23, IL-1β, IL-17, IL-22, TNF-α, IFN-γ, and IL-13) that sets the stage for inflammation and stimulates innate and adaptive immune responses. For example, through binding to DR3, TL1A potentially drives inflammatory Th1 and Th17 responses. Furthermore, binding of TL1A to DR3 on fibroblasts directly activates fibroblasts, resulting in inflammation-independent collagen dynamics and fibrosis. Circulating TL1A levels are low in healthy subjects but elevated in patients with many autoimmune diseases, and TL1A has been shown to be upregulated in the mucosa and serum of patients with IBD. In mice, chronic TL1A expression leads to structural disease caused by increased collagen deposition. In dextran sulfate sodium (DSS) and adoptive transfer mouse models, TL1A transgenic mice developed more severe colitis than wild-type animals when challenged with DSS, and antibodies against TL1A reduced inflammation, reduced collagen levels, and reversed fibrosis, even when treatment was administered late in the disease course after inflammation and fibrosis had been established. Furthermore, TL1A polymorphisms have been shown to be associated with susceptibility to IBD and disease severity.

[0256] Fibrosis is an important clinical phenotype exhibited by IBD patients. 70% of patients with Crohn's disease (CD) develop strictures / perforations, and strictures are the leading indication for surgery in CD. Unfortunately, the use of anti-inflammatory agents over the past decade has not substantially changed the rate of structural disease or the need for surgery. Furthermore, in ulcerative colitis (UC), subclinical fibrosis significantly impacts patient symptoms. For example, subclinical fibrosis can contribute to symptoms of diarrhea, abdominal pain, urgency, and incontinence. Subclinical fibrosis is also a potential cause of persistent symptoms after resolution of inflammation. Furthermore, a Cleveland Clinic study of 89 consecutive colectomy specimens revealed submucosal fibrosis in 100% of specimens. Therefore, treatment of fibrosis constitutes an unmet need in IBD.

[0257] The potential of TL1A as a therapeutic target in intestinal fibrosis was demonstrated in studies evaluating the effects of anti-TL1A antibodies in mouse models of IBD. These studies utilized two mouse models of chronic colitis: adoptive T cell transfer and chronic DSS. In both models, a neutralizing TL1A monoclonal antibody (mAb) or an isotype control antibody was administered twice weekly to mice with established colitis (T cell transfer n = 14, DSS n = 28). In both disease models, treatment with TL1A mAb reduced colonic collagen deposition levels to those seen in healthy control mice, suggesting that blocking TL1A signaling not only prevented the progression of colonic fibrosis but also reversed established fibrosis to levels similar to those measured before the onset of inflammation. These data indicate that intestinal fibrosis mediated by increased levels of TL1A can be treated with anti-TL1A antibodies.

[0258] In one aspect, provided herein are methods of treating inflammation and / or fibrosis with anti-TL1A antibodies. In some embodiments, the treatment of fibrosis is independent of the treatment of inflammation. In some embodiments, the treatment of inflammation is independent of the treatment of fibrosis. In one aspect, provided herein are methods of treating skin diseases and / or conditions with anti-TL1A antibodies. In one aspect, provided herein are methods of treating systemic sclerosis with anti-TL1A antibodies. Systemic sclerosis is primarily a fibrotic disease. In some examples, the treatment of systemic sclerosis includes the treatment of fibrosis. In some examples, the treatment of fibrosis includes the treatment of systemic sclerosis. In some examples, the treatment of systemic sclerosis is independent of the treatment of fibrosis, or vice versa. Further non-limiting examples of indications for use with anti-TL1A antibodies herein include hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis or scleroderma, lupus, dermatomyositis, eczema, epidermolysis bullosa, and bullous pemphigoid. In some embodiments, the subject with systemic sclerosis has a skin symptom of systemic sclerosis. In some embodiments, the subject with systemic sclerosis has systemic sclerosis-associated interstitial lung disease. In some embodiments, the subject has scleroderma. In certain embodiments, the anti-TL1A antibody binds to membrane-bound and soluble forms of TL1A with high affinity and specificity and blocks the binding of TL1A to its functional receptor DR3.

[0259] The term "and / or" when used in a phrase including a list of members is intended to include all members individually and all combinations of a complete or partial list of members. For example, a phrase such as "A and / or B" herein is intended to include both A and B, A or B, A alone, and B alone. Similarly, the term "and / or" when used in a phrase such as "A, B, and / or C" is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A alone; B alone; and C alone.

[0260] 4.1 General Techniques The techniques and procedures described or referenced herein include those that are generally well understood and / or commonly employed by those of skill in the art using conventional methodology, such as, for example, the widely used methodology described in Sambrook et al., Molecular Cloning: A Laboratory Manual (3rd ed. 2001); Current Protocols in Molecular Biology (Ausubel et al. eds., 2003); Therapeutic Monoclonal Antibodies: From Bench to Clinic (An ed. 2009); Monoclonal Antibodies: Methods and Protocols (Albitar ed. 2010); and Antibody Engineering Vols 1 and 2 (Kontermann and Dubel eds., 2nd ed. 2010).

[0261] 4.2 Anti-TL1A antibody TL1A exists in both monomeric and trimeric forms in vivo and in vitro. The present disclosure provides that, although the trimeric form is the biologically active form that can bind to the physiological receptor, death receptor 3 ("DR3"), and induce TL1A-mediated signaling (e.g., Zhan, C et al., Structure 19:162-171 (2011)), monomeric TL1A accounts for a large fraction of the TL1A pool in a subject. One of the inventors' estimates is that monomeric TL1A may represent 60% of the total TL1A in the circulation. The term "total TL1A" refers to both monomeric and trimeric TL1A. The present disclosure further provides that anti-TL1A antibodies that bind to both monomeric and trimeric TL1A are advantageous over antibodies that bind only to trimeric TL1A, even though monomeric TL1A is biologically inactive. As provided herein and further demonstrated in Section 5, such advantages include a more efficient reduction in TL1A concentration in a subject's diseased tissue, including the concentration of trimeric TL1A in the diseased tissue; a more efficient reduction in TL1A concentration in a subject's blood, including the concentration of trimeric TL1A in the blood; a more sustained reduction in TL1A concentration (including trimeric TL1A concentration) in a subject's diseased tissue; and / or a more sustained reduction in TL1A concentration (including trimeric TL1A concentration) in a subject's blood.

[0262] In one aspect, provided herein are antibodies or antigen-binding fragments thereof that bind to tumor necrosis factor-like protein 1A (for brevity, referred to herein as "TL1A," and such antibodies or antigen-binding fragments thereof, "anti-TL1A antibodies or antigen-binding fragments," or "anti-TL1A antibodies"), wherein the antibodies or antigen-binding fragments bind to both monomeric and trimeric TL1A. Additional embodiments of anti-TL1A antibodies, including embodiments with exemplary CDRs, framework sequences, constant region sequences, Fc mutations, variable regions, Fc regions, and other features, are provided further in this section (Section 4.2). Assays for screening, testing, and validation of anti-TL1A antibodies are provided in Section 4.3. Methods for generating, improving, mutating, cloning, expressing, and isolating anti-TL1A antibodies are provided in Section 4.4. Pharmaceutical compositions of anti-TL1A antibodies are described and provided in Section 4.5. Methods of using anti-TL1A antibodies are provided in Section 4.6. Further specific and validated embodiments of anti-TL1A antibodies and methods of using them are provided in Section 5. Accordingly, the present disclosure provides various combinations of anti-TL1A antibodies, pharmaceutical compositions of such anti-TL1A antibodies, methods of producing anti-TL1A antibodies, methods of assaying anti-TL1A antibodies, and methods of using anti-TL1A antibodies for therapy.

[0263] In one embodiment of the various anti-TL1A antibodies or antigen-binding fragments thereof provided herein, the antibody or antigen-binding fragment blocks binding of TL1A to death receptor 3 ("DR3"). In another embodiment, the antibody or antigen-binding fragment blocks binding of trimeric TL1A to DR3. In a further embodiment, the antibody or antigen-binding fragment blocks TL1A-mediated DR3 signaling. In yet another embodiment, the antibody or antigen-binding fragment blocks increased IFNγ secretion by various immune cells. In a specific embodiment, the antibody or antigen-binding fragment blocks increased IFNγ secretion by various B cells, T cells, natural killer cells, and / or peripheral blood mononuclear cells, including macrophages.

[0264] As described herein, the present disclosure provides anti-TL1A antibodies or antigen-binding fragments for binding to both monomeric and trimeric TL1A. Accordingly, in one embodiment of the various anti-TL1A antibodies or antigen-binding fragments thereof provided herein, the dissociation equilibrium constant (K D-monomer The binding affinity of an antibody or antigen-binding fragment to monomeric TL1A, as measured by the dissociation equilibrium constant (K D-trimer ) corresponds to the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A. D-monomer and / or K D-trimer can be determined via any of the methods known and practiced by those of skill in the art, as well as any of the applicable assays and methods described herein, including in this section (Section 4.2) and Section 5.

[0265] The term "bind" or "binding" refers to interactions between molecules, including, for example, forming a complex. The interaction can be a non-covalent interaction, including, for example, hydrogen bonding, ionic bonding, hydrophobic interactions, and / or van der Waals interactions. A complex can also include the association of two or more molecules held together by covalent or non-covalent bonds, interactions, or forces. The strength of all non-covalent interactions between a single antigen-binding site on an antibody and a single epitope on a target molecule, such as TL1A, is the affinity of the antibody or functional fragment for that epitope. The association rate (k on ) to the dissociation rate (k off ) ratio (k off / k on ) is the dissociation constant K, which is inversely proportional to the affinity D It is. K D The lower the value, the higher the affinity of the antibody. D The value of k varies for different complexes of antibody and antigen. on and k off The dissociation constant K of the antibodies provided herein depends on both Dcan be determined using any method provided herein or any other method known to those skilled in the art. The affinity at one binding site does not necessarily reflect the true strength of the interaction between the antibody and the antigen. When a complex antigen containing multiple repeating antigenic determinants, such as a multivalent TL1A trimer, contacts an antibody containing multiple binding sites, the interaction between the antibody and the antigen at one site will increase the probability of reaction at a second site. The strength of such multiple interactions between a multivalent antibody and an antigen is called avidity. The avidity of an antibody may be a better measure of its binding capacity than the affinity of its individual binding sites.

[0266] "Binding affinity" generally refers to the strength of the sum of non-covalent interactions between a single binding site of a molecule (e.g., a binding protein such as an antibody) and its binding partner (e.g., an antigen). Unless otherwise indicated, as used herein, "binding affinity" refers to the intrinsic binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., an antibody and an antigen). As noted above, the affinity of a binding molecule X for a binding partner Y is generally determined by the dissociation constant (K D ) Affinity can be measured by common methods known in the art, including those described herein. Low affinity antibodies generally bind to antigens slowly and tend to dissociate easily, whereas high affinity antibodies generally tend to bind to antigens quickly and remain bound for a long time. Various methods for measuring binding affinity are known in the art, any of which may be used for the purposes of the present disclosure. Specific exemplary embodiments include the following. In one embodiment, "K D " or "K D The "K value" can be measured by assays known in the art, for example, by binding assays. D can be measured, for example, in an RIA performed using the Fab version of the antibody of interest and its antigen (Chen et al., 1999, J. Mol Biol 293:865-81). D or K DThe value can also be measured by using a surface plasmon resonance assay by Biacore®, for example, using a Biacore® TM-2000 or Biacore® TM-3000, or by biolayer interferometry, for example, using an Octet® QK384 system. "on rate" or "rate of association" or "association rate" or "k on " can also be determined with the same surface plasmon resonance or biolayer interferometry techniques as above, using, for example, a Biacore® TM-2000 or Biacore® TM-3000, or an Octet® QK384 system.

