51 results about "ADAMTS" patented technology

ADAMTS-7 expression and activity are up regulated in patients that have cancers of epithelial origin. Accordingly, the present invention is directed to methods diagnosis of cancers of epithelial origin (e.g. breast cancer, prostate cancer, bladder cancer, brain cancer and hepatic cancer). In particular, the presence of ADAMTS-7 in a biological sample is indicative of cancer of epithelial origin. Thus, measuring the level of ADAMTS-7 in biological samples (e.g. urine or blood) provides a quick, easy, and safe screen that can be used to diagnose cancer in a patient.

The present invention relates to specific substrates for a von Willebrand factor cleaving enzyme, ADAMTS-13, as well as to diagnosis of ADAMTS-13 deficient patients, diagnostic compositions, and kits employing the substrates. Particularly preferable substrate polypeptides for ADAMTS-13 are the polypeptide which begins at amino acid 1587 and ends at amino acid 1668 of SEQ ID NO: 1 in the Sequence Listing, and the polypeptide which begins at amino acid 1596 and ends at amino acid 1668 of SEQ ID NO: 1 in the Sequence Listing. These substrate polypeptides for ADAMTS-13 have high substrate specificity and also superior quantitativeness, and a suitable size for production by recombinant methods.

Disclosed are compositions useful for treating Alzheimer's disease, atherosclerosis, arteriosclerosis, osteoarthritis and other degenerative joint diseases, Huntington's chorea, Parkinson's disease, optic atrophy, retinitis pigmentosa, macular degeneration, muscular dystrophy, aging-associated degenerative processes, asthma, dermatitis, laminitis, pemphigoid, pemphigus, reactive airway disease (e.g., COPD, IAD), inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), multiple sclerosis, rheumatoid arthritis, periodontal disease, systemic lupus erythematosus, sarcoidosis, psoriasis, type I diabetes, ischemia-reperfusion injury, chronic inflammatory diseases, geriatric wasting, cancer cachexia, cachexia associated with chronic inflammation, sick feeling syndrome, and other inflammatory and / or degenerative diseases, disorders, conditions, and processes in humans and other animals. In one embodiment, the compositions include at least 4 of the following: a MMP1 inhibitor, a MMP2 inhibitor, a MMP3 inhibitor, a MMP7 inhibitor, a MMP9 inhibitor, an ADAMTS-4 inhibitor, a MMP13 inhibitor, and a MMP14 inhibitor. In another embodiment, the compositions include a curcuminoid, a polymethoxylated flavone, a catechin, and a boswellic acid.

The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and / or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis. Accordingly, these animals also show that osteoarthritis can be prevented and / or treated by administering to a subject an ADAMTS-5 inhibitory agent and particularly an agent capable of inhibiting the aggrecanase activity of ADAMTS-5.

Described herein are method(s), kit(s), reagent(s) and the like for determining von Willebrand factor (VWF) activity in a sample in the absence of ristocetin.

The invention relates to a diagnostic method for determining the von Willebrand factor (VWF) cleaving activity of ADAMTS-13 in a test medium during which the test medium is mixed with 0.5 to 5 U / ml of a von Willebrand factor (VWF) that does not contain ADAMTS-13, and after incubation, the ADAMTS-13 activity is determined based on the drop in the VWF-mediated aggregation of thrombocytes.

It is intended to provide an antibody showing immunoreactivity selectively to ADAMTS-13 and applications of this antibody in epitope analysis or diagnosis of an ADAMTS-13 autoantibody-positive patient. Alternatively, it is intended to provide a process for producing and use of a modified ADAMTS-13 molecule partially deleted aiming at the application in pharmaceutical products. An antibody specific for ADAMTS-13 which can be obtained from a warm-blooded animal immunized and sensitized with a polypeptide containing a part or the whole of ADAMTS-13 amino acid sequence; a process for producing an antibody comprising a step of immunizing and sensitizing a warm-blooded animal with a polypeptide containing a part or the whole of ADAMTS-13 amino acid sequence; use of the above-described antibody including a method of detecting and purifying ADAMTS-13; and a modified ADAMTS-13 molecule partially deleted are provided.

