Abstract: A method of treating or preventing a thrombotic disease in a subject in need thereof comprises administering to the subject an effective amount of a pharmaceutical composition comprising an inhibitor of an apoptosis signal regulating kinase 1 (ASK1) protein. A method of identifying an inhibitor of an apoptosis signal regulating kinase 1 (ASK1) protein useful for treating or preventing a thrombotic disease, comprising (a) contacting a candidate agent with a test sample comprising the ASK1 protein, and (b) comparing the ASK1 protein activity in the test sample with the ASK1 protein activity in a control sample that has not been contacted with the candidate agent, whereby a decrease in the ASK1 protein activity in the test sample compared with the control sample indicates that the candidate agent is an ASK1 inhibitor.

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: This invention provides methods of preventing or treating cardiac ischemia-reperfusion injury in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to a subject in need thereof, wherein the peptide is D-Arg-2 6-Dmt-Lys-Phe-NH2 (SS-31).

Abstract: An extract for preventing or treating thrombotic diseases, particularly, an extract of at least one of leeches and earthworms having a molecular weight of no more than 5,800 daltons is provided, wherein the extract includes 15% to 38% amino acid, 40% to 60% saccharide and 0.3% to 1% hypoxanthine. Processes for preparation, pharmaceutical compositions and uses thereof are also provided. Compared to conventional arts, the extract has safety greatly improved and drug actions maintained and even improved.

Abstract: Invented is a method of treating thrombocytopenia in a human, in need thereof which comprises the in vivo administration of a therapeutically effective amount of a peptide or a non-peptide TPO receptor agonist and an anti-clotting agent or agents, and optional further active ingredients, to such human.

Abstract: The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.

Abstract: The present invention relates 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. 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.

Abstract: The present invention is directed to methods of using combination therapies containing [2-({4-[(dimethylamino)iminomethyl]phenyl}carbonylamino)-5-methoxyphenyl]-N-(5-chloro(2-pyridyl))carboxamide for the treatment of thrombotic disease(s) and pharmaceutical compositions thereof.

Abstract: Recombinant proteins comprised of multiple selectin binding domains derived from the glycopeptide PSGL-1, in a novel tandem configuration, are disclosed, including their fusions with immunoglobulins and/or other polypeptides. Polynucleotides encoding such proteins, compositions and kits containing such proteins, and methods of using such proteins are also disclosed.

Abstract: Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH2—SO3H)COOH or Arg-Gly-NH—CH(CH2—SO3H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting integrins including but not necessarily limited to ?5?1-Integrin, ?v?3-Integrin and ?v?5-Integrin, inhibiting cellular adhesion to RGD binding sites, preventing or treating viral or other microbial infections, inhibiting angiogenesis in tumors, retinal tissue or other tissues or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.

Abstract: The invention relates to a new polynucleotide which encodes a polypeptide expressed in the salivary glands of ticks, more particularly the Ixodes ricinus arthropod tick, during the slow-feeding phase of the blood meal have, said polynucleotide and related polypeptide may be used in different constructions and for different applications which are also included in the present invention.

Abstract: Enclosed is an antagonist, which includes a peptide chain represented by an amino acid sequence. The amino acid sequence has a short sequence, C-X1X2X3X4X5-N, which is situated before and neighbored to the third cysteine (Cys, C) of the N-terminus, wherein X1 is an amino acid with aromatic ring, hydrophobic property or long chain, and X2, X3, X4 and X5 are glutamine (G), serine (S), alanine (A) and proline (P) respectively. In one embodiment, X1 is phenylalanine (F). The present antagonists can be used to inhibit or treat with the diseases caused by the activated cells expressing CXCR1 and/or CXCR2 receptor, for example, the acute or chronic inflammatory reaction induced with polymorphonuclear neutrophils (PMNs) expressing CXCR1 and/or CXCR2 receptor, and angiogenesis accompanied by tumor growth inhibition.

Abstract: The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier.

Abstract: The present invention relates to a composition for treating diseases associated with autoantibodies specific for platelet proteins, in particular autoimmune thrombocytopenic purpura. The composition, comprising an epitope of a platelet protein, treats diseases by tolerization.

