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Selecting for developability of polypeptide drugs in eukaryotic cell display systems

机译:在真核细胞展示系统中选择多肽药物的可开发性

摘要

Use of the surface presentation level of binders (e.g., antibodies, receptors) on cultured higher eukaryotic cells in vitro as a predictive indicator of developability characteristics, e.g., solubility, of the binders. Display libraries of higher eukaryotic cells, e.g., mammalian cells, adapted for use in screening surface-displayed binders for developability and affinity of target binding. High-throughput screening of display libraries with in-built selection for developability including binder solubility, capability to be formulated at high concentrations, low propensity for non-specific binding, and half-life. Enrichment of populations of binders for developability characteristics and/or other qualities such as target binding and affinity, by controlling cell surface presentation of binders from an inducible promoter operably linked to binder-encoding DNA.
机译:结合物(例如抗体,受体)在体外培养的高等真核细胞上的表面呈递水平的使用,作为结合物的可显影性例如溶解性的预测指标。适合用于筛选表面展示的结合物的可显影性和靶标结合亲和力的高等真核细胞,例如哺乳动物细胞的展示文库。高通量筛选展示库,并内置选择可开发性,包括粘合剂溶解度,高浓度配制能力,非特异性结合倾向低和半衰期。通过控制可操作地连接至编码结合剂的DNA的诱导型启动子的结合剂的细胞表面呈递,富集结合剂群体的可开发性特征和/或其他质量,例如靶结合和亲和力。

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