The present invention provides an epitope recognized by an antibody (hereinafter, also referred to as an anti-ADAMTS-13 antibody) against a cleaving protease (hereinafter, also referred to as ADAMTS-13) specific to von Willebrand factor (hereinafter, also referred to as vWF), and a polypeptide comprising the epitope region. The present invention also provides a polypeptide located in a region from position 449 to position 687 in an amino acid sequence composing the ADAMTS-13, which is recognized by the anti-ADAMTS-13 antibody, or a peptide fragment derived from the polypeptide.

Provided are assays and kits to detect ADAMTS13 activity using peptide substrates and ADAMTS13 / Factor XI complexes using ELISA. These assays and kits can be used for diagnostic applications and to evaluate treatment of thrombotic or hemostatic disorders, for example, thrombotic thrombocytopenic purpura (TTP). Also provided is a novel form of ADAMTS13 found on platelets, and anti-ADAMTS13 antibodies.

The present invention relates to hepatic fibrosis-suppressing agents that are suitable for treating or preventing fibrotic liver diseases such as cirrhosis, which comprise as an active ingredient a substance that inhibits the production or accumulation of chondroitin sulfate proteoglycans including chondroitinase ABC and ADAMTS-4; and methods of screening for the agents.The present inventors discovered for the first time that hepatic fibrosis could be efficiently suppressed by suppressing the production or accumulation of chondroitin sulfate proteoglycans. Specifically, fibrosis of liver tissues can be suppressed by administering chondroitinase ABC, a chondroitin sulfate proteoglycan-degrading enzyme, or by using siRNA to suppress the expression of C4ST-1, C6ST-1, or C6ST-2, a sulfotransferase for chondroitin sulfate proteoglycans. Compounds such as nucleic acids that are used as siRNA can be used as effective agents for suppressing hepatic fibrosis. Furthermore, hepatic fibrosis-suppressing agents can be found by screening for compounds that suppress the production or accumulation of chondroitin sulfate proteoglycans.

The present invention relates to an antibody, recombinant or synthetic antigen-binding fragments thereof able to recognize and bind an epitope comprised in the spacer domain of ADAMTS-5, nucleic acid and expression vector encoding the same, method of production and uses thereof.

The present invention relates to specific substrates for a von Willebrand factor cleaving enzyme, ADAMTS-13, as well as to diagnosis of ADAMTS-13 deficient patients, diagnostic compositions, and kits employing the substrates. Particularly preferable substrate polypeptides for ADAMTS-13 are the polypeptide which begins at amino acid 1587 and ends at amino acid 1668 of SEQ ID NO: 1 in the Sequence Listing, and the polypeptide which begins at amino acid 1596 and ends at amino acid 1668 of SEQ ID NO: 1 in the Sequence Listing. These substrate polypeptides for ADAMTS-13 have high substrate specificity and also superior quantitativeness, and a suitable size for production by recombinant methods.

The invention discloses an siRNA (small interfering ribonucleic acid) composition inhibiting an ADAMTS-5 (a disintegrin-like and metalloproteinase with thrombospondin type 1motifs-5) gene and an ADAM17 (a disintegrin-like and metalloproteinase with thrombospondin type 1motifs 17) gene and an application of the siRNA composition. The invention discloses the chemically modified double-chain siRNA molecular composition which comprises at least one of double-chain siRNA molecules as shown as (1) and at least one double-chain siRNA molecules as shown as (2). The siRNA composition can serve as a treatment medicine of arthritis and relevant inflammation, and the siRNA composition and a preparation of the siRNA composition can be injected locally through a bone articular cavity to inhibit inflammatory factor expression to achieve treatment of the joint inflammation.

