当前位置: X-MOL 学术mAbs › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Design of next-generation therapeutic IgG4 with improved manufacturability and bioanalytical characteristics
mAbs ( IF 5.6 ) Pub Date : 2020-10-12 , DOI: 10.1080/19420862.2020.1829338
Zhiqiang Chen 1 , Yueming Qian 1 , Yuanli Song 1 , Xuankuo Xu 1 , Li Tao 2 , Nesredin Mussa 1 , Sanchayita Ghose 1 , Zheng Jian Li 1
Affiliation  

ABSTRACT

Manufacturability of immunoglobulin G4 (IgG4) antibodies from the Chemistry, Manufacture, and Controls (CMC) perspective has received little attention during early drug discovery. Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists between rational design of IgG4 candidates and their manufacturing suitability. Here, we illustrate that undesirable two-peak elution profiles in cation-exchange chromatography are attributed to the S228P mutation (in IgG4 core-hinge region) intentionally designed to prevent Fab-arm exchange. A new scaffolding platform for engineering IgG4 antibodies amenable to bioprocessing and bioanalysis is proposed by introducing an “IgG1-like” single-point mutation in the hinge or CH1 region of IgG4S228P. This work offers insight into the design, discovery, and development of innovative therapeutic antibodies that are well suited for robust biomanufacturing and quality control.



中文翻译:

设计具有改进的可制造性和生物分析特性的下一代治疗性 IgG4

摘要

从化学、制造和控制 (CMC) 的角度来看,免疫球蛋白 G4 (IgG4) 抗体的可制造性在早期药物发现过程中很少受到关注。尽管蛋白质工程在改善抗体生物物理特性方面取得了成功,但 IgG4 候选物的合理设计与其制造适用性之间仍存在明显差距。在这里,我们说明了阳离子交换色谱中不良的双峰洗脱图谱归因于 S228P 突变(在 IgG4 核心铰链区域),旨在防止 Fab 臂交换。通过在 IgG4S228P 的铰链或 CH1 区引入“IgG1 样”单点突变,提出了一种用于工程化 IgG4 抗体的新支架平台,适用于生物加工和生物分析。这项工作提供了对设计、发现、

更新日期:2020-10-12
down
wechat
bug