Class / Patent application number | Description | Number of patent applications / Date published |
514700400 | Lipid or cholesterol affecting (e.g., dyslipidemia, etc.) | 53 |
20100267630 | USE OF LEPTIN IN THE PREVENTION OF UNHEALTHY FOOD HABITS AND CARDIOVASCULAR DISEASES - The present invention is addressed to the use of leptin, a fragment of leptin or a mimetic product of leptin action, in the preparation of a pharmaceutical composition, a food composition and/or a nutritional supplement for the prevention of unhealthy food habits and/or cardiovascular disorders during adulthood. | 10-21-2010 |
20100267631 | APOLIPOPROTEIN A-I MIMICS - Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder. | 10-21-2010 |
20110046056 | APOA-1 PEPTIDE MIMETICS - The invention relates to peptide mimetics for treating disorders associated with hypercholesterolemia and cardio-vascular disease. In particular, the invention relates to peptides that mimic the activity of apolipoprotein A-I (Apo AI). | 02-24-2011 |
20110118181 | PCSK9 INHIBITORS AND METHODS OF USE THEREOF - A method for identifying a compound for preventing or treating a LDLR-associated disease, a VLDLR-associated disease or an ApoER2-associated disease, said method comprising determining whether: a) a level of expression of Annexin A2 nucleic acid or encoded polypeptide; b) a level of Annexin A2 activity; or c) a combination of a) and b), is increased in the presence of a test compound relative to in the absence of said test compound, wherein said increase is indicative that said test compound can be used for preventing or treating a LDLR-associated disease, a VLDLR-associated disease, an ApoER2-associated disease. | 05-19-2011 |
20110118182 | PROCESS FOR THE EXTRACTION, PURIFICATION AND ENZYMATIC MODIFICATION OF SOY 7S GLOBULIN ALPHA' SUBUNIT FOR USE AS HYPOCHOLESTEROLEMIZING AGENT - A purified amino-terminal polypeptide fragment of the soy β-conglycinin α′ subunit is prepared by selective extraction of defatted soy with an aqueous solution of sodium bisulfite, precipitation with ethanol, and Metal Affinity Chromatography (MAC) under denaturing conditions to obtain the α′ subunit. The α′ subunit is then enzymatically treated with chymotrypsin and subjected to further MAC to recover the amino-terminal fragment of the polypeptide (MW 28,000 Da). | 05-19-2011 |
20110263496 | EXENDINS TO LOWER CHOLESTEROL AND TRIGLYCERIDES - Provided herein are pharmaceutical formulations containing exendins, exendin agonists, or exendin analog agonists that are administered at therapeutic plasma concentration levels over a sustained period of time to lower total cholesterol levels; to lower LDL-cholesterol levels; to lower triglyceride levels; to treat dyslipidemia; to treat and slow the progression of atherosclerosis; and to treat, prevent, and reduce the risk of heart attacks and strokes in patients. In the pharmaceutical formulations and methods of the invention, the exendin may be exendin-4, an exendin-4 agonist, or an exendin-4 analog agonist. The pharmaceutical formulations may be polymer-based pharmaceutical formulations that may be administered once weekly. An exemplary pharmaceutical formulation comprises 5% (w/w) of exenatide, about 2% (w/w) of sucrose, and about 93% (w/w) of a poly(lactide-co-glycolide) polymer, wherein the poly(lactide-co-glycolide) polymer is in the form of microshperes encapsulating the exenatide. | 10-27-2011 |
20110263497 | APO A-I MIMETIC PEPTIDES AND METHODS OF TREATMENT - A method including advancing a delivery device through a lumen of a blood vessel to a particular region in the blood vessel; and introducing a synthetic apolipoprotein A-1 (Apo A-I) mimetic peptide into a wall of the blood vessel at the particular region, wherein the peptide has a property that renders the peptide effective in reverse cholesterol transport. A composition including a synthetic apolipoprotein A-I (Apo A-I) mimetic peptide, or combination of an Apo A-I synthetic peptide and an Acyl CoA cholesterol: acyltransferase (ACAT) inhibitor in a form suitable for delivery into a blood vessel, the peptide including an amino acid sequence in an order reverse to an order of an endogenous Apo A-I related peptide. A composition including an apolipoprotein A-1 (Apo A-I) synthetic peptide in a form suitable for delivery into a blood vessel, the peptide including an amino acid backbone that has less amino acid residues relative to endogenous Apo A-I and a chimera of helix 1 and helix 9 of Apo A-I. | 10-27-2011 |
