Conjugated anti-cd38 antibodies

Abstract

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies.

1 .- 21 . (canceled) 
     
     
         22 . An isolated antibody which specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2),
 wherein the heavy chain variable region of the antibody comprises an amino acid sequence having an identity of at least 90% to SEQ ID NO:9, and the light chain variable region of the antibody comprises an amino acid sequence having an identity of at least 90% to SEQ ID NO:10;   wherein the antibody binds to human CD38 (SEQ ID NO:1) with a KD of 10 −8  M or a greater affinity, and wherein the affinity is measured by a standard Biacore assay; and   wherein the antibody is covalently attached to a drug moiety.   
     
     
         23 . The isolated antibody of  claim 22 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:9, and the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:10. 
     
     
         24 . The isolated antibody of  claim 22 , further comprising an Fc domain. 
     
     
         25 . The isolated antibody of  claim 24 , wherein the Fc domain is a human Fc domain. 
     
     
         26 . The isolated antibody of  claim 25 , wherein the Fc domain is a variant Fc domain. 
     
     
         27 . The isolated antibody of  claim 22 , wherein the drug moiety is attached to the antibody using a linker. 
     
     
         28 . The isolated antibody of  claim 27 , wherein the drug moiety is selected from the group consisting of an auristatin, a maytansinoid, a calicheamicin, a dolastatin, and a trichothecene. 
     
     
         29 . An isolated antibody which specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2),
 wherein the heavy chain variable region of the antibody comprises an amino acid sequence having an identity of at least 90% to SEQ ID NO:11, and the light chain variable region of the antibody comprises an amino acid sequence having an identity of at least 90% to SEQ ID NO:12;   wherein the antibody binds to human CD38 (SEQ ID NO:1) with a KD of 10 −8  M or a greater affinity, and wherein the affinity is measured by a standard Biacore assay; and   wherein the antibody is covalently attached to a drug moiety.   
     
     
         30 . The isolated antibody of  claim 29 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:11, and the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:12. 
     
     
         31 . The isolated antibody of  claim 29 , further comprising an Fc domain. 
     
     
         32 . The isolated antibody of  claim 31 , wherein the Fc domain is a human Fc domain. 
     
     
         33 . The isolated antibody of  claim 32 , wherein the Fc domain is a variant Fc domain. 
     
     
         34 . The isolated antibody of  claim 29 , wherein the drug moiety is attached to the antibody using a linker. 
     
     
         35 . The isolated antibody of  claim 34 , wherein the drug moiety is selected from the group consisting of an auristatin, a maytansinoid, a calicheamicin, a dolastatin, and a trichothecene. 
     
     
         36 . A method of treating cancer cells expressing CD38 comprising administering to a patient in need thereof an isolated antibody that specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2), comprising:
 a) a heavy chain variable region comprising an amino acid sequence having an identity of at least 90% to SEQ ID NO:9,   b) a light chain variable region comprising an amino acid sequence having an identity of at least 90% to SEQ ID NO:10; and   c) a covalently attached drug moiety,   wherein the antibody binds to human CD38 (SEQ ID NO:1) with a KD of 10 −8  M or a greater affinity, and wherein the affinity is measured by a standard Biacore assay.   
     
     
         37 . The method of  claim 36 , wherein the heavy chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:9, and the light chain variable region comprises an amino acid sequence having an identity of at least 95% to SEQ ID NO:10. 
     
     
         38 . An isolated nucleic acid encoding the heavy chain variable region of  claim 22 . 
     
     
         39 . An isolated nucleic acid encoding the light chain variable region of  claim 22 . 
     
     
         40 . An isolated nucleic acid composition comprising:
 a) a first nucleic acid encoding the heavy chain variable region of  claim 22 ; and   b) a second nucleic acid encoding the light chain variable region of  claim 22 .   
     
     
         41 . An expression vector comprising the nucleic acid of  claim 38  and the nucleic acid of  claim 39 . 
     
     
         42 . A host cell comprising the isolated nucleic acid composition of  claim 40 . 
     
     
         43 . A host cell comprising the expression vector of  claim 41 . 
     
     
         44 . A method of producing an antibody that specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2), comprising culturing the host cell of  claim 42 , wherein the antibody is produced. 
     
     
         45 . A method of producing an antibody that specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2), comprising culturing the host cell of  claim 43 , wherein the antibody is produced. 
     
     
         46 . An isolated nucleic acid encoding the heavy chain variable region of  claim 29 . 
     
     
         47 . An isolated nucleic acid encoding the light chain variable region of  claim 29 . 
     
     
         48 . An isolated nucleic acid composition comprising:
 a) a first nucleic acid encoding the heavy chain variable region of  claim 29 ; and   b) a second nucleic acid encoding the light chain variable region of  claim 29 .   
     
     
         49 . An expression vector comprising the nucleic acid of  claim 46  and the nucleic acid of  claim 47 . 
     
     
         50 . A host cell comprising the isolated nucleic acid composition of  claim 48 . 
     
     
         51 . A host cell comprising the expression vector of  claim 49 . 
     
     
         52 . A method of producing an antibody that specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2), comprising culturing the host cell of  claim 50 , wherein the antibody is produced. 
     
     
         53 . A method of producing an antibody that specifically binds human CD38 (SEQ ID NO:1) and cynomolgus CD38 (SEQ ID NO:2), comprising culturing the host cell of  claim 51 , wherein the antibody is produced.