Anti-gcc antibody molecules and methods for use of same

Abstract

Antibodies and antigen-binding fragments of antibodies that bind GCC are 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 that competes for binding with, or binds to the same epitope as, a reference antibody molecule,
 wherein the reference antibody molecule comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region and the heavy chain variable region are selected from: the light chain variable region of antibody MIL-44-148-2 according to SEQ ID NO: 13, the heavy chain variable region of antibody MIL-44-148-2 according to SEQ ID NO: 11, the light chain variable region of antibody MIL-44-67-4 according to SEQ ID NO: 17, and the heavy chain variable region of antibody MIL-44-67-4 according to SEQ ID NO: 15.   
     
     
         2 . The anti-GCC antibody molecule of  claim 1 , wherein said anti-GCC antibody molecule is a monoclonal antibody. 
     
     
         3 . The anti-GCC antibody molecule of  claim 1 , wherein said anti-GCC antibody molecule is a rabbit or rabbit-derived antibody. 
     
     
         4 . The anti-GCC antibody molecule of  claim 1 , wherein said anti-GCC antibody molecule is a rabbit monoclonal antibody. 
     
     
         5 . The anti-GCC antibody molecule of  claim 1 , wherein said anti-GCC antibody molecule is conjugated to a detectable label. 
     
     
         6 . The anti-GCC antibody molecule of  claim 5 , wherein the detectable label comprises a fluorophore. 
     
     
         7 . The anti-GCC antibody molecule of  claim 6 , wherein the fluorophore comprises a rare earth chelate, fluorescein or a derivative thereof, rhodamine or a derivative thereof, a dansyl, an umbelliferone, a luceriferase, luciferin, or a 2,3-dihydrophthalazinedione. 
     
     
         8 . The anti-GCC antibody molecule of  claim 5 , wherein the detectable label comprises horseradish peroxidase (HRP), alkaline phosphatase, galactosidase, glucoamylase, lysozyme, a saccharide oxidase, a heterocyclic oxidase, lactoperoxidase, microperoxidase, biotin, avidin, a spin label, a bacteriophage label, or a stable free radical. 
     
     
         9 . The anti-GCC antibody molecule of  claim 5 , wherein the detectable label comprises a radionuclide or isotope. 
     
     
         10 . A kit comprising the anti-GCC antibody molecule of  claim 1  and instructions for use. 
     
     
         11 . An anti-GCC antibody molecule that competes for binding with, or binds to the same epitope as, a reference antibody molecule,
 wherein the reference antibody molecule comprises (i) light chain CDR1, CDR2, and CDR3 of antibody MIL-44-148-2 according to SEQ ID NOs: 27-29, respectively, or light chain CDR1, CDR2, and CDR3 of antibody MIL-44-67-4 according to SEQ ID NOs: 39-41, respectively, and (ii) heavy chain CDR1, CDR2, and CDR3 of antibody MIL-44-148-2 according to SEQ ID NOs: 21-23, respectively, or heavy chain CDR1, CDR2, and CDR3 of antibody MIL-44-67-4 according to SEQ ID NOs: 33-35, respectively.   
     
     
         12 . The anti-GCC antibody molecule of  claim 11 , further comprising rabbit or rabbit-derived light and heavy variable region frameworks. 
     
     
         13 . The anti-GCC antibody molecule of  claim 11 , wherein said anti-GCC antibody molecule is conjugated to a detectable label. 
     
     
         14 . The anti-GCC antibody molecule of  claim 13 , wherein the detectable label comprises a fluorophore. 
     
     
         15 . The anti-GCC antibody molecule of  claim 14 , wherein the fluorophore comprises a rare earth chelate, fluorescein or a derivative thereof, rhodamine or a derivative thereof, a dansyl, an umbelliferone, a luceriferase, luciferin, or a 2,3-dihydrophthalazinedione. 
     
     
         16 . The anti-GCC antibody molecule of  claim 13 , wherein the detectable label comprises horseradish peroxidase (HRP), alkaline phosphatase, galactosidase, glucoamylase, lysozyme, a saccharide oxidase, a heterocyclic oxidase, lactoperoxidase, microperoxidase, biotin, avidin, a spin label, a bacteriophage label, or a stable free radical. 
     
     
         17 . The anti-GCC antibody molecule of  claim 13 , wherein the detectable label comprises a radionuclide or isotope. 
     
     
         18 . A kit comprising the anti-GCC antibody molecule of  claim 11  and instructions for use. 
     
     
         19 . The anti-GCC antibody molecule of  claim 1 , wherein the reference antibody molecule comprises a heavy chain variable region according to SEQ ID NO: 11 and a light chain variable region according to SEQ ID NO: 13. 
     
     
         20 . The anti-GCC antibody molecule of  claim 11 , wherein the reference antibody molecule comprises a heavy chain CDR1, CDR2, and CDR3 according to SEQ ID NOs: 21-23, respectively, and a light chain CDR1, CDR2, and CDR3 according to SEQ ID NOs: 27-29, respectively.