JP2007524847A5 - - Google Patents
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- JP2007524847A5 JP2007524847A5 JP2006538558A JP2006538558A JP2007524847A5 JP 2007524847 A5 JP2007524847 A5 JP 2007524847A5 JP 2006538558 A JP2006538558 A JP 2006538558A JP 2006538558 A JP2006538558 A JP 2006538558A JP 2007524847 A5 JP2007524847 A5 JP 2007524847A5
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- Prior art keywords
- cystatin
- alzheimer
- biomarker
- peptide
- disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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| US7707134B2 (en) * | 2005-01-14 | 2010-04-27 | Siemens Medical Solutions Usa, Inc. | System and method for molecular diagnosis of depression based on boosting classification |
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| WO2006106115A2 (de) * | 2005-04-06 | 2006-10-12 | Mosaiques Diagnostics And Therapeutics Ag | Polypeptidmarker zur diagnose von alzheimer |
| WO2006110621A2 (en) * | 2005-04-11 | 2006-10-19 | Cornell Research Foundation, Inc. | Multiplexed biomarkers for monitoring the alzheimer's disease state of a subject |
| US20100098682A1 (en) * | 2005-06-14 | 2010-04-22 | D Adamio Luciano | Effect of Bri Proteins on Ass Production |
| EP1907838B1 (en) * | 2005-06-16 | 2011-06-01 | Vermillion, Inc. | Fragment of neurosecretory protein vgf as a biomarker for alzheimer's disease |
| WO2007012052A1 (en) * | 2005-07-20 | 2007-01-25 | Medical College Of Georgia Research Institute | Use of protein profiles in disease diagnosis and treatment |
| CN117903302A (zh) | 2005-11-30 | 2024-04-19 | Abbvie 公司 | 抗-Aβ球聚体抗体，其相关产品，生产所述抗体的方法，所述抗体的应用以及使用方法 |
| PT1976877E (pt) | 2005-11-30 | 2014-04-29 | Abbvie Inc | Anticorpos monoclonais contra proteína beta-amilóide e suas utilizações |
| WO2007105442A1 (ja) * | 2006-02-22 | 2007-09-20 | Kyowa Hakko Kogyo Co., Ltd. | 摂食障害または摂水障害の治療薬 |
| EP2322531A3 (en) * | 2006-02-28 | 2011-09-07 | Phenomenome Discoveries Inc. | Methods for the diagnosis of dementia and other neurological disorders |
| EP1996949A4 (en) | 2006-03-11 | 2010-01-20 | Univ Leland Stanford Junior | BETA-2 MICROGLOBULIN AS A BIOMARKER FOR PERIPHERAL ARTERY DISEASE |
| WO2007136614A2 (en) * | 2006-05-19 | 2007-11-29 | Merck & Co., Inc. | Assays and methods for the diagnosis and progression of alzheimer's disease using a multi-analyte marker panel |
| WO2007139777A2 (en) * | 2006-05-26 | 2007-12-06 | Merck & Co., Inc. | Methods for the diagnosis and prognosis of alzheimer's disease using csf protein profiling |
| US7851172B2 (en) * | 2006-07-25 | 2010-12-14 | University Of Kentucky Research Foundation | Biomarkers of mild cognitive impairment and alzheimer's disease |
| EP2076172A4 (en) * | 2006-10-27 | 2012-03-21 | Aretais Inc | USE OF COHERENT RAMAN PROCEDURES FOR MEDICAL DIAGNOSTIC AND THERAPEUTIC PURPOSES AND CALIBRATION METHOD THEREFOR |