Abstract: Disclosed herein are monoclonal antibodies specific for factor XI (fXI) that prevent activation of fXI by factor XIIa (fXIIa). The monoclonal antibodies are universal fXI antibodies, capable of binding all mammalian species tested. The anti-fXI monoclonal antibodies prolong clotting time in mammalian plasmas. Moreover, administration of the fXI monoclonal antibodies disclosed herein results in inhibition of thrombosis without altering hemostasis in animal models of thrombosis. Thus, provided herein are monoclonal antibodies specific for fXI that block activation of fXI by fXIIa, compositions and immunoconjugates comprising such antibodies and their methods of use.

Abstract: The present invention relates to improved Nanobodies™ against von Willebrand Factor (vWF), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

Abstract: The present disclosure relates to a pharmaceutical composition for use in the preventive and/or therapeutic treatment of thrombosis-related diseases or conditions relating to high level of plasminogen activator inhibitor 1 (PAI-1) expression, which composition comprises: A) a fragment of a polypeptide or protein of prolactin (PRL)-growth hormone (GH)-placental lactogen (PL)-family and homologous derivatives thereof, which fragment comprises from 6 to 14 consecutive amino acid residues of the amino acid sequence having general formula (I); or B) a peptide or a recombinant protein comprising said peptide, wherein the peptide is from 6 to 50 amino acids in length and has the activity to inhibit PAI-1, said peptide comprising from 6 to 14 consecutive amino acid residues of the amino acid sequence of general formula (I); or C) a polynucleotide encoding said fragment of a polypeptide or protein of A) or said peptide or recombinant protein of B).

Abstract: The invention relates to antibodies that specifically bind to tissue factor pathway inhibitor (TFPI) and that reduce the clotting time of blood. Such antibodies have utility in the treatment of subjects with a coagulopathy.

Abstract: Fusion proteins comprising a single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.

Abstract: A method of modulating growth factor responses of cells expressing C3a receptor (C3aR) and C5a receptor (C5aR) and at least one growth factor receptor includes administering to the cells at least one agent that modulates C3aR and/or C5aR signaling of the cells.

Abstract: This application relates to agents capable of specifically recognizing GPIb?, a key receptor required for platelet adhesion and aggregation. More specifically, this application relates to monoclonal antibodies and derivatives thereof capable of specifically recognizing both the murine and the human GPIb?. These monoclonal antibodies and derivatives are particularly useful in the treatment or prevention of thrombosis as well as research tools.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat thrombosis or hypercoagulation in patients having, or at risk of developing, diseases associated with abnormal blood coagulation or fibrinolysis and/or patients which are at increased risk or are being treated by a regimen that renders the patient at increased susceptibility to hypercoagulation or thrombosis such as patients who have previously had a stroke or heart attack or persons on a treatment regimen with a drug or chemotherapy and/or radiation that is associated with increased risk of thrombosis or hypercoagulation. In preferred embodiments these patients will comprise those exhibiting elevated D-dimer or other coagulation cascade related proteins and optionally will further exhibit elevated C reactive protein prior to treatment.

Abstract: The present invention discloses inhibitory antibodies against Factor VIII with modified glycosylation, either by enzymatic deglycosylation or by site directed mutagenesis. Said antibodies with modified glycosylation have equal affinity for FVIII but show different inhibiting properties. The use of one or a mixture of said antibodies allow modulation of the inhibition of factor VIII to levels between 40 and 95%. The present invention further discloses pharmaceutical compositions comprising inhibitory antibodies against Factor VIII with modified glycosylation, combinations of these antibodies and methods for treating haemostasis disorders using said antibodies and antibody mixtures.

Abstract: The present invention relates to the therapeutic application of the Kazal-type serine protease inhibitor Infestin or domains thereof or modified Kazal-type serine protease inhibitors based on Infestin homologs, which prevent the formation and/or stabilization of three-dimensional arterial or venous thrombi by interfering with proteins involved in activation of the so-called intrinsic coagulation pathway. The present invention also relates to the use of Kazal-type serine protease inhibitors or fragments thereof or modified Kazal-type serine protease inhibitors in the treatment or prophylaxis of a condition or disorder related to arterial thrombus formation, i.e. stroke or myocardial infarction, inflammation, complement activation, fibrinolysis, angiogenesis and/or diseases linked to pathological kinin formation such as hypotonic shock, edema including hereditary angioedema, bacterial infections, arthritis, pancreatitis, or articular gout, Disseminated Intravasal Coagulation (DIC) and sepsis.

