Abstract: The present invention includes a novel protein, also referred to herein as simukunin, that inhibits the function of several physiologically important enzymes. Simukunin is a potent inhibitor of the blood coagulation cascade, inhibiting Factor Xa and functioning as an efficient anticoagulant. Simukunin also inhibits the serine proteases elastase and cathepsin and demonstrates anti-inflammatory properties. Also included are methods of making and using simukunin.

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: Methods for producing cell lines with high levels of biologically active recombinant vitamin K dependent proteins are described. The transfected cell lines do not include heterologous genes for processing enzymes and are not subject to selection pressure such as methotrexate resistance. Cell lines producing Factor VII/VIIa and Factor IX are described. These cell lines can be used for isolation of Factor VII/VIIa and/or Factor IX for treatment of Hemophilia.

Abstract: Disclosed are compositions and methods related to clot-binding compounds. For example, disclosed are compositions comprising a surface molecule and at least one modified clot-binding compound. The modified clot-binding compound can selectively bind to clotted plasma protein, wherein the composition causes clotting and amplifies the accumulation of the composition in tumors. The modified clot-binding compound can enhance the clotting in tumors compared to its unmodified derivative. The disclosed targeting is useful for treatment of cancer and other diseases and disorders.

Abstract: ClotGel is a single-component hemostatic agent designed for use as an adjunct or primary treatment in moderate intraoperative hemorrhage and in trauma. It can be applied topically to the wound either on the skin in a laparatomy or as non-invasive manner in surgical procedures. Its crosslinking technology generates an adhesive stable fibrin clot using a single component (fibrin II) required for hemostasis. The agent is a mixture of lyophilized polymerized fibrin II and fibrin II monomer which is polymerized and stabilized when in contact with the blood. The attachment properties of the gel, as well as the rapid formation of a fibrin clot, ensures that a strong stable fibrin clot is formed within 1 minute of application.

Abstract: Compositions and methods for generating activated protein C and methods of use thereof are disclosed.

Abstract: The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, Victoza (liraglutide), Tresiba (insulin degludec), Ryzodeg (insulin degludec/insulin aspart), IDegLira (liraglutide and insulin degludec), NovoSeven (recombinant human coagulation factor VIIa), NovoSeven RT (recombinant human coagulation factor VIIa), or Turoctocog alfa (third-generation recombinant coagulation factor VIII).

Abstract: The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, GAMMAGARD LIQUID (an immune globulin infusion (human)); ADVATE (Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method, (rAHF)); BAX 111 (vonicog alfa, or [618-threonine,709-aspartic acid] von Willebrand factor Homo sapiens (1381A>T,1472H>D variant)); or an adeno-associated viral vector containing a liver-specific human factor IX expression cassette, e.g., sscAAV2/8-LP1-hFIXco.

Abstract: A virally safe, thrombin-free factor-XIa concentrate or a coagulation factor concentrate which contains factor XIa as an active pharmaceutical ingredient and which is obtained by fractionation of plasma or serum or by genetic engineering and is suitable for the treatment of coagulation disorders attributable to diminished and/or delayed thrombin formation.

Abstract: Methods for purifying fucoidan in extracts from brown seaweed are disclosed. In particular, methods of purifying fucoidan in the extract to remove heavy metal ions, bacterial and endotoxin contaminants, and other impurities are disclosed. The methods include the use of a chelating agent, selective precipitation, and filtration.

Abstract: Disclosed is an anticoagulant polypeptide and applications thereof. The anticoagulant polypeptide comprises a polypeptide formed by an amino acid sequence as represented in Seq. ID No. 1; or comprises a derived polypeptide that selectively inhibits coagulation factor XIa and is formed by an amino acid sequence, as represented in Seq. ID No. 1, that has undergone one or multiple amino acid residue substitutions, deletions, or insertions. The anticoagulant polypeptide is a selective inhibitor for coagulation factor XIa, has anticoagulant activity and small side-effect, and can be used in preparing medicines for the prevention and treatment of thrombotic diseases.

