Phase II Commercialization of Continuous Countercurrent Tangential Chromatography

 描述（由申请人提供）：本SBIR第II阶段修订提案要求为Chromatan Corporation提供175，000美元的额外资金，用于商业化用于纯化高价值生物制品的连续逆流切向色谱（CCTC）技术，例如，单克隆抗体用于治疗不同类型的癌症，风湿性关节炎，克罗恩病，多发性硬化症和其他严重疾病。这笔资金将用于开发和商业化一种独特的色谱树脂，该树脂将专门适用于四氯化碳系统。与传统的柱色谱法相比，这一发展将使药物制造商能够将总体捕获纯化成本降低65%以上，根据批量大小，每次临床活动可为药物制造商节省500，000 - 3，000，000美元。下游加工目前占重组蛋白产品生产总成本的80%。通过使用浆液形式的树脂颗粒，CCTC克服了传统柱色谱的许多局限性，该浆液通过由一系列静态混合器和中空纤维膜组件组成的一次性流动路径泵送。该系统消除了色谱柱填料，并具有完全一次性的流路，可轻松扩展用于处理来自大规模临床活动的生物反应器流出物。本修订提案的重点是开发一种专门为CTC设计的定制树脂。这种树脂将具有较小的粒度（10 - 20 μm）， 更快的结合动力学，以及更高的动态结合能力。这一发展将对闭路循环系统的性能产生以下有利影响：1。将从细胞培养液中纯化mAb的CCTC系统的生产力提高了四倍（与使用45 μm树脂颗粒获得的生产力相比）。2.与当前的CCTC系统相比，降低缓冲液消耗要求，并将产品mAb浓度提高至少50%。3.将mAb产率从现有的85- 90%提高至≥95%。4.与使用45 μm颗粒的当前CCTC系统相比，mAb纯化成本降低约50%。

 DESCRIPTION (provided by applicant): This SBIR Phase II revision proposal requests $175,000 of additional funding for the Chromatan Corporation to commercialize the Continuous Countercurrent Tangential Chromatography (CCTC) technology for the purification of high value biological products, e.g., monoclonal antibodies for the treatment of different types of cancers, Rheumatoid Arthritis, Crohn's, Multiple Sclerosis and other serious diseases. The funding will be used in order to develop and commercialize a unique chromatography resin that will be specifically suited for the CCTC system. This development will enable drug manufacturers to decrease the overall capture purification costs by over 65% when compared with traditional column chromatography saving drug manufacturers $500,000 - $3,000,000 per clinical campaign depending on batch size. Downstream processing currently accounts for as much as 80% of the overall cost of production of recombinant protein products. CCTC overcomes many of the limitations of conventional column chromatography by using resin particles in the form of a slurry, which is pumped through a disposable flow path consisting of a series of static mixers and hollow fiber membrane modules. The CCTC system eliminates column packing and has a fully disposable flow path that is easily scalable for processing bioreactor effluents from large scale clinical campaigns. This revised proposal is focused on development of a custom resin specifically designed for CCTC. This resin will have a smaller particle size (10 - 20 μm), leading to much faster binding kinetics, as well as higher dynamic binding capacity. This development will have the following favorable impacts on the performance of the CCTC system: 1. Increase the productivity of the CCTC system for mAb purification from cell culture fluid by an additional four-fold (compared to that obtained using 45 μm resin particles). 2. Reduce buffer consumption requirements and increase the product mAb concentration by at least 50% in comparison with the current CCTC system. 3. Increase the yield of mAb to ≥95% from existing 85-90%. 4. Decrease the mAb purification cost by ~50% in comparison with the current CCTC system using 45 μm particles.