Biorector Model for Optimization of Recombinant Protein Products

Advances made in recent years in recombinant DNA technology and high-level expression of foreign proteins in genetically engineered cells have also brought new problems to solve Bioreactor operators have discovered that large-scale cultivations of plasmid-containing bacteria do not behave exactly as those of plasmid-free cells; plasmid stability isa major hurdle; and the protein product might not be in soluble form. These and other problems represent new challenges for bioreactor modeling. Models to optimize bioprocess variables, including both genetic and bioreactor parameters have not been developed, resulting in non-optimum yield of recombinant products. To provide a cost-effective tool for control, Systems & Processes Engineering Corporation proposes to develop a bioreactor model for optimization of recombinant protein products. SPEC will work with the program sponsor to develop a model specifically for PEF processes. In Phase I SPEC will assess protein turnover rates for model protein expression systems and develop a detailed metabolic model to include factors for metabolic stress and cellular and bioreactor parameters. SPEC has extensive experience in modeling, simulation, and algorithm development. SPEC will work in collaboration with Professor Carl A. Batt of Cornell University who has broad experience with bioreactors, recombinant proteins, and high-level protein expression systems. BENEFITS: Successful development of a model for optimization of bioreactor performance can significantly aid in research and development of new genetic and bioreactor parameters. Optimization of expression systems in bioreactor processes will lead to lower cost and improved quality in the production of antibodies and other protein products. Providing products of equal or better quality at lower costs will have a significant commercial impact.