32 results about "Factor VIII vWF" patented technology

We provide new monoclonal antibody inhibitors of coagulases, staphylocoagulase (“SC”) and von Willebrand factor-binding protein (“vWbp”) for treatment of S. aureus. The monoclonal antibodies are useful in targeting the SC N-terminus of SC and vWbp (respectively) and inhibiting prothrombin activation. The monoclonal antibodies are able to bind to and interfere with, modulate, and / or inhibit the binding interactions between the coagulase protein and its ligan protein prothrombin the activation of prothrombin.

The invention belongs to the technical field of medicines, and discloses application of pantethine in preparation of medicines for preventing and / or treating thrombotic diseases or medicines for inhibiting platelet activation or regulating vascular endothelial cell functions. In-vivo and in-vitro experiments prove that pantethine can remarkably relieve thrombus load in a mouse thrombus model, down-regulate expression of vWF (von Willebrand Factor), up-regulate expression of TFPI (Tissue Factor Path Inhibitor) and TH BD (Thromboregulatory Protein), and antagonize platelet adhesion, aggregation and activation induced by a platelet activator. The action mechanism is closely related to inhibition of reactive oxygen species (ROS) generation and NF-kappa B signal channel activation, and improvement of endothelial cell functions. It can be known from the invention that pantethine plays an antithrombotic role from multiple aspects, and is suitable for preparation of antithrombotic drugs for prevention or treatment. The invention provides a new drug choice for prevention and treatment of thrombotic diseases.

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 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.

A method comprising the steps of: (a) assessing an expression level of at least one protein, selected from Table 1, 2 or 3 in a sample from a subject, where in the at least one protein may be selected from the list comprising: Beta-Ala-His dipeptidase, Apolipoprotein L1, Methanethiol oxidase, Vitamin K-dependent protein S, von Willebrand factor, Plasminogen, Selenoprotein P, Protein disulfide-isomerase A6 and Inter-alpha-trypsin inhibitor heavy chain H3, and (b) using the expression level to determine whether the subject has endometriosis.

Various aspects of the invention relate to recombinant polypeptides that specifically bind human von Willebrand Factor. Such recombinant polypeptides typically include a modified extracellular domain of platelet glycoprotein lbα that typically comprises at least one mutation selected from G233T, D235V, and K237V, and such recombinant polypeptides optionally include an oligomerization domain.

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.

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 herein are antibodies, compositions, and methods of use thereof. The disclosed antibodies bind to von Willebrand factor in blood plasma of a subject. Such antibodies are useful for methods of treatment, such methods of treating one or more blood disorders characterized by excessive bleeding. Also provided herein are methods of treating blood disorders by administering a combination of an anti-VWF antibody and von Willebrand Factor.

The invention relates to the technical field of biological pharmacy, and discloses a high-purity and high-activity von willebrand factor preparation process which comprises the following steps: S1, carrying out gradient centrifugal treatment on fresh plasma, namely selecting the fresh plasma, carrying out centrifugal treatment, and collecting secondary supernate rich in von willebrand factors; the collected secondary supernatant passes through an immunoaffinity chromatography column coupled with an anti-von willebrand factor antibody, S3, mild elution and ultrafiltration concentration, S4, gel filtration chromatography secondary purification, and S5, protective agent addition and preparation forming. According to the method, the rotating speed and time of secondary centrifugation are dynamically adjusted by combining protein concentration and turbidity through a centrifugal parameter self-adaptive optimization algorithm, impure protein precipitation is reduced, the relative content of vWF in secondary supernate is increased by 15%-20%, then two-stage purification of specific monoclonal antibody affinity chromatography and gel filtration chromatography is carried out, the purity of vWF is stabilized at 98.2%-98.6%, the difference between batches is smaller than or equal to 2.4%, and the quality of vWF is improved. The process is obviously superior to the traditional process.

The present invention relates to the use of a polypeptide comprising a truncated von Willebrand factor (VWF) for improving the in vitro stability of coagulation factor VIII (FVIII) in a composition, wherein the composition comprises FVIII and the polypeptide, and the molar ratio of the polypeptide to FVIII in the composition is greater than 20.

This disclosure relates to a novel assay for the platelet binding activity of the Von Willebrand factor. The assay uses polypeptides comprising an immunoglobulin single variable domain that specifically binds an autoinhibitory module on the C terminal end or on the N terminal end of von Willebrand Factor (VWF) A1 domain or the von Willebrand Factor (VWF) A1 domain.

The present invention relates to a fusion protein comprising a factor VIII (FVIII) heavy chain, an FVIII light chain, a von Willebrand factor (VWF) fragment, and at least two copies of an extended peptide (EP), wherein the EP has at least 90% amino acid sequence identity with SEQ ID NO: 1 and further comprises a cluster of O-glycosylation sites, each cluster containing at least two O-glycosylated amino acids. This complex exhibits improved pharmacokinetic properties compared to FVIII. The present invention further relates to a polynucleotide encoding the fusion protein, as well as a vector and host cell containing the polynucleotide.

To provide Factor VIII complex comprising XTEN and von Willebrand factor protein and uses thereof.SOLUTION: The invention discloses a chimeric protein comprising a VWF protein with D' domain and D3 domain of VWF, at least one XTEN sequence and a FVIII protein, where the VWF fragment, the XTEN sequence or the FVIII protein are linked or associated with each other. The chimeric protein may comprise further one or more Ig constant region or a part thereof (e.g., Fc region).SELECTED DRAWING: None

The disclosure provides a method for treating and / or preventing graft rejection with A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member-13 (ADAMT S13). The disclosure provides a method for increasing ADAMTS13-mediated von Willebrand factor (VWF) cleavage in a subject that received a graft by administering ADAMTS13. The disclosure also provides a method of determining the likelihood that a subject will rejection a graft.