Abstract: The invention relates to hyperglycosylated human coagulation factor IX polypeptides, to processes for preparing said polypeptides, to pharmaceutical compositions comprising said polypeptides and to the use of the compounds for the treatment of diseases alleviated by human coagulation factor IX, in particular, but not exclusively hemophilia.

Abstract: The invention concerns a pentasaccharide compound of formula (I) and the salts thereof. The invention also concerns a pharmaceutical composition comprising the synthetic pentasaccharide compound of formula (I) and its salts. The invention further concerns these compounds for use as a medicament, and in particular intended to treat blood clotting disorders, to prevent ischaemia reperfusion injury associated with solid organ transplantation, or to reduce the risk of blood clotting in an extracorporeal blood circuit during cardiac surgery, extracorporeal membrane oxygenation, or during circulatory assistance such as artificial heart.

Abstract: The invention relates to a recombinant factor VIII that includes one or more mutations at an interface of A1 and C2 domains of recombinant factor VIII. The one or more mutations include substitution of one or more amino acid residues with either a cysteine or an amino acid residue having a higher hydrophobicity. This results in enhanced stability of factor VIII. Methods for making the recombinant factor VIII, pharmaceutical compositions containing the recombinant factor VIII, and use of the recombinant factor VIII for treating hemophilia A are also disclosed.

Abstract: The invention relates to the use of phosphorylated Acetyl-CoA carboxylase (ACC) in platelets from a subject as a biomarker for blood coagulation, preferably blood coagulation in the subject, preferably encompassing activation of the coagulation cascade as well as platelet activation, preferably thrombin-induced platelet activation. The invention encompasses uses and methods for the diagnosis or the monitoring of blood coagulation in the subject. The invention further relates to uses and methods for screening for anti-coagulants or pro-coagulants.

Abstract: A method of selectively introducing a substituent into a protein proximal to a binding site on the protein for a homing peptide, comprising: (a) contacting the protein with a compound comprising a homing peptide having the ability to bind to the binding site of the protein; and (b) allowing a moiety on the protein proximal to the binding site to react with the compound comprising the homing peptide, thereby to transfer the substituent G onto the protein.

Abstract: Provided are pro-coagulant compounds (e.g., pro-coagulant peptides or peptide derivatives) and methods of using and making those compounds. Further provided are conjugates between a pro-coagulant compound of the present disclosure (e.g., pro-coagulant peptide or peptide derivative) and a polypeptide selected from FIX, FVIIa, FVIII, and platelet targeting moieties (e.g., PDG-13), wherein the compound is linked to the polypeptide optionally via a linker. The compounds and conjugates are useful for the treatment of coagulation disorders, such as hemophilia A and hemophilia B. Further provided are methods of using and making the conjugates.

Abstract: Compositions are disclosed containing a polymeric mixture diluted into an aqueous solution, which can be usefully applied to any surface mat is hydbcphoixc to act, for example, as an aotifoggiag coating with minimal optical distortion and excellent transparency. The compositions can also be used as lubricious agents on medical implants, shunts, and surgical supplies to minimize tissue trauma, to maximize bio-compatibility, and to increase healing by enhancing better irrigation and flow in adjacent tissue.

Abstract: Methods of inhibiting, treating or preventing blood loss in a subject undergoing surgery through the administration of an effective amount of the novel serine protease inhibitor MDCO-2010 or its salts or esters are disclosed.

Abstract: The present invention relates to the field of blood clotting. Specifically, the invention relates to particular inhibitors of artificial activation of the blood clotting process through contact with foreign surfaces.