The invention discloses siRNA for inhibiting a gene ADAMTS-5 and application of the siRNA. The invention discloses a chemically modified double-chain siRNA molecule which is formed in the way that any chemical modification from (1) to (13) in the Specification is performed on at least one of the chains in the siRNA molecule in A (in the Specification), and the complementation is performed. The siRNA disclosed by the invention can be used as a medicine for treating arthritis and related inflammations, and the siRNA and a preparation thereof can be injected into local parts of bone joint cavities to inhibit the expression of inflammatory factors and further realize treatment of joint inflammation.

It is intended to provide an antibody showing immunoreactivity selectively to ADAMTS-13 and applications of this antibody in epitope analysis or diagnosis of an ADAMTS-13 autoantibody-positive patient. Alternatively, it is intended to provide a process for producing and use of a modified ADAMTS-13 molecule partially deleted aiming at the application in pharmaceutical products. An antibody specific for ADAMTS-13 which can be obtained from a warm-blooded animal immunized and sensitized with a polypeptide containing a part or the whole of ADAMTS-13 amino acid sequence; a process for producing an antibody comprising a step of immunizing and sensitizing a warm-blooded animal with a polypeptide containing a part or the whole of ADAMTS-13 amino acid sequence; use of the above-described antibody including a method of detecting and purifying ADAMTS-13; and a modified ADAMTS-13 molecule partially deleted are provided.

The present invention features methods of using ADAMTS-8 proteins or their functional derivatives to cleave aggrecan or other proteoglycan molecules. The present invention also features methods for identifying ADAMTS-8 modulators that are capable of inhibiting or enhancing ADAMTS-8 proteolytic activities. In addition, the present invention features pharmaceutical compositions comprising ADAMTS-8 proteins or their derivatives or modulators. These pharmaceutical compositions can be used to treat diseases that are characterized by deficiencies or abnormalities in proteoglycan cleavage or metabolism.

A human ADAMTS-1 protein, a gene encoding the same, a pharmaceutical composition containing the protein as an active ingredient, and a method for immunologically analyzing the human ADAMTS-1 protein are disclosed. The protein can decrease the number of leukocytes and platelets, and at the same time, increase the number of erythrocytes.

The present invention discloses compounds according to Formula I:Wherein R1, R2, R3a, R3b, and Cy are as defined herein.The present invention relates to compounds inhibiting ADAMTS, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and / or treatment of inflammatory conditions, and / or diseases involving degradation of cartilage and / or disruption of cartilage homeostasis by administering a compound of the invention.

The present invention discloses compounds according to Formula I:Wherein R1, R2, R3a, R3b, R6, Cy, and the subscript n are as defined herein.The present invention relates to compounds inhibiting ADAMTS, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and / or treatment of inflammatory diseases, and / or diseases involving degradation of cartilage and / or disruption of cartilage homeostasis by administering the compound of the invention.

The invention discloses an aconite extract injection for treating osteoarthritis as well as a preparation method and application of the aconite extract injection, and belongs to the technical field of traditional Chinese medicine production. The preparation method comprises the steps: weighing radix aconiti and radix aconiti kusnezoffii as raw materials, adding uniformly mixed medicine powder into an alcohol solution, performing sealed soaking, transferring into a high-pressure reaction kettle, performing pressurized extraction, performing depressurization, performing filtering, separating medicine liquid from a filter residue, adding 8-10 volume times of water into the filter residue, performing uniform mixing, transferring into the high-pressure reaction kettle, performing pressurized extraction, concentrating the two medicine liquids until no alcohol odor exists, performing filtering, adding absolute alcohol to allow the alcohol content to reach 75%, performing standing overnight, performing filtering, concentrating the medicine liquid until no alcohol odor exists, performing dilution with injection water to be 10 times, and performing encapsulation and sterilization to obtain the aconite extract injection. The aconite extract injection has the significant influence on MMP-3, ADAMTS, IL-1 beta, IL-18, TNF-alpha and the like, and is confirmed to have a protective effect on chondrocyte damage caused by arthritis.

A human ADAMTS-1 protein, a gene encoding the same, a pharmaceutical composition containing the protein as an active ingredient, and a method for immunologically analyzing the human ADAMTS-1 protein are disclosed. The protein can decrease the number of leukocytes and platelets, and at the same time, increase the number of erythrocytes.

