Methods of treating inflammatory bowel disease using IL-22 Fc fusion proteins
The invention relates to IL-22 polypeptides, IL-22 Fc fusion proteins and IL-22 agonists, composition comprising the same, methods of making and methods of using the composition for the treatment of diseases. The invention also relates to IL-22 receptor associated reagents and methods of use thereof.
1. A method of treating IBD, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein comprising an IL-22 polypeptide linked to an IgG4 Fc region by a linker, wherein the Fc region is not glycosylated, and wherein the linker consists of the amino acid sequence RVESKYGPP (SEQ ID NO: 44).
2. A method of treating IBD, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:16.
3. The method of claim 2 or 1 , wherein the IBD is ulcerative colitis.
4. The method of claim 2 or 1 , wherein the IBD is Crohn's disease.
5. A method of treating IBD, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:8.
6. A method of treating inflammatory bowel disease (IBD), the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein, the IL-22 Fc fusion protein comprising an IL-22 polypeptide linked by a linker to an IgG4 Fc region that is not glycosylated, wherein the IL-22 Fc fusion protein binds to IL-22 receptor and comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO:8, and wherein the linker consists of the amino acid sequence RVESKYGPP (SEQ ID NO: 44).
7. The method of claim 6 , wherein the amino acid sequence of the IL-22 Fc fusion protein has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:8.
8. The method of claim 6 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:10.
9. The method of claim 6 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:16.
10. The method of claim 6 , wherein the IL-22 polypeptide is a human IL-22 polypeptide.
11. The method of claim 6 , wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO:4.
12. The method of claim 6 , wherein the IL-22 receptor is a human IL-22 receptor.
13. The method of claim 6 , wherein the amino acid residue at position 297 as in the EU index of the IgG4 Fc region is Gly.
14. The method of claim 6 , wherein the amino acid residue at position 297 as in the EU index of the IgG4 Fc region is Ala.
15. The method of claim 6 , wherein the IL-22 Fc fusion protein is a dimeric IL-22 Fc fusion protein.
16. The method of claim 6 , wherein the IL-22 Fc fusion protein is a monomeric IL-22 Fc fusion protein.
17. The method of claim 6 , wherein the IL-22 Fc fusion protein is administered in a formulation comprising a pharmaceutically acceptable carrier.
18. The method of claim 6 , wherein the subject is administered at least one additional therapeutic agent.
19. The method of claim 6 , wherein the IL-22 Fc fusion protein is administered intravenously.
20. The method of claim 6 , wherein the IL-22 Fc fusion protein is administered subcutaneously.
21. The method of claim 6 , wherein the IL-22 Fc fusion protein is administered intraperitoneally.
22. The method of claim 6 , wherein the IBD is ulcerative colitis.
23. The method of claim 6 , wherein the IBD is Crohn's disease.
24. The method of claim 6 , wherein the subject is a human.
25. A method of treating IBD, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein comprising the amino acid sequence of SEQ ID NO:8.
26. The method of any one of claims 5 , 2 , 1 wherein the subject is a human.
27. A method of treating ulcerative colitis, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein comprising the amino acid sequence of SEQ ID NO:8.
28. A method of treating ulcerative colitis, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:8.
29. A method of treating Crohn's disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein comprising the amino acid sequence of SEQ ID NO:8.
30. A method of treating Crohn's disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:8.