Bioengineering of a New Decoy Receptor Drug Delivery Technology

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$111,999.00
Award Year:
2009
Program:
SBIR
Phase:
Phase I
Contract:
1R43NS066514-01
Award Id:
94072
Agency Tracking Number:
NS066514
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
ARMAGEN TECHNOLOGIES, INC., 914 COLORADO AVE, SANTA MONICA, CA, 90401
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
137142589
Principal Investigator:
KAWAIHUI
() -
Business Contact:
PAULLEE
() -
rboado@armagen.com
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): Decoy receptors are potential new pharmaceuticals to treat brain diseases, such as brain injury, spinal cord injury, stroke, or neurodegeneration. However, decoy receptor drugs are large molecule pharmaceuticals that do not cross the blood-brain barrier (BBB). The present work will produce a novel recombinant fusion protein that is able to both (a) bind a human BBB receptor to trigger transport into the brain, and (b) bind human tumor necrosis factor (TNF)-1, to block cy toxic effects of this inflammatory cytokine. A new approach to the BBB delivery of large molecules such decoy receptors is the molecular Trojan horse technology. A bi-functional fusion protein is produced with genetic engineering, wherein the decoy recepto r extracellular domain (ECD) is fused to a BBB molecular Trojan horse. The latter is a genetically engineered monoclonal antibody (MAb) that is able to cross the human BBB by receptor-mediated transcytosis on endogenous BBB peptide transport systems. The p resent work will produce a novel fusion gene encoding the ECD of the human TNF receptor type II and a genetically engineered MAB molecular Trojan horse, which will allow the production of the corresponding fusion protein, AGT-110. The fusion protein genes will be incorporated in a eukaryotic expression vector followed by permanent transfection of host cells. These phase I SBIR studies will enable production of a permanently transfected host cell line for future manufacturing of AGT-110. PUBLIC HEALTH RELEVANCE: Decoy receptors are potential new pharmaceuticals to treat brain diseases, such as brain injury, spinal cord injury, stroke, or neurodegeneration. However, decoy receptor drugs are large molecule pharmaceuticals that do not cross the blood-brai n barrier (BBB). The present work will produce a novel recombinant fusion protein that is able to both (a) bind a human BBB receptor to trigger transport into the brain, and (b) bind human tumor necrosis factor-alpha, to block cytoxic effects of this infla mmatory cytokine.

* information listed above is at the time of submission.

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