JP4879906B2 - 関節変性疾患及び炎症性疾患の治療に有用な分子標的及び化合物、並びにそれらの同定方法 - Google Patents
関節変性疾患及び炎症性疾患の治療に有用な分子標的及び化合物、並びにそれらの同定方法 Download PDFInfo
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Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2566561T3 (es) | 2001-07-12 | 2016-04-13 | University Of Massachusetts | Producción in vivo de ARN pequeños de interferencia que median el silenciamiento génico |
| US7306923B2 (en) * | 2004-06-14 | 2007-12-11 | Galapagos N.V. | Methods for identification, and compounds useful for the treatment of degenerative & inflammatory diseases |
| ES2431643T3 (es) | 2005-11-01 | 2013-11-27 | Abbvie Biotechnology Ltd | Métodos para determinar la eficacia de adalimumab en sujetos que tienen espondilitis anquilosante utilizando CTX-II y MMP3 como biomarcadores |
| WO2008058018A2 (en) | 2006-11-02 | 2008-05-15 | Mayo Foundation For Medical Education And Research | Predicting cancer outcome |
| WO2008155397A2 (en) | 2007-06-20 | 2008-12-24 | Galapagos N.V. | Molecular targets and compounds, and methods to identify the same, useful in the treatment of bone and joint degenerative diseases |
| WO2009143372A2 (en) * | 2008-05-21 | 2009-11-26 | Intradigm Corporation | Compositions comprising a-raf, b-raf, and c-raf sirna and methods of use thereof |
| EP2806054A1 (en) | 2008-05-28 | 2014-11-26 | Genomedx Biosciences Inc. | Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer |
| US10407731B2 (en) | 2008-05-30 | 2019-09-10 | Mayo Foundation For Medical Education And Research | Biomarker panels for predicting prostate cancer outcomes |
| EP2313506A1 (en) * | 2008-07-11 | 2011-04-27 | Medizinische Universität Innsbruck | Antagonists of nr2f6 for augmenting the immune response |
| RU2492871C2 (ru) | 2008-08-01 | 2013-09-20 | АКСИС, Инс. | Терапевтическое или профилактическое средство для лечения остеоартрита |
| US20150283164A1 (en) * | 2008-11-14 | 2015-10-08 | Christine Victoria Ichim | Treatment of Myelodysplastic Syndrome by Inhibition of NR2F2 |
| US20150203846A1 (en) * | 2008-11-14 | 2015-07-23 | Christine Victoria Ichim | Treatment of Myelodysplastic Syndrome by Inhibition of NR2F6 |
| US20150297627A1 (en) * | 2008-11-14 | 2015-10-22 | Christine Victoria Ichim | Methods and Compositions for treatment of cancer by inhibition of NR2F2 |
| GB2512153B (en) * | 2008-11-17 | 2014-11-12 | Veracyte Inc | Methods and compositions of molecular profiling for disease diagnostics |
| US10236078B2 (en) | 2008-11-17 | 2019-03-19 | Veracyte, Inc. | Methods for processing or analyzing a sample of thyroid tissue |
| US9495515B1 (en) | 2009-12-09 | 2016-11-15 | Veracyte, Inc. | Algorithms for disease diagnostics |
| JP2012517821A (ja) * | 2009-02-19 | 2012-08-09 | ガラパゴス・ナムローゼ・フェンノートシャップ | 炎症を包含する疾患の診断及び治療に有用な同定方法及び化合物 |
| US9074258B2 (en) | 2009-03-04 | 2015-07-07 | Genomedx Biosciences Inc. | Compositions and methods for classifying thyroid nodule disease |
| WO2010115841A1 (en) | 2009-04-01 | 2010-10-14 | Galapagos Nv | Methods and means for treatment of osteoarthritis |
| JP6078339B2 (ja) | 2009-05-07 | 2017-02-08 | ベラサイト インコーポレイテッド | 甲状腺状態の診断のための方法および組成物 |
| WO2011051350A1 (en) * | 2009-10-27 | 2011-05-05 | Ucb Pharma S.A. | Function modifying nav 1.7 antibodies |
| US10446272B2 (en) | 2009-12-09 | 2019-10-15 | Veracyte, Inc. | Methods and compositions for classification of samples |
| EP2512501A4 (en) * | 2009-12-17 | 2014-01-01 | Five Prime Therapeutics Inc | METHODS FOR PROMOTING HAIR GROWTH USING FGFR3 EXTRACELLULAR DOMAINS |
| CA2788527A1 (en) | 2010-01-29 | 2011-08-04 | Axis Inc. | Pharmaceutical composition for osteoarthritis treatment or prevention and manufacturing method therefor |
