Strategy and validation of a nonclinicalgeneric plug-and-play antidrug antibodymethod for human monoclonal antibodybiotherapeutics: supplementary tables

The measurement of antidrug antibodies (ADA) in nonclinical studies provides limited value because theformation and incidence of nonclinical ADA does not translate to clinical experience. The formation andpresence of ADA in nonclinical species can, however, correlate to reduced drug exposure and safetyobservations including vasculitis and immune complex disease. Generic ADA methods for humanizedmonoclonal antibody biotherapeutics mitigate the need to develop bespoke ADA methods duringnonclinical drug development. A drug-tolerant, sensitive, generic ADA immunoassay has been developedand validated for measuring ADA in cynomolgus monkey serum samples, allowing for immediatequalification of future monoclonal antibody biotherapeutics. This approach allows us to differentiatecomplexed and free ADA in a rapidly deployable manner when needed.

在非临床研究中检测抗药物抗体（antidrug antibodies, ADA）的价值有限，因为非临床模型中ADA的产生与发生率无法外推至临床实际场景。不过，非临床实验动物体内ADA的产生与存在，可与药物暴露量降低及包括血管炎、免疫复合物病在内的安全性观察指标相关联。针对人源化单克隆抗体生物治疗药物的通用ADA检测方法，可减少非临床药物研发阶段定制化ADA检测方法的开发需求。本研究已开发并验证了一种耐药物、高灵敏度的通用ADA免疫分析法，用于检测食蟹猴血清样本中的ADA，可快速完成后续单克隆抗体生物治疗药物的ADA检测适用性验证。该方法可在有需求时快速部署应用，精准区分结合型与游离型ADA。