Mucin Derived Polypeptides

Abstract

The present technology relates to isolated MUC17, Muc3 or MUC3 derived polypeptides and polynucleotides encoding the same. The MUC17, Muc3 or MUC3 derived polypeptides and polynucleotides can be used to treat gastrointestinal tract diseases and disorders. Also described herein are pharmaceutical compositions comprising MUC17, Muc3 or MUC3 derived polypeptides and/or polynucleotides encoding the same alone or in combination along with a pharmaceutically acceptable carrier, diluent or excipient for the treatment of gastrointestinal disorders and diseases, including, irritable bowel disease and its associated colitides, for example, Crohn's Disease.

1 . A mucin derived polypeptide comprising
 an amino acid sequence recited in any one of SEQ ID NO: 1, SEQ ID NO: 2 SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, or a therapeutically acceptable salt thereof.   
     
     
         2 . The polypeptide of  claim 1  consisting of
 the amino acid sequence recited in any one of SEQ ID NO: 1, SEQ ID NO: 2 SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, or a therapeutically acceptable salt thereof. 
 
     
     
         3 . The polypeptide of  claim 1 , wherein the polypeptide comprises a tag or partial mucin protein. 
     
     
         4 . The polypeptide of  claim 1  further comprising
 at least one of CRD1 and CRD2 EGF-like domains that are chemically synthesized. 
 
     
     
         5 . The polypeptide of  claim 1 , wherein
 the polypeptide is produced recombinantly.   
     
     
         6 . The polypeptide of  claim 5 , wherein
 the polypeptide is recombinantly made in  E. coli.      
     
     
         7 . The polypeptide of  claim 5 , wherein the the polypeptide is recombinantly made in yeast cells, insect cells or CHO cells. 
     
     
         8 . The polypeptide of  claim 1  further comprising one or more of a plural His tag, a FLAG-tag and a GST-tag. 
     
     
         9 . The polypeptide of  claim 8 , wherein the tag further comprises: a detection marker, a biotin marker, a fluorescence marker, a green fluorescence protein, a red fluorescence protein, alkaline phosphatase, glucose oxidase, horse radish peroxidase, a chemiluminescence marker, a radioisotope marker, an S-protein marker or combinations thereof. 
     
     
         10 . The polypeptide of  claim 9 , wherein the detection marker, if present, is a streptavidin/avidin marker, the green fluorescence protein, if present, is GFP or EGFP, and the red fluorescence protein, if present, is DsRed or drFP583. 
     
     
         11 . A polynucleotide encoding a polypeptide of  claim 1  or a complement thereof. 
     
     
         12 . A vector comprising the polynucleotide of  claim 11 . 
     
     
         13 . A host cell comprising the vector of  claim 12 , the vector being operable to express the polypeptide of  claim 1 . 
     
     
         14 . A pharmaceutical composition comprising a therapeutically effective amount of a derived polypeptide of  claim 1  and a pharmaceutical excipient. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition is formulated for oral, parental, or rectal administration in a solid, liquid or aerosol form. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the pharmaceutical composition further comprises a second active agent. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the second agent is selected from the group consisting of: aminosalicylates, acetaminophen, laxatives, non-steroidal anti-inflammatory drug substances (NSAIDS), antibiotics, corticosteroids, anti-diarrheals and immune modifying agents. 
     
     
         18 . A method for treating a gastrointestinal disease or disorder in a subject in need thereof, the method comprising administering a therapeutically effective amount of a polypeptide of  claim 1 . 
     
     
         19 . The method of  claim 18 , wherein administering the therapeutically effective amount of the polypeptide comprises administering the polypeptide orally, parentally, rectally or combinations thereof. 
     
     
         20 . The method of  claim 19 , wherein the therapeutically effective amount of the polypeptide is administered orally or rectally. 
     
     
         21 . The method of  claim 18 , wherein the gastrointestinal disease or disorder comprises irritable bowel disease (IBD), irritable bowel syndrome, ulcerative colitis, mucositis, Crohn's disease, chronic colitis, microscopic colitis, indeterminate colitis, ileal inflammation and diverticulitis. 
     
     
         22 . The method of  claim 18 , wherein the therapeutically effective amount of the polypeptide administered to a subject is administered in an amount ranging from about 0.01 to about 100 mg/kg body weight/day. 
     
     
         23 . The method of  claim 18 , wherein the therapeutically effective amount of the polypeptide administered to a subject is administered in an amount ranging from about 0.5 to about 5 mg/kg body weight/day.