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: Provide are a peptide gel with practically sufficient mechanical strength and a self-assembling peptide capable of forming the peptide gel. The self-assembling peptide is formed of the following amino acid sequence: a1b1c1b2a2b3 db4a3b5c2b6a4 where: a1 to a4 each represent a basic amino acid residue; b1 to b6 each represent an uncharged polar amino acid residue and/or a hydrophobic amino acid residue, provided that at least five thereof each represent a hydrophobic amino acid residue; c1 and c2 each represent an acidic amino acid residue; and d represents a hydrophobic amino acid residue.

Abstract: The present invention relates to composition(s) comprising collagen, calcium ions and alginate, wherein the composition polymerizes in situ when contacted with blood. The composition may further comprise an erythrocyte aggregation agent and/or a platelet activation agent. The composition may be formulated into two separate formulations. The first formulation comprises collagen in a calcium-containing solution and a second formulation comprises an aqueous alginate solution. The two formulations can be mixed prior to the contact with blood or mixed coincident with the contact with blood.

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 disclosure provides for one or more peptoids, methods of manufacture thereof, and methods of use thereof, including the use of one more peptoids in neutralizing the anticoagulant activity of heparin.

Abstract: The disclosure provides for one or more peptoids, methods of manufacture thereof, and methods of use thereof, including the use of one more peptoids in neutralizing the anticoagulant activity of heparin.

Abstract: The present invention relates to modified cDNA sequences coding for vitamin K-dependent polypeptides, in particular human Factor VII, human Factor VIIa, human Factor IX and human protein C and their derivatives with improved stability and extended plasma half life, recombinant expression vectors containing such cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.

Abstract: An improved method for the detection of parvovirus B19 in a sample is provided, the improvement consisting of detecting a parvovirus B19 non-structural protein in said sample.

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

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: Factor VIII variants and methods of use thereof are disclosed.

Abstract: The invention relates to a chimeric protein comprising at least one clotting factor and at least a portion of an immunoglobulin constant region. The invention relates to a method of treating a hemostatic disorder comprising administering a therapeutically effective amount of a chimeric protein wherein the chimeric protein comprises at least one clotting factor and at least a portion of an immunoglobulin constant region.

Abstract: There is provided in accordance with the practice of this invention a demannosylated Factor VIII, the immunogenicity of which is substantially decreased or abolished in Human. The modified factor VIII is disclosed together with the modified amino acid sequence, changed by at least one substitution. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory anti-FVIII antibodies.

Abstract: The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt thereof. The present invention also provides pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The invention, in general, features a method of treatment and/or prevention of a thrombotic pathological condition, in a mammal, which includes administering to the mammal in need of such treatment a therapeutically effective amount of a composition including an antibody directed against the C1 domain of Factor VIII, which is a partially inhibitory antibody of Factor VIII.

Abstract: Modified Factor IX (FIX) polypeptides and uses thereof are provided. Such modified FIX polypeptides include FIXa and other forms of FIX. Among the modified FIX polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Abstract: The present invention relates to an adhesive hydrogel composition containing catechol group-coupled chitosan and Pluronic comprising a thiol group coupled to the end thereof, and more specifically, to an adhesive composition which is safe in vivo and in vitro, is temperature sensitive, and has an excellent hemostatic effect and thus can be used as a bioadhesive, and a medical adhesive, an adhesion barrier and a surface adsorption inhibitor comprising the same.

Abstract: Acridine containing cisplatin compounds have been disclosed that show greater efficacy against cancer than other cisplatin compounds. Methods of delivery of those more effective cisplatin compounds to the nucleus in cancer cells is disclosed using one or more amino acids, one or more sugars, one or more polymeric ethers, C1-6alkylene-phenyl-NH—C(O)—R15, folic acid, ?v?3 integrin RGD binding peptide, tamoxifen, endoxifen, epidermal growth factor receptor, antibody conjugates, kinase inhibitors, diazoles, triazoles, oxazoles, erlotinib, and/or mixtures thereof; wherein R15 is a peptide.

