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

AIR 选项 1：技术转化 - 孤儿药物 Human Biobetter Alpha-1-抗胰蛋白酶的植物制造

• 批准号: 1343481
• 负责人: Karen McDonald
• 金额: $ 15万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1343481&HistoricalAwards=false
• 关键词: AIR; Option; Technology; Translation; Plant

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.

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、廉价且环保地生产安全有效的人类治疗药物的需求。 翻译的基于植物的生物制造平台具有以下独特的特点：从野生型、非转基因本塞姆氏烟草（烟草的近亲）收获的叶子用作生产宿主，重组治疗蛋白的瞬时表达发生在封闭的系统中，新型黄瓜花叶病毒表达系统用于提高表达水平，重组蛋白的糖基化在生产后的体外过程中进行修饰，提供了一种示例性的高度可扩展的方法，显着降低了资本投资和制造成本，最大限度地减少了环境与该市场领域领先的竞争生产技术相比，在安全性和一致性方面影响并提高了产品质量。 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，从而实现这一目标以及围绕我们技术的专利情况，确定监管途径并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，这是一个校内孵化器，支持技术转化为风险投资，提供许可、融资、注册和其他方面的指导，例如市场评估和运营自由分析，因为它们与潜力有关将基于植物的生物制造平台转化为一条可能带来竞争性商业现实的道路。 我们目前的估计表明，商业化后 5 年内，潜在的经济影响预计将节省数亿美元的医疗保健费用。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，随之而来的是对美国生物技术竞争力的贡献。 从长远来看，社会影响将是人类治疗成本大幅降低，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。