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 relates to antibody molecules against anticoagulants, in particular dabigatran, and their use as antidotes of such anticoagulants.

Abstract: Isolated monoclonal antibodies that bind human tissue factor pathway inhibitor (TFPI) are provided. Isolated nucleic acid molecules encoding monoclonal antibodies that bind TFPI are also contemplated. Pharmaceutical compositions comprising the anti-TFPI monoclonal antibodies and methods of treating deficiencies or defects in coagulation by administration of the antibodies are also provided. Methods of producing the antibodies are also provided.

Abstract: A nanoparticle, a chemical structure, and a treatment method for treating a patient having a disorder. The nanoparticle includes a poly L-arginine polymer and a Factor VIIa inhibitor conjugated to or encapsulated in the poly L-arginine polymer. The chemical structure includes a Factor VIIa inhibitor that includes at least one nitric oxide (NO) donor. The treatment method administers a therapeutic effective amount of the nanoparticle or chemical structure to the patient to treat the disorder. The disorder may be a vascular disorder, pulmonary hypertension, cardiac insufficiency, a neurological disorder, and combinations thereof.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: Polypeptides and polynucleotides encoding same comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a coagulation factor and not to an amino terminus are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using same are also disclosed.

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: This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH; SEQ ID NOS: 1 and 15) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia/reperfusion (I/R) injury and other disorders.

Abstract: The present invention relates to immobilized biologically active entities having heparin cofactor II binding activity.

Abstract: A liquid aqueous composition comprising (i) a factor VII polypeptide; (ii) an agent suitable for keeping pH in the range of from about 4.0 to about 8.0; (iii) an agent selected from the list of: a calcium salt, a magnesium salt, or a mixture thereof; wherein the concentration of (iii) is at least 15 mM is described.

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: 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.

Abstract: The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs.

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: The invention discloses a hemostatic composition comprising crosslinked gelatin in particulate form suitable for use in hemostasis, wherein the composition is present in paste form containing 15.0 to 19.5% (w/w), preferably 16.0 to 19.5% (w/w), 16.5 to 19.5% (w/w), 17.0 to 18.5% (w/w) or 17.5 to 18.5% (w/w), more preferred 16.5 to 19.0% (w/w) or 16.8 to 17.8% (w/w), especially preferred 16.5 to 17.5% (w/w), and wherein the composition comprises an extrusion enhancer.

Abstract: An in situ gel-forming composition is disclosed. The in situ gel-forming composition comprises one or more absorbable polymers, solvents such as N-methyl-2-pyrrolidone, polyethylene glycol or DMSO, and optionally one or more bioactive agent. The composition forms a hydrogel or semi-solid mass on contact with an aqueous environment. The method of using in situ gel-forming composition for various applications is also disclosed.

Abstract: The invention discloses a hemostatic composition comprising: a) a biocompatible polymer in particulate form suitable for use in hemostasis, and b) one hydrophilic polymeric component comprising reactive groups.

Abstract: The invention discloses a hemostatic composition comprising: a) a biocompatible polymer in particulate form suitable for use in hemostasis, and b) one hydrophilic polymeric component comprising reactive groups.

Abstract: Described herein are polypeptides that home to developing microvasculature, (also referred to as developing microvessels), such as newly developing microvasculature in mammals, particularly in humans, and to DNA that encodes such polypeptides. These polypeptides are referred to herein as developing microvasculature homing polypeptides. In a specific embodiment, the homing peptides are collateral vessel endothelia (CVE) homing polypeptides, which have been shown to home to collateral vessel endothelia after ischemia.

Abstract: The invention discloses a hemostatic composition comprising: a) a biocompatible polymer in particulate form suitable for use in hemostasis, and b) one hydrophilic polymeric component comprising reactive groups.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: It is an object of the present invention to provide a cosmetic or external skin preparation that has an improved feel in use, e.g., excellent stretching on the skin surface, excellent permeation into the skin, and no stickiness, or crinkles. A cosmetic or an external skin preparation, and a medical instrument, comprising at least one lipid peptide-based gelator that contains a low-molecular lipid peptide of Formula (1): (where R1 to R3 are independently an organic group) or a pharmaceutically usable salt thereof.