[0267] Therefore, the relative binding affinity of an anti-TL1A antibody or antigen-binding fragment for TL1A monomer and TL1A trimer is expressed as K D-monomer and K. D-trimer In one embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-monomer is K D-trimer In another embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, the K D-monomer is K D-trimer In further embodiments of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-trimer is K D-monomer In another embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, the K D-trimer is K D-monomer within 10%, 20%, 30%, 40%, or 50% of the

[0268] More specifically, in one embodiment of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-monomer is at most 5 × 10 -12 M, at most 6 × 10 -12 M, at most 7 × 10-12 M, at most 8 × 10 -12 M, at most 9 × 10 -12 M, at most 1 × 10 -11 M, at most 2 × 10 -11 M, at most 3 × 10 -11 M, at most 4 × 10 -11 M, at most 5 × 10 -11 M, at most 6 × 10 -11 M, at most 7 × 10 -11 M, at most 8 × 10 -11 M, at most 9 × 10 -11 M, at most 1 × 10 -10 M, at most 2 × 10 -10 M, at most 3 × 10 -10 M, at most 4 × 10 -10 M, at most 5 × 10 -10 M, at most 6 × 10 -10 M, at most 7 × 10 -10 M, at most 8 × 10 -10 M, at most 9 × 10 -10 M, or at most 1 × 10 -9 In another embodiment, K D-monomer is about 5 x 10 -12 M, about 6 x 10 -12 M, about 7 x 10 -12 M, about 8 x 10 -12 M, about 9 x 10 -12 M, about 1 x 10 -11 M, approx. 2 x 10 -11 M, about 3 x 10 -11 M, approx. 4 x 10 -11 M, about 5 x 10 -11 M, about 6 x 10 -11 M, about 7 x 10 -11 M, about 8 x 10 -11 M, about 9 x 10 -11 M, about 1 x 10 -10 M, approx. 2 x 10 -10 M, about 3 x 10 -10 M, approx. 4 x 10 -10 M, about 5 x 10 -10 M, about 6 x 10 -10 M, about 7 x 10 -10 M, about 8 x 10 -10 M, about 9 x 10 -10 M, or approximately 1 x 10-9 In further embodiments of the various anti-TL1A antibodies or antigen-binding fragments provided herein, K D-trimer is at most 5 × 10 -12 M, at most 6 × 10 -12 M, at most 7 × 10 -12 M, at most 8 × 10 -12 M, at most 9 × 10 -12 M, at most 1 × 10 -11 M, at most 2 × 10 -11 M, at most 3 × 10 -11 M, at most 4 × 10 -11 M, at most 5 × 10 -11 M, at most 6 × 10 -11 M, at most 7 × 10 -11 M, at most 8 × 10 -11 M, at most 9 × 10 -11 M, at most 1 × 10 -10 M, at most 2 × 10 -10 M, at most 3 × 10 -10 M, at most 4 × 10 -10 M, at most 5 × 10 -10 M, at most 6 × 10 -10 M, at most 7 × 10 -10 M, at most 8 × 10 -10 M, at most 9 × 10 -10 M, or at most 1 × 10 -9 In yet another embodiment, K D-trimer is about 5 x 10 -12 M, about 6 x 10 -12 M, about 7 x 10 -12 M, about 8 x 10 -12 M, about 9 x 10 -12 M, about 1 x 10 -11 M, approx. 2 x 10 -11 M, about 3 x 10 -11 M, approx. 4 x 10 -11 M, about 5 x 10 -11 M, about 6 x 10 -11 M, about 7 x 10 -11 M, about 8 x 10 -11 M, about 9 x 10 -11 M, about 1 x 10 -10 M, approx. 2 x 10 -10 M, about 3 x 10 -10 M, approx. 4 x 10-10 M, about 5 x 10 -10 M, about 6 x 10 -10 M, about 7 x 10 -10 M, about 8 x 10 -10 M, about 9 x 10 -10 M, or approximately 1 x 10 -9 M. The present disclosure further provides D-monomer and K. D-trimer K, including this section (Section 4.2) and this paragraph. D-monomer and K. D-trimer It is provided that the value or range of

[0269] In a further particular embodiment, K D-monomer In another particular embodiment, K D-trimer In a further embodiment, K D-monomer is approximately 59 pM, and K D-trimer is about 59 pM. D-monomer In another particular embodiment, K D-trimer In a further embodiment, K D-monomer is approximately 60 pM, and K D-trimer is about 60 pM. In one particular embodiment, K D-monomer In another particular embodiment, K D-trimer In a further embodiment, K D-monomer is at most 60 pM, and K D-trimer is at most 60 pM.

[0270] In one aspect, provided herein is an antibody that binds to TL1A. As used herein, the term "antibody" refers to any form of antibody that exhibits the desired biological activity or binding activity. Thus, it is used in the broadest sense and specifically covers, but is not limited to, monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized, fully human antibodies, chimeric antibodies, and camelized single domain antibodies.

[0271] Generally, the basic antibody structural unit comprises a tetramer. Each tetramer contains two identical pairs of polypeptide chains, each pair having one "light chain" (approximately 25 kDa) and one "heavy chain" (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region of approximately 100-110 amino acids in length, primarily responsible for antigen recognition. The carboxy-terminal portion of the heavy chain may define a constant region primarily responsible for effector function. Human light chains are typically classified as kappa and lambda light chains. Human heavy chains are further classified as mu, delta, gamma, alpha, or epsilon, defining the antibody isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Within the light and heavy chains, the variable and constant regions are connected by a "J" region of approximately 12 or more amino acids, and the heavy chain also contains a "D" region of approximately 10 or more amino acids in length. See generally, Fundamental Immunology Ch. 7 (Paul, W., ed., 2nd ed. Raven Press, NY (1989)).

[0272] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, an intact antibody generally has two binding sites. Except for bifunctional or bispecific antibodies, the two binding sites are generally the same.

[0273] Typically, both heavy and light chain variable domains contain three hypervariable regions, also called complementarity-determining regions (CDRs), located within relatively conserved framework regions (FRs). The CDRs are usually aligned by the framework regions, enabling binding to a specific epitope. Generally, from N- to C-terminus, both light and heavy chain variable domains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The assignment of amino acids to each domain is generally based on the information in Sequences of Proteins of Immunological Interest, Kabat, et al.; National Institutes of Health, Bethesda, Md.; 5 thed.; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chem. 32:1-75; Kabat, et al., (1977) J. Biol. Chem. 252:6609-6616; Chothia, et al., (1987) J Mol. Biol. 196:901-917 or Chothia, et al., (1989) Nature 342:878-883.

[0274] As used herein, unless otherwise indicated, "antibody fragment" or "antigen-binding fragment" refers to an antigen-binding fragment of an antibody, i.e., an antibody fragment that retains the ability to specifically bind to the antigen bound by the full-length antibody, e.g., a fragment that retains one or more CDR regions. Examples of antibody-binding fragments include, but are not limited to, Fab, Fab', F(ab'), and Fv fragments; bispecific antibodies; linear antibodies; single-chain antibody molecules (e.g., sc-Fv); nanobodies and multispecific antibodies formed from antibody fragments.

[0275] In some embodiments, an antibody includes an antigen-binding fragment, which refers to a portion of an antibody comprising the antigenic determining variable region of the antibody. Examples of antigen-binding fragments include, but are not limited to, Fab, Fab', F(ab'), 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 (e.g., Fab, Fab', F(ab')2, and Fv fragments), single-chain Fv (scFv) variants, CDR-grafted antibodies, multispecific antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins containing antigenic determinants of an antibody, and any other modified immunoglobulin molecule containing an antigen recognition site, provided that the antibody exhibits the desired biological activity. Antibodies may be any of the five major immunoglobulin classes: IgA, IgD, IgE, IgG, and IgM, or their subclasses (isotypes) (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), based on the identity of their heavy chain constant domains, designated alpha, delta, epsilon, gamma, and mu, respectively. Different classes of immunoglobulins have distinct and known subunit structures and three-dimensional configurations. Antibodies may be naked or conjugated to other molecules, such as toxins, radioisotopes, etc.

[0276] In some embodiments, a humanized antibody refers 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 a non-limiting example, a humanized antibody contains less than about 40% non-human sequences in the variable region. In some examples, a humanized antibody contains less than about 20% non-human sequences in the full-length antibody sequence. In a further non-limiting example, a humanized antibody contains 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 contains 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 sequences in the framework regions of each of the heavy and light chain variable regions. In another example, a humanized antibody comprises less than about 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. In some examples, humanized antibodies are human immunoglobulins in which residues from a complementarity-determining region (CDR) are replaced by 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 may contain 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 may contain 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 an IGHV1-46*02 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations, or no amino acid mutations. The humanized light chain variable domain may comprise an IGKV3-20 framework with less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid mutations, or no amino acid mutations.

[0277] In some embodiments, a chimeric antibody refers to an antibody in which the sequences of its immunoglobulin molecules are 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 with the desired specificity, affinity, and capacity derived from one species of mammal (e.g., mouse, rat, rabbit, etc.), while the constant regions are homologous to antibody sequences derived from another species (usually human), thereby avoiding eliciting an immune response in that species.

[0278] The terms "complementarity-determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art to refer to non-contiguous sequences of amino acids in an antibody variable region that confer antigen specificity and / or binding affinity. Generally, there are three CDRs (CDR-H1, CDR-H2, CDR-H3) in each heavy chain variable region and three CDRs (CDR-L1, CDR-L2, CDR-L3) in each light chain variable region. The terms "framework region" and "FR" are known in the art to refer to the non-CDR portions of the heavy and light chain variable regions. Generally, there are four FRs (FR-H1, FR-H2, FR-H3, and FR-H4) in each full-length heavy chain variable region and four FRs (FR-L1, FR-L2, FR-L3, and FR-L4) in each full-length light chain variable region.The precise amino acid sequence boundaries of a given CDR or FR can be determined from Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (Kabat numbering scheme); Al-Lazikani et al., (1997) JMB273, 927-948 (Chothia numbering scheme); MacCallum et al., J. Mol. Biol. 262:732-745 (1996), “Antibody-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., 2003 Jan;27(1):55-77 ("IMGT" numbering scheme), Honegger A and Pluckthun A, "Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool," J Mol Biol, 2001 Jun;309(3):657-70, ("Aho" numbering scheme), and Whitelegg NR and Rees AR, "WAM: an improved algorithm for modeling antibodies on the WEB," Protein Eng. 2000 Dec;13(12):819-24 ("AbM" numbering scheme).In certain embodiments, the CDRs of the antibodies described herein may be defined by a method selected from Kabat, Chothia, IMGT, Aho, AbM, or a combination thereof.

[0279] 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 period of time, with higher affinity, or some combination of the foregoing, than with other substances, including unrelated proteins.

[0280] In some embodiments, the terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to amino acid polymers of any length. The polymers may be linear or branched, may comprise modified amino acids, and may be interrupted by non-amino acids. The terms also encompass modified natural amino acid polymers or amino acid polymers modified by intervening modifications, such as disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or fusion and / or conjugation with another polypeptide, such as, for example, a labeling component. Also included within the definition are polypeptides containing, for example, one or more analogs of an amino acid (such as, for example, an unnatural amino acid), as well as other modifications known in the art.

[0281] In some embodiments, proteins such as antibodies described herein comprise hydrophobic amino acids. Non-limiting examples of hydrophobic amino acids include glycine (Gly), proline (Pro), phenylalanine (Phe), alanine (Ala), isoleucine (Ile), leucine (Leu), and valine (Val). In some embodiments, proteins such as antibodies described herein comprise hydrophilic amino acids. Non-limiting examples of hydrophilic amino acids include serine (Ser), threonine (Thr), aspartic acid (Aap), glutamic acid (Glu), cysteine ​​(Cys), asparagine (Asn), glutamine (Gln), arginine (Arg), and histidine (His). In some embodiments, proteins such as antibodies described herein comprise amphipathic amino acids. Non-limiting examples of amphipathic amino acids include lysine (Lys), tryptophan (Trp), tyrosine (Tyr), and methionine (Met). In some embodiments, proteins such as antibodies described herein comprise aliphatic amino acids. Non-limiting examples of aliphatic amino acids include alanine (Ala), isoleucine (Ile), leucine (Leu), and valine (Val). In some embodiments, proteins such as antibodies described herein comprise aromatic amino acids. Non-limiting examples of aromatic amino acids include phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). In some embodiments, proteins such as antibodies described herein comprise acidic amino acids. Non-limiting examples of acidic amino acids include aspartic acid (Asp) and glutamic acid (Glu). In some embodiments, proteins such as antibodies described herein comprise basic amino acids. Non-limiting examples of basic amino acids include arginine (Arg), histidine (His), and lysine (Lys). In some embodiments, proteins such as antibodies described herein comprise hydroxyamino acids. Non-limiting examples of hydroxyamino acids include serine (Ser) and threonine (Thr). In some embodiments, proteins such as antibodies described herein comprise sulfur-containing amino acids.Non-limiting examples of sulfur-containing amino acids include cysteine ​​(Cys) and methionine (Met). In some embodiments, proteins such as antibodies described herein comprise amide amino acids. Non-limiting examples of amide amino acids include asparagine (Asn) and glutamine (Gln).

