OPTIMIZED ANTI-TL1A ANTIBODIES
Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of inflammatory bowel disease (IBD), such as Crohn's Disease (CD) and ulcerative colitis (UC).
1 - 48 . (canceled)
49 . A method of preparing an inflammatory bowel disease (IBD), Crohn's disease, or colitis treatment, comprising incubating a cell comprising a nucleic acid encoding an antibody or antigen-binding fragment that specifically binds tumor necrosis factor ligand 1A (TL1A) in a culture medium under conditions sufficient to secrete the antibody or antigen-binding fragment into the culture medium.
50 . The method of claim 49 , wherein the cell is a eukaryotic cell.
51 . The method of claim 49 , wherein the cell is a Chinese Hamster Ovary (CHO) cell.
52 . The method of claim 49 , wherein the cell is a COS cell, a HeLa cell, an L cell, or a multiple myeloma cell.
53 . The method of claim 49 , wherein the cell is a C127 cell, a 3T3 cell, or a BHK cell.
54 . The method of claim 49 , wherein the antibody or antigen-binding fragment that specifically binds TL1A comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 553; an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 554 to 564 or 574 to 577; and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 565 to 568 or 578 to 581; and a light chain variable region comprising: an LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 569 or 570; an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 488; and an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 571 to 573 or 582 to 585.
55 . The method of claim 49 , wherein the antibody or antigen-binding fragment that specifically binds TL1A comprises: a heavy chain variable region comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOs: 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, or 541; and a light chain variable region comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOs: 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, or 540.
56 . The method of claim 49 , wherein the antibody or antigen-binding fragment that specifically binds TL1A comprises a heavy chain variable region comprising: an HCDR1, an HCDR2, and an HCDR3 selected from any one of SEQ ID NOs: 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, or 541; and a light chain variable region comprising an LCDR1, an LCDR2, and an LCDR3 selected from any one of SEQ ID NOs: 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, or 540, wherein the CDRs are defined by the Kabat, Chothia, or IMGT method or a combination thereof.
57 . The method of claim 49 , further comprising subjecting the culture medium to at least one purification step.
58 . The method of claim 57 , wherein the purification step comprises high-performance liquid chromatography (HPLC) purification, column chromatography, or gel electrophoresis, or any combination thereof.
59 . The method of claim 57 , wherein the purification step comprises immunoadsorption, immunoaffinity chromatography, ammonium sulfate precipitation, or gel electrophoresis, or any combination thereof.
60 . A method of preparing an inflammatory bowel disease (IBD), Crohn's disease, or colitis treatment, the method comprising admixing an antibody or antigen-binding fragment that specifically binds tumor necrosis factor ligand 1A (TL1A) and a pharmaceutically acceptable excipient, carrier, or diluent.
61 . The method of claim 60 , wherein the antibody or antigen-binding fragment that specifically binds TL1A comprises a heavy chain variable region comprising: an HCDR1 comprising an amino acid sequence set forth by SEQ ID NO: 553; an HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 554 to 564 or 574 to 577; and an HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 565 to 568 or 578 to 581; and a light chain variable region comprising: an LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 569 or 570; an LCDR2 comprising an amino acid sequence set forth by SEQ ID NO: 488; and an LCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 571 to 573 or 582 to 585.
62 . The method of claim 60 , wherein the antibody or antigen-binding fragment that specifically binds TL1A comprises: a heavy chain variable region comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOs: 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, or 541; and a light chain variable region comprising an amino acid sequence at least about 90% identical to any one of SEQ ID NOs: 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, or 540.
63 . The method of claim 60 , wherein the antibody or antigen-binding fragment that specifically binds TL1A comprises a heavy chain variable region comprising: an HCDR1, an HCDR2, and an HCDR3 selected from any one of SEQ ID NOs: 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, or 541; and a light chain variable region comprising an LCDR1, an LCDR2, and an LCDR3 selected from any one of SEQ ID NOs: 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, or 540, wherein the CDRs are defined by the Kabat, Chothia, or IMGT method or a combination thereof.