Antibodies against human cd38

Abstract

Isolated monoclonal antibodies which bind to human CD38 and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies.

1 - 74 . (canceled) 
     
     
         75 . A method for detecting the presence of CD38 antigen, or a cell expressing CD38, in a sample comprising:
 (a) contacting the sample with an antibody that binds to human CD38 (SEQ ID NO: 52), wherein the antibody does not bind to a variant of human CD38 wherein Asp in position 202 has been substituted with Gly to the same degree that it binds to human CD38 under conditions that allow for formation of a complex between the antibody and CD38; and   (b) analyzing whether a complex has been formed.   
     
     
         76 . The method of  claim 75 , wherein the sample is a human tissue sample. 
     
     
         77 . The method of  claim 75 , which is performed in vitro. 
     
     
         78 . The method of  claim 75 , which is performed in vivo. 
     
     
         79 . The method of  claim 75 , wherein the cell expressing CD38 is a tumor cell. 
     
     
         80 . The method of  claim 75 , wherein the method is used to diagnose the level of invasive cells in a tissue, wherein the formation of a complex between the antibody and CD38 correlates with the presence of invasive cells in the tissue. 
     
     
         81 . The method of  claim 75 , wherein the formation of the complex is detected using a method selected from the group consisting of: enzyme linked immunosorbent assay, RIA, FACS assay, plasma resonance assay, chromatography, tissue immunohistochemistry, Western blot, and immunoprecipitation. 
     
     
         82 . The method of  claim 75 , wherein the antibody comprises a detectable label selected form the group consisting of an enzyme, prosthetic group, fluorescent label, luminescent label, and radioactive label. 
     
     
         83 . The method of  claim 75 , wherein the formation of the complex is detected using a secondary antibody comprising a detectable label. 
     
     
         84 . The method of  claim 83 , wherein the detectable label is selected from the group consisting of an enzyme, prosthetic group, fluorescent label, luminescent label, and radioactive label. 
     
     
         85 . The method of  claim 75 , wherein the antibody comprises:
 (i) a VH CDR1 having the sequence as set forth in any of the sequences SEQ ID NOs: 3, 8, 13, 18, and 23, a VH CDR2 having the sequence as set forth in any of the sequences SEQ ID NOs: 4, 9, 14, 19, and 24, a VH CDR3 having the sequence as set forth in any of the sequences SEQ ID NOs: 5, 10, 15, 20, and 25, a VL CDR1 having the sequence as set forth in any of the sequences SEQ ID NOs: 28, 33, 38, 43, and 48, a VL CDR2 having the sequence as set forth in any of the sequences SEQ ID NOs: 29, 34, 39, 44, and 49, a VL CDR3 having the sequence as set forth in any of the sequences SEQ ID NOs: 30, 35, 40, 45, and 50,   (ii) a VH CDR1 having the sequence as set forth in SEQ ID NO: 3, a VH CDR2 having the sequence as set forth in SEQ ID NO: 4, a VH CDR3 having the sequence as set forth in SEQ ID NO: 5, a VL CDR1 having the sequence as set forth in SEQ ID NO: 28, a VL CDR2 having the sequence as set forth in SEQ ID NO: 29, and a VL CDR3 having the sequence as set forth in SEQ ID NO: 30,   (iii) a VH CDR1 having the sequence as set forth in SEQ ID NO: 8, a VH CDR2 having the sequence as set forth in SEQ ID NO: 9, a VH CDR3 having the sequence as set forth in SEQ ID NO: 10, a VL CDR1 having the sequence as set forth in SEQ ID NO: 33, a VL CDR2 having the sequence as set forth in SEQ ID NO: 34, and a VL CDR3 having the sequence as set forth in SEQ ID NO: 35,   (iv) a VH CDR1 having the sequence as set forth in SEQ ID NO: 13, a VH CDR2 having the sequence as set forth in SEQ ID NO: 14, a VH CDR3 having the sequence as set forth in SEQ ID NO: 15, a VL CDR1 having the sequence as set forth in SEQ ID NO: 38, a VL CDR2 having the sequence as set forth in SEQ ID NO: 39, and a VL CDR3 having the sequence as set forth in SEQ ID NO: 40,   (v) a VH CDR1 having the sequence as set forth in SEQ ID NO: 18, a VH CDR2 having the sequence as set forth in SEQ ID NO: 19, a VH CDR3 having the sequence as set forth in SEQ ID NO: 20, a VL CDR1 having the sequence as set forth in SEQ ID NO: 43, a VL CDR2 having the sequence as set forth in SEQ ID NO: 44, and a VL CDR3 having the sequence as set forth in SEQ ID NO: 45,   (vi) a VH CDR1 having the sequence as set forth in SEQ ID NO: 23, a VH CDR2 having the sequence as set forth in SEQ ID NO: 24, a VH CDR3 having the sequence as set forth in SEQ ID NO: 25, a VL CDR1 having the sequence as set forth in SEQ ID NO: 48, a VL CDR2 having the sequence as set forth in SEQ ID NO: 49, and a VL CDR3 having the sequence as set forth in SEQ ID NO: 50, or   (vii) a variant of any of the antibodies defined above, wherein the variant preferably has at most 1, 2, or 3 amino acid modifications, more preferably amino-acid substitutions, such as conservative amino acid substitutions in one or more of the sequences.   
     
