Disclosed are methods and isolated cells useful for the improved production of function fXa derivative protein that acts as a fXa inhibitor antidote. One aspect relates to an isolated cell comprising the r-Antidote polynucleotide and Furin polynucleotide. Another aspect relates to a method for preparing the cleaved two-chain r-Antidote by expressing, in a cell, the pre-processed r-Antidote polypeptide and a Furin polypeptide.

The present disclosure relates to solutions and methods of preparing lyophilized formulations of factor Xa (fXa) antidotes. A suitable aqueous formulation suitable for lyophilization can include a fXa antidote, a solubilizing agent, and a stabilizer, wherein the formulation does not collapse during lyophilization.

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.

The disclosure provides compositions and methods for counteracting the effects of direct activated Factor X (FXa) inhibitors in a subject by administering a variant of FXa.

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 present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 401 or 408 is mutated.

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 solutions and methods of preparing lyophilized formulations of factor Xa (fXa) antidotes. A suitable aqueous formulation suitable for lyophilization can include a fXa antidote, a solubilizing agent, a stabilizer, and a crystalline component, wherein the formulation does not collapse during lyophilization.

Factor X/Xa variants and methods of use thereof are disclosed.

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