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. A nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically to human B7RP1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising a CDR1 comprising SEQ ID NO: 27, a CDR2 comprising SEQ ID NO: 28, and a CDR3 comprising SEQ ID NO: 29; and the light chain variable region comprising a CDR1 comprising SEQ ID NO: 15, a CDR2 comprising SEQ ID NO: 16, and a CDR3 comprising SEQ ID NO: 17.
2. A nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically to human B7RP1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising SEQ ID NO: 7 or 8.
3. A nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically to human B7RP1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, the light chain variable region comprising SEQ ID NO: 1.
4. The nucleic acid molecule of claim 2 wherein the light chain variable region comprises a CDR1 comprising SEQ ID NO: 15, a CDR2 comprising SEQ ID NO: 16, and a CDR3 comprising SEQ ID NO: 17.
5. The nucleic acid molecule of claim 3 wherein the heavy chain variable region comprises a CDR1 comprising SEQ ID NO: 27, a CDR2 comprising SEQ ID NO: 28, and a CDR3 comprising SEQ ID NO: 29.
6. A nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically to human B7RP1 comprising:
a) a heavy chain variable region comprising SEQ ID NO: 7 and a light chain variable region comprising SEQ ID NO: 1; or
b) a heavy chain variable region comprising SEQ ID NO: 8 and a light chain variable region comprising SEQ ID NO: 1.
7. The nucleic acid molecule of claim 6 , wherein the heavy chain variable region comprises SEQ ID NO: 8, and the light chain variable region comprises SEQ ID NO: 1.
8. A nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically to human B7RP1, wherein the antibody or antigen-binding fragment thereof comprises any one of SEQ ID NOS: 44, 45, 46, 70, or 71.
9. A nucleic acid molecule that encodes an antibody or antigen-binding fragment thereof that binds specifically to human B7RP1, wherein the antibody or antigen-binding fragment thereof 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.
10. A nucleic acid molecule that encodes an antibody or an antigen-binding fragment thereof that binds to human B7RP1, wherein the antibody or antigen-binding fragment thereof 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.
11. The nucleic acid molecule of any one of claims 1 to 10 , wherein the antibody or antigen-binding fragment thereof is a single-chain antibody, a single chain Fv antibody, an Fab antibody, an Fab′ antibody, or an (Fab′)2 antibody.
12. The nucleic acid molecule of any one of claims 1 to 5 and 8 to 10 , wherein the antibody or antigen-binding fragment thereof is a fully human antibody or antigen-binding fragment thereof.
13. The nucleic acid molecule of any one of claims 1 to 10 , wherein the antibody or antigen-binding fragment thereof blocks interaction between B7RP1 and ICOS.
14. The nucleic acid molecule of any of claims 1 to 10 , wherein the antibody or antigen-binding fragment thereof blocks T cell-dependent B cell antigen response.
15. A vector comprising the nucleic acid of any one of claims 1 to 10 .
16. A host cell in culture comprising the vector of claim 15 .
17. A method of producing an antibody or antigen-binding fragment thereof, that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions a host cell transformed or transfected with the nucleic acid molecule of any one of claims 1 to 10 ; and
isolating the antibody or antigen-binding fragment thereof produced by the expression of the nucleic acid.
18. A nucleic acid molecule comprising a nucleotide sequence that encodes a polypeptide that binds specifically to human B7RP1, wherein the polypeptide comprises any one of SEQ ID NO: 1, 7, 8, 44, 45, 46, 70, or 71 or a combination thereof.
19. The nucleic acid molecule of claim 18 , wherein the polypeptide blocks interaction between B7RP1 and ICOS.
20. The nucleic acid molecule of claim 18 , wherein the polypeptide blocks T cell-dependent B cell antigen response.
21. A vector comprising the nucleic acid molecule of claim 18 .
22. A host cell in culture comprising the vector of claim 21 .
23. A method of producing a polypeptide that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions a host cell transformed or transfected with the nucleic acid molecule of claim 18 ; and
isolating the polypeptide produced by the expression of the nucleic acid.
24. A host cell in culture comprising a first nucleic acid molecule and a second nucleic acid molecule, wherein the first nucleic acid molecule encodes a heavy chain variable region comprising a CDR1 comprising SEQ ID NO: 27, a CDR2 comprising SEQ ID NO: 28, and a CDR3 comprising SEQ ID NO: 29; and the second nucleic acid molecule encodes a light chain variable region comprising a CDR1 comprising SEQ ID NO: 15, a CDR2 comprising SEQ ID NO: 16, and a CDR3 comprising SEQ ID NO: 17, and wherein the first and second nucleic acid molecules encode an antibody or antigen binding fragment thereof that specifically binds to human B7RP1.
