JP7225090B2 - 接触活性化系に関連する疾患の代謝物バイオマーカー - Google Patents
接触活性化系に関連する疾患の代謝物バイオマーカー Download PDFInfo
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- JP7225090B2 JP7225090B2 JP2019514825A JP2019514825A JP7225090B2 JP 7225090 B2 JP7225090 B2 JP 7225090B2 JP 2019514825 A JP2019514825 A JP 2019514825A JP 2019514825 A JP2019514825 A JP 2019514825A JP 7225090 B2 JP7225090 B2 JP 7225090B2
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2905545T3 (es) | 2010-01-06 | 2022-04-11 | Takeda Pharmaceuticals Co | Proteínas de unión a calicreína plasmática |
| KR102424183B1 (ko) * | 2014-01-21 | 2022-07-26 | 다케다 파머수티컬 컴패니 리미티드 | 혈장 칼리크레인 결합 단백질 및 유전성 혈관부종을 치료하는 데 있어서의 이의 용도 |
| EP3122782A4 (en) | 2014-03-27 | 2017-09-13 | Dyax Corp. | Compositions and methods for treatment of diabetic macular edema |
| MX2019002918A (es) | 2016-09-16 | 2019-07-18 | Dyax Corp | Biomarcadores de metabolitos para enfermedades asociadas con el sistema de activacion por contacto. |
| EP3513196A1 (en) | 2016-09-16 | 2019-07-24 | Dyax Corp. | Protein biomarkers for diseases associated with the contact activation system |
| EP3521828A1 (en) * | 2018-01-31 | 2019-08-07 | Centogene AG | Method for the diagnosis of hereditary angioedema |
| CA3144694A1 (en) | 2019-07-25 | 2021-01-28 | Jose A. Horcajadas | Identification of viable human embryos |
| CN110514772A (zh) * | 2019-08-09 | 2019-11-29 | 中国医学科学院基础医学研究所 | 透明肾细胞癌代谢标志物在肾细胞癌早期筛查和诊断产品中的应用 |
| CN113495137A (zh) * | 2021-06-29 | 2021-10-12 | 江苏省中医院 | 两种代谢标志物单独或联合在制备诊断克罗恩病的试剂盒中的应用 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070218047A1 (en) | 2004-01-28 | 2007-09-20 | Bayer Healthcare Ag | Diagnostics and Therapeutics for Diseases Associated with Kallikrein 2 (KLK2) |
| JP2012211908A (ja) | 2009-08-12 | 2012-11-01 | Human Metabolome Technologies Inc | うつ病のバイオマーカー、うつ病のバイオマーカーの測定法、コンピュータプログラム、及び記憶媒体 |
| JP2013509593A (ja) | 2009-10-30 | 2013-03-14 | ネステク ソシエテ アノニム | 過敏性腸症候群の診断方法 |
| WO2015061183A1 (en) | 2013-10-21 | 2015-04-30 | Dyax Corp. | Assays for determining plasma kallikrein system biomarkers |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6057287A (en) | 1994-01-11 | 2000-05-02 | Dyax Corp. | Kallikrein-binding "Kunitz domain" proteins and analogues thereof |
| EP0739355B1 (en) | 1994-01-11 | 2004-09-08 | Dyax Corporation | Kallikrein-inhibiting "kunitz domain" proteins and analogues thereof |
| US20040152633A1 (en) | 2001-05-31 | 2004-08-05 | Jorgensen Marianne Ulrich | Kunitz-type sequences and polypeptides |
| ATE528014T1 (de) | 2002-06-07 | 2011-10-15 | Dyax Corp | Polypeptid mit modifizierten kunitz domains |
| US7153829B2 (en) * | 2002-06-07 | 2006-12-26 | Dyax Corp. | Kallikrein-inhibitor therapies |
| EP1598428A1 (en) | 2004-05-18 | 2005-11-23 | Georg Dewald | Methods and kits to detect Hereditary angioedema type III |
| ITMI20041963A1 (it) * | 2004-10-15 | 2005-01-15 | Luso Farmaco Inst | "antagonisti non-peptidici della bradichinina e loro composizioni farmaceutiche" |
| US20070218519A1 (en) | 2005-10-11 | 2007-09-20 | Tethys Bioscience, Inc. | Diabetes-associated markers and methods of use thereof |
| US7276480B1 (en) | 2005-12-30 | 2007-10-02 | Dyax Corp. | Prevention and reduction of blood loss |
| US7625944B2 (en) * | 2006-07-31 | 2009-12-01 | Activesite Pharmaceuticals, Inc. | Inhibitors of plasma kallikrein |
| WO2008019052A2 (en) | 2006-08-03 | 2008-02-14 | Numira Biosciences, Inc. | Methods and compositions for identifying biomarkers |
| WO2008046510A1 (en) | 2006-10-16 | 2008-04-24 | Bayer Healthcare Ag | Fn1 as a biomarker, therapeutic and diagnostic target |
| EP2102357B1 (en) | 2006-10-16 | 2013-11-27 | Bayer Intellectual Property GmbH | Ltbp2 as a biomarker, therapeutic and diagnostic target |
| WO2008046528A1 (en) | 2006-10-16 | 2008-04-24 | Bayer Healthcare Ag | Npr3 as a biomarker, therapeutic and diagnostic target |
| WO2008046512A1 (en) | 2006-10-16 | 2008-04-24 | Bayer Schering Pharma Aktiengesellschaft | Prss23 as a biomarker, therapeutic and diagnostic target |
| WO2008046508A1 (en) | 2006-10-16 | 2008-04-24 | Bayer Healthcare Ag | Tgfb2 as a biomarker, therapeutic and diagnostic target |
| EP2074429B1 (en) | 2006-10-16 | 2012-04-04 | Bayer Pharma Aktiengesellschaft | Ctgf as a biomarker, therapeutic and diagnostic target |
| US20100081136A1 (en) | 2006-10-16 | 2010-04-01 | Stefan Golz | Crtac as a biomarker, therapeutic and diagnostic target |