| JP2012246222A (ja) | 2010-01-29 | 2012-12-13 | Axis Inc | 変形性関節症治療剤または予防剤を製造するための使用 |
| KR101684246B1 (ko) | 2010-01-29 | 2016-12-08 | 가부시키가이샤 아크시스 | 변형성 관절증 치료제를 포함하는 주사제 |
| JP6023705B2 (ja) | 2010-06-23 | 2016-11-09 | カッパーアールエヌエー,インコーポレイテッド | ナトリウムチャネル、電位依存性、αサブユニット(SCNA)に対する天然アンチセンス転写物の阻害によるSCNA関連疾患の治療 |
| US20130267443A1 (en) | 2010-11-19 | 2013-10-10 | The Regents Of The University Of Michigan | ncRNA AND USES THEREOF |
| WO2013090620A1 (en) | 2011-12-13 | 2013-06-20 | Genomedx Biosciences, Inc. | Cancer diagnostics using non-coding transcripts |
| WO2013166264A2 (en) * | 2012-05-02 | 2013-11-07 | University Of Georgia Research Foundation, Inc. | Methods for altering virus replication |
| ES2945036T3 (es) | 2012-08-16 | 2023-06-28 | Veracyte Sd Inc | Pronóstico del cáncer de próstata mediante biomarcadores |
| US11976329B2 (en) | 2013-03-15 | 2024-05-07 | Veracyte, Inc. | Methods and systems for detecting usual interstitial pneumonia |
| WO2015021308A1 (en) * | 2013-08-07 | 2015-02-12 | Astute Medical, Inc. | Assays for timp2 having improved performance in biological samples |
| US12297505B2 (en) | 2014-07-14 | 2025-05-13 | Veracyte, Inc. | Algorithms for disease diagnostics |
| EP3770274A1 (en) | 2014-11-05 | 2021-01-27 | Veracyte, Inc. | Systems and methods of diagnosing idiopathic pulmonary fibrosis on transbronchial biopsies using machine learning and high dimensional transcriptional data |
| TW201718620A (zh) | 2015-07-27 | 2017-06-01 | 阿尼拉製藥公司 | 黃嘌呤脫氫酶(XDH)iRNA組成物及其使用方法 |
| WO2017141157A1 (en) * | 2016-02-15 | 2017-08-24 | Istituti Clinici Scientifici Maugeri Spa Sb | Method of allele specific silencing for the treatment of autosomal dominant catecholaminergic polymorphic ventricular tachycardia (cpvt) |
| US11414708B2 (en) | 2016-08-24 | 2022-08-16 | Decipher Biosciences, Inc. | Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy |
| AU2018210695B2 (en) | 2017-01-20 | 2024-07-18 | The University Of British Columbia | Molecular subtyping, prognosis, and treatment of bladder cancer |
| US11873532B2 (en) | 2017-03-09 | 2024-01-16 | Decipher Biosciences, Inc. | Subtyping prostate cancer to predict response to hormone therapy |
| CN110709103B (zh) | 2017-04-05 | 2024-02-02 | 机敏医药股份有限公司 | 用于生物学样品中具有改善的性能的timp2的测定法 |
| WO2018205035A1 (en) | 2017-05-12 | 2018-11-15 | Genomedx Biosciences, Inc | Genetic signatures to predict prostate cancer metastasis and identify tumor agressiveness |
| US11217329B1 (en) | 2017-06-23 | 2022-01-04 | Veracyte, Inc. | Methods and systems for determining biological sample integrity |
| GB201711208D0 (en) | 2017-07-12 | 2017-08-23 | Iontas Ltd | Ion channel inhibitors |
| EA202090393A1 (ru) | 2017-07-28 | 2020-05-20 | Кёрин Фармасьютикал Ко., Лтд. | Терапевтическое средство от фиброза |
| CA3085576A1 (en) | 2017-12-13 | 2019-06-20 | The Research Foundation For The State University Of New York | Peptides and other agents for treating pain and increasing pain sensitivity |
| WO2021257782A1 (en) | 2020-06-18 | 2021-12-23 | Alnylam Pharmaceuticals, Inc. | XANTHINE DEHYDROGENASE (XDH) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2025059345A1 (en) * | 2023-09-14 | 2025-03-20 | Empirico Inc. | Treatment of hgfac related diseases and disorders |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002040541A2 (en) * | 2000-10-27 | 2002-05-23 | Incyte Genomics, Inc. | Transporters and ion channels |
| WO2003085125A1 (en) * | 2002-04-03 | 2003-10-16 | Agy Therapeutics, Inc. | Use of biomolecular targets in the treatment and visualization of brain tumors |
| WO2004058805A2 (en) * | 2002-12-26 | 2004-07-15 | Asahi Kasei Pharma Corporation | T cell activating gene |
