Abstract: The present invention is directed to the use of cangrelor for the treatment and/or prevention of shunt thrombosis in patients suffering congenital heart diseases undergoing shunt surgery. The invention is also directed to the use of cangrelor for the treatment and/or prevention of stent thrombosis in pediatric patients undergoing stent implantation.

Abstract: A locally-activatable bivalent thrombin binding agent is provided having two thrombin binding moieties for non-overlapping sites on a surface of thrombin linked together by a linker. The linker is a polypeptide having 5 to 30 amino acid residues existing in a folded state under an environmental condition where the binding agent is inactive. The linker changes conformation from the folded state to an unfolded state in response to a change in bulk temperature and/or to the presence of hyper-mobile water thereby activating the binding agent. Such locally-activatable thrombin binding agents can be administered systemically while only targeting specific sites of coagulation or inflammation since the thrombin binding agent will only activate at the site where the existence of atherosclerotic plaques has changed the local bulk temperature and/or created hyper-mobile water sufficiently to unfold the linker and activate the binding agent.

Abstract: A method for reducing or maintaining platelet inhibition in a patient by administering cangrelor prior to an invasive procedure is described. The method of this invention can be used for patients in need of antiplatelet therapy or at risk of thrombosis. The method can further be used in patients who were previously treated with long-acting platelet inhibitors without increasing the risk of excessive bleeding.

Abstract: The present invention is directed to the following: methods of treating or preventing stent thrombosis using pharmaceutical compositions comprising cangrelor and optionally bivalirudin; methods of reducing mortality in a subject undergoing stent implantation using pharmaceutical compositions comprising cangrelor and optionally bivalirudin; medicaments comprising cangrelor and optionally bivalirudin useful for treating or preventing stent thrombosis, or useful for reducing mortality in a subject undergoing stent implantation; pharmaceutical compositions comprising cangrelor and bivalirudin; and methods of preparing a medicament comprising cangrelor and optionally bivalirudin useful for treating or preventing stent thrombosis, or useful for reducing mortality in a subject undergoing stent implantation.

Abstract: Methods of treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing percutaneous coronary intervention (PCI), comprising administering to the patient a pharmaceutical composition comprising cangrelor. The method may further comprise administering an additional therapeutic agent to the patient, the additional therapeutic agent comprising a P2Y12 inhibitor. Pharmaceutical compositions useful for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI. The pharmaceutical compositions comprise cangrelor. Methods of preparing a pharmaceutical composition for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI, comprising admixing cangrelor with one or more pharmaceutically acceptable excipients. An ischemic event may include stent thrombosis, myocardial infarction, ischemia-driven revascularization, and mortality.

Abstract: A medicament for therapeutic treatment and/or improvement of sepsis in a patient with severe sepsis accompanied with one or more organ dysfunctions, wherein a value of International Normalized Ratio (INR) of a plasma specimen obtained from said patient is more than 1.4, which comprises thrombomodulin as an active ingredient.

Abstract: The present invention relates a method for the treatment of intracranial bleeding comprising administration of a therapeutically effective amount of tPa and a therapeutically effective amount of carbamylated erythropoietin.

Abstract: Described herein is the discovery that cell and tissue survival can be dramatically increased following radiation exposure through inhibition of the interaction between TSP-1 and CD47. This effect is shown using antisense molecules, peptides, and antibodies, which can now be used as radioprotectant agents. These agents find application in minimizing, reducing and/or preventing tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage and by increasing tumor ablation following radiation treatment.

Abstract: A pharmaceutical composition comprising an effective amount of a mutant thrombomodulin is disclosed. The mutant thrombomodulin comprises an ammo acid sequence that is at least 80% identical to SEQ ID NO: 2 and has residues corresponding to Ala364 and Ala391 of SEQ ID NO: 2. The mutant thrombomodulin has little or no protein C activation activity, and is effective in promoting wound healing and accelerating closure of an open wound in a diabetic.

Abstract: The present invention relates to a chromogenic method for simultaneously determining the activity of multiple coagulation proteases or for simultaneously determining the inhibition of multiple coagulation proteases in a single test reaction. For this purpose, use is made of two chromogenic substrates which have different absorption maxima and whose color signals can be separated spectrally.

Abstract: The present invention relates to inhibitors of antithrombin III and the medical use thereof in treating or preventing bleeding. The inhibitors are preferably used in subjects suffering from an acquired or genetic bleeding disorder, such as haemophilia, or in a subjects having a clinical condition characterised by excessive bleeding, such as surgery, trauma and internal bleeding. The inhibitor of antithrombin III can e.g. a peptide, an aptamer or an antibody or antibody fragment that specifically binds to and inhibits antithrombin III.

