Posted by Adam Awdish on
Innovative Grade US Origin Monkey Cynomolgus Plasma and Innovative Grade US Origin Monkey Rhesus Plasma from Innovative Research was used in the following study:
Zhu Chen, Kenneth Ellsworth, James Milligan, Elizabeth Oldham, Dietmar Seiffert, Vaishnavi Ganti, Mohammad Tabrizifard, Bianka Prinz
US Patent Pending
August 13, 2020
Thromboembolic disorders are one of the leading causes of death in the Western world despite the availability of numerous types of anticoagulants, like vitamin K antagonists (VKAs), heparins, and direct thrombin inhibitors. Though these drugs are effective in reducing thrombosis, they also come with some serious side effects. VKAs, for example, come with significant bleeding risk, have a slow onset and offset of action, and multiple dietary and drug interactions. Alternatively, non-vitamin K antagonist oral anticoagulants (NOACs) have demonstrated comparable efficacy to VKAs with less food and drug interactions and no need for monitoring, however, they still increase the risk of bleeding. This is largely because NOACs target proteins (coagulation Factor Xa (FXa) and thrombin) that are essential for normal coagulation (hemostasis).
In the classic waterfall model of the blood clotting cascade, coagulation is triggered by either the extrinsic (tissue factor (TF)-activated) pathway or the intrinsic (contact-activated) pathway, which both help in thrombin generation and fibrin formation. Thrombin further contributes to FXIa generation by direct activation of FXI in a feedback mechanism.
The antibodies described in this patent are capable of selectively binding to coagulation Factor XI (anti-FXI antibodies) and inhibiting blood coagulation and associated thrombosis without compromising hemostasis. Compositions include anti-coagulation Factor XI antibodies capable of binding to an epitope of the apple 3 (A3) domain of coagulation Factor XI. These antibodies exhibit neutralizing activity by inhibiting the conversion of the zymogen form FXI to its activated form (FXIa) under the action of FXIIa and inhibiting FXIa-mediated activation of FIX. The antibodies are useful for FXI inhibition, which may result in a clinically relevant anti-thrombotic effect with a reduced risk of bleeding complications, and thus an expanded therapeutic index compared to inhibition of more downstream clotting factors. The present invention provides an antibody or antigen binding fragment comprising at least the six complimentary determining regions (CDRs) of an anti-FXI antibody. In further embodiments, the antibody or antigen binding fragment binds the A3 domain of coagulation FXI and inhibits activation of FXI and/or Factor XIa-mediated activation of Factor IX.
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