Predicting Antibody Developability Profiles Through Early Stage Discovery Screening
Predicting Antibody Developability Profiles Through Early Stage Discovery Screening
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DOI：
10.1080/19420862.2020.1743053
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发表时间：
2020-01-01
期刊：
影响因子：
5.3
通讯作者：
Fayadat-Dilman, Laurence
中科院分区：
文献类型：
--
作者：
Bailly, Marc;Mieczkowski, Carl;Fayadat-Dilman, Laurence
单克隆抗体在多个治疗领域的新药开发中发挥着越来越重要的作用。 “可开发性”一词涵盖了分子通过评估其物理化学性质成功从发现到开发的可行性。这些特性包括自相互作用和聚集的趋势、热稳定性、胶体稳定性以及通过序列工程优化其特性。根据生物学功能、功效、安全性和可开发性选择最佳抗体分子，以实现简化且成功的 CMC 阶段。在早期抗体生成和筛选过程中实施高效实用的高通量可开发工作流程（100 s-1,000 s 分子）对于选择最佳先导候选物至关重要。这涉及对关键可开发性参数的仔细评估，结合结合亲和力和使用少量纯化材料进行生物特性评估（
Monoclonal antibodies play an increasingly important role for the development of new drugs across multiple therapy areas. The term 'developability' encompasses the feasibility of molecules to successfully progress from discovery to development via evaluation of their physicochemical properties. These properties include the tendency for self-interaction and aggregation, thermal stability, colloidal stability, and optimization of their properties through sequence engineering. Selection of the best antibody molecule based on biological function, efficacy, safety, and developability allows for a streamlined and successful CMC phase. An efficient and practical high-throughput developability workflow (100 s-1,000 s of molecules) implemented during early antibody generation and screening is crucial to select the best lead candidates. This involves careful assessment of critical developability parameters, combined with binding affinity and biological properties evaluation using small amounts of purified material (