Poly(ethylene glycol) derivatives with proximal reactive groups
AssigneeShearwater Corporation
InventorsJ. Milton Harris, Antoni Kozlowski
Life of this patent
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Abstract
An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
Claims24
A method for preparing an activated water soluble polymer, said polymer comprising a polymer backbone having at least one terminus bonded to a branching moiety through a hydrolytically stable linkage, the branching moiety being covalently bonded to at least two reactive groups, each reactive group comprising a reactive moiety, comprising:
- providing a first polymer comprising the polymer backbone linked to a reactive end group;
- providing a branched reactive compound having at least three free reactive groups linked to a branching moiety, one of said at least three free groups being capable of reacting with the reactive end group of the first polymer;
- and
- reacting the reactive end group of the first polymer with one of the at least three free groups of the branched reactive compound to form a hydrolytically stable linkage between the polymer backbone of the first polymer and the branched reactive compound, thereby forming a second polymer having at least two free reactive groups at a terminus thereof, each reactive group comprising a reactive moiety.
A method for preparing an activated water soluble polymer represented by mPEG —O—CH(CH2SO2CH═CH2)2, where mPEG represents methoxy poly(ethylene glycol), comprising the steps of:
- providing mPEG —O—Ms, wherein Ms represents mesylate;
- providing NaO—CH(CH2—O—Bz)2, wherein Bz represents a benzyl moiety;
- reacting mPEG—O—Ms with NaO—CH(CH2—O—Bz)2 to form mPEG—O—CH(CH2OBz)2;
- converting mPEG—O—CH(CH2OBz)2 to mPEG—O—CH(CH2OH)2;
- substituting a mesylate group for both hydroxyl groups in mPEG—O—CH(CH2OH)2 to form mPEG—O—CH(CH2OMs)2;
- converting mPEG—O—CH(CH2OMs)2 into mPEG—O—CH(CH2SCH2CH2OH)2;
- oxidizing the sulfur atom into a sulfone group;
- and
- converting the sulfone alcohol group into a vinyl sulfone group, thus forming mPEG—O—CH(CH2SO2CH═CH2)2.
Dependencies are inferred from the claim text.