Abstract: A medicament for therapeutic treatment and/or improvement of sepsis in a patient with severe sepsis accompanied with one or more organ dysfunctions, wherein a value of International Normalized Ratio (INR) of a plasma specimen obtained from said patient is more than 1.4, which comprises thrombomodulin as an active ingredient.

Abstract: This document relates to compositions containing cardiogenic factors, to methods to obtain cells by culturing initial cells in the presence of such factors; and methods of administering the obtained cells to heart tissue.

Abstract: The present invention relates to the use of thrombomodulin analogues for the manufacture of a medicament for the treatment of coagulopathy with hyperfibrinolysis, such as haemophilia disorders. These thrombomodulin analogs exhibit at therapeutically effective dosages an antifibrinolytic effect. Novel protein modifications together with methods for their identification are disclosed.

Abstract: The present invention relates to the use of a composition including of at least a mutated antithrombin having an anticoagulant activity substantially reduced with respect to the anticoagulant activity of the non mutated antithrombin, or having no anticoagulant activity, for the preparation of a drug intended for the prevention or the treatment of pathologies associated with cellular injury, such as infection, inflammation or hypoxic injury.

Abstract: The present invention relates to antibody molecules against anticoagulants, in particular dabigatran, and their use as antidotes of such anticoagulants.

Abstract: In one aspect, the disclosure provides formulations that stabilize proteins, wherein the formulations comprise a buffer. In some embodiments, the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate. In some embodiments, the protein is a therapeutic protein. In some embodiments, the therapeutic protein is antithrombin.

Abstract: In one aspect, the disclosure provides methods for the treatment of pre-eclampsia and severe pre-eclampsia comprising administering antithrombin. In some embodiments, the antithrombin used in the methods disclosed herein is ATryn®.

Abstract: The present invention provides a method for manufacturing a virus-free protein drug, comprising (a) a filtration step of filtering a virus-containing protein solution through a small-pore size virus removal membrane to obtain a virus-free protein solution, the filtration step (a) comprising (q) a low-pressure filtration step of filtering the solution through the small-pore size virus removal membrane at a filtration pressure of 0.30 kgf/cm2 or lower to obtain the virus-free protein solution, wherein the solution prior to filtration in the low-pressure filtration step (q) has a pH (X) and a salt ionic strength (Y (mM)) that satisfy the following equations 1 and 5: 0?Y?150X?590 (Equation 1) and 3.5?X?8.0 (Equation 5) or the following equations 4 and 5: Y=0 (Equation 4) and 3.5?X?8.0 (Equation 5).

Abstract: In one aspect, the disclosure provides methods of suppressing blood clotting and/or preventing hemorrhage in a subject having extracorporeal membrane oxygenation comprising administering antithrombin. In some embodiments, the antithrombin used in the methods disclosed herein is ATryn®.

Abstract: A medicament for therapeutic treatment and/or improvement of sepsis in a patient with severe sepsis accompanied with one or more organ dysfunctions, wherein a value of International Normalized Ratio (INR) of a plasma specimen obtained from said patient is more than 1.4, which comprises thrombomodulin as an active ingredient.

Abstract: The present invention generally relates to therapeutic compositions for the treatment of mammalian disease and related methods. It more specifically relates to compositions comprising peptides for the treatment of inflammation and methods for delivering the peptides. In one composition aspect, the composition comprises a peptide, and the peptide comprises one or more hexapeptides that are capable of forming fibrils.

Abstract: The present invention relates to antidotes of anticoagulants targeting factor Xa which antidotes are used in combination with blood coagulating agents or other heparin antidotes to prevent or reduce bleeding in a subject. The antidotes described herein have reduced or no intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is or will be undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: A locally-activatable bivalent thrombin binding agent is provided having two thrombin binding moieties for non-overlapping sites on a surface of thrombin linked together by a linker. The linker is a polypeptide having 5 to 30 amino acid residues existing in a folded state under an environmental condition where the binding agent is inactive. The linker changes conformation from the folded state to an unfolded state in response to a change in bulk temperature and/or to the presence of hyper-mobile water thereby activating the binding agent. Such locally-activatable thrombin binding agents can be administered systemically while only targeting specific sites of coagulation or inflammation since the thrombin binding agent will only activate at the site where the existence of atherosclerotic plaques has changed the local bulk temperature and/or created hyper-mobile water sufficiently to unfold the linker and activate the binding agent.

