Recent advances in factor XII(a) inhibitors: an updated patent landscape (2020-present).

INTRODUCTION

Factor XII (FXII) is a liver-derived plasma zymogen that autoactivates on anionic surfaces to FXIIa, which drives the contact blood coagulation pathway, kallikrein-kinin signaling, fibrinolysis, and classical complement. Although congenital FXII(a) deficiency is largely asymptomatic, dysregulated activity is linked to thrombosis, hereditary angioedema (HAE), and neuroinflammation, making FXII(a) an attractive therapeutic target.

AREAS COVERED: This review provides a brief overview of FXII/FXIIa structure and function to highlight its suitability as a therapeutic target. It then summarizes patents published between 2020 and 2025 (patent search using Espacenet, Google Patents, and SciFinder) covering FXII(a)-targeting agents across diverse modalities, including small molecules, proteins and peptides, monoclonal antibodies, oligonucleotides, and siRNAs.

EXPERT OPINION: Patent analysis indicates that most FXII(a) inhibitors remain in early preclinical development, though a growing subset has shown in vivo efficacy in models of thrombosis, HAE, sepsis, and neuroinflammation. The breadth and pace of 2020-2025 filings, together with accumulating translational data, should accelerate progression from patents to clinical candidates, particularly for contact-activation indications (e.g. device-related thrombosis). Resolving full-length FXII/α-FXIIa structures would further enable allosteric inhibitors design.