Antibodies that specifically bind to TL1A and methods of treating respiratory tract diseases
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 respiratory tract disease, comprising administering to a subject in need of treatment for a respiratory tract disease 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: 29, 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: 30, provided that when the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 1, the light chain variable region does not comprise the amino acid sequence of SEQ ID NO: 2, wherein the antibody specifically binds to TNF-Like ligand 1A (TL1A) and wherein the antibody is capable of inhibiting the interaction of TL1A with the death receptor 3 (DR3).
2. The method according to claim 1 , wherein the respiratory tract disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, allergic rhinitis, pulmonary fibrosis, or cystic fibrosis.
3. The method according to claim 1 , wherein the light chain variable region CDR3 comprises the amino acid sequence of SEQ ID NO: 20.
4. The method according to claim 1 , wherein the light chain variable region CDR3 comprises the amino acid sequence of SEQ ID NO: 22.
5. The method according to claim 4 , wherein the respiratory tract disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, allergic rhinitis, pulmonary fibrosis, or cystic fibrosis.
6. The method according to claim 1 , wherein the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 24, and the light chain variable region CDR3 comprises the amino acid sequence of SEQ ID NO: 22.
7. The method according to claim 1 , wherein the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 25, and the light chain variable region CDR3 comprises the amino acid sequence of SEQ ID NO: 22.
8. The method according to claim 1 , wherein the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 26, and the light chain variable region CDR3 comprises the amino acid sequence of SEQ ID NO: 22.
9. The method according to claim 1 , wherein the light chain variable region CDR3 comprises the amino acid sequence of SEQ ID NO: 27.
10. A method for treating a respiratory tract disease, comprising administering to a subject in need of treatment for a respiratory tract disease 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: 28, 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: 29, 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, provided that when the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 1, the light chain variable region does not comprise the amino acid sequence of SEQ ID NO: 2, wherein the antibody specifically binds to TNF-Like ligand 1A (TL1A) and wherein the antibody is capable of inhibiting the interaction of TL1A with the death receptor 3 (DR3).
11. The method according to claim 10 , wherein the heavy chain variable region CDR2 comprises the amino acid sequence of SEQ ID NO: 16.
12. The method according to claim 10 , wherein the heavy chain variable region CDR2 comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 23.
13. The method according to claim 10 , wherein the heavy chain variable region CDR2 comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 24.
14. The method according to claim 10 , wherein the heavy chain variable region CDR2 comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 25.
15. The method according to claim 10 , wherein the heavy chain variable region CDR2 comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region CDR1 comprises the amino acid sequence of SEQ ID NO: 26.
16. A method for treating a respiratory tract disease, comprising administering to a subject in need of treatment for a respiratory tract disease 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) and wherein the antibody is capable of inhibiting the interaction of TL1A with the death receptor 3 (DR3).
17. The method according to claim 16 , wherein the respiratory tract disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, allergic rhinitis, pulmonary fibrosis, or cystic fibrosis.
18. The method according to claim 16 , wherein the respiratory tract disease is asthma.
19. The method according to claim 16 , wherein the antibody comprises a human IgG1 heavy chain constant region.
20. The method according to claim 16 , wherein the antibody comprises a human light chain lambda constant region.
21. The method according to claim 16 , wherein the antibody comprises a human IgG1 heavy chain constant region and a human light chain lambda constant region.
22. The method according to claim 21 , wherein the respiratory tract disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, allergic rhinitis, pulmonary fibrosis, or cystic fibrosis.
23. The method according to claim 21 , wherein the respiratory tract disease is asthma.
24. A method for treating a respiratory tract disease, comprising administering to a subject in need of treatment for a respiratory tract disease a recombinant antibody comprising 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.
25. The method according to claim 24 , wherein the respiratory tract disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, allergic rhinitis, pulmonary fibrosis, or cystic fibrosis.
26. The method according to claim 24 , wherein the respiratory tract disease is asthma.
27. The method according to claim 24 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:61.
28. The method according to claim 24 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60.
29. The method according to claim 24 , 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. The method according to claim 29 , wherein the respiratory tract disease is asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, allergic rhinitis, pulmonary fibrosis, or cystic fibrosis.
31. The method according to claim 29 , wherein the respiratory tract disease is asthma.