Compositions and methods for treating gluten intolerance and disorders arising therefrom

Abstract

The invention described herein relates to methods and compositions for treatment of gluten intolerance and related conditions (e.g., celiac disease and gluten sensitivity), or inhibition of inflammation and/or immune response in the intestine due to antigenic food peptides, by administration of a pharmaceutical composition comprising one or more Nepenthes enzymes.

1 . A method for attenuating or preventing intestinal inflammation arising from the presence of peptidic food antigens in a patient in need thereof, which method comprises administering to the patient an effective amount of a pharmaceutical composition comprising an enzyme selected from the group consisting of nepenthesin I, nepenthesin II, neprosin, a variant thereof, and mixtures thereof, so as to cleave said antigens into non-antigenic peptides, thereby attenuating or preventing said intestinal inflammation. 
     
     
         2 . The method of  claim 1 , wherein the intestinal inflammation is characterized by infiltration and/or proliferation of intraepithelial lymphocytes (IELs) in the intestine of the patient, and further wherein the infiltration and/or proliferation of IELs in the intestine is attenuated or prevented. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the peptidic food antigens include partially hydrolyzed gluten protein. 
     
     
         6 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the patient suffers from a disease selected from the group consisting of gluten sensitivity, celiac disease, attention deficit hyperactivity disorder, autism, rheumatoid arthritis, fibromyalgia, nutrient malabsorption, and dermatitis herpetiformis. 
     
     
         10 . The method of  claim 1 , wherein the inflammation is due to celiac disease aggravated by the presence of gluten. 
     
     
         11 . A method for attenuating or preventing a manifestation of celiac disease arising from the presence of antigenic partially hydrolyzed wheat protein in an intestine of a patient having celiac disease, which method comprises administering to the patient an effective amount of an enzyme composition comprising an enzyme selected from the group consisting of nepenthesin I, nepenthesin II, neprosin, variant thereof, and a mixture thereof, so as to cleave said partially hydrolyzed wheat protein into non-antigenic peptides, thereby attenuating or preventing a manifestation of celiac disease. 
     
     
         12 . The method of  claim 11 , wherein the partially hydrolyzed wheat protein is a partially hydrolyzed gluten protein. 
     
     
         13 . The method of  claim 1 , wherein the pharmaceutical composition is a sustained-release formulation. 
     
     
         14 . The method of  claim 1 , wherein the pharmaceutical composition comprises an extract of  Nepenthes  pitcher fluid. 
     
     
         15 . The method of  claim 1 , wherein at least one of nepenthesin I, nepenthesin II, neprosin, or variant thereof is a recombinant protein. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the pharmaceutical composition is between about pH 5 and about pH 8. 
     
     
         18 . A method for attenuating or preventing intraepithelial lymphocytosis due to the presence of peptidic food antigens in an intestine of a patient in need thereof, which method comprises administering to the patient an effective amount of enzyme pharmaceutical composition comprising an enzyme selected from the group consisting of nepenthesin I, nepenthesin II, neprosin, and mixtures thereof, under conditions wherein said antigens are degraded so as to attenuate or prevent intraepithelial lymphocytosis in the intestine. 
     
     
         19 - 24 . (canceled) 
     
     
         25 . The method of  claim 1 , wherein the effective amount of the pharmaceutical composition is between about 1 mg and about 1 g. 
     
     
         26 - 31 . (canceled) 
     
     
         32 . A solid pharmaceutical composition comprising neprosin and a pharmaceutically acceptable buffering agent, wherein the neprosin is a protein comprising an amino acid sequence having at least 90% sequence homology to the amino acid sequence of SEQ ID NO.: 1 and further wherein the buffering agent maintains the composition at a pH of 6.5 or above prior to administration, such that said composition is formulated for oral administration. 
     
     
         33 . The pharmaceutical composition of  claim 32 , wherein the amino acid sequence of the neprosin comprises an amino acid sequence having at least 90% sequence homology to the amino acid sequence of SEQ ID NO.: 1 without the signal sequence. 
     
     
         34 . The pharmaceutical composition of  claim 33 , further comprising at least one additional  Nepenthes  enzyme or variant thereof. 
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the at least one additional  Nepenthes  enzyme or variant thereof is nepenthesin I, nepenthesin II, and/or a variant thereof. 
     
     
         36 . The pharmaceutical composition of  claim 32 , which is a sustained release formulation. 
     
     
         37 - 39 . (canceled) 
     
     
         40 . The pharmaceutical composition of  claim 34 , wherein the neprosin and/or  Nepenthes  enzyme(s) comprises a propeptide. 
     
     
         41 . (canceled) 
     
     
         42 . A pharmaceutical formulation comprising the composition of  claim 32 , wherein the neprosin is present in multiple layers such that the neprosin is released continuously while the formulation is present in the stomach. 
     
     
         43 - 50 . (canceled)