103 results about "Hemophilias" patented technology

The invention relates to pharmaceutical compositions comprising an iRNA agent, e.g., double stranded ribonucleic acid (dsRNA) agent and methods of using such compositions to treat a bleeding event in a subject having a hemophilia (e.g., with or without inhibitors).

Disclosed are systems and methods for building and using a machine-learning model to facilitate intelligent selection of treatment strategies for subjects suffering from hemophilia. Sensor data (e.g., that characterizes movement of or a physiological characteristic of particular a subject) can be used as an input to a machine-learning model workflow. The sensor data may affect a model selection, model configuration, model result, pre-processing and / or post-processing. A result of the workflow may inform or influence a treatment selection, treatment schedule, treatment dosage and / or activity recommendation for the particular subject.

The invention relates to the field of biological medicines, in particular to application of an SR604 injection to preparation of a medicine for preventing and / or treating hemorrhagic diseases. The SR604 injection provided by the invention contains an SR604 antibody, and the injection dosage of the SR604 antibody in the SR604 injection is selected from 0.025 mg / kg to 0.8 mg / kg. The injection provided by the invention can be used for preventing and / or treating hemorrhagic diseases, the number of hemorrhagic events and the annual hemorrhagic rate of a patient are remarkably reduced by controlling the injection dosage and the injection frequency, and the injection has a relatively good treatment effect on hemophilia A, hemophilia B and congenital blood coagulation factor VII deficiency.

To provide FVIII drugs with increased in vivo half-life while retaining sufficient biological activity, and prevention methods for hemophilia subjects.SOLUTION: The invention provides a conjugate comprising recombinant FVIII (rFVIII) and a zwitterionic polymer, where the polymer comprises one or more monomer units and where at least one monomer unit comprises a zwitterionic group. Optionally, the zwitterionic group comprises phosphorylcholine. In some conjugates, the polymer is covalently bonded to at least one of an amino group, a hydroxyl group, a sulfhydryl group and a carboxyl group of rFVIII.SELECTED DRAWING: Figure 2

Variants of coagulation factor VIII (FVIII) and expression cassettes encoding the FVIII variants thereof are described. A variant FVIII includes a glycoepitope of the FVIII protein including an N2118Q mutation. The N2118Q mutation can be combined with other mutations including a BDD-FVIII, N6, V3, RH, furin-cleavage site deletion. X10, K12, and / or F309S mutation to form additional FVIII variants. The FVIII variants with the N2118Q mutation and expression cassettes thereof can result in reduced immunogenicity of the resulting protein. When combined with other FVIII mutations, higher gene expression, increased secretion, increased stability, and higher FVIII functional activity can be achieved by the expressed FVIII variants. The variant FVIII and expression cassettes described here can be useful in protein replacement therapy and / or gene therapy for the treatment of hemophilia A.

The invention discloses a long-fragment PCR (Polymerase Chain Reaction) amplification reaction solution and application thereof. The PCR amplification reaction solution is composed of a 2XPCR buffer solution, dNTP, LA Taq enzyme, betaine and distilled water. In the PCR amplification reaction liquid, the volumes of the 2XPCR buffer solution, the dNTP, the LA Taq enzyme, the betaine and the distilled water in the total volume of 25l are respectively 12.5 l, 5.0 l, 0.25 l, 4.0 l and 0.45 l. According to the present invention, the PCR amplification reaction liquid can effectively amplify the long fragment PCR product, the product amplification with the longest detection reaching 12 kb can be used for the detection of the hemophilia A intron 22 inversion, the effective amplification reagent is provided for the long fragment PCR amplification, and the problem of difficult long fragment amplification is solved.

The application discloses a liver-targeted gene editing system based on endogenous promoter hijacking and application, and belongs to the field of biological medicine. The system is composed of an LNP-wrapped modified Cas nuclease mRNA (first component) and a promoter-free viral vector carrying a therapeutic transgene donor (second component). The system uses LNP to realize the transient burst expression of Cas nuclease in the liver, mediates the generation of double-strand breaks at the site of endogenous high-expression genes, induces the site-specific integration of therapeutic transgenes without exogenous promoters, and hijacks the expression driven by endogenous promoters by using the splice acceptor (SA) mechanism. The application solves the risk of carcinogenesis caused by random integration of exogenous strong promoters and the immunotoxicity of long-term expression of nucleases through a "double safety lock" design. Experimental results prove that the system has high editing efficiency, long-term stability and no off-target, and can be used for various liver-derived metabolic diseases such as hemophilia, hypercholesterolemia and the like.

