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MANUFACTURING OF TROJAN HORSE-TNFR DECOY RECEPTOR FUSION PROTEIN

Award Number: R43AG042181
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2012
PERIOD OF PERFORMANCE END DATE: 09/30/2012

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MANUFACTURING OF TROJAN HORSE-TNFR DECOY RECEPTOR FUSION PROTEIN - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2012 ( Subtotal = $148,530 )
2012	2012	ARMAGEN TECHNOLOGIES INC	914 COLORADO BOULEVARD	LOS ANGELES	CA	90401		USA	Aging Research	000	1	3/8/2012	NEW	$148,530
														Subtotal = $148,530

Grand Total All Awards = $148,530

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MANUFACTURING OF TROJAN HORSE-TNFR DECOY RECEPTOR FUSION PROTEIN

Award Number: R43AG042181

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2012

PERIOD OF PERFORMANCE END DATE: 09/30/2012

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