Factor XIa inhibitors: A review of the patent literature

Research output: Contribution to journalReview article

Authors

External Institution(s)

  • Virginia Commonwealth University

Details

Original languageEnglish (US)
Pages (from-to)323-345
Number of pages23
JournalExpert Opinion on Therapeutic Patents
Volume26
Issue number3
StatusPublished - Mar 3 2016
Peer-reviewedYes

Abstract

Introduction: Anticoagulants are the mainstay for prevention and/or treatment of thrombotic disorders. Each clinically used anticoagulant is associated with significant adverse consequences, especially bleeding. Factor XIa (FXIa), a key factor involved in the amplification of procoagulation signal, has been suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. Areas covered: Our literature search uncovered dozens of industrial and academic patents on the discovery of novel FXIa/FXI inhibitors. Small peptidomimetics, sulfated glycosaminoglycan mimetics, polypeptides, antisense oligonucleotides, and monoclonal antibodies have been developed as inhibitors of FXIa. Although many agents are in early discovery/development phases, the activity and safety of a few have been evaluated in various animal models and in humans. Expert opinion: FXIa is a promising drug target for development of effective anticoagulants with limited bleeding complications. Literature reveals a major trend in the number of patent applications over the last three years. These inhibitors exploit different approaches for target inhibition. Allosteric modulation of FXIa and biosynthetic inhibition of FXI are mechanistically unique. Despite initial results in patients undergoing knee anthroplasty as with antisense oligonucleotides, major advances should be realized, particularly with respect to pharmacokinetics, for FXI/FXIa inhibitors to enter the clinic.

    Research areas

  • FXI/FXIa, active site inhibitors, allosteric inhibitors, antisense oligonucleotides, drug discovery, enzyme inhibition, monoclonal antibodies, polypeptides, safe anticoagulant, thrombosis

Citation formats

APA

Al-Horani, R. A., & Desai, U. R. (2016). Factor XIa inhibitors: A review of the patent literature. Expert Opinion on Therapeutic Patents, 26(3), 323-345. https://doi.org/10.1517/13543776.2016.1154045

Harvard

Al-Horani, RA & Desai, UR 2016, 'Factor XIa inhibitors: A review of the patent literature', Expert Opinion on Therapeutic Patents, vol. 26, no. 3, pp. 323-345. https://doi.org/10.1517/13543776.2016.1154045