Methods of accelerating or improving wound healing using IL-22 FC fusion proteins

Patent metadata

Field	Value
Publication number	US-10544198-B2
Application number	US-201715454662-A
Country	US
Kind code	B2
Filing date	Mar 9, 2017
Priority date	Mar 15, 2013
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Genentech Inc

Inventors

• Scheer Justin
• Ouyang Wenjun
• Vandlen Richard
• Hass Philip E
• Stefanich Eric Gary
• Wang Xiaoting
• Kolumam Ganesh A
• Lee Wyne P

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P39/02

  Antidotes · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title