FACTOR IX CONJUGATES WITH AN INCREASED HALF-TIME

摘要

1. The conjugate of factor IX and polyethylene glycol (FIX-PEG), in which one or more polyethylene glycol groups are associated with factor IX through a cysteine residue. ! 2. A conjugate of factor IX and polyethylene glycol (FIX-PEG), in which one or more polyethylene glycol groups are linked to factor IX through one or more reduced cysteine disulfide bonds. ! 3. The FIX-PEG conjugate according to claim 2, wherein the fragment containing one or more PEGs bridges one or more cysteine disulfide bonds in accordance with the following formula! ! in which R1 represents a linking group, which may be a direct bond, an alkylene group (preferably a C1-10 alkylene group) or optionally substituted with an aryl or heteroaryl group; ! in which aryl groups include phenyl and naphthyl groups; ! in which suitable heteroaryl groups include pyridine, pyrrole, furan, pyran, imidazole, pyrazole, oxazole, pyridazine, pyrimidine and purine; ! in which the connection with the polymer may be via a hydrolytically labile bond or via an unstable bond. ! 4. The FIX-PEG conjugate according to claim 3, wherein the fragment containing one or more PEG bridges one or more cysteine disulfide bonds in accordance with the following formula! ! 5. The FIX-PEG conjugate according to claims 1 to 3 or 4, wherein the fragment containing one or more PEG has a molecular weight of about 10 kDa. ! 6. The FIX-PEG conjugate according to claims 1 to 3, or 4, having one PEG-containing fragment. ! 7. The FIX-PEG conjugate according to claims 1 to 3, or 4, having two PEG-containing fragments. ! 8. The composition containing the conjugate according to any one of claims 1 to 7, which also contains pharmaceutical