三硫化物对不同抗体构造物的结构和功能的影响
Zhiyuan Sun1, Maggie Huang1, Izabela Sokolowska1
1Analytical Development, Discovery, Product Development & Supply, Janssen Research & Development, LLC, Malvern, PA 19355, USA.
Journal of pharmaceutical sciences
|August 18, 2023
概括
三硫化,一种常见的抗体修饰,不会影响多特异性抗体 (MsAbs) 的功能. 这一发现表明三硫化物是抗体产品的非关键质量属性 (非CQA).
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 生物制药开发 生物制药开发
背景情况:
- 三硫化是重组抗体中经常出现的翻译后修饰 (PTM).
- 虽然对单特异性抗体 (MsAbs) 的影响已知,但对多特异性抗体的影响仍未评估.
研究的目的:
- 开发和验证基于质谱的方法,以进行全面的三硫化物表征.
- 评估三硫化物对双特异性 (BsAb) 和三特异性抗体 (TsAb) 的结构和功能影响.
主要方法:
- 开发一种使用电子激活解离 (EAD) 来识别和量化三硫化物的非减少映射方法.
- 建立高通量Fab质量分析方法,用于在工艺开发过程中进行常规的三硫化物监测.
主要成果:
- 三硫化物形成发生在MsAbs,BsAbs和TsAbs的类似地点.
- 三硫化物没有影响评估抗体的大小异质性,电荷异质性或生物活性.
- 试验室稳定性和体内快速转化表明三硫化物的影响有限.
结论:
- 三硫化物可以被归类为抗体产品的非关键质量属性 (非CQA).
- 开发的质谱法适用于表征和监测三硫化物修饰.
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