37 results about "Von Willebrand disease" patented technology

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a nucleic acid encoding a mutant von Willebrand Factor protein to correct a point mutation associated with a disease or disorder, e.g., with von Willebrand disease. The methods provided are useful for correcting a vWF point mutation within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.

A method of clotting blood includes the step of administering a therapeutically effective amount of a composition comprising zeolite as the active ingredient to a wound from which the blood emanates. A method of arresting blood flowing from a wound includes the steps of providing a patient being inflicted with a bleeding wound and administering a therapeutically effective amount of a composition comprising zeolite as the active ingredient to the bleeding wound. A method of facilitating the formation of blood clots includes the step of contacting blood with a negatively charged surface wherein upon contacting the blood with the negatively charged surface a clotting mechanism is initiated. In any of the foregoing methods, the blood has a compromised ability to form clots. The blood may be from a person diagnosed with hemophilia or von Willebrand disease.

In a method of clotting blood in which the blood exhibits a reduced tendency to clot and may be from a person undergoing an anticoagulant therapy or having type A or B hemophilia or von Willebrand disease, a therapeutically effective amount of a composition comprising clay as the active ingredient is administered to a wound from which the blood emanates. Upon contacting the blood, this clay, which may be kaolin, bentonite, or any type of layered clay, causes the blood to clot. In a method of arresting blood flowing from a wound, a therapeutically effective amount of a composition comprising clay as the active ingredient is administered to the bleeding wound. In this method, the blood has a reduced tendency to clot and may be from a person undergoing an anticoagulant therapy or having at least one of hemophilia A or B or von Willebrand disease.

The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences of the present invention encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe309 is mutated. The nucleic acid sequences of the present invention also encode amino acid sequences corresponding to known human FVIII sequences, wherein the APC cleavage sites, Arg336 and Ile562, are mutated. The nucleic acid sequences of the present invention further encode amino acid sequences corresponding to known human FVIII sequences, wherein the B-domain is deleted, the von Willebrand factor binding site is deleted, a thrombin cleavage site is mutated, an amino acid sequence spacer is inserted between the A2- and A3-domains. Methods of producing the FVIII proteins of the invention, nucleotide sequences encoding such proteins, pharmaceutical compositions containing the nucleotide sequences or proteins, as well as methods of treating patients suffering from hemophilia, are also provided.

The invention relates to the adhesion of platelet GpIbα to strand β3 of domain A1 of von Willebrand factor (vWF), the strand β3 comprising amino acid residues at amino acid position 560-566 and / or a functional part or equivalent thereof, the platelet GpIbα, the GpIbα region comprising an amino acid sequence corresponding to a beta-switch loop of platelet GpIbα, comprising amino acid residues at amino acid position 227-242 and / or a functional part or equivalent thereof. The invention provides a method of interfering with adhesion of blood platelets to vWF that includes modulating adhesion. The invention further provides proteinaceous compounds, antibodies, medicaments and pharmaceutical compositions to that end. The invention also provides means and methods to increase platelet adhesion by topical application of a compound increasing platelet adhesion.

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.

This invention relates to treatment of von Willebrand Disease by administration of Factor VIII muteins that are covalently bound, at a predefined site that is not an N-terminal amine, to one or more biocompatible polymers such as polyethylene glycol. The mutein conjugates retain FVIII procoagulant activity and have improved pharmacokinetic properties in subjects lacking von Willebrand Factor.

The invention relates generally to the field of nucleic acids and more particularly to aptamers capable of binding to von Willebrand Factor useful as therapeutics in and diagnostics of thrombotic diseases and / or other diseases or disorders in which von Willebrand Factor mediated platelet aggregation has been implicated. The invention further relates to materials and methods for the administration of aptamers capable of binding to von Willebrand Factor.

The present invention provides an epitope recognized by an antibody (hereinafter, also referred to as an anti-ADAMTS-13 antibody) against a cleaving protease (hereinafter, also referred to as ADAMTS-13) specific to von Willebrand factor (hereinafter, also referred to as vWF), and a polypeptide comprising the epitope region. The present invention also provides a polypeptide located in a region from position 449 to position 687 in an amino acid sequence composing the ADAMTS-13, which is recognized by the anti-ADAMTS-13 antibody, or a peptide fragment derived from the polypeptide.

A method of detecting thrombosis or the degree of thrombophilia by measuring a von Willebrand factor cleaving protease, and a kit for detecting thrombosis or the degree of thrombophilia, comprising an antibody or a fragment thereof specifically binding to a von Willebrand factor-cleaving protease, are disclosed. The detection method and the detection kit have an excellent convenience, rapidity, and specificity.

