Polymer conjugates of interferon beta-1a and uses
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Accused Products
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
62 Claims
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1-40. -40. (canceled)
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41. A composition comprising a glycosylated interferon-beta-1a comprising the amino acid sequence set forth in any one of SEQ ID NOs:
- 27-40 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 (42, 43, 44, 54, 57)
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45. A physiologically active interferon-beta composition comprising a physiologically active interferon-beta-1a comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2740, 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 (46, 47, 48)
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49. A physiologically active interferon-beta composition comprising a physiologically active glycosylated interferon-beta-1a comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 27-40, 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 (50, 51, 52, 55)
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53. A stable, aqueously soluble, conjugated interferon-beta-1a complex comprising a interferon-beta-1a comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2740, 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 protcolysis.
- View Dependent Claims (56)
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58. A protein comprising the amino acid sequence set forth in any one of SEQ ID NOs:
- 25-40 coupled to a non-naturally-occurring polymer at the C-terminal end of said protein, said polymer comprising a polyalkylene glycol moiety.
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59. A protein comprising the amino acid sequence set forth in any one of SEQ ID NOs:
- 25-40 coupled to a non-naturally-occurring polymer, said polymer comprising a polyalkylene glycol moiety, and said polymer is attached to an amino, carboxylic, hydroxyl, guanidyl, or glycan moiety of said protein.
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60. A protein comprising the amino acid sequence set forth in any one of SEQ ID NOs:
- 2540 coupled to a non-naturally-occurring polymer at the N-terminal end of said protein, said polymer comprising a polyalkylene glycol moiety.
- View Dependent Claims (62)
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61. A method of treating multiple sclerosis in a subject comprising administering to a subject in need thereof a therapeutically effect amount of a protein comprising the amino acid sequence set forth in any one of SEQ ID NOs:
- 2540 coupled to a non-naturally-occurring polymer, said polymer comprising a polyalkylene glycol moiety.
Specification