[0282] In some embodiments, "polynucleotide" or "nucleic acid" are used interchangeably herein to refer to a polymer of nucleotides of any length, including DNA and RNA. Nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by a DNA or RNA polymerase. Polynucleotides can also include modified nucleotides, such as, but not limited to, methylated nucleotides and their analogs or non-nucleotide components. Modifications to the nucleotide structure can be imparted before or after assembly of the polymer. Polynucleotides can be further modified after multimerization, such as by conjugation with a labeling component.

[0283] The percent sequence identity (%) to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical to those in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, without considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in a variety of known ways, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences, including the algorithm required to achieve maximum alignment over the entire length of the sequences being compared, can be determined. However, for purposes of this specification, percent amino acid sequence identity values ​​are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and the source code has been submitted, along with user documentation, to the U.S. Copyright Office, Washington, DC 20559, and is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or may be compiled from the source code. The ALIGN-2 program must be compiled for use on UNIX operating systems, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

[0284] In situations where ALIGN-2 is used for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can be rephrased as a given amino acid sequence A having or containing a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and Y is the total number of amino acid residues in B. It will be understood that if 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 equal the % amino acid sequence identity of B to A. Unless otherwise specified, all % amino acid sequence identity values ​​used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0285] In some embodiments, the term "about" means within 10% of the specified amount. For example, an antibody variable region with about 80% identity to a reference variable region may have 72%-88% identity to the reference variable region.

[0286] In certain aspects, antibodies that specifically bind to TL1A are described herein (Entrez Gene: 9966; UniProtKB: O95150). In some embodiments, the antibodies specifically bind to soluble TL1A. In some embodiments, the antibodies specifically bind to membrane-bound TL1A. In some embodiments, anti-TL1A antibodies are provided having a heavy chain comprising the following four heavy chain framework regions (HCFRs) and three heavy chain complementarity-determining regions (HCDRs): HCFR1, HCDR1, HCFR2, HCDR2, HCFR3, HCDR3, and HCFR4; and a light chain comprising the following four light chain framework regions (LCFRs) and three light chain complementarity-determining regions (LCDRs): LCFR1, LCDR1, LCFR2, LCDR2, LCFR3, LCDR3, and LCFR4. Anti-TL1A antibodies can comprise any of the regions provided herein, e.g., in the tables, examples, and sequences.

[0287] Exemplary Anti-TL1A CDRs

[0288] In certain embodiments, an anti-TL1A antibody comprises an HCDR1 set forth by SEQ ID NO: 1. In certain embodiments, an anti-TL1A antibody comprises an HCDR2 set forth by any one of SEQ ID NOs: 2-5. In certain embodiments, an anti-TL1A antibody comprises an HCDR3 set forth by any one of SEQ ID NOs: 6-9. In certain embodiments, an anti-TL1A antibody comprises an LCDR1 set forth by SEQ ID NO: 10. In certain embodiments, an anti-TL1A antibody comprises an LCDR2 set forth by SEQ ID NO: 11. In certain embodiments, an anti-TL1A antibody comprises an LCDR3 set forth by any one of SEQ ID NOs: 12-15. In a non-limiting example, an anti-TL1A antibody comprises an HCDR1 set forth by SEQ ID NO: 1, an HCDR2 set forth by SEQ ID NO: 2, an HCDR3 set forth by SEQ ID NO: 6, an LCDR1 set forth by SEQ ID NO: 10, an LCDR2 set forth by SEQ ID NO: 11, and an LCDR3 set forth by SEQ ID NO: 12. In some examples, an anti-TL1A antibody comprises the CDRs of antibody J in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody J2 in Table 10. In some examples, the anti-TL1A antibody comprises the CDRs of antibody K in Table 10.

[0289] In certain embodiments, an anti-TL1A antibody comprises an HCDR1 described by SEQ ID NO: 401, 407, 413, or 450. In certain embodiments, an anti-TL1A antibody comprises an HCDR2 described by SEQ ID NO: 402, 408, 414, or 451. In certain embodiments, an anti-TL1A antibody comprises an HCDR3 described by SEQ ID NO: 403, 409, 415, or 452. In certain embodiments, an anti-TL1A antibody comprises an LCDR1 described by SEQ ID NO: 404, 410, 416, or 453. In certain embodiments, an anti-TL1A antibody comprises an LCDR2 described by SEQ ID NO: 405, 411, 417, or 454. In certain embodiments, an anti-TL1A antibody comprises an LCDR3 described by SEQ ID NO: 406, 412, 418, or 455.

[0290] In certain embodiments, the anti-TL1A antibody comprises an HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 selected from Table 6. [Table 1-1] [Table 1-2]

[0291] In certain embodiments, the anti-TL1A antibody comprises the CDRs set forth in antibody A, B, C, D, E, F, G, H, I, A2, B2, C2, D2, E2, F2, G2, H2, I2, J, J2, K, M, or N in Table 10. [Table 2]

[0292] In certain embodiments, the anti-TL1A antibody comprises the heavy chain CDRs set forth in an antibody selected from Table 7. [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6] [Table 3-7]

[0293] In certain embodiments, the anti-TL1A antibody comprises the light chain CDRs set forth in an antibody selected from Table 8. Table 4-1 Table 4-2 Table 4-3 Table 4-4 Table 4-5

[0294] In certain embodiments, the anti-TL1A antibody comprises the CDRs set forth in any one of the antibodies in Table 1. For example, anti-TL1A antibodies include antibodies A15, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A5 3, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A 68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A9 9, A100, A101, A102, A103, A104, A105, A107, A108, A109, A110, A111, A1 12, A113, A114, A115, A116, A117, A118, A119, A120, A121, A122, A123, A 124, A125, A126, A127, A128, A129, A130, A132, A133, A134, A135, A136, A137, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A14 8, A149, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A1 60, A161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A 172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN CDRs.In a non-limiting example, the anti-TL1A antibody comprises the CDRs of antibody A219.

[0295] Antibody CDRs can be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0296] Exemplary Anti-TL1A Framework Regions

[0297] In certain embodiments, an anti-TL1A antibody comprises a heavy chain (HC) framework 1 (FR1) set forth by SEQ ID NO: 304. In certain embodiments, an anti-TL1A antibody comprises a HC FR2 set forth by any one of SEQ ID NOs: 305 or 313. In certain embodiments, an anti-TL1A antibody comprises a HC FR3 set forth by any one of SEQ ID NOs: 306-307, 314-315. In certain embodiments, an anti-TL1A antibody comprises a HC FR4 set forth by SEQ ID NO: 308. In certain embodiments, an anti-TL1A antibody comprises a LC FR1 set forth by SEQ ID NO: 309. In certain embodiments, an anti-TL1A antibody comprises a LC FR2 set forth by SEQ ID NO: 310. In certain embodiments, an anti-TL1A antibody comprises a LC FR3 set forth by SEQ ID NO: 311. In certain embodiments, an anti-TL1A antibody comprises a LC FR4 set forth by SEQ ID NO: 312. In a non-limiting example, an anti-TL1A antibody comprises a HC FR1 described by SEQ ID NO: 304, a HC FR2 described by SEQ ID NO: 305, a HC FR3 described by SEQ ID NO: 306, a HC FR4 described by SEQ ID NO: 308, a LC FR1 described by SEQ ID NO: 309, a LC FR2 described by SEQ ID NO: 310, a LC FR3 described by SEQ ID NO: 311, and a LC FR4 described by SEQ ID NO: 312. In a non-limiting example, an anti-TL1A antibody comprises a HC FR1 described by SEQ ID NO: 304, a HC FR2 described by SEQ ID NO: 305, a HC FR3 described by SEQ ID NO: 307, a HC FR4 described by SEQ ID NO: 308, a LC FR1 described by SEQ ID NO: 309, a LC FR2 described by SEQ ID NO: 310, a LC FR3 described by SEQ ID NO: 311, and a LC FR4 described by SEQ ID NO: 312.

[0298] In certain embodiments, the anti-TL1A antibody comprises a heavy chain framework region described in an antibody selected from Table 7. In certain embodiments, the anti-TL1A antibody comprises a light chain framework region described in an antibody selected from Table 8. In certain embodiments, the anti-TL1A antibody comprises a framework region described in any one of the antibodies in Table 1.For example, anti-TL1A antibodies include antibodies A15, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53. , A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A6 8, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A81, A82, A83, A 85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A107, A108, A109, A110, A111, A112 , A113, A114, A115, A116, A117, A118, A119, A120, A121, A122, A123, A12 4, A125, A126, A127, A128, A129, A130, A132, A133, A134, A135, A136, A13 7, A138, A139, A140, A141, A142, A143, A144, A145, A146, A147, A148, A1 49, A150, A151, A152, A153, A154, A155, A156, A157, A158, A159, A160, A 161, A162, A163, A164, A165, A166, A167, A168, A169, A170, A171, A172, A173, A174, A175, A176, A177, A178, A179, A180, A181, A182, A183, A184, A210, A211, A212, A213, A214, A215, A216, A217, A218, A219, A220, A221, A222, A223, A224, A500, A501, AJ, AK, AM, or AN framework regions. In a non-limiting example, the anti-TL1A antibody comprises the framework region of antibody A219.In another non-limiting example, the anti-TL1A antibody comprises the framework region of an antibody comprising SEQ ID NOs: 420 and 430. In another non-limiting example, the anti-TL1A antibody comprises the framework region of an antibody comprising SEQ ID NOs: 421 and 431. In another non-limiting example, the anti-TL1A antibody comprises the framework region of an antibody comprising SEQ ID NOs: 424 and 434.

[0299] Antibody CDR and framework regions may be defined by the Aho, Kabat, Chothia, or IMGT methods.

[0300] In some embodiments, the anti-TL1A antibody comprises a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*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 collectively comprise no amino acid modifications or collectively comprise fewer than nine amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework. In some embodiments, the amino acid modification comprises (a) a modification at amino acid position 45 in the heavy chain variable region, (b) a modification at amino acid position 47 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, or a combination of two or more modifications selected from (a) to (h), according to the Aho or Kabat numbering. In some embodiments, the amino acid modification comprises (a) R45K, (b) A47R, (c) M55I, (d) V78A, (e) M80I, (f) R82T, (g) V89A, or (h) M91L in the heavy chain variable region, or a combination of two or more modifications selected from (a)-(h), according to Aho or Kabat numbering. In some embodiments, the amino acid modification comprises A47R. In some embodiments, the amino acid modification comprises A47R, M55I, V78A, M80I, R82T, V89A, and M91L; A47R, M80I, and R82T; A47R, M80I, R82T, V89A, and M91L; or A47R, M55I, V78A, M80I, V89A, and M91L. In some embodiments, the amino acid modifications include R45K and A47R. In some embodiments, the amino acid modifications include R45K, A47R, V89A, and M91L. In some embodiments, the amino acid modifications include R45K, A47R, and M80I.In some embodiments, the amino acid modifications include R45K, A47R, M80I, and M91L; R45K, A47R, V78A, M80I, V89A, and M91L; R45K, A47R, M55I, V78A, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, V89A, and M91L; R45K, A47R, M55I, M80I, R82T, V89A, and M91L; R45K, A47R, M80I, and V89A; R45K, A47R, M80I, R82T, V89A, M91L; or R45K, A47R, M55I, M80I, V89A, and M91L. In some embodiments, the amino acid modification comprises R45. In some embodiments, the amino acid modification comprises R45K and V78A. In some embodiments, the amino acid modification comprises V78A. In some embodiments, the amino acid modification comprises V78A and V89A; V78A and M80I; or V78A, M80I, and R82T. In some embodiments, the amino acid modification comprises V89A. In some embodiments, the amino acid modification comprises M80I. 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 according to Aho or Kabat numbering. In some embodiments, the amino acid modification comprises L54P in the light chain variable region according to Aho or Kabat numbering. In some embodiments, the amino acid modification comprises L55W in the light chain variable region according to Aho or Kabat numbering.

