Monoclonal antibodies are a class of biotherapeutics used for an increasing variety of disorders, including cancer, autoimmune, neurodegenerative, and viral diseases. Besides their antigen specificity, therapeutic use also mandates control of their solution interactions and colloidal properties in order to achieve a stable, efficacious, non-immunogenic, and low viscosity antibody solution at concentrations in the range of 50-150 mg/mL. This requires characterization of their reversible self-association, aggregation, and weak attractive and repulsive interactions governing macromolecular distance distributions in solution. Simultaneous measurement of these properties, however, has been hampered by solution nonideality. Based on a recently introduced sedimentation velocity method for measuring macromolecular size distributions in a mean-field approximation for hydrodynamic interactions, we demonstrate simultaneous measurement of polydispersity and weak and strong solution interactions in a panel of antibodies with concentrations up to 45 mg/mL. By allowing approximately an order of magnitude higher concentrations than previously possible in sedimentation velocity size distribution analysis, this approach can substantially improve efficiency and sensitivity for characterizing polydispersity and interactions of therapeutic antibodies at or close to formulation conditions.

中文翻译：

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测量浓缩治疗性抗体溶液中的聚集体、自缔合和弱相互作用。

单克隆抗体是一类用于治疗各种疾病的生物治疗剂，包括癌症、自身免疫性疾病、神经退行性疾病和病毒性疾病。除了它们的抗原特异性外，治疗用途还要求控制它们的溶液相互作用和胶体特性，以在 50-150 mg/mL 的浓度范围内获得稳定、有效、非免疫原性和低粘度的抗体溶液。这需要表征它们的可逆自缔合、聚集以及控制溶液中大分子距离分布的弱吸引力和排斥相互作用。然而，这些属性的同时测量受到非理想解决方案的阻碍。基于最近引入的用于测量大分子尺寸分布的沉降速度方法，在平均场近似流体动力学相互作用中，我们展示了在一组浓度高达 45 mg/mL 的抗体中同时测量多分散性和弱和强溶液相互作用。通过允许比以前在沉降速度尺寸分布分析中可能的浓度高大约一个数量级，这种方法可以显着提高在或接近制剂条件下表征治疗性抗体的多分散性和相互作用的效率和灵敏度。我们展示了在一组浓度高达 45 mg/mL 的抗体中同时测量多分散性和弱和强溶液相互作用。通过允许比以前在沉降速度尺寸分布分析中可能的浓度高大约一个数量级，这种方法可以显着提高在或接近制剂条件下表征治疗性抗体的多分散性和相互作用的效率和灵敏度。我们展示了在一组浓度高达 45 mg/mL 的抗体中同时测量多分散性和弱和强溶液相互作用。通过允许比以前在沉降速度大小分布分析中可能的浓度高大约一个数量级，这种方法可以显着提高在或接近制剂条件下表征治疗性抗体的多分散性和相互作用的效率和灵敏度。