Abstract: The present disclosure provides terminally activated monofunctional POZ derivatives having a range of functional active groups allowing conjugation of the monofunctional POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed terminally activated monofunctional POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives.

Abstract: Conjugates between a protein and a water soluble polymer comprising multiple degradable carbonate linkages are 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: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.

Abstract: The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Abstract: The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Abstract: Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— wherein n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.

Abstract: The invention provides corticosteroids that are chemically modified by covalent attachment of a water soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits a reduced biological membrane crossing rate as compared to the biological membrane crossing rate of the corticosteroid not attached to the water soluble oligomer.

Abstract: Conjugates between a protein and a water soluble polymer comprising multiple degradable carbonate linkages are provided.

Abstract: The present disclosure provides novel POZ-2 derivatives, methods for synthesizing POZ-2 derivatives and intermediates useful in such methods. In one embodiment, the POZ-2 derivative comprises two linear POZ chains of the present disclosure linked directly or indirectly to a branching moiety that contains a functional group for linking the POZ-2 derivative to the target molecule. Target molecule-POZ-2 conjugates are also described. In certain embodiment, the POZ-2 derivatives have low polydispersity values and a decreased amount of impurities produced by unwanted side reactions, such as, but not limited to, chain transfer.

Abstract: Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— wherein n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.

Abstract: A water soluble polymer comprising multiple degradable carbonate linkages in a backbone and, for each carbonate linkage in the backbone, an oligomer linked thereto by the carbonate linkage, wherein the oligomer is branched.

Abstract: An activated, substantially water-soluble polyoxazoline is provided having 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 polyoxazoline and the biologically active agent.

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 (polyethylene glycol) and the biologically active agent.

Abstract: The present disclosure provides terminally activated monofunctional POZ derivatives having a range of functional active groups allowing conjugation of the monofunctional POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed terminally activated monofunctional POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives.

Abstract: This invention provides a method related to the preparation of derivatives of poly(ethylene glycol).

Abstract: PEG and related polymer derivatives having weak, hydrolytically unstable linkages near the reactive end of the polymer are provided for conjugation to drugs, including proteins, enzymes, small molecules, and others. These derivatives provide a sufficient circulation period for a drug-PEG conjugate, followed by hydrolytic breakdown of the conjugate and release of the bound molecule. In some cases, drugs that demonstrate reduced activity when permanently coupled to PEG maintain a therapeutically suitable activity when coupled to a degradable PEG in accordance with the invention. The PEG derivatives of the invention can be used to impart improved water solubility, increased size, a slower rate of kidney clearance, and reduced immunogenicity to a conjugate formed by attachment thereto. Controlled hydrolytic release of the bound molecule into an aqueous environment can then enhance the drug's delivery profile by providing a delivery system which employs such polymers and utilizes the teachings provided herein.

Abstract: A water soluble polymer comprising multiple degradable carbonate linkages in a backbone and, for each carbonate linkage in the backbone, an oligomer linked thereto by the carbonate linkage, wherein the oligomer is branched.

Abstract: This invention provides a method for preparing, in high purity and high yield, heterobifunctional derivatives of poly(ethylene glycol) or related polymers. A chromatographic purification step is not necessary in the method. In accordance with the method of the invention, an intermediate polymer having a formula of W-Poly-OH is provided bearing a removable group W at one terminus. The intermediate polymer W-Poly-OH is first altered by modifying the OH group to a first functional group X, followed by the removal of W to generate a second hydroxyl group. The latter hydroxyl group may then be further converted to a second functional group Y, thus providing the desired heterobifunctional derivative.

Abstract: A water soluble polymer is described, the water soluble polymer comprising multiple hydrolytically degradable carbonate linkages in a backbone and, for each carbonate linkage in the backbone, an oligomer linked thereto by the carbonate linkage, wherein the oligomer is branched and, prior to being linked by the carbonate linkage, has the formula: R3[O—(—CHR1CH2—O—)n—]mH where R3 is a core branching moiety, R1 is H, (n) can range from 2 to 2000, and m is at least 3.