ES2402142T3 - Biomarcadores para la enfermedad del hígado graso y métodos que utilizan los mismos - Google Patents
Biomarcadores para la enfermedad del hígado graso y métodos que utilizan los mismos Download PDFInfo
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- ES2402142T3 ES2402142T3 ES08845659T ES08845659T ES2402142T3 ES 2402142 T3 ES2402142 T3 ES 2402142T3 ES 08845659 T ES08845659 T ES 08845659T ES 08845659 T ES08845659 T ES 08845659T ES 2402142 T3 ES2402142 T3 ES 2402142T3
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| US98494207P | 2007-11-02 | 2007-11-02 | |
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| US4245908P | 2008-04-04 | 2008-04-04 | |
| US42459P | 2008-04-04 | ||
| PCT/US2008/082013 WO2009059150A2 (en) | 2007-11-02 | 2008-10-31 | Biomarkers for fatty liver disease and methods using the same |
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| ES2402142T3 true ES2402142T3 (es) | 2013-04-29 |
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| ES08845659T Active ES2402142T3 (es) | 2007-11-02 | 2008-10-31 | Biomarcadores para la enfermedad del hígado graso y métodos que utilizan los mismos |
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Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPWO2009001862A1 (ja) * | 2007-06-25 | 2010-08-26 | 味の素株式会社 | 内臓脂肪蓄積の評価方法 |
| EP2227689B1 (en) * | 2007-11-02 | 2012-12-26 | Metabolon, Inc. | Biomarkers for fatty liver disease and methods using the same |
| CA2724247A1 (en) | 2008-05-28 | 2009-12-23 | Basf Se | Means and methods for assessing liver toxicity |
| EP2286235A1 (en) * | 2008-05-28 | 2011-02-23 | Basf Se | Means and methods for assessing liver enzyme induction |
| EP2381259B1 (en) * | 2008-12-24 | 2016-09-21 | Keio University | Method for measuring liver disease markers and test method for pharmaceutical preparation |
| CN102741426B (zh) * | 2009-09-11 | 2015-03-25 | 香港中文大学 | 用于评估肝病变的方法 |
| JP2011232164A (ja) * | 2010-04-27 | 2011-11-17 | Keio Gijuku | 肝臓疾患マーカー、その測定方法、装置及び医薬品の検定方法 |
| WO2012000770A1 (en) | 2010-06-10 | 2012-01-05 | Metanomics Health Gmbh | Methods to diagnose liver diseases |
| WO2011158590A1 (ja) * | 2010-06-18 | 2011-12-22 | 学校法人 慶應義塾 | 肝臓疾患マーカー、その測定方法、装置及び医薬品の検定方法 |
| US8728824B2 (en) | 2011-06-22 | 2014-05-20 | Quest Diagnostics Investments Inc. | Mass spectrometric determination of fatty acids |
| WO2013002381A1 (ja) | 2011-06-30 | 2013-01-03 | 味の素株式会社 | 脂肪性肝疾患の評価方法、脂肪性肝疾患評価装置、脂肪性肝疾患評価方法、脂肪性肝疾患評価プログラム、脂肪性肝疾患評価システム、情報通信端末装置、および脂肪性肝疾患の予防・改善物質の探索方法 |
| BR112015006284A2 (pt) * | 2012-09-21 | 2017-07-04 | Governing Council Univ Toronto | cpmf como um biomarcador para diabetes e métodos associados |
| CN107076753B (zh) * | 2014-09-30 | 2019-01-18 | 深圳华大基因科技有限公司 | 肥胖人群特异性生物标志组合物及其用途 |
| US20170370954A1 (en) * | 2014-11-19 | 2017-12-28 | Metabolon, Inc. | Biomarkers for Fatty Liver Disease and Methods Using the Same |