25. A host cell in culture comprising a first nucleic acid molecule and a second nucleic acid molecule, wherein either the first nucleic acid molecule encodes a heavy chain variable region comprising SEQ ID NO: 7 or 8 and the second nucleic acid molecule encodes a light chain variable region, or the first nucleic acid molecule encodes a heavy chain variable region and the second nucleic acid molecule encodes a light chain variable region comprising SEQ ID NO: 1, and wherein the first and second nucleic acid molecules encode an antibody or antigen binding fragment thereof that specifically binds to human B7RP1.
26. The host cell of claim 25 wherein the second nucleic acid molecule encodes a light chain variable region comprising a CDR1 comprising SEQ ID NO: 15, a CDR2 comprising SEQ ID NO: 16, and a CDR3 comprising SEQ ID NO: 17.
27. The host cell of claim 25 wherein the first nucleic acid molecule encodes a heavy chain variable region comprising a CDR1 comprising SEQ ID NO: 27, a CDR2 comprising SEQ ID NO: 28, and a CDR3 comprising SEQ ID NO: 29.
28. A host cell in culture comprising a first nucleic acid molecule and a second nucleic acid molecule, wherein either the first nucleic acid molecule encodes a heavy chain comprising SEQ ID NO: 44, 46, 70 or 71 and the second nucleic acid molecule encodes a light chain variable region, or the first nucleic acid molecule encodes a heavy chain and the second nucleic acid molecule encodes a light chain variable region comprising SEQ ID NO: 45, and wherein the first and second nucleic acid molecules encode an antibody or antigen binding fragment thereof that specifically binds to human B7RP1.
29. The host cell of claim 25 wherein:
(a) the first nucleic acid molecule encodes a heavy chain variable region comprising SEQ ID NO: 7 and the second nucleic acid molecule encodes a light chain variable region comprising SEQ ID NO: 1; or
(b) the first nucleic acid molecule encodes a heavy chain variable region comprising SEQ ID NO: 8 and the second nucleic acid molecule encodes a light chain variable region comprising SEQ ID NO: 1.
30. The host cell of claim 28 wherein:
(a) the first nucleic acid molecule encodes a heavy chain comprising SEQ ID NO: 44 and the second nucleic acid molecule encodes a light chain comprising SEQ ID NO: 45; or
(b) the first nucleic acid molecule encodes a heavy chain comprising SEQ ID NO: 46 and the second nucleic acid molecule encodes a light chain comprising SEQ ID NO: 45.
31. The host cell of claim 28 wherein:
(a) the first nucleic acid molecule encodes a heavy chain comprising SEQ ID NO: 70 and the second nucleic acid molecule encodes a light chain comprising SEQ ID NO: 45; or
(b) the first nucleic acid molecule encodes a heavy chain comprising SEQ ID NO: 71 and the second nucleic acid molecule encodes a light chain comprising SEQ ID NO: 45.
32. The host cell of any one of claims 24 , 25 , 26 to 28 , or 29 to 31 , wherein the antibody or antigen-binding fragment thereof is a single-chain antibody, a single chain Fv antibody, an Fab antibody, an Fab′ antibody, or an (Fab′)2 antibody.
33. The host cell of any one of claims 24 , 25 , 26 to 28 , or 29 to 31 , wherein the antibody or antigen-binding fragment thereof is a fully human antibody or antigen-binding fragment thereof.
34. The host cell of any one of claims 24 , 25 , 26 to 28 , or 29 to 31 , wherein the antibody or antigen-binding fragment thereof blocks interaction between B7RP1 and ICOS.
35. The host cell of any of claims 24 , 25 , 26 to 28 , or 29 to 31 , wherein the antibody or antigen-binding fragment thereof blocks T cell-dependent B cell antigen response.
36. The host cell of any one of claims 24 , 25 , 26 to 28 , or 29 to 31 which comprises a first vector and a second vector, wherein the first vector comprises the first nucleic acid molecule and the second vector comprises the second nucleic acid molecule.
37. A method of producing an antibody or antigen-binding fragment thereof, that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions the host cell of any one of claims 1 to 3 ; and
isolating the antibody or antigen-binding fragment thereof produced by the expression of the nucleic acid.
38. A method of producing an antibody or antigen-binding fragment thereof, that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions a host cell transformed or transfected with the nucleic acid molecule of claim 11 ; and
isolating the antibody or antigen-binding fragment thereof produced by the expression of the nucleic acid.
39. A method of producing an antibody or antigen-binding fragment thereof, that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions a host cell transformed or transfected with the nucleic acid molecule of claim 12 ; and
isolating the antibody or antigen-binding fragment thereof produced by the expression of the nucleic acid.
40. A method of producing an antibody or antigen-binding fragment thereof, that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions a host cell transformed or transfected with the nucleic acid molecule of claim 13 ; and
isolating the antibody or antigen-binding fragment thereof produced by the expression of the nucleic acid.
41. A method of producing an antibody or antigen-binding fragment thereof, that binds specifically to human B7RP1 comprising:
culturing under appropriate conditions a host cell transformed or transfected with the nucleic acid molecule of claim 14 ; and
isolating the antibody or antigen-binding fragment thereof produced by the expression of the nucleic acid.