20110288017 | APO-LIPOPROTEIN PROPEPTIDE - This invention relates generally to a peptide being a fragment of the mammalian apolipoprotein AI peptide, said peptide comprising the sequence RHFWQQ (human, macaque and pig), the sequence WEFWQQ (rat), and the sequence WHVWQQ (mouse), or suitable modifications thereof, or equivalent synthetic peptides. In contrast to the entire protein, these short peptides have the ability to enter the nucleus of a cell. By binding directly to the DNA or to a protein that is attached to the DNA, these peptides undertake a role as a transcription factor. In particular, these peptides bind to the LXRβ receptor within the nucleus of the human cell. Therefore, they may be used as a drug to effectively treat disorders such as hyperlipidemia, inflammation (arthritis), and Alzheimer's disease. | 11-24-2011 |
20110288018 | BEVERAGE LOWERING SERUM CHOLESTEROL - A beverage including protein, plant sterol ester and/or plant stanol ester, a fruit and/or vegetable preparation, and a stabiliser. | 11-24-2011 |
20110301085 | PROTEIN HYDROLYSATE AND PLANT STEROL CONTAINING COMPOSITION FOR IMPROVING SERUM LIPID PROFILE AND PREVENTING ATHEROSCLEROSIS - The invention relates to a terapeutical composition comprising a protein hydrolysate and a plant sterol, wherein the weight ratio of the plant sterol to the protein hydrolysate is from 1:0.02 to 1:150. The invention also relates to a terapeutical composition comprising a protein hydrolysate and a synthetic emulsifier and/or a lipid based gain fraction having emulsifying properties. Said compositions can be used in a pharmaceutical, nutraceutical or food product for improving serum lipid profile. | 12-08-2011 |
20120021982 | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTION - The present invention features pharmaceutical compositions and methods of using the pharmaceutical compositions for treating left ventricular diastolic dysfunction. In particular, the pharmaceutical compositions include an apolipoprotein complex comprising a lipid fraction and a protein fraction. | 01-26-2012 |
20120115779 | AGENT FOR SUPPRESSING ELEVATION OF BLOOD TRIGLYCERIDE CONCENTRATION - An agent for suppressing elevation of a blood triglyceride concentration, comprising a polyglutamic acid as an active ingredient. | 05-10-2012 |
20120135923 | Use of Melanocortins to Treat Dyslipidemia - The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of dyslipidemia and associated complications such as alcoholic and non-alcoholic fatty liver disease. | 05-31-2012 |
20120157380 | PEGYLATED HUMAN APOA-1 AND PROCESS FOR PRODUCTION THEREOF - An isolated mono-pegylated apolipoproteinA-1, compositions comprising such, and methods of treating cardiovascular diseases using mono-pegylated apolipoproteinA-1 are provided as well as processes for making isolated mono-pegylated apolipoproteinA-1 and compositions containing such. | 06-21-2012 |
20120208751 | Methods for Regulating Neurotransmitter Systems by Inducing Counteradaptations - The present invention relates to methods for regulating neurotransmitter systems by inducing a counteradaptation response. According to one embodiment of the invention, a method for regulating a neurotransmitter includes the step of repeatedly administering a ligand for a receptor in the neurotransmitter system, with a ratio of administration half-life to period between administrations of no greater than 1/2. The methods of the present invention may be used to address a whole host of undesirable mental, neurological and physiological conditions. | 08-16-2012 |
