Human anti-B7RP1 neutralizing antibodies
View Patent ↗This invention provides antibodies that interact with or bind to human B7 related protein-1 (B7RP1) and antibodies that bind to and neutralize the function of B7RP1 thereby. The invention also provides pharmaceutical compositions of said antibodies and methods for neutralizing B7RP1 function, and particularly for treating immune disorders (e.g., inappropriate immune response) by administering a pharmaceutically effective amount of anti-B7RP1 antibodies. Methods of detecting the amount of B7RP1 in a sample using anti-B7RP1 antibodies are also provided.
1. An isolated antibody or an antigen binding fragment thereof, that specifically binds human B7RP1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises SEQ ID NO: 8.
2. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof binds specifically to human B7RP1 but not to mouse B7RP1.
3. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof binds specifically to human B7RP1 and mouse B7RP1.
4. An isolated antibody or an antigen binding fragment thereof that binds specifically to human B7RP1 comprising a heavy chain variable region comprising SEQ ID NO: 8 and a light chain variable region comprising SEQ ID NO: 1.
5. An isolated antibody or an antigen binding fragment thereof, that specifically binds human B7RP1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region, and a light chain variable region, wherein the light chain variable region comprises SEQ ID NO: 1.
6. The isolated antibody or antigen binding fragment thereof of claim 5 , wherein the antibody or antigen binding fragment thereof binds specifically to human B7RP1 but not to mouse B7RP1.
7. The isolated antibody or antigen binding fragment thereof of claim 5 , wherein the antibody or antigen binding fragment thereof binds specifically to human B7RP1 and mouse B7RP1.
8. An isolated antibody or an antigen binding fragment thereof that binds specifically to human B7RP1, comprising a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, and a heavy chain CDR 3 comprising SEQ ID NO: 29; and a light chain CDR1 comprising SEQ ID NO: 15, a light chain CDR2 comprising SEQ ID NO: 16, and a light chain CDR3 comprising SEQ ID NO: 17.
9. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , wherein the heavy chain and light chain comprise a single-chain antibody.
10. The antibody or antigen binding fragment thereof of claim 9 , which is a single-chain Fv antibody.
11. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , which is a Fab antibody.
12. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , which is Fab′ antibody.
13. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , which is a (Fab′) 2 antibody.
14. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , wherein the antibody or antigen binding fragment is fully human.
15. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , wherein the antibody or antigen binding fragment thereof blocks interaction between B7RP-1 and ICOS.
16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the antibody or an antigen binding fragment thereof, of any of claim 1 , 4 , 5 , or 8 .
17. An isolated antibody or antigen binding fragment thereof that binds specifically to human B7RP1 wherein the antibody or antigen binding fragment binds to a region of B7RP1 consisting of SEQ ID NO: 67 and does not bind a region of B7RP1 consisting of SEQ ID NO: 68.
18. The antibody or antigen binding fragment thereof of claim 17 , which comprises a single-chain antibody.
19. The antibody or antigen binding fragment thereof of claim 18 , which is a single-chain Fv antibody.
20. The antibody or antigen binding fragment thereof of claim 17 , which is a Fab antibody.
21. The antibody or antigen binding fragment thereof of claim 17 , which is Fab′ antibody.
22. The antibody or antigen binding fragment thereof of claim 17 , which is a (Fab′) 2 antibody.
23. The antibody or antigen binding fragment thereof of claim 17 , wherein the antibody or antigen binding fragment is fully human.
24. The antibody or an antigen binding fragment thereof of claim 17 , wherein the antibody or antigen binding fragment thereof blocks interaction between B7RP-1 and ICOS.
25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the antibody or antigen binding fragment thereof of any of claims 17 - 23 .
26. An isolated antibody that binds to human B7RP1 wherein the antibody is competitive with an antibody that comprises a light chain variable region of SEQ ID NO: 1 or a heavy chain variable region of SEQ ID NO: 8, or both SEQ ID NO: 1 and SEQ ID NO:8 for binding to human B7RP1.
27. An isolated antibody or antigen binding fragment thereof that binds specifically to human B7RP1, wherein the antibody or antigen binding fragment thereof comprises a light chain amino acid sequence of SEQ ID NO: 45; or a heavy chain amino acid sequence of SEQ ID NO: 46 or SEQ ID NO: 71; or a combination selected from a light chain of SEQ ID NO: 45 and a heavy chain of SEQ ID NO: 46 or a light chain of SEQ ID NO: 45 and a heavy chain of SEQ ID NO: 71.
28. The antibody or antigen binding fragment thereof of claim 27 , wherein the heavy chain and light chain comprise a single-chain antibody.
29. The antibody or antigen binding fragment thereof of claim 28 , which is a single-chain Fv antibody.
30. The antibody or antigen binding fragment thereof of claim 27 , which is a Fab antibody.
31. The antibody or antigen binding fragment thereof of claim 27 , which is Fab′ antibody.
32. The antibody or antigen binding fragment thereof of claim 27 , which is a (Fab′) 2 antibody.
33. The antibody or antigen binding fragment thereof of claim 27 , wherein the antibody or antigen binding fragment is fully human.
34. The antibody or an antigen binding fragment thereof of claim 27 , wherein the antibody or antigen binding fragment thereof blocks interaction between B7RP-1 and ICOS.
35. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the antibody of any of claim 26 or 27 - 33 .
36. The antibody or an antigen binding fragment thereof of claim 1 , 4 , 5 , or 8 , wherein the antibody or antigen binding fragment thereof blocks T cell-dependent B cell antigen response.
37. The antibody or an antigen binding fragment thereof of claim 17 , wherein the antibody or antigen binding fragment thereof blocks T cell-dependent B cell antigen response.
38. The antibody or an antigen binding fragment thereof of claim 27 , wherein the antibody or antigen binding fragment thereof blocks T cell-dependent B cell antigen response.
39. An isolated antibody or an antigen binding fragment thereof that binds to human B7RP1 wherein the antibody or antigen binding fragment is competitive with an antibody that comprises a light chain variable region of SEQ ID NO: 1 and a heavy chain variable region of SEQ ID NO: 8 for binding to human B7RP1.