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 discloses inhibitory antibodies against Factor VIII with modified glycosylation, either by enzymatic deglycosylation or by site directed mutagenesis. Said antibodies with modified glycosylation have equal affinity for FVIII but show different inhibiting properties. The use of one or a mixture of said antibodies allow modulation of the inhibition of factor VIII to levels between 40 and 95%. The present invention further discloses pharmaceutical compositions comprising inhibitory antibodies against Factor VIII with modified glycosylation, combinations of these antibodies and methods for treating haemostasis disorders using said antibodies and antibody mixtures.

Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: A soluble compound for preventing or reducing blood coagulation comprising an antithrombotic agent and a membrane binding element, wherein the antithrombotic agent has a weight of less than about 5,000 daltons. Also disclosed is a soluble compound for preventing or reducing blood coagulation comprising an anticoagulant joined to a membrane binding element via a joining element, wherein the joining element between the anticoagulant and the membrane binding element is less than about 10,000 daltons in weight. These compounds can be used in therapy and, in particular, in preventing or reducing blood coagulation. As a result, a method of treatment is provided comprising administering an effective amount of the compounds to a subject to prevent or reduce blood coagulation as well as a method of perfusing an organ, tissue or cell comprising contacting the compounds with the organ, tissue or cell to prevent or reduce blood coagulation.

Abstract: The present application describes lactam-containing compounds and derivatives thereof of Formula I: P4—P-M-M4??I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Abstract: The present invention relates to compositions and methods for inhibiting thrombosis without compromising hemostasis. Compositions include anti-factor XI monoclonal antibodies (aXIMabs) capable of binding to an epitope on the heavy chain of human FXI, particularly the A3 domain of the heavy chain of human FXI. Compositions also include epitope-binding fragments, variants, and derivatives of the monoclonal antibodies, cell lines producing these antibody compositions, and isolated nucleic acid molecules encoding the amino acid sequences of the antibodies. The invention further includes pharmaceutical compositions comprising the anti-factor XI monoclonal antibodies of the invention, or epitope-binding fragments, variants, or derivatives thereof, in a pharmaceutically acceptable carrier.

Abstract: The present invention relates to an anticoagulant and a composition for preventing thrombus formation, which contain poly-gamma-glutamic acid (PGA) as an active ingredient. The inventive PGA is a water-soluble, anionic, biodegradable and edible amino acid polymer material, which has an anticoagulant effect of preventing thrombi from being accumulated in blood vessels, shows an excellent sustained-release effect and is harmless to the human body. Thus, it is useful as a high-value-added anticoagulant and a food or beverage composition for preventing thrombus formation.

Abstract: The present invention provides an HDL comprising an agent selected from the group consisting of antiproteases, antixoxidants, antimitotics, anti-apoptotic agents and agents involved in the iron metabolism for use as a medicament.

Abstract: Provided herein are methods and compositions, including pharmaceutical compositions, for treating thrombosis, vascular inflammation, and thrombocytopenia. The methods and compositions of the present invention are also useful for extending the useful storage shelf life of platelets.

Abstract: The present invention relates to the use of a enzyme treated fish protein hydrolyzate (FPH). The FPH material lowers the concentration of cholesterol in plasma, and triglycerides in the liver. FPH also induces a favorable change in the fatty acid pattern, and lowers the concentration of homocysteine in plasma. A preferable embodiment of the invention relates to the use of FPH as an anti-atherogenic and cardio protective agent, either given as a pharmaceutical or as a functional food.

Abstract: Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Abstract: It is intended to provide drugs for treating ischemic diseases which are safe and have little side effects. Namely, drugs having a combination of an antithrombotic agent and a pyrazolone derivative defined in the description or its pharmaceutically acceptable salt.

Abstract: The present invention relates to pharmaceutical formulations of Aviptadil and its derivatives. The stability of the Aviptadil formulation was shown to be improved by a formulation having a defined concentration of Aviptadil prepared in a buffer having a defined pH range.