20120232005 | LIPOPROTEIN COMPLEXES AND MANUFACTURING AND USES THEREOF - The present disclosure relates to lipoprotein complexes and lipoprotein populations and their use in the treatment and/or prevention of dyslipidemic diseases, disorders, and/or conditions. The disclosure further relates to recombinant expression of apolipoproteins, purification of apolipoproteins, and production of lipoprotein complexes using thermal cycling-based methods. | 09-13-2012 |
20130023472 | LDL QUANTITATION AND METHOD OF USE - The present invention features, in certain aspects, methods of promoting endocytosis of LDL with α1PI or peptides derived from α1PI. The present invention also provides methods for decreasing LDL levels in response to α | 01-24-2013 |
20130123173 | CREATION OF OXIDATION-RESISTANT HDL MIMETIC PEPTIDES - The present invention provides non-naturally occurring polypeptides that are oxidation resistant and have cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABACI that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation; and diagnostic methods employing the peptides to evaluated cholesterol efflux activity. | 05-16-2013 |
20130172250 | Exendins To Lower Cholesterol And Triglycerides - Provided herein are pharmaceutical formulations containing exendins, exendin agonists, or exendin analog agonists that are administered at therapeutic plasma concentration levels over a sustained period of time to lower total cholesterol levels; to lower LDL-cholesterol levels; to lower triglyceride levels; to treat dyslipidemia; to treat and slow the progression of atherosclerosis; and to treat, prevent, and reduce the risk of heart attacks and strokes in patients. In the pharmaceutical formulations and methods of the invention, the exendin may be exendin-4, an exendin-4 agonist, or an exendin-4 analog agonist. The pharmaceutical formulations may be polymer-based pharmaceutical formulations that may be administered once weekly. An exemplary pharmaceutical formulation comprises 5% (w/w) of exenatide, about 2% (w/w) of sucrose, and about 93% (w/w) of a poly(lactide-co-glycolide) polymer, wherein the poly(lactide-co-glycolide) polymer is in the form of microshperes encapsulating the exenatide. | 07-04-2013 |
20130252887 | COMPOSITIONS AND METHODS FOR TREATING ANTIPHOSPHOLIPID SYNDROME - The invention features compositions and methods of using a dimeric inhibitor, e.g., A1-A1, to selectively target β2GPI in β2GPI/antibody complexes. The compositions can be administered to subjects (e.g., a mammal, such as a human) having or likely to develop APS, or one or more symptoms of APS, in order to treat or inhibit the disease or treat or reduce its symptoms. The inhibitors of the invention include two ligand-binding A1 modules, e.g., from ApoER2, connected by a flexible linker. | 09-26-2013 |
20130261054 | METHODS FOR TREATMENT OF NEPHROTIC SYNDROME AND RELATED CONDITIONS - The present disclosure provides a method for treating and/or preventing nephrotic syndrome, such as but not limited to MCD and MN, and conditions related to nephrotic syndrome, such as but not limited to, proteinuria and edema, as well as diabetic nephropathy, diabetes mellitus, lupus nephritis or primary glomerular disease. The present disclosure further provides methods for reducing proteinuria and other disease states as discussed herein. Such methods comprise the therapeutic delivery of an Angptl4 polypeptide or Angptl4 polypeptide derivative to a subject. | 10-03-2013 |
20130288961 | METHODS FOR TREATING STEATOTIC DISEASE - Methods for treating fatty liver disease, e.g., hepatic steatosis, using peptide fragments of the C-terminal end of glucagon-like peptide-1 (GLP-1), e.g., GLP-1(28-36). | 10-31-2013 |
20130310315 | METHOD FOR ASSESSING A SUBJECT'S RISK OF HAVING A CARDIOVASCULAR DISEASE - The present invention relates to a method for assessing a subject's risk of having a cardiovascular disease comprising the step of measuring the level of IF1 in a body fluid sample obtained from said subject wherein the level of EF1 is negatively correlated with the risk of said subject of having cardiovascular disease. | 11-21-2013 |
