EA034964B1 - Биомаркеры, имеющие прогностическое значение в отношении ответа на лечение активатором альфа 7 никотиновых ацетилхолиновых рецепторов - Google Patents
Биомаркеры, имеющие прогностическое значение в отношении ответа на лечение активатором альфа 7 никотиновых ацетилхолиновых рецепторов Download PDFInfo
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Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP3431485B2 (en) | 2010-10-01 | 2024-09-04 | ModernaTX, Inc. | Engineered nucleic acids and methods of use thereof |
| WO2012135805A2 (en) | 2011-03-31 | 2012-10-04 | modeRNA Therapeutics | Delivery and formulation of engineered nucleic acids |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2763701B1 (en) | 2011-10-03 | 2018-12-19 | Moderna Therapeutics, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
| KR20140102759A (ko) | 2011-12-16 | 2014-08-22 | 모더나 세라퓨틱스, 인코포레이티드 | 변형된 뉴클레오사이드, 뉴클레오타이드 및 핵산 조성물 |
| DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
| CA2892529C (en) | 2012-11-26 | 2023-04-25 | Moderna Therapeutics, Inc. | Terminally modified rna |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| EA201690675A1 (ru) | 2013-10-03 | 2016-08-31 | Модерна Терапьютикс, Инк. | Полинуклеотиды, кодирующие рецептор липопротеинов низкой плотности |
| PT3848028T (pt) * | 2014-10-20 | 2024-09-20 | Oyster Point Pharma Inc | Métodos de tratamento de estados oculares |
| DK3439661T3 (da) | 2016-04-07 | 2021-10-18 | Oyster Point Pharma Inc | Fremgangsmåder til behandling af øjenlidelser |
| US11433057B2 (en) * | 2016-05-20 | 2022-09-06 | Vanda Pharmaceuticals Inc. | Method for improving or enhancing cognition |
| CN107188900B (zh) * | 2017-05-27 | 2019-09-06 | 北京师范大学 | α7烟碱型乙酰胆碱受体的配体化合物及其应用 |
| EP3941352A1 (en) | 2019-03-19 | 2022-01-26 | Cambridge Cognition Limited | Method and uses of diagnosing and recommending treatment for a psychotic disorder |
| CN116731008B (zh) * | 2023-06-15 | 2025-10-24 | 西北大学 | 标记肺癌靶点烟碱型乙酰胆碱受体的免洗型荧光探针及制备方法 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683194A (en) | 1984-05-29 | 1987-07-28 | Cetus Corporation | Method for detection of polymorphic restriction sites and nucleic acid sequences |
| US5075216A (en) | 1988-09-23 | 1991-12-24 | Cetus Corporation | Methods for dna sequencing with thermus aquaticus dna polymerase |
| DE69433811T2 (de) | 1993-01-07 | 2005-06-23 | Sequenom, Inc., San Diego | Dns - sequenzierung durch massenspektronomie |
| US5498531A (en) | 1993-09-10 | 1996-03-12 | President And Fellows Of Harvard College | Intron-mediated recombinant techniques and reagents |
| US6953855B2 (en) | 1998-12-11 | 2005-10-11 | Targacept, Inc. | 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof |
| EP1303636A1 (en) | 2000-04-05 | 2003-04-23 | Glaxo Group Limited | Iterative analysis of non-responding population in the design of pharmacogenetic studies |
| GB0010955D0 (en) * | 2000-05-05 | 2000-06-28 | Novartis Ag | Organic compounds |
| DE10156719A1 (de) | 2001-11-19 | 2003-05-28 | Bayer Ag | Heteroarylcarbonsäureamide |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| DE10211415A1 (de) | 2002-03-15 | 2003-09-25 | Bayer Ag | Bicyclische N-Biarylamide |
| DE10211416A1 (de) | 2002-03-15 | 2003-09-25 | Bayer Ag | Essig- und Propionsäureamide |
| DE10234424A1 (de) | 2002-07-29 | 2004-02-12 | Bayer Ag | Benzothiophen-, Benzofuran- und Indolharnstoffe |
| GB0220581D0 (en) * | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| CA2499128C (en) | 2002-09-25 | 2012-07-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
| US20050065178A1 (en) | 2003-09-19 | 2005-03-24 | Anwer Basha | Substituted diazabicycloakane derivatives |
| WO2006065233A1 (en) | 2004-12-10 | 2006-06-22 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US20050245531A1 (en) | 2003-12-22 | 2005-11-03 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| PE20060437A1 (es) | 2004-06-18 | 2006-06-08 | Novartis Ag | COMPUESTOS AZA-BICICLONONANOS COMO LIGANDOS COLINERGICOS DE nAChR |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| GB0521508D0 (en) | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
| GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525673D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| TW200813067A (en) | 2006-05-17 | 2008-03-16 | Astrazeneca Ab | Nicotinic acetylcholine receptor ligands |
