Abstract: The pharmaceutically acceptable salts of bicycle-substituted pyrazolon azo derivatives represented by the general formula (I), their preparation methods, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor. The definitions of substituents in the general formula (I) are the same as the description.

Abstract: The present invention relates to methods and kits for determining heparanase procoagulant activity in a biological sample. The invention also relates to diagnostic methods for the detection and/or monitoring of a coagulation-related pathologic disorder in a mammalian subject. The invention further relates to compositions comprising heparanase and at least one tissue factor, uses and methods based thereon in the treatment, amelioration and prevention of coagulation-related pathologic conditions. The invention still further relates to methods for screening a coagulation modulatory compound, methods and uses based thereon in the treatment, amelioration and prevention of coagulation-related pathologic conditions.

Abstract: The present invention relates to a method for treatment or prevention of a hemorrhagic condition in a patient by administering plasminogen activator inhibitor-1 (“PAI-1”) and/or an inhibitor of deubiquitinating enzyme CYLD (“CYLD”) to a patient. Pharmaceutical compositions that include one or both of PAI-1 and an inhibitor of CYLD are also disclosed.

Abstract: The present invention relates to compositions comprising factor VII coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of coagulation factor-related diseases, disorders, and conditions.

Abstract: The present invention relates to the use of at least one antibody and/or one inhibitor for inhibiting factor XII and for 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 is directed to a method for therapeutic repair of an injury to bone or tissue comprising providing a structural component, wherein the structural component repairs the injury; and providing a therapeutic fluid, wherein the therapeutic fluid is located within the structural component.

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: The present invention relates to a closed container holding a composition of an activated Factor VII polypeptide in an amount of in the range of 2.5-90 mg per imL volume of the container. The invention also relates to various processes for the preparation of such closed containers, a kit including such containers and a method of using the kit.

Abstract: The invention relates to a method of purifying PEGylated proteins by removing impurities from samples containing PEGylated proteins, in particular, but not exclusively vitamin K-dependent blood coagulation factors such as Factor IX (FIX), to proteins purified by said method and to the use of said purified proteins in therapy, in particular but not exclusively, for the treatment of diseases alleviated by blood coagulation factors such as the prophylactic treatment of hemophilia.

Abstract: The invention is in the field of coagulation diagnostics and relates to a heparin-insensitive method for determining direct coagulation factor inhibitors in a sample, in particular direct thrombin and factor Xa inhibitors.

Abstract: ClotFoam is a sealant and hemostatic agent for use in cases of non-compressible hemorrhage for moderate to severe bleeding. It can be applied in the operating room through laparoscopic ports, or directly over lacerated tissue in laparotomy procedures or outside the operating room through a mixing needle and/or a spray injection method following intracavitary severe trauma or surgery. Its crosslinking technology generates an adhesive scaffold that carries a fibrin sealant required for hemostasis. Clotfoam produces a foam that spreads throughout a body cavity reaching the lacerated tissue to seal tissue and promote the coagulation cascade. The composition is biocompatible and non-inflammatory. The invention uses fibrin monomer polymerized by a change of pH as active sealing component. The viscoelastic properties of the foam as well as the rapid formation of a fibrin clot ensure that the sealant remains at the site of application without being washed away by blood.

Abstract: Silent brain ischemia (SBI) or ischemia of other organs can result from an embolism that is introduced into the arterial system during a medical procedure. The application provides a method of administering a FXII inhibitor in a patient receiving a medical procedure and animal models useful for studying ischemia including SBI and ischemia in other organs, and for evaluating candidate therapeutics.

Abstract: Provided are salt-free antibody and other protein formulations that are substantially isosmotic and of low viscosity. Also provided are methods for the treatment of diseases using the disclosed formulations.

Abstract: The invention relates to chemically as well as physically stable kits and compositions comprising polypeptides, in particular Factor VII or Factor VII-related polypeptides, such that these compositions can be stored, handled and used at room temperature.

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: Methods and apparatus for a free-standing biodegradable patch suitable for medical applications, especially intravascular, minimally-invasive and intraoperative surgical applications are provided, wherein the patch comprises a free-standing film or device having a mixture of a solid fibrinogen component and a solid thrombin component that, when exposed to an aqueous environment, undergoes polymerization to form fibrin. In alternative embodiments the patch may comprise a solid fibrinogen component, with or without an inorganic calcium salt component. The patch may take a non-adherent form during delivery to a target location within a vessel or tissue, and thereafter may be activated to adhere to vessel wall or tissue, and may include a number of additives, including materials to improve the mechanical properties of the patch, or one or more therapeutic or contrast agents.