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.

The invention provides a method of detecting or predicting a relapse of multiple sclerosis in an individual having a form of multiple sclerosis, comprising: (a) providing a blood sample of the individual; (b) testing the blood sample to determine a protein activity or protein level, wherein the protein is Factor VIII, von Willebrand Factor, or Protein C; and (c) detecting or predicting a relapse of multiple sclerosis in the individual if the protein activity or protein level is elevated compared to the protein activity or protein level in an individual not having the form of multiple sclerosis and the patient's own baseline value. The invention also provides a method of treating an individual having multiple sclerosis who is experiencing a relapse or is predicted to experience a relapse, comprising treating the individual by administering a dose of a steroid or an anticoagulant compound effective to reduce symptoms of multiple sclerosis.

Methods for using lumacaftor or a pharmaceutically acceptable salt thereof for treating thrombosis and for restoring the autoinhibitory function of von Willebrand factor (VWF) under pro-thrombotic inflammatory conditions while maintaining hemostasis.

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.

The present invention relates to single antibody domains, especially single antibody domains that specifically bind plasmin-cleaved von Willebrand factor (VWF). The invention further relates a method for detecting plasmin-cleaved VWF. This method further allows for the determining the activity of a therapeutic agent regulating plasmin-mediated cleavage of VWF, or the determination of a vascular event in a subject. The invention further describes kits comprising these single antibody domains.

Provided herein are antibodies, compositions, and methods of use thereof. The disclosed antibodies bind to a von Willebrand factor in the plasma of a subject. Such antibodies are useful in methods of treatment, such as methods of treating one or more blood conditions characterized by excessive bleeding.

Methods of diagnosing and monitoring liver diseases are disclosed. The method includes measuring in a blood sample of the subject an amount of Von Willebrand factor (VWF) and at least one protein biomarker selected from the group consisting of sulfhydryl oxidase 1 (QSOX1), complement component C7 (C7), intercellular adhesion molecule- 1 (ICAM) and platelet glycoprotein V (GP5). Kits for diagnosing and monitoring are also disclosed.

Described herein are compositions and polypeptides comprising a collagen-binding peptide (CBP) and a von Willebrand factor binding peptide (VBP), as well as methods of use thereof.

The present invention provides VWF protective agents, including aptamers and antibodies for the treatment and or amelioration of complications or disorders arising from aberrant binding or function of VWF.

The invention relates to a monoclonal antibody with a von Willebrand factor (VWF) resisting effect and application of the monoclonal antibody with the von Willebrand factor (VWF) resisting effect. The monoclonal antibody or antigen binding fragment drug combination with the anti-von willebrand factor effect can be applied to reduction of the VWF level in vivo; therefore, thrombotic microvascular diseases (including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome and atypical hemolytic uremic syndrome), cardiovascular diseases, stroke, atherosclerosis, Alzheimer's disease, vascular dementia and bacterial and viral infectious diseases caused by various reasons can be prevented and treated.

The invention relates to a von willebrand factor lyase 13 activity detection kit and preparation and application thereof. The detection method is a magnetic particle chemiluminescence immunoassay method, and the kit comprises a reagent M, a reagent R1 and a reagent R2. The reagent M is a magnetic particle coated with an antibody and is combined with one end of the VWF substrate protein in the reaction, and the coated antibody is an anti-MBP tag antibody; the reagent R1 contains a VWF73 substrate protein, one end of the protein contains an MBP label, the other end of the protein contains a His label, and the protein can be respectively combined with antibodies with the two labels to form a sandwich compound; the reagent R2 is an enzyme-labeled antibody reagent, and an enzyme-labeled antibody is an anti-His label antibody. According to the present disclosure, high-speed and high-sensitivity detection is achieved, and the diagnosis and monitoring of thrombotic thrombocytopenic purpura (TTP) are facilitated.

The present invention relates to a fusion protein including: a mutant ADAMTS13 that contains at least a metalloprotease domain (M domain) and is missing a spacer domain (S domain); and antigen-binding molecules that bind to a von Willebrand factor (vWF). The mutant ADAMTS13 is preferably one satisfying to (N1) or (N2). (N1) In addition to a S domain, T2-T8 domains are also missing from the ADAMTS13. (N2) In addition to a S domain, T2-T8 domains and a CUB1-2 domain are also deleted from the ADAMTS13.

The current invention relates to a polypeptide comprising a truncated form of ADAMTS13 and an immunoglobulin targeting agent, wherein the targeting agent is able to bind to a von Willebrand factor (VWF) via a VWF-binding domain at a site of a thrombus.

A protease-resistant ADAMTS13 mutant protein or nucleic acid encoding the ADAMTS13 mutant protein is provided. The ADAMTS13 mutant protein comprises a mammalian ADAMTS13 protein in which one or more protease cleavage sites within the protein are replaced with amino acid sequence that is resistant to protease cleavage, and the mutant protein retains von Willebrand factor (VWF)-cleaving activity. The protease-resistant ADAMTS13 mutant is useful as a thrombolytic agent to treat common thrombotic disorders, including stroke, myocardial infarction, venous thromboembolism, and rare microvascular thrombotic disorders like thrombotic thrombocytopenia purpura (TTP).