在双特异性抗体中冷诱导的蛋白质聚合:特征和机制性见解
Xiaofeng Lu1, Blanca Domingo-Yenes1, Noah Cohen2
1Drug Product Development, CMC Biologics, AbbVie, 1000 Gateway Blvd, South San Francisco, CA 94080, United States.
Journal of pharmaceutical sciences
|February 28, 2025
概括
在冷解过程中,双特异抗体 (BsAbs) 中的蛋白质聚合是由冰的相互作用和二分化驱动的,特别是在-20°C. 本研究确定了这些生物制剂的特定序列负债和缓解策略.
科学领域:
- 生物制药的发展.
- 蛋白质聚合蛋白质的聚合.
- 抗体工程是一种抗体工程.
背景情况:
- 双特异性抗体 (BsAbs) 是关键的治疗药物,但容易聚合.
- 高分子量物种 (HMWS) 的形成会影响药物的有效性和安全性.
- 了解聚合驱动因素对于生物制药的稳定性至关重要.
研究的目的:
- 在冷解过程中调查BsAb聚合的主要机制和驱动因素.
- 确定导致HMWS在-20°C和-80°C之间形成的因素.
- 探索BsAb聚合的内在结构因素和缓解策略.
主要方法:
- 评估结应力:温度,结度,冰形成,冷却速度,冷变性.
- 通过实验分析识别蛋白质聚合机制.
- 单链可变片段 (scFv) 的分子结构建模,以评估内在驱动因素.
主要成果:
- 蛋白质二聚化被确定为主要的聚合机制.
- 蛋白与冰的相互作用被证实是主要的聚合驱动因素.
- 与 -80°C相比,在-20°C的高分子流动性会加剧聚合.
- 在scFv域内发生的固态冲突被确定为潜在的内在聚合驱动因素.
结论:
- 在冷解过程中的BsAb聚合是特定序列的负担.
- 冰的相互作用和蛋白质二元化是关键的驱动因素,受储存温度和分子流动性的影响.
- 获得的见解可以为预防和减轻双特异抗体产品聚合的策略提供信息.
关键词:
双特异性抗体 双特异性抗体配方 配方 配方 是一个结 结 结 是一种高分子量物种 (HMWS) 形成.蛋白质聚合蛋白质的聚合.单链可变碎片 (scFv) 是指一个单链可变碎片.稳定的稳定性 稳定的稳定性更多相关视频
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