利用陶酸作为一种有效的抛光策略,以在双特异抗体净化过程中去除与产品和工艺相关的杂质
Nattha Ingavat1, Xinhui Wang1, Jia Min Liew1
1Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Bioresources and bioprocessing
|April 22, 2024
概括
陶酸 (CHT) 有效地净化双特异抗体 (bsAbs),达到超过97%的纯度和减少杂质. 此外,CHT还可以缓解聚合,其性能优于传统的阴离子交换染色学 (CEX).
科学领域:
- 生物制药工艺开发 生物制药过程开发
- 蛋白质净化 蛋白质净化
- 染色体学 染色体学 是一种染色学.
背景情况:
- 双特异性抗体 (bsAbs) 是有前途的治疗方法,但由于结构复杂性和杂质概况,它们存在下游处理挑战.
- 陶酸 (CHT) 是一种混合模式的色谱介质,具有双重结合能力 (金属亲和和离子交换),可用于蛋白质净化.
研究的目的:
- 为了研究CHT作为双特异抗体 (bsAb) 净化抛光步骤的有效性.
- 为了将CHT性能与bsAb杂质去除和聚合减轻的传统阴离子交换染色学 (CEX) 进行比较.
主要方法:
- 研究了三种模型双特异性抗体 (bsAbs) 的CHT抛光后蛋白A化物.
- 与阴离子交换染色学 (CEX) 相比,基准的CHT性能.
- 优化了CHT的负载后洗 (PLW) 条件,以增强低分子量 (LMW) 杂质的去除.
主要成果:
- 对不对称和对称的IgG类bsAbs.CHT抛光实现了至少97%的产品纯度.
- 与CEX相比,CHT显示出更高的聚合物清除率,产生低高分子量 (HMW) 杂质 (0.5%) 并减轻染色学诱导的聚合.
- 在CHT上优化PLW可将LMW杂质降低高达48%.
结论:
- CHT是一种高效的抛光介质,用于双特异抗体 (bsAb) 净化,具有高纯度和优异的杂质清除能力.
- 与CEX相比,CHT显著降低了染色学诱导的聚合,这是bsAb处理的关键优势.
- 建议CHT的独特C站点合作机制来推动其杂质清除和聚合减轻能力.
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