Methods and compositions for treating celiac disease

Abstract

The invention features the treatment of gastrointestinal disorders associated with an innate immune response tiggered by alpha amylase inhibitor CM3, alpha amylase inhibitor 0.19 (0.19), CM1, CM2, CMa, CMd, CM16, CMb, CMX1/CMX3, CMX2, and/or alpha amylase inhibitor 0.53 (0.53). To this end, the invention features pharmaceutical compositions including neutralizing antibodies to CM3, 0.19, CM1, CM2, CMa, CMd, CM16, CMb, CMX1/CMX3, CMX2, and/or 0.53, food products containing reduced levels of CM3, 0.19, CM1, CM2, CMa, CMd, CM16, CMb, CMX1/CMX3, CMX2, and/or 0.53 protein, the use of oral TLR4 inhibitors to block the effect of said alpha-amylase inhibitors, assays for identifying CM3, 0.19, CM1, CM2, CMa, CMd, CM16, CMb, CMX1/CMX3, CMX2, and/or 0.53 content in food products, and assays for diagnosing subjects with a disorder related to CM3, 0.19, CM1, CM2, CMa, CMd, CM16, CMb, CMX1/CMX3, CMX2, and/or 0.53 triggered innate immune responses.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising an antibody against alpha Amylase Inhibitor CM3 (CM3). 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said antibody is a polyclonal antibody. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said antibody is a monoclonal antibody. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein said antibody is humanized. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein said antibody is formulated for oral administration. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein said antibody is formulated in milk or colostrum. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein said antibody is generated in the milk or colostrum of a mammal. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein said mammal is a cow or a goat. 
     
     
         9 . The pharmaceutical composition of  claim 5 , wherein said antibody is formulated to be active in the intestine. 
     
     
         10 . A method of treating a gastrointestinal disorder comprising administering the pharmaceutical composition of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein said gastrointestinal disorder is selected from the group consisting of celiac disease, ulcerative colitis, and Crohn's disease. 
     
     
         12 . The method of  claim 10 , wherein said pharmaceutical composition is administered immediately prior to, concomitant with or after a meal. 
     
     
         13 . The method of  claim 10 , wherein said pharmaceutical composition is administered once or twice daily. 
     
     
         14 - 31 . (canceled) 
     
     
         32 . A pharmaceutical composition comprising an antibody against a protein selected from the group consisting of Alpha Amylase Inhibitor 0.19 (0.19), CM1, CM2, CMa, CMd, CM16, CMb, CMX1/CMX3, CMX2, alpha Amylase Inhibitor 0.53 (0.53), and structurally and functionally related compounds. 
     
     
         33 . The pharmaceutical composition of  claim 32 , wherein said antibody is a polyclonal antibody. 
     
     
         34 . The pharmaceutical composition of  claim 32 , wherein said antibody is a monoclonal antibody. 
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein said antibody is humanized. 
     
     
         36 . The pharmaceutical composition of  claim 32 , wherein said antibody is formulated for oral administration. 
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein said antibody is formulated in milk or colostrum. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein said antibody is generated in the milk or colostrum of a mammal. 
     
     
         39 . The pharmaceutical composition of  claim 38 , wherein said mammal is a cow or a goat. 
     
     
         40 . The pharmaceutical composition of  claim 36 , wherein said antibody is formulated to be active in the intestine. 
     
     
         41 . A method of treating a gastrointestinal disorder comprising administering the pharmaceutical composition of  claim 32 . 
     
     
         42 . The method of  claim 41 , wherein said gastrointestinal disorder is selected from the group consisting of celiac disease, ulcerative colitis, and Crohn's disease. 
     
     
         43 . The method of  claim 42 , wherein said pharmaceutical composition is administered immediately prior to a meal. 
     
     
         44 . The method of  claim 43 , wherein said pharmaceutical composition is administered once or twice daily. 
     
     
         45 - 66 . (canceled) 
     
     
         67 . The method of  claim 3 , wherein said antibody is isolated from a hybridoma. 
     
     
         68 . The method of  claim 34 , wherein said antibody is isolated form a hybridoma.