36 results about "ADAMTS13" patented technology

The present invention provides culture mediums that are useful for the expression of ADAMTS proteins, such as ADAMTS13. Methods for the expression and purification of ADAMTS proteins are also provided. In some embodiments, the mediums and methods of the invention are useful for the expression of ADAMTS proteins having high specific activities. Also provided are ADAMTS, e.g., ADAMTS13, protein compositions with high specific activities, which are expressed and purified according to the methods provided herein.

Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and / or cell culture supernatant with a low ammonium (NH4+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

Methods of analyzing the electrophoretic mobility distribution of von Willebrand factor (vWF) multimers include providing a sample medium comprising a plurality vWF multimers. The vWF multimers are electrophoretically separated by electrohoretic mobility in the sample medium by subjecting said sample medium to an electric field to provide separated vWF multimers. The separated vWF multimers in the sample medium are exposed to a light source to produce scattered light. The scattered light is detected, and the electrophoretic mobility distribution of the separated vWF multimers is determined from the detected scattered light.

A method for determining a condition of disseminated intravascular coagulation (DIC), by analyzing the amount and / or enzyme activity of a von Willebrand factor (vWF)-cleaving protease (ADAMTS13) (preferably also the amount of vWF) in a patient suffering from DIC, and a kit for determining a condition of DIC, comprising an antibody or a fragment thereof which specifically binds to ADAMTS13, are disclosed. According to the present invention, a differential diagnosis of patients with thrombotic thrombocytopenic purpura (TTP) can be carried out from among patients with DIC, which could not be distinguished on the basis of only clinical findings or known markers.

Relating to the field of use of disease biomarkers, the invention discloses liver cirrhosis biomarkers VWF (von willebrand factor) and ADAMTS13 (adisintegrin and metalloproteinase with thrombospondin motifs 13) and use thereof in liver cirrhosis diagnostic reagents. The VWF is composed of protein with an amino acid sequence accession number of GI 317373549 in a NCBI database, and the ADAMTS13 is composed of protein with an amino acid sequence accession number of GI 74749836 in a NCBI database. Use of the biomarkers VWF and ADAMTS13 for liver cirrhosis diagnosis on subjects has the advantages of simplicity and feasibility, safe and non-invasive diagnostic process and easy acceptance by patients, unified diagnosis standard insusceptible to subjective factors, high diagnosis result specificity and sensitivity, and easy mass screening and selection, etc.

The invention relates to the field of use of a biomarker for a disease, and discloses biomarkers von willebrand Factor (VWF) and ADAMTS13 and use thereof in a cirrhosis diagnosis reagent. The VWF disclosed by the invention is formed by protein of which the accession number of an amino acid sequence in a database for the national center of biotechnology information (NCBI) is GI317373549; the ADAMTS13 is formed by protein of which the accession number in the database for the NCBI is GI74749836. A testee is subjected to cirrhosis diagnosis by the biomarkers VWF and ADAMTS13, and the biomarkers have the advantages of being simple and feasible, safe and free of a wound in the diagnosis process, easy to be accepted by a patient, small in effect on diagnostic criteria unification caused by personal subjective factors, high in specificity and sensitivity on diagnosis result, easy to carry out a lot of screening for selection, and the like.

The present invention relates to methods of treatment by human ADAMTS13 inhibition in circulatory assist device induced haemorrhagic complication such as a bleeding disorder, in particular, bleeding after left ventricular assist device implantation. The present invention further relates to specific monoclonal antibodies inhibiting ADAMTS13 function.

The invention relates to application of ADAMTS13 to preparation of drugs for vascular remodeling, especially application of ADAMTS13 to preparation of drugs used for promoting vascular remodeling after stroke, belonging to the field of biopharmacy. The experimental results of the invention prove that the loss of ADAMTS13 leads to decrease in both revascularization and vascular integrity and aggravation of vascular damage in the peripheral cortex of cerebral ischemia mice; exogenous recombinant ADAMTS13 can significantly increase revascularization, promote the repair of vascular functions and improve the behavioral functions of the cerebral ischemic mice; ADAMTS13 plays an important role in regulating revascularization in the recovery phase of cerebral ischemic; inhibition of revascularization and vascular maturation due to the loss of ADAMTS13 may be related to the opening of vascular permeability; and ADAMTS13 promotes vascular remodeling after cerebral ischemia through the VWF-Ang-2 / Gal-3-pVEGFR-2 pathway.

