The present disclosure provides unit dose formulations and methods to reduce, stop or prevent bleeding in a patient undergoing anticoagulant therapy with a factor Xa inhibitor. The methods entail at least partial neutralization of the factor Xa inhibitors. The unit dose formulations and methods of the present disclosure can be effective even after actual bleeding has initiated.

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, -endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

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 subject matter is directed to a method of manufacturing and purifying an intraveneous injection of prothrombin complex concentration (PCC) from plasma Fraction III, comprising reconstituting a Fraction III paste in a buffer to create a Fraction III suspension; adjusting pH and temperature of the Fraction III suspension; performing PEG precipitation; centrifuging the Fraction III suspension and collecting a supernatant; filtering the supernatant; performing solvent detergent virus inactivation of the supernatant; undergoing weak anion exchange chromatography of the supernatant; twice washing and eluting two to three times; ultra-filtering the supernatant; adjusting pH of the supernatant; adjusting activity of a human factor IX of the supernatant; performing aseptic filtration and nano filtration for virus removal; and filling and lyophilizing to obtain the intraveneous injection of PCC.

Provided herein is a single component sealant formulation (e.g. in a liquid form), methods for its preparation, and use. The formulation includes fibrinogen; vitamin K-dependent clotting zymogens comprising at least Factor II (FII) and Factor X (FX).

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

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

The present invention relates antidotes to anticoagulants targeting factor Xa. The antidoes are 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 stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

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.