Manufacturing of Trojan Horse-TNFR Decoy Receptor Fusion Protein

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$148,530.00
Award Year:
2012
Program:
SBIR
Phase:
Phase I
Contract:
1R43AG042181-01
Agency Tracking Number:
R43AG042181
Solicitation Year:
2012
Solicitation Topic Code:
NIA
Solicitation Number:
PA11-096
Small Business Information
ARMAGEN TECHNOLOGIES, INC.
26679 Agoura Rd., Suite 100, Calabasas, CA, -
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
137142589
Principal Investigator:
RUBEN BOADO
(310) 917-1275
rboado@armagen.com
Business Contact:
RUBEN BOADO
(310) 917-1275
rboado@armagen.com
Research Institution:
Stub




Abstract
DESCRIPTION (provided by applicant): Tumor necrosis factor (TNF)- plays a pro-inflammatory role in brain diseases. The biologic TNF inhibitors (TNFI), such as the TNF decoy receptor cannot be developed for brain diseases, because the TNFIs are large molecules that do not cross the blood-brain barrier (BBB). The present work continues the drug development of a re-engineered form of the human type II TNF receptor (TNFR), wherein the TNFR is produced as an IgG fusion protein. The IgG part is a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb part of the HIRMAb-TNFR fusion protein acts as a molecular Trojan horse to ferry the fused decoy receptor across the BBB via receptor-mediated transport on the endogenous BBB insulin receptor. The pre-SBIR feasibility stage of this research describes the engineering, expression, biochemical validation, and in vivo plasma pharmacokinetics and BBB transport in the Rhesus monkey of the HIRMAb-TNFR fusion protein. The proposed phase I SBIR research will develop a manufacturing scheme for production of the HIRMAb-TNFR fusion protein. This manufacturing will be designed to produce a therapeutic product that meets FDA specifications with regard to purity, potency, safety, and impurities, so that the manufacturing can be replicated in future GMP production of the fusion protein for clinical trials. The small scale manufacturing methodology developed in phase I will then be scaled up in phase II to the 50L bioreactor stage for manufacturing of the HIRMAb-TNFR fusion protein at production levels that can support future clinical trials. PUBLIC HEALTH RELEVANCE: Biologic tumor necrosis factor inhibitors (TNFI), such as the tumor necrosis factor (TNF) decoy receptor, cannot be developed for brain diseases, because these large molecule drugs do not cross the blood-brain barrier (BBB). The present research will re-engineer the human type II TNF receptor (TNFR) as an IgG-TNFR fusion protein, where the IgG part is a genetically engineered monoclonal antibody that crosses the BBB via transport on the endogenous insulin receptor. The IgG acts as a molecular Trojan horse to ferry across the BBB the TNFI.

* information listed above is at the time of submission.

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