一个目标亲和度丰富工作流程,以表征治疗抗体内的关键后翻译性修改
Jethro E Prinston1, Wenjing Peng2, Kathleen Provoncha3
1Protein Biochemistry, Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, United States.
Journal of pharmaceutical sciences
|March 1, 2025
概括
识别具有改变标结合的抗体变异对药物质量至关重要. 一种新型亲和染色法成功分离和表征了具有影响力的翻译后修饰 (PTM),包括Fab糖化,确保了治疗疗效.
科学领域:
- 生物制药开发 生物制药开发
- 分析化学 分析化学
- 蛋白质化学 蛋白质化学
背景情况:
- 单克隆抗体 (mAb) 的有效性取决于特定的标结合.
- 抗体碎片化和翻译后修改 (PTMs) 可以影响目标亲和力.
- 在制药开发过程中,描述影响药品质量的PTM是必不可少的.
研究的目的:
- 提出使用半准备性亲和性染色学来识别和表征治疗抗体中的PTMs的概念证明.
- 评估已识别的PTM对药品质量和关键质量属性 (CQA) 的影响.
主要方法:
- 使用半准备性亲和性染色体与固定联体标 (I型细胞因子受体).
- 将治疗性抗体的亚等效应用于亲和系列.
- 采集并分析了使用各种特征分析 (大小,电荷,结合亲和力,基于细胞的功效) 具有差异性目标亲和力的抗体部分.
主要成果:
- 成功识别了新的和特定的PTM,包括Fab糖化,影响药品质量.
- 证明亲和性染色学可以基于连接体结合来分离抗体变异.
- 亲和度丰富分量的表征提供了对影响关键质量属性的PTM的见解.
结论:
- 开发的亲和染色学策略有效地识别了影响治疗抗体质量的PTM.
- 鉴定Fab糖化是PTM显著影响药物质量和潜在的CQA.
- 亲和度丰富分量的正交对角性表征可以指导用于PTM检测的敏感释放试验的开发.
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