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

该PFI：AIR技术翻译项目的重点是翻译一种新型生物制造平台，该平台使用植物瞬时表达治疗性蛋白质，以满足快速，廉价和环保生产安全有效的人类治疗药物的需求。 翻译的植物基生物制造平台具有以下独特功能：从野生型非转基因本氏烟草收获的叶（烟草的近缘种）作为生产宿主，重组治疗性蛋白在封闭系统中瞬时表达，利用新型黄瓜花叶病毒表达系统提高表达水平，并且重组蛋白的糖基化在生产后的体外过程中被修饰，提供了示例性的高度可扩展的方法，其显著降低了资本投资和制造成本，与该市场领域的领先竞争生产技术相比，最大限度地减少了对环境的影响，并在安全性和一致性方面提高了产品质量。 该项目通过开发一个基于技术经济工程的模型来实现这一目标，以量化基于植物的生物制造设施生产人类孤儿药α-1-抗胰蛋白酶（AAT）的资本投资成本和总生产成本，评估市场潜力和围绕我们技术的专利景观，确定监管途径，完善我们的财务和收入模式，使植物制造的AAT更接近市场，并使我们能够寻求临床开发的合作伙伴关系。 目前的合作伙伴包括加州大学戴维斯分校工程转化技术中心，这是一个校园孵化器，支持将技术转化为风险投资，以提供许可，融资，注册和其他方面的指导，例如市场评估和自由操作分析，因为它们涉及到转化植物为基础的生物制造平台的潜力沿着可能导致竞争性商业现实的道路。 我们目前的估计表明，在商业化后的5年内，潜在的经济影响预计将为医疗保健节省数亿美元。随着其他生物仿制药/生物改良剂的应用开发，其经济影响可能会增长到每年数十亿美元，并随之对美国在生物技术方面的竞争力做出贡献。 从长远来看，社会影响将是人类治疗药物的成本大大降低，以及用于治疗疾病的新的、更安全、可靠和可扩展的生物制剂供应。

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.