Humanized Anti-CCR2 Antibodies and Methods of Use Therefor

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.

1 .- 38 . (canceled) 
     
     
         39 . A method of inhibiting the interaction of a cell bearing mammalian CC-chemokine receptor 2 (CCR2) with a ligand thereof, comprising contacting said cell with an effective amount of a humanized antibody or antigen-binding fragment thereof that has binding specificity for CCR2, inhibits binding of said ligand to the CCR2 and inhibits one or more functions associated with binding of said ligand to CCR2. 
     
     
         40 . The method of  claim 39 , 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. 
     
     
         41 . The method of  claim 40 , wherein the T cells are selected from the group consisting of CD8+ cells, CD25+ cells, CD4+ cells and CD45RO+ cells. 
     
     
         42 . The method of  claim 39 , wherein the ligand is a chemokine. 
     
     
         43 . The method of  claim 42 , wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4 and combinations thereof. 
     
     
         44 . The method of  claim 39 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the light chain of the 1D9 antibody and a framework region sequence of the variable light chain of the HF21/28 antibody. 
     
     
         45 . The method of  claim 39 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the variable heavy chain of monoclonal antibody 1D9 and a framework region sequence of the variable heavy chain of the 4B4′CL antibody. 
     
     
         46 . The method of  claim 44 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequences of the variable heavy chain of monoclonal antibody 1D9. 
     
     
         47 . The method of  claim 46 , wherein the humanized antibody or antigen-binding fragment thereof further comprises a framework region sequence of the variable heavy chain of the 4B4′CL antibody. 
     
     
         48 . The method of  claim 39 , wherein the humanized antibody or antigen-binding fragment thereof comprises three complementarity determining region sequence of the variable light chain of monoclonal antibody 1D9, a framework region sequence of the variable light chain of the HF 21/28 antibody, three complementarity determining region sequences of the variable heavy chain of monoclonal antibody 1D9 and a framework region sequence of the variable heavy chain of the 4B4′CL antibody. 
     
     
         49 . The method of  claim 48 , wherein the humanized antibody or antigen-binding fragment thereof comprises a heavy chain constant region or portion thereof. 
     
     
         50 . The method of  claim 49 , wherein the human constant region or portion thereof is of the gamma type. 
     
     
         51 . The method of  claim 50 , wherein the human constant region or portion thereof is mutated to minimize binding to Fc receptors, the ability to fix complement or both. 
     
     
         52 . The method of  claim 48 , wherein the humanized antibody or antigen-binding fragment thereof, comprises a light chain constant region. 
     
     
         53 . The method of  claim 52 , wherein the human light chain constant region is of the kappa type. 
     
     
         54 . The method of  claim 48 , wherein the light chain variable region of the humanized antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO:12. 
     
     
         55 . The method of  claim 48 , wherein the heavy chain variable region of the humanized antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO:17. 
     
     
         56 . The method of  claim 48 , wherein the light chain variable region of the humanized antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO:12, and the heavy chain variable region of the humanized antibody or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO:17. 
     
     
         57 . The method of  claim 56 , wherein the humanized antibody or antigen-binding fragment thereof, comprises a heavy chain constant region or portion thereof. 
     
     
         58 . The method of  claim 57 , wherein the human constant region or portion thereof is of the gamma type. 
     
     
         59 . The method of  claim 58 , wherein the human constant region or portion thereof is mutated to minimize binding to Fc receptors, the ability to fix complement or both. 
     
     
         60 . The method of  claim 56 , wherein the humanized antibody or antigen-binding fragment thereof, comprises a light chain constant region. 
     
     
         61 . The method of  claim 60 , wherein the human light chain constant region is of the kappa type.