Patent ID: 8546493

Claim:
A method for preparing a branched, monofunctional, water-soluble polymer, the method comprising: (i) reacting a monomethoxypoly(ethylene glycol)polymer comprising a single reactive moiety, W, and having the structure mPEG-W, where W is the single reactive moiety, with a linker molecule comprising from 1 to 10 carbon atoms and having the structure X—C(Y)(R)—Z, where X and Y each independently comprise reactive groups that can react with W to form hydrolytically stable linkage fragments P and Q, respectively, Z is a moiety that (a) comprises a single ionizable reactive site that is capable of reacting with ion exchange chromatography media, and (b) is not reactive with either X or Y, and R is H, methyl or another alkyl group, under conditions effective to provide an impure branched monofunctional, water-soluble polymer having the structure: “mPEG-P—C(R)(Z)-Q-mPEG”, and one or more polymeric impurities, where neither the linker molecule nor the resulting linkage fragments P or Q comprises aromatic or ester groups, and (ii) purifying the impure branched monofunctional, water-soluble polymer from step (i) by ion exchange chromatography under conditions effective to essentially remove the polymeric impurities to thereby provide purified mPEG-P—C(R)(Z)-Q-mPEG in essentially pure form.