Anti-sez6 antibody drug conjugates and methods of use

Abstract

Provided are novel anti-SEZ6 antibodies and antibody drug conjugates, and methods of using such anti-SEZ6 antibodies and antibody drug conjugates to treat cancer.

What is claimed is: 
     
         1 . An isolated antibody that specifically binds human SEZ6 wherein the antibody comprises a heavy chain sequence of SEQ ID NO:3 and a light chain sequence of SEQ ID NO:4. 
     
     
         2 . The antibody of  claim 1  wherein the antibody is conjugated to a calicheamicin payload. 
     
     
         3 . The antibody of  claim 2  wherein the calicheamicin payload comprises N—Ac calicheamicin. 
     
     
         4 . The antibody of  claim 3  wherein the calicheamicin payload comprises Formula II. 
     
     
         5 . A nucleic acid encoding all or part of an antibody of any one of  claims 1 - 4 . 
     
     
         6 . A vector comprising the nucleic acid of  claim 5 . 
     
     
         7 . A host cell comprising the nucleic acid of  claim 5  or the vector of  claim 6 . 
     
     
         8 . A SEZ6 ADC of the structure: 
       
         
           
           
               
               
           
         
       
       wherein Ab comprises an anti-SEZ6 antibody having a heavy chain sequence of SEQ ID NO:3 and a light chain sequence of SEQ ID NO:4 and wherein n is 2. 
     
     
         9 . A method of treating small cell lung cancer comprising administering a SEZ6 ADC of  claim 8  to a subject in need thereof. 
     
     
         10 . A pharmaceutical composition comprising the SEZ6 ADC of  claim 8 . 
     
     
         11 . The pharmaceutical composition of  claim 10  wherein the SEZ6 ADC of  claim 8  is the predominant ADC species. 
     
     
         12 . The pharmaceutical composition of  claim 11  wherein the predominant ADC species comprises greater than about 70% of the ADC species present in the composition. 
     
     
         13 . The pharmaceutical composition of  claim 11  wherein the predominant ADC species comprises greater than about 80% of the ADC species present in the composition. 
     
     
         14 . The pharmaceutical composition of  claim 11  wherein the predominant ADC species comprises greater than about 90% of the ADC species present in the composition. 
     
     
         15 . A method of treating small cell lung cancer comprising administering any one of the pharmaceutical compositions of  claims 8 - 14 . 
     
     
         16 . A method of producing an ADC of  claim 8  comprising the step of conjugating a hSEZ6-1.ss1 antibody having a heavy chain sequence of SEQ ID NO:3 and a light chain sequence of SEQ ID NO:4 with a drug linker comprising Formula II 
     
     
         17 . The method of  claim 16  further comprising the step of lyophilizing the ADC. 
     
     
         18 . A method of treating small cell lung cancer in a subject in need thereof comprising administering a SEZ6 ADC having a safety margin greater than 6 wherein the SEZ6 ADC comprises the structure: 
       
         
           
           
               
               
           
         
       
       wherein Ab comprises an anti-SEZ6 antibody having a heavy chain sequence of SEQ ID NO:3 and a light chain sequence of SEQ ID NO: 4 and wherein n is 2. 
     
     
         19 . The method of  claim 18  wherein the safety margin is about 10. 
     
     
         20 . A calicheamicin drug linker, or a pharmaceutically acceptable salt or solvate thereof comprising the structure: