Phase II Commercialization of Continuous Countercurrent Tangential Chromatography

连续逆流切向色谱的第二阶段商业化

• 批准号: 8831526
• 负责人: Oleg Shinkazh
• 金额: $ 17.5万
• 依托单位: CHROMATAN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8831526
• 关键词: Accounting; Antibodies; Binding; Biological Products; Biological Response Modifier Therapy; Bioreactors; Buffers; Caliber; Cell Culture Techniques; Chromatography; Clinical; Column Chromatography; Consumption; Custom; Cyclic GMP; Development; Devices; Diffusion; Disease; Documentation; Drops; Fiber; Funding; Goals; Harvest; Hour; Housing; Kinetics; Lead; Life; Liquid substance; Living Costs; Location; Malignant Neoplasms; Manufacturer Name; Marketing; Mechanics; Membrane; Monoclonal Antibodies; Multiple Sclerosis; Particle Size; Performance; Pharmaceutical Preparations; Phase; Plant Resins; Process; Production; Productivity; Proteins; Pump; Qualifying; Recombinant Proteins; Request for Proposals; Rheumatoid Arthritis; Savings; Series; Site; Small Business Innovation Research Grant; Software Validation; Solutions; System; Technology; Testing; Time; Ultrafiltration; Validation; Work; cancer type; commercialization; cost; countercurrent chromatography; crosslink; design; design and construction; flexibility; next generation; novel; operation; particle; pressure; prototype; public health relevance; residence; scale up; success; therapeutic protein; validation studies

 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.

 描述（由申请人提供）：本 SBIR II 期修订提案要求 Chromatan 公司提供 175,000 美元的额外资金，以将连续逆流切向色谱 (CCTC) 技术商业化，用于纯化高价值生物产品，例如用于治疗不同类型癌症、类风湿关节炎、克罗恩病、多发性硬化症和其他严重疾病的单克隆抗体。这笔资金将用于开发和商业化一种特别适合 CCTC 系统的独特色谱树脂。与传统柱色谱法相比，这一开发将使药品制造商能够将总体捕获纯化成本降低 65% 以上，根据批次大小，每个临床活动可为药品制造商节省 500,000 - 3,000,000 美元。目前下游加工占重组蛋白产品生产总成本的80%之多。 CCTC 通过使用浆料形式的树脂颗粒克服了传统柱色谱的许多限制，该树脂颗粒被泵送通过由一系列静态混合器和中空纤维膜模块组成的一次性流路。 CCTC 系统消除了柱填充，并具有完全一次性的流路，可轻松扩展以处理大规模临床活动中的生物反应器流出物。该修订提案的重点是开发专为 CCTC 设计的定制树脂。该树脂的粒径较小（10 - 20 μm），领先 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 CCTC 系统的性能产生以下有利影响： 1. 将 CCTC 系统从细胞培养液中纯化 mAb 的生产率提高四倍（与使用 45 μm 树脂颗粒获得的生产率相比）。 2. 与现有 CCTC 系统相比，减少缓冲液消耗要求，并将产品 mAb 浓度提高至少 50%。 3. 将mAb的产率从现有的85-90%提高到≥95%。 4. 与当前使用 45 μm 颗粒的 CCTC 系统相比，mAb 纯化成本降低约 50%。

项目成果

Performance optimization of continuous countercurrent tangential chromatography for antibody capture.

用于抗体捕获的连续逆流切向色谱的性能优化。

• DOI: 10.1002/btpr.2250
• 发表时间: 2016
• 期刊: Biotechnology progress
• 影响因子: 2.9
• 作者: Dutta,AmitK;Tan,Jasmine;Napadensky,Boris;Zydney,AndrewL;Shinkazh,Oleg
• 通讯作者: Shinkazh,Oleg

Purification of monoclonal antibodies from clarified cell culture fluid using Protein A capture continuous countercurrent tangential chromatography.

使用蛋白质A捕获连续的逆时性切线色谱法从澄清的细胞培养液中纯化单克隆抗体。

• DOI: 10.1016/j.jbiotec.2015.02.026
• 发表时间: 2015-11-10
• 期刊: Journal of biotechnology
• 影响因子: 4.1
• 作者: Dutta AK;Tran T;Napadensky B;Teella A;Brookhart G;Ropp PA;Zhang AW;Tustian AD;Zydney AL;Shinkazh O
• 通讯作者: Shinkazh O