US 9,040,664 B2 · Materials and methods for preparing protein-polymer conjugates

Abstract

The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.

Claims10

Dependent claims

A method for preparing a site-specific insulin-PEG conjugate comprising:

(a) contacting insulin protein with PEG in an aqueous solution in the presence of at least one organic solvent selected from the group consisting of ethanol, methanol, DMSO, dioxane, DMF, and NMP and at least one metal chelator selected from the group consisting of metal ion chelators, EDTA, deferoxamine (DEF), diethylenetriamine pentaacetic acid (DTPA), and bis(aminoethyl)glycolether N,N,N′,N′-tetraacetic acid (EGTA), to form the site-specific insulin-PEG conjugate by a predominant reaction of the insulin protein at residue PheB1 without protecting the insulin protein at GlyA1 and LysB29 residues, and
(b) isolating the conjugate.

Dependencies are inferred from the claim text.

Facts

Application

10/553,570Filed 8 Apr 2004 · us provisional application

Priority

11 Apr 2003

Published

US 2007/0083006 A112 Apr 2007

Granted

26 May 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 47/60
Obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes: the organic…
A61K 9/5031
Organic macromolecular compounds: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene…
A61K 38/28
Hormones: insulins
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes

Materials and methods for preparing protein-polymer conjugates

Life of this patent

Materials and methods for preparing protein-polymer conjugates

Life of this patent

Abstract

Claims10