改进了扩散相互作用参数测量,以预测缩的mAb溶液的粘度
Yangjie Wei1, Wei Qi1, Erick Maglalang1
1Drug Product Technologies, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California 91320, United States.
Molecular pharmaceutics
|October 31, 2023
概括
预测单克隆抗体 (mAb) 粘度对于药物开发至关重要. 通过添加盐来抑制电荷,测量蛋白质-蛋白质相互作用的改进试验显著提高了治疗mAbs.的粘度预测准确性.
科学领域:
- 生物制药开发 生物制药开发
- 蛋白质生物物理学 蛋白质生物物理学
- 配方科学科学 配方科学
背景情况:
- 治疗单克隆抗体 (mAb) 候选者的开发能力评估需要强大的预测测定,以便早期选择.
- 缩mAbs的高粘度对制造性,稳定性和管理提出了挑战,需要准确的预测.
- 在稀释溶液中的扩散相互作用参数 (k_D) 已被用来预测mAb粘度,但有局限性.
研究的目的:
- 开发和验证一种高通量试验,用于预测高度的mAb粘度.
- 为了改善稀释溶液测量和高度粘度之间的相关性.
- 确定最佳条件来测量具有粘度预测力的蛋白质-蛋白质相互作用.
主要方法:
- 使用高通量测定测量蛋白质与蛋白质相互作用 (k_D).
- 通过添加盐来抑制静电排斥和探测短距离相互作用来修改试验.
- 选了盐类型和度,优化方法在测试mAb集上得到了验证.
主要成果:
- 标准k_D方法显示弱相关性 (R^2=0.24) 与mAb粘度在140 mg/mL时.
- 使用盐的优化k_D方法显著改善了37mAbs.的相关性 (R^2=0.80).
- 改进的方法准确地预测粘度在6-230cP的范围内.
结论:
- 通过考虑短距离相互作用,优化的k_D试验可以更准确地预测mAb粘度.
- 这种改进的试验对治疗mAb候选者的开发性评估有价值.
- 该方法可以更可靠地选择具有有利粘度配置的候选物,用于后期开发.
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