在双特异性抗体中对氨酸葡萄化进行系统的表征
Michael R Reyda1, Qinqin Ji1, Maggie Huang1
1Protein Analytical Development, Therapeutics Development & Supply, Johnson & Johnson Innovative Medicine, Malvern, PA, USA.
mAbs
|January 9, 2026
概括
双特异抗体 (bsAbs) 中的氨酸糖化会导致酸性转移,但不会影响结构或生物活性. 一种新的质量方法提供了有效的过程一致性和可比性监测.
科学领域:
- 生物制药特征的表征
- 蛋白质的翻译后修改.
- 分析化学是一种分析化学.
背景情况:
- 双特异性抗体 (bsAbs) 是关键的治疗方法.
- 在制造过程中,可能会出现充电变体,包括氨酸糖化.
- 了解修改对于产品质量至关重要.
研究的目的:
- 在bsAb中特征化氨酸葡萄化.
- 评估糖化对bsAb结构和功能的影响.
- 开发一种常规的葡萄化监测方法.
主要方法:
- 用于定量测量的特定网站图 (Glu-C/Asp-N).
- 综合分析方法来评估结构和生物活性.
- 一种子单位质量方法的开发和合格.
主要成果:
- 葡萄糖化发生在表面氨酸残留物上随机发生.
- 葡萄糖化导致了酸性同电点 (pI) 转移.
- 没有对高阶结构或生物活性 (ADCC,结合,FcγR相互作用) 的显著影响.
- 为了高通量量化,开发了一种适合目的的亚单位质量方法.
结论:
- 氨酸葡萄化是一种关于bsAb结构和功能的中性修饰.
- 开发的质量方法适用于工艺监测和可比性研究.
- 这项工作提供了关于在bsAb开发中管理充电变体的见解.
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