BJTJ-1837, a novel FXI activation-blocking antibody.
Res Pract Thromb Haemost
; 7(2): 100067, 2023 Feb.
Article
en En
| MEDLINE
| ID: mdl-36936858
ABSTRACT
Background:
Factor (F)XI contributes to thrombosis development while it plays a limited role in normal hemostasis. FXI targeting has the potential for preventing and treating thrombosis with little bleeding risk.Objectives:
The aim of this study was to develop novel antibody therapeutics against FXI for the treatment of thrombosis-related diseases.Methods:
Mouse hybridoma technology was applied to screen for anti-FXI antibodies. Surface plasma resonance, enzyme inhibition, activated partial thromboplastin time, and prothrombin time assays were conducted to characterize the binding affinity and activity of antibodies. A cynomolgus monkey arterial venous shunt model was applied to validate the antithrombotic activities.Results:
A humanized antibody, BJTJ-1837, reported here bound to the protease domain of FXI and activated FXI with high affinity. BJTJ-1837 fully inhibited the activation of FXI by activated FXII and thrombin. BJTJ-1837 also demonstrated strong anticoagulant activity in human and cynomolgus monkey plasma as measured by activated partial thromboplastin time. Moreover, BJTJ-1837 showed favorable antithrombotic activity with a dose-dependent protection in an arterial venous shunt thrombosis model in cynomolgus monkeys without the bleeding adverse effect. Furthermore, BJTJ-1837 displayed favorable pharmacokinetic and pharmacodynamic properties and good developability.Conclusion:
As a potential antithrombotic therapeutic agent with a safe profile, BJTJ-1837 is a very promising FXI activation-blocking antibody candidate.
Texto completo:
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Bases de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Res Pract Thromb Haemost
Año:
2023
Tipo del documento:
Article
País de afiliación:
China