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: Here, we present a photodegradable microparticle system that can be employed to entrap and deliver bioactive proteins to cells during culture. By using a photosensitive delivery system, experimenters can achieve a wide variety of spatiotemporally regulated release profiles with a single microparticle formulation, thereby enabling one to probe many questions as to how protein presentation can be manipulated to regulate cell function. Photodegradable microparticles were synthesized via inverse suspension polymerization with a mean diameter of 22 ?m, and degradation was demonstrated upon exposure to several irradiation conditions. The protein-loaded depots were incorporated into cell cultures and release of bioactive protein was quantified during the photodegradation process. This phototriggered release allowed for the delivery of TGF-?1 to stimulate PE25 cells and for the delivery of fluorescently labeled Annexin V to assay apoptotic 3T3 fibroblasts during culture.

Abstract: A method for relieving menstrual pain and reducing menstrual blood loss in a female is provided. The method comprises administering intravaginally to the female a first therapeutically effective amount of a non-steroidal anti-inflammatory drug (NSAID) that relieves menstrual pain and a second therapeutically effective amount of an active agent that reduces menstrual blood loss, wherein the NSAID and the active agent are simultaneously administered by the same drug delivery device, wherein the active agent is any one of an antifibrinolytic agent and a hemostatic agent.

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: Modifications of vitamin K-dependent polypeptides that lead to enhanced protein function on a weight or molar basis and/or increase of protein lifetime in the circulation are described. Both objectives are important for using vitamin K-dependent polypeptides for pro- and anti-coagulation therapies, as well as for other uses in the circulation.

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: The present invention relates to compounds of the Formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, X1, X2, X3 and X4 have the meanings indicated in the claims, and which are valuable pharmacologically active compounds. They are reversible inhibitors of the interaction between the plasma protein von Willebrand factor (vWF) and the blood platelet receptor glycoprotein Ib-IX-V complex (GPIb), and are suitable, for example, for the therapy and prophylaxis of athero-thrombotic diseases. The invention furthermore relates to processes for the preparation of compounds of the Formula (I), their use, in particular as active ingredients in medicaments, and pharmaceutical compositions comprising them.

Abstract: Cell attachment coatings for articles such as implantable medical devices and cell culture vessels are disclosed. The coatings include an intermediate coater layer which includes a phosphorous-containing component that is bonded in the coating by reacted photoreactive functional groups. The coating also include a second coated layer including an immobilized ECM protein or peptide that includes an active portion of an ECM protein that is able to serve as an outer layer to contact cells during use. The coatings promoted enhanced cell binding and growth.

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: A method, medicated feminine sanitary products and compositions for reducing menstrual blood loss in a female are provided. The method comprises delivering an active agent to the uterine cavity by administering intravaginally to the female a therapeutically effective amount of the active agent on a medicated feminine sanitary product during menstrual bleeding, wherein the medicated feminine sanitary product is routinely utilized to absorb the menstrual flow, wherein the active agent is incorporated in the medicated feminine sanitary product as a pharmaceutically acceptable composition, the active agent is any of an antifibrinolytic and a hemostatic agent.

Abstract: The present invention provides fusion proteins comprising a mucin-domain polypeptide covalently linked to an active protein that has improved properties (e.g. pharmacokinetic and/or physicochemical properties) compared to the same active protein not linked to mucin-domain polypeptide, as well as methods for making and using the fusion proteins of the invention.

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 a von Willebrand Factor for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes. Furthermore, the present invention relates to a method of treating and/or preventing a disorder related to a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes comprising administering a pharmaceutically effective amount of a von-Willebrand-Factor (vWF) to a patient in need thereof. The present invention also relates to a composition comprising vWF and a composition comprising FVIII for simultaneous, separate or sequential use for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes.

Abstract: Disclosed is a biocompatible, hemostatic, cross-linked gelatin composition comprising a biocompatible material comprising cross-linked gelatin and a sufficient amount of wetting agent to permit uniform wetting of the sponge in the presence of an aqueous solution.

Abstract: Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.