20130331324 | USE OF MELANOCORTINS TO TREAT DYSLIPIDEMIA - The present invention relates to peptide ligands of the melanocortin receptors, in particular the melanocortin-4 receptor, and as such, are useful in the treatment of dyslipidemia and associated complications such as alcoholic and non-alcoholic fatty liver disease. | 12-12-2013 |
20140005108 | METHOD FOR DECREASING LOW DENSITY LIPOPROTEIN LEVELS | 01-02-2014 |
20140018293 | MINIMIZING INTESTINAL DYSFUNCTION - Techniques are discloded for treating or reducing sumptoms associated with abdominal dysfunction or ileus following surgery or other abdominal episode by treating the area with a combination of one or more protease, antibacterial compound, and inflammatory lipid mediator. | 01-16-2014 |
20140045747 | METHODS FOR INCREASING AND MOBILIZING HEMATOPOIETIC STEM CELLS - A method is provided for increasing the number of hematopoietic stem cells in the bone marrow, increasing the mobilization of these cells to migrate from the bone marrow to the bloodstream and elsewhere, and increasing the number of differentiating hematopoietic stem cells in the bloodstream. | 02-13-2014 |
20140057846 | PRODUCTS AND METHODS USING SOY PEPTIDES TO LOWER TOTAL AND LDL CHOLESTEROL LEVELS - Controlled studies demonstrate that products and related methods using soy related peptides lower total and LDL cholesterol levels in individuals. In one exemplary embodiment of the present disclosure, a product containing an effective amount of lunasin peptides that lowers cholesterol levels in an individual that consumes the lunasin peptides is provided. In another exemplary embodiment of the present disclosure, a composition containing an effective amount of lunasin peptides or lunasin peptide derivatives and one or more enzyme inhibitors is provided. In a related exemplary embodiment of the present disclosure, a method for lowering or reducing cholesterol levels in an individual is provided where a product containing an effective amount of lunasin peptides to an individual is provided and a claim that the product lowers or reduces cholesterol, total cholesterol, LDL cholesterol or lipid levels in an individual that consumes the composition is made. | 02-27-2014 |
20140107029 | Methods and Apparatus for Creating Particle Derivatives of HDL with Reduced Lipid Content - The present invention is directed to systems, apparatus and methods for creating derivatives of at least one form of HDL without substantially affecting LDL. These derivatives of HDL are particles with reduced lipid content, particularly reduced cholesterol content. These particles have the capacity to bind cholesterol and are administered to a patient to enhance cellular cholesterol efflux and reduce cholesterol levels in cells, tissues, organs, and blood vessels. The present method is useful for treating atherogenic vascular disease and may be combined with other therapies such as statins, inhibitors of cholesterol absorption, niacin, anti-inflammatories, exercise and dietary restriction. | 04-17-2014 |
20140162949 | TREATMENT WITH HUMAN GROWTH HORMONE ANALOGUES - The present invention concerns an improved therapeutic regimen for GHD therapy. In particular, the invention concerns methods for bolus dose administration of a human growth hormone-XTEN (hGH-XTEN) fusion protein. | 06-12-2014 |
20140171365 | PEGYLATED HUMAN HDL PARTICLE AND PROCESS FOR PRODUCTION THEREOF - Compositions comprising pegylated high density lipoprotein (HDL) particles, methods for producing compositions comprising pegylated HDL particles, and methods of treating various diseases and conditions using pegylated HDL particles are provided. | 06-19-2014 |
20140287994 | PEPTIDES HAVING REDUCED TOXICITY THAT STIMULATE CHOLESTEROL EFFLUX - The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation. | 09-25-2014 |
