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: Compositions and methods for targeting substances to fibrinogen, fibrin monomers, or fibrin polymers are provided. These compositions and methods generally involve the use of fibrin knob peptides that bind fibrin(ogen), which can be used to detect fibrin(ogen) and modulate fibrin polymerization and fibrinolysis.

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: Methods and apparatus are disclosed for determining new anticoagulant therapy factors for monitoring oral anticoagulant therapy to help prevent excessive bleeding or deleterious blood clots that might otherwise occur before, during or after surgery. The inventive methods and apparatus provide an International Normalization Ratio (INR) based on a coagulation reaction with a blood sample of a living being. Embodiments include methods and apparatus for determining an anticoagulant therapy factor without requiring use of a mean normal prothrombin time determination or an ISI, and may be carried out with the patient sample and a coagulation reagent, where the coagulation reagent may be selected from a number of coagulation reagents.

Abstract: Methods and apparatus are disclosed for determining a new anticoagulant therapy factors for monitoring oral anticoagulant therapy to help prevent excessive bleeding or deleterious blood clots that might otherwise occur before, during or after surgery. New anticoagulant therapy factors maybe based upon the time to maximum acceleration from the time of reagent injection (TX) into a plasma sample, Embodiments include methods and apparatus for determining an anticoagulant therapy factor without requiring use of a mean normal prothrombin time determination or ISI, and may be carried out with the patient sample and a coagulation reagent.

Abstract: Described is a pharmaceutical preparation for treating blood coagulation disorders comprising an effective amount of vWF propeptide as well as a method for producing such a preparation.

Abstract: Method of increasing blood platelet formation by administering a parathyroid hormone (PTH) or at least one PTH derivative as an active ingredient.

Abstract: The assay of soluble endothelial protein C receptor (sEPCR) is useful to monitor effective thrombin levels and a hypercoagulable state. An assay for sEPCR is therefore useful to monitor ongoing effectiveness of anticoagulant therapy. A sEPCR ELISA assay is particularly useful for this purpose. A state of hypercoagulability in patients or normal individuals can also be identified by such an assay.

Abstract: The present invention is related to a novel composition of matter and methods of using the same. More particularly, the invention describes mutant human factor IX which has an increased resistance to inhibition by heparin. Methods of making and using this composition for the therapeutic intervention of hemophilia are disclosed.

Abstract: The application discloses Factor VIII polypeptides comprising internal deletions of amino acids within the area of residues 741 to 1689, wherein the thrombin cleavage sites at about 741 and about 1689 are present, and a site at about 1648 is not present, as compared to human Factor VIII.

Abstract: The present invention provides a pharmaceutical composition for treatment and prevention of bleeding disorders caused by platelet disorders, not caused by defect in blood coagulation factors or von Willebrand Factor but caused by reduction of circulating platelet count or platelet dysfunction, said composition comprising a hemostatic effective amount of Factor VIII and/or von Willebrand Factor. Also provided is a method for treating said bleeding, comprising administering a hemostatic effective amount of Factor VIII and/or von Willebrand Factor to patients suffering from bleeding disorders caused by platelet disorders.

Abstract: Disclosed are compositions for treating blood coagulation disorders and allows for manipulation of the blood coagulation cascade. More particularly the invention, relates to compositions for altering bleeding that include a mixture of at least one blood coagulation factor in a low dose and phospholipid vesicles. The invention has a variety of important uses including controlling bleeding in a mammal that has or is suspected of having a potentially life-threatening blood coagulation disorder.

Abstract: Described is a pharmaceutical preparation for treating blood coagulation disorders comprising an effective amount of vWf propeptide as well as a method for producing such a prepartion.

Abstract: Method for preparing a factor VIII solution that is essentially free of viruses and essentially devoid of vWF (von Willebrand factor) and factor VIII-vWF complexes by (a) obtaining a starting factor VIII solution devoid of factor VIII-vWF complexes; and (b) filtering the solution through a hydrophilic virus filter.

Abstract: Method of increasing blood platelet formation by administering a parathyroid hormone (PTH) or at least one PTH derivative as an active ingredient.

