Antibodies have strong affinity to their target molecules, a characteristic that is utilized in antibody drugs. For antibody drugs, target molecule specificity and long duration pharmacokinetics, along with strong affinity to the target molecule are important characteristics. Plasminogen activator inhibitor-1 (PAI-1) is one of the key regulators of the fibrinolysis system, and the benefits of PAI-1 activity inhibition have been widely reported for multiple thrombosis and fibrosis-related diseases. Here, we generated a novel antibody, AS3288802, with high selectivity for active PAI-1. AS3288802 exhibited prolonged and strong inhibition of PAI-1 activity in cynomolgus monkey blood in vivo. Given that AS3288802 showed prolonged antigen inhibition activity due to its high target molecule selectivity, we propose that increasing target molecule selectivity may be a key strategy for lengthening the efficacy duration of antibody drugs. AS3288802 may be a promising anti-PAI-1 antibody drug with multiple clinical applications including thrombosis and fibrosis-related diseases.

抗体对其靶分子具有很强的亲和力，这是抗体药物中利用的一个特征。对于抗体药物，靶分子的特异性和持续时间长的药代动力学以及对靶分子的强亲和力是重要的特征。纤溶酶原激活剂抑制剂-1 (PAI-1) 是纤溶系统的关键调节剂之一，PAI-1 活性抑制的益处已被广泛报道用于多种血栓形成和纤维化相关疾病。在这里，我们生成了一种新型抗体 AS3288802，对活性 PAI-1 具有高选择性。AS3288802在体内对食蟹猴血液中的PAI-1活性表现出持久而强烈的抑制作用. 鉴于 AS3288802 由于其高靶分子选择性而表现出延长的抗原抑制活性，我们提出提高靶分子选择性可能是延长抗体药物疗效持续时间的关键策略。AS3288802 可能是一种有前景的抗 PAI-1 抗体药物，具有多种临床应用，包括血栓形成和纤维化相关疾病。