简化影响高度单克隆抗体配方长期聚合率的生物物理因素
James K Forder1, Erinc Sahin2, Christopher J Roberts1
1Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19713, United States.
Molecular pharmaceutics
|December 11, 2025
概括
药物开发中的蛋白质聚合难以预测. 这项研究发现,冷藏储存的稳定性与更高的温度不同,净价值是单克隆抗体的关键因素.
科学领域:
- 生物制药的发展.
- 蛋白质聚合动力学 蛋白质聚合动力学
- 机器学习在药物发现中的作用
背景情况:
- 蛋白质聚合是开发治疗性蛋白质的一个主要挑战,影响制造,储存和患者安全.
- 在各种条件下预测聚合对于识别稳定的候选药物至关重要.
- 单克隆抗体 (MAbs) 是一种易于聚合的重要类型的蛋白质治疗药物.
研究的目的:
- 系统地评估影响单克隆抗体 (MAb) 聚合率的因素,在各种溶液条件和温度下进行.
- 为了比较加速稳定性研究 (30-50°C) 与MAb聚合的冷藏储存条件的预测能力.
- 应用机器学习模型来识别管理高度MAb聚合的关键属性.
主要方法:
- 在不同的pH值,离子强度,MAb度和化温度下研究了四种MAbs的稳定性.
- 基于构造稳定性和净蛋白质-蛋白质相互作用 (自我相互作用) 的分析结果.
- 利用可解释的机器学习模型来量化聚合现象,重点关注冷藏条件.
主要成果:
- 聚合率表现出非Arrhenius行为,这意味着它们不遵循一个简单的温度依赖模式.
- 与冷藏条件相比,加速稳定性研究 (30-50°C) 提供了误导性的稳定性排名.
- 净价值 (蛋白质电荷相互作用的度量) 是冷藏储存中MAb聚合的最重要的预测因素.
结论:
- 标准加速稳定性测试可能不准确地反映在典型的冷藏储存下MAb的稳定性.
- 冷藏条件对于准确评估MAb聚合倾向至关重要.
- 净价值是预测MAb聚合并确保药物配方稳定性的关键参数.
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