Compositions and Methods for Treating Celiac Sprue Disease

Abstract

The invention provides compositions and methods for treating celiac sprue.

We claim: 
     
         1 . A polypeptide comprising an amino acid sequence at least 75% identical to an amino acid sequence according to SEQ ID NO:35, wherein
 (a) the polypeptide degrades a PQPQLP (SEQ ID NO:34) peptide at pH 4;   (b) residue 278 is Ser, residue 78 is Glu, and residue 82 is Asp; and   (c) the polypeptide comprises an amino acid change from SEQ ID NO: 67 at one or more residues selected from the group consisting of 73, 102, 103, 104, 130, 165, 168, 169, 172, and 179.   
     
     
         2 . A polypeptide comprising an amino acid sequence at least 75% identical to an amino acid sequence according to SEQ ID NO:1, wherein
 (a) the polypeptide degrades a PQPQLP (SEQ ID NO:34) peptide at pH 4;   (b) residue 467 is Ser, residue 267 is Glu, and residue 271 is Asp; and   (c) the polypeptide comprises an amino acid change from SEQ ID NO: 33 at one or more residues selected from the group consisting of 119, 262, 291, 292, 293, 319, 354, 357, 358, 361, and 368.   
     
     
         3 . The polypeptide of  claim 1  or  2 , comprising an amino acid sequence at least 85% identical to an amino acid sequence according to SEQ ID NO:1 or SEQ ID NO: 35. 
     
     
         4 . The polypeptide of  claim 1  or  2 , comprising an amino acid sequence at least 95% identical to an amino acid sequence according to SEQ ID NO:1 or SEQ ID NO: 35. 
     
     
         5 . The polypeptide of  claim 1 , comprising an amino acid sequence according to SEQ ID NO:35. 
     
     
         6 . The polypeptide of  claim 2 , comprising an amino acid sequence according to SEQ ID NO:1. 
     
     
         7 . The polypeptide of any one of  claims 1 - 6 , wherein the polypeptide, comprises an amino acid sequence according to any one of SEQ ID NO:2-66. 
     
     
         8 . The polypeptide of any one of  claims 1 - 8 , wherein the polypeptide comprises an amino acid sequence according to SEQ ID NO:32 or SEQ ID NO: 66. 
     
     
         9 . A polypeptide comprising an amino acid sequence according to SEQ ID NO:1, wherein the polypeptide comprises at least one amino acid change from SEQ ID NO: 33. 
     
     
         10 . A polypeptide comprising an amino acid sequence according to SEQ ID NO:35, wherein the polypeptide comprises at least one amino acid change from SEQ ID NO: 67. 
     
     
         11 . The polypeptide of  claim 9  or  10 , comprising an amino acid sequence according to any one of SEQ ID NO:2-66. 
     
     
         12 . The polypeptide of any one of  claims 9 - 11 , wherein the polypeptide comprises an amino acid sequence according to SEQ ID NO:32 or SEQ ID NO:66. 
     
     
         13 . A nucleic acid encoding the polypeptide of any one of  claims 1 - 12 . 
     
     
         14 . A nucleic acid expression vector comprising the isolated nucleic acid of  claim 13 . 
     
     
         15 . A recombinant host cell comprising the nucleic acid expression vector of  claim 14 . 
     
     
         16 . A pharmaceutical composition, comprising the polypeptide of any one of  claims 1 - 12 , the nucleic acid of  claim 13 , the nucleic acid expression vector of  claim 14 , and/or the recombinant host cell of  claim 15 , and a pharmaceutically acceptable carrier. 
     
     
         17 . A method for treating celiac sprue, comprising administering to an individual with celiac sprue an amount effective to treat the celiac sprue of a polypeptide according to any one of  claims 1 - 12 , or a polypeptide comprising an amino acid selected from the group consisting of SEQ ID NO:33 or SEQ ID NO:67. 
     
     
         18 . A method for treating celiac sprue, comprising administering to an individual with celiac sprue an amount effective of the pharmaceutical composition of  claim 16  to treat the celiac sprue. 
     
     
         19 . The method of any one of  claims 17 - 18 , wherein the polypeptide or the pharmaceutical composition is administered orally. 
     
     
         20 . The method of any one of  claims 17 - 19 , wherein the polypeptide comprises an amino acid sequence according to SEQ ID NO:32 or SEQ ID NO:66.