| DE102006056337A1 (de) * | 2006-11-29 | 2008-06-05 | B.R.A.H.M.S Ag | In vitro Verfahren zur Diagnose und Frühdiagnose von neurodegenerativen Erkrankungen |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| GB0701626D0 (en) * | 2007-01-22 | 2007-03-07 | Cambridge Entpr Ltd | Methods and biomarkers for diagnosing and monitoring psychotic disorders |
| CA2695167C (en) | 2007-02-08 | 2011-11-01 | Phenomenome Discoveries Inc. | Methods for the treatment of elevated cholesterol levels |
| US20100311767A1 (en) | 2007-02-27 | 2010-12-09 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
| EP2198292A4 (en) | 2007-08-21 | 2010-09-08 | Univ Washington | IMPROVED MORBUS ALZHEIMER DIAGNOSIS |
| CA2718955C (en) | 2008-03-21 | 2015-10-13 | Manuela G. Neuman | Methods and kits for the differential diagnosis of alzheimer's disease versus frontotemporal dementia and for the diagnosis of frontotemporal dementia comprising fas-l and ck 18 as biomarkers |
| AU2009282117B2 (en) | 2008-08-11 | 2016-05-12 | Banyan Biomarkers, Inc. | Biomarker detection process and assay of neurological condition |
| US20140342381A1 (en) * | 2008-08-11 | 2014-11-20 | Banyan Biomarkers, Inc. | Devices and methods for biomarker detection process and assay of neurological condition |
| US20110263450A1 (en) * | 2008-09-26 | 2011-10-27 | The University Of Melbourne | Alzheimer's disease biomarkers |
| GB0818650D0 (en) | 2008-10-10 | 2008-11-19 | Uni I Oslo | Methods |
| US20120094315A1 (en) * | 2008-12-09 | 2012-04-19 | Stephanie Fryar-Williams | Biomarkers for the diagnosis and/or prediction of susceptibility to mental and neurodegenerative disorders |
| WO2010087771A1 (en) | 2009-01-30 | 2010-08-05 | Alphabeta Ab | Compound and method for treatment of alzheimer's disease |
| WO2011005893A2 (en) * | 2009-07-07 | 2011-01-13 | Abbott Laboratories | Biomarkers and methods for detecting alzheimer's disease |
| EP2459742B1 (en) | 2009-07-29 | 2016-04-06 | Pharnext | New diagnostic tools for alzheimer disease |
| US20110097747A1 (en) * | 2009-10-26 | 2011-04-28 | Kevin Jones | Monoclonal antibody binds antigen associated with human tumors |
| CN104744591B (zh) | 2010-04-15 | 2022-09-27 | Abbvie德国有限责任两合公司 | β淀粉样蛋白结合蛋白 |
| EP3533803B1 (en) | 2010-08-14 | 2021-10-27 | AbbVie Inc. | Anti-amyloid-beta antibodies |
| WO2012037232A2 (en) * | 2010-09-16 | 2012-03-22 | University Of Miami | Compositions, methods and kits for detecting and treating alzheimer's disease |
| JP6012923B2 (ja) * | 2010-12-22 | 2016-10-25 | 株式会社Ｍｃｂｉ | 認知機能障害疾患のバイオマーカーおよび該バイオマーカーを用いる認知機能障害疾患の検出方法 |
| WO2012138284A1 (en) * | 2011-04-05 | 2012-10-11 | Alphabeta Ab | Amyloidosis target useful in methods of treatment and for screening of compounds |
| US20140302532A1 (en) | 2011-04-12 | 2014-10-09 | Quanterix Corporation | Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury |
| US9835621B2 (en) | 2011-07-14 | 2017-12-05 | University Of Kentucky Research Foundation | Process for detection of alzheimer's disease from a serum sample |
| WO2013153461A2 (en) | 2012-04-13 | 2013-10-17 | Oasis Diagnostics Corporation | Specific salivary biomarkers for risk detection, early diagnosis, prognosis and monitoring of alzheimer's and parkinson's diseases |
