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

这个PFI：空气技术翻译项目专注于翻译一种新型的生物制造平台，该平台使用植物瞬时表达治疗性蛋白质，以满足快速、廉价和环保地生产安全有效的人类治疗药物的需求。翻译后的植物生物制造平台具有以下独特功能：使用野生型、非转基因烟草的叶片作为生产宿主，在包含系统中瞬时表达重组治疗蛋白，使用新型黄瓜花叶病毒表达系统提高表达水平，并在后期生产的体外过程中对重组蛋白的糖基化进行修饰，提供了一种示范性的高度可扩展的方法，与该市场领域的领先竞争生产技术相比，该方法显著降低了资本投资和制造成本，将对环境的影响降至最低，并提高了产品质量。该项目通过开发基于技术经济工程的模型来量化以植物为基础的生物制造设施的资本投资成本和总生产成本，以生产人类孤儿药物α-1-抗胰蛋白酶(AAT)，评估我们技术周围的市场潜力和专利格局，确定监管途径，完善我们的财务和收入模型，使植物AAT更接近市场，并使我们能够为临床开发寻求合作伙伴关系。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，在许可、融资、合并和其他方面提供指导，如市场评估和运营自由分析，因为这些方面与将植物性生物制造平台转化为可能导致竞争性商业现实的道路有关。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是数亿美元的医疗节省。随着其他生物仿制药/生物制剂的应用被开发出来，每年的经济影响可能增长到数十亿美元，随之而来的是对美国生物技术竞争力的贡献。从长远来看，社会影响将是人类疗法的成本大大降低，以及用于治疗疾病的新的、更安全、可靠和可扩展的生物制品供应。

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.