多属性监测方法用于工程抗体的过程开发,用于特定站点的结合
Alistair R Hines1, Matthew Edgeworth1, Paul W A Devine1
1Analytical Sciences, Biopharmaceutical Development R&D, AstraZeneca, Cambridge, CB2 0AA, United Kingdom.
概括
一种新的质谱法快速分析抗体药物合物,监测氨酸醇状态,糖化,二硫化键和碎片化. 这有助于开发高质量的抗体治疗药物用于癌症治疗.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 生物技术是生物技术.
背景情况:
- 抗体药物合物 (ADC) 是癌症治疗中至关重要的生物治疗药物.
- 特定位点的结合,通常是通过工程化囊蛋白,确保控制药物对抗体的比率.
- 先进的分析方法对于制造具有一致质量的新型抗体支架至关重要.
研究的目的:
- 开发一种快速的,基于质谱的多属性监测 (MAM) 方法.
- 同时评估工程抗体中间体的关键质量属性.
- 为了了解制造工艺和产品质量.
主要方法:
- 开发一种12分钟液态染色体质谱法 (LC-MS) 方法.
- 同时监测囊二醇的氧化状态,N链糖化,链间二硫化键的减少和聚片段的碎片化.
- 在生物处理过程中应用MAM方法来分析抗体中间体.
主要成果:
- 在生物反应器中检测到氧化硫醇,在收获时出现了减少的变体.
- 很大一部分N结合甘氨酸 (~20%) 含有酸,超过野生型IgG1水平.
- 在C239i常数域中确定了新的碎片化地点,并探索了与葡萄糖形式的相关性.
结论:
- 高通量LC-MS MAM方法提供了对抗体中介性质的快速洞察.
- 这种分析方法支持工程抗体支架的开发和制造.
- 了解醇状态,糖化和碎片化等质量属性是ADC发展的关键.
关键词:
抗体中介物 抗体中介物抗体与药物联合体 (ADC)生物制造工艺是生物制造工艺.葡萄糖酶化是什么? 葡萄糖酶化是什么?质谱学 (MS) 是一种质谱学.多属性监控 (MAM) 是一种多属性监控.特定地点的结合.更多相关视频
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