Nucleic acids encoding 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. An isolated nucleic acid encoding an interleukin (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 of RVESKYGPP (SEQ ID NO:44).
2. The nucleic acid of claim 1 , wherein the amino acid sequence has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:8.
3. The nucleic acid of claim 1 , wherein the amino acid residue at position 297 as in the EU index of the IgG4 Fc region is Gly.
4. The nucleic acid of claim 1 , wherein the amino acid residue at position 297 as in the EU index of the IgG4 Fc region is Ala.
5. The nucleic acid of claim 1 , wherein the IL-22 polypeptide is a human IL-22 polypeptide.
6. The nucleic acid of claim 1 , wherein the IL-22 polypeptide comprises the amino acid sequence of SEQ ID NO:4.
7. The nucleic acid of claim 1 , wherein the IL-22 receptor is a human IL-22 receptor.
8. A vector comprising the nucleic acid of claim 1 .
9. An isolated host cell comprising the vector of claim 8 .
10. The host cell of claim 9 , wherein the host cell is a prokaryotic cell or eukaryotic cell.
11. The host cell of claim 10 , wherein the host cell is an E. coli cell or a Chinese hamster ovary (CHO) cell.
12. The host cell of claim 11 , wherein the host cell is a CHO cell.
13. A method of making an IL-22 Fc fusion protein comprising the step of culturing the host cell of claim 9 under conditions suitable for expression of the IL-22 Fc fusion protein encoded by the nucleic acid.
14. The method of claim 13 , further comprising the step of obtaining the IL-22 Fc fusion protein from the cell culture or culture medium.
15. The method of claim 13 , wherein the host cell is an E. coli cell.
16. The method of claim 13 , wherein the host cell is a CHO cell.
17. An isolated nucleic acid encoding an IL-22 Fc fusion protein that comprises the amino acid sequence of SEQ ID NO:8.
18. An isolated nucleic acid encoding an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:8.
19. An isolated nucleic acid comprising the polynucleotide sequence of SEQ ID NO:7.
20. An isolated nucleic acid encoding an IL-22 Fc fusion protein that comprises the amino acid sequence of SEQ ID NO:10.
21. The nucleic acid of claim 20 , comprising the polynucleotide sequence of SEQ ID NO:9.
22. An isolated nucleic acid encoding an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:10.
23. An isolated nucleic acid encoding an IL-22 Fc fusion protein that comprises the amino acid sequence of SEQ ID NO:16.
24. An isolated nucleic acid encoding an IL-22 Fc fusion protein consisting of the amino acid sequence of SEQ ID NO:16.
25. An isolated nucleic acid comprising the polynucleotide sequence of SEQ ID NO:15.
26. An isolated nucleic acid encoding an IL-22 Fc fusion protein that comprises 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).