9 results about "ADAMTS13" patented technology

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.

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 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.

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 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.