Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai, 200131, China.
Manufacturing Science and Technology (MSAT), WuXi Biologics, 108 Meiliang Road W, MaShan Binhu District, Wuxi, 214092, China.
Protein Expr Purif. 2021 May;181:105822. doi: 10.1016/j.pep.2021.105822. Epub 2021 Jan 9.
WuXiBody is a novel bispecific antibody (bsAb) platform developed by WuXi Biologics. BsAbs based on WuXiBody can adopt either asymmetric or symmetric format. In general, recombinant production of asymmetric bsAbs has a more complex impurity profile than that of symmetric ones, as assembly of the former usually involves an increased number of distinct chains. Consequently, purification of asymmetric bsAb typically poses greater challenges to the downstream team. Recently while purifying a WuXiBody-based bsAb in asymmetric format, we learned that MMC ImpRes mixed-mode chromatography under linear pH or salt gradient elution can effectively remove two out of the three low-molecular-weight byproducts post Protein A chromatography but not the third one, which was eventually removed under pH-salt dual gradient elution. This finding suggests that MMC ImpRes chromatography performed under pH-salt dual gradient elution provides better resolution than that performed under pH/salt mono gradient elution.
药明生物开发的新型双特异性抗体（bsAb）平台——WuXiBody。基于 WuXiBody 的 bsAbs 可以采用不对称或对称格式。一般来说，不对称 bsAbs 的重组生产比对称 bsAbs 的杂质谱更复杂，因为前者的组装通常涉及更多不同的链。因此，不对称 bsAb 的纯化通常对下游团队构成更大的挑战。最近，在纯化一种不对称格式的基于 WuXiBody 的 bsAb 时，我们了解到，在 pH 线性或盐梯度洗脱下，MMC ImpRes 混合模式色谱可以有效地去除 Protein A 色谱后三种低分子量副产物中的两种，但不能去除第三种，第三种最终在 pH-盐双梯度洗脱下被去除。这一发现表明，在 pH-盐双梯度洗脱下进行的 MMC ImpRes 色谱比在 pH/盐单梯度洗脱下进行的色谱具有更好的分辨率。