| WO2014040042A2 (en) | 2012-09-10 | 2014-03-13 | The Johns Hopkins University | Diagnostic assay for alzheimer's disease |
| US20140271463A1 (en) * | 2013-03-12 | 2014-09-18 | Stichting Vu-Vumc | Bri2 as a novel biomarker for alzheimer's disease |
| WO2014144663A1 (en) * | 2013-03-15 | 2014-09-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| US20160186263A1 (en) | 2013-05-09 | 2016-06-30 | Trustees Of Boston University | Using plexin-a4 as a biomarker and therapeutic target for alzheimer's disease |
| WO2015020523A1 (en) | 2013-08-07 | 2015-02-12 | Stichting Vu-Vumc | Biomarkers for early diagnosis of alzheimer's disease |
| JP2017505756A (ja) | 2013-12-13 | 2017-02-23 | ザ ジェネラル ホスピタル コーポレイション | 可溶性高分子量（ｈｍｗ）タウ種およびその用途 |
| WO2015152724A2 (en) | 2014-04-02 | 2015-10-08 | Stichting Vu-Vumc | Biomarkers for the detection of frontotemporal dementia |
| US9753036B2 (en) | 2014-04-29 | 2017-09-05 | Edp Biotech Corporation | Methods and compositions for screening and detecting biomarkers |
| GB201504432D0 (en) * | 2015-03-17 | 2015-04-29 | Electrophoretics Ltd | Materials and methods for diagnosis and treatment of alzheimers disease |
| EP3452828A4 (en) * | 2016-05-06 | 2019-12-04 | Nanosomix Inc. | SYNAPTIC PROTEIN BIOMARKERS AND DIFFERENTIAL DIAGNOSIS OF MORBUS ALZHEIMER AND OTHER NEURODEGENERATIVE ILLNESSES |
| WO2017194995A1 (en) * | 2016-05-11 | 2017-11-16 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | A method for determining the temporal progression of a biological phenomenon and associated methods and devices |
| JPWO2018030252A1 (ja) * | 2016-08-09 | 2019-06-20 | 大塚製薬株式会社 | 尿バイオマーカーを用いたアルツハイマー病の診断補助方法 |
| JP6702836B2 (ja) * | 2016-09-28 | 2020-06-03 | ハルメク・ベンチャーズ株式会社 | 認知症判定得点算出装置及びそのプログラム |
| WO2018081649A1 (en) | 2016-10-28 | 2018-05-03 | Banyan Biomarkers, Inc. | Antibodies to ubiquitin c-terminal hydrolase l1 (uch-l1) and glial fibrillary acidic protein (gfap) and related methods |
| ES2600386B8 (es) * | 2016-11-16 | 2017-08-04 | Grifols Worldwide Operations Limited | Método de diagnóstico in vitro de la enfermedad de alzheimer basado en el nivel redox de la albúmina en el líquido cefalorraquídeo |
| JP6359159B2 (ja) * | 2017-07-25 | 2018-07-18 | 株式会社Ｍｃｂｉ | 認知機能障害疾患のバイオマーカーおよび該バイオマーカーを用いる認知機能障害疾患の検出方法 |
| JP7412003B2 (ja) * | 2018-01-18 | 2024-01-12 | ユニバーシティー オブ ノース テキサス ヘルス サイエンス センター アット フォートワース | アルツハイマー病に罹患している患者の特定の亜集団を治療するためのｎｓａｉｄ及びドネペジルについてのコンパニオン診断 |
| WO2019175380A2 (en) * | 2018-03-16 | 2019-09-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antigenic peptides deriving from secretogranin v and uses thereof for the diagnosis and treatment of type 1 diabetes |
| BR112020018828A2 (pt) * | 2018-03-16 | 2021-02-09 | Quest Diagnostics Investments Llc | métodos para detecção de cromogranina através de uma espectrometria de massa |
| CN112703402A (zh) * | 2018-07-19 | 2021-04-23 | 吉宁特有限公司 | 基于标志物分子将个体鉴定为具有淀粉样蛋白阳性痴呆症或处于发展淀粉样蛋白阳性痴呆症的风险中的方法和相关用途 |
| CN113508300A (zh) * | 2018-10-04 | 2021-10-15 | 曼尼托巴大学 | 用于人类阿尔茨海默病的新型生物标记物 |