Abstract: A hemostat comprises a non-porous patch made of a bio-resorbable tissue compatible material, said patch having a tissue-facing surface and a top surface; an optional hemostatic agent that is disposed on said tissue-facing surface or optionally dispersed throughout said patch or optionally as a separate carrier layer, and at least one aperture or slit that penetrates said patch at least partially from said tissue-facing surface to said top surface.

Abstract: The invention features a powdered composition including a pharmaceutically active compound and a protein or a hydrolyzed protein. In particular, the powdered composition forms a stable solution or dispersion suitable for oral administration in which the protein or the hydrolyzed protein is bound to the pharmaceutically active compound. The invention also provides a method of administering the composition, such as to a patient with dysphasia; liquid or semi-solid formulations of the composition; methods for preparing the composition; and kits including the composition.

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: 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: A method of treating a patient who has extravasation of blood from an intravascular compartment to an extravascular compartment. An agent is administered to the patient which mitigates a harmful effect of break-down products of blood at an extravascular site, resulting in the patient having reduced morbidity and mortality. The morbidity and mortality of the patient is further reduced by concomitant administration of a suspension of submicron protein spheres having a molecular weight of ranging from 780 billion Daltons to less than 0.8 billion Daltons.

Abstract: The field of the invention is the treatment of acquired bleeding, a clinical condition associated with severe traumatic, peri- or post-operative bleeding. A novel treatment is proposed in which synergistic procoagulatory properties of Prothrombin Complex Concentrates (PCC) together with medicaments comprising FVIII and/or vWF are exploited.

Abstract: The invention relates to a method for improving the procoagulant properties of TF expressed in eukaryotic cells by contacting microvesicles derived from said eukaryotic cells with a negatively-charged phospholipid such as phosphatidylserine. The invention also relates to microvesicles obtained using said method as well as to the uses thereof as procoagulant agents, for wound healing and for promoting angiogenesis.

Abstract: Disclosed are compositions and methods useful for treating wounded, injured, and inflamed tissue. The compositions and methods are based on peptide sequences, such as CAR peptides and truncated CAR peptides, that are selectively targeted to wounded tissue and are internalized by a cell, penetrate tissue, or both. The disclosed peptides promote and enhance wound healing.

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 the discovery of the Aegyptin gene and Aegyptin protein, a molecule that interacts with collagen and inhibits platelet adhesion, activation and aggregation. Novel biological tools, prophylactics, therapeutics, diagnostics, and methods of use of the foregoing are also disclosed.

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: Disclosed is a biocompatible device surface-coated on the base material thereof with a biocompatible polymer layer having antithrombogenicity and endothelialization activity, and embedded in or attached to a living body for use. The polymer layer comprises a polymer matrix formed by the crosslinking of a cell-adhesive peptide-containing polymer.

Abstract: The present invention is directed to a hemostatic textile, comprising: a material comprising a combination of glass fibers and one or more secondary fibers selected from the group consisting of silk fibers; ceramic fibers; raw or regenerated bamboo fibers; cotton fibers; rayon fibers; linen fibers; ramie fibers; jute fibers; sisal fibers; flax fibers; soybean fibers; corn fibers; hemp fibers; lyocel fibers; wool; lactide and/or glycolide polymers; lactide/glycolide copolymers; silicate fibers; polyamide fibers; feldspar fibers; zeolite fibers, zeolite-containing fibers, acetate fibers; and combinations thereof; the hemostatic textile capable of activating hemostatic systems in the body when applied to a wound. Additional cofactors such as thrombin and hemostatic agents such as RL platelets, RL blood cells; fibrin, fibrinogen, and combinations thereof may also be incorporated into the textile. The invention is also directed to methods of producing the textile, and methods of using the textile to stop bleeding.

