DiLeo Michael, Ley Arthur, Nixon Andrew E, Chen Jie
Process Sciences, Discovery Research, 55 Network Drive, Dyax Corp., Burlington, MA01803, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Nov 15;1068-1069:136-148. doi: 10.1016/j.jchromb.2017.09.050. Epub 2017 Oct 3.
The capture process employed in monoclonal antibody downstream purification is not only the most critically impacted process by increased antibody titer resulting from optimized mammalian cell culture expression systems, but also the most important purification step in determining overall process throughput, product quality, and economics. Advances in separation technology for capturing antibodies from complex feedstocks have been one focus of downstream purification process innovation for past 10 years. In this study, we evaluated new generation chromatography resins used in the antibody capture process including Protein A, cation exchange, and mixed mode chromatography to address the benefits and unique challenges posed by each chromatography approach. Our results demonstrate the benefit of improved binding capacity of new generation Protein A resins, address the concern of high concentration surge caused aggregation when using new generation cation exchange resins with over 100mg/mL binding capacity, and highlight the potential of multimodal cation exchange resins for capture process design. The new landscape of capture chromatography technologies provides options to achieve overall downstream purification outcome with high product quality and process efficiency.
单克隆抗体下游纯化中采用的捕获过程不仅是受优化哺乳动物细胞培养表达系统导致抗体滴度增加影响最关键的过程，也是决定整体工艺通量、产品质量和经济性的最重要纯化步骤。在过去十年中，从复杂原料中捕获抗体的分离技术进展一直是下游纯化工艺创新的一个重点。在本研究中，我们评估了用于抗体捕获过程的新一代色谱树脂，包括蛋白A、阳离子交换和混合模式色谱，以探讨每种色谱方法带来的益处和独特挑战。我们的结果证明了新一代蛋白A树脂结合能力提高的益处，解决了使用结合能力超过100mg/mL的新一代阳离子交换树脂时高浓度冲击导致聚集的问题，并突出了多模式阳离子交换树脂在捕获工艺设计中的潜力。捕获色谱技术的新态势为实现具有高产品质量和工艺效率的整体下游纯化结果提供了选择。
