合阴离子和离子交换染色学用于快速分离单克隆抗体电荷变体
Patrycja Zimoch-Rumanek1, Dorota Antos2
1Doctoral School of the Rzeszow University of Technology/PL, Poland.
Journal of chromatography. A
|August 17, 2024
概括
一种新的染色学方法有效地使用合阴离子交换 (CEX) 和阴离子交换 (AEX) 染色学分离单克隆抗体 (mAb) 电荷变异. 在最佳的加载条件下,这种工艺可以实现高纯度的酸性,主性和性变体.
科学领域:
- 生物制药工艺开发的发展过程.
- 染色学分离科学 染色学分离科学
- 单克隆抗体 (mAb) 特性表征
背景情况:
- 单克隆抗体 (mAbs) 是关键的治疗药物,但它们的电荷变异可能会影响疗效和安全性.
- 这些充电变体的有效分离对于生产高质量的mAb产品至关重要.
研究的目的:
- 开发和设计一种可靠的方法来分离单克隆抗体 (mAb) 电荷变异.
- 使用合阴离子交换 (CEX) 和阴离子交换 (AEX) 染色学系统进行变体净化.
- 为了优化高负载能力的过程,并实现不同的酸性 (av),主要 (mv) 和基本 (bv) mAb分数.
主要方法:
- 开发一个合的CEX和AEX染色学过程.
- 利用动态模型指导过程设计和模拟.
- 模型的实验性校准使用mAb变体频段配置文件.
- 在CEX中实施两步pH梯度,并在AEX中实施一个阶段pH变化,用于变异化.
主要成果:
- 成功地将mAb分成三个富化产品:酸性 (av),主要 (mv) 和基本 (bv) 变种.
- 实现了高负载密度:CEX中1026毫克mL-1和AEX中高达300600毫克mL-1.
- 证明了过程配置和负载取决于mAb变体组成.
- 通过优化装载条件,展示了产品产量和纯度之间的平衡.
结论:
- 开发的合CEX-AEX染色法程序为mAb电荷变异分离提供了有效的策略.
- 动态建模方法有助于设计和优化复杂的色谱过程.
- 该系统实现的高负载能力适用于工业规模的生物制药制造.
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