Use of alcohol co-solvents to improve pegylation reaction yields

• US 20090252703A1
• Filed: 10/12/2007
• Published: 10/08/2009
• Est. Priority Date: 10/19/2006
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Wright, Marie E., D'Amico, Derin C., Gegg, Colin V. JR.
• Application Number:
  US11/974,472
• Publication Number:
  US 20090252703A1
• Time in Patent Office: Days
• US Class Current: 424/85.200
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: C07K 1/1077 by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids

Abstract

Disclosed is a method of producing a composition of matter. The method involves obtaining a pharmacologically active peptide; and conjugating the peptide to a pharmaceutically acceptable polyethylene glycol (PEG) by reacting the peptide with a PEG-aldehyde compound at a free amine moiety on the peptide in a buffer solution comprising an alcohol co-solvent.

Claims

1. A method of producing a composition of matter, comprising the steps of:

(a) obtaining a pharmacologically active peptide; and

(b) conjugating the obtained pharmacologically active peptide to a pharmaceutically acceptable polyethylene glycol (PEG) by reacting the peptide with a PEG-aldehyde compound at a free amine moiety on the peptide in a buffer solution comprising an alcohol co-solvent, whereby the composition of matter is produced.

2. The method of claim 1, wherein the alcohol co-solvent comprises a structure selected from structural Formulae IV, V and VI:

3. The method of claim 2, wherein if X is O, Y is independently H or F;

and if X is NR⁵, Y is H.

4. The method of claim 1, wherein the alcohol co-solvent is selected from 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoro-2-propanol (HF-i-PA), and 2-trifluoromethyl-1,1,1,3,3,3-hexafluoro-2-propanol (HF-t-BuOH).

5. The method of claim 1, wherein the concentration of the alcohol co-solvent in the buffer solution is about 30% to about 100% (v/v).

6. The method of claim 1, wherein the pharmacologically active peptide is selected from insulin, interleukin (IL)-1ra, leptin, soluble tumor necrosis factor receptor type 1, soluble tumor necrosis factor receptor type 2, keratinocyte growth factor, erythropoietin, thrombopoietin (TPO), TPO-mimetic peptides, granulocyte colony-stimulating factor, darbepoietin, glial cell line-derived neurotrophic factor, calcitonin, amylin, adrenomedullin, calcitonin gene-related peptide (CGRP) peptide antagonists, BAFF antagonist peptides, ang-2-binding peptides, NGF-binding peptides, myostatin-binding peptides, and toxin peptides.