Patent Number: 7,824,669

Title: In vivo stimulation of peripheral blood progenitor cells by granulocyte-macrophage colony stimulating factor (GM-CSF) cysteine muteins and their PEGylated variants

Abstract: The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby. Also disclosed are therapeutic methods for using the cysteine variants of the invention.

Inventors: Cox, III; George N. (Louisville, CO), Doherty; Daniel H. (Boulder, CO)

Assignee: Bolder Biotechnology, Inc.

International Classification: A61K 45/00 (20060101); C07K 14/535 (20060101); A61K 38/19 (20060101); C12N 15/09 (20060101); C12N 15/19 (20060101)

Expiration Date: 2019-11-02 0:00:00