This invention relates to a process for the preparation of a very high purity von Willebrand factor concentrate from a biological fraction containing von Willebrand factor, including a separation by anion exchange chromatography using a vinyl polymer support of weak base type, the said separation comprising the steps of loading of the chromatographic support with the fraction containing von Willebrand factor, previously equilibrated with a suitable buffer, with a predetermined flowrate allowing the retention of the von Willebrand factor, washing of the support with an acidic buffer with a flowrate higher than the flowrate of the step a) until the not-retained proteins and the contaminants are removed, flushing and equilibrating of the chromatographic support with the buffer and using the flowrate of the step a), and elution of the von Willebrand factor by increasing of the ionic strength of the step c). The invention also relates to a von Willebrand factor concentrate for therapeutic use likely to be obtained by implementing of the process wherein the rate of Factor VIII:C / FvW:RCo is less than 0.06%.

The present invention is directed to liquid, aqueous pharmaceutical compositions containing Factor VII polypeptides, and methods for preparing and using such compositions, as well as vials containing such compositions, and the use of such compositions in the treatment of a Factor VII-responsive syndrome, e.g., bleeding disorders, including those caused by clotting Factor deficiencies (e.g. haemophilia A, haemophilia B, coagulation Factor VII deficiency); by thrombocytopenia or von Willebrand's disease, or by clotting Factor inhibitors, and intra cerebral haemorrhage, or excessive bleeding from any cause. The preparations may also be administered to patients in association with surgery or other trauma or to patients receiving anticoagulant therapy. More particularly, the invention relates to liquid compositions stabilised against chemical and / or physical degradation. The main embodiment is represented by a liquid, aqueous pharmaceutical composition comprising a Factor VII polypeptide (i); a buffering agent (ii) suitable for keeping pH in the range of from about 4.0 to about 9.0; at least one metal-containing agent (iii), wherein said metal is selected from the group consisting of first transition series metals of oxidation state +II, except zinc, such as chromium, manganese, iron, cobalt, nickel, and copper; and a non-ionic surfactant (iv).

The invention relates to an in-vitro method for diagnosing Von Willebrand Disease (VWD) and an increased bleeding risk associated with Von Willebrand Disease and / or acquired or congenital platelet function defects that reduce the interactions of Von Willebrand Factor (VWF) with platelets. The in-vitro method of the invention may also be used to diagnose further bleeding risks. The test is suitable for use as a screening test based on whole blood and has the additional benefit of being suitable as a point of care test. The method involves the incubation of a sample containing platelets and hemostasis factors with an activator of platelet aggregation and the measurement of the viscoelastic change after inducing coagulation, e.g., by means of thromboelastography (TEG).

The present invention relates to novel truncated fragments of von Willebrand factor (VWF) and the use of such fragments and nucleic acids encoding such fragments in the treatment of von Willebrand disease (VWD) and haemophilia.

A method for diagnosing von Willebrand disease and novel polypeptides which bind to von Willebrand factor.

The invention relates to negative functional modulators of erythropoietin (EPO) for use in the treatment of cancers, in the therapy of autoimmune -based and non-autoimmune based chronic inflammatory diseases, and in the treatment of patients under-going organ or tissue transplant, or for the treatment of hemophilic arthropathy, hemophilia A and B, von Willebrand disease, angiodysplasia, proliferative disorders and neurological diseases characterized in their pathogenesis by primary neuroinflammation and / or neuroinflammation secondary to other causes. Such modulators are anti-EPO antibodies and their derivatives: anti-EPO receptor antibodies (EPOR), antisense oligonucleotides, decoy DNA, decoy RNA, ribozyme, antagomir, shRNA, LNA and / or siRNAs that inhibit the expression of the gene encoding EPO or EPOR.

The present invention relates to a method for treating gastrointestinal bleeding in a subject with severe von Willebrand Disease comprising administering to the subject at least one dose of recombinant von Willebrand Factor (rVWF) ranging from about 40 IU / kg to about 100 IU / kg, wherein the first dose further comprises recombinant Factor VIII (rFVIII).

