基于机械建模的基离子交换色谱法开发一种双特异性抗体-同极体分离工艺
Zichen Wang1, Guohong Qin1, Xiaoying Liang1
1Nanjing Chia Tai-Tianqing Pharmaceutical Co.Ltd, Fanghua Pharmaceutical Research Institute, Department of Biology, Nanjing 210046, China.
概括
一个机械模型优化了二特异性抗体净化中的阴离子交换染色学,显著减少了同聚体杂质. 这种方法提高了双特异性抗体 (bsAb) 的产量和纯度,简化了生物过程的开发.
科学领域:
- 生物制药制造业 生物制药制造业
- 染色学分离 染色学分离
- 蛋白质化学 蛋白质化学
背景情况:
- 再组合产生双特异抗体 (bsAbs) 面临的净化挑战是由于同质体的形成.
- 阴离子交换色谱 (CEC) 是有效的基于电荷的分离,但复杂的优化.
研究的目的:
- 开发和验证CEC的机械模型,以优化bsAb净化.
- 为了高效地将bsAbs从同聚体杂质中分离出来.
主要方法:
- 采用了阴离子交换色谱的机械模型.
- 扩展的兰迈尔和硬质质量作用 (SMA) 吸附模型进行了比较.
- 由于其精简的校准和预测能力,选择了SMA.
主要成果:
- 优化的化剂度为120mM NaCl.
- 实现了96.4%的bsAb产量,同聚体含量从26.4%降至0.5%.
- 证明了高模型准确性,预测-实验偏差在1.5%以内.
结论:
- 经过验证的染色学机械模型准确地预测了化行为.
- 这种模型有助于高效优化用于bsAb净化的CEC过程.
- 优化的工艺显著提高了bsAb纯度和产量.
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