Compositions comprising anti-cd38 antibodies and carfilzomib

Abstract

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and carfilzomib compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.

1 : A method of treating multiple myeloma in a subject comprising administering an anti-CD38 antibody and a carfilzomib compound to the subject, wherein the anti-CD38 antibody is selected from the group consisting of:
 a) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 14, and 15, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17, and 18;   b) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 25, 26, and 27, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 28, 29, and 30;   c) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 1, 2, and 3, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 4, 5, and 6;   d) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 7, 8, and 9, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 10, 11, and 12;   e) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 19, 20, and 21, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 22, 23, and 24;   f) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 31, 32, and 33, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 34, 35, and 36; and   g) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 81, and 15, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17 and 18.   
     
     
         2 - 3 . (canceled) 
     
     
         4 : The method of  claim 1 , wherein the cancer is a relapsed multiple myeloma or a refractory multiple myeloma. 
     
     
         5 : The method of  claim 1 , wherein the carfilzomib compound is carfilzomib. 
     
     
         6 : The method of  claim 1 , wherein the anti-CD38 antibody is administered in an effective amount, preferably a synergistic amount. 
     
     
         7 : The method of  claim 1 , wherein the anti-CD38 antibody and/or the carfilzomib compound are administered in a therapeutically effective amount 
     
     
         8 : The method of  claim 1 , wherein the anti-CD38 antibody is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). 
     
     
         9 - 10 . (canceled) 
     
     
         11 : The method of  claim 1 , wherein said antibody comprises a heavy chain having a V H  variable region represented by SEQ ID NO: 66, and a light chain having a V L  variable region represented by either SEQ ID NO: 62 or SEQ ID NO: 64. 
     
     
         12 : The method of  claim 1 , wherein said antibody comprises a heavy chain having a V H  variable region represented by SEQ ID NO: 72, and a light chain having a V L  variable region represented by either SEQ ID NO: 68 or SEQ ID NO: 70. 
     
     
         13 : The method of  claim 1 , wherein the anti-CD38 antibody is administered intravenously. 
     
     
         14 : The method of  claim 1 , wherein the carfilzomib compound is administered intravenously. 
     
     
         15 : The method of  claim 1 , wherein the anti-CD38 antibody and the carfilzomib compound are administered sequentially. 
     
     
         16 : The method of  claim 1 , further comprising administering a dexamethasone compound to the subject. 
     
     
         17 : The method of  claim 16 , wherein the dexamethasone compound is administered orally. 
     
     
         18 : The method of  claim 16 , wherein the anti-CD38 antibody, the carfilzomib compound, and the dexamethasone compound are administered sequentially. 
     
     
         19 . (canceled) 
     
     
         20 : A kit for the treatment of multiple myeloma comprising:
 a) an anti-CD38 antibody selected from the group consisting of:
 i) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 14, and 15, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17, and 18; 
 ii) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 25, 26, and 27, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 28, 29, and 30; 
 iii) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 1, 2, and 3, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 4, 5, and 6; 
 iv) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 7, 8, and 9, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 10, 11, and 12; 
 v) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 19, 20, and 21, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 22, 23, and 24; 
 vi) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 31, 32, and 33, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 34, 35, and 36; and 
 vii) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 81, and 15, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17 and 18; and 
   b) a label having one or more messages that the anti-CD38 antibody shall be administered in combination with a carfilzomib compound, and, optionally, with dexamethasone.   
     
     
         21 - 23 . (canceled) 
     
     
         24 : The kit of  claim 20 , wherein the anti-CD38 antibody is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). 
     
     
         25 - 26 . (canceled) 
     
     
         27 : The method of  claim 16 , wherein the dexamethasone compound is dexamethasone.