USA flag logo/image

An Official Website of the United States Government

Glycine rich sequences with pharmacokinetic enhancing properties of PEG polymers

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
85689
Program Year/Program:
2008 / SBIR
Agency Tracking Number:
GM079873
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
AMUNIX, INC.
500 Ellis Street, Suite B MOUNTAIN VIEW, CA 94043-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2008
Title: Glycine rich sequences with pharmacokinetic enhancing properties of PEG polymers
Agency: HHS
Contract: 2R44GM079873-02
Award Amount: $1,010,925.00
 

Abstract:

DESCRIPTION (provided by applicant): The market for protein-based biopharmaceuticals is rapidly expanding. However, the clinical utility of many proteins is limited by their short serum half-life, requiring frequent injections. The most common approach to improve serum half-life is PEGylation. The chemical conjugation of Polyethylene glycol (PEG) to therapeutic proteins typically results in product mixtures that include inactive isomers and reduce the overall potency of the product. The chemical PEGylation of proteins significantly increases manufacturing costs, requiring precise process control and analytical assays to ensure reproducibility of product composition. The current project describes polypeptide chains (called rPEGs) that mimic the physicochemica l properties of chemical PEG. rPEGs are hydrophilic and have very large hydrodynamic radii. Most importantly, rPEGs can be recombinantly fused to therapeutic proteins resulting in homogeneous products. The fusion of rPEGs to biopharmaceutical is expected t o provide benefits that are similar to chemical PEGylation (long serum half-life, reduced immunogenicity) while offering improved product potency, homogeneity, and significantly reduced manufacturing costs. Phase I of this project was extremely successful and demonstrated the feasibility of the rPEG technology. rPEG sequences that closely mimic the properties of chemical PEG were developed. We demonstrated that a 20 kDa rPEG sequence has an apparent molecular weight of 180 kDa. Fusion of rPEG to the model p rotein GFP increased its serum half-life in rats from 1-3 h to approximately 10 h, similar to the effect of chemical PEGylation. Furthermore, this rPEG-GFP fusion elicited only a very weak immune response in rats. Our phase II goal is to apply rPEG technol ogy to human growth hormone (hGH). hGH is currently used for the treatment of dwarfism in children. 2006 sales exceeded 3B. Due to its rapid plasma elimination, hGH treatment requires daily injections. No long-acting form of hGH has been approved and chem ical PEGylation of hGH had limited success due to the formation of mixtures containing inactive isomers. We aim to develop methods for the production, purification, and formulation of rPEG-hGH. The resulting product will be thoroughly characterized in vitr o and in vivo. The resulting data package will allow rPEG- hGH to enter clinical development. The methods and data developed during the project will validate rPEG technology and enable its broad application to other protein pharmaceuticals. PUBLIC H EALTH RELEVANCE: The utility of many biopharmaceuticals is limited by their short serum half-life, which requires frequent injections. The goal of this project is to develop recombinant peptide chains (called rPEG) that mimic the properties of polyethylene glycol. These rPEGs can be directly fused to protein pharmaceuticals to increase their serum half-life. We will validate rPEG technology by developing a long-acting version of human growth hormone for the treatment of dwarfism in children.

Principal Investigator:

Volker Schellenberger
4085408129
VSCHELLENBERGER@AMUNIX.COM

Business Contact:


VSchellenberger@amunix.com
Small Business Information at Submission:

AMUNIX, INC.
AMUNIX, INC. 500 Ellis Street, Suite B MOUNTAIN VIEW, CA 94043

EIN/Tax ID: 176081280
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No