Methods and Compositions for the Treatment of Gastrointestinal Disorders

Abstract

Compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudoobstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation, and constipation associated with neuropathic disorders as well as other conditions and disorders are described. The compositions feature peptides that activate the guanylate cyclase C (GC-C) receptor.

1 - 57 . (canceled) 
     
     
         58 . A method for treating a patient with a gastrointestinal disorder, the method comprising administering to the patient a composition comprising a polypeptide consisting of the amino acid sequence Asn Asp Glu Cys Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu (SEQ ID NO:73), wherein one or two amino acids are substituted by a D-isomer of the amino acid, wherein the gastrointestinal disorder is selected from the group consisting of a gastrointestinal motility disorder, irritable bowel syndrome, constipation, gastroesophageal reflux disease, functional heartburn, dyspepsia, functional dyspepsia, nonulcer dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction and colonic pseudo-obstruction. 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 58 , wherein the gastrointestinal disorder is dyspepsia, functional dyspepsia or nonulcer dyspepsia. 
     
     
         61 . The method of  claim 60 , wherein the gastrointestinal disorder is functional dyspepsia. 
     
     
         62 - 63 . (canceled) 
     
     
         64 . The method of  claim 58 , wherein the gastrointestinal disorder is irritable bowel syndrome. 
     
     
         65 . The method of  claim 64 , wherein the irritable bowel syndrome is constipation-predominant irritable bowel syndrome (c-IBS). 
     
     
         66 . The method of  claim 58 , wherein the gastrointestinal disorder is constipation. 
     
     
         67 . The method of  claim 66 , wherein the constipation is idiopathic constipation. 
     
     
         68 . The method of  claim 58 , wherein the gastrointestinal disorder is gastroparesis. 
     
     
         69 . A The method of  claim 58 , wherein the gastrointestinal disorder is a gastrointestinal motility disorder. 
     
     
         70 . (canceled) 
     
     
         71 . A method for treating a patient suffering from constipation-predominant irritable bowel syndrome, the method comprising orally administering to the patient a composition comprising a polypeptide consisting of the amino acid sequence Asn Asp Glu Cys Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu (SEQ ID NO: 73), wherein one or two amino acids are substituted by the D-isomer of the amino acid. 
     
     
         72 . The method of  claim 71 , wherein two amino acids are substituted by the D-isomer of the amino acid. 
     
     
         73 . A method for treating a patient suffering from constipation, the method comprising orally administering to the patient a composition comprising a polypeptide consisting of the amino acid sequence Asn Asp Glu Cys Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu (SEQ ID NO: 73), wherein one or two amino acids are substituted by the D-isomer of the amino acid. 
     
     
         74 . The method of  claim 73 , wherein two amino acids are substituted by the D-isomer of the amino acid. 
     
     
         75 - 93 . (canceled) 
     
     
         94 . The method of  claim 58 , wherein two amino acids are substituted by the D-isomer of the amino acid.