Antibody drug conjugates (adc) that bind to 158p1d7 proteins

Abstract

Antibody drug conjugates (ADC's) that bind to 158P1D7 protein and variants thereof are described herein. 158P1D7 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in glioblastoma, lung cancer, bladder cancer, and breast cancer. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

1 . (canceled) 
     
     
         2 . An antibody drug conjugate comprising an antibody or antigen binding fragment thereof which binds to a 158P1D7 protein, wherein the antibody or antigen binding fragment is conjugated to monomethyl auristatin E (MMAE), and wherein the antibody or antigen binding fragment thereof comprises:
 (i) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain variable region comprising an amino acid sequence at least 80% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO:8;   (ii) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain variable region consisting of the amino acid sequence ranging from position 1 to position 113 of SEQ ID NO:8;   (iii) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain consisting of the amino acid sequence ranging from position 1 to position 219 of SEQ ID NO:8;   (iv) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain variable region consisting of the amino acid sequence of the light chain variable region of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under ATCC Accession No. PTA-13102;   (v) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs in the heavy chain variable region sequence set forth in SEQ ID NO:7 and a light chain consisting of the amino acid sequence of a light chain of an antibody produced by a Chinese Hamster Ovary (CHO) deposited under ATCC Accession No. PTA-13102;   (vi) a heavy chain variable region comprising an amino acid sequence at least 80% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO:7 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8;   (vii) a heavy chain variable region consisting of the amino acid sequence ranging from position 1 to position 120 of SEQ ID NO:7 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8;   (viii) a heavy chain consisting of the amino acid sequence ranging from position 1 to position 446 of SEQ ID NO:7 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8;   (ix) a heavy chain variable region consisting of the amino acid sequence of the heavy chain variable region of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under American Type Culture Collection (ATCC) Accession No. PTA-13102 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8;   (x) a heavy chain consisting of the amino acid sequence of the heavy chain of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under ATCC Accession No. PTA-13102 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs in the light chain variable region sequence set forth in SEQ ID NO:8;   (xi) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:7 according to Kabat numbering and a light chain variable region comprising an amino acid sequence at least 80% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO:8;   (xii) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:7 according to Kabat numbering and a light chain consisting of the amino acid sequence ranging from position 1 to position 219 of SEQ ID NO:8;   (xiii) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:7 according to Kabat numbering and a light chain variable region consisting of the amino acid sequence of the light chain variable region of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under ATCC Accession No. PTA-13102;   (xiv) a heavy chain variable region comprising complementarity determining regions (CDRs) consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:7 according to Kabat numbering and a light chain consisting of the amino acid sequence of a light chain of an antibody produced by a Chinese Hamster Ovary (CHO) deposited under ATCC Accession No. PTA-13102;   (xv) a heavy chain variable region comprising an amino acid sequence at least 80% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO:7 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:8 according to Kabat numbering;   (xvi) a heavy chain consisting of the amino acid sequence ranging from position 1 to position 446 of SEQ ID NO:7 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:8 according to Kabat numbering;   (xvii) a heavy chain variable region consisting of the amino acid sequence of the heavy chain variable region of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under American Type Culture Collection (ATCC) Accession No. PTA-13102 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:8 according to Kabat numbering; or   (xviii) a heavy chain consisting of the amino acid sequence of the heavy chain of an antibody produced by a Chinese Hamster Ovary (CHO) cell deposited under ATCC Accession No. PTA-13102 and a light chain variable region comprising CDRs consisting of the amino acid sequences of the CDRs set forth in SEQ ID NO:8 according to Kabat numbering.   
     
     
         3 . The antibody drug conjugate of  claim 2 , wherein the antigen binding fragment thereof is an Fab, F(ab′)2, Fv, or scFv fragment. 
     
     
         4 . The antibody drug conjugate of  claim 2 , wherein the antibody is a fully human antibody. 
     
     
         5 . The antibody drug conjugate of  claim 2 , wherein the antibody is recombinantly produced. 
     
     
         6 . The antibody drug conjugate of  claim 2 , wherein the antibody or antibody binding fragment thereof is conjugated to the MMAE via a linker. 
     
     
         7 . The antibody drug conjugate of  claim 6 , wherein the linker comprises valine citrulline. 
     
     
         8 . The antibody drug conjugate of  claim 6 , wherein the antibody drug conjugate has the following structure: 
       
         
           
           
               
               
           
         
         s wherein L-represents the antibody or antigen binding fragment thereof and p ranges from 1 to 10. 
       
     
     
         9 . The antibody drug conjugate of  claim 8 , wherein the p ranges from 2 to 5. 
     
     
         10 . A pharmaceutical composition that comprises a therapeutically effective amount of the antibody drug conjugate of  claim 2  and a pharmaceutically acceptable excipient. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the composition is for treatment of glioblastoma cancer, lung cancer, bladder cancer, or breast cancer. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the composition is administered in combination with radiation or a chemotherapeutic agent. 
     
     
         13 . The pharmaceutical composition of  claim 10 , further comprising a chemotherapeutic agent in a human unit dose form. 
     
     
         14 . A method of treating cancer in a subject, comprising administering to said subject a therapeutically effective amount of the antibody drug conjugate of  claim 2   
     
     
         15 . The method of  claim 14 , wherein the cancer expresses 158P1D7. 
     
     
         16 . The method of  claim 14 , wherein the subject is a human subject. 
     
     
         17 . The method of  claim 14 , comprising administering about 1 to about 5 mg/kg of the antibody drug conjugate to the subject. 
     
     
         18 . The method of  claim 14 , wherein the cancer is selected from the group consisting of glioblastoma, lung cancer, bladder cancer, and breast cancer. 
     
     
         19 . The method of  claim 18 , wherein the cancer is bladder cancer.