| EP2018380B1 (en) | 2006-05-19 | 2011-10-19 | Abbott Laboratories | Cns active fused bicycloheterocycle substituted azabicyclic alkane derivatives |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| WO2009066107A1 (en) | 2007-11-21 | 2009-05-28 | Astrazeneca Ab | Use of a nicotinic receptor agonist |
| CA2740311C (en) | 2008-10-13 | 2013-09-17 | F. Hoffmann-La Roche Ag | Diazonium-free method to make an indazole intermediate in the synthesis of bicyclic 5-(trifluormethoxy)-1h-3-indazolecarboxylic acid amides |
| WO2010056622A1 (en) | 2008-11-11 | 2010-05-20 | Targacept, Inc. | TREATMENT WITH ALPHA α7-SELECTIVE LIGANDS |
| TW201031664A (en) * | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| JO3250B1 (ar) * | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
-
2012
- 2012-10-18 CA CA3083244A patent/CA3083244C/en active Active
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- 2012-10-18 AU AU2012324458A patent/AU2012324458B2/en active Active
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Non-Patent Citations (6)
| Title |
|---|
| ANATOLY A. MAZUROV, SPEAKE JASON D., YOHANNES DANIEL: "Discovery and Development of α7 Nicotinic Acetylcholine Receptor Modulators", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 54, no. 23, 8 December 2011 (2011-12-08), pages 7943 - 7961, XP055060345, ISSN: 00222623, DOI: 10.1021/jm2007672 * |
| GEORG WINTERER, KIRSTIN MITTELSTRASS, INA GIEGLING, CLAUDIA LAMINA, CHRISTOPH FEHR, HERMANN BRENNER, LUTZ P. BREITLING, BARBARA NI: "Risk gene variants for nicotine dependence in the CHRNA5-CHRNA3-CHRNB4 cluster are associated with cognitive performance", AMERICAN JOURNAL OF MEDICAL GENETICS PART B: NEUROPSYCHIATRIC GENETICS, WILEY-LISS, vol. 153B, no. 8, 1 December 2010 (2010-12-01), pages 1448 - 1458, XP055059810, ISSN: 15524841, DOI: 10.1002/ajmg.b.31126 * |
| JOHANSSON I; INGELMAN-SUNDBERG M: "CNVs of human genes and their implication in pharmacogenetics", CYTOGENETIC AND GENOME RESEARCH, ALLERTON PRESS, NEW YORK, NY, US, vol. 123, no. 1-4, 1 March 2009 (2009-03-01), US, pages 195 - 204, XP009168924, ISSN: 1424-8581, DOI: 10.1159/000184709 * |
| L. E. HONG, YANG X., WONODI I., HODGKINSON C. A., GOLDMAN D., STINE O. C., STEIN E. S., THAKER G. K.: "A CHRNA5 allele related to nicotine addiction and schizophrenia", GENES, BRAIN AND BEHAVIOR, BLACKWELL MUNKSGAARD, vol. 10, no. 5, 1 July 2011 (2011-07-01), pages 530 - 535, XP055059804, ISSN: 16011848, DOI: 10.1111/j.1601-183X.2011.00689.x * |
| N. A. HORENSTEIN, LEONIK F. M., PAPKE R. L.: "Multiple Pharmacophores for the Selective Activation of Nicotinic �7-Type Acetylcholine Receptors", MOLECULAR PHARMACOLOGY, AMERICAN SOCIETY FOR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 74, no. 6, 1 December 2008 (2008-12-01), pages 1496 - 1511, XP055060348, ISSN: 0026895X, DOI: 10.1124/mol.108.048892 * |
| NADINE PETROVSKY, BORIS B QUEDNOW, ULRICH ETTINGER, ANNE SCHMECHTIG, RAINALD M�SSNER, DAVID A COLLIER, KAI-UWE K�HN, WOLFGANG MAIE: "Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers", NEUROPSYCHOPHARMACOLOGY, NO LONGER PUBLISHED BY ELSEVIER, vol. 35, no. 7, 1 June 2010 (2010-06-01), pages 1429 - 1439, XP055059821, ISSN: 0893133X, DOI: 10.1038/npp.2010.12 * |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112014007485B1 (pt) | 2022-05-31 |
| EP2768507B1 (en) | 2019-12-11 |
| EP2768507A2 (en) | 2014-08-27 |
| EA201490832A1 (ru) | 2015-12-30 |
| KR102043077B1 (ko) | 2019-11-11 |
| IN2014CN03647A (enExample) | 2015-10-09 |
| TWI635861B (zh) | 2018-09-21 |
| JO3766B1 (ar) | 2021-01-31 |
| KR20140081822A (ko) | 2014-07-01 |
| TW201322980A (zh) | 2013-06-16 |
| CN103930112B (zh) | 2018-11-09 |
| ES2776996T3 (es) | 2020-08-03 |
| AU2012324458A1 (en) | 2014-05-01 |
| CA2852268A1 (en) | 2013-04-25 |
| CN103930112A (zh) | 2014-07-16 |
| MX2014004621A (es) | 2014-08-22 |
| WO2013057687A2 (en) | 2013-04-25 |
| JP2015501306A (ja) | 2015-01-15 |
| BR112014007485A2 (pt) | 2017-04-04 |
| CA3083244C (en) | 2023-01-03 |
| JP6162705B2 (ja) | 2017-07-12 |
| WO2013057687A3 (en) | 2013-07-11 |
| CA3083244A1 (en) | 2013-04-25 |
| MX374644B (es) | 2025-03-06 |
| CA2852268C (en) | 2020-08-25 |
| AU2012324458B2 (en) | 2016-05-19 |
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