WuXiBody is a bispecific antibody (bsAb) platform developed by WuXi Biologics. Its key feature is the replacement of one parental antibody's CH1/CL region with the T cell receptor (TCR) constant domain, a design that promotes cognate heavy chain (HC)-light chain (LC) pairing. BsAbs based on WuXiBody can adopt either asymmetric or symmetric format. For purifying a WuXiBody-based symmetric bsAb, we identified a LC-missing species as a major byproduct. While for bsAbs based on other platforms removal of such byproduct can pose considerable challenge to the downstream team, in this case WuXiBody's unique design makes separation relatively straightforward. We previously showed that Capto MMC ImpRes mixed-mode chromatography under bind-elute mode can effectively remove this LC-missing species. However, the dynamic binding capacity (DBC) of Capto MMC ImpRes is relatively low under the selected condition, making the process less desirable for large-scale manufacturing. In this study, we demonstrated that when Capto MMC ImpRes chromatography is conducted under weak partitioning mode, high throughput, good yield, and effective byproduct removal are simultaneously achieved.

WuXiBody 是由药明生物开发的双特异性抗体（bsAb）平台。其关键特征是用 T 细胞受体 (TCR) 恒定域替换一个亲本抗体的 CH1/CL 区域，这种设计促进了同源重链 (HC)-轻链 (LC) 配对。基于 WuXiBody 的 BsAb 可以采用不对称或对称格式。为了纯化基于 WuXiBody 的对称 bsAb，我们确定了一种 LC 缺失物种作为主要副产品。虽然对于基于其他平台的 bsAb，去除此类副产品可能会给下游团队带来相当大的挑战，但在这种情况下，WuXiBody 的独特设计使得分离相对简单。我们之前表明，Capto MMC ImpRes 混合模式色谱在结合洗脱模式下可以有效去除这种 LC 缺失的物种。然而，Capto MMC ImpRes 的动态结合能力 (DBC) 在所选条件下相对较低，使得该工艺不太适合大规模制造。在本研究中，我们证明，当 Capto MMC ImpRes 色谱在弱分配模式下进行时，可同时实现高通量、良好收率和有效的副产物去除。