Interferon-alpha polypeptides and conjugates
View Patent ↗The present invention provides interferon-alpha polypeptides and conjugates, and nucleic acids encoding the polypeptides. The invention also includes compositions comprising these polypeptides, conjugates, and nucleic acids; cells containing or expressing the polypeptides, conjugates, and nucleic acids; methods of making the polypeptides, conjugates, and nucleic acids; and methods of using the polypeptides, conjugates, and nucleic acids.
1. An isolated or recombinant polypeptide comprising a sequence which differs in 0 to 8 amino acid positions from the sequence of SEQ ID NO:3, which polypeptide exhibits antiviral activity.
2. The polypeptide of claim 1 , wherein the antiviral activity of the polypeptide is equal to or greater than the antiviral activity of huIFN-alpha 2b or huIFN-alpha 2a.
3. The polypeptide of claim 2 , wherein the antiviral activity of the polypeptide is at least two-fold greater than the antiviral activity of huIFN-alpha 2b or huIFN-alpha 2a.
4. The polypeptide of claim 1 , wherein the polypeptide further exhibits antiproliferative activity and wherein the ratio of antiviral activity/antiproliferative activity is at least two-fold greater than the ratio of antiviral activity/antiproliferative activity exhibited by huIFN-alpha 2b or huIFN-alpha 2a.
5. The polypeptide of claim 4 , wherein the polypeptide exhibits a ratio of antiviral/antiproliferative activity at least four-fold greater than the ratio of antiviral activity/antiproliferative activity exhibited by huIFN-alpha 2b or huIFN-alpha 2a.
6. A composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable excipient.
7. A conjugate comprising
(a) the polypeptide of claim 1 ; and
(b) a non-polypeptide moiety covalently attached to the polypeptide, wherein the conjugate exhibits antiviral activity.
8. The conjugate of claim 7 , comprising at least two non-polypeptide moieties.
9. The conjugate of claim 7 , wherein the non-polypeptide moiety is a polymer.
10. The conjugate of claim 9 , wherein the polymer is a polyethylene glycol.
11. The conjugate of claim 10 , comprising a polyethylene glycol moiety covalently attached to a cysteine residue.
12. The conjugate of claim 10 , comprising a polyethylene glycol moiety covalently attached to a lysine residue or to the N-terminal amino group.
13. The conjugate of claim 10 , comprising a polyethylene glycol moiety covalently attached to a lysine residue.
14. The conjugate of claim 10 , comprising a polyethylene glycol moiety attached to the N-terminal amino group.
15. The conjugate of claim 10 , comprising a polyethylene glycol moiety attached to a lysine residue and a polyethylene glycol moiety attached to the N-terminal amino group.
16. The conjugate of claim 7 , wherein the non-polypeptide moiety is a sugar.
17. The conjugate of claim 16 , wherein the sugar is attached to an N-glycosylation site.
18. A composition comprising the conjugate of claim 7 and a pharmaceutically acceptable excipient.
19. A method for preparing a conjugate, the method comprising
(i) providing the polypeptide of claim 1 , and
(ii) attaching at least one non-polypeptide moiety to an attachment group of the polypeptide, wherein the resulting conjugate exhibits antiviral activity.
20. The method of claim 19 , wherein the non-polypeptide moiety is a polymer.
21. The method of claim 20 , wherein the polymer is a polyethylene glycol.
22. The method of claim 21 , wherein the attachment group is a cysteine residue.
23. The method of claim 21 , wherein the attachment group is a lysine residue or the N-terminal amino group.
24. The method of claim 21 , wherein the attachment group is a lysine residue.
25. The method of claim 21 , wherein the attachment group is the N-terminal amino group.
26. The method of claim 21 , wherein at least two polyethylene glycol moieties are attached to the polypeptide and wherein each polyethylene glycol moiety is covalently attached to a different amino acid residue of the polypeptide.
27. The method of claim 26 , wherein the at least two polyethylene glycol moieties are attached to different lysine residues.
28. The method of claim 26 , wherein one of the at least two polyethylene glycol moieties is attached to the N-terminal amino group and one of the at least two polyethylene glycol moieties is attached to a lysine residue.