Recombinant anti-CCR2 antibodies and methods of use therefor
First Claim
Patent Images
1. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a light chain framework region derived from the light chain of the HF-21/28 antibody.
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Abstract
The present invention relates to a humanized antibody or functional fragment thereof which binds to a mammalian (e.g., human) CC-chemokine receptor 2 (CCR2) or a portion of the receptor and blocks binding of a ligand to the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR2 with a ligand thereof, and to use of the antibodies and fragments in therapeutic, prophylactic and diagnostic methods.
81 Citations
62 Claims
- 1. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a light chain framework region derived from the light chain of the HF-21/28 antibody.
- 5. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from a heavy chain of human origin.
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8. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and a suitable carrier.
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9. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from a heavy chain of human origin, and a suitable carrier.
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10. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a heavy chain framework region derived from the heavy chain of the 4B4′
- CL antibody.
- View Dependent Claims (11, 12, 13)
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14. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from a light chain of human origin, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody.
- View Dependent Claims (15, 16)
-
17. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
-
18. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from a light chain of human origin, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
- 19. A humanized immunoglobulin light chain comprising CDR1, CDR2 and CDR3 of the light chain of monoclonal antibody 1D9 and a light chain framework region derived from a human light chain.
- 22. A humanized immunoglobulin heavy chain comprising CDR1, CDR2 and CDR3 of the heavy chain of monoclonal antibody 1D9 and a heavy chain framework region derived from a human heavy chain.
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25. A humanized immunoglobulin light chain comprising an amino acid sequence selected from the group consisting of:
-
a) SEQ ID NO;
12;
b) SEQ ID NO;
13;
c) SEQ ID NO;
14; and
d) SEQ ID NO;
15.
-
-
26. A humanized immunoglobulin heavy chain comprising an amino acid sequence selected from the group consisting of:
-
a) SEQ ID NO;
17;
b) SEQ ID NO;
18;
c) SEQ ID NO;
19; and
d) SEQ ID NO;
20.
-
-
27. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises a variable region selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO;
13, SEQ ID NO;
14 and SEQ ID NO;
15, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from a heavy chain of human origin.
- 12, SEQ ID NO;
-
28. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9, and wherein said heavy chain comprises a variable region selected from the group consisting of SEQ ID NO:
- 17, SEQ ID NO;
18, SEQ ID NO;
19 and SEQ ID NO;
20.
- 17, SEQ ID NO;
-
29. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin or fragment comprising a heavy chain and a light chain, wherein said light chain comprises a variable region selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO;
13, SEQ ID NO;
14 and SEQ ID NO;
15, and wherein said heavy chain comprises a variable region selected from the group consisting of SEQ ID NO;
17, SEQ ID NO;
18, SEQ ID NO;
19 and SEQ ID NO;
20.
- 12, SEQ ID NO;
- 30. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising CDR1, CDR2 and CDR3 of the light chain of monoclonal 1D9 antibody and a framework region derived from a human light chain framework region, and a suitable carrier.
-
32. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising CDR1, CDR2 and CDR3 of the heavy chain of monoclonal 1D9 antibody and a framework region derived from a human heavy chain framework region, and a suitable carrier.
-
33. A pharmaceutical composition according to 32 wherein the human heavy chain framework region is the heavy chain framework region of the 4B4′
- CL antibody.
-
34. A humanized immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO:
- 12.
-
35. A humanized immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO:
- 17.
-
36. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a light chain comprising the amino acid sequence of SEQ ID NO:
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
17.
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
-
37. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a light chain comprising the amino acid sequence of SEQ ID NO:
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
17, and a suitable carrier.
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
-
38. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9, a light chain framework region derived from the light chain of the HF-21/28 antibody, and a heavy chain framework region derived from the heavy chain of the 4B4′
- CL antibody.
-
39. A humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody.
-
40. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9, a light chain framework region derived from the light chain of the HF-21/28 antibody, and a heavy chain framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
-
41. A pharmaceutical composition comprising a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2) comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
-
42. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a light chain framework region derived from the light chain of the HF-21/28 antibody.
-
43. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from a heavy chain of human origin.
-
44. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and a suitable carrier.
-
45. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from a heavy chain of human origin, and a suitable carrier.
-
46. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a heavy chain framework region derived from the heavy chain of the 4B4′
- CL antibody.
-
47. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from a light chain of human origin, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody.
-
48. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
-
49. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from a light chain of human origin, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
-
50. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises a variable region selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO;
13, SEQ ID NO;
14 and SEQ ID NO;
15, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from a heavy chain of human origin.
- 12, SEQ ID NO;
-
51. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9, and wherein said heavy chain comprises a variable region selected from the group consisting of SEQ ID NO:
- 17, SEQ ID NO;
18, SEQ ID NO;
19 and SEQ ID NO;
20.
- 17, SEQ ID NO;
-
52. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises a variable region selected from the group consisting of SEQ ID NO:
- 12, SEQ ID NO;
13, SEQ ID NO;
14 and SEQ ID NO;
15, and wherein said heavy chain comprises a variable region selected from the group consisting of SEQ ID NO;
17, SEQ ID NO;
18, SEQ ID NO;
19 and SEQ ID NO;
20.
- 12, SEQ ID NO;
- 53. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising CDR1, CDR2 and CDR3 of the light chain of monoclonal 1D9 antibody and a framework region derived from a human light chain framework region, and a suitable carrier.
- 55. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising CDR1, CDR2 and CDR3 of the heavy chain of monoclonal 1D9 antibody and a framework region derived from a human heavy chain framework region, and a suitable carrier.
-
57. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a light chain comprising the amino acid sequence of SEQ ID NO:
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
17.
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
-
58. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a light chain comprising the amino acid sequence of SEQ ID NO:
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
17, and a suitable carrier.
- 12 and a heavy chain comprising the amino acid sequence of SEQ ID NO;
-
59. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9, a light chain framework region derived from the light chain of the HF-21/28 antibody, and a heavy chain framework region derived from the heavy chain of the 4B4′
- CL antibody.
-
60. An antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody.
-
61. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising an antigen binding region from monoclonal antibody 1D9, a light chain framework region derived from the light chain of the HF-21/28 antibody, and a heavy chain framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
-
62. A pharmaceutical composition comprising an antigen binding fragment of a humanized immunoglobulin having binding specificity for CC-chemokine receptor 2 (CCR2), said immunoglobulin comprising a heavy chain and a light chain, wherein said light chain comprises three complementarity determining regions from the light chain of monoclonal antibody 1D9 and a framework region derived from the light chain of the HF-21/28 antibody, and wherein said heavy chain comprises three complementarity determining regions from the heavy chain of monoclonal antibody 1D9 and a framework region derived from the heavy chain of the 4B4′
- CL antibody, and a suitable carrier.
Specification