Proteins for the treatment of epithelial barrier function disorders

Abstract

The disclosure relates to therapeutic proteins and pharmaceutical compositions comprising said proteins, which have utility in treating various human diseases. In particular aspects, the disclosed therapeutic proteins are useful for treating human gastrointestinal inflammatory diseases and gastrointestinal conditions associated with decreased epithelial cell barrier function or integrity. Further, the disclosed therapeutic proteins are useful for treating human inflammatory bowel disease, including inter alia, Crohn's disease and ulcerative colitis.

1 - 77 . (canceled) 
     
     
         78 . A pharmaceutical composition, comprising a protein comprising an amino acid sequence having at least about 90% sequence identity to the sequence set forth in SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:13 or SEQ ID NO:19, and a pharmaceutically acceptable carrier. 
     
     
         79 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises an amino acid sequence having at least about 95% sequence identity to the sequence set forth in SEQ ID NO: 1 SEQ ID NO:9, SEQ ID NO: 13 or SEQ ID NO: 19. 
     
     
         80 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises an amino acid sequence having at least about 97% sequence identity to the sequence set forth in SEQ ID NO: 1 SEQ ID NO:9, SEQ ID NO: 13 or SEQ ID NO: 19. 
     
     
         81 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises an amino acid sequence having at least about 98% sequence identity to the sequence set forth in SEQ ID NO: 1, SEQ ID NO:9, SEQ ID NO: 13 or SEQ ID NO: 19. 
     
     
         82 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises an amino acid sequence having at least about 99% sequence identity to the sequence set forth in SEQ ID NO: 1, SEQ ID NO:9, SEQ ID NO: 13 or SEQ ID NO: 19. 
     
     
         83 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 1, SEQ 1D NO:9, SEQ ID NO: 13 and SEQ ID NO: 19. 
     
     
         84 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises the amino acid sequence of SEQ ID NO: 1. 
     
     
         85 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises the amino acid sequence of SEQ ID NO:9. 
     
     
         86 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         87 . The pharmaceutical composition of  claim 78 , wherein the therapeutic protein comprises the amino acid sequence of SEQ ID NO: 19. 
     
     
         88 . The pharmaceutical composition of  claim 78 , formulated for rectal, parenteral, intravenous, topical, oral, dermal, transdermal, or subcutaneous administration. 
     
     
         89 . The pharmaceutical composition of  claim 78 , formulated such that the therapeutic protein has activity in the gastrointestinal lumen and/or intestines of the patient. 
     
     
         90 . The pharmaceutical composition of  claim 78 , wherein the amino acid sequence comprises at least one modification. 
     
     
         91 . The pharmaceutical composition of  claim 90 , wherein the modification is at least one amino acid substitution. 
     
     
         92 . The pharmaceutical composition of  claim 90 , wherein the modification is a post translational modification. 
     
     
         93 . The pharmaceutical composition of  claim 92 , wherein the post transcriptional modification is pegylation. 
     
     
         94 . The pharmaceutical composition of  claim 92 , wherein the post transcriptional modification is glycosylation, ubiquitination, nitrosylation, methylation, acetylation, or lipidation. 
     
     
         95 . The pharmaceutical composition of  claim 92 , wherein the post transcriptional modification is phosphorylation, glycosylation, ubiquitination, nitrosylaton, methylation, acetylation, lipidation, or proteolysis.