Antibodies against monocyte chemotactic proteins

1. A method of reducing chemotaxis in a subject suffering from glomerulonephritis, scleroderma, cirrhosis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or fragment thereof capable of inhibiting chemotaxis in the subject, wherein said antibody or fragment thereof binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprise MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment comprises:

a) a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO: 31; and

b) a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32, a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34

wherein the isolated antibody is administered in an amount sufficient to reduce the chemotactic activity of at least one of MCP-1, MCP-2, or MCP-3.

2. The method of claim 1 , wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain region as set forth in SEQ ID NO:27 and a variable light chain region as set forth in SEQ ID NO:28.

3. The method of claim 1 , wherein the at least one other β-chemokine is MCP-2.

4. The method of claim 1 , wherein the antibody is a chimeric antibody.

5. The method of claim 1 , wherein the antibody is a humanized antibody.

6. The method of claim 1 , wherein the fragment is an Fab fragment.

7. The method of claim 1 , wherein the antibody is modified by reducing or eliminating at least one potential glycosylation site.

8. The method of claim 1 , wherein the antibody is modified by conjugation to a carrier selected from polyethylene glycol and albumen.

9. The method of claim 1 , wherein the constant region of the antibody is modified to reduce at least one constant region-mediated biological effector function relative to an unmodified antibody selected from the group of binding to an Fc receptor, opsonization, phagocytosis, and antigen-dependent cellular cytotoxicity.

10. A method of reducing chemotaxis in a subject suffering from glomerulonephritis, scleroderma, cirrhosis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof capable of inhibiting chemotaxis in the subject, wherein said antibody comprises a heavy chain variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27, wherein the isolated antibody is administered in an amount sufficient to reduce the chemotactic activity of at least one of MCP-1, MCP-2, or MCP-3.

11. The method of claim 10 , wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine.

12. The method of claim 11 , wherein the at least one other β-chemokine comprises MCP-2.

13. A method of reducing chemotaxis in a subject suffering from glomerulonephritis, scleroderma, cirrhosis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof capable of inhibiting chemotaxis in the subject, wherein said antibody comprises a light chain variable region complementarity determining region (CDR) from an antibody light chain variable region as set forth in SEQ ID NO:28, wherein the isolated antibody is administered in an amount sufficient to reduce the chemotactic activity of at least one of MCP-1, MCP-2, or MCP-3.

14. The method of claim 13 , wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine.

15. The method of claim 14 , wherein the at least one other β-chemokine comprises MCP-2.

16. A method of reducing chemotaxis in a subject suffering from glomerulonephritis, scleroderma, cirrhosis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated single-chain antibody antigen-binding fragment capable of inhibiting chemotaxis in the subject, wherein said single-chain antibody fragment specifically binds MCP-1 and at least one other monocyte chemotactic protein, wherein said single-chain antibody comprises a heavy chain variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27 or a light chain variable region complementarity determining region (CDR) from an antibody light chain variable region set forth in SEQ ID NO:28, wherein said single-chain antibody fragment does not have agonistic chemotactic activity for MCP-2, wherein the isolated single-chain antibody fragment is administered in an amount sufficient to reduce the chemotactic activity of at least one of MCP-1 or MCP-3.

17. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment comprises a variable heavy chain region as set forth in SEQ ID NO: 27 and a variable light chain region as set forth in SEQ ID NO:28.

18. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said single-chain antibody comprises:

i. a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:31; and

ii. a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32 a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34.

19. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment specifically binds to MCP-1, MCP-2, and MCP-3.

20. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment is a monoclonal antibody.

21. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment is a humanized antibody.

22. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment is selected from the group consisting of an Fab fragment, an Fab' fragment, an F(ab) 2 fragment, and an Fv fragment.

23. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment is an Fab fragment.

24. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment is conjugated to polyethylene glycol or albumen.

25. The method of claim 16 , wherein the single-chain antibody antigen-binding fragment has a Kd for binding affinity to MCP-1 of 1 pM or less or 0.4 pM to about 0.7 pM.

26. A method of reducing chemotaxis in a subject suffering from glomerulonephritis, scleroderma, cirrhosis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or fragment thereof capable of blocking chemotaxis, wherein said antibody or antigen-binding fragment comprises:

a) a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO: 31; and

b) a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32, a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34,

wherein the isolated antibody is administered in an amount sufficient to reduce the chemotactic activity of at least one of MCP-1, MCP-2, or MCP-3.