Claims
- 1. An antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor.
- 2. An antibody or antigen-binding fragment according to claim 1 wherein said antibody or antigen-binding fragment thereof inhibits one or more functions associated with binding of the ligand to the receptor.
- 3. An antibody or antigen-binding fragment thereof according to claim 1 wherein the mammalian CC-chemokine receptor 2 is a human CC-chemokine receptor 2.
- 4. An antibody or antigen-binding fragment thereof according to claim 1 wherein the ligand is a chemokine.
- 5. An antibody or antigen-binding fragment thereof according to claim 4 wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4 and combinations thereof.
- 6. An antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or fragment is a monoclonal antibody or fragment thereof.
- 7. An antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or fragment is a human antibody or fragment thereof.
- 8. An antibody or antigen-binding fragment thereof according to claim 1, wherein said antigen-binding fragment is selected from the group consisting of an Fv fragment, an Fab fragment, an Fab′ fragment and an F(ab′)2 fragment.
- 9. An antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or fragment is a humanized antibody or fragment thereof.
- 10. An antibody or antigen-binding fragment thereof according to claim 1, wherein said antibody or fragment is a recombinant antibody or fragment thereof.
- 11. A test kit for use in detecting the presence of a mammalian CC-chemokine receptor 2 in a biological sample comprising
a) at least one antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor; and b) one or more ancillary reagents suitable for detecting the presence of a complex between said antibody or antigen-binding fragment thereof and said mammalian CC-chemokine receptor 2 or a portion thereof.
- 12. A method of inhibiting the interaction of a cell bearing mammalian CC-chemokine receptor 2 with a ligand thereof, comprising contacting said cell with an effective amount of an antibody or antigen-binding fragment thereof which binds to mammalian CC-chemokine receptor 2 and inhibits binding of said ligand to the receptor.
- 13. A method according to claim 12 wherein the cell is selected from the group consisting of lymphocytes, monocytes, granulocytes, T cells, basophils, and cells comprising a recombinant nucleic acid encoding CCR2 or a portion thereof.
- 14. A method according to claim 13 wherein the T cells are selected from the group consisting of CD8+ cells, CD25+ cells, CD4+ cells and CD45RO+ cells.
- 15. A method according to claim 12 wherein the ligand is a chemokine.
- 16. A method according to claim 15 wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4 and combinations thereof.
- 17. A method of inhibiting HIV infection of a cell, comprising contacting a cell with an effective amount of a composition comprising an antibody or antigen-binding fragment thereof which binds to mammalian CC-chemokine receptor 2 and inhibits HIV entry into said cell.
- 18. A method according to claim 17 wherein the cell is selected from the group consisting of lymphocytes, monocytes, macrophages, granulocytes, T cells, and cells comprising a recombinant nucleic acid encoding CCR2 or a portion thereof.
- 19. A method according to claim 18 wherein the T cells are selected from the group consisting of CD8+cells, CD25+cells, CD4+cells and CD45RO+cells.
- 20. A method of treating HIV in a patient comprising administering to the patient a composition comprising an effective amount of an antibody or antigen-binding fragment thereof which binds to mammalian CC-chemokine receptor 2 and inhibits HIV entry into said cell.
- 21. A method of detecting expression of mammalian CC-chemokine receptor 2 or portion thereof by a cell, comprising:
a) contacting a composition comprising a cell to be tested with an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor; and b) detecting binding of said antibody or antigen-binding fragment thereof, wherein the binding of said antibody or antigen-binding fragment thereof indicates the presence of said receptor or portion of said receptor on said cell.
- 22. The method of claim 21 wherein the composition is a sample comprising human cells.
- 23. A method of detecting a mammalian CC-chemokine receptor 2 or portion of said receptor, comprising:
a) contacting a sample to be tested with an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor under conditions appropriate for binding of said antibody or fragment thereof thereto; and b) detecting or measuring binding of said antibody or antigen-binding fragment thereof, wherein the binding of said antibody or antigen-binding fragment thereof to material in said sample is indicative of the presence of a mammalian CC-chemokine receptor 2 or portion of said receptor in said sample.