| RU2617236C1 (ru) * | 2015-12-02 | 2017-04-24 | государственное бюджетное образовательное учреждение высшего профессионального образования "Северо-Западный государственный медицинский университет им. И.И. Мечникова" Министерства здравоохранения Российской Федерации | Способ определения целесообразности проведения иммунологического обследования у пациентов неалкогольной жировой болезнью печени |
| US12285464B2 (en) | 2016-04-18 | 2025-04-29 | The Trustees Of Columbia University In The City Of New York | Therapeutic targets involved in the progression of nonalcoholic steatohepatitis (NASH) |
| JP7036805B2 (ja) | 2016-05-29 | 2022-03-15 | 深▲じぇん▼市▲絵▼云生物科技有限公司 | 肝疾患関連バイオマーカーおよびその使用方法 |
| EP3502703A1 (en) | 2017-12-22 | 2019-06-26 | Metanomics Health GmbH | Method for the assessment of nafld |
| CN109060977B (zh) * | 2018-07-13 | 2024-07-02 | 深圳市绘云生物科技有限公司 | 用于肝纤维化和肝硬化诊断的生物标志物和试剂盒及使用方法 |
| US11693005B2 (en) | 2018-08-07 | 2023-07-04 | Florida Atlantic University Board Of Trustees | Methods for identifying treatments that reduce the actions of substances of abuse and addiction |
| JP6998023B2 (ja) * | 2018-09-26 | 2022-02-10 | 株式会社島津製作所 | 非アルコール性脂肪肝疾患の検出方法、非アルコール性脂肪肝疾患検出用キットおよび非アルコール性脂肪肝疾患検出用バイオマーカー |
| US20200241005A1 (en) * | 2019-01-25 | 2020-07-30 | Viscient Biosciences, Inc. | Compositions and methods for the diagnosis and treatment of diseases of the liver |
| US20230203583A1 (en) * | 2020-05-04 | 2023-06-29 | University Of Florida Research Foundation, Incorporated | Biomarkers for assessing liver disease |
| US20230137741A1 (en) | 2021-11-01 | 2023-05-04 | Matterworks Inc | Methods and compositions for analyte quantification |
| US12100484B2 (en) | 2021-11-01 | 2024-09-24 | Matterworks Inc | Methods and compositions for analyte quantification |
| CN116165385B (zh) * | 2023-04-25 | 2023-07-18 | 南方医科大学南方医院 | 用于肝癌诊断的血清代谢标志物及其筛选方法和应用 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61260896A (ja) * | 1985-05-15 | 1986-11-19 | Sekisui Chem Co Ltd | 胆汁酸の分析方法 |
| WO1996037777A1 (en) * | 1995-05-23 | 1996-11-28 | Nelson Randall W | Mass spectrometric immunoassay |
| US7329489B2 (en) | 2000-04-14 | 2008-02-12 | Matabolon, Inc. | Methods for drug discovery, disease treatment, and diagnosis using metabolomics |
| AU2001262943A1 (en) | 2000-04-14 | 2001-10-30 | Metabolon, Inc. | Methods for drug discovery, disease treatment, and diagnosis using metabolomics |
| AU2002308701A1 (en) * | 2001-05-14 | 2002-11-25 | University Of Maryland, Baltimore | Novel alanine transaminase enzyme and methods of use |
| JP2003139753A (ja) * | 2001-11-02 | 2003-05-14 | Mitsubishi Pharma Corp | 胆汁酸１８成分の一斉分析法 |
| ES2226549B1 (es) * | 2002-12-18 | 2006-07-16 | One Way Liver Genomics, S.L. | Metodo para el diagnostico de esteatohepatitis no alcoholica (nash) mediante el empleo de marcadores moleculares. |
| US20040121305A1 (en) * | 2002-12-18 | 2004-06-24 | Wiegand Roger Charles | Generation of efficacy, toxicity and disease signatures and methods of use thereof |
