Proteins for the treatment of epithelial barrier function disorders
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. A synthetic therapeutic protein, comprising: an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 19.
2. The protein of claim 1 , comprising: an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 19.
3. The protein of claim 1 , comprising: an amino acid sequence having at least 97% sequence identity to SEQ ID NO: 19.
4. The protein of claim 1 , comprising: an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 19.
5. The protein of claim 1 , comprising: an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 19.
6. The protein of claim 1 , comprising: the amino acid sequence of SEQ ID NO: 19.
7. The protein of claim 1 , wherein the amino acid at position 147 is valine.
8. The protein of claim 1 , wherein the amino acid at position 151 is serine.
9. The protein of claim 1 , wherein the amino acid at position 147 is valine, and the amino acid at position 151 is serine.
10. The protein of claim 1 , wherein the amino acid at position 84 is aspartic acid.
11. The protein of claim 1 , wherein the amino acid at position 84 is aspartic acid, and the amino acid at position 147 is valine, and the amino acid at position 151 is serine.
12. The protein of claim 1 , wherein the amino acid at position 83 is serine.
13. The protein of claim 1 , wherein the amino acid at position 83 is serine, and the amino acid at position 147 is valine, and the amino acid at position 151 is serine.
14. The protein of claim 1 , wherein the amino acid at position 53 is serine.
15. The protein of claim 1 , wherein the amino acid at position 53 is serine, and the amino acid at position 84 is aspartic acid, and the amino acid at position 147 is valine, and the amino acid at position 151 is serine.
16. The protein of claim 1 , wherein the amino acid at position 53 is serine, and the amino acid at position 83 is serine, and the amino acid at position 147 is valine, and the amino acid at position 151 is serine.
17. The protein of claim 1 , wherein the amino acid at position 147 is not cysteine, the amino acid at position 151 is not cysteine, the amino acid at position 83 is not asparagine, and/or the amino acid at position 53 is not asparagine.
18. A pharmaceutical composition, comprising: the protein of claim 1 and a pharmaceutically acceptable carrier.