[0301] In some embodiments, the anti-TL1A antibody is SEQ ID NO: 301 (X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2]RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR[HCDR3]WGQGTTVTVSS) or SEQ ID NO: 302 (X1VQLVQSGAEVKKPGASVKVSCKAS[HCDR1]WVX2QX3PGQGLEWX4G[HCDR2]RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYC[HCDR3]WGQGTTVTVSS). In some examples, X1 is Q. In some examples, X1 = E. In some examples, X2 = R. In some examples, X2 = K. In some examples, X3 = A. In some examples, X3 = R. In some examples, X4 = M. In some examples, X4 = I. In some examples, X5 = V. In some examples, X5 = A. In some examples, X6 = M. In some examples, X6 = I. In some examples, X7 = R. In some examples, X7 = T. In some examples, X8 = V. In some examples, X8 = A. In some examples, X9 = M. In some embodiments, X9=L. In some embodiments, X1 is at position 1 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X2 is at position 45 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X3 is at position 47 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X4 is at position 55 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X5 is at position 78 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X6 is at position 80 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X7 is at position 82 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X8 is at position 89 of IGHV1-46*02 as determined by Aho or Kabat numbering. In some embodiments, X9 is at position 91 of IGHV1-46*02 as determined by Aho or Kabat numbering.

[0302] In one aspect, provided herein is a first embodiment of an anti-TL1A antibody comprising a heavy chain framework comprising IGHV1-46*02, or a variant thereof, wherein the 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 from the IGHV1-46*02 framework. Additional embodiments include: (2) the anti-TL1A of embodiment (1), wherein the heavy chain framework comprises SEQ ID NO: 301; (3) the anti-TL1A of embodiment 2, wherein X1 = Q; (4) the anti-TL1A of embodiment 2, wherein X1 = E; (5) the anti-TL1A of any one of embodiments 2-4, wherein X2 = R. (6) Anti-TL1A of any one of embodiments 2 to 4, wherein X2=K. (7) Anti-TL1A of any one of embodiments 2 to 6, wherein X3=A. (8) Anti-TL1A of any one of embodiments 2 to 6, wherein X3=R. (9) Anti-TL1A of any one of embodiments 2 to 8, wherein X4=M. (10) Anti-TL1A of any one of embodiments 2 to 8, wherein X4=I. (11) Anti-TL1A of any one of embodiments 2 to 10, wherein X5=V. (12) Anti-TL1A of any one of embodiments 2 to 10, wherein X5=A. (13) Anti-TL1A of any one of embodiments 2 to 12, wherein X6=M. (14) Anti-TL1A of any one of embodiments 2 to 12, wherein X6=I. (15) Anti-TL1A of any one of embodiments 2 to 14, wherein X7=R. (16) The anti-TL1A of any one of embodiments 2 to 14, wherein X7 = T. (17) The anti-TL1A of any one of embodiments 2 to 16, wherein X8 = V. (18) The anti-TL1A of any one of embodiments 2 to 16, wherein X8 = A. (19) The anti-TL1A of any one of embodiments 2 to 18, wherein X9 = M. (20) The anti-TL1A of any one of embodiments 2 to 4, wherein X9 = L. (21) The anti-TL1A of any one of embodiments 1 to 20, comprising antibody A. (22) The anti-TL1A of any one of embodiments 1 to 20, comprising antibody B. (23) The anti-TL1A of any one of embodiments 1 to 20, comprising antibody C.(24) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody D. (25) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody E. (26) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody F. (27) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody G or I. (28) Anti-TL1A of any one of embodiments 1 to 20, comprising antibody H. (34) Anti-TL1A of any one of embodiments 1 to 33, comprising a light chain framework comprising IGKV3-20*01 or a variant thereof, wherein the variant comprises about 1 to about 2 substitutions, or about 1 to about 20 amino acid substitutions, or 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-TL1A antibody of embodiment 34, wherein X10 is L. (36) The anti-TL1A antibody of embodiment 34, wherein X10 is P. (37) The anti-TL1A antibody of any one of embodiments 34 to 36, wherein X11 is L. (38) The anti-TL1A antibody of any one of embodiments 34 to 36, wherein X11 is W.

[0303] In some embodiments, the anti-TL1A antibody is SEQ ID NO: 303 (EIVLTQSPGTLSLSPGERATLSC[LCDR1]WYQQKPGQAPRX10X11IY[LCDR2]GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC[LCDR3]FGGGTKLEIK). In some examples, X10 is L. In some examples, X10 is P. In some examples, X11 is L. In some examples, X11 is W. In some embodiments, X10 is at position 54 of IGKV3-20*01 as determined by Aho or Kabat numbering. In some embodiments, X11 is at position 55 of IGKV3-20*01 as determined by Aho or Kabat numbering.

[0304] In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising IGHV1-46*02. In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising from about 1 to about 20 amino acid substitutions from SEQ ID NO: 316. In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising from about 1 to about 9 amino acid substitutions from SEQ ID NO: 316. In some embodiments, the anti-TL1A antibody comprises a heavy chain framework comprising a variant of IGHV1-46*02 comprising from 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 from SEQ ID NO: 316. In some examples, the heavy chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises R45K as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises A47R as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises M55I as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises V78A as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises M80I as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises R82T as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises V89A as determined by Aho or Kabat numbering. In some examples, the heavy chain framework substitution comprises M91L as determined by Aho or Kabat numbering.

[0305] In some embodiments, the anti-TL1A antibody comprises a light chain framework comprising IGKV3-20*01. In some embodiments, the anti-TL1A antibody comprises a variant of IGKV3-20*01 comprising about 1 to about 20 amino acid substitutions from SEQ ID NO: 317. In some embodiments, the anti-TL1A antibody comprises a variant of IGKV3-20*01 comprising about 1 amino acid substitution from SEQ ID NO: 317. In some embodiments, the anti-TL1A antibody comprises a light chain framework comprising a variant of IGKV3-20*01 comprising about 2 amino acid substitutions from SEQ ID NO: 317. In some embodiments, the anti-TL1A antibody comprises a light chain framework comprising a variant of IGKV3-20*01 comprising 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 from SEQ ID NO: 317. In some instances, the light chain framework substitution comprises Q1E, as determined by Aho or Kabat numbering. In some instances, the light chain framework substitution comprises R45K, as determined by Aho or Kabat numbering.

[0306] In some embodiments, the anti-TL1A antibody comprises a heavy chain FR1 described by SEQ ID NO: 304. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR2 described by SEQ ID NO: 305. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR2 described by SEQ ID NO: 313. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 306. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 307. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 314. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR3 described by SEQ ID NO: 315. In some embodiments, the anti-TL1A antibody comprises a heavy chain FR4 described by SEQ ID NO: 308. In some embodiments, the anti-TL1A antibody comprises a light chain FR1 described by SEQ ID NO: 309. In some embodiments, the anti-TL1A antibody comprises a light chain FR2 described by SEQ ID NO: 310. In some embodiments, the anti-TL1A antibody comprises a light chain FR3 set forth by SEQ ID NO: 311. In some embodiments, the anti-TL1A antibody comprises a light chain FR4 set forth by SEQ ID NO: 312.

[0307] In some embodiments, the anti-TL1A antibody comprises the framework region of Table 9A. [Table 5-1] [Table 5-2]

[0308] Exemplary Anti-TL1A Variable Regions

[0309] In one aspect, the present specification provides a heavy chain variable region comprising an amino acid sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOs: 101 to 169 or 420 to 427. and a light chain variable region that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOs: 201-220 or 430-437.

[0310] Further provided herein is a first embodiment of an anti-TL1A antibody comprising a heavy chain variable region and a light chain variable region. Additional non-limiting embodiments include: (Embodiment 2) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, or a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 101. (Embodiment 3) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 102. (Embodiment 4) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 103. (Embodiment 5) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 104.(Embodiment 6) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 105. (Embodiment 7) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 106, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 106. (Embodiment 8) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, or wherein the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 107. (Embodiment 9) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, or wherein the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 108.(Embodiment 10) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109, or wherein the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 109. (Embodiment 11) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 110, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 110. (Embodiment 12) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 111, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 111. (Embodiment 13) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 112, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 112.(Embodiment 14) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 113, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 113. (Embodiment 15) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 114. (Embodiment 16) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 115, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 115. (Embodiment 17) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 116.(Embodiment 18) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 117. (Embodiment 19) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 118, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 118. (Embodiment 20) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 119. (Embodiment 21) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 120, or wherein the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 120.(Embodiment 22) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 121. (Embodiment 23) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 122. (Embodiment 24) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 123, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 123. (Embodiment 25) The heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, or the heavy chain variable region comprises a sequence at least about 1, 2, 3, 4, 5, 6, 7, or 80% identical to SEQ ID NO: 124. (Embodiment 26) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 125, or wherein the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 125. (Embodiment 27) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 126. (Embodiment 28) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 127. (Embodiment 29) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 128.(Embodiment 30) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 129, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 129. (Embodiment 31) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 130. (Embodiment 32) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 131, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 131. (Embodiment 33) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 132.(Embodiment 34) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 133, or the heavy chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 133. (Embodiment 35) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 134, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 134. (Embodiment 36) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 135, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 135. (Embodiment 37) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 136, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 136.(Embodiment 38) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 137, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 137. (Embodiment 39) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 138, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 138. (Embodiment 40) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 139, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 139. (Embodiment 41) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 140, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 140.(Embodiment 42) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 141, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 141. (Embodiment 43) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 142, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 142. (Embodiment 44) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 143, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 143. (Embodiment 45) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 144, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 144.(Embodiment 46) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 145, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 145. (Embodiment 47) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 146, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 146. (Embodiment 48) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 147, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 147. (Embodiment 49) The heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 148, or the heavy chain variable region comprises a sequence at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 1 identical to SEQ ID NO: 148. (Embodiment 50) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 149, or wherein the heavy chain variable region comprises a sequence with about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 149. (Embodiment 51) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 150, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 150. (Embodiment 52) ​​An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 151, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 151. (Embodiment 53) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 152, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 152.(Embodiment 54) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 153, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 153. (Embodiment 55) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 154, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 154. (Embodiment 56) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 155, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 155. (Embodiment 57) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 156, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 156.(Embodiment 58) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 157, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 157. (Embodiment 59) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 158, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 158. (Embodiment 60) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 159, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 159. (Embodiment 61) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 160, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 160.(Embodiment 62) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 161, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 161. (Embodiment 63) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 162, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 162. (Embodiment 64) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 163, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 163. (Embodiment 65) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 164, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 164.(Embodiment 66) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 165, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 165. (Embodiment 67) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 166, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 166. (Embodiment 68) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 167, or wherein the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 167. (Embodiment 69) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 168 or 169, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 168 or 169.(Embodiment 70) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, 421, or 422, or the heavy chain variable region comprises a sequence that has about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 420, 421, or 422.

[0311] (Embodiment 71) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 201. (Embodiment 72) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 202. (Embodiment 73) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 203, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 203. (Embodiment 74) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 204.(Embodiment 75) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 205. (Embodiment 76) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 206. (Embodiment 77) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 207, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 207. (Embodiment 78) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 208, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 208.(Embodiment 79) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 209, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 209. (Embodiment 80) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 210, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 210. (Embodiment 81) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 211, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 211. (Embodiment 82) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 212, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 212.(Embodiment 83) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 213, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 213. (Embodiment 84) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 214, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 214. (Embodiment 85) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 215, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 215. (Embodiment 86) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 216, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 216.(Embodiment 87) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 217, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 217. (Embodiment 88) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 218, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 218. (Embodiment 89) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 219 or 220, or the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 219 or 220. (Embodiment 90) An anti-TL1A antibody of any one of embodiments 1 to 70, wherein the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430, 431, or 432, or wherein the light chain variable region comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions or deletions compared to SEQ ID NO: 430, 431, or 432.

