PFI:AIR-TT: Translation of multimodal membrane adsorbers for protein purifications

PFI:AIR-TT：用于蛋白质纯化的多模式膜吸附器的转化

• 批准号: 1640645
• 负责人: Scott Husson
• 金额: $ 20万
• 依托单位: Clemson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1640645&HistoricalAwards=false
• 关键词: PFI; AIR; TT; Translation; multimodal

This PFI: AIR Technology Translation project focuses on translating multimodal membranes towards commercialization to fill the market need for products that increase purification speeds during biologics drug discovery and preclinical research and development efforts. The multimodal membranes are important because they will help to get biologics to market faster where they are needed to service the large and growing population of patients with long-term, chronic conditions such as cancers, cardiovascular diseases, and autoimmune disorders. The project will result in research-scale, cation-exchange multimodal membrane chromatography (CEX-MMC) column prototypes. This CEX-MMC column has the following unique features: rapid purification of biologics, tolerance of feedstock ionic strength, high biologics binding capacity, and disposability. These features increase productivity and decrease purification costs of biologics by reducing processing times and number of steps, the costs of consumables, and fixed capital expenses when compared to the leading competing chromatography columns in this market space. Market entry will result from use of these products in research and early stage development laboratories, where purification speed is essential and customers are willing to try new technologies.This project addresses remaining technology gaps as it translates from research discovery toward commercial application. The first generation CEX-MMC developed in the NSF lineage award demonstrated unprecedented protein binding capacity at high ionic strength. Dynamic binding capacity results showed that the CEX-MMC column has high productivity; however, protein binding kinetics must be improved. In this project, new membrane coatings will be designed to enhance protein binding kinetics. In addition, nearly all performance data have been collected using pure-component protein solutions and low titer cell culture supernatant, and almost no work has been done to quantify biological activity of the product or removal of aggregates and other impurities. In this project, antibody media will be prepared using commercial cell lines and used to collect these essential performance data. Two biopharmaceutical companies have committed to collaboration for assessing the performance of the prototypes using industry representative process parameters and monoclonal antibody feed streams. Evaluation of protein recovery, purity, and removal of protein aggregates will be measured following the CEX-MMC column purification step. These are critical performance measures that need to be determined for the Minimally Viable Product (MVP) prior to commercialization. Strategic commercialization and educational plans are designed to validate remaining parts of the business model canvas and create new networks among inventors, entrepreneurs, potential investors and potential customers. Broader impacts also include training graduate and undergraduate students to better understand technology commercialization and entrepreneurship and pursue careers developing new purification technologies for biomanufacturing. Graduate and undergraduate students will attend lectures on technology commercialization held at CUBEInC, Clemson University's life science incubator. A collateral benefit of these lectures is that they will give all project personnel regular opportunities for direct communication with business leaders; entrepreneurs; and potential partners, customers, and investors in the life sciences. Students also will complete a course on technology commercialization designed for engineering students. MBA students will advance understanding of the market value, space, potential customers, and competition landscape and seek collaborations for launch with selected industry partners; and evaluate potential distribution channels and estimate the associated costs. The team will use this knowledge continually to refine the overall strategy for translation of the research discoveries onto a path towards commercialization.

该PFI：AIR技术转化项目的重点是将多模态膜转化为商业化，以满足市场对在生物制剂药物发现和临床前研发工作中提高纯化速度的产品的需求。多模态膜很重要，因为它们将有助于生物制剂更快地进入市场，需要它们为大量且不断增长的长期慢性疾病患者提供服务，如癌症，心血管疾病和自身免疫性疾病。该项目将产生研究规模的阳离子交换多模式膜色谱（CEX-MMC）柱原型。该CEX-MMC色谱柱具有以下独特功能：快速纯化生物制剂、耐受原料离子强度、高生物制剂结合能力和一次性使用。与该市场领域领先的竞争色谱柱相比，这些功能通过减少处理时间和步骤数量、耗材成本和固定资本支出，提高了生产率并降低了生物制剂的纯化成本。 在研究和早期开发实验室中使用这些产品将进入市场，在这些实验室中，纯化速度至关重要，客户愿意尝试新技术。该项目解决了从研究发现到商业应用的剩余技术差距。在NSF谱系奖中开发的第一代CEX-MMC在高离子强度下表现出前所未有的蛋白结合能力。动态结合容量结果表明，CEX-MMC柱具有较高的生产率;然而，蛋白结合动力学必须改进。在这个项目中，将设计新的膜涂层来增强蛋白质结合动力学。此外，几乎所有的性能数据都是使用纯组分蛋白质溶液和低滴度细胞培养上清液收集的，几乎没有进行任何工作来量化产品的生物活性或去除聚集体和其他杂质。在本项目中，将使用商业细胞系制备抗体培养基，并用于收集这些基本性能数据。两家生物制药公司已承诺合作，使用行业代表性工艺参数和单克隆抗体进料流评估原型的性能。在CEX-MMC色谱柱纯化步骤后，将测定蛋白回收率、纯度和蛋白聚集体清除率的评价。这些是在商业化之前需要确定的最小可行产品（MVP）的关键性能指标。战略商业化和教育计划旨在验证商业模式画布的其余部分，并在发明者、企业家、潜在投资者和潜在客户之间建立新的网络。更广泛的影响还包括培训研究生和本科生，以更好地了解技术商业化和创业精神，并从事开发生物制造新净化技术的职业。研究生和本科生将参加在克莱姆森大学生命科学孵化器CUBEInC举行的技术商业化讲座。这些讲座的一个附带好处是，它们将为所有项目人员提供与商业领袖、企业家以及生命科学领域的潜在合作伙伴、客户和投资者进行直接交流的定期机会。学生还将完成为工程专业学生设计的技术商业化课程。MBA学生将进一步了解市场价值，空间，潜在客户和竞争格局，并寻求与选定的行业合作伙伴合作推出;评估潜在的分销渠道并估计相关成本。该团队将不断利用这些知识来完善将研究发现转化为商业化道路的整体战略。