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 . A method for treating a hematological cancer associated with the undesired presence of CD38+ cells, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising:
 (A) an isolated human antibody that specifically binds an epitope of CD38 (SEQ ID NO: 22), wherein said antibody mediates killing of a CD38+ target cell by antibody dependent cellular cytotoxicity with at least five-fold better efficacy than chimeric OKT10 antibody (SEQ ID NOS: 23 and 24) under the same or substantially the same conditions when a human PBMC cell is employed as the effector cell, wherein said CD38+ target cell is selected from the group consisting of LP-1 (DSMZ: ACC41) and RPMI-8226 (ATCC: CCL-155), and wherein the ratio of effector cells to target cells is between about 30:1 and about 50:1; and   (B) a pharmaceutically acceptable carrier or excipient therefor.   
     
     
         86 . The method of  claim 85 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 5 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 13. 
     
     
         87 . The method of  claim 85 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 6 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 14. 
     
     
         88 . The method of  claim 85 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 7 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 15. 
     
     
         89 . The method of  claim 85 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 8 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 16. 
     
     
         90 . The method of  claim 85 , wherein the antibody is an IgG. 
     
     
         91 . The method of  claim 90 , wherein the antibody is an IgG1. 
     
     
         92 . A method for treating a hematological cancer associated with the undesired presence of CD38+ cells, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising:
 (A) an isolated human antibody that specifically binds to an epitope of CD38 (SEQ ID NO: 22), wherein said antibody mediates killing of a CD38-transfected CHO cell by cell dependent cytotoxicity with at least two-fold better efficacy than chimeric OKT10 antibody (SEQ ID NOS: 23 and 24) under the same or substantially the same conditions; and   (B) a pharmaceutically acceptable carrier or excipient therefor.   
     
     
         93 . The method of  claim 92 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 5 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 13. 
     
     
         94 . The method of  claim 92 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 6 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 14. 
     
     
         95 . The method of  claim 92 , wherein the antibody comprises an H-CDR1, H-CDR2 and H-CDR3 depicted in SEQ ID NO: 7 and an L-CDR1, L-CDR2 and L-CDR3 depicted in SEQ ID NO: 15. 
     
     
         96 . The method of  claim 92 , wherein the antibody is an IgG. 
     
     
         97 . The method of  claim 96 , wherein the antibody is an IgG1. 
     
     
         98 . The method of  claim 85 , wherein the hematological cancer is multiple myeloma. 
     
     
         99 . The method of  claim 85 , wherein the hematological cancer is chronic lymphocytic leukemia. 
     
     
         100 . The method of  claim 85 , wherein the hematological cancer is chronic myelogenous leukemia. 
     
     
         101 . The method of  claim 85 , wherein the hematological cancer is acute myelogenous leukemia 
     
     
         102 . The method of  claim 85 , wherein the hematological cancer is acute lymphocytic leukemia. 
     
     
         103 . The method of  claim 92 , wherein the hematological cancer is multiple myeloma. 
     
     
         104 . The method of  claim 92 , wherein the hematological cancer is chronic lymphocytic leukemia. 
     
     
         105 . The method of  claim 92 , wherein the hematological cancer is chronic myelogenous leukemia. 
     
     
         106 . The method of  claim 92 , wherein the hematological cancer is acute myelogenous leukemia 
     
     
         107 . The method of  claim 92 , wherein the hematological cancer is acute lymphocytic leukemia.