Polymer conjugates of interferon beta-1a and uses

1. A composition comprising the glycosylated interferon-beta-1a of SEQ ID NO: 25 coupled to a non-naturally-occurring polymer at an N-terminal end of said glycosylated interferon-beta-1a, said polymer comprising a polyalkylene glycol moiety.

2. The composition of claim 1 , wherein the polyalkylene moiety is coupled to the interferon-beta by way of a group selected from an aldehyde group, a maleimide group, a vinylsulfone group, a haloacetate group, plurality of histidine residues, a hydrazine group and an aminothiol group.

3. The composition of claim 1 , wherein the interferon-beta-1a of SEQ ID NO: 25 is an inlerferon-beta-1a fusion protein.

4. The composition of claim 3 , wherein the interferon-beta-1a fusion protein comprises a portion of an immunoglobulin molecule.

5. A composition comprising the glycosylated interferon-beta-1a of SEQ ED NO: 26 coupled to a non-naturally-occurring polymer at the N-terminus of said glycosylated interferon-beta-1a, said polymer comprising a polyalkylene glycol moiety.

6. The composition of claim 5 , wherein the glycosylated interferon-beta-1a of SEQ ID NO: 26is an interferon-beta-1a fusion protein.

7. The composition of claim 6 , wherein the interferon-beta-1a fusion protein comprises a portion of an immunoglobulin molecule.

8. A physiologically active interferon-beta composition comprising a physiologically active interferon-beta-1a comprising the amino acid sequence of SEQ ID NO: 25 coupled to a polymer comprising a polyalkylene glycol moiety, wherein the interferon-beta-1a is coupled to the polymer at a site on the interferon-beta-1a that is an N- terminal end, wherein the physiologically active interferon-beta 1a and the polyalkylene glycol moiety are arranged such that the physiologically active interferon-beta-1a in the physiologically active interferon-beta composition has an activity at least 2-fold greater relative to physiologically active interferon-beta-1b, when measured by an antiviral assay.

9. The composition of claim 8 , wherein the interferon-beta-1a is coupled to the polymer at a site by way of a glycan moiety the interferon-beta-1a.

10. The composition of claim 8 , wherein interferon-beta-1a is an interferon-beta-1a fusion protein.

11. The composition of claim 10 , wherein the interferon-beta-1a fusion protein comprises a portion of an immunoglobulin molecule.

12. A physiologically active interferon-beta composition comprising a pysiologically active glycosylated interferon-beta-1a comprising the amino acid sequence of SEQ ID NO: 25 N-terminally coupled to a polymer comprising a polyalkylene glycol moiety. wherein the physiologically active interferon-beta-1a and the polyalkylene glycol moiety are arranged such that the physiologically active interferon-beta-1a in the physiologically active interferon-beta composition has equal activity relative to physiologically active interferon-beta lacking said moiety, when measured by an antiviral assay.

13. The composition of claim 12 , wherein the interferon-beta is coupled to the polymer at a site by way of a glycan moiety on the interferon-beta.

14. The composition of claim 12 , wherein the interferon-beta-1a is an interferon beta fusion protein.

15. The composition of claim 14 , wherein the interferon beta fusion protein comprises a portion of an immunoglobulin molecule.

16. A stable, aqueously soluble, conjugated interferon-beta-1a complex comprising a interferon-beta-1a comprising the amino acid sequence of SEQ ID NO: 25 N-terminally coupled to a polyethylene glycol moiety, wherein the interferon-beta-1a is coupled to the polyethylene glycol moiety by a labile bond, wherein the labile bond is cleavable by biochemical hydrolysis and/or proteolysis.

17. A interferon-beta composition according to claims 12 , or 16 , wherein the polymer has a molecular weight of from about 5 to about 40 kilodaltons.

18. A pharmaceutical composition comprising the interferon-beta composition of claim 17 .

19. A physiologically active interferon-beta composition comprising a physiologically active interferon-beta-1a comprising the amino acid sequence of SEQ ID NO:26 coupled to a non-naturally-occurring polymer at the N-terminus of said glycosylated interferon-beta-1a, said polymer comprising a polyalkylene glycol moiety wherein the physiologically active interferon-beta-1a and the polyalkylene glycol moiety are arranged such that the physiologically active interferon-beta-1a in the physiologically active interferon-beta composition has an activity at least 2-fold greater relative to physiologically active interferon-beta-1b, when measured by an antiviral assay.

20. The composition of claim 19 , wherein the interferon-beta-1a is an interferon-beta-1a fusion protein.

21. The composition of claim 20 , wherein the interferon-beta-1a fusion protein comprises a portion of an immunoglobulin molecule.

22. A physiologically active interferon-beta composition comprising a physiologically active glycosylated interferon-beta-1a, comprising the amino acid sequence of SEQ ID NO: 25, N-terminally coupled to a polymer comprising a polyalkylene glycol moiety, wherein the physiologically active interferon-beta-1a and the polyalkylene glycol moiety are arranged such that the physiologically active interferon-beta-1a in the physiologically active interferon-beta composition has equal activity relative to physiologicaily active interferon-beta lacking said moiety, when measured by an antiviral assay.

23. The composition of claim 22 , wherein the interferon-beta-1a is an interferon beta fusion protein.

24. The composition of claim 23 , wherein the interferon beta fusion protein comprises a portion of an immunoglobulin molecule.