     
         86 . The method of  claim 75 , wherein the antibody comprises a VH CDR1 having the sequence as set forth in SEQ ID NO: 3, a VH CDR2 having the sequence as set forth in SEQ ID NO: 4, a VH CDR3 having the sequence as set forth in SEQ ID NO: 5, a VL CDR1 having the sequence as set forth in SEQ ID NO: 28, a VL CDR2 having the sequence as set forth in SEQ ID NO: 29, and a VL CDR3 having the sequence as set forth in SEQ ID NO: 30. 
     
     
         87 . The method of  claim 75 , wherein the antibody comprises a VH region comprising any one of the sequences as set forth in SEQ ID NOs: 2, 7, 12, 17, and 22, and a VL region comprising any one of the sequences as set forth in SEQ ID NOs: 27, 32, 37, 42, and 47. 
     
     
         88 . The method of  claim 75 , wherein the antibody comprises:
 (i) a VH region comprising the sequence as set forth in SEQ ID NO: 2, and a VL region comprising the sequence as set forth in SEQ ID NO: 27,   (ii) a VH region comprising the sequence as set forth in SEQ ID NO: 7, and a VL region comprising the sequence as set forth in SEQ ID NO: 32,   (iii) a VH region comprising the sequence as set forth in SEQ ID NO: 12, and a VL region comprising the sequence as set forth in SEQ ID NO: 37,   (iv) a VH region comprising the sequence as set forth in SEQ ID NO: 17, and a VL region comprising the sequence as set forth in SEQ ID NO: 42, or   (v) a VH region comprising the sequence as set forth in SEQ ID NO: 22, and a VL region comprising the sequence as set forth in SEQ ID NO: 47.   
     
     
         89 . The method of  claim 75 , wherein the antibody comprises a VH region comprising the sequence as set forth in SEQ ID NO: 2, and a VL region comprising the sequence as set forth in SEQ ID NO: 27. 
     
     
         90 . The method of  claim 75 , wherein the antibody possesses the following binding characteristics: (i) it does not bind to a variant of human CD38 wherein Asp in position 202 has been substituted with Gly to the same degree that it binds to human CD38, (ii) it binds to a variant of human CD38 wherein Gln in position 272 has been substituted with Arg to the same degree that it binds to human CD38, and (iii) it binds to a variant of human CD38 wherein the Ser in position 274 has been substituted with Phe to the same degree that it binds to human CD38. 
     
     
         91 . The method of  claim 75 , wherein the antibody binds to human CD38 with a K D  of 10 −8  M or less. 
     
     
         92 . The method of  claim 75 , wherein the antibody is a full length IgG1, IgG2, IgG3, IgG4, IgD, IgA, IgE, or IgM antibody. 
     
     
         93 . The method of  claim 75 , wherein the antibody is an antibody fragment or a single-chain antibody. 
     
     
         94 . The method of  claim 75 , wherein the antibody is an effector function-deficient antibody. 
     
     
         95 . The method of  claim 75 , wherein the antibody is a monovalent antibody. 
     
     
         96 . The method of  claim 75 , wherein the antibody is a human monovalent antibody. 
     
     
         97 . The method of  claim 75 , wherein the antibody is a bivalent antibody.