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

这个PFI: AIR技术翻译项目的重点是将多模态膜转化为商业化，以满足市场对生物制剂药物发现和临床前研究和开发过程中提高净化速度的产品的需求。多模态膜很重要，因为它们将有助于更快地将生物制剂推向市场，这些生物制剂需要服务于大量和不断增长的长期慢性疾病患者，如癌症、心血管疾病和自身免疫性疾病。该项目将产生具有研究规模的阳离子交换多模态膜色谱（CEX-MMC）柱原型。该CEX-MMC色谱柱具有以下独特的特点：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。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品的纯化成本。在研究和早期开发实验室中使用这些产品将导致市场进入，在这些实验室中，净化速度至关重要，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质结合能力。动态结合力结果表明，CEX-MMC色谱柱具有较高的产率；然而，蛋白质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成分蛋白质溶液和低滴度细胞培养上清收集的，几乎没有工作来量化产品的生物活性或去除聚集体和其他杂质。在这个项目中，抗体培养基将使用商业细胞系制备，并用于收集这些基本的性能数据。两家生物制药公司已经承诺合作，使用行业代表性的工艺参数和单克隆抗体饲料流来评估原型的性能。在CEX-MMC柱纯化步骤后，将测量蛋白质回收率、纯度和蛋白质聚集体去除的评估。这些都是最小可行产品（MVP）在商业化之前需要确定的关键性能指标。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，并在发明家、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更好地了解技术商业化和创业精神，并追求为生物制造开发新的净化技术的职业。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举办的技术商业化讲座。这些讲座的附带好处是，它们将为所有项目人员提供与商业领袖直接沟通的定期机会；企业家;以及生命科学领域的潜在合作伙伴、客户和投资者。学生还将完成一门为工科学生设计的技术商业化课程。MBA学生将加深对市场价值、空间、潜在客户和竞争格局的理解，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算相关成本。该团队将利用这些知识不断完善整体战略，将研究发现转化为商业化的道路。

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.