Methods of accelerating or improving wound healing 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 accelerating or improving wound healing in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an interleukin (IL)-22 Fc fusion protein and at least one pharmaceutically acceptable carrier,
wherein the IL-22 Fc fusion protein comprises an IL-22 polypeptide linked by a linker to an IgG4 Fc region that is not glycosylated, wherein the IL-22 Fc fusion protein 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 of RVESKYGPP (SEQ ID NO:44).
2. A method of accelerating or improving wound healing in a subject, 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 by a linker to an IgG4 Fc region that is not glycosylated, wherein the IL-22 Fc fusion protein 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 of RVESKYGPP (SEQ ID NO:44).
3. The method of claim 1 or 2 , wherein the IL-22 Fc fusion protein comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO:8.
4. The method of claim 1 or 2 , wherein the IL-22 Fc fusion protein consists of the amino acid sequence of SEQ ID NO:8 or SEQ ID NO:10.
5. The method of claim 1 or 2 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:8.
6. The method of claim 1 or 2 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:10.
7. The method of claim 1 or 2 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:16.
8. The method of claim 1 or 2 , wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO:4.
9. The method of claim 1 or 2 , wherein the Fc region comprises an altered glycosylation consensus site.
10. The method of claim 1 or 2 , wherein the Fc region comprises an insertion, a deletion, or a substitution mutation that results in an aglycosylated Fc region.
11. The method of claim 1 or 2 , wherein in the Fc region the amino acid residue at position 297 as in the EU index is changed and/or the amino acid residue at position 299 as in the EU index is changed.
12. The method of claim 11 , wherein the amino acid residue at position 297 as in the EU index is Gly, Ala, Gln, Asp, or Glu.
13. The method of claim 12 , wherein the amino acid residue at position 297 as in the EU index is Gly or Ala.
14. The method of claim 13 , wherein the amino acid residue at position 297 as in the EU index is Gly.
15. The method of claim 11 , wherein the amino acid residue at position 299 as in the EU index is Ala, Gly, or Val.
16. The method of claim 1 or 2 , wherein the IL-22 fusion protein is a dimeric IL-22 Fc fusion protein.
17. The method of claim 1 or 2 , wherein the IL-22 fusion protein is a monomeric IL-22 Fc fusion protein.
18. The method of claim 1 or 2 , wherein the IL-22 Fc fusion protein is produced by a process comprising the step of culturing a host cell capable of expressing the IL-22 Fc fusion protein under conditions suitable for expression of the IL-22 Fc fusion protein.
19. The method of claim 18 , wherein the host cell is a Chinese hamster ovary (CHO) cell.
20. The method of claim 1 or 2 , wherein the subject is human.
21. The method of claim 1 or 2 , wherein the wound is a chronic wound or an infected wound.
22. The method of claim 1 or 2 , wherein the subject is diabetic.
23. The method of claim 22 , wherein the diabetic subject has type II diabetes.
24. The method of claim 1 or 2 , wherein the wound is a diabetic foot ulcer.
25. The method of claim 1 or 2 , wherein the subject is co-administered at least one additional therapeutic agent for accelerating or improving wound healing.
26. The method of claim 1 , wherein the pharmaceutical composition is administered intravenously, subcutaneously, intraperitoneally, or topically.
27. The method of claim 26 , wherein the pharmaceutical composition is administered topically.
28. The method of claim 26 , wherein the pharmaceutical composition is administered subcutaneously.
29. The method of claim 1 , wherein the pharmaceutical composition is administered until there is complete wound closure.
30. The method of claim 1 , wherein the pharmaceutically acceptable carrier is a gelling agent.
31. The method of claim 30 , wherein the gelling agent is a polysaccharide.
32. The method of claim 31 , wherein the polysaccharide is a cellulosic agent.
33. The method of claim 30 , wherein the gelling agent is methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, POE-POP block polymers, alginate, hyaluronic acid, polyacrylic acid, hydroxyethyl methylcellulose or hydroxypropyl methylcellulose.
34. The method of claim 33 , wherein the gelling agent is hydroxypropyl methylcellulose.
35. The method of claim 33 , wherein the pharmaceutical composition is for topical administration.
36. The method of claim 1 , wherein the pharmaceutical composition comprises an additional therapeutic agent.
37. The method of claim 2 , wherein the IL-22 Fc fusion protein is administered intravenously, subcutaneously, intraperitoneally, or topically.
38. The method of claim 37 , wherein the IL-22 Fc fusion protein is administered topically.
39. The method of claim 37 , wherein the IL-22 Fc fusion protein is administered subcutaneously.
40. The method of claim 2 , wherein the IL-22 Fc fusion protein is administered until there is complete wound closure.