Polymer conjugates of interferon beta-1a and uses
First Claim
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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.
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Abstract
An interferon beta polypeptide comprising interferon-beta 1a coupled to a polymer containing a polyalkylene glycol moiety wherein the interferon-beta-1a and the polyalkylene glycol moiety are arranged such that the interferon-beta-1a has an enhanced activity relative to another therapeutic form of interferon beta (interferon-beta-1b) and exhibits no decrease in activity as compared to non-conjugated interferon-beta-1a. The conjugates of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications.
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Citations
24 Claims
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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.
- View Dependent Claims (2, 3, 4)
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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.
- View Dependent Claims (6, 7)
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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.
- View Dependent Claims (9, 10, 11)
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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.
- View Dependent Claims (13, 14, 15, 17, 18)
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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.
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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.
- View Dependent Claims (20, 21)
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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.
- View Dependent Claims (23, 24)
Specification