Methods for treating metabolic syndrome 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 for treating metabolic syndrome in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of an IL-22 Fc fusion protein,
wherein the IL-22 Fc fusion protein binds to IL-22 receptor and 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. The method of claim 1 , wherein the subject has one or more of the following: abdominal obesity, hyperglycemia, dyslipidemia, and hypertension.
3. The method of claim 1 , wherein the subject is in need of a change in HDL/LDL lipid profile.
4. The method of claim 1 , wherein the subject is human.
5. The method of claim 1 , wherein the Fc region comprises an altered glycosylation consensus site.
6. The method of claim 1 , wherein the Fc region comprises an amino acid insertion, deletion, or substitution that results in an aglycosylated Fc region.
7. The method of claim 1 , wherein in the Fc region the amino acid residue at position 297 as in the EU index is substituted and/or the amino acid residue at position 299 as in the EU index is substituted.
8. The method of claim 7 , wherein the amino acid residue at position 297 as in the EU index is Gly, Ala, Gln, Asp, or Glu.
9. The method of claim 8 , wherein the amino acid residue at position 297 as in the EU index is Gly or Ala.
10. The method of claim 9 , wherein the amino acid residue at position 297 as in the EU index is Gly.
11. The method of claim 7 , wherein the amino acid residue at position 299 as in the EU index is Ala, Gly, or Val.
12. The method of claim 1 , wherein the IL-22 polypeptide is a human IL-22 polypeptide.
13. The method of claim 1 , wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO:4.
14. The method of claim 1 , wherein the IL-22 receptor is a human IL-22 receptor.
15. The method of claim 1 , wherein the amino acid sequence has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:8.
16. The method of claim 1 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:8.
17. The method of claim 1 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:10.
18. The method of claim 1 , wherein the IL-22 Fc fusion protein comprises the amino acid sequence of SEQ ID NO:16.
19. The method of claim 1 , wherein the IL-22 Fc fusion protein consists of the amino acid sequence of SEQ ID NO:8, SEQ ID NO:10, or SEQ ID NO:16.
20. The method of claim 1 , 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.
21. The method of claim 20 , wherein the process further comprises the step of obtaining the IL-22 Fc fusion protein from the cell culture or culture medium.
22. The method of claim 20 , wherein the host cell is a Chinese hamster ovary (CHO) cell.
23. The method of claim 1 , wherein the IL-22 Fc fusion protein is a dimeric IL-22 Fc fusion protein.
24. The method of claim 1 , wherein the IL-22 Fc fusion protein is a monomeric IL-22 Fc fusion protein.
25. The method of claim 1 , wherein the IL-22 Fc fusion protein is administered intravenously, subcutaneously, or intraperitoneally.
26. The method of claim 1 , wherein the subject is co-administered at least one additional therapeutic agent.
27. The method of claim 1 , wherein the IL-22 Fc fusion protein is administered in a pharmaceutical composition comprising the IL-22 Fc fusion protein and at least one pharmaceutically acceptable carrier.
28. The method of claim 27 , wherein the pharmaceutical composition is administered intravenously, subcutaneously, or intraperitoneally.
29. The method of claim 27 , wherein the pharmaceutical composition comprises an additional therapeutic agent.