Long-acting interferons and derivatives thereof and methods thereof
A polypeptide and polynucleotides encoding same comprising carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to an IFN protein are disclosed. Pharmaceutical compositions comprising the polypeptide and polynucleotides of the invention and methods of using same are also disclosed.
1. A CTP-modified interferon protein consisting of an interferon (IFN) protein, one chorionic gonadotrophin carboxy terminal peptide (CTP) attached to the amino terminus of said interferon protein and two chorionic gonadotrophin carboxy terminal peptides attached to the carboxy terminus of said interferon protein.
2. The CTP-modified interferon protein of claim 1 , wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.
3. The CTP-modified interferon protein of claim 1 , wherein said interferon is a type I interferon.
4. The CTP-modified interferon protein of claim 3 , wherein said type I interferon is IFN-α or IFN-β.
5. The CTP-modified interferon protein of claim 1 , wherein said interferon is IFN-γ.
6. The CTP-modified interferon protein of claim 1 , wherein at least one CTP is glycosylated.
7. The CTP-modified interferon protein of claim 1 , wherein at least one CTP is truncated.
8. The CTP-modified interferon protein of claim 1 , wherein the sequence of said polypeptide consists of the amino acid sequence of MOD 9013 as set forth in SEQ ID NO: 9.
9. The CTP-modified interferon protein of claim 1 , wherein at least one CTP is attached to said interferon protein via a linker.
10. The CTP-modified interferon protein of claim 9 , wherein said linker is a peptide bond.
11. The CTP-modified interferon protein of claim 1 , wherein said interferon protein includes a signal peptide.
12. The CTP-modified interferon protein of claim 11 , wherein the amino acid sequence of said signal peptide is as set forth in SEQ ID NO: 19.
13. A pharmaceutical composition comprising the CTP-modified interferon protein of claim 1 and a pharmaceutically acceptable carrier.
14. A method of reducing the clearance rate of an interferon protein, consisting of the step of attaching one chorionic gonadotrophin carboxy terminal peptide (CTP) to the amino terminus of said interferon protein and two chorionic gonadotrophin carboxy terminal peptides to the carboxy terminus of said interferon protein, thereby reducing the clearance rate of an interferon protein.
15. The method of claim 14 , wherein the sequence of at least one chorionic gonadotrophin carboxy terminal peptide consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.
16. The method of claim 14 , wherein the sequence of said CTP-modified interferon protein consists of the amino acid sequence of MOD 9013 as set forth in SEQ ID NO: 9.
17. The method of claim 14 , wherein said interferon protein includes a signal peptide.
18. The method of claim 17 , wherein the amino acid sequence of said signal peptide is as set forth in SEQ ID NO: 19.
19. The method of claim 14 , wherein said interferon is a type I interferon.
20. The method of claim 14 , wherein at least one CTP is truncated.
21. A method of reducing the dosing frequency of an interferon protein therapy in a subject, consisting of the step of attaching one chorionic gonadotrophin carboxy terminal peptide (CTP) to the amino terminus of said interferon protein, and two chorionic gonadotrophin carboxy terminal peptides (CTPs) to the carboxy terminus of said interferon protein, thereby reducing the dosing frequency of an interferon protein therapy in a subject.
22. The method of claim 21 , wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.
23. The method of claim 21 , wherein said interferon protein includes a signal peptide.
24. The method of claim 23 , wherein the amino acid sequence of said signal peptide is as set forth in SEQ ID NO: 19.
25. The method of claim 21 , wherein the sequence of said CTP-modified interferon protein consists of the amino acid sequence of MOD 9013 as set forth in SEQ ID NO: 9.
26. The method of claim 21 , wherein said interferon is a type I interferon.
27. The method of claim 21 , wherein at least one CTP is truncated.
28. A method of improving the area under the curve (AUC) of an interferon protein in a subject, consisting of the step of attaching one chorionic gonadotrophin carboxy terminal peptide (CTP) to the amino terminus of said interferon protein and two chorionic gonadotrophin carboxy terminal peptides (CTPs) to the carboxy terminus of said interferon protein, thereby improving the area under the curve (AUC) of an interferon protein in a subject.
29. The method of claim 28 , wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.
30. The method of claim 28 , wherein said interferon protein includes a signal peptide.
31. The method of claim 30 , wherein the amino acid sequence of said signal peptide is as set forth in SEQ ID NO: 19.
32. The method of claim 28 , wherein the sequence of said CTP-modified interferon protein consists of the amino acid sequence of MOD 9013 as set forth in SEQ ID NO: 9.
33. The method of claim 28 , wherein said interferon is a type I interferon.
34. The method of claim 28 , wherein at least one CTP is truncated.