Douglas Nolan, Thomas R. Chin, Mick Eamsureya, Sheldon Oppenheim, Olga Paley, Christina Alves, George Parks
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引用次数: 0
摘要
单克隆抗体（mAbs）需要较高的纯度才能获得监管部门的批准和安全用药。高分子量（HMW）物质是与 mAb 疗法相关的常见杂质。疏水相互作用色谱 (HIC) 树脂通常用于去除这些高分子量杂质。确定合适的疏水相互作用色谱树脂是一个时间和资源密集型过程。在本研究中，我们利用对 mAbs 表面疏水性、表面电荷和热稳定性的测量结果，以及对 HIC 树脂疏水性和 zeta 电位的测量结果，模拟了七种 mAbs 在 13 种 HIC 树脂上的色谱行为，拟合质量很高（调整后 R2 为 0.80）。我们发现 zeta 电位是一个新的关键建模参数。使用这些模型选择 HIC 树脂来清除试验 mAb 的 HMW 时，我们能够达到 60% 的 HMW 清除率和 89% 的回收率。这些模型可用于加快工业环境中 mAb 的下游工艺开发。
Modeling the behavior of monoclonal antibodies on hydrophobic interaction chromatography resins
Monoclonal antibodies (mAbs) require a high level of purity for regulatory approval and safe administration. High-molecular weight (HMW) species are a common impurity associated with mAb therapies. Hydrophobic interaction chromatography (HIC) resins are often used to remove these HMW impurities. Determination of a suitable HIC resin can be a time and resource-intensive process. In this study, we modeled the chromatographic behavior of seven mAbs across 13 HIC resins using measurements of surface hydrophobicity, surface charge, and thermal stability for mAbs, and hydrophobicity and zeta-potential for HIC resins with high fit quality (adjusted R2 > 0.80). We identified zeta-potential as a novel key modeling parameter. When using these models to select a HIC resin for HMW clearance of a test mAb, we were able to achieve 60% HMW clearance and 89% recovery. These models can be used to expedite the downstream process development for mAbs in an industry setting.
期刊介绍：
Bioresources and Bioprocessing (BIOB) is a peer-reviewed open access journal published under the brand SpringerOpen. BIOB aims at providing an international academic platform for exchanging views on and promoting research to support bioresource development, processing and utilization in a sustainable manner. As an application-oriented research journal, BIOB covers not only the application and management of bioresource technology but also the design and development of bioprocesses that will lead to new and sustainable production processes. BIOB publishes original and review articles on most topics relating to bioresource and bioprocess engineering, including: -Biochemical and microbiological engineering -Biocatalysis and biotransformation -Biosynthesis and metabolic engineering -Bioprocess and biosystems engineering -Bioenergy and biorefinery -Cell culture and biomedical engineering -Food, agricultural and marine biotechnology -Bioseparation and biopurification engineering -Bioremediation and environmental biotechnology
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