11 results about "Clotting factors" patented technology

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 present application relates to the technical field of medicine, and provides a kind of haena polysaccharide and its preparation method and application and target endogenous coagulation pathway anticoagulant and / or antithrombotic drug.The haena polysaccharide provided by the present application is fucosylated chondroitin sulfate polysaccharide, the weight average molecular weight is 9-13 million, the molar ratio of glucuronic acid, N-acetylglucosamine and fucose is 1:0.8-1.2:0.5-0.8, and the mass percentage content of sulfate group is 25-40%.The haena polysaccharide provided by the present application can target endogenous coagulation pathway terminal rate-limiting enzyme (iFXase), and has no obvious effect on coagulation factors in other coagulation pathways, realizes the effect of anticoagulation and non-hemorrhage, and can be widely applied in acute and recovery period treatment of ischemic stroke, solves the safety problem of using anticoagulant and antithrombotic drug for clinical ischemic stroke patients, and opens up a new field of research and development of target endogenous coagulation pathway rate-limiting enzyme anticoagulant drug.

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.

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.

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.

This invention discloses an isolated anti-FXI and / or anti-FXIa antibody or its antigen-binding fragment, which specifically binds to human FXI or FXIa, and provides a drug targeting FXI that effectively prevents or treats thrombosis with minimal side effects to meet medical needs. Because currently approved anticoagulants interfere with hemostasis, leading to an increased risk of bleeding, there is a significant unmet medical need for safer anticoagulants. Although thrombosis can be treated or prevented with anticoagulants (e.g., heparin, warfarin, aspirin, or factor Xa inhibitors), these treatments have significant adverse effects. Genetic and pharmacological evidence in humans and animals suggests that lowering coagulation factor XI (FXI) can successfully prevent and manage thrombosis with minimal bleeding.

The present invention relates to monoclonal antibodies and antigen-binding fragments thereof that bind to human Factor XI and activated Factor XI ("Factor XIa"), as well as to pharmaceutical compositions and treatment methods comprising them.

The present invention relates to in vitro sialylated human factor H protein or biologically active sialylated fragments or biologically active sialylated variants thereof for use in treating paroxysmal nocturnal hemoglobinuria, for treating thromboinflammation, for treating pathological platelet aggregate formation for treating microangiopathy, and / or for treating Long COVID. Combination with a C5 inhibitor, e.g. eculizumab, is also envisaged.

This invention belongs to the field of biotechnology, and relates to an anticoagulant fusion protein HSA-Qinghaienin(c) and its encoding gene, as well as their applications. Specifically, it relates to the preparation of an anticoagulant fusion protein and its application in preventing in vivo thrombus formation and in the preparation of anticoagulant coating biomaterials. Compared with existing anticoagulant coatings, the anticoagulant coating on the material surface based on the anticoagulant fusion protein HSA-Qinghaienin(c) proposed in this invention exhibits significant advantages. Through the self-polymerization of polydopamine, the adhesion between the coating and the substrate material is greatly improved, ensuring the stability and durability of the coating. HSA in the anticoagulant fusion protein HSA-Qinghaienin(c) can inhibit the adsorption of plasma proteins and platelets, while Qinghaienin(c) targets FⅫ in the intrinsic coagulation pathway, inhibiting the activation of this coagulation factor without inducing the risk of bleeding. HSA-Qinghaienin(c) can play a "two birds with one stone" role in the anticoagulant function of biomaterials.