| US11621087B2 (en) | 2019-09-24 | 2023-04-04 | International Business Machines Corporation | Machine learning for amyloid and tau pathology prediction |
| US11657189B2 (en) | 2020-03-30 | 2023-05-23 | Kyndryl, Inc. | Object loss prevention using cognitive computing |
| JP7109499B2 (ja) * | 2020-05-07 | 2022-07-29 | 一般社団法人脳と心の健康科学研究所 | 認知症判定得点算出装置及びそのプログラム |
| WO2022070798A1 (ja) * | 2020-09-29 | 2022-04-07 | 康弘 橋本 | アルツハイマー病病態鑑別用組み合わせマーカー及びそれを用いたアルツハイマー病病態鑑別方法 |
| CN115066615A (zh) * | 2020-12-28 | 2022-09-16 | 株式会社Mcbi | 判定辅助信息生成方法、判定辅助信息生成系统以及信息处理装置 |
| CN115078570B (zh) * | 2022-05-30 | 2024-05-28 | 郑州大学第一附属医院 | Tau蛋白639位硫氰酸氨基酸修饰在快速质谱法检测阿尔茨海默症中的应用 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| US5010175A (en) | 1988-05-02 | 1991-04-23 | The Regents Of The University Of California | General method for producing and selecting peptides with specific properties |
| SE462454B (sv) | 1988-11-10 | 1990-06-25 | Pharmacia Ab | Maetyta foer anvaendning i biosensorer |
| IE66205B1 (en) | 1990-06-14 | 1995-12-13 | Paul A Bartlett | Polypeptide analogs |
| US5650489A (en) | 1990-07-02 | 1997-07-22 | The Arizona Board Of Regents | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US6283761B1 (en) | 1992-09-08 | 2001-09-04 | Raymond Anthony Joao | Apparatus and method for processing and/or for providing healthcare information and/or healthcare-related information |
| US5288514A (en) | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
| ATE242485T1 (de) | 1993-05-28 | 2003-06-15 | Baylor College Medicine | Verfahren und massenspektrometer zur desorption und ionisierung von analyten |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5593853A (en) | 1994-02-09 | 1997-01-14 | Martek Corporation | Generation and screening of synthetic drug libraries |
| US5539083A (en) | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
| US5525735A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies Nv | Methods for synthesizing diverse collections of pyrrolidine compounds |
| US5549974A (en) | 1994-06-23 | 1996-08-27 | Affymax Technologies Nv | Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof |
| US5569588A (en) | 1995-08-09 | 1996-10-29 | The Regents Of The University Of California | Methods for drug screening |
| NZ516848A (en) | 1997-06-20 | 2004-03-26 | Ciphergen Biosystems Inc | Retentate chromatography apparatus with applications in biology and medicine |
| CA2323638A1 (en) | 1998-04-03 | 1999-10-14 | Phylos, Inc. | Addressable protein arrays |
| US6406921B1 (en) | 1998-07-14 | 2002-06-18 | Zyomyx, Incorporated | Protein arrays for high-throughput screening |
| EP1123509B1 (en) | 1998-10-23 | 2004-12-29 | EVOTEC Neurosciences GmbH | Methods of diagnosing or prognosing alzheimer's disease |
| WO2000056934A1 (en) | 1999-03-24 | 2000-09-28 | Packard Bioscience Company | Continuous porous matrix arrays |
| AU774336B2 (en) | 1999-04-27 | 2004-06-24 | Ciphergen Biosystems, Inc. | Probes for a gas phase ion spectrometer |
