Mucosal vascular addressins and uses thereof

Abstract

The present invention relates to isolated antibodies and antigen-binding fragments that selectively bind human MAdCAM.

1 . An isolated antibody or antigen-binding fragment thereof that binds naturally occurring human MAdCAM, wherein said naturally occurring human MAdCAM comprises a polypeptide with at least 90% sequence identity to SEQ ID NO:2 or SEQ ID NO:4, said naturally occurring human MAdCAM binds α4β7, and wherein said isolated antibody or antigen-binding fragment thereof inhibits binding of said naturally occurring human MAdCAM to human α4β7. 
     
     
         2 . The isolated antibody or antigen-binding fragment of  claim 1 , wherein said human MAdCAM comprises amino acids 19-406 of SEQ ID NO:2. 
     
     
         3 . The isolated antibody or antigen-binding fragment of  claim 1 , wherein said human MAdCAM comprises amino acids 19-382 of SEQ ID NO:4. 
     
     
         4 . The isolated antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment selectively binds to the extracellular region of human MAdCAM. 
     
     
         5 . The isolated antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment selectively binds amino acids 19-225 of SEQ ID NO:2. 
     
     
         6 . The isolated antibody or antigen-binding fragment of  claim 1 , wherein said antibody or antigen-binding fragment selectively binds amino acids 19-225 of SEQ ID NO:4. 
     
     
         7 . The isolated antibody or antigen-binding fragment of  claim 1 , wherein said antibody inhibits α4β7-dependent adhesion. 
     
     
         8 . A pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 1  and a physiologically acceptable carrier. 
     
     
         9 . An isolated cell that produces an antibody or antigen-binding fragment of  claim 1 . 
     
     
         10 . A method of treating an inflammatory disease of mucosal tissue, comprising administering an effective amount of the antibody or antigen-binding fragment of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein said inflammatory disease is inflammatory bowel disease. 
     
     
         12 . A method of detecting naturally occurring human MAdCAM in a sample, comprising contacting said sample with an antibody or antigen-binding fragment of  claim 1 , and detecting antibody-MAdCAM or antigen-binding fragment-MAdCAM complexes which are formed. 
     
     
         13 . The isolated antibody of  claim 1 , wherein said human MAdCAM comprises SEQ ID NO:17.