2. Academic Validation
  3. AS3288802, a highly selective antibody to active plasminogen activator inhibitor-1 (PAI-1), exhibits long efficacy duration in cynomolgus monkeys

AS3288802, a highly selective antibody to active plasminogen activator inhibitor-1 (PAI-1), exhibits long efficacy duration in cynomolgus monkeys

  • Biologicals. 2020 Sep:67:21-28. doi: 10.1016/j.biologicals.2020.08.001.
Risa Kashiwagi 1,  Rui Sato 1,  Mari Masumoto 1,  Masayasu Yoshino 1,  Hirotsugu Tanaka 2
Affiliations

Affiliations

  • 1 Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8411.
  • 2 Astellas Innovation Management LLC, 1030 Massachusetts Avenue, Cambridge, MA, 02138, United States. Electronic address: [email protected].
PMID: 32828642 DOI: 10.1016/j.biologicals.2020.08.001
Abstract

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.

Keywords

Antibody drug; Antigen selective antibody; Plasminogen activator inhibitor-1 (PAI-1).

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