| US7452678B2 (en) * | 2003-06-24 | 2008-11-18 | Bristol-Myers Squibb Company | Identification of biomarkers for liver toxicity |
| RU2422450C2 (ru) * | 2003-11-19 | 2011-06-27 | Метабазис Терапеутикс, Инк. | Новые фосфорсодержащие тиромиметики |
| US7078064B2 (en) * | 2003-12-03 | 2006-07-18 | George Zabrecky | Compositions and methods useful for treating and preventing chronic liver disease, chronic HCV infection and non-alcoholic steatohepatitis |
| JP4682980B2 (ja) * | 2004-04-23 | 2011-05-11 | 味の素株式会社 | 非アルコール性脂肪肝炎鑑別方法 |
| EP1619257A1 (en) * | 2004-07-23 | 2006-01-25 | One Way Liver Genomics, S.L. | Method for the in vitro diagnosis of non-alcoholic steatohepatitis |
| US20060160237A1 (en) * | 2004-12-06 | 2006-07-20 | Applera Corporation | Method of screening urine for organic acids |
| US7860656B2 (en) * | 2005-02-03 | 2010-12-28 | Assistance Publique-Hopitaux De Paris (Ap-Hp) | Diagnosis method of hepatic steatosis using biochemical markers |
| US20070004045A1 (en) * | 2005-06-07 | 2007-01-04 | Xia Xu | Analysis of large numbers of estrogens and other steroids and applications thereof |
| TW200745556A (en) * | 2006-01-24 | 2007-12-16 | Ind Tech Res Inst | Biomarkers for liver fibrotic injury |
| JP5227168B2 (ja) | 2006-03-29 | 2013-07-03 | ヤマサ醤油株式会社 | 肝障害の検出方法、判定方法及び予測方法 |
| US20090111122A1 (en) * | 2006-04-06 | 2009-04-30 | Eisai R&D Management Co., Ltd. | METHOD FOR NON-INVASIVE EXAMINATION OF NON-ALCOHOLIC STEATOHEPATITIS BY QUANTIFICATION OF CYTOCHROME-c, AND TEST KIT |
| WO2007136674A1 (en) | 2006-05-19 | 2007-11-29 | The Cleveland Clinic Foundation | Detection and monitoring of liver damage |
| CN101523221A (zh) * | 2006-08-08 | 2009-09-02 | 利普米克斯科技公司 | 非酒精性脂肪肝病(nafld)和非酒精性脂肪性肝炎(nash)的标记及其使用方法 |
| US20090075284A1 (en) * | 2006-09-19 | 2009-03-19 | The Regents Of The University Of Michigan | Metabolomic profiling of prostate cancer |
| JP5299960B2 (ja) * | 2006-11-06 | 2013-09-25 | 公立大学法人横浜市立大学 | 脂肪性肝疾患の診断方法、診断装置、診断プログラム、診断薬及び脂肪性肝疾患用治療薬のスクリーニング方法 |
| WO2008156662A1 (en) * | 2007-06-14 | 2008-12-24 | George Mason Intellectual Properties, Inc. | Methods of diagnosing non-alcoholic steatohepatitis (nash) |
| EP2164977B1 (en) * | 2007-07-17 | 2013-10-30 | Metabolon, Inc. | Biomarkers for pre-diabetes and methods using the same |
| EP2227689B1 (en) * | 2007-11-02 | 2012-12-26 | Metabolon, Inc. | Biomarkers for fatty liver disease and methods using the same |
| WO2010045180A1 (en) * | 2008-10-13 | 2010-04-22 | Metabolon, Inc. | Biomarkers for inflammatory bowel disease and methods using the same |
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- 2008-10-31 JP JP2010532284A patent/JP5270684B2/ja active Active
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| EP2546649A2 (en) | 2013-01-16 |
| WO2009059150A2 (en) | 2009-05-07 |
| US9977034B2 (en) | 2018-05-22 |
| US20150377910A1 (en) | 2015-12-31 |
| EP2227689A2 (en) | 2010-09-15 |
| EP2546649A3 (en) | 2013-03-27 |
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