[0312] (Embodiment 91) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 92) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 93) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.(Embodiment 94) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 95) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0313] (Embodiment 96) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 103, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 97) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 106, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 98) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.(Embodiment 99) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 100) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.

[0314] (Embodiment 101) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 102) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 109, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 103) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 203.(Embodiment 104) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 108, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 105) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0315] (Embodiment 106) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 107, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 107) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 110, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 108) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 111, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.(Embodiment 109) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 112, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 110) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 113, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0316] (Embodiment 111) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 112) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 115, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 113) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.(Embodiment 114) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 115) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 118, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.

[0317] (Embodiment 116) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 114, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 117) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 102, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 118) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 104, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.(Embodiment 119) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 120) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 119, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0318] (Embodiment 121) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 101, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 122) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 105, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204. (Embodiment 123) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 120, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 204.(Embodiment 124) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 125) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.

[0319] (Embodiment 126) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 207. (Embodiment 127) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 123, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202. (Embodiment 128) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 202.(Embodiment 129) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 125, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 130) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 116, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.

[0320] (Embodiment 131) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 117, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 132) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 133) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.(Embodiment 134) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 127, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 135) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 121, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0321] (Embodiment 136) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 137) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 138) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 122, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206.(Embodiment 139) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 140) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 124, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.

[0322] (Embodiment 141) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 142) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 128, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 206. (Embodiment 143) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 129, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.(Embodiment 144) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 145) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 131, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.

[0323] (Embodiment 146) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 147) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 133, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 148) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 134, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205.(Embodiment 149) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 135, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 205. (Embodiment 150) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 126, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 151) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 130, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201.(Embodiment 152) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 132, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 201. (Embodiment 153) The anti-TL1A antibody of embodiment 1, comprising A500. (Embodiment 154) The anti-TL1A antibody of embodiment 1, comprising A501. (Embodiment 155) The anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 420, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 430. (Embodiment 156) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 421, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 431.(Embodiment 157) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 422, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 432. (Embodiment 158) An anti-TL1A antibody of embodiment 1, wherein the heavy chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 427, or the light chain variable region comprises a sequence at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 437.

[0324] Exemplary Anti-TL1A Constant Regions

[0325] In some embodiments, one or more amino acid modifications may be introduced into the fragment crystallizable (Fc) region of a human or humanized antibody, thereby generating a variant Fc region. The Fc region may include the C-terminal region of an immunoglobulin heavy chain, which region includes a hinge region, a CH2 domain, a CH3 domain, or any combination thereof. As used herein, Fc region includes native-sequence Fc regions and variant Fc regions. A variant Fc region may comprise a human Fc region sequence (e.g., a human IgG1, IgG2, IgG3, or IgG4 Fc region) containing an amino acid modification (e.g., substitution, addition, or deletion) at one or more amino acid positions. In exemplary embodiments, the Fc region comprises any one of SEQ ID NOs: 320-367. In some embodiments, an anti-TL1A antibody comprises a constant region comprising any one of SEQ ID NOs: 319, 368-381.

[0326] In some embodiments, the antibodies of the present disclosure have reduced effector functions compared to human IgG. Effector function refers to biological events 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 cellular phagocytosis (ADCP), cytokine secretion, immune complex-mediated antigen uptake by antigen-presenting cells, downregulation of cell surface receptors (e.g., B cell receptors), and B cell activation. In some examples, 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 antibodies on target cells and subsequently cause lysis of the target cells. In some examples, complement-dependent cytotoxicity (CDC) refers to the lysis of target cells in the presence of complement, where the complement pathway is initiated by the binding of C1q to target-bound antibodies.

[0327] Some Fc regions naturally lack effector function, and some Fc regions may contain mutations that reduce effector function: for example, IgG4 has reduced ADCC and CDC activity, and IgG2 has reduced ADCC activity.

[0328] The present disclosure provides antibodies comprising a non-variant Fc region, i.e., antibodies comprising an Fc region characterized by exhibiting reduced ADCC by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or more compared to an antibody having the same sequence identity except for the ADCC-reducing substitutions (e.g., human IgG1, SEQ ID NO: 320). The present disclosure provides antibodies comprising a non-variant Fc region, i.e., antibodies comprising an Fc region characterized by exhibiting reduced CDC by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or more compared to an antibody having the same sequence identity except for the CDC-reducing substitutions (e.g., human IgG1, SEQ ID NO: 320). In certain embodiments, antibodies of the present disclosure have reduced effector function compared to human IgG1. In certain embodiments, the antibodies herein have no detectable ADCC activity. In certain embodiments, the reduced and / or decreased ADCC activity may be due to a reduced affinity exhibited by the antibodies of the invention for Fc ligands and / or receptors. In certain embodiments, the antibodies herein do not exhibit detectable CDC activity. In certain embodiments, the reduced and / or decreased CDC activity may be due to a reduced affinity exhibited by the antibodies of the invention for Fc ligands and / or receptors. Measurement of effector function may be performed as described in Example 3.

[0329] In some embodiments, antibodies comprising an Fc region described herein exhibit reduced affinity for C1q relative to an unmodified antibody (e.g., a human IgG1 having SEQ ID NO: 320). 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, at least 100-fold, or at least 200-fold less affinity for the C1q receptor than the unmodified antibody. In some embodiments, the antibodies herein...

Claims

1. A method for treating inflammation in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

2. The method of claim 1 , wherein the subject has inflammation in the skin.

3. A method for treating fibrosis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

4. The method of claim 3 , wherein the subject has fibrosis in the skin.

5. A method for treating a skin disease and / or condition in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

6. The method of any one of claims 1 to 5, wherein the subject has a chronic skin disorder.

7. The method of any one of claims 1 to 6, wherein the subject has systemic sclerosis.

8. The method of any one of claims 1 to 6, wherein the subject has psoriasis.

9. The method of any one of claims 1 to 6, wherein the subject has lupus.

10. The method of any one of claims 1 to 6, wherein the subject has eczema.

11. The method of any one of claims 1 to 6, wherein the subject has dermatomyositis.

12. 7. The method of any one of claims 1 to 6, wherein the subject has systemic sclerosis or scleroderma, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

13. The method of any one of claims 1 to 6, wherein the subject has hidradenitis suppurativa.

14. The method of any one of claims 1 to 6, wherein the subject has atopic dermatitis.

15. The method of any one of claims 1 to 6, wherein the subject has vitiligo.

16. The method of any one of claims 1 to 6, wherein the subject has alopecia areata.

17. The method according to any one of claims 1 to 2 and 6, wherein the inflammation in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

18. The method according to any one of claims 3 to 4 and 6, wherein the fibrosis in the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

19. The method according to any one of claims 5 to 6, wherein the disease and / or condition of the skin is hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata.

20. A method for treating hidradenitis suppurativa in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

21. A method for treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

22. A method for treating psoriasis in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

23. A method for treating vitiligo in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

24. A method of treating alopecia areata in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof that binds to tumor necrosis factor-like protein 1A (anti-TL1A antibody or antigen-binding fragment).

25. The method of any one of claims 1 to 24, wherein the anti-TL1A antibody or antigen-binding fragment is administered in a pharmaceutical composition.

26. 27. The method of claim 26, wherein the pharmaceutical composition comprises the anti-TL1A antibody or antigen-binding fragment at a concentration of greater than about 150 mg / mL.

27. 27. The method of claim 26, wherein the concentration is greater than about 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, or 250 mg / mL.

28. 27. The method of claim 26, wherein the concentration is from about 150 mg / mL to about 250 mg / mL.

29. 27. The method of claim 26, wherein the concentration is from about 175 mg / mL to about 225 mg / mL.

30. 30. The method of any one of claims 25 to 29, wherein the pharmaceutical composition is administered subcutaneously.

31. 31. The method of any one of claims 25 to 30, wherein about 150 mg to about 500 mg of the anti-TL1A antibody or antigen-binding fragment is present in the composition.

32. 32. The method of any one of claims 25 to 31, wherein the composition has a total volume of about 2 mL or less.

33. The method of any one of claims 25 to 32, wherein the pharmaceutical composition comprises a therapeutically effective dose of the anti-TL1A antibody or antigen-binding fragment.

34. 34. The method of any one of claims 25-33, wherein the composition has a total volume of about 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, or 0.8 mL or less.

35. 35. The method of any one of claims 25 to 34, wherein the composition has a total volume of about 0.5 mL to about 1.5 mL.

36. The method of any one of claims 25 to 35, wherein the composition has a viscosity of less than about 20 cP.

37. 37. The method of claim 36, wherein the composition has a viscosity of less than about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, or 5 cP.

38. 38. The method of any one of claims 25 to 37, wherein the composition has a viscosity of from about 1 cP to about 20 cP.

39. 39. The method of any one of claims 25 to 38, wherein the pharmaceutical composition has an aggregation rate of anti-TL1A antibodies or antigen-binding fragments of less than about 5% of the total anti-TL1A antibodies or antigen-binding fragments in the composition as measured by size exclusion chromatography.

40. 40. The method of claim 39, wherein the aggregation is less than about 4.5, 4, 3.5, 3, 2.5, 2, 1.5, 1, or 0.5%.

41. The method of any one of claims 25 to 39, wherein the composition comprises a surfactant.

42. 42. The method of claim 41, wherein the surfactant comprises a non-ionic surfactant.

43. 43. The method of claim 42, wherein the non-ionic surfactant comprises polysorbate-20.

44. 44. The method of any one of claims 41 to 43, wherein the surfactant is present at a concentration of about 0.005% to about 0.05% of the composition.

45. 45. The method of claim 44, wherein the surfactant is present at a concentration of about 0.01% to about 0.02% of the composition.

46. The method of any one of claims 25 to 45, wherein the composition comprises a salt.

47. 47. The method of claim 46, wherein the salt comprises sodium chloride, glycine, lysine hydrochloride, arginine hydrochloride, arginine glutamate, potassium chloride, magnesium chloride, or calcium chloride, or a combination thereof.

48. 48. The method of claim 47, wherein the salt comprises sodium chloride.

49. 48. The method of claim 47, wherein the salt comprises lysine-HCl.

50. 50. The method of any one of claims 46 to 49, wherein the salt is present in the composition at a concentration of about 10 mM to about 100 mM.

51. 51. The method of claim 50, wherein the salt is present in the composition at a concentration of about 25 mM.

52. 51. The method of claim 50, wherein the salt is present in the composition at a concentration of about 40 mM.

53. The method of any one of claims 25 to 52, wherein the composition comprises a stabilizer.

54. 54. The method of claim 53, wherein the stabilizer comprises a sugar, a polyol, an amino acid, or a polymer, a cyclodextrin (e.g., HP-b-CD), or a combination thereof.

55. 55. The method of claim 54, wherein the stabilizer comprises the sugar.

56. 56. The method of claim 55, wherein the sugar comprises sucrose, glucose, trehalose, maltose, or lactose, or a combination thereof.

57. 57. The method of claim 56, wherein the sugar comprises sucrose.

58. 58. The method of any one of claims 53 to 57, wherein the stabilizer is present in the composition at a concentration of about 50 mM to about 300 mM.

59. 59. The method of claim 58, wherein the stabilizer is present at a concentration of about 200 mM to about 280 mM.

60. 60. The method of claim 59, wherein the stabilizer is present at a concentration of about 220 to about 240 mM.

61. The method of any one of claims 25 to 60, wherein the composition comprises a buffering agent.

62. 62. The method of claim 61, wherein the buffer comprises acetate, phosphate, citrate, glutamate, succinate, gluconate, histidine, glycylglycine, citric acid, tris(tris(hydroxymethyl)aminomethane), or diethanolamine, or a combination thereof.

63. 63. The method of claim 62, wherein the buffer comprises an acetate buffer.

64. 64. The method of any one of claims 61 to 63, wherein the buffering agent is present in the composition at a concentration of about 10 mM to about 50 mM.

65. 65. The method of claim 64, wherein the composition comprises about 20 mM buffer.

