Human G-Protein Chemokine Receptor (CCR5) HDGNR10

Abstract

The present invention relates to a novel human protein called Human G-protein Chemokine Receptor (CCR5) HDGNR10, and isolated polynucleotides encoding this protein. The invention is also directed to human antibodies that bind Human G-protein Chemokine Receptor (CCR5) HDGNR10 and to polynucleotides encoding those antibodies. Also provided are vectors, host cells, antibodies, and recombinant methods for producing Human G-protein Chemokine Receptor (CCR5) HDGNR10 and human anti-Human G-protein Chemokine Receptor (CCR5) HDGNR10 antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating diseases, disorders, and/or conditions related to this novel human protein and these novel human antibodies.

1 . An isolated polynucleotide encoding a first antibody at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% identical to a second antibody comprising an amino acid sequence selected from the group consisting of:
 (a) at least one CDR region of a VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (b) at least two CDR regions of a VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (c) at least three CDR regions of a VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (d) at least one CDR region of a VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (e) at least two CDR regions of a VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line; and   (f) at least three CDR regions of a VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line.   
     
     
         2 . An isolated first antibody at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% identical to a second antibody comprising an amino acid sequence selected from the group consisting of:
 (a) at least one CDR region of a VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (b) at least two CDR regions of a VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (c) at least three CDR regions of a VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (d) at least one CDR region of a VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line;   (e) at least two CDR regions of a VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line; and   (f) at least three CDR regions of a VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line.   
     
     
         3 . A method of inhibiting chemokine binding to CCR5, in order to treat or ameliorate any one of the following inflammatory diseases or disorders selected from the group consisting of:
 (a) transplantation;   (b) graft-versus-host disease;   (c) rheumatoid arthritis;   (d) pulmonary disease;   (e) hypersensitivity;   (f) multiple sclerosis;   (g) dermatitis;   (h) psoriasis; and   (i) airway inflammation;   
       comprising administering an isolated antibody or fragment thereof to an animal in need thereof, wherein the antibody or fragment thereof specifically binds a CCR5 polypeptide, and wherein the antibody or fragment thereof comprises:
 (a) the VH domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line deposited under ATCC Deposit Accession Number PTA-4054 and the VL domain of the antibody expressed by the XF27/28.43E2 hybridoma cell line deposited under ATCC Deposit Accession Number PTA-4054; or 
 (b) the VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3 of the antibody expressed by the XF27/28.43E2 hybridoma cell line deposited under ATCC Deposit Accession Number PTA-4054. 
 
     
     
         4 . The method of  claim 3 , wherein the CCR5 polypeptide is expressed on the surface of a cell, and wherein the CCR5 polypeptide is encoded by a polynucleotide encoding amino acids 1 to 352 of SEQ ID NO:22. 
     
     
         5 . The method of  claim 4 , wherein the antibody or fragment thereof binds to the second extracellular loop of the CCR5 polypeptide. 
     
     
         6 . The method of  claim 3 , wherein the antibody or fragment thereof is selected from the group consisting of:
 (a) a whole immunoglobulin molecule;   (b) an scFv;   (c) a Fab fragment;   (d) an Fab′ fragment;   (e) an F(ab′)2;   (f) an Fv; and   (g) a disulfide linked Fv.   
     
     
         7 . The method of  claim 3 , wherein the antibody or fragment thereof is selected from the group consisting of:
 (a) a monoclonal antibody or fragment thereof;   (b) a human antibody or fragment thereof;   (c) a chimeric antibody or fragment thereof; and   (d) a humanized antibody or fragment thereof.   
     
     
         8 . The method of  claim 3 , wherein the antibody or fragment thereof comprises a heavy chain immunoglobulin constant domain. 
     
     
         9 . The method of  claim 8 , wherein the heavy chain immunoglobulin constant domain is selected from the group consisting of:
 (a) an IgM constant domain;   (b) an IgG1 constant domain;   (c) an IgG2 constant domain;   (d) an IgG3 constant domain;   (e) an IgG4 constant domain; and   (f) an IgA constant domain.   
     
     
         10 . The method of  claim 8 , wherein the heavy chain immunoglobulin constant domain is human. 
     
     
         11 . The method of  claim 3 , wherein the antibody or fragment thereof comprises a light chain immunoglobulin constant domain. 
     
     
         12 . The method of  claim 11 , wherein the light chain immunoglobulin constant domain is selected from the group consisting of:
 (a) a kappa constant domain; and   (b) a lambda constant domain.   
     
     
         13 . The method of  claim 11 , wherein the light chain immunoglobulin constant domain is human. 
     
     
         14 . The method of  claim 3 , wherein the antibody or fragment thereof comprises a human IgG4 heavy chain immunoglobulin constant domain and a human kappa light chain immunoglobulin constant domain. 
     
     
         15 . The method of  claim 3 , wherein the antibody or fragment thereof is an antagonist of CCR5. 
     
     
         16 . The method of  claim 3 , wherein the antibody or fragment thereof inhibits the binding of Eotaxin, RANTES, MCP-1, MCP-2, MCP-3, MIP-1beta or MIP-1alpha to CCR5. 
     
     
         17 . The method of  claim 3 , further comprising administering one or more agents employed for treating inflammatory disorders selected from the group consisting of:
 (a) an antibiotic;   (b) a cytokine;   (c) a corticosteroid;   (d) a salicyclic acid derivative;   (e) an antimetabolite;   (f) an immunosuppressive agent; and   (g) an anti-angiogenic factor.   
     
     
         18 . The method of  claim 3 , further comprising administering one or more agents employed for treating inflammatory disorders selected from the group consisting of:
 (a) ciprofloxacin;   (b) metronidazole;   (c) mercaptopurine;   (d) methotrexate;   (e) azathioprine;   (f) cyclosporine;   (g) prednisone;   (h) methylprednisone;   (i) thalidomide; and   (j) interleukin-11.   
     
     
         19 . The method of  claim 3 , wherein the isolated antibody or fragment thereof is administered by a route selected from the group consisting of:
 (a) intradermal;   (b) intramuscular;   (c) intraperitoneal;   (d) intravenous;   (e) subcutaneous;   (f) intranasal;   (g) epidural; and   (h) oral.   
     
     
         20 . The method of  claim 3 , wherein the animal is a human.