The invention relates to 55 newly discovered proteins, which are present in isolated purified protein complexes, derived medicinal products, recombinant DNA, engineered DNA, cDNA, monoclonal and natural products or synthesized products as part of nutrition, food, and/or supplemental products and their applications.

The present invention relates to methods and compositions for improving the productivity of recombinant vitamin K dependent protein expression in host cells.

The present disclosure relates to compositions and methods for the treatment of bleeding disorders, such as hemophilia A, hemophilia B, von Willebrand (vWF) disease, and factor XII deficiency, by reducing the circulating concentration of tissue factor pathway inhibitor (TFPI), with a factor Xa derivative.

The present disclosure relates to antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. In one embodiment, the derivatives described herein lack or have reduced intrinsic coagulant activity.

The present invention provides a stable cell line overexpressing a recombinant vitamin K-dependent (VKD) protein and both a recombinant vitamin K epoxide reductase (VKOR) and a recombinant vitamin K dependent gamma carboxylase (VKGC), wherein the amount of fully carboxylated VKD protein produced in the cell is increased 10% as compared to the amount of fully carboxylated VKD protein produced in the cell in the absence of the recombinant VKOR and the recombinant VKGC.

The invention provides chimeric clotting factors comprising an activatable clotting factor and an enhancer moiety. The activatable clotting factor allows the chimeric clotting factor to be activated at the site of coagulation. The enhancer moiety can additionally improve procoagulation activities of the chimeric clotting factors. The chimeric clotting factors can further be improved by fusion to a half-life extender, which improves a pharmacokinetics property of the chimeric clotting factor. The invention also includes methods of making and methods of using these chimeric clotting factors.

The present disclosure relates to compositions and methods useful for assessing the efficacy in a patient having suffered from intracranial hemorrhage while undergoing an anticoagulation treatment with a factor Xa (fXa) inhibitor. The method can include administering to the patient a fXa derivative that has reduced catalytic activity as compared to the wild-type fXa protein, is capable of binding to the factor Xa inhibitor and cannot assemble into a prothrombinase complex; obtaining a blood sample from the patient following the administration; and measuring an anti-fXa activity in the sample, wherein the anti-fXa activity reflects the hemostatic efficacy in the patient. Once the assessment is made, suitable medical interventions can be implemented.

This disclosure relates to recombinant FXa polypeptides that can be used as antidotes to completely or partially reverse an anti-coagulant effect of a coagulation inhibitor in a subject, preferably a direct factor Xa inhibitor. Disclosed herein are recombinant factor Xa proteins and a method of completely or partially reversing an anti-coagulant effect of a coagulation inhibitor in a subject.

The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor X and factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of reversing anticoagulation, stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Disclosed herein are compositions and methods for improving hemostasis in the treatment of bleeding disorders and reversal of anticoagulant activity. Effective ratios of prothrombin (FII) and activated factor X (FXa) for the treatment of bleeding disorders that are as efficacious as FEIBA®, but require a lower concentration of FII are described herein.