Abstract:

Antibody, especially monoclonal antibody has become an important therapeutic drug which has a broad market demand and prospect. Nowadays the bottleneck of antibody production has shifted from antibody expression to downstream processing. The typical antibody purification process starts with protein A affinity chromatographic to capture the antibody and includes two subsequent polishing steps for impurity removal, such as ionic exchange, hydrophobic interaction or hydroxyapatite chromatography. There are some limitations restricting the development in antibody industry. Therefore, the researchers are committed to develop novel purification methods, including mixed-mode chromatography (MMC) and short peptide biomimetic chromatography which remedy the weakness of traditional methods. According to the recent advances in the purification of monoclonal antibody drugs, protein A affinity chromatography and the novel chromatographic methods and their applications in monoclonal antibody purification are reviewed in the present article.

Key words: antibody drug, monoclonal antibody, purification, chromatography, mixed-mode, short peptide biomimetic, molecular simulation

摘要：

抗体，特别是单克隆抗体是一类重要的生物技术药物，具有巨大的市场前景。目前抗体药物生产的瓶颈已由抗体表达转移到抗体的分离纯化中，其中层析是最关键的技术。典型的抗体纯化过程首先通过蛋白A亲和层析对抗体进行捕获，然后进一步精制，主要方法包括离子交换层析、疏水相互作用层析以及羟基磷灰石层析等，这些传统的层析方法不可避免存在一定的局限性。为此，研究者致力于开发合适的新方法，如疏水性电荷诱导层析和短肽仿生层析等，很好地弥补了传统层析方法的不足。本文根据近年来国内外在单抗药物分离纯化方面所取得的研究进展，着重介绍了在单抗分离纯化中的常用的层析技术及研究进展。

关键词: 抗体药物, 单克隆抗体, 纯化, 层析, 混合模式, 短肽仿生, 分子模拟