利用分离单克隆抗体池的生物分析特征,在病毒过过程中识别容易聚合和不太容易过的蛋白质形式
Solomon Isu1, Lilia Vinskus1, Derek Silva1
1Process Solutions, MilliporeSigma, Burlington, Massachusetts, USA.
Biotechnology progress
|March 7, 2024
概括
预测单克隆抗体 (mAb) 的过性对于生物治疗开发至关重要. 这项研究揭示了与mAb过器性能相关的分子水平质量属性,从而实现了优化病毒过过程.
科学领域:
- 生物制药制造业 生物制药制造业
- 下游加工 下游加工
- 蛋白质化学 蛋白质化学
背景情况:
- 单克隆抗体 (mAbs) 是重要的生物治疗药物,需要强大的制造工艺.
- 目前的mAb净化依赖于经验方法,通常包括预过,以防止病毒过器污染.
- 缺乏mAb过能力的预测模型,阻碍了高效的下游工艺开发.
研究的目的:
- 研究影响单克隆抗体过能力的分子水平因素.
- 建立mAb质量属性与病毒过器性能之间的相关性.
- 为了减少流程开发时间,材料损失和与病毒过相关的成本.
主要方法:
- 使用pH级梯度分化来从散装料中分离mAb变异.
- 分析了生物物理特性 (寡合体状态,同电点,扩散相互作用,糖形状).
- 分成池的可过性 (负载和吞吐量) 用Viresolve Pro病毒过器进行了评估.
主要成果:
- 在特定的mAb质量属性和可过性之间发现了显著的相关性.
- 分解产生了具有明显生物物理性质和不同波器性能的池.
- 统计分析揭示了病毒过过程中mAb行为的关键决定因素.
结论:
- 了解分子水平的mAb特性可以预测可过性,优化病毒去除步骤.
- 这种方法为更高效和更具成本效益的生物治疗下游加工提供了一条途径.
- 这些发现弥合了在病毒过过程中预测mAb行为方面的知识差距.
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