Factor IX(a) inhibitors: an updated patent review (2003-present)

Anticoagulation with no bleeding complications is the current objective of drug discovery programs in the area of treating and/or preventing thromboembolism. Despite the promises of therapeutics targeting factors XI(a) and XII(a), none has been approved thus far. Clinically used thrombin- and/or factor Xa-based anticoagulants continue to be associated with a significant bleeding risk which limits their safe use in a broad range of thrombotic patients. Research findings in animals and humans indicate that it is possible to target factor IX(a) (FIX(a)) to achieve anticoagulation with a limited risk of bleeding.

A review of patents literature has retrieved >35 patents on the development of molecules targeting FIX(a) since 2003. Small molecules, antibodies, and aptamers have been developed to target FIX(a) to potentially promote effective and safer anticoagulation. Most of these agents are in the pre-clinical development phase and few have been tested in clinical trials.

FIX(a) system is being considered to develop new anticoagulants with fewer bleeding complications. Our survey indicates that the number of FIX(a)-targeting agents is mediocre. The agents under development are diverse. Although additional development is essential, moving one or more of these agents to the clinic will facilitate achieving better clinical outcomes.