157 results about "Hemophilias" patented technology

The present invention provides codon optimized Factor IX sequences, vectors and host cells comprising codon optimized Factor IX sequences, polypeptides encoded by codon optimized Factor IX sequences, and methods of producing such polypeptides. The present invention also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor IX nucleic acid sequence or the polypeptide encoded thereby.

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.

The present disclosure provides, inter alia, methods for treating hemophilia A as well as computer-based-systems, including software-based pharmacokinetic model systems, and their use to determine dosing information for subjects who have hemophilia A.

The invention relates to the field of monoclonal antibodies, in particular to a von Willebrand factor cleavage protease (ADAMTS13) monoclonal antibody as well as a preparation method and application thereof. The ADAMTS13 monoclonal antibody provided by the invention is high in sensitivity and strong in affinity and can effectively inhibit ADAMTS13 enzyme activity, in addition, the invention also develops an in-vitro diagnosis detection kit applying the antibody, and the kit has the advantages of wide detection range, few interfering substances, short detection time and good stability and repeatability. And a new thought is provided for treatment and research of diseases.

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

The invention provides a dual-signal peptide, the dual-signal peptide comprises a first signal peptide and a second signal peptide, the first signal peptide comprises an exogenous signal peptide, the second signal peptide comprises an endogenous signal peptide of a blood coagulation factor VIII, and the first signal peptide and the second signal peptide are connected in series. According to the dual-signal peptide, the secretion effect and the blood coagulation activity of the blood coagulation factor VIII are substantially improved, the production of FVIII can be greatly improved, the industrial production efficiency of FVIII is improved, the application of FVIII in hemophilia treatment drugs is further promoted, and the treatment cost is reduced.

The present invention provides: a codon-optimized polynucleotide encoding factor IX (FIX); a recombinant AAV-producing plasmid comprising the polynucleotide; a recombinant AAV produced by the plasmid; and use of the recombinant AAV for treating hemophilia B. The plasmid comprising the polynucleotide can produce a recombinant AVV that exhibits high FIX expression and activity and has excellent productivity and high quality.

Embodiments provide devices, preparations and methods for delivering therapeutic agents (TAs) such as clotting factors (CFs, e.g., Factor 8) within the GI tract. Many embodiments provide a swallowable device e.g., a capsule for delivering TAs into the intestinal wall (IW). Embodiments also provide TA preparations configured to be contained within the capsule, advanced from the capsule into the IW and / or surrounding tissue (ST) and degrade to release the TA into the bloodstream to produce a therapeutic effect (e.g., improved clotting). The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW or ST (e.g., the peritoneal cavity). Embodiments are particularly useful for delivery of CFs for treatment of clotting disorders (e.g., hemophilia) where such CFs are poorly absorbed and / or degraded within the GI tract.

The present disclosure provides methods treating reversible hemophilic arthropathy of a joint in a human having hemophilia comprising administering to the human an effective amount of a chimeric protein or composition comprising a clotting factor and an Fc region.

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.

The present invention relates to methods of increasing hemoglobin in an individual suffering from severe hemophilia A by prophylactic administration of emicizumab. Pharmaceutical compositions comprising emicizumab are also provided.

The present invention relates to single domain antibodies (sdAbs) against TREM (triggering receptors expressed on myeloid cells) like transcript-1 (TLT-1) molecules that are present on activated platelets at the site of an injury, and especially on a subset of activated platelets, coated platelets. Furthermore, the present invention relates to fusion proteins comprising sdAbs against TLT-1 and an extracellular (soluble) domain of tissue factor (sTF), to direct targeting of such fusion proteins to activated platelets at the site of injury through binding of the sdAbs to TLT-1, a membrane protein receptor that is only present on activated platelets. Specific interaction of sdAbs with the TLT-1 receptor positions the sTF domain of the fusion to interact with, and activate, FVII. As a result, a targeted procoagulant effect is achieved at the site of injury via activated platelets. The fusion proteins are useful to treat individuals that have a bleeding disorder, such as hemophilia A, hemophilia B, or acute bleeding due to traumatic injury.

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.

The invention provides a recombinant blood coagulation factor VIII preparation and a preparation method and application thereof, and belongs to the field of biological medicine. The recombinant blood coagulation factor VIII preparation provided by the invention is prepared from the following components: 500 to 1500 IU / mL of recombinant blood coagulation factor VIII, 20 to 100 mM of glycine, 50 to 100 mM of raffinose, 2 to 10 mM of divalent calcium salt, 0.5 to 5 percent of dextran-40 and 0.05 to 0.15 percent of tween-80, the preparation is simple in component, so that the recombinant blood coagulation factor VIII is long in preservation time and stable in activity, and can be used for preparing drugs for treating hemophilia.

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 disclosure provides, inter alia, methods for treating hemophilia A, as well as computer-based systems including a software-based pharmacokinetic model system, and uses thereof for determining agent information for a subject suffering from hemophilia A.

Provided are the polypeptide variants of the human factor VIII and polynucleotide sequences encoding the same optimized for gene therapy. Also provided are recombinant adeno-associated virus vectors for delivering the polypeptide variants and methods for treating type A hemophilia by using the said vectors.

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.