- 24. A method according to claim 23, wherein the sample is a cellular fraction which, in normal individuals, comprises a mammalian CC-chemokine receptor 2 or portion of said receptor.
- 25. A method of inhibiting a function associated with binding of a chemokine to a mammalian CC-chemokine receptor 2 or a functional portion of said receptor, comprising contacting a composition comprising the receptor or portion with an effective amount of an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody inhibits binding of said chemokine to mammalian CC-chemokine receptor 2 and inhibits one or more functions associated with binding of the ligand to the receptor.
- 26. A method according to claim 25 wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4 and combinations thereof.
- 27. A method of detecting or identifying an agent which binds a mammalian CC-chemokine receptor 2 or ligand-binding variant thereof, comprising combining
a) an agent to be tested; b) an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor; and c) a composition comprising a mammalian CC-chemokine receptor 2 or a ligand-binding variant thereof, under conditions suitable for binding of said antibody or antigen-binding fragment to said mammalian CC-chemokine receptor 2 or ligand-binding variant thereof, and detecting or measuring binding of said antibody or antigen-binding fragment to said mammalian CC-chemokine receptor 2 or ligand-binding variant thereof.
- 28. A method according to claim 27 wherein the formation of a complex between said antibody or antigen-binding fragment and said mammalian CC-chemokine receptor 2 or ligand-binding variant is monitored, and wherein a decrease in the amount of complex formed relative to a suitable control is indicative that the agent binds said receptor or ligand-binding variant thereof.
- 29. A method according to claim 27 wherein the composition comprising a mammalian CC-chemokine receptor 2 or a ligand-binding variant thereof is a cell bearing recombinant CC-chemokine receptor 2 or ligand-binding variant thereof.
- 30. A method according to claim 29, wherein the composition comprising a mammalian CC-chemokine receptor 2 or a ligand-binding variant thereof is a membrane fraction of said cell bearing recombinant CC-chemokine receptor 2 or ligand-binding variant thereof.
- 31. A method according to claim 27 wherein the antibody or antigen-binding fragment thereof is labeled with a label selected from the group consisting of a radioisotope, spin label, antigen label, enzyme label, fluorescent group and chemiluminescent group.
- 32. A method according to claim 27 wherein the agent is an antibody having specificity for a mammalian CC-chemokine receptor 2 or antigen-binding fragment thereof.
- 33. A method of inhibiting HIV infection in a patient, comprising administering to the patient a composition comprising an effective amount of an antibody or antigen-binding fragment thereof which binds to mammalian CC-chemokine receptor 2 and inhibits binding of HIV to the receptor.
- 34. A method of inhibiting leukocyte trafficking in a patient, comprising administering to the patient a composition comprising an effective amount of an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2 and inhibits binding of a ligand to the receptor.
- 35. A method according to claim 34 wherein the ligand is a chemokine.
- 36. A method according to claim 35 wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4 and combinations of the foregoing.
- 37. A composition comprising an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor, and an optional physiologically acceptable vehicle.
- 38. An antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor with an IC50 of less than about 1.0 μg/ml.
- 39. An antibody or antigen-binding fragment thereof according to claim 38 wherein the IC50 is less than about 0.05 μg/ml.
- 40. An antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor, and wherein the antibody or antigen-binding fragment binds the receptor with an affinity of at least about 0.1×10−9 M.
- 41. An antibody or antigen-binding fragment thereof according to claim 40, wherein the affinity is at least about 1×10−9 M.
- 42. An antibody or antigen-binding fragment thereof according to claim 40, wherein the affinity is at least about 3×10−9 M.
- 43. A method of treating a CC-chemokine receptor 2-mediated disorder in a patient, comprising administering to the patient an effective amount of an antibody or antigen-binding fragment thereof which binds to a mammalian CC-chemokine receptor 2, wherein said antibody or antigen-binding fragment thereof inhibits binding of a ligand to the receptor.
RELATED APPLICATION
[0001] This application is a continuation of U.S. patent application Ser. No. 09/121,781, filed Jul. 23, 1998, the entire teachings of which are incorporated herein by reference.
Continuations (1)
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Number |
Date |
Country |
Parent |
09121781 |
Jul 1998 |
US |
Child |
09898513 |
Jul 2001 |
US |