| AU779028B2 (en) | 1999-04-29 | 2005-01-06 | Ciphergen Biosystems, Inc. | Sample holder with hydrophobic coating for gas phase mass spectrometers |
| EP1236173A2 (en) | 1999-10-27 | 2002-09-04 | Biowulf Technologies, LLC | Methods and devices for identifying patterns in biological systems |
| WO2002002824A1 (en) | 2000-07-03 | 2002-01-10 | University Of South Florida | Methods and assays for diagnosing alzheimer's disease |
| US6925389B2 (en) | 2000-07-18 | 2005-08-02 | Correlogic Systems, Inc., | Process for discriminating between biological states based on hidden patterns from biological data |
| JP2004522980A (ja) * | 2000-11-16 | 2004-07-29 | シファーゲン バイオシステムズ， インコーポレイテッド | 質量スペクトルを分析する方法 |
| WO2002090974A2 (de) * | 2001-05-09 | 2002-11-14 | Biovision Ag | Verfahren zum nachweis einer progedienten, chronisch-demenziellen erkrankung, zugehörige peptide und nachweisreagenzien |
| US7113896B2 (en) | 2001-05-11 | 2006-09-26 | Zhen Zhang | System and methods for processing biological expression data |
| JP4264002B2 (ja) | 2001-07-17 | 2009-05-13 | バイオ−ラド ラボラトリーズ インコーポレイテッド | ラテックスベース吸着チップ |
| PL369446A1 (en) * | 2001-09-25 | 2005-04-18 | Immuno-Biological Laboratories Co, Ltd. | Recombinant anti-osteopontin antibody and use thereof |
| US7842498B2 (en) | 2001-11-08 | 2010-11-30 | Bio-Rad Laboratories, Inc. | Hydrophobic surface chip |
| US20030100016A1 (en) | 2001-11-23 | 2003-05-29 | George Jackowski | Complement C3 precursor biopolymer markers predictive of Alzheimers disease |
| WO2003064594A2 (en) | 2002-01-25 | 2003-08-07 | Ciphergen Biosystems, Inc. | Monomers and polymers having energy absorbing moieties of use in desorption/ionization of analytes |
| US20020193950A1 (en) | 2002-02-25 | 2002-12-19 | Gavin Edward J. | Method for analyzing mass spectra |
| WO2004001421A2 (en) * | 2002-06-21 | 2003-12-31 | Innogenetics N.V. | Method for the diagnosis and differential diagnosis of neurological diseases |
| CA2745731C (en) * | 2002-08-23 | 2015-05-12 | Bayer Schering Pharma Aktiengesellschaft | Biomarkers for diagnosing alzheimer's disease |
| US7632686B2 (en) * | 2002-10-03 | 2009-12-15 | Anderson Forschung Group | High sensitivity quantitation of peptides by mass spectrometry |
| JO3421B1 (ar) | 2011-06-20 | 2019-10-20 | H Lundbeck As | طريقة لإعطاء 1-((1ار.3س)-6-كلورو-3-فينيل-اندان-1-ايل)-1.2.2-ترايميثيل- بيبيرازين واملاجها لمعالجة انفصام الشخصية |
-
2004
- 2004-11-06 EP EP04810948.2A patent/EP1694816B1/en not_active Expired - Lifetime
- 2004-11-06 WO PCT/US2004/037994 patent/WO2005047484A2/en not_active Ceased
- 2004-11-06 EP EP11156064A patent/EP2369347A1/en not_active Withdrawn
- 2004-11-06 JP JP2006538558A patent/JP4796967B2/ja not_active Expired - Fee Related
- 2004-11-06 EP EP11156065A patent/EP2369348A1/en not_active Withdrawn
- 2004-11-06 US US10/982,545 patent/US7794948B2/en not_active Expired - Fee Related
-
2010
- 2010-07-28 US US12/845,025 patent/US20110129920A1/en not_active Abandoned
-
2011
- 2011-01-24 JP JP2011012368A patent/JP5479379B2/ja not_active Expired - Fee Related
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