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

这个PFI：空气技术转换项目专注于将多模膜转化为商业化，以满足市场对在生物制药、药物发现和临床前研发工作中提高提纯速度的产品的需求。多模膜很重要，因为它们将有助于将生物制品更快地推向市场，在需要它们的地方，它们将服务于大量且不断增长的长期慢性病患者，如癌症、心血管疾病和自身免疫性疾病。该项目将产生研究规模的阳离子交换多峰膜色谱(CEX-MMC)柱原型。这种CEX-MMC色谱柱具有以下独特的特点：生物制品的快速纯化、对原料离子强度的耐受性、高生物制品结合容量和一次性。与市场上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，提高了生物制剂的生产率并降低了纯化成本。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转化为商业应用的剩余技术差距。第一代CEX-MMC在NSF谱系奖中开发，在高离子强度下显示出前所未有的蛋白质结合能力。动态结合能力结果表明，CEX-MMC柱具有较高的结合效率，但蛋白质结合动力学有待提高。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。在这个项目中，将使用商业细胞系制备抗体介质，并用于收集这些重要的性能数据。两家生物制药公司已承诺合作，使用具有行业代表性的工艺参数和单抗饲料流来评估原型的性能。在CEX-MMC柱纯化步骤之后，将测量蛋白质回收率、纯度和蛋白质聚集体的去除的评估。这些是最低生存能力产品(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剩余部分，并在发明者、企业家、潜在投资者和潜在客户之间创建新的网络。更广泛的影响还包括培训研究生和本科生更好地理解技术商业化和企业家精神，并从事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举行的关于技术商业化的讲座。这些讲座的一个附带好处是，它们将使所有项目人员有机会定期与商业领袖、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。学生还将完成一门为工科学生设计的技术商业化课程。MBA学生将增进对市场价值、空间、潜在客户和竞争格局的了解，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总体战略。

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.