Abstract: The present invention concerns the use of peptides derived from and antibodies generated against Factor VIII and the inhibition of Factor VIII interaction with LRP. Furthermore, the present invention concerns a method to inhibit LRP interaction with Factor VIII as well as a method to decrease Factor VIII degradation and/or prolong Factor VIII half-life in a biological fluid and/or a method to treat patients suffering from a blood coagulation disorder, especially Haemophilia A. The present invention also concerns a pharmaceutical composition useful for the decrease of Factor VIII degradation in a biological fluid, the inhibition of Factor VIII interaction with LRP, and/or the prolongation of Factor VIII half-life in a biological fluid for treatment of a blood coagulation disorder, especially Haemophilia A.

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 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 relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.

Abstract: The present invention provides conjugates encompassed by the following structure, wherein: D is a residue of an active agent bearing at least one amino group; and PEG-m is a methoxy end-capped poly(ethylene glycol), and further wherein the active agent is a coagulation factor having a molecular weight of greater than 100 kDa. Methods of making conjugates, and methods for administering conjugates, are also provided.

Abstract: The present invention relates to binding molecules such as antibodies that specifically bind plasma coagulation factor XI and that inhibit factor XI activation and/or activity. The factor XI-binding molecules of the invention may used in methods for preventing or treating diseases, disorders and/or conditions that are mediated by factor XI activation and/or wherein inhibition of factor XI has a beneficial effect.

Abstract: A covering for delivering a therapeutic agent to a surgical site is provided. The covering may include a single or multi-compartment structure configured to at least partially retain the therapeutic agent until the covering is placed at a surgical site. Upon placement, the covering may facilitate transfer of the therapeutic agent to the surgical site. In some embodiments, the covering comprises an antimicrobial agent, a hemostatic agent, an anti-inflammatory agent, and/or a growth factor.

Abstract: A peptide or peptide derivative comprising: (i) WDLYFEIVW (SEQ ID NO: 1); or (ii) a variant amino acid sequence comprising one, two, three or four L-amino acid substitutions in WDLYFEIVW (SEQ ID NO: 1); or (iii) the retro-inverso variant of the peptide or peptide derivative of either one of parts (i) and (ii), wherein said peptide or peptide derivative has procoagulant activity. A peptide or peptide derivative comprising: (i) an amino acid sequence comprising imfwydcye; or (ii) a variant amino acid sequence comprising one, two, three, four, five or six amino acid substitutions in imfwydcye, wherein said peptide or peptide derivative has procoagulant activity.

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 invention provides methods of making and using compounds of the formula shown, which are inhibitors of human plasmin and plasma kallikrein. (Formula I) The compounds are useful for the prevention of blood loss, and as components of fibrin adhesives.

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: The present invention relates to chimeric derivatives of serine protease zymogen containing the activation peptide of factor X or a fragment thereof for improving the half-life of said derivatives. Preferably, said chimeric derivatives are protein C and factor X derivatives. The invention also relates to said derivatives for the prevention or treatment of blood coagulation disorders.

Abstract: Factor VIII polypeptides having FVIII:C activity that contain modifications in the A3 and/or C1 and/or C2 domains of the sequence of the light chain of Factor VIII, characterized by the binding affinity to low density lipoprotein receptor protein, and methods for producing the same.

Abstract: The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. Peptide complexes also are provided. 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, treat a blood coagulation disorder in a subject, purify TFPI, and identify a TFPI-binding compound.

Abstract: A hemostatic material as a high-performance medical material is described, which is capable of stopping bleeding in short time and is easy to handle and produce. The hemostatic material contains a nano-fiber that contains: a polymer, and a polypeptide having a peptide fragment represented by formula (1): -(Pro-Y-Gly)n- ??(1) wherein Y represents hydroxyproline or proline, and n represents an integer ranging from 5 to 9000.

Abstract: The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.

Abstract: The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors.

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, will 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. A fibrin foam may be made by injecting fibrinogen foam into a clotting protein, such as thrombin.

Abstract: The present invention provides non-anticoagulant sulfated or sulfonated polysaccharides (NASPs), which accelerate the blood clotting process. Also provided are pharmaceutical formulations comprising a NASP of the invention in conjunction with a pharmaceutically acceptable excipient and, in various embodiments, these formulations are unit dosage formulations. The invention provides a NASP formulation, which is orally bioavailable. Also provided are methods for utilizing the compounds and formulations of the invention to promote blood clotting in vivo as therapeutic and prophylactic agents and in vitro as an aid to studies of the blood clotting process.