Anti-cd38 human antibodies and uses therefor

Abstract

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for CD38, which plays an integral role in various disorders or conditions. These antibodies, accordingly, can be used to treat, for example, hematological malignancies such as multiple myeloma. Antibodies of the invention also can be used in the diagnostics field, as well as for investigating the role of CD38 in the progression of disorders associated with malignancies. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use. The invention also provides isolated novel epitopes of CD38 and methods of use therefore.

1 - 84 . (canceled) 
     
     
         85 . An isolated human monoclonal antibody comprising six complementarity determining regions that binds a peptide consisting of the amino acid sequence DVVHVMLNGSRSKIFDKNSTFGS (SEQ ID NO: 47). 
     
     
         86 . A composition comprising the isolated human monoclonal antibody of  claim 85  and a pharmaceutically acceptable carrier. 
     
     
         87 . An isolated human monoclonal antibody comprising six complementarity determining regions that binds a peptide consisting of the amino acid sequence, DVVHVMLNGSRSKIFDKNSTFGS (SEQ ID NO: 47), or that binds a 13-amino acid sequence subset thereof. 
     
     
         88 . The antibody of  claim 87 , wherein the peptide consists of the amino acid sequence selected from the group consisting of DVVHVMLNGSRSKIFDKNSTFGS (SEQ ID NO: 47), DVVHVMLNGSRSK (SEQ ID NO: 48), VVHVMLNGSRSKI (SEQ ID NO: 49), VHVMLNGSRSKIF (SEQ ID NO: 50), HVMLNGSRSKIFD (SEQ ID NO: 51), VMLNGSRSKIFDK (SEQ ID NO: 52), MLNGSRSKIFDKN (SEQ ID NO: 53), LNGSRSKIFDKNS (SEQ ID NO: 54), NGSRSKIFDKNST (SEQ ID NO: 55), GSRSKIFDKNSTF (SEQ ID NO: 56), SRSKIFDKNSTFG (SEQ ID NO: 57), and RSKIFDKNSTFGS (SEQ ID NO: 58). 
     
     
         89 . The antibody of  claim 88 , wherein the peptide consists of the amino acid sequence selected from the group consisting of DVVHVMLNGSRSK (SEQ ID NO: 48), VHVMLNGSRSKIF (SEQ ID NO: 50), VMLNGSRSKIFDK (SEQ ID NO: 52), LNGSRSKIFDKNS (SEQ ID NO: 54), and RSKIFDKNSTFGS (SEQ ID NO: 58). 
     
     
         90 . The antibody of  claim 89 , wherein the peptide consists of the amino acid sequence, VHVMLNGSRSKIF (SEQ ID NO: 50). 
     
     
         91 . A composition comprising the isolated human monoclonal antibody of  claim 87  and a pharmaceutically acceptable carrier. 
     
     
         92 . A composition comprising the isolated human monoclonal antibody of  claim 90  and a pharmaceutically acceptable carrier. 
     
     
         93 . A method of treating the overexpression of CD38 in a patient in need thereof of a therapeutically effective amount of the antibody of  claim 85 . 
     
     
         94 . The method of  claim 93 , wherein the patient has multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia. 
     
     
         95 . The method of  claim 94 , wherein the patient has rheumatoid arthritis or systemic lupus erythematosus. 
     
     
         96 . A method of treating the overexpression of CD38 in a patient in need thereof with a therapeutically effective amount of the antibody of  claim 87 . 
     
     
         97 . The method of  claim 96 , wherein the patient has multiple myeloma, chronic lyphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia. 
     
     
         98 . The method of  claim 97 , wherein the patient has rheumatoid arthritis or systemic lupus erythematosus. 
     
     
         99 . A method of treating the overexpression of CD38 in a patient in need thereof with a therapeutically effective amount of the antibody of  claim 90 . 
     
     
         100 . The method of  claim 99 , wherein the patient has multiple myeloma, chronic lyphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia. 
     
     
         101 . A method of treating cancer in a subject in need thereof, wherein the cancer comprises cells that overexpress CD38, comprising administering to the subject a therapeutically effective amount of the antibody of  claim 85 . 
     
     
         102 . The method of  claim 101 , wherein the patient has multiple myeloma, chronic lyphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia. 
     
     
         103 . A method of treating the cancer in a subject in need thereof, wherein the cancer comprises cells that overexpress CD38 in a patient in need thereof with a therapeutically effective amount of the antibody of  claim 90 . 
     
     
         104 . The method of  claim 103 , wherein the patient has multiple myeloma, chronic lyphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia.