Abstract: Disclosed are water soluble polymeric conjugates comprising the structure POLY-[Y—S—S-A]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, S—S is a disulfide group attached to an sp3 hybridized carbon of Y; and A is a covalently linked residue of a pharmacologically active molecule. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are polymeric reagents useful to prepare such conjugates, and methods of their formation and use.

Abstract: Disclosed are water soluble polymeric reagents comprising the structure POLY-[Y—S—W]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, and S—W is a thiol, protected thiol, or thiol-reactive derivative. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are conjugates of such polymeric reagents with pharmaceutically relevant molecules, and methods of their formation and use.

Abstract: Disclosed are water soluble polymeric reagents comprising the structure POLY-[Y—S—W]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, and S—W is a thiol, protected thiol, or thiol-reactive derivative. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are conjugates of such polymeric reagents with pharmaceutically relevant molecules, and methods of their formation and use.

Abstract: Polymeric reagents comprising a polymer attached, either directly or through one or more atoms, to a ketone or a related functional group such as ketone hydrate, thione, monothiohydrate, dithiohydrate, hemiketal, monothiohemiketal, dithiohemiketal, ketal, or dithioketal are provided. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Abstract: A method of preparing a multiarm polymer includes reacting a branched polyol with one or more functionalizing reagents to effect substitution of an ionizable functional group or a protected ionizable functional group, Y, to form a mixture comprising (i) unsubstituted branched polyol containing no Y groups; (ii) a monosubstituted polyol comprising one Y group, and (iii) a multisubstituted polyol (e.g., a disubstituted polyol comprising two Y groups); followed by purifying the mixture to separate the monosubstituted polyol from other species Thereafter, a water-soluble and non-peptidic polymer segment is attached to the monosubstituted branched polyol at the site of at least one of the hydroxyl groups. The invention also provides purified monosubstituted branched polyols and multiarm polymers prepared by the method and polyol precursors for use in the method.

Abstract: The present invention provides conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. The conjugates as well as the polymeric reagents used to form the conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.

Abstract: Polymeric reagents are provided comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Abstract: Disclosed are water soluble polymeric reagents comprising the structure POLY-[Y—S—W]x, where POLY is a water soluble polymer; Y is a hydrocarbon-based spacer group, x is 1 to 25, and S—W is a thiol, protected thiol, or thiol-reactive derivative. Preferably, the water soluble polymer is a PEG polymer. Also disclosed are conjugates of such polymeric reagents with pharmaceutically relevant molecules, and methods of their formation and use.

Abstract: The present invention is directed to hydrolytically stabilized maleimide-functionalized water soluble polymers and to methods for making and utilizing such polymers and their precursors.

Abstract: Methods for forming maleimide functionalized polymers are provided. In one such embodiment, a maleimide functionalized polymer is prepared in a method that includes a step of carrying out a reverse Diels-Alder reaction. Intermediates useful in the methods, as well as methods for preparing the intermediates, are also provided. Also provided are polymeric reagents, methods of using polymeric reagents, compounds and conjugates.

Abstract: The invention provides methods for preparing polymers bearing a terminal propionic acid. The method involves first reacting a water soluble and non-peptidic polymer comprising at least one hydroxyl group with a tertiary alkyl acrylate in the presence of a catalyst to form a propionic acid ester of the polymer, wherein the polymer has a weight average molecular weight of at least about 10,000 Da; and then treating the propionic acid ester of the polymer with a strong acid to form a propionic acid of the polymer.

Abstract: The present invention provides, among other things, methods for preparing functionalized and other polymers from polymer from polymer alcohols such as poly(ethylene glycol)s. In addition, polymer compositions, conjugates, polymeric reagents, are also provided.

Abstract: Polymeric reagents comprising a polymer attached, either directly or through one or more atoms to a ketone or a related functional group such as ketone hydrate, thione, monothiohydrate, dithiohydrate, hemiketal, monothiohemiketal, dithiohemiketal, ketal, or dithioketal are provided. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Abstract: The present invention provides water-soluble, polymer derivatives having a thiol-selective terminus suitable for selective coupling to thiol groups, such as those contained in the cysteine residues of proteins.

Abstract: Polymeric reagents are provided comprising a moiety of atoms arranged in a specific order, wherein the moiety is positioned between a water-soluble polymer and a reactive group. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.