20140303081 | APOPTOSIS-TARGETING NANOPARTICLES - Nanoparticles include a core and one or more targeting moieties, as well as one or more contrast agents or one or more therapeutic agents. The contrast agents or therapeutic agents may be contained or embedded within the core. If the nanoparticle includes therapeutic agents, the agents are preferably released from the core at a desired rate. The core may be biodegradable and may release the agents as the core is degraded or eroded. The targeting moieties preferably extend outwardly from the core so that they are available for interaction with cellular components, which interactions will target the nanoparticles to the appropriate cells, such as apoptotic cells; organelles, such as mitochondria; or the like. The targeting moieties may be tethered to the core or components that interact with the core. | 10-09-2014 |
20140336113 | COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING HYPERLIPIDEMIA, FATTY LIVER, ATHEROSCLEROSIS AND OTHER DISORDERS ASSOCIATED WITH METABOLIC SYNDROME - The present invention relates to compositions and methods for treating diseases associated with dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, steatohepatitis, atherosclerosis, obesity, hyperglycemia, metabolic syndrome, and related aspects of and conditions associated with metabolic syndrome. The compositions and methods disclosed herein are useful for regulating the lipid balance (lipid homeostasis) in a subject. Compositions and methods including a Nuclear Transport Modifier may be administered to a subject to modulate the transport of transcription factors, mediated by nuclear import adaptors, into the nucleus of a cell resulting in a decrease in cholesterol and triglyceride levels in the blood and liver, a decrease in atherosclerotic lesion size, a decrease in body weight and in hyperglycemia, a reduction of fatty liver inflammation, and an improvement in liver function. | 11-13-2014 |
20140378376 | Dosage Regime for Apolipoprotein Formulations - An apolipoprotein formulation is provided at a fixed dosage that is efficacious in the prophylactic and/or therapeutic treatment of diseases or conditions including, but not limited to cardiovascular disease, acute coronary syndrome, atherosclerosis, unstable angina pectoris, and myocardial infarction. More particularly, the fixed dosage apolipoprotein formulation displays relatively reduced inter-patient variability compared to weight-adjusted dosages. Typically, the apolipoprotein formulation is a reconstituted high density lipoprotein formulation comprising ApoA1, one or more lipids such as phosphatidylcholine, sphingomyelin and/or phosphatidylglycerol and, optionally, a detergent such as cholate at a level that does not induce liver toxicity. | 12-25-2014 |
20150094261 | SYNTHETIC BILE ACID COMPOSITIONS AND METHODS - Bile acids and related compositions and methods of synthesis and use. More specifically, deoxycholic acid and related compositions, said compositions being free of all moieties of animal origin and free of pyrogenic moieties. | 04-02-2015 |
20150141330 | APOLIPOPROTEIN A-I MIMICS - Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder. | 05-21-2015 |
20150291682 | MIMETIC PEPTIDES - The invention relates to mimetic peptides of epitope(s) of Apolipoprotein A-I, diagnostic immunoassays comprising such mimetic peptides, as well as methods for diagnosing and methods for preventing and/or treating a cardiovascular disease. | 10-15-2015 |
20150316566 | HDL THERAPY MARKERS - The present application relates to companion diagnostic assays for therapeutic agents that mimic HDL or elevate HDL expression levels. The present application also related to methods of treatment of familial hypoalphalipoproteinemias. | 11-05-2015 |
20150343027 | Hypotonic Aqueous Composition with Reduced Chloride Content, With or Without Phospholipids - An aqueous composition for application in a method for surgical or therapeutic treatment of the human or animal body or in a diagnostic procedure which is practiced on the human or animal body, the composition comprising osmotically active particles and containing less than 70 μl | 12-03-2015 |