Abstract: Methods of treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing percutaneous coronary intervention (PCI), comprising administering to the patient a pharmaceutical composition comprising cangrelor. The method may further comprise administering an additional therapeutic agent to the patient, the additional therapeutic agent comprising bivalirudin or a P2Y12 inhibitor. Pharmaceutical compositions useful for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI. The pharmaceutical compositions comprise cangrelor, and optionally bivalirudin. Methods of preparing a pharmaceutical composition for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI, comprising admixing cangrelor with one or more pharmaceutically acceptable excipients. An ischemic event may include stent thrombosis, myocardial infarction, ischemia-driven revascularization, and mortality.

Abstract: Methods of treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing percutaneous coronary intervention (PCI), comprising administering to the patient a pharmaceutical composition comprising cangrelor. The method may further comprise administering an additional therapeutic agent to the patient, the additional therapeutic agent comprising a P2Y12 inhibitor. Pharmaceutical compositions useful for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI. The pharmaceutical compositions comprise cangrelor. Methods of preparing a pharmaceutical composition for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI, comprising admixing cangrelor with one or more pharmaceutically acceptable excipients. An ischemic event may include stent thrombosis, myocardial infarction, ischemia-driven revascularization, and mortality.

Abstract: An inhibitor of FXII/FXIIa for the prevention of the formation and/or stabilization of thrombi during and/or after a medical procedure performed on a human or animal subject comprising contacting blood of said human or animal subject with artificial surfaces, wherein said inhibitor of FXII/FXIIa is administered before and/or during and/or after said medical procedure.

Abstract: Method for lyophilization is provided, in particular methods for lyophilization of formulations comprising AT III. Also provided are compositions prepared by therefrom. Also provided are kits comprising the compositions and/or lyophilized products.

Abstract: Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

Abstract: The present invention relates to a chimeric hirudin protein comprising a carrier attached to the N-terminus of hirudin, with an intervening plasmin cleavage site. The chimeric hirudin protein contains a relatively inactive form of hirudin. However, when such chimeric hirudin protein being cleaved by plasmin in the vicinity of a clot and, ultimately causing the release of active hirudin and the reduction of the size of the clot. The chimeric hirudin protein exhibited much slower clearance in mice than unfused wild-type hirudin.

Abstract: Substrates for thrombin and assays for determining the level of bioactive thrombin in a sample are disclosed, wherein the substrate has the general formula: A-X—Z-A? wherein one of either A or A? comprises a luminescent chelate and the other one of A or A? comprises a first partner of a binding pair, X forms a tri- or tetra-peptide, and Z comprises a linker.

Abstract: A medicament for therapeutic treatment and/or improvement of sepsis in a patient with severe sepsis accompanied with one or more organ dysfunctions, wherein a value of International Normalized Ratio (INR) of a plasma specimen obtained from said patient is more than 1.4, which comprises thrombomodulin as an active ingredient.

Abstract: The present invention relates to isolated 18-mer peptides corresponding to amino acid residues 369-386 of human plasminogen activator inhibitor 1 (PAI-1) and fragments thereof, compositions that include such peptides, and uses of such compositions for treating thromboembolic diseases and pathological conditions associated with neurological damage.

Abstract: The invention relates to methods for the preparation of high purity Bivalirudin. The polypeptide is prepared in a high purity of at least 98.5% (by HPLC), wherein the total impurities amount to less than 1.5%, comprising not more than 0.5% [Asp9-Bivalirudin] and each is impurity less than 1.0%, and preferably having a purity of at least about 99.0% by HPLC, wherein the total impurities amount to less than 1.0%, comprising not more than 0.5% [Asp9-Bivalirudin] and each impurity is less than 0.5%.

Abstract: The invention relates to methods for the preparation of high purity Bivalirudin. The polypeptide is prepared in a high purity of at least 98.5% (by HPLC), wherein the total impurities amount to less than 1.5%, comprising not more than 0.5% [Asp9-Bivalirudin] and each is impurity less than 1.0%, and preferably having a purity of at least about 99.0% by HPLC, wherein the total impurities amount to less than 1.0%, comprising not more than 0.5% [Asp9-Bivalirudin] and each impurity is less than 0.5%.

Abstract: The invention relates to methods for the preparation of high purity Bivalirudin. The polypeptide is prepared in a high purity of at least 98.5% (by HPLC), wherein the total impurities amount to less than 1.5%, comprising not more than 0.5% [Asp9-Bivalirudin] and each is impurity less than 1.0%, and preferably having a purity of at least about 99.0% by HPLC, wherein the total impurities amount to less than 1.0%, comprising not more than 0.5% [Asp9-Bivalirudin] and each impurity is less than 0.5%.