Abstract: A pharmaceutical composition for parenteral administration comprising a therapeutically effective amount of a protein or polypeptide and substantially neutral colloidal particles. The particles comprise approximately 1-20 mole percent of an amphipathic lipid derivatized with a biocompatible hydrophilic polymer which carriers substantially no net charge. The protein or polypeptide is capable of externally binding the colloidal particles, or is capable of binding polyethylene glycol, and is not encapsulated in the colloidal particles. A preferred protein is factor VIII, whose half-life is extended and which is protected from serum inhibitor antibodies by injecting it as a component of the composition.

Abstract: The present invention provides preparations of Factor VIIa polypeptides or Factor VIIa-related polypeptides that exhibit predetermined glycoform patterns. The preparations of the invention exhibit improved functional properties and are useful for treating Factor VII-mediated conditions.

Abstract: A DNA-construct has been disclosed which is suitable for a tissue-specific expression of a blood coagulation factor like Factor IX, which comprises a DNA coding for an amino acid sequence of a blood coagulation factor and a DNA coding for a promoter which is specific for the expression in hematopoietic cells.

Abstract: The present invention is directed to medical devices or pharmaceutical composition, each containing a synthetic, biodegradable, biocompatible polymer that is the reaction product of a polybasic acid or derivative thereof, a monoglyceride, and a cationic polyol.

Abstract: The invention provides fusion toxins that contain one or more regions of diphtheria toxin and a portion of urokinase-type plasminogen activator, as well as the nucleic acids that encode the fusion toxins and methods of using the fusion toxins.

Abstract: Novel human protein C derivatives are described. These derivatives have increased anti-coagulation activity and resistance to inactivation by serpins, compared to wild-type protein C and retain the biological activity of the wild-type human protein D. These derivatives will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of acute coronary syndromes, vascular occlusive disorders, hyper coagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Abstract: The invention relates to a pharmaceutical composition comprising Factor VIIa for subcutan, intramuscular or interdermal administration. Factor VIIa administered subcutanously, intramuscularly or intradermally shows a sufficient transport into the bloodstream in biologically active form and in adequate concentrations, and favorable pharmacokinetic properties.

Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.

Abstract: A modified Factor VIII cDNA is disclosed wherein the B-domain of the wild type factor cDNA has been deleted and a truncated Factor IX intron 1 has been inserted in two locations of the Factor VIII cDNA and as a promoter a cDNA is used which is suitable for the expression in hematopoietic cell lines and specifically in platelets.

Abstract: Specific amino acid loci of human factor VIII interact with inhibitory antibodies of hemophilia patients after being treated with factor VIII. Modified factor VIII is disclosed in which the amino acid sequence is changed by a substitution at one or more of the specific loci. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory antibodies.

Abstract: A method of treating palmar and plantar fibromatosis is disclosed. The method includes administering to a patient of a therapeutically effective amount of a composition comprising 13-cis-retinoic acid. Preferably, the treatment method includes administering to a patient of an initial dosage of a composition comprising 13-cis-retinoic acid for an initial treatment period, and thereafter administering a maintenance dosage of the composition.

Abstract: Novel polypeptides or derivatives comprising the factor VIIIa binding site on factor IXa are disclosed. The novel polypeptides or derivatives have anti-coagulation activity. Nucleic acids encoding those polypeptides are also disclosed. Methods for identifying an agent having anti-coagulation activity are also disclosed. These methods comprise determining whether the agent displaces the polypeptide or derivative from its factor VIIa binding site. The agent identified in these methods is also useful in methods for treating a patient to prevent thrombosis. The treatment methods comprise administration of the agent to the patient. Additional methods are also disclosed for treating a patient to prevent thrombosis, comprising treating the patient with a polypeptide or derivative comprising the factor VIIIa binding site on factor IXa. Methods of preventing coagulation in a blood sample are also disclosed, comprising adding the polypeptides or derivatives described above to the blood sample.

