16 results about "ADAMTS13" patented technology

The invention relates to the technical field of biological medicine, in particular to application of ADAMTS13 to occlusive cardiovascular and cerebrovascular diseases. On one hand, the invention provides the biomarker ADAMTS13 for establishing the collateral circulation of the patient suffering from the occlusive cardiovascular and cerebrovascular diseases, and the biomarker ADAMTS13 can be used as a target spot for diagnosing, preventing and treating the occlusive cardiovascular and cerebrovascular diseases and can effectively predict the establishment of the collateral circulation of the patient suffering from the occlusive cardiovascular and cerebrovascular diseases and prevent the development of adverse cardiovascular events; the method has important value on clinical cardiovascular events, and can improve the survival rate of patients with occlusive vascular diseases and improve long-term prognosis; on the other hand, the invention provides an ADAMTS13 recombinant protein, the amino acid sequence of which is as shown in SEQ ID No: 1, and the ADAMTS13 recombinant protein can improve the proliferation, migration, invasion and tube forming capabilities of endothelial cells, and has important clinical application value for developing drugs for preventing and / or treating occlusive cardiovascular and cerebrovascular diseases.

The invention discloses a novel pathogenic mechanism of immune thrombocytopenic purpura (iTTP), and provides a product for precise diagnosis and targeted therapy of the iTTP based on the mechanism. Specifically, the invention relates to an allosteric defect type ADAMTS13 binding molecule based on VH1-69 spectrum antibody 4-20 and key residue E59 mutation of ADADTS13 Spacer domain, and a stable mutation ADAMTS13 protein mutant introduced into G491 and allosteric pathway residues, and through long-range conformation conduction of a 4-20 antibody and a Spacer-Cys interface and E59 side chain volume regulation and control, allosteric inhibition of an autoantibody on ADAMTS13 is realized, and the enzyme activity recovery rate is improved. The problem that in the prior art, antibody-mediated ADAMTS13 function inhibition is difficult to reverse is solved, and the method is suitable for precise diagnosis and targeted therapy of iTTP patients.

Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange / hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration / diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.

Disclosed are methods and systems for the analysis activity of enzyme disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in a sample. The methods and systems disclosed herein can be useful for diagnosis of thrombotic thrombocytopenic purpura in a patient.

The present application relates to the field of antibodies, in particular, the present application relates to a kind of antibody for ADAMTS-13 detection and its application.The ADAMTS13 monoclonal antibody provided by the present application, the light chain sequence of the monoclonal antibody includes CDR1 shown as SEQ ID NO.3, CDR2 shown as SEQ ID NO:4, CDR3 shown as SEQ ID NO:5;Heavy chain sequence includes CDR1 shown as SEQ ID NO:6, CDR2 shown as SEQ ID NO:7 and CDR3 shown as SEQ ID NO:8.In addition, the present application also provides detection kit comprising the monoclonal antibody, which can effectively detect the presence and / or content of ADAMTS13 in biological sample.

The present invention provides gene therapy plasmids and transgenes comprising a variant of ADAMTS13, recombinant virus vectors for delivery of said viral plasmids and transgenes and medical uses relating to the treatment of ADAMTS13 insufficiency.

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 application relates to the field of biomedical technology, in particular to a substrate modified peptide for detecting ADAMTS13 enzyme activity and a detection method and application. The application provides a substrate modified peptide for detecting ADAMTS13 enzyme activity, the amino acid sequence of the substrate modified peptide is shown as SEQ ID NO. 1, and the modification method is that a 5-FAM group is marked at the 4th amino acid and a Dabcyl group is marked at the 15th amino acid. The substrate modified peptide and the detection method provided by the application are not only high in accuracy, but also significantly improve the detection sensitivity.

The invention relates to ADAMTS13 protein variants comprising residues 1 to 685 of ADAMTS13 and wherein one or more N-linked glycosylation sites are added as compared to wild-type ADAMTS13 and / or one or more existing N-linked glycosylation sites are shifted as compared to wild-type ADAMTS13. The invention further relates to compositions comprising such ADAMTS13 variants, methods for their preparation and uses thereof, in particular as an antithrombotic agent, and in the treatment of thrombotic disease, thrombotic microangiopathy, thrombotic thrombocytopeniaurpura (TTP), hemolytic-uremic syndrome (HUS), ischemic stroke, systemic thrombosis, COVID19, antiphospholipid syndrome, pre-eclampsia / HELLP syndrome, sepsis and sickle cell disease.

Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange / hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration / diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.

The present disclosure includes a fusion protein or molecule, called a "Macromolecule that depletes ADAMTS13-specific antibodies'; including a targeting component that specifically binds to a cell surface receptor or other cell surface molecule, and an antigen component fused directly or indirectly to the targeting component. The antigen component is configured to specifically bind target antigen-specific antibodies. The present disclosure also includes a method of depleting target antigen-specific antibodies from a patient by treating the patient with a macromolecule that targets ADAMTS13-specific antibodies having an antigen component configured to specifically bind the target antigen-specific antibodies.

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).

A preparation of an antibody or an antibody derivative that can prevent or treat acquired von Willebrand syndrome (AVWS) accompanied by a disease in need of mechanical assisted circulation. The antibody or an antibody derivative has specific binding activity against ADAMTS13, von Willebrand factor (VWF) cleaving protease, which is a causative factor of the acquired von Willebrand syndrome (AVWS) in humans, and can reduce the excessive cleavage of VWF by ADAMTS13.