The emergence of factor Xa inhibitors for the treatment of cardiovascular diseases: a patent review.
BACKGROUND
Factor Xa (FXa) is a critical enzyme in the coagulation cascade responsible for thrombin generation, the final enzyme that leads to fibrin clot formation. Significant success has recently been reported with compounds such as rivaroxaban, apixaban and edoxaban in the treatment and prevention of venous thromboembolism (VTE) and more recently in the prevention of stroke in atrial fibrillation (AF). The success these agents have demonstrated is now being reflected by a narrowing of new FXa patents over the past few years. The new patents appear to be structural modifications of previously published, small molecule inhibitors and bind in a similar manner to the FXa enzyme.


METHODS
SciFinder®, PubMed and Google websites were used as the main source of literature retrieval. Patent searches were conducted in the patent databases: HCAPlus, WPIX and the full text databases (USPAT2, USPATFULL, EPFULL, PCTFULL) using the following keywords: ((FXa) OR (F OR factor) (W) (Xa)) (S) (inhibit? or block? or modulat? or antagonist? or regulat?). The search was restricted to patent documents with the entry date on or after 1 January 2009. Literature and information related to clinical development was retrieved from Thomson Reuter's Pharma.


CONCLUSIONS
A large body of Phase II and Phase III data is now available for FXa inhibitors such as rivaroxaban, apixaban, edoxaban and betrixaban. The clinical data demonstrate favorable benefit-risk profiles compared with the standards of care for short- and long-term anticoagulation (i.e., low molecular weight heparins (LMWHs) and wafarin). The potential exists that these agents will eventually be the agents of choice for the treatment of a host of cardiovascular disease states, offering improved efficacy, safety, and ease of use compared with existing anticoagulants.
Bristol-Myers Squibb Co., Research and Development, 311 Pennington-Rocky Hill Road, Pennington, NJ 08534 , USA. donald.pinto@bms.com
Donald J P
DJ
Pinto
Jennifer X
JX
Qiao
Robert M
RM
Knabb
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001665:Binding Sites; D001777:Blood Coagulation / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006801:Humans; D015394:Molecular Structure; D010330:Patents as Topic; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D015951:Factor Xa