Abstract: A pharmaceutical composition for parenteral administration comprising a therapeutically effective amount of a protein or polypeptide and substantially neutral colloidal particles. The particles comprise approximately 1-20 mole percent of an amphipathic lipid derivatized with a biocompatible hydrophilic polymer which carriers substantially no net charge. The protein or polypeptide is capable of externally binding the colloidal particles, or is capable of binding polyethylene glycol, and is not encapsulated in the colloidal particles. A preferred protein is factor VIII, whose half-life is extended and which is protected from serum inhibitor antibodies by injecting it as a component of the composition.

Abstract: The invention relates to the use of glycylglycine, optionally in combination with a sugar, and/or a sugar alcohol, and/or an amino acid, as a bulking agent in freeze-drying.

Abstract: A method for the preparation of bone gel and bone putty which comprises producing a viscous supernatant by dissolving demineralized bone matrix in water or a solution comprising water and at least one component normally found in human blood serum, at a temperature above about 25° C. Agitation and/or ultrasound or pressure accelerates dissolution of the demineralized bone. The resulting viscous supernatant is cooled, then mixed with demineralized or non-demineralized bone matrix particles to form a gel-like suspension or putty-like material.

Abstract: The present invention provides a method for preparing biodegradable porous polymer scaffolds for tissue engineering, comprising: a) fabricating a polymer sample from a polymer solution containing at least one biodegradable polymer and an effervescent mixture; b) effervescing the polymer sample in the presence of an effervescent medium such as an aqueous alcohol solution; and c) drying. The method for preparing biodegradable polymer scaffolds of the present invention has the advantages that the process is simple, that pore size can be easily controlled, that the problem caused by the secretion and existence of the toxic substance can be avoid by using a material harmless to human body, and that high efficiency can be achieved. In addition, biodegradable porous polymer scaffolds prepared by above method have the advantages that high porosity can be achieved and an open cell structure in which pores are interconnected is obtained.

Abstract: The invention is directed toward a sterile bone structure for application to a bone defect site to promote new bone growth at the site comprising a partially demineralized cortical bone structure, said bone structure comprising a cross sectional surface are ranging from 85% to 95% of the original bone surface area before demineralization with the remaining partially demineralized cortical bone structure having an outer demineralized layer ranging in thickness from about 0.05 mm to about 0.14 mm and a mineralized core.

Abstract: A description is given of a one-component tissue adhesive containing, in aqueous solution, fibrinogen, F XIII, a thrombin inhibitor, prothrombin factors, calcium ions and, where appropriate, a plasmin inhibitor and of a process for the production thereof. This adhesive can be reconstituted from a freeze-dried form with water. It can contain aLL active substances in pasteurized form and is then free of the risk of transmission of hepatitis and HTLV III.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: The invention relates to a modified B-domainless form of porcine factor VIII, to a DNA encoding the same, and to the use thereof for treatment of hemophilia.

Abstract: A composition for enteral administration having a non-ionic vegetable oil GIT absorption enhancer capable of increasing the enteral absorbability of drugs, especially oral absorbability of hydrophilic and macromolecular drugs. The non-ionic vegetable oil GIT absorption enhancer, particularly Babassu oil or a derivative thereof, is capable of enhancing the uptake of a drug from the gastrointestinal tract so as to allow therapeutically effective amounts of the drug to be transported across the GIT of an animal such as a human without significant toxic side effects.

Abstract: A pharmaceutical preparation contains protein C and a thrombolytically active substance that does not activate protein C. This preparation prevents reocclusion usually occurring in the course of thrombolysis therapy.

Abstract: This invention provides a claycy and sticky substance as a new biomaterial that cannot be found in the current medical field, which is bioresorbable, shows tackiness, plasticity and shape holding ability at a temperature of approximately from 30 to 40° C. and can give unrestricted shapes at body temperature or more by increasing its fluidity. This clayey and sticky substance comprises a copolymer of two or more bioresorbable monomers, preferably any one of copolymers of p-dioxanone with D-lactic acid, L-lactic acid, D,L-lactic acid, trimethylene carbonate and &egr;-caprolactone, or a mixture of two or more of these copolymers. This clayey and sticky or clayey substance is suited for a hemostatic material, an adhesive material for tissues, a prosthetic material for tissue reconstruction use, a carrier of drug delivery system, a plugging material, an accretion-preventing material and a scaffold material for tissue engineering use.

