CSL Behring GmbH, R&D, Marburg, Germany.
CSL Limited, BIO21 Institute, Parkville, VIC, Australia.
Methods Mol Biol. 2021;2178:49-62. doi: 10.1007/978-1-0716-0775-6_6.
Monoclonal antibodies (mAbs) are the fastest-growing segment in the drug market with eight of the top 20 selling drugs being mAbs and combined sales of close to 60 billion US$/year. The development of new therapeutic mAbs requires the purification of a large number of candidate molecules during initial screenings, subsequent affinity maturation campaigns, and finally the engineering of variants to improve half-life, functionality, or biophysical properties of potential lead molecules. A successful strategy to purify this ever-increasing number of mAbs in a timely manner has been the miniaturization and automation of the purification process using automatic liquid handlers (ALHs) such as Tecan's Evo or PerkinElmer's Janus platforms. These systems can be equipped with miniaturized columns, which are available in a wide variety of sizes and affinity matrices to cater to the need of the respective application. Various publications have described the setup of ALHs including the respective purification procedure. However, despite being very precise regarding the overall approach, most publications do not focus on the technical optimization and potential pitfalls, which can be crucial to obtain a robust process. To fill this gap, the present publication is aiming to point at some technical difficulties and suggesting potential ways to overcome these problems in order to facilitate the setup of new ALH systems for the purification of antibodies.
单克隆抗体 (mAbs) 是药物市场中增长最快的部分，前 20 种畅销药物中有 8 种是 mAbs，年销售额接近 600 亿美元。开发新的治疗性 mAbs 需要在初步筛选、随后的亲和力成熟活动以及最终工程变体以提高潜在先导分子的半衰期、功能或物理性质期间，对大量候选分子进行纯化。一种成功的策略是使用自动液体处理机 (ALH) 及时对 mAbs 进行微型化和自动化纯化，例如 Tecan 的 Evo 或 PerkinElmer 的 Janus 平台。这些系统可以配备微型化的柱子，这些柱子有多种尺寸和亲和基质可供选择，以满足各自应用的需求。已经有各种出版物描述了 ALH 的设置，包括各自的纯化程序。然而，尽管大多数出版物在整体方法上非常精确，但它们并不关注技术优化和潜在的陷阱，这些对于获得稳健的工艺至关重要。为了填补这一空白，本出版物旨在指出一些技术难点，并提出潜在的方法来克服这些问题，以促进新的 ALH 系统的建立，用于抗体的纯化。
