Patent ID: 7939630

Claim:
A process for the preparation of a protein-polymer conjugate of formula I, wherein one of X and X′ is a polymer and the other is a hydrogen atom; Q is a linking group; W is selected from the group consisting of a keto group, an ester group, a sulphone group, a reduced keto group, a reduced ester group, and a reduced sulphone group; and if X represents a polymer, X′ and W together with the interjacent atoms may form a ring; A is a C 1-5 alkylene or alkenylene chain; B is a bond or a C 1-4 alkylene or alkenylene chain; and Z is a single protein linked to A and B via two thiol groups generated by the reduction of a disulfide bridge in the protein; said method comprising the steps of: (a) reducing a disulfide bridge in the protein; and (b) reacting the reduced protein with either (i) a compound of formula II wherein X, X′, Q, A and B are defined as in formula I; W′ is selected from the group consisting of a keto group, an ester group, and a sulphone group, and if X represents a polymer, X′ and W′ together with the interjacent atoms may form a ring; and L is independently a leaving group; or (ii) a compound of formula III wherein X, X′, Q and A are defined as in formula I, W′ is selected from the group consisting of a keto group, an ester group, and a sulphone group, and if X represents a polymer, X′ and W′ together with the interjacent atoms may form a ring; L is a leaving group; and m is an integer from 1 to 4.