Compositions and methods for the diagnosis and treatment of tumor

Abstract

The invention is directed to antibody drug conjugate compositions of matter useful for the diagnosis and treatment of tumors in mammals and to methods of using those compositions of matter for the same.

1 . An isolated antibody that specifically binds a TAT10772 polypeptide, said antibody comprising three light chain hypervariable regions (HVR-L1, HVR-L2 and HVR-L3) and three heavy chain hypervariable regions (HVR-H1, HVR-H2 and HVR-H3) wherein:
 (a) HVR-L1 comprises the amino acid sequence of SEQ ID NO:119;   (b) HVR-L2 comprises the amino acid sequence of SEQ ID NO:121;   (c) HVR-L3 comprises the amino acid sequence of SEQ ID NO:122;   (d) HVR-H1 comprises the amino acid sequence of SEQ ID NO:123;   (e) HVR-H2 comprises the amino acid sequence of SEQ ID NO:125; and   (f) HVR-H3 comprises the amino acid sequence of SEQ ID NO:183.   
     
     
         2 . The isolated antibody of  claim 1  comprising one or both of (i) the VH sequence shown as SEQ ID NO:208 and (ii) the VL sequence shown as SEQ ID NO:211. 
     
     
         3 . The isolated antibody of  claim 1  wherein Ab is selected from an antibody fragment, a chimeric antibody, or a humanized antibody. 
     
     
         4 . The isolated antibody of  claim 1  wherein Ab is conjugated to a radioactive isotope. 
     
     
         5 . The isolated antibody of  claim 1  wherein Ab is detectably labeled. 
     
     
         6 . The isolated antibody of  claim 1  wherein Ab is produced in bacteria or CHO cells. 
     
     
         7 . An antibody drug conjugate comprising an antibody covalently attached by a linker to one or more toxin drug moieties, the compound having the formula:
   Ab-(L-D) p      or a pharmaceutically acceptable salt or solvate thereof, wherein:   Ab is an antibody according to  claim 1 ;   L is a linker;   D is a toxin drug moiety; and   p is 1 to about 20.   
     
     
         8 . The antibody drug conjugate of  claim 7  wherein D is a maytansinoid. 
     
     
         9 . The antibody drug conjugate of  claim 8  wherein the maytansinoid is DM1. 
     
     
         10 . The antibody drug conjugate of  claim 7  wherein D is an auristatin. 
     
     
         11 . The antibody drug conjugate of  claim 10  wherein the auristatin is MMAE or MMAF. 
     
     
         12 . The antibody drug conjugate of  claim 7  wherein L is MC-val-cit-PAB or MC. 
     
     
         13 . The antibody drug conjugate of  claim 7  wherein L is SMCC, SPP, or BMPEO. 
     
     
         14 . The antibody drug conjugate of  claim 7  wherein p is about 2 to about 5. 
     
     
         15 . The antibody drug conjugate of  claim 7  selected from the formula Ab-MC-val-cit-PAB-MMAE, Ab-MC-val-cit-PAB-MMAF, Ab-MC-MMAE, Ab-MC-MMAF, Ab-SPP-DM1 and Ab-SMCC-DM1. 
     
     
         16 . The antibody drug conjugate of  claim 7  wherein Ab is attached to the linker through a cysteine thiol of the antibody. 
     
     
         17 . A pharmaceutical formulation comprising the antibody drug conjugate of  claim 7  and a pharmaceutically acceptable diluent, carrier or excipient. 
     
     
         18 . An article of manufacture comprising
 an antibody drug conjugate compound of  claim 7 ;   a container; and   a package insert or label indicating that the antibody drug conjugate compound can be used to treat cancer characterized by the overexpression of a TAT10772 polypeptide.   
     
     
         19 . The article of manufacture of  claim 18  wherein the cancer is prostate cancer, cancer of the urinary tract, pancreatic cancer, lung cancer, breast cancer, colon cancer or ovarian cancer.