Abstract: 3-Hydroxy-7-hydroxy steroids and 3-oxo-7-hydroxy steroids, especially the 7?-isomers thereof, and pharmaceutically acceptable esters thereof are useful for protection against ischaemia-induced damage to peripheral organs, such as the heart or kidneys, as well as treatment of spiral cord injury.

Abstract: Various nucleic acid-based matrixes are provided, comprising nucleic acid monomers as building blocks, as well as nucleic acids encoding proteins, so as to produce novel biomaterials. The nucleic acids are used to form dendrimers that are useful as supports, vectors, carriers or delivery vehicles for a variety of compounds in biomedical and biotechnological applications. In particular, the macromolecules may be used for the delivery of drugs, genetic material, imaging components or other functional molecule to which they can be conjugated. An additional feature of the macromolecules is their ability to be targeted for certain organs, tumors, or types of tissues. Methods of utilizing such biomaterials include delivery of functional molecules to cells.

Abstract: The present invention relates to the use of at least one antibody and/or one inhibitor for inhibiting factor XII and preventing the formation and/or the stabilization of three-dimensional thrombi. It also relates to a pharmaceutical formulation and the use of factor XII as an anti-thrombotic target.

Abstract: The invention concerns the use and the production of non-neurotoxic plasminogen activating factors, derived, for example, from the common vampire Desmodus rotundus (DSPA), for therapeutic treatment of stroke in humans. The invention provides a novel therapeutic base for treating stroke in humans.

Abstract: The present invention provides a compound including a peptidomimetic which interacts sterically with the binding site of a F11R molecule, the peptidomimetic including a peptidomimetic having the SEQ ID NO: 4D. The present invention also provides a method for treating a disorder comprising administering peptide 4D to a mammal.

Abstract: Medical devices having a catalyst capable of catalyzing the generation of nitric oxide in vivo and methods of treating a vascular condition using the devices are provided.

Abstract: The present invention relates to new pyrimidinone inhibitors of lipoprotein-associated phospholipase A2 activity, pharmaceutical compositions thereof, and methods of use thereof

Abstract: Chimeric therapeutics are disclosed that include a modified viral core protein and a nucleic acid bound to the modified viral core protein. The nucleic acid may be substantially homologous to a specific gene target. In some embodiments, the nucleic acid bound to the modified viral core protein is substantially non-immunogenic. Also disclosed are particles and compositions that include disclosec chimeric therapeutics.

Abstract: Provided herein is an animal having a persistent hypercoagulable state by implanting a cell, for example a tumor cell, in which the gene of human tissue factor is implanted to an experimental animal such as a mouse and then growing the cell, thereby persistently supplying human tissue factor to the experimental animal. This animal model is useful for research and development of therapeutic agents for diseases having a persistent hypercoagulable state. Also provided are preventive or therapeutic agents for diseases having a persistent hypercoagulable state, a hypercoagulable state resulting from infections, venous thrombosis, arterial thrombosis, and diseases resulting from the hypertrophy of vascular media, the agent comprising an antibody against human tissue factor (human TF) as an active ingredient.

Abstract: The invention relates to substances which inhibit the binding of oxidized proteins to CD36 or inhibit the functions of CD36 that are induced by the interaction of CD36 with oxidized proteins. The invention also relates to the use of these substances as medicaments for humans and animals. In one embodiment, a medicament includes an oxidized protein, an oxidized peptide, or structural analog or mimetic thereof. Methods for prophylaxis or therapy of acute infections, inhibition of angiogenesis, and improvement of hemostasis include administering to an animal or human in need thereof an effective amount of a medicament including an oxidized protein, an oxidized peptide, or structural analog or mimetic thereof. An example of an acute infection is Human Immunodeficiency Virus (HIV).

Abstract: Described herein are peptide derivatives and peptidomimetics as inhibitors for transglutaminases, methods for their preparation, pharmaceutical compositions containing said compounds as well as uses of said transglutaminase inhibitors in particular for the treatment of coeliac disease and transglutaminase dependent diseases.

Abstract: Method are disclosed for local and systemic administration HDL, recombinant HDL or HDLm for the prevention, treatment, or amelioration of a vascular disorder, disease or occlusion such as restenosis or vulnerable plaque.

Abstract: Disclosed herein are recombinant proteins capable of inducing platelet aggregation and uses thereof.