66. 66. The method of any one of claims 25 to 65, wherein the composition has a pH of from about 4.5 to about 8.

0.

67. 67. The method of claim 66, wherein the composition has a pH of about 4.5 to about 7.

5.

68. 68. The method of claim 67, wherein the composition has a pH of about 5 to about 5.

5.

69. 69. The method of claim 68, wherein the composition has a pH of about 5.

3.

70. 70. The method of any one of claims 1-69, wherein the anti-TL1A antibody or antigen-binding fragment is administered to the subject in a first dose of up to about 1000 mg.

71. 70. The method of any one of claims 1-69, wherein the anti-TL1A antibody or antigen-binding fragment is administered to the subject in a first dose of about 150 mg to about 1000 mg.

72. 72. The method of claim 71, wherein the first dose is from about 500 mg to about 1000 mg.

73. 73. The method of claim 72, wherein the first dose is from about 500 mg to about 800 mg.

74. 74. The method of any one of claims 70-73, wherein the first dose is administered to the subject at a first time point and the second dose is administered to the subject at a second time point.

75. 75. The method of claim 74, wherein the second time point is 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 31 days after the first time point.

76. 75. The method of claim 74, wherein the second time point is about 1, 2, 3, or 4 weeks after the first time point.

77. 77. The method of any one of claims 74-76, wherein the second dose comprises up to about 1000 mg of anti-TL1A antibody or antigen-binding fragment.

78. 77. The method of any one of claims 74-76, wherein the second dose comprises from about 150 mg to about 1000 mg.

79. 79. The method of claim 78, wherein the second dose comprises from about 150 mg to about 600 mg.

80. 80. The method of any one of claims 74-79, wherein a third dose of an anti-TL1A antibody or antigen-binding fragment is administered to the subject at a third time point.

81. 81. The method of claim 80, wherein the third time point is 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 31 days after the second time point.

82. 81. The method of claim 80, wherein the third time point is about 1, 2, 3, or 4 weeks after the second time point.

83. 83. The method of any one of claims 80-82, wherein the third dose comprises up to about 1000 mg of anti-TL1A antibody or antigen-binding fragment.

84. 83. The method of any one of claims 80-82, wherein the third dose comprises from about 150 mg to about 1000 mg.

85. 85. The method of claim 84, wherein the third dose comprises from about 150 mg to about 600 mg.

86. 86. The method of any one of claims 80-85, wherein a fourth dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a fourth time point.

87. 87. The method of claim 86, wherein the fourth time point is 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 31 days after the third time point.

88. 87. The method of claim 86, wherein the fourth time point is about 1, 2, 3, or 4 weeks after the third time point.

89. 89. The method of any one of claims 86-88, wherein the fourth dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

90. 89. The method of any one of claims 86-88, wherein the fourth dose comprises from about 150 mg to about 1000 mg.

91. 91. The method of claim 90, wherein the fourth dose comprises from about 150 mg to about 600 mg.

92. 92. The method of any one of claims 86-91, wherein a fifth dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a fifth time point.

93. 93. The method of claim 92, wherein the fifth time point is 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 31 days after the fourth time point.

94. 93. The method of claim 92, wherein the fifth time point is about 1, 2, 3, or 4 weeks after the fourth time point.

95. 95. The method of any one of claims 92-94, wherein the fifth dose comprises up to about 1000 mg of anti-TL1A antibody or antigen-binding fragment.

96. 95. The method of any one of claims 92-94, wherein the fifth dose comprises from about 150 mg to about 1000 mg.

97. 97. The method of claim 96, wherein the fifth dose comprises from about 150 mg to about 600 mg.

98. 98. The method of any one of claims 92-97, wherein a sixth dose of the anti-TL1A antibody or antigen-binding fragment is administered to the subject at a sixth time point.

99. 99. The method of claim 98, wherein the sixth time point is 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 31 days after the fifth time point.

100. 99. The method of claim 98, wherein the sixth time point is about 1, 2, 3, or 4 weeks after the fifth time point.

101. 101. The method of any one of claims 98-100, wherein the sixth dose comprises up to about 1000 mg of the anti-TL1A antibody or antigen-binding fragment.

102. 101. The method of any one of claims 98-100, wherein the sixth dose comprises from about 150 mg to about 1000 mg.

103. 103. The method of claim 102, wherein the sixth dose comprises from about 150 mg to about 600 mg.

104. 104. The method of any one of claims 70-103, wherein additional doses of the anti-TL1A antibody or antigen-binding fragment are administered to the subject at each of one or more additional time points.

105. 105. The method of claim 104, wherein the one or more additional time points comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 additional time points.

106. 105. The method of claim 104, wherein the composition is administered to the subject at about 12 additional time points.

107. 107. The method of any one of claims 104-106, wherein each additional time point is independently 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 31 days after the previous time point.

108. 107. The method of any one of claims 104-106, wherein each additional time point is independently about 1, 2, 3, or 4 weeks after the previous time point.

109. 109. The method of claim 108, wherein at least one of the additional time points is about two weeks after the previous time point.

110. 110. The method of any one of claims 104-109, wherein the additional dose comprises up to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment.

111. 110. The method of any one of claims 104-109, wherein the additional dose comprises about 150 mg to about 1000 mg of an anti-TL1A antibody or antigen-binding fragment.

112. 112. The method of claim 111, wherein the additional dose is about 175 mg to about 300 mg of an anti-TL1A antibody or antigen-binding fragment.

113. 1. A method for neutralizing monomeric and trimeric TL1A in a subject having skin inflammation and / or skin fibrosis, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment; the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A; the antibody or antigen-binding fragment blocks the interaction of TL1A with DR3; the concentration of TL1A in diseased tissue of the subject is reduced to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; A method in which the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

114. 114. The method of claim 113, wherein the subject has one or more inflammatory conditions selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

115. 115. The method of claim 113 or 114, wherein the subject has hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

116. 1. A method of reducing the concentration of TL1A in diseased tissue of a subject having skin inflammation and / or skin fibrosis, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment; thereby reducing the concentration of TL1A in the diseased tissue of the subject to less than the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; A method in which the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

117. 1. A method of treating skin inflammation and / or skin fibrosis in a subject in need thereof, comprising: (a) administering to said subject an anti-TL1A antibody or antigen-binding fragment; the anti-TL1A antibody or antigen-binding fragment is administered at an effective dose such that the concentration of TL1A in the diseased tissue of the subject after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject who does not have skin inflammation and / or skin fibrosis; A method in which the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

118. 1. A method of treating skin inflammation and / or skin fibrosis in a subject in need thereof, comprising: (a) administering to the subject an effective dose of an anti-TL1A antibody or antigen-binding fragment; (b) reducing the concentration of TL1A in diseased tissue of the subject to below the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis; A method in which the diseased tissue comprises any one or more selected from the group consisting of the epidermis, dermis, subcutaneous tissue, connective tissue in the skin, fibrotic tissue in the skin, other tissues having skin inflammation and / or skin fibrosis, and other tissues involved in the pathogenesis of said skin inflammation and / or skin fibrosis.

119. 119. The method of any one of claims 113-118, wherein the effective dose comprises an induction regimen.

120. The method of any one of claims 113 to 119, further comprising (c) maintaining TL1A in the diseased tissue of the subject at a concentration less than the concentration of TL1A in the corresponding tissue of the control subject.

121. 121. The method of claim 120, wherein the TL1A in the diseased tissue of the subject is maintained with a maintenance regimen of the anti-TL1A antibody or antigen-binding fragment.

122. 122. The method of claim 121, wherein the induction regimen and the maintenance regimen are the same.

123. 122. The method of claim 121, wherein the induction regimen and the maintenance regimen are different.

124. 124. The method of any one of claims 121 to 123, wherein the maintenance regimen is administered after the induction regimen.

125. 125. The method of any one of claims 114-124, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100-fold or more TL1A during the induction regimen compared to the corresponding tissue in the control subject.

126. 125. The method of any one of claims 114-124, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of initiating the induction regimen.

127. 125. The method of any one of claims 114-124, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to the corresponding tissue in the control subject.

128. 128. The method of any one of claims 119-127, wherein the induction regimen comprises a single administration of the anti-TL1A antibody or antigen-binding fragment.

129. 129. The method of claim 128, wherein the anti-TL1A antibody or antigen-binding fragment is administered at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

130. 128. The method of any one of claims 119-127, wherein the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment.

131. the induction regimen comprising: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 500 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10, or (v) The method of any one of claims 119-127 and 130, comprising administration of 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10.

132. 131. The method of any one of claims 119-127 and 130, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

133. 133. The method of any one of claims 119-127, 130, and 132, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

134. 133. The method of any one of claims 119-127, 130, and 132, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first two doses, followed by administration once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

135. 135. The method of any one of claims 120-134, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject.

136. 132. The method of any one of claims 120-131, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

137. 132. The method of any one of claims 120-131, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks or more of initiation of the maintenance regimen.

138. 138. The method of any one of claims 121-137, wherein the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment.

139. the maintenance regimen comprising: (i) 500 mg / dose every 2 weeks; (ii) 400 mg / dose every 2 weeks; (iii) 300 mg / dose every 2 weeks; (iv) 250 mg / dose every 2 weeks; (v) 200 mg / dose every 2 weeks; (vi) 150 mg / dose every 2 weeks; (vii) 100 mg / dose every 2 weeks; (viii) 50 mg / dose every 2 weeks; (ix) 500 mg / dose every 4 weeks; (x) 400 mg / dose every 4 weeks; (xi) 300 mg / dose every 4 weeks; (xii) 250 mg / dose every 4 weeks; (xiii) 200 mg / dose every 4 weeks; (xiv) 150 mg / dose every 4 weeks; (xv) 100 mg / dose every 4 weeks; (xvi) 50 mg / dose every 4 weeks; (xvii) 500 mg / dose every 6 weeks; (xviii) 400 mg / dose every 6 weeks; (xix) 300 mg / dose every 6 weeks; (xx) 250 mg / dose every 6 weeks; (xxi) 200 mg / dose every 6 weeks; (xxii) 150 mg / dose every 6 weeks; (xxiii) 100 mg / dose every 6 weeks; (xxiv) 50 mg / dose every 6 weeks; (xxv) 500 mg / dose every 8 weeks; (xxvi) 400 mg / dose every 8 weeks; (xxvii) 300 mg / dose every 8 weeks; (xxviii) 250 mg / dose every 8 weeks; (xxix) 200 mg / dose every 8 weeks; (xxx) 150 mg / dose every 8 weeks; (xxxi) 100 mg / dose every 8 weeks, or (xxxii) The method of any one of claims 121-138, comprising administration of the anti-TL1A antibody or antigen-binding fragment at 50 mg / dose every 8 weeks.

140. 139. The method of any one of claims 121-138, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

141. 141. The method of any one of claims 121-138 and 140, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

142. 142. The method of any one of claims 121-141, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every four weeks.

143. 142. The method of any one of claims 121-141, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every four weeks.

144. 144. The method of any one of claims 121-143, wherein the maintenance regimen lasts for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

145. The method of any one of claims 116 to 144, wherein the antibody or antigen-binding fragment binds to both monomeric and trimeric TL1A, and the antibody or antigen-binding fragment blocks binding of TL1A to DR3.

146. 146. The method of any one of claims 113-145, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the monomeric TL1A in the subject's blood is occupied by the anti-TL1A antibody or antigen-binding fragment.

147. 147. The method of any one of claims 113-146, wherein at least 60%, 65%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the trimeric TL1A in the subject's blood is occupied by the anti-TL1A antibody or antigen-binding fragment.

148. Dissociation equilibrium constant (K Ｄ－ｍｏｎｏｍｅｒ The binding affinity of the antibody or antigen-binding fragment to monomeric TL1A, as measured by a dissociation equilibrium constant (K Ｄ－ｔｒｉｍｅｒ 148. The method of any one of claims 113 to 147, wherein the binding affinity of the antibody or antigen-binding fragment to trimeric TL1A is measured by:

149. The above K Ｄ－ｍｏｎｏｍｅｒ However, the above K Ｄ－ｔｒｉｍｅｒ 149. The method of claim 148, wherein the nucleotide sequence is within 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times of the nucleotide sequence.

