Enzon, Inc.

Fmc Corporation

Cullen, Thomas G.

Martinez, Anthony J.

Anthony J Martinez

Richard B Greenwald

Annapurna Pendri

Thomas G Cullen

Yun Hwang Choe

Clinton J Peake

Ernest L Plummer

Philip A Cruickshank

Ronald Eugene Montgomery

Jacob J Vukich

Terminally-branched polymeric linkers and polymeric conjugates containing the same

Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Non-antigenic branched polymer conjugates

Biodegradable high molecular weight polymeric linkers and their conjugates

Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.

Non-antigenic amine derived polymers and polymer conjugates

The present invention is directed to polymeric- prodrug transport forms of the formula: ##STR1## wherein: B is a leaving group, OH, a residue of a hydroxyl-containing moiety or ##STR2## wherein B.sub.1 is a leaving group, OH or a residue of a hydroxyl-containing moiety;

Terminally-branched polymeric linkers and polymeric conjugates

Water-soluble non-antigenic polymer linkable to biologically active

The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifloroacetic acid. The resultant polymer carboxylic acids are of sufficient plurty so that expensive and time consuming purification steps required for pharmaceutical grade polymers are avoided.

Method of preparing polyalkyene oxide carboxylic acids

The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifluoroacetic acid. The resultant polymer carboxylic acids are of sufficient purity so that expensive and time containing purification steps required for pharmaceutical grade polymers are avoided.

Method of preparing polyalkylene oxide carboxylic acids

The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifluoroacetic acid. The resultant polymer carboxylic acids are of sufficient purity so that expensive and time consuming purification steps required for pharmaceutical grade polymers are avoided.

Water-soluble cyclic imide thione activated polyalkylene oxides having improved hydrolytic stability are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.

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Hamilton Square, NJ, United States of America

Anthony J Martinez