AIR Option 1: Technology Translation - Plant Based Manufacturing of Orphan Drug Human Biobetter Alpha-1-Antitrypsin

University Of California-Davis, Davis CA

Investigators

Abstract

This PFI: AIR Technology Translation project focuses on translating a novel biomanufacturing platform that uses plants for transient expression of therapeutic proteins to fill the need for rapid, inexpensive, and environmentally-friendly production of safe and effective human therapeutics. The translated plant-based biomanufacturing platform has the following unique features: harvested leaves from wild-type, nontransgenic Nicotiana benthamiana (a relative of tobacco) are used as production hosts, transient expression of the recombinant therapeutic protein takes place in a contained system, a novel Cucumber mosaic virus expression system is used to increase expression level, and glycosylation of the recombinant protein is modified in a post-production, in-vitro process providing an exemplary highly scalable approach that significantly reduces capital investment and manufacturing costs, minimizes environmental impact and improves product quality in terms of safety and consistency when compared to the leading competing production technologies in this market space. The project accomplishes this goal by developing a technoeconomic engineering-based model to quantify the capital investment costs and total production costs for a plant-based biomanufacturing facility to produce a human orphan drug, alpha-1-antitrypsin (AAT), evaluating the market potential and patent landscape surrounding our technology, identifying the regulatory pathway and refining our finance and revenue model to bring plant-made AAT closer to the market and position us to pursue partnerships for clinical development. Current partners include the UC Davis Engineering Translational Technology Center, an on-campus incubator that supports technology translation into venture to provide guidance in licensing, financing, incorporation and other aspects such as market assessment and freedom to operate analysis as they pertain to the potential to translate the plant-based biomanufacturing platform along a path that may result in a competitive commercial reality. Our current estimates indicate that the potential economic impact is expected to be hundreds of millions of dollars in healthcare savings over 5 years following commercialization. As applications are developed for other biosimilars/biobetters, the economic impact could grow into the billions of dollars per year with an attendant contribution to U.S. competitiveness in biotechnology. The societal impact, long term, will be much lower costs of human therapeutics and new, safer, reliable and expandable supply of biologics for treatment of diseases.