Protein production for Manufacturing
Therapeutic recombinant proteins including antibodies have been used for a wide range of indications. The revenue for protein-based therapeutics is expected to expand at an annualized rate of 13.5% per year, and the expected value (in sales) of this market is predicted to be $498 billion by 2020 (Research and Markets, Nov 2013). Therapeutic recombinant proteins are widely produced in cells called host cells. Proper structure of the expressed proteins is essential for their biological function and proteins with a structural defect are promptly detected by the host cell (cellular quality control system) and eventually degraded. Therefore, protein folding systems and cellular quality control systems have a significant impact on the production of recombinant proteins. Many technologies have been developed to control these systems, but these approaches act on all secreted proteins being made by the host cell with unwanted cellular effects that limit the applicability and efficiency of these technologies.
TapBoost Applications: Manufacturing
TapBoost was designed to assist and enable the production of the next generation of biotherapeutics. Productivity of biotherapeutics (protein or antibody drugs) using cell culture is highly variable, ranging from 1.0g per liter, with a strong correlation to the processing fidelity of cellular machinery. Common belief is that the potential of a cell to produce optimal levels of biotherapeutics depends heavily upon the cell’s ability to properly fold the target protein or antibody into a functional, soluble and secretable form. TapBoost incorporates a novel intracellular molecular system that increases the cellular output of functional disease-relevant proteins and antibodies.
Example – Monoclonal Antibodies Production
Using TapBoost, we produced two kinds of monoclonal antibody (Avastin®: anti-VEGF-A antibody and Humira®: anti-TNFα antibody. These antibodies are well secreted on their own. However, more production was observed when they were expressed using TapBoost. The activity of the secreted antibody was confirmed based on its epitope- binding ability (ELISA). Purified recombinant VEGF-A and TNFα were coated for anti-VEGF antibody (Avastin®) and anti-TNFα antibody (Humira®), respectively. The produced antibody was incubated and the bound antibody was detected by HRP (horseradish peroxidase)-labeled anti-human IgG antibody. The assay shows that the antibodies produced with TapBoost hold the activity. TapBoost enhances the production of currently sold antibodies, and the produced antibodies are active.