Enhancing the Pharmacokinetic Profile of Protein-based Drugs

Many protein-based drugs have limited efficacy due to a short half-life or require intravenous delivery because of low bioavailability. Extend Biosciences is developing proprietary carrier molecules that allow proteins to access an intrinsic transport pathway for efficient delivery to the vascular space and then maintain a sustained presence in circulation. This novel technology would be of particular importance in the development of longer-lasting versions of bioscavenger proteins that could then be delivered subcutaneously or intramuscularly and become bioavailable within minutes of administration. In this project, one of Extend Biosciences carrier molecules will be conjugated to two bioscavenger proteins of interest to the military. The modified bioscavengers will be tested for their improved half-life and rapid bioavailability in an appropriate animal model. Safety of the modified proteins will be assessed by testing whether the modified proteins induce toxicity or an immune response. A successful project will enable the prophylactic or acute on-site treatment options to counteract the threat of intoxication and death by organophosphate compounds. This project will demonstrate the feasibility of improving the half-life and bioavailability of bioscavenger proteins that could be applied to numerous other protein-based drugs including those used in Chemical and Biological Defense treatments.