Antibodies against monocyte chemotactic proteins
View Patent ↗The invention provides antibodies that bind to a plurality of β-chemokines, particularly monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. The invention also provides cells producing the antibodies, and methods of making and using the same.
1. An isolated antibody heavy chain comprising a variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27.
2. An isolated antibody light chain comprising a variable region complementarity determining region (CDR) from an antibody light chain variable region set forth SEQ ID NO:28.
3. An isolated antibody or antigen-binding fragment thereof, comprising 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.
4. An isolated antibody or antigen-binding fragment thereof, which binds a plurality of β-chemokines, wherein said β-chemokines comprises MCP-1 and at least one other β-chemokine, said antibody or antigen-binding fragment comprising a variable region complementarity determining region (CDR) from a heavy chain variable region set forth in SEQ ID NO:27.
5. The antibody or antigen-binding fragment of claim 4 , wherein the at least one other β-chemokine includes MCP-2.
6. An antibody or antigen-binding fragment thereof, which binds a plurality of β-chemokines, wherein said β-chemokines comprise MCP-1 and at least one other β-chemokine, said antibody or antigen-binding fragment comprising a variable region complementarity determining region (CDR) from a light chain variable region set forth in SEQ ID NO:28.
7. The antibody or antigen-binding fragment of claim 6 , wherein the at least one other β-chemokine is MCP-2.
8. An isolated antibody or antigen-binding fragment thereof, which binds a plurality of β-chemokines, wherein said β-chemokines comprise MCP-1 and at least one other β-chemokine, said antibody or antigen-binding fragment comprising:
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.
9. The antibody of claim 8 , wherein the at least one other β-chemokine is MCP-2.
10. The antibody of claim 8 , herein the antibody is a chimeric antibody.
11. The antibody of claim 8 , wherein the antibody is a humanized antibody.
12. The antibody of claim 8 , wherein the fragment is an Fab fragment.
13. An antibody or antigen-binding fragment of claim 8 , wherein the antibody is modified by reducing or eliminating at least one potential glycosylation site.
14. An antibody or antigen-binding fragment of claim 8 , wherein the antibody is modified by conjugation to a carrier selected from polyethylene glycol and albumen.
15. An antibody or antigen-binding fragment of claim 8 , 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.
16. An isolated single chain antibody antigen-binding fragment that specifically binds to MCP-1 and at least one other monocyte chemotactic protein comprising 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 antibody fragment does not have agonistic chemotactic activity for MCP-2.
17. The antibody antigen-binding fragment of claim 16 , comprising 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 antibody antigen-binding fragment of claim 16 , which binds a plurality of β-chemokines, wherein said β-chemokines comprise MCP-1 and at least one other β-chemokine, said antibody or antigen-binding fragment comprising:
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 antibody antigen-binding fragment of claim 16 that specifically binds to MCP-1, MCP-2, and MCP-3.
20. The antibody antigen-binding fragment of claim 16 , wherein said fragment is a monoclonal or antigen-binding fragment.
21. The antibody antigen-binding fragment of claim 16 , wherein said antibody is a humanized antibody.
22. The antigen-binding fragment of claim 16 , wherein said 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 antibody antigen-binding fragment of claim 16 , wherein the fragment is an Fab fragment.
24. The antibody antigen-binding fragment of claim 16 , wherein said fragment is conjugated to polyethylene glycol or albumen.
25. The antibody antigen-binding fragment of claim 16 , wherein said antibody or antigen-binding fragment has a Kd for binding affinity to MCP-1 of 1pM or less or 0.4pM to about 0.7pM.
26. An antibody or antigen-binding fragment of claim 16 , 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.
27. A hybridoma cell wherein said hybridoma cell produces an antibody fragment of claim 16 .
28. The hybridoma cell of claim 27 , wherein said hybridoma cell is selected from the group consisting of 11K2.1 with ATCC Accession No. PTA-3987, 6D21.1 with ATCC Accession No. PTA-3989, 4N4.1 with ATCC Accession No. PTA-3994, 5A13.1 with ATCC Accession No. PTA-3995, 7H1.1 with ATCC Accession No. PTA-3985, 1A1.1 with ATCC Accession No. PTA-3990, 615.1 with ATCC Accession No. PTA-3986, 2024.1 with ATCC Accession No. PTA-3993, 9B11.1 with ATCC Accession No. PTA-3992, 9B12.1 with ATCC Accession No. PTA-3996, 9C11.1 with ATCC Accession No. PTA-3988, and 12F15.1 with ATCC Accession No. PTA-3991.
29. A pharmaceutical composition comprising an antibody or antigen-binding fragment of claim 16 .