47 results about "Factor VIII vWF" patented technology

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.

Provided herein are antibodies that bind to von Willebrand factor to an epitope positioned at a cysteine knot (CK) domain. Such antibodies are useful for methods of treatment, such methods of treating one or more blood disorders characterized by excessive bleeding.

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.

A recombinant von Willebrand Factor (VWF) protein comprising one or more mutations and uses thereof are described. A recombinant protein complex comprising a von Willebrand factor sequence and one artificial Factor VIII sequence is described. A recombinant protein complex comprising a Factor VIII sequence and one artificial von Willebrand sequence is described. A recombinant protein complex is described that includes one artificial von Willebrand factor sequence and one artificial Factor VIII sequence. Also described are nucleic acid sequences and a vector encoding a VWF sequence and a pharmaceutical composition for inducing blood clotting that includes a VWF protein.

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.

To provide a glycosylated von Willebrand factor (VWF) fusion protein with improved pharmacokinetics.SOLUTION: The invention relates to a fusion protein comprising a main protein and one or more extension peptides, wherein the amino acid sequence of the main protein is identical or similar to the amino acid sequence of a mammalian protein or a fragment thereof, and the extension peptide comprises a cluster of O-glycosylated amino acids. The main protein is preferably VWF. The fusion protein has an increased half life as compared to the main protein and may be used to increase the half-life of a binding partner, e.g. FVIII. The invention further relates to a complex formed by the fusion protein, a polynucleotide encoding the fusion protein as well as a vector and host cell comprising the polynucleotide.SELECTED DRAWING: Figure 1

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 invention relates to a fusion protein comprising: a Factor VIII (FVIII) heavy chain; an FVIII light chain; a fragment of von Willebrand Factor (VWF); and at least two copies of an extension peptide (EP); wherein the EP has at least 90 % amino acid sequence identity to SEQ ID NO: 1 and contains a cluster of O-glycosylation sites, wherein the cluster contains at least two O-glycosylated amino acids. The complex shows improved pharmacokinetic properties in comparison to FVIII. The invention further relates to a polynucleotide encoding the fusion protein as well as a vector and host cell comprising the polynucleotide.

To provide an FVIII formulation requiring less frequent administration, i.e., an FVIII formulation with a half-life longer than 1.5 to 2 times the half-life limitation.SOLUTION: The present invention provides a chimeric protein comprising (i) a first polypeptide which comprises FVIII fused to a first immunoglobulin (Ig) constant region or a portion thereof and (ii) a second polypeptide which comprises a von Willebrand factor (VWF) protein comprising a D' domain and a D3 domain of VWF fused to a second Ig constant region or a portion thereof by an XTEN sequence in between, where the XTEN sequence contains less than 288 amino acid residues, and where the first polypeptide is linked to or associated with the second polypeptide. Certain embodiments include the chimeric protein as described herein, where the XTEN sequence in the second polypeptide consists of an amino acid sequence having a length between 12 amino acids and 287 amino acids.SELECTED DRAWING: Figure 1

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.

The present invention relates to the field of monoclonal antibodies. Specifically, the present invention relates to a monoclonal antibody against von Willebrand factor-cleaving protease (ADAMTS13), a preparation method thereof, and an application thereof. The ADAMTS13 monoclonal antibody provided by the present invention has high sensitivity and strong affinity, and can effectively inhibit the enzyme activity of ADAMTS13. In addition, the present invention also develops an in vitro diagnostic detection kit using this antibody. The kit has the advantages of a wide detection range, few interfering substances, a short detection time, good stability and repeatability, providing new ideas for the treatment and research of diseases.

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.

[Problem] To provide: a method for identifying a new depression marker and assisting determination of depression on the basis of the depression marker; and diagnosis kit for depression based on the depression marker. [Solution] This method for assisting the determination of depression is characterized by including a step for measuring the amount of von Willebrand factor present in extracellular vesicles in a biological sample collected from a subject and comparing the measured amount with a predetermined value.

The present invention concerns clusterin for use in the treatment of thrombotic microangiopathies, and a pharmaceutical composition comprising clusterin for use in the treatment of thrombotic microangiopathies, said composition not comprising von Willebrand factor protease. The present invention also concerns an ex vivo method for stratifying a patient suffering, or likely to be suffering, from TMA, comprising the following steps: 1) measuring, in a biological sample from said patient, the amount LC of clusterin, and 2) comparing the amount Lc measured in step 1) with an amount Lref of clusterin by calculating the score S1=LC / Lref, in which: •If S1≤1, the patient is considered to be likely to benefit from a treatment of the TMA with clusterin, •If S1>1, the patient is not considered to be likely to benefit from treatment of TMA with clusterin.

The present invention is based on the finding that administration of polypeptides comprising at least one immunoglobulin single variable domains against vWF to human TTP patients provides a significant decrease in the time to response. The invention provides a polypeptide comprising at least one immunoglobulin single variable domain (ISVD) against von Willebrand Factor (vWF) for use in treating a vWF-related disease in a human in need thereof. The invention further relates to dosage unit forms, kits and medical uses for treating TTP.

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.