马杜拉胺是一种新型的糖化调节剂,用于哺乳动物食批量和稳定状态 perfusion 过程
Patrick Romann1, Thomas Vuillemin2, Silvia Pavone3
1Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland; Research Division Biochemical Engineering, Institute of Chemical Environmental and Bioscience Engineering, Vienna University of Technology, Vienna, Austria.
Journal of biotechnology
|February 10, 2024
概括
新的调节剂,如maduramycin,可以在治疗性蛋白质中选择性地增加高曼诺斯 (HM) M5甘氨酸. 这些工具增强了生物制造过程,为改进的抗体-药物合物和生物类似物提供了对糖化控制.
科学领域:
- 生物技术是生物技术.
- 葡萄糖生物学 葡萄糖生物学
- 生物制药制造业 生物制药制造业
背景情况:
- 控制高曼诺斯 (HM) 糖含量对于治疗性蛋白质至关重要,特别是对于抗体-药物合物和生物类似物.
- 目前增加HM甘氨酸的方法有限,特别是M5甘氨酸亚型.
研究的目的:
- 确定新型调节剂,可以在单克隆抗体 (mAb) 产品中选择性增加M5甘氨酸.
- 开发用于料批量和 perfusion 过程的料策略,以控制 HM 甘氨酸含量.
主要方法:
- 选聚乙烯离子体化合物,包括maduramycin,以检测它们对mAb糖化酶的作用.
- 与kifunensine进行比较,这是一种α-曼诺酶I抑制剂.
- 开发用于调节器应用的双螺栓添加和连续养策略.
主要成果:
- 马杜拉胺和其他多离子体在不同的细胞系中选择性地增加了M5甘氨酸.
- 基宁素主要增加了M8-M9甘氨酸,显示出对maduramycin的反作用.
- 在料批量和 perfusion 培养中成功实施养策略,实现了与高 HM glycans 相一致的产品质量.
结论:
- 新型HM甘氨酸调节剂,特别是马杜拉胺,扩大了生物治疗甘氨基化控制的可用工具.
- 这些调制器在料批量和 perfusion 过程中都是有效的,支持连续制造.
- 调节器的联合使用允许微调特定的HM甘氨酸配置文件.
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