Patent EA-004789-B1 (EA)
Title: Polymer conjugates of interferon beta-1a and their uses
Inventor: PEPINSKY BLAKE
IPC: A61K47/50
Filed: 1999-10-15
Abstract: 1. A composition comprising a glycosylated interferon-beta-1a with an amino acid sequence SEQ ID NO:25 coupled to a non naturally-occurring polymer at an N-terminal end of said glycosylated interferon-beta-1a, wherein said polymer comprising a polyalkylene glycol moiety. 2. The composition of claim 1, wherein the polyalkylene moiety is coupled to the interferon-beta-1a 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 glycosylated interferon-beta-1a is more active than interferon-beta-1 b when measured in an antiviral assay. 4. The composition of claim 3, wherein the interferon-beta-1a retains 50-100% the potency of interferon-beta-1a lacking said polymer, as measured in an antiviral assay. 5. A interferon-beta-1a composition of claim 1, wherein the polymer has a molecular weight of from about 5 to about 40 kilodaltons. 6. A pharmaceutical composition comprising the interferon-beta-1a composition of claim 5. 7. The composition, wherein comprising a mutant interferon-beta coupled to a non naturally-occurring polymer at an N-terminal end of said mutant interferon-beta, wherein said polymer comprising a polyalkylene glycol moiety, wherein said mutant interferon-beta is a peptide comprising an aminoacid sequence selected from the group comprising SEQ ID NO: 26-40. 8. A physiologically active interferon-beta composition comprising a physiologically active interferon-beta-1a with amino acid sequence SEQ ID NO: 25 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 an enhanced activity relative to physiologically active interferon-beta-1b, when measured by an antiviral assay. 9. The composition of claim 8, wherein a) the interferon-beta-1a is coupled to the polymer that is at an N-terminal end. b) the interferon-beta-1a is coupled to the polymer that is at or near the C-terminal end. c) the interferon-beta-1a is coupled to the polymer by way of a glycan moiety. 10. A stable, aqueously soluble, conjugated interferon-beta-1a complex comprising a interferon-beta 1a coupled to a polyethylene glycol moiety, wherein the interferon-beta-1a has amino acid sequence SEQ ID NO: 25 and coupled to a polyalkylene glycol moiety by a labile bond at an N-terminal end wherein the labile bond is cleavable by biochemical hydrolysis and/or proteolysis. 11. Use of the interferon-beta-1a with an amino acid sequence SEQ ID NO: 25 for preparing a pharmaceutical composition for prophylactic or therapeutic treatment of inflammatory, autoimmune, antiogen, tumor or virus diseases treatable with the interferon-beta-1a in a mammal, wherein said inteferon-beta-1a with amino acid sequence SEQ ID NO: 25 is coupled to a polyethylene glycol moiety. 12. Use according to claim 11, wherein a) the inteferon-beta-1a is coupled to the polymer at an N-terminal end; b) the interferon-beta-1a is coupled to the polymer at or near the C-terminal end; c) the interferon-beta-1a is coupled to the polymer by way of a glycan moiety. 13. A method of prolonging the activity of interferon-beta-1a with an amino acid sequence SEQ ID NO: 25in an in vivo or in vitro system, comprising coupling said interferon-beta 1a to a non-naturally-occurring polymer moiety to yield a conjugate polymer-interferon-beta 1 a composition, and introducing said conjugate polymer-interferon-beta composition to the in vivo or in vitro system. 14. Use according to claim 13, wherein a) the interferon-beta-1a is coupled to the polymer at an N-terminal end; b) the interferon-beta-1a is coupled to the polymer at or near the C-terminal end; c) the interferon-beta-1a is coupled to the polymer by way of a glycan moiety. 15. The method according to claim 13, wherein said polymer comprises polyalkylene glycol moiety.