20 results about "Hemophilias" patented technology

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 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 invention relates to a gene therapy vehicle for use in preventing, arresting and / or treating hemophilic arthropathy of a joint in a patient having hemophilia B, where the gene therapy vehicle comprises a nucleic acid that encodes a coagulation factor having Factor IX activity.

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.

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.

The application provides a completely humanized anti-human blood coagulation factor IX monoclonal antibody or an antigen binding fragment thereof and application thereof. The antibody provided by the application has high affinity to human blood coagulation factor IX and significant inhibitory activity, and belongs to a neutralizing antibody, and has a good treatment prospect for thrombus diseases. The functional antibody is directly screened from blood plasma of hemophilia B patients by a mass spectrometry + de novo sequencing technology, and has the advantages of complete human origin, high safety and the like.

This invention provides a method for treating patients with bleeding disorders such as hemophilia. [Solution] The present invention relates to an iRNA, such as a double-stranded ribonucleic acid (dsRNA), composition that targets the Serpinc1 gene, and to a method of using such an iRNA, such as a dsRNA, composition to inhibit the expression of Serpinc1 and to treat subjects with Serpinc1-related diseases, such as bleeding disorders such as hemophilia.

Production was attempted for antibodies that neutralize the activity of a bispecific antibody having F.VIII function-substituting activity, for use in a method for measuring the reactivity of F.VIII in the presence of a bispecific antibody having F.VIII function-substituting activity. As a result, it was discovered that by using the produced antibodies, F.VIII activity in the plasma of a hemophilia A patient can be evaluated accurately by performing APTT-based one-stage clotting assay on a wide range of bispecific antibodies having F.VIII function-substituting activity. It was also discovered that F.VIII inhibitor titer in the plasma of a hemophilia A patient carrying F.VIII inhibitor can be evaluated accurately by APTT-based Bethesda assay.

Methods of accelerating clot formation and increasing clot deposition in a hemophiliac subject. A vagal nerve stimulator (VNS) may be implanted in a hemophiliac subject. The hemophiliac subject may have developed antibodies to factor VIII and not been administered a clotting factor within the last 48 hours. The vagus nerve of the subject may be stimulated in a manner that increases platelet intracellular calcium and / or activates splenic acetylcholine-synthesizing T lymphocytes using the implanted VNS.

This invention relates to a gene encoding coagulation factor IX. F9 This study investigates animal models of nonsense mutations, methods for screening hemophilia drugs using these models, and the application of the screened stRNAs in the preparation of hemophilia drugs. Based on an analysis of the probability of nonsense mutations in coagulation factor IX in hemophilia patients, the study verifies that stRNAs can read the coagulation factor IX encoding gene. F9 The function and efficiency of the premature termination codon (PTC) were investigated. Seven Arg-stRNAs were designed to target the coagulation factor IX R75* mutation, and readthrough efficiency was tested at the cellular level. A mouse model of the coagulation factor IX R75* mutation was constructed, and Arg-stRNA was delivered via AAV, restoring the expression of endogenous coagulation factor IX and reducing clotting time, demonstrating the effectiveness of stRNA in treating hemophilia B.

The present invention relates to methods and compositions for treating hemophilia, providing novel therapies using double-stranded oligonucleotide compounds to improve quality of life and joint function in patients with hemophilia A and hemophilia B.

The present invention generally relates to the use of bispecific FVIII mimic antibodies in the treatment of hemophilia, such as hemophilia A with or without inhibitors, and particularly to methods of treating the disease, such as dosage regimens and compositions used in such methods.

The present disclosure provides lentiviral vectors comprising a nucleic acid sequence encoding a polypeptide with factor IX (FIX) activity, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, wherein the lentiviral gene delivery enables stable integration of the transgene expression cassette into the genome of targeted cells (e.g., hepatocytes) of pediatric (e.g., neonatal) or adult subjects, achieving an improvement in FIX expression at low lentiviral vector doses. The present disclosure also provides methods of treating bleeding disorders such as hemophilia (e.g., hemophilia B) comprising administering to a subject in need thereof a liver-targeted lentiviral vector comprising a nucleic acid sequence encoding a polypeptide with FIX activity sequence at low dosages.

Disclosed herein are method of treating hemophilia A in a subject comprising injecting the subject with mesenchymal stromal / stem cells (MSC) modified to express high levels of Factor VIII protein. The MSC are isolated prenatally, at birth, or after the subject's birth. The modified MSC may also express high levels von Willebrand factor protein.

This invention discloses a method, targets, and applications for the diagnosis and treatment of hemophilic arthritis. The method includes: obtaining cartilage and synovial membrane samples from patients with hemophilic arthritis undergoing total knee arthroplasty; performing single-cell RNA sequencing, single-cell ATAC sequencing, and spatial transcriptomics analysis to determine the main cell types and key cell subpopulations constituting the microenvironment of hemophilic arthritis; identifying the molecular characteristics and differentiation processes of chondrocyte and synovial fibroblast subpopulations; measuring intercellular interactions in the knee joint microenvironment of the samples; and identifying specific regulatory transcription factors in hemophilic arthritis through paired epigenetic analysis to identify diagnostic and therapeutic targets for hemophilic arthritis. This method integrates single-cell multi-omics analysis to analyze the cellular characteristics of synovial and cartilage tissues and their interactions in the epigenetic pathogenic mechanism, identifying potential therapeutic targets.