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在抗体配方中缓解聚酸盐降解诱导的可见颗粒形成:从根源原因识别到战略解决方案

Ting Hu¹, Meiqi Yi², Zheng Zhang²

¹Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Biologics Technical Development, BeOne Medicines, Beijing, China.

International journal of pharmaceutics

|October 29, 2025

概括

聚酸盐20 (PS20) 被宿主细胞蛋白质降解导致生物制药中的颗粒形成. 这项研究确定了脂酶A2 (PLA2) 是主要的罪祸首,其消除可以防止PS20降解和颗粒形成.

科学领域:

生物制药配方开发发展
蛋白质稳定蛋白质稳定
药物产品质量药物产品质量

背景情况:

聚酸盐20 (PS20) 对于稳定生物制药中的治疗蛋白质至关重要.
宿主细胞蛋白 (HCPs) 降解PS20,产生自由脂肪酸 (FFAs),导致粒子形成.
确定负责PS20降解的特定医疗保健人员是行业面临的重大挑战.

研究的目的:

研究单克隆抗体 (mAb-1) 配方中意外粒子形成的原因.
确定主要的主体细胞蛋白质,负责聚二酸盐20的降解.
制定一种策略,以减轻PS20的降解和颗粒形成.

主要方法:

使用了胺酸酶抑制剂和基于活性的蛋白质分析来识别潜在的PS20降解酶.
在mAb-1生产细胞系中使用候选脂酶 (PLA2和PLBL2) 的向基因淘汰.
在药物产品 (DP) 中评估了PS20降解和FFA颗粒的形成.

主要成果:

脂酶A2 (PLA2) 和脂酶B样2 (PLBL2) 被确定为PS20降解的潜在贡献者.
针对性地淘汰Pla2,在mAb-1DP中显著降低了PS20降解和FFA颗粒的形成.
Plbd2的淘汰证明PLBL2不是PS20降解的主要贡献者.

结论:

脂酶A2 (PLA2) 被确定为主要的主体细胞蛋白质,负责聚酸20的降解.
在生产细胞中消除PLA2有效地减轻了PS20的降解和相关的颗粒形成.
这项研究提供了一个强大的策略,用于识别和控制生物制药配方中HCP诱导的PS20降解.

关键词:

这就是CRISPR/Cas9的作用.配方的稳定性配方的稳定性宿主细胞蛋白质 (HCP) 是一种颗粒颗粒的粒子脂酶A2 (PLA2) 是一种酶.聚酸盐20 (PS20) 是一种多酸盐.表面活性剂是什么?表面活性剂是什么?

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