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: Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) in combination with a gastrointestinal epithelial barrier permeation enhancer is orally administered to a subject in a manner sufficient to enhance blood coagulation in the subject. Compositions and kits for practicing methods of the invention are also described.

Abstract: The present invention provides a pharmaceutical preparation in powder-like form, comprising a therapeutically effective amount of a human Factor IX (hFIX) encapsulated by a lipophilic biodegradable polymer or copolymer to form a microsphere, whereby the pharmaceutical preparation provides a sustained release of hFIX and a prolonged biological activity.

Abstract: A peptide having the following amino acid sequence: Z1-LVRYTKKVPQVSTPTL-Z2(ALB-408) and its biologically active fragments and/or variants and/or derivatives, especially amidated, acetylated, sulfated, phosphorylated and/or glycosylated derivatives, and peptides obtainable by multiple synthesis which have the biological activity of ALB408-423; wherein Z represents number of from 0 to 10 amino acid residues.

Abstract: Provided are prophylactic and therapeutic methods of treatment of subjects for the purpose of inhibiting vaso-occlusive events, including embolism, by administering agents, including anagrelide and anagrelide derivatives, which reduce the number of circulating platelets to low normal or to below normal levels. Methods and pharmaceutical preparations comprising such agents are provided.

Abstract: The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.

Abstract: The present invention provides von Willebrand Factor-polymer conjugates and Factor VIII-polymer conjugates, each having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.

Abstract: The present invention relates to modified therapeutic proteins, such as e.g. coagula-tion factors. In particular, the present invention relates to conjugated Factor VIII molecules such as e.g. FVII, FVIII, or FIX comprising a hydrophobic side group.

Abstract: The field of the invention is the treatment of acquired bleeding, a clinical condition associated with severe traumatic, peri- or post-operative bleeding. A novel treatment is proposed in which synergistic pro-coagulatory properties of Prothrombin Complex Concentrates (PCC) together with medicaments comprising FVIII and/or vWF are exploited.

Abstract: The present invention is directed to a hemostatic or tissue sealing material having (a) a peptide having a sequence SEQ ID NO: 1 or an amino acid analog sequence thereof, and (b) a scaffold for said peptide or amino acid analogue sequence. The scaffold is preferably hemostatic, such as a natural or genetically engineered absorbable polymer, a synthetic absorbable polymer, or combinations thereof. The natural or genetically engineered absorbable polymers can be selected from the group consisting of a protein, a polysaccharide, or combinations thereof.

Abstract: Protein replacement therapy for patients with hemophilia or other inherited protein deficiencies is often complicated by pathogenic antibody responses, including antibodies that neutralize the therapeutic protein or that predispose to potentially life-threatening anaphylactic reactions by formation of IgE. Using murine hemophilia B as a model, we have developed a prophylactic protocol against such responses that is non-invasive and does not include immune suppression or genetic manipulation of the patient's cells. Oral delivery of coagulation factor IX (F. IX) expressed in chloroplasts, bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies in protein replacement therapy. Inhibitor titers were mostly undetectable and up to 100-fold lower in treated mice when compared to controls. Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after 4 to 6 exposures to intravenous F. IX protein. While only 20-25% of control animals survived after 6-8 F.

Abstract: This invention relates to methods of inhibiting binding between a cell expressing integrin receptors specific for one or more integrins selected from the group consisting of ?IIb?3, ?v?3, ?v?5, or ?5?1, said method comprising contacting the cell with a monomeric disintegrin or monomeric disintegrin domain which comprises a C-terminal sequence non-native to the disintegrin or disintegrin domain, said C-terminal sequence encoding a functional integrin-binding loop.

Abstract: The present invention provides novel methods of increasing the survival of a coagulation protein by inhibiting the interaction with a clearance receptor. The invention also provides methods of preparing compositions that inhibit coagulation protein clearance receptors. Conjugated coagulation proteins, including compositions and formulations thereof, are also provided by the present invention.

Abstract: The present invention provides methods of treating coagulation disease, including hemophilia and von Willebrand disease by administering recombinant von Willebrand Factor alone or in combination with Factor VIII.