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 when given subcutaneously. Extend Biosciences is developing proprietary carrier molecules that will allow proteins to access a transport pathway for efficient delivery to the vascular space and then maintain a sustained presence in circulation. This would be of particular importance in the development of longer-lasting versions of bioscavenger proteins that could then be delivered subcutaneously 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 as further proof-of-concept for the technology. The modified bioscavengers will be assayed in vitro to ensure that the carrier molecule does not disrupt functional activity. Following success in Phase I, the Phase II studies would test the modified bioscavengers for their improved half-life and bioavailability when delivered subcutaneously in an appropriate animal model, and test whether the modified protein induces toxicity or an immune response. 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.