20150355203 | USE OF LYMPHOCYTE ACTIVATION GENE 3 (LAG-3) EXPRESSION PROFILING AS A BIOMARKER FOR ASSESSING INFLAMMASOMES, CHRONIC INFLAMMATORY DISEASES AND DYSFUNCTIONAL HDL - A method for determining whether a subject has or is predisposed to abnormal expression of inflammasomes and/or to dysfunctional HDL suitable for use in diagnosing atherosclerosis, chronic inflammatory disease, Incident Cardiovascular Disease (ICD) and other pathologies characterized by an inflammatory response. Specifically, a protein assay that measures LAG-3 can be used as a diagnostic predictor of pathologies such as infection, inflammation, chronic inflammatory disease, and coronary artery disease. The diagnostic is combined with the therapeutic use of a remediating drug for treatment. | 12-10-2015 |
20160000866 | CTHRC1 RECEPTOR AND METHODS OF USE THEREOF - The invention features compositions and methods for treating and preventing steatosis, osteoporosis, and muscle weakness featuring the receptor for the collagen triple helix repeat containing-1 (Cthrc1) protein. | 01-07-2016 |
20160024182 | Oxidant Resistant Apolipoprotein A-1 and Mimetic Peptides - A purified polypeptide includes an ApoA1 mimetic or fragment thereof that are resistant to oxidation. | 01-28-2016 |
20160030513 | Notch1 Decoy Antagonists Protect From Obesity-Induced Insulin Resistance and Fatty Liver - The present invention provides a method of treating a subject suffering from a fatty liver disease which comprises administering to the subject a Notch decoy protein or Jagged inhibitor in an amount effective to treat the subject's fatty liver disease. | 02-04-2016 |
20160031935 | SMALL MOLECULE MODULATORS OF PCSK9 AND METHODS OF USE THEREOF - A compound of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or racemic mixture or stereoisomer thereof, and methods for preventing or treating an LDL-cholesterol-related disease or disorder using such compound(s), and kits and compositions comprising such compound(s). | 02-04-2016 |
20160095901 | LIPOPROTEIN COMPLEXES AND MANUFACTURING AND USES THEREOF - The present disclosure relates to lipoprotein complexes and lipoprotein populations and their use in the treatment and/or prevention of dyslipidemic diseases, disorders, and/or conditions. The disclosure further relates to recombinant expression of apolipoproteins, purification of apolipoproteins, and production of lipoprotein complexes using thermal cycling-based methods. | 04-07-2016 |
20160136242 | Glial Cell Line Derived Neurotrophic Factor, Obesity, and Obesity-Related Diseases and Conditions - The disclosure relates to therapeutic methods for regulating weight gain, metabolic syndrome, and insulin resistance. In certain embodiments, the disclosure relates to methods of treating or preventing obesity, metabolic syndrome, or insulin resistance by administering an effective amount of a pharmaceutical composition comprising one or more GDNF receptor agonists to a subject in need thereof. | 05-19-2016 |
20160143994 | MYONECTIN (CTRP15), COMPOSITIONS COMPRISING SAME, AND METHODS OF USE - Disclosed is the novel myokine known as myonectin (CTRP15) an isolated nucleic acid encoding the myonectin (CTRP15) gene, and the amino acid sequence encoding the myonectin (CTRP15) protein. Methods of isolation of the nucleic acid, protein, polypeptides and methods of making anybodies to myonectin (CTRP15) protein are provided. The use of myonectin (CTRP15) in the modulation of lipid and/or glucose metabolism, suppressing the expression of autophagy genes, inhibiting LC3 lipidation and autophagosome-dependent p62 degradation, and activating the Akt/mTOR pathway is also provided. | 05-26-2016 |
20160145297 | HYDROXY-ETHYLENE DERIVATIVES FOR THE TREATMENT OF ARTHROSIS - The present invention relates to compounds of the formula I and in particular medicaments comprising at least one compound of the formula I for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia. | 05-26-2016 |
20160175396 | METHODS FOR TREATING OR PREVENTING FATTY LIVER DISEASE USING CTRP3 | 06-23-2016 |
20160176946 | PROCESS FOR PREPARING APOLIPOPROTEIN A-I (APO A-I) | 06-23-2016 |
20160176947 | CONTAMINANT REMOVAL METHOD | 06-23-2016 |
20170233812 | GENETIC MARKERS FOR PREDICTING RESPONSIVENESS TO THERAPY WITH HDL-RAISING OR HDL MIMICKING AGENT | 08-17-2017 |