Treatment of inflammatory bowel disease by inhibiting binding and/or signalling through alpha4beta7 and its ligands and MAdCAM

Abstract

The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM.

What is claimed is:  
     
         1 . A method for treating an individual having a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM, comprising: 
 administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM.    
     
     
         2 . The method of  claim 1  wherein antibody is a monoclonal antibody or an antigen binding fragment thereof.  
     
     
         3 . The method of  claim 2  wherein the monoclonal antibody or antigen binding fragment thereof inhibits adhesion of leukocytes expressing an integrin containing the β7 chain and endothelium expressing MAdCAM.  
     
     
         4 . The method of  claim 3  wherein the monoclonal antibody or antigen binding fragment thereof binds α4β7 integrin.  
     
     
         5 . The method of  claim 4  wherein the monoclonal antibody or antigen binding fragment thereof binds β7.  
     
     
         6 . The method of  claim 3  wherein the monoclonal antibody or antigen binding fragment thereof binds MAdCAM.  
     
     
         7 . The method of  claim 3  wherein the monoclonal antibody or antigen binding fragment thereof has the antigenic specificity of a monoclonal antibody selected from the group consisting of FIB 21, FIB 30, FIB 504 and ACT-1.  
     
     
         8 . The method of  claim 7  wherein the monoclonal antibody or antigen binding fragment thereof is selected from the group consisting of FIB 21, FIB 30, FIB 504 and ACT-1 or antigen binding fragments thereof.  
     
     
         9 . The method of  claim 8  wherein the monoclonal antibody is ACT-1.  
     
     
         10 . The method of  claim 3  wherein the monoclonal antibody is selected from the group consisting of a chimeric antibody and a humanized antibody.  
     
     
         11 . The method of  claim 3  wherein the leukocytes are lymphocytes.  
     
     
         12 . The method of  claim 3  wherein the leukocytes are monocytes.  
     
     
         13 . The method of  claim 3  wherein the disease is inflammatory bowel disease.  
     
     
         14 . The method of  claim 13  wherein the disease is ulcerative colitis.  
     
     
         15 . The method of  claim 13  wherein the disease is Crohn's disease.  
     
     
         16 . The method of  claim 13  wherein the disease is Celiac disease, enteropathy associated with seronegative arthropathies, microscopic or collagenous colitis, eosinophilic gastroenteritis, or pouchitis.  
     
     
         17 . The method of  claim 13  wherein the monoclonal antibody or antigen binding fragment thereof binds α4β7.  
     
     
         18 . The method of  claim 13  wherein the monoclonal antibody or antigen binding fragment thereof binds MAdCAM.  
     
     
         19 . The method of  claim 13  wherein the monoclonal antibody or antigen binding fragment thereof has the antigenic specificity of a monoclonal antibody selected from the group consisting of FIB 21, FIB30, FIB 504 and ACT-1.  
     
     
         20 . The method of  claim 19  wherein the monoclonal antibody or antigen binding fragment thereof is selected from the group consisting of FIB 21, FIB30, FIB 504 and ACT-1 or antigen binding fragments thereof.  
     
     
         21 . The method of  claim 20  wherein the monoclonal antibody is ACT-1.  
     
     
         22 . The method of  claim 13  wherein the monoclonal antibody is selected from the group consisting of a chimeric antibody and a humanized antibody.  
     
     
         23 . The method of  claim 13  wherein more than one monoclonal antibody which inhibits the binding of leukocytes to endothelial MAdCAM is administered.  
     
     
         24 . The method of  claim 13  wherein more than one monoclonal antibody which inhibits the binding of leukocytes to endothelial ligands is administered.  
     
     
         25 . The method of  claim 24  wherein at least one monoclonal antibody inhibits the binding of leukocytes to an endothelial ligand other than MAdCAM.  
     
     
         26 . A method for treating inflammatory bowel disease in an individual comprising administering to the individual an effective amount of an antibody which binds endothelial MAdCAM or the α4β7 integrin.  
     
     
         27 . The method of  claim 26  wherein antibody is a monoclonal antibody or an antigen binding fragment thereof.  
     
     
         28 . The method of  claim 27  wherein the monoclonal antibody or antigen binding fragment thereof binds α4β7 integrin.  
     
     
         29 . The method of  claim 28  wherein the monoclonal antibody or antigen binding fragment thereof binds β7.  
     
     
         30 . The method of  claim 27  wherein the monoclonal antibody or antigen binding fragment thereof binds MAdCAM.  
     
     
         31 . The method of  claim 27  wherein the monoclonal antibody or antigen binding fragment thereof has the antigenic specificity of a monoclonal antibody selected from the group consisting of FIB 21, FIB 30, FIB 504 and ACT-1.  
     
     
         32 . The method of  claim 31  wherein the monoclonal antibody or antigen binding fragment thereof is selected from the group consisting of FIB 21, FIB 30, FIB 504 and ACT-1 or antigen binding fragments thereof.  
     
     
         33 . The method of  claim 32  wherein the monoclonal antibody is ACT-1.  
     
     
         34 . The method of  claim 27  wherein the monoclonal antibody is selected from the group consisting of a chimeric antibody and a humanized antibody.  
     
     
         35 . The method of  claim 27  wherein the disease is ulcerative colitis.  
     
     
         36 . The method of  claim 27  wherein the disease is Crohn's disease.  
     
     
         37 . The method of  claim 27  wherein the disease is Celiac disease, enteropathy associated with seronegative arthropathies, microscopic or collagenous colitis, eosinophilic gastroenteritis, or pouchitis.