Antibodies that specifically bind to TL1A and methods of treating gastrointestinal disease
Recombinantly expressed variant antibodies that have enhanced affinity for TL1A and enhanced potency relative to the parent antibody from which they were derived are provided. The antibodies inhibit the interaction between TL1A and the death receptor 3 (DR3). The antibodies, or a composition thereof, may be used to treat one or more of asthma, COPD, pulmonary fibrosis, cystic fibrosis, inflammatory bowel disease, a gastrointestinal disease associated with cystic fibrosis, Crohn's disease, colitis, ulcerative colitis, irritable bowel syndrome, eosinophilic esophagitis, atopic dermatitis, eczema, scleroderma, arthritis, or rheumatoid arthritis.
1. A method for treating a gastrointestinal disease, comprising administering to a subject in need thereof a recombinant antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4, and wherein the gastrointestinal disease is inflammatory bowel disease, eosinophilic esophagitis, irritable bowel syndrome, or a gastrointestinal disease associated with cystic fibrosis.
2. The method according to claim 1 , wherein the antibody comprises a human IgG1 heavy chain constant region.
3. The method according to claim 1 , wherein the antibody comprises a human light chain lambda constant region.
4. The method according to claim 1 , wherein the antibody comprises a human IgG1 heavy chain constant region and a human light chain lambda constant region.
5. The method according to claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 61.
6. The method according to claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60.
7. The method according to claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60 and a light chain comprising the amino acid sequence of SEQ ID NO: 61.
8. The method according to claim 1 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
9. The method according to claim 8 , wherein the colitis is ulcerative colitis.
10. The method according to claim 2 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
11. The method according to claim 10 , wherein the colitis is ulcerative colitis.
12. The method according to claim 3 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
13. The method according to claim 12 , wherein the colitis is ulcerative colitis.
14. The method according to claim 4 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
15. The method according to claim 14 , wherein the colitis is ulcerative colitis.
16. The method according to claim 5 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
17. The method according to claim 16 , wherein the colitis is ulcerative colitis.
18. The method according to claim 6 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
19. The method according to claim 18 , wherein the colitis is ulcerative colitis.
20. The method according to claim 7 , wherein the inflammatory bowel disease is Crohn's disease or colitis.
21. The method according to claim 20 , wherein the colitis is ulcerative colitis.
22. A method for treating inflammatory bowel disease, comprising administering to a subject in need thereof a recombinant antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 21, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 17, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 18, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22.
23. The method according to claim 22 , wherein the antibody comprises a human IgG1 heavy chain constant region and a human light chain lambda constant region.
24. The method of claim 22 , wherein the inflammatory bowel disease is Crohn's disease.
25. The method of claim 22 , wherein the inflammatory bowel disease is ulcerative colitis.
26. A method for treating ulcerative colitis, comprising administering to a subject in need thereof a recombinant human IgG1 antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 15, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 21, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 17, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 18, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22.
27. A method for treating ulcerative colitis, comprising administering to a subject in need thereof a recombinant human IgG1 antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4.
28. A method for treating Crohn's disease, comprising administering to a subject in need thereof a recombinant human IgG1 antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO: 15, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 21, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 17, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 18, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22.
29. A method for treating ulcerative colitis, comprising administering to a subject in need thereof a recombinant human IgG1 antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60 and a light chain comprising the amino acid sequence of SEQ ID NO: 61.
30. A method for treating Crohn's disease, comprising administering to a subject in need thereof a recombinant human IgG1 antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4.
31. A method for treating Crohn's disease, comprising administering to a subject in need thereof a recombinant human IgG1 antibody that binds to TNF-like ligand 1A (TL1A), wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60 and a light chain comprising the amino acid sequence of SEQ ID NO: 61.