| FR2914066B1 (fr) * | 2007-03-20 | 2009-05-22 | Polyintell Sarl | Kit d'analyse comprenant au moins deux polymeres a empreintes moleculaires et au moins un marqueur, ainsi que le procede d'analyse l'utilisant |
| US10539580B2 (en) * | 2008-04-29 | 2020-01-21 | Psychemedics Corporation | Solid phase multi-analyte assay |
| WO2010045180A1 (en) * | 2008-10-13 | 2010-04-22 | Metabolon, Inc. | Biomarkers for inflammatory bowel disease and methods using the same |
| US20110098993A1 (en) | 2009-10-27 | 2011-04-28 | Anaxomics Biotech Sl. | Methods and systems for identifying molecules or processes of biological interest by using knowledge discovery in biological data |
| EP2502079B1 (en) * | 2009-11-20 | 2015-01-28 | Pharnext | New diagnostic tools for charcot-marie-tooth disease |
| ES2905545T3 (es) | 2010-01-06 | 2022-04-11 | Takeda Pharmaceuticals Co | Proteínas de unión a calicreína plasmática |
| JP2013522652A (ja) | 2010-03-23 | 2013-06-13 | パーデュー・リサーチ・ファウンデーション | 代謝物プロファイリングを用いた再発乳癌の早期検出 |
| US20120040383A1 (en) | 2010-08-12 | 2012-02-16 | Wei Jia | Methods and Kits Relating To Metabolite Biomarkers For Colorectal Cancer |
| IL269565B2 (en) | 2011-01-06 | 2024-06-01 | Dyax Corp | Plasma kallikrein binding proteins |
| JP5986440B2 (ja) | 2012-07-05 | 2016-09-06 | 国立医薬品食品衛生研究所長 | アルツハイマー病の発症を予測する方法 |
| US10220089B2 (en) * | 2012-08-29 | 2019-03-05 | California Institute Of Technology | Diagnosis and treatment of autism spectrum disorder |
| US20140086825A1 (en) * | 2012-09-24 | 2014-03-27 | William J. McFaul | Methods and kits for assessing, modulating and treating substances affecting bodily processes |
| CN111044725B (zh) | 2013-01-20 | 2024-03-29 | 武田药品工业株式会社 | 缓激肽介导的病症的评估和治疗 |
| PL2946206T3 (pl) | 2013-01-20 | 2019-07-31 | Dyax Corp. | Ocena, testy i leczenie zaburzeń mediowanych przez PKAL |
| JP2016514141A (ja) | 2013-03-14 | 2016-05-19 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | B2−ブラジキニン受容体媒介の血管浮腫の治療方法 |
| NZ712167A (en) * | 2013-03-15 | 2018-05-25 | Intrexon Corp | Boron-containing diacylhydrazines |
| EP2884282A1 (en) * | 2013-12-13 | 2015-06-17 | CONARIS research institute AG | Use of tryptophan as a biomarker for patient selection, dosing and therapy monitoring for pharmaceutical compositions targeting the intestinal microbiota in diseases featuring tryptophan deficiency |
| AU2015243857A1 (en) | 2014-04-08 | 2016-10-20 | Metabolon, Inc. | Small molecule biochemical profiling of individual subjects for disease diagnosis and health assessment |
| AU2015321470B2 (en) | 2014-09-22 | 2018-11-15 | National Health Research Institutes | Use of 5-methoxytryptophan as diagnostic agent of inflammatory diseases |
| US20180298110A1 (en) * | 2015-03-30 | 2018-10-18 | Dyax Corp. | Plasma kallikrein inhibitors and uses thereof for preventing hereditary angioedema attack |
| US10870115B2 (en) | 2015-08-13 | 2020-12-22 | Dyax Corp. | Evacuated blood collection tubes containing protease inhibitors for the assessment of contact system activation |
| JP6570472B2 (ja) | 2016-03-30 | 2019-09-04 | 株式会社マンダム | 毛髪の損傷の評価方法 |
| EP3513196A1 (en) | 2016-09-16 | 2019-07-24 | Dyax Corp. | Protein biomarkers for diseases associated with the contact activation system |
| MX2019002918A (es) | 2016-09-16 | 2019-07-18 | Dyax Corp | Biomarcadores de metabolitos para enfermedades asociadas con el sistema de activacion por contacto. |
| BR112019005172A2 (pt) | 2016-09-16 | 2019-07-02 | Dyax Corp. | método e kit para analisar uma amostra |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070218047A1 (en) | 2004-01-28 | 2007-09-20 | Bayer Healthcare Ag | Diagnostics and Therapeutics for Diseases Associated with Kallikrein 2 (KLK2) |
| JP2012211908A (ja) | 2009-08-12 | 2012-11-01 | Human Metabolome Technologies Inc | うつ病のバイオマーカー、うつ病のバイオマーカーの測定法、コンピュータプログラム、及び記憶媒体 |
| JP2013509593A (ja) | 2009-10-30 | 2013-03-14 | ネステク ソシエテ アノニム | 過敏性腸症候群の診断方法 |
| WO2015061183A1 (en) | 2013-10-21 | 2015-04-30 | Dyax Corp. | Assays for determining plasma kallikrein system biomarkers |
Non-Patent Citations (1)
| Title |
|---|
| THON, V. et al.,Lack of dehydroepiandrosterone in type I and II hereditary angioedema and role of danazol in steroid hormone conversion,Allergy,Vol.62,2007年,pp.1320-1325 |
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