| WO2005121778A2 (en) * | 2004-06-14 | 2005-12-22 | Galapagos N.V. | Methods for identification, and compounds useful for the treatment of degenerative & inflammatory diseases |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| JPH0238040B2 (ja) | 1983-06-29 | 1990-08-28 | Matsushita Electric Ind Co Ltd | Sojushinsochi |
| US5354844A (en) | 1989-03-16 | 1994-10-11 | Boehringer Ingelheim International Gmbh | Protein-polycation conjugates |
| US5693622A (en) | 1989-03-21 | 1997-12-02 | Vical Incorporated | Expression of exogenous polynucleotide sequences cardiac muscle of a mammal |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| EP0786522A2 (en) | 1992-07-17 | 1997-07-30 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecules for treatment of stenotic conditions |
| US5459036A (en) | 1993-03-19 | 1995-10-17 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Extracellular signal-regulated kinase, sequences, and methods of production and use |
| FR2714830B1 (fr) | 1994-01-10 | 1996-03-22 | Rhone Poulenc Rorer Sa | Composition contenant des acides nucléiques, préparation et utilisations. |
| FR2715847B1 (fr) | 1994-02-08 | 1996-04-12 | Rhone Poulenc Rorer Sa | Composition contenant des acides nucléiques, préparation et utilisations. |
| NZ296748A (en) * | 1994-11-02 | 1999-11-29 | Univ New York State Res Found | Peripheral nervous system specific sodium channel proteins, DNA coding therefor, compositions and methods |
| FR2727679B1 (fr) | 1994-12-05 | 1997-01-03 | Rhone Poulenc Rorer Sa | Nouveaux agents de transfection et leurs applications pharmaceutiques |
| FR2730637B1 (fr) | 1995-02-17 | 1997-03-28 | Rhone Poulenc Rorer Sa | Composition pharmaceutique contenant des acides nucleiques, et ses utilisations |
| US6699983B1 (en) * | 1995-12-21 | 2004-03-02 | Sunnybrook Health Sciences Centre | Integrin-linked kinase and its uses |
| US20090081228A1 (en) * | 1996-03-15 | 2009-03-26 | Munin Corporation | Cyr61 compositions and methods |
| US6162613A (en) | 1998-02-18 | 2000-12-19 | Vertex Pharmaceuticals, Inc. | Methods for designing inhibitors of serine/threonine-kinases and tyrosine kinases |
| US6413776B1 (en) | 1998-06-12 | 2002-07-02 | Galapagos Geonomics N.V. | High throughput screening of gene function using adenoviral libraries for functional genomics applications |
| US7067144B2 (en) * | 1998-10-20 | 2006-06-27 | Omeros Corporation | Compositions and methods for systemic inhibition of cartilage degradation |
| WO2000036096A1 (en) | 1998-12-16 | 2000-06-22 | Vertex Pharmaceuticals Incorporated | Crystallized p38 complexes |
| US6753314B1 (en) | 1999-04-01 | 2004-06-22 | Curagen Corporation | Protein-protein complexes and methods of using same |
| BR0006019A (pt) | 1999-04-06 | 2001-03-13 | Univ East Carolina | Oligonucleotìdeo de anti-sentido de adenosina baixo, composições, kit & método para tratamento de distúrbios de vias aéreas associados com broncoconstricção, inflamação pulmonar, alergia(s) & depleção de surfactante |
| US7332337B2 (en) | 2000-05-16 | 2008-02-19 | Galapagos Nv | Viral vectors having tissue tropism for T-lymphocytes, B- and mast cells |
| US7235233B2 (en) | 2000-09-26 | 2007-06-26 | Crucell Holland B.V. | Serotype 5 adenoviral vectors with chimeric fibers for gene delivery in skeletal muscle cells or myoblasts |
| JP2004533206A (ja) | 2000-10-11 | 2004-11-04 | アバロン ファーマシューティカルズ | 化学療法のための標的としてのガン関連遺伝子 |
| WO2002070744A2 (en) | 2001-03-07 | 2002-09-12 | Galapagos Genomics B.V. | Adenoviral library assay for e2f regulatory genes and methods and compositions for screening compounds |
| US20030092028A1 (en) * | 2001-06-01 | 2003-05-15 | Yuanhong Ma | Methods and Reagents For Diagnosis and Treatment of Insulin Resistance and Related Condition |
