Anti-gcc antibody molecules and related compositions and methods

Abstract

Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The antibodies bind an extracellular domain of GCC and can be internalized. In some embodiments, the antibodies are humanized, chimeric or human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.

What is claimed is: 
     
         1 . An anti-GCC antibody molecule, comprising a light chain variable region and a heavy chain variable region, wherein the light chain variable region comprises one, two, or three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) of any one of the antibody molecules disclosed in Table 5, and wherein the heavy chain variable region comprises one, two, or three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) of any one of the antibody molecule disclosed in Table 5. 
     
     
         2 . The anti-GCC antibody molecule of  claim 1 , wherein the anti-GCC antibody molecule is one of the antibody molecules disclosed in Tables 1 and 2. 
     
     
         3 . An antibody molecule that binds to the same, or substantially the same, epitope on GCC as the anti-GCC antibody molecule of  claim 1 . 
     
     
         4 . An antibody molecule that competes for binding to GCC with the anti-GCC antibody molecule of  claim 1 . 
     
     
         5 . An immunoconjugate of formula (I):
   AbX-Z) m   (I)
   or a pharmaceutically acceptable salt thereof, wherein:   Ab is the anti-GCC antibody molecule of  claim 1 ;   X is a linker moiety which connects Ab and Z;   Z is a therapeutic agent or a label; and   m is the number of —X-Z moieties per anti-GCC antibody molecule in the immunoconjugate of formula (I), and m is an integer from 1 to 15.   
     
     
         6 . An isolated nucleic acid encoding the antibody molecule, or one or both of the light and heavy chain variable regions of the antibody molecule, of  claim 1 . 
     
     
         7 . An isolated cell comprising the isolated nucleic acid of  claim 6 . 
     
     
         8 . A method of producing an antibody molecule of  claim 1 , comprising culturing the cell of  claim 7  under conditions that allow production of an antibody molecule, thereby producing the antibody molecule of  claim 1 . 
     
     
         9 . A vector comprising the isolated nucleic acid of  claim 6 . 
     
     
         10 . A method of detecting a GCC molecule comprising contacting the molecule with the antibody molecule of  claim 1  and determining if the antibody molecule binds to the GCC molecule. 
     
     
         11 . A pharmaceutical composition comprising the antibody molecule of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . A pharmaceutical composition comprising the immunoconjugate of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         13 . A method of treating a subject for a disorder, comprising administering to the subject, a therapeutically effective amount of an antibody molecule of  claim 1 , thereby treating the subject. 
     
     
         14 . A method of treating a subject for a disorder, comprising administering to the subject, a therapeutically effective amount of an immunoconjugate of  claim 5 , thereby treating the subject. 
     
     
         15 . The method of  claim 14 , wherein the disorder is cancer. 
     
     
         16 . The method of  claim 15 , wherein the cancer is a cancer of the gastrointestinal system, or a metastatic lesion thereof. 
     
     
         17 . The method of  claim 15 , wherein the cancer is primary or metastatic colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer, or lung cancer. 
     
     
         18 . The method of  claim 14 , further comprising administering to the subject an additional therapeutic agent. 
     
     
         19 . The method of  claim 18 , wherein the immunoconjugate and the additional therapeutic agent is administered simultaneously or sequentially to the subject. 
     
     
         20 . A container comprising the pharmaceutical composition of  claim 11 . 
     
     
         21 . A container comprising the pharmaceutical composition of  claim 12 . 
     
     
         22 . A kit comprising the anti-GCC antibody molecule of  claim 1 . 
     
     
         23 . A kit comprising the immunoconjugate of  claim 5 . 
     
     
         24 . A method of producing an immunoconjugate, the method comprising: providing the anti-GCC antibody molecule of  claim 1 ; and contacting the anti-GCC antibody molecule with a non-antibody moiety comprising a therapeutic agent or label under conditions that allow the production of an immunoconjugate, thereby producing the immunoconjugate.