Abstract: The invention relates to methods for the preparation of high purity Bivalirudin. The polypeptide is prepared in a high purity of at least 98.5% (by HPLC), wherein the total impurities amount to less than 1.5%, comprising not more than 0.5% [Asp9-Bivalirudin] and each is impurity less than 1.0%, and preferably having a purity of at least about 99.0% by HPLC, wherein the total impurities amount to less than 1.0%, comprising not more than 0.5% [Asp9-Bivalirudin] and each impurity is less than 0.5%.

Abstract: The invention relates to methods for the preparation of high purity Bivalirudin. The polypeptide is prepared in a high purity of at least 98.5% (by HPLC), wherein the total impurities amount to less than 1.5%, comprising not more than 0.5% [Asp9-Bivalirudin] and each is impurity less than 1.0%, and preferably having a purity of at least about 99.0% by HPLC, wherein the total impurities amount to less than 1.0%, comprising not more than 0.5% [Asp9-Bivalirudin] and each impurity is less than 0.5%.

Abstract: The invention relates to methods for the preparation of high purity Bivalirudin. The polypeptide is prepared in a high purity of at least 98.5% (by HPLC), wherein the total impurities amount to less than 1.5%, comprising not more than 0.5% [Asp9-Bivalirudin] and each is impurity less than 1.0%, and preferably having a purity of at least about 99.0% by HPLC, wherein the total impurities amount to less than 1.0%, comprising not more than 0.5% [Asp9-Bivalirudin] and each impurity is less than 0.5%.

Abstract: A method for pharmacological prevention and suppression of aortic aneurysm development is disclosed. The method comprises administering a therapeutically effective amount of recombinant thrombomodulin to a subject in need thereof. The recombinant thrombomodulin prevents formation and/or retards progression of an aortic aneurysm.

Abstract: The invention relates to thrombin inhibitors derived from the salivary glands of haematophagous arthropods and in particular to bivalent and trivalent thrombin inhibitors that act by interacting with thrombin at two or three different sites.

Abstract: The present invention is directed to a reinforced absorbable hemostat comprising at least one hemostatic agent in a single layer of nonwoven synthetic fabric having a mixture of compressed fiber staples of a polyglycolide/polylactide copolymer and a polydioxanone.

Abstract: Method for lyophilization is provided, in particular methods for lyophilization of formulations comprising AT III. Also provided are compositions prepared by therefrom. Also provided are kits comprising the compositions and/or lyophilized products.

Abstract: Disclosed is a composition for treating retinopathy comprising thrombin derived peptide as an effective component.

Abstract: The present invention is directed to a synthetic fabric comprising a multi-layered nonwoven fabric made from staples of a polyglycolide/polylactide copolymer, each layer having a different density. The multi-layer fabric can be used as a reinforced absorbable hemostat medical device.

Abstract: The present invention relates to the use of thrombomodulin analogues for the manufacture of a medicament for the treatment of coagulopathy with hyperfibrinolysis, such as haemophilia disorders. These thrombomodulin analogs exhibit at therapeutically effective dosages an antifibrinolytic effect. Novel protein modifications together with methods for their identification are disclosed.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with venous thrombosis. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: The invention provides methods of making and using compounds of the formula: or a pharmaceutically acceptable salt thereof; wherein n is an integer between 1 and 2 inclusively; m is an integer between 0 and 2 inclusively; X is selected from the group consisting of CH or N; R1 is selected from the group consisting of —CH2NH2, and R2 is selected from the group consisting of —H, —OH, —NH2 and acetyl; R3 is selected from the group consisting of —H, benzyloxycarbonyl and benzylsulfonyl; and R4 is selected from the group consisting of —OH, wherein p is an integer between 0 and 2 inclusively, Y is selected from the group consisting of —O—, —S—, —S(?O)—, —SO2—, methylene, —CH(OH)—, —CH(NH2)—, —CH(CH2—OH)—, —CH(CH2—NH2)— or —N(R6)—, R5 is selected from the group consisting of —H or a simple (C1-C3) alkyl and R6 is selected from the group consisting of —H, a simple (C1-C3) alkyl or a simple (C1-C3) acyl.

Abstract: The present invention is directed to a reinforced absorbable hemostat comprising at least one hemostatic agent in a single layer of nonwoven synthetic fabric having a mixture of compressed fiber staples of a polyglycolide/polylactide copolymer and a polydioxanone.

Abstract: The invention relates to fusion proteins that bind the enzyme thrombin and enhance the activation of the substrate Factor VII to the product Factor VIIa. The invention is also directed to polynucleotides, vectors, host cells, pharmaceutical compositions, and methods of treatment.