Abstract: Novel polypeptides having Factor VIII activity are provided as well as compositions and methods for their preparation. The polypeptides comprise derivatives and fragments of Factor VIII and have sequences substantially similar to portions of naturally occuring Factor VIII. The polypeptides find use in treatment of Hemophilia A.

Abstract: The present invention relates to a process for the preparation of a product of blood coagulation factors II, VII, IX and X which is virtually free of virus, the process comprising heating an aqueous liquid containing these factors in the presence of calcium ions and a chelating agent and, optionally, an amino acid, a saccharide or sugar alcohol, antithrombin III and/or heparin. The product can be used for the treatment of blood coagulation disorders.

Abstract: There is disclosed a highly purified complex comprising the components factor VIII and vWF having a specific activity of at least 70, preferably 100 to 300 U factor VIII:C/mg, a stable pharmaceutical preparation containing this complex as well as a method of producing the same.

Abstract: The present invention relates to biologically active peptides which specifically inhibit the Factor IX-dependent pathway of blood coagulation. These peptides are based on a specific motif which represents a sequence of Factor VIII (amino acid 1811-1818) involved in binding to activated Factor IX as well as to the intact Factor IX zymogen. Binding of said peptides to Factor IX or activated derivatives thereof effectively inhibits complex assembly with Factor VIII. These peptides thereby specifically interfere in the Factor IX-dependent pathway of thrombin formation, while leaving other haemostatic pathways unaffected. By virtue of this unique specificity, the peptides of this invention are particularly useful in novel pharmaceutical compositions for the treatment of thrombotic disorders.

Abstract: The invention is a fibrin glue that avoids the use of fibrinogen and thus eliminates the need for premixing and premature clot formation. The fibrin glue of the invention comprises thrombin, thromboplastin and calcium and may have clotting Factors, VII, IX and X, and the like. The invention also comprises a biosealant for use with the fibrin glue without fibrinogen or for use alone. The biosealant is a two component mixture of gelatin/resorcinol and glyoxal/glutaraldehyde/4-(p-maleimidophenyl) butyric acid. The two components are mixed on use.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: A fibroin fluid obtained by adding carbon dioxide to a fibroin aqueous solution and then completely removing the carbon dioxide by pressure reduction or heating has fibroin microstructures which are dispersed in a dispersing medium, the fibroin fluid, unlike a conventional fibroin gel, having a fluidity sufficient for bringing it into the sate of a cream, having the property of excellent humidity retention and being widely usable as an agent for decreasing cholesterol or cosmetic.

Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. The invention relates to novel methods of treatment and uses of modified Factor VII for preventing or treating myocardial injury associated with post-ischemic reperfusion, for improving regional myocardial blood flow during reperfusion, and maintaining or improving vascular patency in a patient, as well as topical application of modified Factor VII at vascular sites susceptible to thrombus formation.

Abstract: There is provided the use of a thrombin inhibitor in the manufacture of a product for use in the control of wound healing processes within the body, in particular, the inhibition or prevention of fibrin-related adhesion and/or scar tissue formation, as well as products for use in the control of wound healing processes within the body comprising polysaccharides (e.g., chitosans) and low molecular weight peptide-based thrombin inhibitors.

Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. Pharmaceutical compositions of the modified Factor VII are used to treat a variety of coagulation-related disorders, including platelet deposition, vascular thrombosis, ischemic reperfusion, acute closure of a coronary artery, vascular restenosis secondary to balloon angioplasty, endarterectomy, reductive atherectomy, stent placement, laser therapy or rotablation.

Abstract: The invention is a fibrin glue that avoids the use of fibrinogen and thus eliminates the need for premixing and premature clot formation. The fibrin glue of the invention comprises thrombin, thromboplastin and calcium and may have clotting Factors, VII, IX and X, and the like. The invention also comprises a biosealant for use with the fibrin glue without fibrinogen or for use alone. The biosealant is a two component mixture of gelatin/resorcinol and glyoxal/glutaraldehyde/4-(p-maleimidophenyl) butyric acid. The two components are mixed on use.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.