150. The above K Ｄ－ｍｏｎｏｍｅｒ The method of claim 148 or 149, wherein the .alpha.-tocopherol concentration is 0.06 nM or less.

151. The above K Ｄ－ｔｒｉｍｅｒ The method of any one of claims 148 to 150, wherein the concentration of ATP is 0.06 nM or less.

152. 152. The method of any one of claims 115-151, wherein the subject has one or more conditions of skin inflammation and / or skin fibrosis selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

153. 153. The method of any one of claims 114-152, wherein the subject has systemic sclerosis, psoriasis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

154. 153. The method of any one of claims 114 to 152, wherein the subject has hidradenitis suppurativa.

155. The method of any one of claims 114 to 152, wherein the subject has atopic dermatitis.

156. 153. The method of any one of claims 114 to 152, wherein the subject has psoriasis.

157. 153. The method of any one of claims 114 to 152, wherein the subject has vitiligo.

158. 153. The method of any one of claims 114 to 152, wherein the subject has alopecia areata.

159. 152. The method of any one of claims 115 to 151, wherein the skin inflammation and / or skin fibrosis is hidradenitis suppurativa.

160. 152. The method of any one of claims 115 to 151, wherein the skin inflammation and / or skin fibrosis is atopic dermatitis.

161. 152. The method of any one of claims 115 to 151, wherein the skin inflammation and / or skin fibrosis is psoriasis.

162. 152. The method of any one of claims 115 to 151, wherein the skin inflammation and / or skin fibrosis is vitiligo.

163. 152. The method of any one of claims 115 to 151, wherein the skin inflammation and / or skin fibrosis is alopecia areata.

164. 152. The method of any one of claims 115 to 151, wherein the skin inflammation and / or skin fibrosis is selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, or alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

165. The effective dose or the induction regimen is determined by a dose determination method, the dose determination method comprising: (i) receiving a parameter of TL1A overproduction in said diseased tissue compared to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (a) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or population pharmacokinetic (popPK) model; (iii) determining the effective dose or the induction regimen such that the concentration of TL1A in the diseased tissue of the subject after step (a) is less than the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis.

166. The method of claim 165, wherein the parameter of TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200-fold or more overproduction compared to TL1A production in the normal reference tissue.

167. The maintenance regimen is determined by a dose-determining method, the dose-determining method comprising: (i) receiving a parameter of TL1A overproduction in said diseased tissue compared to TL1A production in a normal reference tissue; (ii) integrating the parameters received in (i) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model or population pharmacokinetic (popPK) model; (iii) determining the maintenance regimen such that the concentration of TL1A in the diseased tissue of the subject after step (c) is less than the concentration of TL1A in the corresponding tissue of a control subject not having skin inflammation and / or skin fibrosis.

168. 168. The method of claim 167, wherein the parameter of TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100-fold or more overproduction compared to TL1A production in the normal reference tissue.

169. The step (i) of the dose determination method comprises determining the association rate of the antibody to TL1A (k ｏｎ－ｍＡｂ ), the dissociation rate of the antibody from TL1A (k ｏｆｆ－ｍＡｂ ), the synthesis rate of TL1A in normal tissues (k ｓｙｎ－ｎｏｒｍａｌ ), the synthesis rate of TL1A in diseased tissues (k ｓｙｎ－ｄｉｓｅａｓｅ ), and / or the degradation rate of TL1A (k ｄｅｇ－ｔｏｔａｌ－ＴＬ１Ａ 169. The method of any one of claims 165 to 168, further comprising receiving a

170. The association rate of the antibody to TL1A (k ｏｎ－ｍＡｂ ) is the association rate of the antibody to monomeric TL1A (k ｏｎ－ｍｏｎｏｍｅｒ ) and the association rate of the antibody to trimeric TL1A (k ｏｎ－ｔｒｉｍｅｒ ) and the dissociation rate of the antibody from TL1A (k ｏｆｆ－ｍＡｂ ) is the dissociation rate of the antibody from monomeric TL1A (k ｏｆｆ－ｍｏｎｏｍｅｒ ) and the dissociation rate of the antibody from trimeric TL1A (k ｏｆｆ－ｔｒｉｍｅｒ ) and / or the degradation rate of TL1A (k ｄｅｇ－ｔｏｔａｌ－ＴＬ１Ａ ) is the degradation rate of monomeric TL1A (k ｄｅｇ－ＴＬ１Ａ－ｍｏｎｏｍｅｒ ) and the degradation rate of trimeric TL1A (k ｄｅｇ－ＴＬ１Ａ－ｔｒｉｍｅｒ 170. The method of claim 169, comprising:

171. The step (i) of the dose determination method comprises determining the association rate (k ｏｎ－ｍＡｂ－ＦｃＲｎ ), the dissociation rate of the antibody from FcRn (k ｏｆｆ－ｍＡｂ－ＦｃＲｎ ), the association rate of the antibody-TL1A complex to the FcRn receptor (k ｏｎ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ 171. The method of any one of claims 165 to 170, further comprising receiving a

172. The association rate (k ｏｎ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ ) is the association rate of the antibody-monomer-TL1A complex to the FcRn receptor (k ｏｎ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k ｏｎ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ ) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ ) is the dissociation rate of the antibody-monomer-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ 172. The method of claim 171, comprising:

173. The step (i) of the dose determination method includes measuring the clearance rate (k ｄｅｇ－ｍＡｂ－ＦｃＲｎ 173. The method of any one of claims 165 to 172, further comprising receiving a

174. The clearance rate (k ｄｅｇ－ｍＡｂ－ＦｃＲｎ ) is the clearance rate of the antibody from FcRn bound by the antibody-monomer-TL1A complex (k ｄｅｇ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ ) and the clearance rate of the antibody-trimer-TL1A complex-bound FcRn receptor (k ｄｅｇ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ 174. The method of claim 173, comprising:

175. In the dose determination method, (1) k ｏｎ－ｍｏｎｏｍｅｒ and k ｏｎ－ｔｒｉｍｅｒ are the same or different, (2) k ｏｆｆ－ｍｏｎｏｍｅｒ and k ｏｆｆ－ｔｒｉｍｅｒ are the same or different, (3) k ｄｅｇ－ｍｏｎｏｍｅｒ and k ｄｅｇ－ｔｒｉｍｅｒ are the same or different, (4) k ｏｎ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ and k ｏｎ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (5) k ｏｎ－ｍＡｂ－ＦｃＲｎ and k ｏｎ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ are the same or different, (6) k ｏｎ－ｍＡｂ－ＦｃＲｎ and k ｏｎ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (7) k ｏｆｆ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ and k ｏｆｆ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (8) k ｏｆｆ－ｍＡｂ－ＦｃＲｎ and k ｏｆｆ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ are the same or different, (9) k ｏｆｆ－ｍＡｂ－ＦｃＲｎ and k ｏｆｆ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (10) k ｄｅｇ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ and k ｄｅｇ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (11) k ｄｅｇ－ｍＡｂ－ＦｃＲｎ and k ｄｅｇ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (12) k ｄｅｇ－ｍＡｂ－ＦｃＲｎ and k ｄｅｇ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ are the same or different, or (13) The method according to any one of claims 169 to 174, which is any combination of (1) to (12).

176. In the dose determination method, k ｓｙｎ－ｄｉｓｅａｓｅ But, k ｓｙｎ－ｎｏｒｍａｌ 176. The method of any one of claims 165-175, wherein the denaturation rate is up to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more times greater than the denaturation rate.

177. The step (i) of the dose determination method is to determine the rate of TL1A trimerization (k ｏｎ－ＴＬ１Ａ－ｍｏｎｏｍｅｒ－ｔｏ－ｔｒｉｍｅｒ ) and / or the rate of TL1A monomerization (k ｏｆｆ－ＴＬ１Ａ－ｔｒｉｍｅｒ－ｔｏ－ｍｏｎｏｍｅｒ 177. The method of any one of claims 165 to 176, further comprising receiving a

178. 1. A method for determining an effective dosage regimen for administering an anti-TL1A antibody to a subject having skin inflammation and / or skin fibrosis, the method comprising: (a) receiving a parameter of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (b) integrating the parameters received in (a) into an integrated whole-body physiologically based pharmacokinetic (PBPK) model; (c) determining the effective dose regimen of the anti-TL1A antibody in the PBPK model from (b) such that, after administration of the effective dose regimen, the concentration of TL1A in diseased tissue of the subject with skin inflammation and / or skin fibrosis is less than the concentration of TL1A in corresponding tissue of a control subject without skin inflammation and / or skin fibrosis; The method, wherein the diseased tissue comprises any one or more selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

179. 1. A method for determining an effective dosage regimen for administering an anti-TL1A antibody to a subject having skin inflammation and / or skin fibrosis, the method comprising: (a) receiving a parameter of TL1A overproduction in diseased tissue compared to TL1A production in normal reference tissue; (b) integrating the parameters received in (a) into a population pharmacokinetic (popPK) model; (c) determining the effective dose regimen of the anti-TL1A antibody in the popPK model from (b) such that, after administration of the effective dose regimen, the concentration of TL1A in diseased tissue of the subject with skin inflammation and / or skin fibrosis is less than the concentration of TL1A in corresponding tissue of a control subject without skin inflammation and / or skin fibrosis; The method, wherein the diseased tissue comprises any one or more selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

180. The method of claim 178 or 179, wherein the parameter of TL1A overproduction is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200-fold or more overproduction compared to TL1A production in the normal reference tissue.

181. The step (a) determines the association rate of the antibody to TL1A (k ｏｎ－ｍＡｂ ), the dissociation rate of the antibody from TL1A (k ｏｆｆ－ｍＡｂ ), the synthesis rate of TL1A in normal tissues (k ｓｙｎ－ｎｏｒｍａｌ ), the synthesis rate of TL1A in diseased tissues (k ｓｙｎ－ｄｉｓｅａｓｅ ), and / or the degradation rate of TL1A (k ｄｅｇ－ｔｏｔａｌ－ＴＬ１Ａ 181. The method of any one of claims 178 to 180, further comprising receiving a

182. The association rate of the antibody to TL1A (k ｏｎ－ｍＡｂ ) is the association rate of the antibody to monomeric TL1A (k ｏｎ－ｍｏｎｏｍｅｒ ) and the association rate of the antibody to trimeric TL1A (k ｏｎ－ｔｒｉｍｅｒ ) and the dissociation rate of the antibody from TL1A (k ｏｆｆ－ｍＡｂ ) is the dissociation rate of the antibody from monomeric TL1A (k ｏｆｆ－ｍｏｎｏｍｅｒ ) and the dissociation rate of the antibody from trimeric TL1A (k ｏｆｆ－ｔｒｉｍｅｒ ) and / or the degradation rate of TL1A (k ｄｅｇ－ｔｏｔａｌ－ＴＬ１Ａ ) is the degradation rate of monomeric TL1A (k ｄｅｇ－ＴＬ１Ａ－ｍｏｎｏｍｅｒ ) and the degradation rate of trimeric TL1A (k ｄｅｇ－ＴＬ１Ａ－ｔｒｉｍｅｒ 182. The method of claim 181, comprising:

183. The step (a) is a step of measuring the association rate (k ｏｎ－ｍＡｂ－ＦｃＲｎ ), the dissociation rate of the antibody from FcRn (k ｏｆｆ－ｍＡｂ－ＦｃＲｎ ), the association rate of the antibody-TL1A complex to the FcRn receptor (k ｏｎ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ ), and / or the dissociation rate of the antibody-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ 183. The method of any one of claims 178 to 182, comprising receiving a

184. The association rate (k ｏｎ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ ) is the association rate of the antibody-monomer-TL1A complex to the FcRn receptor (k ｏｎ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ ) and the association rate of the antibody-trimer-TL1A complex to the FcRn receptor (k ｏｎ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ ) and / or the dissociation rate of the antibody-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ＴＬ１Ａ）－ＦｃＲｎ ) is the dissociation rate of the antibody-monomer-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ ) and the dissociation rate of the antibody-trimer-TL1A complex from FcRn (k ｏｆｆ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ 184. The method of claim 183, comprising:

185. The step (a) determines the clearance rate (k ｄｅｇ－ｍＡｂ－ＦｃＲｎ 185. The method of any one of claims 178 to 184, further comprising receiving a

186. The clearance rate (k ｄｅｇ－ｍＡｂ－ＦｃＲｎ ) is the clearance rate of the antibody from FcRn bound by the antibody-monomer-TL1A complex (k ｄｅｇ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ ) and the clearance rate of the antibody-trimer-TL1A complex-bound FcRn receptor (k ｄｅｇ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ 186. The method of claim 185, further comprising:

187. 187. The method of any one of claims 178-186, wherein the subject has one or more inflammatory conditions selected from the group consisting of hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, chronic skin disorders, systemic sclerosis, lupus, eczema, and dermatomyositis.