The present invention features methods of using ADAMTS-8 proteins or their functional derivatives to cleave aggrecan or other proteoglycan molecules. The present invention also features methods for identifying ADAMTS-8 modulators that are capable of inhibiting or enhancing ADAMTS-8 proteolytic activities. In addition, the present invention features pharmaceutical compositions comprising ADAMTS-8 proteins or their derivatives or modulators. These pharmaceutical compositions can be used to treat diseases that are characterized by deficiencies or abnormalities in proteoglycan cleavage or metabolism.

The present invention provides a condensed ring compound and a preparation method and application thereof, the compound has a good inhibitory effect on ADAMTS-5 and / or ADAMTS-4, particularly, the compound exhibits excellent selectivity and bioavailability.

The invention belongs to the technical field of medical molecular biology and protein polypeptide detection, and particularly relates to a substrate, a method and a kit capable of detecting the enzymatic activity of metalloproteinase ADAMTS-13 by utilizing MALDI-TOF-MS. The method comprises the following steps: (1) performing expression and purification of an ADAMTS-13 enzyme digestion substrate GST-vWF82-6XHis recombinant protein; (2) performing enzyme digestion reaction; and (3) enriching the ADAMTS-13 enzyme digestion product by a metal chelating chip, identifying and detecting the ADAMTS-13 enzyme digestion product by MALDI-TOF-MS, and obtaining the enzyme digestion activity of ADAMTS-13 in the serum sample by analysis software. The substrate, the method and the kit for in-vitro quantitative determination of ADAMTS-13 enzyme activity are good in sensitivity and accuracy, simple and convenient to operate, low in price and suitable for wide patient screening.

The invention relates to an ADAMTS-2 gene and application of an expression product of the ADAMTS-2 gene in the diagnosis and treatment of stomach cancer. An inventor integrates the existing gene expression microarray data, six sets of stomach cancer expression data are obtained by retrieving and screening a GEO database, data are processed and analyzed again by utilizing a biological information analysis tool, the ADAMTS-2 gene is screened out, and validation of molecular biology is further performed, an RT-PCR result shows that high expression of the ADAMTS-2 gene is performed in gastric cancer tissues, an interference test indicates that ADAMTS-2-siRNA1 can effectively reduce the expression of the ADAMTS-2 gene. The invention provides a new target spot of diagnosis and treatment of stomach cancer, and has important clinical application value.

The present invention discloses compounds according to Formula I:Wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein.The present invention relates to compounds inhibiting ADAMTS, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and / or treatment of inflammatory diseases, and / or diseases involving degradation of cartilage and / or disruption of cartilage homeostasis by administering the compound of the invention.

The present invention discloses a metalloprotease ADAMTS-7 immunogenic peptide and its product and application; the present invention first discloses a short peptide, including any of the following: the amino acid sequence is shown in Sequence 1 in the sequence table Short peptide; the amino acid sequence is the short peptide shown in sequence 2 in the sequence listing; the amino acid sequence is the short peptide shown in sequence 3 in the sequence listing; the amino acid sequence is the short peptide shown in sequence 4 in the sequence listing. The invention further discloses a conjugate comprising the above short peptide, a vaccine comprising the conjugate and applications thereof. The vaccine containing the short peptide of the present invention can significantly inhibit neointimal neointimal in mouse models of vascular restenosis and atherosclerosis in mice fed with high fat, and can be used for preventing or treating atherosclerosis and / or vascular restenosis.

ADAMTS-7 expression and activity are up regulated in patients that have cancers of epithelial origin. Accordingly, the present invention is directed to methods diagnosis of cancers of epithelial origin (e.g. breast cancer, prostate cancer, bladder cancer, brain cancer and hepatic cancer). In particular, the presence of ADAMTS-7 in a biological sample is indicative of cancer of epithelial origin. Thus, measuring the level of ADAMTS-7 in biological samples (e.g. urine or blood) provides a quick, easy, and safe screen that can be used to diagnose cancer in a patient.