The invention belongs to the field of biological pharmacy, relates to application of recombinant ADAMTS13 to preparation of cerebral hemorrhage medicaments, and especially relates to application of recombinant ADAMTS13 to preparation for medicaments for reducing cerebral hemorrhage caused by tPA thrombolytic therapy on cerebral ischemia. Experiment results show that: VEGF generated by tPA induction at ischemic condition can be blocked by a specific inhibitor of RhoA or Akt, and recombinant ADAMTS13 substantially reduces activation of RhoA and phosphorylation of Akt, which means that recombinant ADAMTS1 is capable of inhibiting tPA-induced VEGF expression through RhoA and Akt pathways. The recombinant ADAMTS13 provided by the invention helps to mitigate damage of tPA to blood cerebral barrier and further to reduce cerebral hemorrhage caused thereby by inhibiting cerebrovascular permeability increase mediated by RhoA and Akt, and therefore combination usage of recombinant ADAMTS13 and tPA is a novel countermeasure and means for increasing thrombolysis security.

This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

The invention relates to an isolated monoclonal antibody that specifically binds to the D4 domain of VWF, competes for binding to VWF D4 domain with ADAMTS13 and partially inhibits ADAMTS 13-mediated degradation of VWF. More particularly, the invention relates to an isolated monoclonal antibody comprising a heavy chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 3 for H-CDR1, SEQ ID NO: 4 for H-CDR2 and SEQ ID NO: 5 for H-CDR3 and a light chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 7 for L-CDR1, SEQ ID NO: 8 for L-CDR2 and SEQ ID NO: 9 for L-CDR3. Antibodies of the invention are presented to be useful in for the prevention or the treatment of bleeding episodes, such as bleeding episodes occurring in patients with aortic stenosis or patients with ventricular assist devices (VAD).

The present invention further relates to specific humanised monoclonal antibodies inhibiting ADAMTS13 function. The present invention relates to methods of treatment by human ADAMTS13 inhibition in circulatory assist device induced haemorrhagic complication such as a bleeding disorder, in particular, bleeding after left ventricular assist device (LVAD) implantation.

The present invention relates to formulations of ADAMTS13 with improved or desirable properties. Accordingly, the present invention provides liquid and lyophilized formulations of ADAMTS13 suitable for pharmaceutical administration. Among other aspects, the present invention provides methods of treating various diseases and conditions associated with VWF and / or ADAMTS13 dysfunction in a subject. Also provided herein are kits comprising formulations of ADAMTS13 useful in the treatment of various diseases and conditions.

The invention provides a detection method of a thrombus-related gene chip, relates to the field of biological detection, and particularly discloses corresponding 62 pathogenic mutation sites in the thrombus-related gene chip, the detection method of the thrombus-related gene chip comprises probes for the following 21 thrombus-related genes: PROC, PROS1, SERPINC1, SERPINA10, THBD, PLG, GCKR, ADAMTS13, F2, MTHFR, SERPIND1, JAK2, PROCR, SERPINE1, F5, PROZ, STAB2, HRG, SLC44A2, SLC4A1 and VWF. According to the detection method of the thrombus-related gene chip, the probes are used for capturing the 21 thrombus-related genes; 62 pathogenic mutation sites of the gene can be specifically captured; a probe capture method next-generation sequencing technology is adopted, mutation of all exons and regulatory regions of the genes can be comprehensively and systematically detected at a time, and the invention aims to be applied to molecular diagnosis and biological research of thrombus caused by gene mutation. The method has the advantages of clear detection target, good coverage, high accuracy, stable detection, short period, low cost and the like.

A method for determining an appropriate treatment option for a patient who has been diagnosed with disseminated intravascular coagulation (DIC) but who may have thrombotic thrombocytopenic purpura (TTP), by analyzing the amount and / or enzyme activity of a von Willebrand factor (vWF)-cleaving protease (ADAMTS13) and the amount of vWF in a patient that has been diagnosed with DIC is disclosed. Using the method of the present invention, a differential diagnosis of patients with thrombotic thrombocytopenic purpura (TTP) can be made from among patients diagnosed with DIC, which could not previously be distinguished on the basis of only clinical findings or known markers. Also disclosed is a kit for determining an appropriate treatment option, the kit comprising an antibody or a fragment thereof which specifically binds to ADAMTS13.

The invention belongs to the technical field of medical bioengineering and discloses a mutant ADAMTS of human von Willebrand factor lyase 13 ‑MDTCS fusion protein and its application in the preparation of medicines for treating thrombotic thrombocytopenic purpura (TTP), the present invention combines ADAMTS with peptides 13 ‑MDTCS binds to human serum albumin to form a fusion protein that preserves the original protein ADAMTS 13 ‑MDTCS biological activity, again significantly increased by ADAMTS 13 ‑MDTCS protein half-life, overcomes existing ADAMTS 13 ‑MDTCS degradation problem, with long-term biological activity, high protein expression, can be used for industrial production.