188. 188. The method of any one of claims 178-187, wherein the subject has hidradenitis suppurativa, atopic dermatitis, psoriasis, vitiligo, alopecia areata, systemic sclerosis, lupus, dermatomyositis, eczema, epidermolysis bullosa, mastocytosis, keloid, acne, rosacea, or bullous pemphigoid, or a combination thereof.

189. (1) k ｏｎ－ｍｏｎｏｍｅｒ and k ｏｎ－ｔｒｉｍｅｒ are the same or different, (2) k ｏｆｆ－ｍｏｎｏｍｅｒ and k ｏｆｆ－ｔｒｉｍｅｒ are the same or different, (3) k ｄｅｇ－ｍｏｎｏｍｅｒ and k ｄｅｇ－ｔｒｉｍｅｒ are the same or different, (4) k ｏｎ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ and k ｏｎ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (5) k ｏｎ－ｍＡｂ－ＦｃＲｎ and k ｏｎ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ are the same or different, (6) k ｏｎ－ｍＡｂ－ＦｃＲｎ and k ｏｎ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (7) k ｏｆｆ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ and k ｏｆｆ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (8) k ｏｆｆ－ｍＡｂ－ＦｃＲｎ and k ｏｆｆ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ are the same or different, (9) k ｏｆｆ－ｍＡｂ－ＦｃＲｎ and k ｏｆｆ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (10) k ｄｅｇ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ and k ｄｅｇ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (11) k ｄｅｇ－ｍＡｂ－ＦｃＲｎ and k ｄｅｇ－（ｍＡｂ－ｔｒｉＴＬ１Ａ）－ＦｃＲｎ are the same or different, (12) k ｄｅｇ－ｍＡｂ－ＦｃＲｎ and k ｄｅｇ－（ｍＡｂ－ｍｏｎｏＴＬ１Ａ）－ＦｃＲｎ are the same or different, or (13) The method according to any one of claims 178 to 188, which is any combination of (1) to (12).

190. k ｓｙｎ－ｄｉｓｅａｓｅ But, k ｓｙｎ－ｎｏｒｍａｌ 190, 200, or more times greater than or equal to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more times greater than or equal to 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150,

191. 191. The method of any one of claims 178-190, wherein the effective dose regimen comprises an induction regimen of the anti-TL1A antibody or antigen-binding fragment.

192. 192. The method of any one of claims 178-191, wherein the effective dosage regimen comprises a maintenance regimen of the anti-TL1A antibody or antigen-binding fragment.

193. 193. The method of claim 192, wherein the induction regimen and the maintenance regimen are the same.

194. 193. The method of claim 192, wherein the induction regimen and the maintenance regimen are different.

195. 195. The method of any one of claims 192-194, wherein the maintenance regimen is administered after the induction regimen.

196. 196. The method of any one of claims 191-195, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 or more times more TL1A during the induction regimen compared to the corresponding tissue in the control subject.

197. 197. The method of any one of claims 191-196, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, or 6 weeks of initiating the induction regimen.

198. 196. The method of any one of claims 178-195, wherein the diseased tissue in the subject produces up to 50, 60, 70, 80, 90, 100 times more TL1A compared to the corresponding tissue in the control subject.

199. 200. The method of any one of claims 191-198, wherein the induction regimen comprises a single administration of the anti-TL1A antibody or antigen-binding fragment.

200. 200. The method of claim 199, wherein the anti-TL1A antibody or antigen-binding fragment is administered at 200 mg / dose, 250 mg / dose, 300 mg / dose, 350 mg / dose, 400 mg / dose, 450 mg / dose, 500 mg / dose, 550 mg / dose, 600 mg / dose, 650 mg / dose, 700 mg / dose, 750 mg / dose, 800 mg / dose, 850 mg / dose, 900 mg / dose, 950 mg / dose, 1000 mg / dose, 1100 mg / dose, 1200 mg / dose, 1250 mg / dose, 1300 mg / dose, 1400 mg / dose, 1500 mg / dose, 1600 mg / dose, 1700 mg / dose, 1750 mg / dose, 1800 mg / dose, 1900 mg / dose, or 2000 mg / dose.

201. 200. The method of any one of claims 191-198, wherein the induction regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment.

202. the induction regimen comprising: (i) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 1000 mg / dose at week 10; (ii) 500 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10; (iii) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 1000 mg / dose at week 6, and 500 mg / dose at week 10; (iv) 1000 mg / dose at week 0, 1000 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10, or (v) The method of any one of claims 191-198 and 201, comprising administration of 1000 mg / dose at week 0, 500 mg / dose at week 2, 500 mg / dose at week 6, and 500 mg / dose at week 10.

203. 202. The method of any one of claims 191-198 and 201, wherein the induction regimen comprises administration of 2000, 1950, 1900, 1850, 1800, 1750, 1700, 1650, 1600, 1550, 1500, 1450, 1400, 1350, 1300, 1250, 1200, 1150, 1100, 1050, 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, or 200 mg / dose.

204. 204. The method of any one of claims 191-198, 201, and 203, wherein the induction regimen comprises administration once every 2, 4, 6, or 8 weeks.

205. 204. The method of any one of claims 191-198, 201, and 203, wherein the induction regimen comprises administration once every 2 or 4 weeks for the first two doses, followed by administration once every 2, 4, 6, or 8 weeks for the remainder of the induction regimen.

206. 206. The method of any one of claims 178-195 and 199-205, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject.

207. 207. The method of any one of claims 192-206, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject during the maintenance regimen.

208. 208. The method of any one of claims 192-207, wherein the diseased tissue in the subject produces up to 10, 15, 20, 25, 30, 35, 40, 45, 50-fold or more TL1A compared to the corresponding tissue in the control subject within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, or 52 weeks or more of initiation of the maintenance regimen.

209. The method of any one of claims 192-208, wherein the maintenance regimen comprises multiple administrations of the anti-TL1A antibody or antigen-binding fragment.

210. the maintenance regimen comprising: (i) 500 mg / dose every 2 weeks; (ii) 400 mg / dose every 2 weeks; (iii) 300 mg / dose every 2 weeks; (iv) 250 mg / dose every 2 weeks; (v) 200 mg / dose every 2 weeks; (vi) 150 mg / dose every 2 weeks; (vii) 100 mg / dose every 2 weeks; (viii) 50 mg / dose every 2 weeks; (ix) 500 mg / dose every 4 weeks; (x) 400 mg / dose every 4 weeks; (xi) 300 mg / dose every 4 weeks; (xii) 250 mg / dose every 4 weeks; (xiii) 200 mg / dose every 4 weeks; (xiv) 150 mg / dose every 4 weeks; (xv) 100 mg / dose every 4 weeks; (xvi) 50 mg / dose every 4 weeks; (xvii) 500 mg / dose every 6 weeks; (xviii) 400 mg / dose every 6 weeks; (xix) 300 mg / dose every 6 weeks; (xx) 250 mg / dose every 6 weeks; (xxi) 200 mg / dose every 6 weeks; (xxii) 150 mg / dose every 6 weeks; (xxiii) 100 mg / dose every 6 weeks; (xxiv) 50 mg / dose every 6 weeks; (xxv) 500 mg / dose every 8 weeks; (xxvi) 400 mg / dose every 8 weeks; (xxvii) 300 mg / dose every 8 weeks; (xxviii) 250 mg / dose every 8 weeks; (xxix) 200 mg / dose every 8 weeks; (xxx) 150 mg / dose every 8 weeks; (xxxi) 100 mg / dose every 8 weeks, or (xxxii) The method of any one of claims 192-209, comprising administration of the anti-TL1A antibody or antigen-binding fragment at 50 mg / dose every 8 weeks.

211. 210. The method of any one of claims 192-209, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 1000, 950, 900, 850, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, or 50 mg / dose.

212. 212. The method of any one of claims 192-209 and 211, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment once every 2, 4, 6, 8, 10, or 12 weeks.

213. 213. The method of any one of claims 192-212, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 250 mg / dose every four weeks.

214. 214. The method of any one of claims 192-213, wherein the maintenance regimen comprises administration of the anti-TL1A antibody or antigen-binding fragment at 100 mg / dose every four weeks.

215. 215. The method of any one of claims 192-214, wherein the maintenance regimen lasts for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, or 52 weeks.

216. 216. The method of any one of claims 178-215, wherein the effective dosage regimen maintains the concentration of TL1A in diseased tissues of the subject below the concentration of TL1A in corresponding tissues of a control subject not having skin inflammation and / or skin fibrosis for at least 4 weeks, 8 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 2 years, and longer.

217. The method of any one of claims 178-216, wherein at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the monomeric TL1A in the subject's blood is occupied by the anti-TL1A antibody or antigen-binding fragment during the effective dose regimen.

218. The method of any one of claims 178-217, wherein at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the trimeric TL1A in the subject's blood is occupied by the anti-TL1A antibody or antigen-binding fragment during the effective dose regimen.

219. Step (a) determines the rate of TL1A trimerization (k ｏｎ－ＴＬ１Ａ－ｍｏｎｏｍｅｒ－ｔｏ－ｔｒｉｍｅｒ ) and / or the rate of TL1A monomerization (k ｏｆｆ－ＴＬ１Ａ－ｔｒｉｍｅｒ－ｔｏ－ｍｏｎｏｍｅｒ 219. The method of any one of claims 178 to 218, further comprising receiving a

220. The method of any one of claims 114 to 219, wherein the concentration of TL1A is the concentration of free TL1A.

221. The method of any one of claims 1 to 220, wherein the anti-TL1A antibody comprises a heavy chain variable region comprising HCDR1 comprising the amino acid sequence described by SEQ ID NO: 1, HCDR2 comprising the amino acid sequence described by any one of SEQ ID NOs: 2-5, and HCDR3 comprising the amino acid sequence described by any one of SEQ ID NOs: 6-9, and a light chain variable region comprising LCDR1 comprising the amino acid sequence described by SEQ ID NO: 10, LCDR2 comprising the amino acid sequence described by SEQ ID NO: 11, and LCDR3 comprising the amino acid sequence described by any one of SEQ ID NOs: 12-15.

222. The method of any one of claims 1 to 221, wherein the anti-TL1A antibody comprises a heavy chain variable framework region comprising a human IGHV1-46*02 framework or a modified human IGHV1-46*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 collectively comprise no amino acid modifications or collectively comprise fewer than nine amino acid modifications from the human IGHV1-46*02 framework and the human IGKV3-20 framework.

223. The method of any one of claims 1 to 222, wherein the anti-TL1A antibody comprises a heavy chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 101-169, and a light chain variable domain comprising an amino acid sequence at least 96% identical to any one of SEQ ID NOs: 201-220.

224. the anti-TL1A antibody is selected from the group consisting of SEQ ID NO: 301 X1VQLVQSGAEVKKPGASVKVSCKAS [HCDR1] WVX2QX3PGQGLEWX4G [HCDR2] RX5TX6TX7DTSTSTX8YX9ELSSLRSEDTAVYYCAR [HCDR3] WGQGTTVTVSS; and a heavy chain variable region comprising SEQ ID NO: 303 and a light chain variable region comprising: EIVLTQSPGTLSLSPGERATTLSC [LCDR1] WYQQKPGQAPRX10X11IY [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; and HCDR1 comprises the amino acid sequence set forth by SEQ ID NO:

1. HCDR2 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 2-5, HCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 6-9, LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 10, LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 11, and LCDR3 comprises the amino acid sequence set forth in any one of SEQ ID NOs: 12 or 13.

Images