Antibodies that specifically bind to TL1A
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 recombinant antibody, comprising 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, wherein the antibody specifically binds to TNF-like ligand 1A (TL1A).
2. The recombinant antibody according to claim 1 , wherein the antibody is capable of inhibiting the interaction of TL1A with the death receptor 3 (DR3).
3. The recombinant antibody according to claim 1 , wherein the antibody is a monoclonal antibody.
4. A composition, comprising the recombinant antibody of claim 1 and a pharmaceutically acceptable carrier, wherein the composition is formulated for administration to a human subject.
5. The recombinant antibody according to claim 1 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3.
6. The recombinant antibody according to claim 1 , wherein the antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
7. The recombinant antibody according to claim 1 , 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.
8. The recombinant antibody according to claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:60.
9. The recombinant antibody according to claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:61.
10. The recombinant antibody according to claim 6 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60.
11. The recombinant antibody according to claim 5 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 61.
12. The recombinant antibody 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.
13. The recombinant antibody according to claim 1 , wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 43.
14. The recombinant antibody according to claim 1 , wherein the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 48.
15. The recombinant antibody according to claim 1 , wherein the antibody comprises a human IgG1 heavy chain constant region and a human light chain lambda constant region.
16. The recombinant antibody according to claim 6 , wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:43.
17. The recombinant antibody according to claim 11 , wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:43.
18. The recombinant antibody according to claim 5 , wherein the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO:48.
19. The recombinant antibody according to claim 8 , wherein the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO:48.
20. A transformed host cell that comprises a polynucleotide encoding the antibody according to claim 1 and which expresses said antibody.
21. A method of making an antibody comprising culturing the host cell according to claim 20 .
22. An in vitro method of detecting TL1A in a sample obtained from a subject comprising contacting the sample with the antibody of claim 1 and detecting the antibody bound to TL1A in the sample.
23. A polynucleotide comprising a nucleic acid sequence encoding an antibody heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3.
24. A host cell comprising a vector comprising the polynucleotide of claim 23 .
25. A polynucleotide comprising a nucleic acid sequence encoding an antibody light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
26. A host cell comprising a vector comprising the polynucleotide of claim 25 .
27. The host cell of claim 26 further comprising a polynucleotide comprising a nucleic acid sequence encoding an antibody light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
28. The recombinant antibody according to claim 1 , wherein the antibody comprises a human IgG1 heavy chain constant region.
29. The recombinant antibody according to claim 28 , wherein the human IgG1heavy chain constant region comprises SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, or SEQ ID NO: 66.
30. The recombinant antibody according to claim 1 , wherein the antibody comprises a human heavy chain IgG4 constant region.
31. The recombinant antibody according to claim 30 , wherein the human heavy chain IgG4 constant region comprises SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, or SEQ ID NO: 69.
32. The recombinant antibody according to claim 1 , wherein the antibody comprises a human heavy chain IgG2 constant region.
33. The recombinant antibody according to claim 32 , wherein the human heavy chain IgG2 constant region comprises SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 70, or SEQ ID NO: 71.
34. The recombinant antibody according to claim 1 , wherein the antibody comprises a human light chain lambda constant region.