Conjugates of superoxide dismutage coupled to high molecular weight polyalkylene glycols
AssigneeOxis International, Inc.
InventorsMark Saifer, Ralph Somack, L. David Williams
Life of this patent
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Abstract
A biologically persistent, water-soluble, substantially non-immunogenic, substantially non-antigenic conjugate of superoxide dismutase is prepared by coupling one to five strands of a polyalkylene glycol which is polyethylene glycol or polyethylene-polypropylene glycol copolymer, wherein said polyalkylene glycol has an average molecular weight of about 35,000-1,000,000.
Claims19
A polyalkylene glycol which is a polyethylene glycol or a polyethylene glycol-polypropylene glycol copolymer wherein all of the polyalkylene glycol has an average molecular weight as determined by HPLC using PEG as standard of about 35,000-200,000 and is unsubstituted at one terminal and is substituted at another terminal by a group of the formula:
- ##STR2##
A polyalkylene glycol which is a polyethylene glycol or a polyethylene glycol-polypropylene glycol copolymer wherein all of the polyalkylene glycol has an average molecular weight as determined by HPLC using PEG as standard of about 35,000-200,000 and is substituted at one terminal by a C.sub.1-4 alkyl group and is substituted at another terminal by a group of the formula:
- ##STR3##
A polyalkylene glycol which is a polyethylene glycol or a polyethylene glycol-polypropylene glycol copolymer wherein all of the polyalkylene glycol has an average molecular weight as determined by HPLC using PEG as standard of about 40,000-150,000 and is unsubstituted or substituted at one terminal by a C.sub.1-4 alkyl group and is substituted at another terminal by a group of the formula:
- ##STR4##
A polyethylene glycol having an average molecular weight as determined by HPLC of about 35,000-200,000 and is unsubstituted or substituted at a first terminal by a C.sub.1-4 alkyl group and is substituted at a second terminal by a group of the formula:
- ##STR5##
A water-soluble conjugate of a protein coupled to a polyalkylene glycol which is a polyethylene glycol or a polyethylene-polypropylene glycol copolymer residue, wherein all of the polyalkylene glycol is substituted at one terminal by a group of the formula:
- ##STR6## prior to coupling with said protein.
A method of forming a reactive carbonate half ester of polyalkylene glycol having the formula:
- PAG-O-CO-X,
- wherein PAG is a polyalkylene glycol and X is a leaving group, comprising:
- contacting the polyalkylene glycol with bis-N-succinimidyl carbonate.
A method of forming a polyalkylene glycol-protein conjugate comprising:
- (a) contacting the polyalkylene glycol with bis-N-succinimidyl carbonate to form an activated polyalkylene glycol;
- and
- (b) contacting the activated polyalkylene glycol with the protein.
Dependencies are inferred from the claim text.