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

Abstract: Tissue factor-bearing yeast derived microvesicles comprising a yeast membrane and a tissue factor protein, or a fragment thereof, or a tissue factor protein or a fragment thereof fused to another peptide as a fusion protein having pro-coagulant activity are disclosed. Said products can be used as pro-coagulant agents in the treatment of hemorrhages in a subject.

Abstract: A fibrin wound dressing is made by mixing quantities of fibrinogen solution and thrombin solution with air. The resulting foam is very light weight, and with the proper attention to the amount of thrombin, is also sufficiently viscous to rest on a vertical surface without dripping. The wound dressing may also be formulated for its ability to continue migration of healing substances, such as PDGF, from the dressing to the wound site. Thrombin substitutes, such as other clotting proteins, may be used instead of thrombin. The resulting foam may also be lyophilized or ground and lyophilized for later reconstitution. A therapeutic drug or other additive may also be added to the wound dressing.

Abstract: The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Abstract: Provide are a peptide gel with practically sufficient mechanical strength and a self-assembling peptide capable of forming the peptide gel. The self-assembling peptide is formed of the following amino acid sequence: a1b1c1b2a2b3db4a3b5c2b6a4 where: a1 to a4 each represent a basic amino acid residue; b1 to b6 each represent an uncharged polar amino acid residue and/or a hydrophobic amino acid residue, provided that at least five thereof each represent a hydrophobic amino acid residue; c1 and c2 each represent an acidic amino acid residue; and d represents a hydrophobic amino acid residue.

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 generally to a method of reducing the level of plasminogen and/or tissue plasminogen activator and/or other protease(s) in a solution comprising fibrinogen and/or Factor VIII and/or von Willebrand factor (VWF), the method comprising: (i) passing a feedstock comprising fibrinogen and/or Factor VIII and/or VWF through a hydrophobic charge-induction chromatographic resin under conditions selected such that the plasminogen and/or tissue plasminogen activator and/or other protease(s) is bound to the resin; and (ii) recovering the solution comprising fibrinogen and/or Factor VIII and/or VWF which passes through the resin; wherein the concentration of the plasminogen and/or tissue plasminogen activator and/or protease(s) in the recovered solution is reduced by at least 50% compared to the feedstock. Also provided are solutions and pharmaceutical formulations comprising the fibrinogen and/or Factor VIII and/or VWF recovered by such methods, and uses thereof.

Abstract: ClotBlock is a lyophilized fibrin hemostatic designed for use an adjunct or primary treatment in moderate to severe hemorrhage. It can be applied directly to the wound in a laparotomy procedure or as non-invasive sealant. Its crosslinking technology generates a strong and safe adhesive fibrin sealant required for high volume hemostasis. The attachment properties of the cake as well as the rapid formation of and stability of the fibrin clot ensures that a strong stable fibrin clot is formed within 1 to 5 minutes depending on the grade of the wound. The agent is safe, biocompatible, biodegradable and can be stored at room temperature for one year.

Abstract: Use of a mutated antithrombin having substantially no activity, in particular no anticoagulant activity, possibly in association with an anticoagulant, for the preparation of a drug intended for the prevention or treatment of pathologies linked to or associated with coagulation disorders.

Abstract: The invention relates to the use of at least one human recombinant histone, especially at least one histone H1 subtype, and/or a therapeutic histone fraction as a basis for the treatment of thrombocytopenia.

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: The present invention provides polypeptides comprising or consisting of an amino acid sequence from thrombin, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof, for use in the treatment or prevention of inflammation and/or excessive coagulation of the blood. Related aspects of the invention provide isolated polypeptides comprising or consisting of an amino acid sequence of any one of SEQ ID NOs: 1 to 7, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof, which exhibit an anti-inflammatory activity, together with isolated nucleic acid molecules, vectors and host cells for making the same. Additionally provided are pharmaceutical compositions comprising a polypeptide of the invention, as well as methods of use of the same in the treatment and/or prevention of inflammation and/or excessive coagulation.