The invention relates to negative functional modulators of erythropoietin (EPO) for use in the treatment of cancers, in the therapy of autoimmune -based and non-autoimmune based chronic inflammatory diseases, and in the treatment of patients under-going organ or tissue transplant, or for the treatment of hemophilic arthropathy, hemophilia A and B, von Willebrand disease, angiodysplasia, proliferative disorders and neurological diseases characterized in their pathogenesis by primary neuroinflammation and / or neuroinflammation secondary to other causes. Such modulators are anti-EPO antibodies and their derivatives: anti-EPO receptor antibodies (EPOR), antisense oligonucleotides, decoy DNA, decoy RNA, ribozyme, antagomir, shRNA, LNA and / or siRNAs that inhibit the expression of the gene encoding EPO or EPOR.

A preparation for treating haemophilia caused by Qi and blood deficiency and von Willebrand disease and a method. The preparation is produced from, by weight, 18-48 parts of raw astragalus membranaceus, 6-15 parts of codonopsis pilosula, 9-24 parts of raw atractylodes macrocephala, 9-24 parts of poria cocos, 6-15 parts of pericarpium citri reticulatae, 6-15 parts of angelica sinensis, 6-15 parts of colla corii asini, 6-15 parts of Chinese wolfberries, 6-15 parts of fructus psoraleae, 6-15 parts of pomegranate peel, 9-24 parts of Chinese dates, and 4-10 parts of honey-fried licorice roots. In the invention, active components in the raw material medicines are extracted in a manner of water boiling, wherein the activities are maintained, so that in the preparation, the dissolution rates of the active components are greatly increased, and the medicines are easy to absorb, thus increasing the bioavailability of the preparation; in addition, the preparation is a pure-traditional Chinese medicine compound preparation, so that no toxic and side effect is generated after long time use by a patient, and the preparation is good in safety. The preparation method is simple and is convenient tocarry out.

Anti-thrombotic agents containing humanized antibodies which bind to von Willebrand factor.

The invention relates to negative functional modulators of erythropoietin (EPO) for use in the treatment of cancers, in the therapy of autoimmune-based and non-autoimmune based chronic inflammatory diseases, and in the treatment of patients undergoing organ or tissue transplant, or for the treatment of hemophilic arthropathy, hemophilia A and B, von Willebrand disease, angiodysplasia, proliferative disorders and neurological diseases characterized in their pathogenesis by primary neuroinflammation and / or neuroinflammation secondary to other causes. Such modulators are anti-EPO antibodies and their derivatives: anti-EPO receptor antibodies (EPOR), antisense oligonucleotides, decoy DNA, decoy RNA, ribozyme, antagomir, shRNA, LNA and / or siRNAs that inhibit the expression of the gene encoding EPO or EPOR.

The invention relates to compositions comprising an isolated sugar for use in the treatment of von Willebrand disease and / or hemophilia A, wherein the sugar is an accessible sugar residue derived from ABO(H) blood group antigen.

The present invention relates, generally, to a transgenic non-human animal model of hemophilia A, wherein the transgenic animal is deficient in endogenous Factor VIII and endogenous von Willebrand Factor, and methods to treat hereditary or acquired hemophilia A or von Willebrand Disease (VWD) by administration of exogenous human VWF.

The invention relates to a preparation for treating hemophilia and von willebrand disease caused by heat stagnation blood aspect and a method. The preparation is made of, by weight ratio, 6-15% of stir-fried cape jasmine fruit, 6-15% of tree peony bark, 6-15% of raw rhubarb, 18-48% of lalang grass rhizome, 6-15% of polygonum aviculare, 6-15% of Japanese thistle herb or root, 6-15% of common cephalanoplos herb, 9-24% of radix rubiae, 18-48% of hairyvein agrimonia herb and bud, 6-15 parts of Chinese arborvitae twig, 6-15% of carbonized catnip and 4-10% of radix glycyrrhizae. According to the preparation, a boiling extraction method is adopted to extract active ingredients in the raw medicines and keep activities thereof, so that not only can the dissolution rate of the active ingredients inthe medicines be improved, but also the absorption to the medicines can be facilitated, thereby improving the biological utilization degree thereof. In addition, the medicine is a pure traditional Chinese medicine compound preparation, so a patient does not produce toxic and side effects after long-term use, and the safety is good. In addition, the preparation method has a simple process and is convenient to operate.

The present invention relates to method for pretreating a subject with severe von Willebrand disease prior to a surgical procedure comprising administering to the subject a dose ranging from about 20 IU / kg to about 60 IU / kg rVWF between about 12 hours and about 24 hours prior to the surgical procedure, and wherein Factor VIII is not administered with the rVWF prior to the surgical procedure.