| US20030198627A1 (en) | 2001-09-01 | 2003-10-23 | Gert-Jan Arts | siRNA knockout assay method and constructs |
| WO2003025148A2 (en) * | 2001-09-19 | 2003-03-27 | Nuvelo, Inc. | Novel nucleic acids and polypeptides |
| US20040072192A1 (en) | 2001-10-11 | 2004-04-15 | Young Paul E | Cancer-linked genes as targets for chemotherapy |
| WO2003083046A2 (en) * | 2002-03-08 | 2003-10-09 | Curagen Corporation | Novel proteins and nucleic acids encoding same |
| WO2003076651A2 (en) * | 2002-03-14 | 2003-09-18 | Qlt Inc. | Cancer associated araf1 protein kinase and its uses |
| US20050084905A1 (en) | 2002-03-21 | 2005-04-21 | Prescott John C. | Identification of kinase inhibitors |
| WO2003081210A2 (en) | 2002-03-21 | 2003-10-02 | Sunesis Pharmaceuticals, Inc. | Identification of kinase inhibitors |
| US20040096836A1 (en) * | 2002-11-19 | 2004-05-20 | Isis Pharmaceuticals Inc. | Modulation of mitogen-activated protein kinase 13 expression |
| US20040110145A1 (en) * | 2002-12-09 | 2004-06-10 | Isis Pharmaceuticals Inc. | Modulation of MALT1 expression |
| WO2004006838A2 (en) * | 2002-07-15 | 2004-01-22 | Sugen, Inc. | Novel kinases |
| US8574827B2 (en) * | 2002-10-29 | 2013-11-05 | Rigel Pharmaceuticals, Inc. | Modulators of angiogenesis and tumorigenesis |
| MXPA05005653A (es) * | 2002-11-27 | 2005-11-23 | Artesian Therapeutics Inc | Determinacion y seleccion terapeutica de genes de insuficiencia cardiaca. |
| AU2003224132A1 (en) | 2003-04-24 | 2004-11-19 | Galapagos Genomics N.V. | Effective sirna knock-down constructs |
| US7344716B2 (en) * | 2003-05-13 | 2008-03-18 | Depuy Spine, Inc. | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines |
| JP2008503712A (ja) * | 2004-06-21 | 2008-02-07 | ガラパゴス・ナムローゼ・フェンノートシャップ | 骨関節炎治療の方法及び手段 |
| DE102004049897B4 (de) | 2004-10-13 | 2007-11-22 | Sirs-Lab Gmbh | Verfahren zur Unterscheidung zwischen nichtinfektiösen und infektiösen Ursachen eines Multiorganversagens |
| US20070224662A1 (en) | 2004-12-17 | 2007-09-27 | Jun Luo | Post-translational modification of proteins in cell-free expression systems |
| DE102005013013A1 (de) | 2005-03-21 | 2006-09-28 | Sirs-Lab Gmbh | Verwendung von Genaktivitäts-Klassifikatoren für die in vitro Klassifizierung von Genexpressionsprofilen von Patienten mit infektiösem/nichtinfektiösem Multiorganversagen |
| US20060216722A1 (en) | 2005-03-25 | 2006-09-28 | Christer Betsholtz | Glomerular expression profiling |
-
2005
- 2005-10-14 US US11/251,465 patent/US7485468B2/en not_active Expired - Fee Related
- 2005-10-17 AT AT05803408T patent/ATE534732T1/de active
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002040541A2 (en) * | 2000-10-27 | 2002-05-23 | Incyte Genomics, Inc. | Transporters and ion channels |
| WO2003085125A1 (en) * | 2002-04-03 | 2003-10-16 | Agy Therapeutics, Inc. | Use of biomolecular targets in the treatment and visualization of brain tumors |
| WO2004058805A2 (en) * | 2002-12-26 | 2004-07-15 | Asahi Kasei Pharma Corporation | T cell activating gene |
| WO2005121778A2 (en) * | 2004-06-14 | 2005-12-22 | Galapagos N.V. | Methods for identification, and compounds useful for the treatment of degenerative & inflammatory diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2360478B1 (en) | 2014-12-10 |
| EP1817411B1 (en) | 2011-11-23 |
| ATE534732T1 (de) | 2011-12-15 |
| US8097408B2 (en) | 2012-01-17 |
| EP2360478A1 (en) | 2011-08-24 |
| WO2006040357A3 (en) | 2006-11-02 |
| EP1817411A2 (en) | 2007-08-15 |
| US7485468B2 (en) | 2009-02-03 |
| WO2006040357A2 (en) | 2006-04-20 |
| US20060094061A1 (en) | 2006-05-04 |
| US20090170720A1 (en) | 2009-07-02 |
| JP2008516593A (ja) | 2008-05-22 |
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