To provide a composition useful for the prevention, inhibition and / or treatment of hemophilic arthropathy of joints in patients with hemophilia B.SOLUTION: A gene therapy vehicle comprising a nucleic acid encoding a coagulation factor having Factor IX activity is provided.SELECTED DRAWING: None

The present disclosure is concerned with piperidinedione compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders associated with the presence of a premature termination codon such as, for example, cystic fibrosis, Duchenne muscular dystrophy, aniridia, Becker muscular dystrophy, spinal muscular atrophy, Hurler syndrome, hemophilia, epidermolysis bullosa (e.g., dystrophic (DEB) form, junctional (JEB) form). Usher syndrome, and cancer, using the compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

To provide a method for treating reversible hemophilic arthropathy of a joint in a human having hemophilia.SOLUTION: Uses of a chimeric protein or composition comprising a coagulation factor and an Fc region are provided. The coagulation factor is selected from the group consisting of Factor VII (FVII), Factor VIIa (FVIIa), Factor VIII (FVIII), Factor IX (FIX), Factor X (FX), von Willebrand Factor (VWF), an antigen-binding portion thereof that specifically binds to FIX and FX, or any combination thereof.SELECTED DRAWING: None

The present invention relates to the field of medicine and hematology, and provides compositions and methods for modulating Factor VIII function. In particular, the present invention provides novel factor VIII variants, compositions comprising the variants, nucleic acid molecules encoding the variants, expression vectors comprising the nucleic acid molecules, and host cells comprising the vectors. The present invention also provides methods of using the variants and / or compositions to modulate the coagulation cascade in a patient in need thereof for the treatment of diseases including, but not limited to, hemophilia, particularly hemophilia A.

Modified human factor VIII polypeptides with enhanced factor VIII activity are described. In some embodiments, the modified human factor VIII polypeptides comprise one or more amino acid substitutions at positions A20, T21, F57, L69, I80, L178, R199, H212, I215, R269, I310, L318, S332, R378, I610 and / or I661. Such polypeptides and viral vectors encoding such polypeptides may be used for treatment of FVIII deficiencies, such as hemophilia A.

The present application relates to devices and methods for determining a drug administration regimen for a subject. Determining an administration regimen for a subject comprises calculating an amount of drug that needs to be administered to the subject per a base period, and determining and evaluating a combination of at least two dosage forms that can be used to administer the amount of drug against at least two different criteria. The methods of the present application can be used to select an administration regimen for a drug that is available in a plurality of dosage forms, especially a drug that is administered on a long-term daily basis, such as in the daily prophylaxis of hemophilia.

The present invention relates to a class of monoclonal antibodies having anti–von Willebrand factor (VWF) effects, and a use thereof. A pharmaceutical composition of the monoclonal antibodies or antigen-binding fragments having anti–von Willebrand factor effects provided by the present invention can be used to reduce VWF levels in the body, thereby preventing and treating thrombotic microangiopathies having various causes (including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, and atypical hemolytic-uremic syndrome), cardiovascular disease, stroke, atherosclerosis, senile dementia, vascular dementia, and bacterial and viral infectious diseases.

The invention relates to the technical field of diabetic hypoglycemia, and discloses a diabetic hypoglycemia response induced vascular injury biomarker which is a combination of high-sensitivity C reactive protein, 8-isoprostaglandin F2alpha, von willebrand factor, free fatty acid and D-dimer. The invention further discloses application of the diabetic hypoglycemic response induced vascular injury biomarker in preparation of a reagent for early auxiliary diagnosis of diabetic hypoglycemic response induced vascular injury. According to the invention, a combination of high-sensitivity C-reactive protein, 8-isoprostaglandin F2alpha, von willebrand factor, free fatty acid and D-dimer is used as a vascular injury biomarker induced by diabetes mellitus hypoglycemia response; acute vascular dysfunction, cardiovascular system injury, microvascular complications and atherosclerosis can be effectively diagnosed, diabetic vasculopathy can be found at an early stage, disease progression can be predicted, and clinical treatment can be guided; the sensitivity and the specificity are high.

Various embodiments of the invention utilize chalcones to treat blood, bleeding, and / or bleeding disorders. As described herein, chalcones significantly reduce blood clotting time in normal / hemophilic blood and normal / hemophilic animal models. As also described herein, chalcones reduce blood clotting time and increase blood clotting efficiency without any apparent risk of immunogenicity or unwanted blood clots. As also described herein, chalcones reduce the inhibitory activity of antithrombin on thrombin-driven blood clotting, thereby increasing the effectiveness of the thrombin mechanism in clotting blood.

The invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D′D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also relates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D′D3 domain.

A pharmaceutical composition comprising blood coagulation factor X for use in the treatment of a subject having hemophilia type A is provided. The present invention relates to a pharmaceutical composition, which is a pharmaceutical composition comprising blood coagulation factor X for use in the treatment of a subject having hemophilia type A wherein the blood coagulation factor X is used in combination with a bispecific antibody that binds to activated blood coagulation factor IX and blood coagulation factor X.

The present invention provides a formulation of a Factor VIII polypeptide, e.g., FVIII-Fc, and methods of using the same. The FVIII polypeptide can be a recombinant FVIII protein, a short-acting FVIII protein, or a long-acting FVIII protein. The pharmaceutical formulation comprising a FVIII polypeptide can be used for individual prophylaxis, weekly prophylaxis, episodic (on-demand) treatment, or perioperative management of hemophilia.

This disclosure provides a method for estimating the bleeding risk of a person with hemophilia A, as well as a computer-based system that includes and implements an Repeat Time to Event (RTTE) model.

Devices and methods for reducing or limiting bleeding in an animal by stimulating the spleen with focused ultrasound (FUS). The devices and methods can be used to treat blood disorders such as hemophilia, or to reduce bleeding during surgery or due to trauma. The methods can be administered to a patient non-invasively by applying ultrasound energy transcutaneously.

The invention relates to an F base modified von Willebrand factor vWF targeting aptamer and an application of the F base modified von Willebrand factor vWF targeting aptamer. Specifically, the invention provides an F base modified vWF targeting aptamer (AF-BT100), the F base modified vWF targeting aptamer comprises a nucleotide core sequence as shown in SEQ ID NO: 1, and the 5'end and the 3 'end are respectively connected with at least two artificial hydrophobic F bases. The invention also comprises a radionuclide-labeled molecular imaging probe [68Ga] Ga-NOTA-AF-BT100, which can realize specific PET imaging in the focus of atherosclerosis, carotid artery thrombosis and acute myocardial infarction. According to the invention, the integrated application of diagnosis and treatment of the pantovascular diseases based on the same vWF targeting aptamer is realized for the first time, and a new strategy is provided for accurate diagnosis and treatment of the pantovascular diseases.

The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains, in particular immunoglobulin single variable domains directed against von Willebrand Factor (vWF).The invention provides formulations which are stable upon storage for prolonged periods of time and over a broad range of temperatures. The formulations of the invention ensure a high stability of the polypeptide, allowing multiple freeze-thaw cycles without chemical or physical deterioration, and provide stability in relation to mechanical stress, such as shake, shear or stir stress. They are suitable for pharmaceutical and diagnostic preparations and compatible with pharmaceutically acceptable diluents.

Provided are the compositions (e.g., pharmaceutical compositions) of coagulation factor X activator (FX activator, e.g., RVV-X) comprising sucrose, histidine, polysorbate 20, and mannitol, and uses of FX activators (e.g., RVV-X) or compositions (e.g., pharmaceutical compositions) thereof for treating a bleeding disorder (e.g., hemophilia) in an individual (e.g., human).

The present disclosure is concerned with substituted uracil compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders associated with the presence of a premature termination codon such as, for example, cystic fibrosis, Duchenne muscular dystrophy, aniridia, Becker muscular dystrophy, spinal muscular atrophy, Hurler syndrome, hemophilia, epidermolysis bullosa (e.g., dystrophic (DEB) form, junctional (JEB) form), Usher syndrome, and cancer, using the compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The invention relates to the technical field of drug delivery systems, in particular to an FVIII ice microneedle as well as a preparation method and application thereof. The preparation method comprises the following steps: providing a mold with a microneedle cavity; a medicine solution containing FVIII is injected into the microneedle cavity of the mold; and freezing the mold into which the medicine solution is injected, so that the medicine solution is solidified and formed in the cavity of the micro-needle, and the FVIII ice micro-needle is obtained. The invention systematically solves a series of problems of easy activity loss, low delivery efficiency, inconvenience in use and the like in transdermal delivery of FVIII protein through a core technical concept of low-temperature freezing forming, and provides a novel hemophilia A treatment dosage form which is high in activity retention rate, safe and convenient to use and suitable for large-scale production.

Provided herein are desmopressin oral liquid formulations. Also provided herein are methods of making and using desmopressin oral liquid compositions for the treatment of certain diseases including diabetes insipidus, enuresis, hemophilia A, von willebrand disease, high blood urea levels and others.