纳酸盐对单克隆抗体聚合因激发诱导的NaCl的影响
Justin K Y Hong1, Wei Liu1, Kai Zheng2
1Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080.
PDA journal of pharmaceutical science and technology
|August 23, 2024
概括
化 (NaCl) 在激发压力下加速单克隆抗体 (mAb) 聚合,影响临床使用期间治疗蛋白质的稳定性. 观察到不同的聚合机制,突出了需要谨慎的配方.
科学领域:
- 生物制药的发展.
- 蛋白质聚合蛋白质的聚合.
- 治疗性单克隆抗体 治疗性单克隆抗体
背景情况:
- 单克隆抗体 (mAbs) 是重要的治疗药物,但容易降解.
- 在制造,储存和临床处理期间的激发应激会导致mAb聚合.
- 在静脉注射 (IV) 袋中用盐水稀释会减少保护性表面活性剂,增加盐度,加剧压力.
研究的目的:
- 为了研究化 (NaCl) 对在激发应力下两个mAbs的聚合的影响.
- 要了解稀释,界面应力和盐度在mAb稳定性上的相互作用.
- 为改善临床使用提供关于mAb配方的见解.
主要方法:
- 研究了两个不同的单克隆抗体 (mAbs) 的聚合.
- 应用于mAb溶液的振动应力,其中化 (NaCl) 度不同.
- 分析了聚合机制,形态学和可逆性.
主要成果:
- 发现化 (NaCl) 可以加速研究的两种mAbs的聚合.
- 在NaCl的存在下,在两个mAbs之间观察到聚合机制,形态和可逆性的明显差异.
- 该研究清楚地表明,盐在临床使用条件下对mAb稳定性的显著影响.
结论:
- NaCl在激发应力下显著影响mAb聚合动力学和特性.
- 了解盐的作用对于开发稳定的mAb配方以供患者使用至关重要.
- 这项研究为生物治疗中通过界面应力介导的蛋白质聚合提供了宝贵的见解.
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