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.

单克隆抗体是一类用于治疗越来越多的疾病的生物疗法，包括癌症，自身免疫性疾病，神经退行性疾病和病毒性疾病。除了其抗原特异性外，治疗用途还要求控制其溶液相互作用和胶体性质，以实现浓度范围为50-150 mg / mL的稳定，有效，非免疫原性和低粘度抗体溶液。这要求表征其可逆的自缔合，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。但是，解决方案的非理想性妨碍了同时测量这些特性。基于最近引入的沉降速度方法，该方法用于测量流体动力学相互作用的平均场近似中的大分子尺寸分布，我们证明了同时测量一组浓度高达45 mg / mL的抗体中的多分散性以及弱溶液和强溶液相互作用。通过允许比先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，该方法可以显着提高表征制剂或接近制剂条件的多分散性和治疗性抗体相互作用的效率和灵敏度。我们证明了同时测量一组浓度高达45 mg / mL的抗体中的多分散性和弱弱溶液相互作用。通过允许比先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，该方法可以显着提高表征制剂或接近制剂条件的多分散性和治疗性抗体相互作用的效率和灵敏度。我们证明了同时测量一组浓度高达45 mg / mL的抗体中的多分散性和弱弱溶液相互作用。通过允许比先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，该方法可以显着提高表征制剂或接近制剂条件的多分散性和治疗性抗体相互作用的效率和灵敏度。