TRAIL receptor-2 polypeptides and antibodies
Polypeptides are provided. Antibodies or antigen binding domains are provided which bind such polypeptides. Also provided are methods of obtaining an antibody that binds tumor necrosis factor (TNF)-related apoptosis-inducing ligand (“TRAIL”) Receptor-2 (TR-2) comprising administering at least one of such polypeptides to an animal and obtaining an antibody that binds TR-2 from the animal. Antibodies reactive with TR-2 are provided. Also provided are cells producing antibodies reactive with TR-2, pharmaceutical compositions comprising antibodies reactive with TR-2, methods using antibodies reactive with TR-2, and kits comprising antibodies reactive with TR-2. Also provided are methods of decreasing or preventing binding of an antibody to TR-2 by administering such a polypeptide.
1. An isolated antibody comprising a heavy chain and a light chain that binds TRAIL Receptor-2 (TR-2), wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 2, and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 36.
2. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 4 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 38.
3. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 6 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 40.
4. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 8 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 42.
5. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 10 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 44.
6. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 12 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 46.
7. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 14 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 48.
8. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 16 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 50.
9. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 18 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 52.
10. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 20 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 54.
11. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 22 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 56.
12. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 24 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 58.
13. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 26 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 60.
14. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 28 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 62.
15. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 30 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 64.
16. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 32 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 66.
17. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 34 and the light chain comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 68.
18. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2, and the light chain comprises the amino acid sequence of SEQ ID NO: 36.
19. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 4 and the light chain comprises the amino acid sequence of SEQ ID NO: 38.
20. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 6 and the light chain comprises the amino acid sequence of SEQ ID NO: 40.
21. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 8 and the light chain comprises the amino acid sequence of SEQ ID NO: 42.
22. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 10 and the light chain comprises the amino acid sequence of SEQ ID NO: 44.
23. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 12 and the light chain comprises the amino acid sequence of SEQ ID NO: 46.
24. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 14 and the light chain comprises the amino acid sequence of SEQ ID NO: 48.
25. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 16 and the light chain comprises the amino acid sequence of SEQ ID NO: 50.
26. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 18 and the light chain comprises the amino acid sequence of SEQ ID NO: 52.
27. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 20 and the light chain comprises the amino acid sequence of SEQ ID NO: 54.
28. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 22 and the light chain comprises the amino acid sequence of SEQ ID NO: 56.
29. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 24 and the light chain comprises the amino acid sequence of SEQ ID NO: 58.
30. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 26 and the light chain comprises the amino acid sequence of SEQ ID NO: 60.
31. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 28 and the light chain comprises the amino acid sequence of SEQ ID NO: 62.
32. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises amino acid sequence of SEQ ID NO: 30 and the light chain comprises amino acid sequence of SEQ ID NO: 64.
33. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 32 and the light chain comprises the amino acid sequence of SEQ ID NO: 66.
34. An isolated antibody comprising a heavy chain and a light chain that binds TR-2, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 34 and the light chain comprises the amino acid sequence of SEQ ID NO: 68.
35. The isolated antibody of any of claims 1 , 2 , 9 , 10 , 15 , 16 , 17 , 18 , 19 , 26 , 27 , 32 , 33 , and 34 , wherein the antibody is a fully human antibody.
36. The isolated antibody of any of claims 1 , 2 , 9 , 10 , 15 , 16 , 17 , 18 , 19 , 26 , 27 , 32 , 33 , and 34 , wherein the antibody is a Fab, a Fab′, a F(ab′)2, an Fv, or a single-chain Fv.
37. A pharmaceutical composition comprising the isolated antibody of any of claims 1 , 2 , 9 , 10 , 15 , 16 , 17 , 18 , 19 , 26 , 27 , 32 , 33 , and 34 a pharmaceutically acceptable carrier.