CA2860809A1 - Nucleic acids specifically binding cgrp - Google Patents
Nucleic acids specifically binding cgrp Download PDFInfo
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- CA2860809A1 CA2860809A1 CA2860809A CA2860809A CA2860809A1 CA 2860809 A1 CA2860809 A1 CA 2860809A1 CA 2860809 A CA2860809 A CA 2860809A CA 2860809 A CA2860809 A CA 2860809A CA 2860809 A1 CA2860809 A1 CA 2860809A1
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- nucleic acid
- acid molecule
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- cgrp
- nucleotide sequence
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| PCT/EP2012/000089 WO2012095303A1 (en) | 2011-01-10 | 2012-01-10 | Nucleic acid molecule having binding affinity to a target molecule and a method for generating the same |
| EP12000105.2 | 2012-01-10 | ||
| PCT/EP2013/000055 WO2013104539A1 (en) | 2012-01-10 | 2013-01-10 | Nucleic acids specifically binding cgrp |
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| PE20161439A1 (es) | 2014-03-21 | 2017-01-26 | Teva Pharmaceuticals Int Gmbh | Anticuerpos antagonistas dirigidos contra el peptido relacionado con el gen de calcitonina y metodos que usan los mismos |
| JP6584868B2 (ja) * | 2015-02-25 | 2019-10-02 | 学校法人 関西大学 | ゲル素材及びその製造方法 |
| EA201890578A1 (ru) * | 2015-09-24 | 2018-12-28 | Тева Фармасьютикалз Интернэшнл Гмбх | Предотвращение, лечение и снижение (персистирующей) посттравматической головной боли |
| ES2607639B1 (es) | 2015-09-30 | 2018-02-28 | Urquima, S.A | Sal de ácido maleico de un intermedio de silodosina |
| WO2018055574A1 (en) | 2016-09-23 | 2018-03-29 | Teva Pharmaceuticals International Gmbh | Treating refractory migraine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6011020A (en) | 1990-06-11 | 2000-01-04 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligand complexes |
| US5840867A (en) | 1991-02-21 | 1998-11-24 | Gilead Sciences, Inc. | Aptamer analogs specific for biomolecules |
| AU732820B2 (en) | 1995-06-02 | 2001-05-03 | Nexstar Pharmaceuticals, Inc. | High-affinity oligonucleotide ligands to growth factors |
| US5582981A (en) | 1991-08-14 | 1996-12-10 | Gilead Sciences, Inc. | Method for identifying an oligonucleotide aptamer specific for a target |
| US6682886B1 (en) | 1994-04-28 | 2004-01-27 | Gilead Sciences, Inc. | Bivalent binding molecules of 7 transmembrane G protein-coupled receptors |
| DE69433747D1 (de) | 1994-08-16 | 2004-06-03 | Human Genome Sciences Inc | Calcitoninrezeptor |
| US6395029B1 (en) | 1999-01-19 | 2002-05-28 | The Children's Hospital Of Philadelphia | Sustained delivery of polyionic bioactive agents |
| US6652886B2 (en) | 2001-02-16 | 2003-11-25 | Expression Genetics | Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents |
| RU2180311C1 (ru) | 2001-07-05 | 2002-03-10 | Мешалкин Георгий Алексеевич | Защитная пробка |
| US7629456B2 (en) | 2001-10-26 | 2009-12-08 | Noxxon Pharma Ag | Modified L-nucleic acid |
| EP1306382A1 (de) | 2001-10-26 | 2003-05-02 | Noxxon Pharma AG | Modifizierte L-Nukleinsäure |
| WO2003070823A2 (en) | 2002-02-20 | 2003-08-28 | The General Hospital Corporation | Conjugates comprising a biodegradable polymer and uses therefor |
| US7879991B2 (en) * | 2002-05-06 | 2011-02-01 | Noxxon Pharma Ag | CGRP binding nucleic acids |
| MXPA05011022A (es) | 2003-04-13 | 2006-04-27 | Enzon Pharmaceuticals Inc | Profarmacos oligonucleotidos polimericos. |
| GB0314472D0 (en) | 2003-06-20 | 2003-07-23 | Warwick Effect Polymers Ltd | Polymer |
| US20090281296A1 (en) | 2004-02-09 | 2009-11-12 | Supramol Parenteral Colloid Gmbh | Process for the production of conjugates from polysaccharides and polynucelotides |
| MXPA06010782A (es) | 2004-03-23 | 2007-03-28 | Complex Biosystems Gmbh | Ligador de profarmaco. |
| CN101098703B (zh) | 2004-11-05 | 2011-08-03 | 费城儿童医院 | 用于分子治疗的生物降解连接剂 |
| EP1877069A2 (de) * | 2005-05-04 | 2008-01-16 | Noxxon Pharma AG | Neue verwendung von spiegelmeren |
| JP2010503707A (ja) | 2006-09-15 | 2010-02-04 | エンゾン ファーマスーティカルズ インコーポレイテッド | オリゴヌクレオチドの送達を目的としたヒンダードエステル系生体分解性リンカー |
| WO2008052774A2 (en) | 2006-10-31 | 2008-05-08 | Noxxon Pharma Ag | Methods for detection of a single- or double-stranded nucleic acid molecule |
| US8871920B2 (en) | 2010-04-21 | 2014-10-28 | Noxxon Pharma Ag | Lipid binding nucleic acids |
| AU2012206750A1 (en) * | 2011-01-10 | 2013-07-18 | Noxxon Pharma Ag | Nucleic acid molecule having binding affinity to a target molecule and a method for generating the same |
-
2013
- 2013-01-10 EP EP13700455.2A patent/EP2802659A1/en not_active Withdrawn
- 2013-01-10 KR KR1020147022328A patent/KR20140111704A/ko not_active Withdrawn
- 2013-01-10 RU RU2014132706A patent/RU2014132706A/ru not_active Application Discontinuation
- 2013-01-10 MX MX2014008456A patent/MX2014008456A/es unknown
- 2013-01-10 US US14/371,210 patent/US9163243B2/en not_active Expired - Fee Related
- 2013-01-10 CN CN201380009019.6A patent/CN104136612A/zh active Pending
- 2013-01-10 AU AU2013209130A patent/AU2013209130A1/en not_active Abandoned
- 2013-01-10 SG SG11201403769YA patent/SG11201403769YA/en unknown
- 2013-01-10 BR BR112014016939A patent/BR112014016939A2/pt not_active IP Right Cessation
- 2013-01-10 HK HK14111873.3A patent/HK1198370A1/xx unknown
- 2013-01-10 CA CA2860809A patent/CA2860809A1/en not_active Abandoned
- 2013-01-10 WO PCT/EP2013/000055 patent/WO2013104539A1/en not_active Ceased
- 2013-01-10 JP JP2014551569A patent/JP2015506174A/ja active Pending
-
2014
- 2014-07-03 IL IL233515A patent/IL233515A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20140111704A (ko) | 2014-09-19 |
| US9163243B2 (en) | 2015-10-20 |
| MX2014008456A (es) | 2014-11-25 |
| HK1198370A1 (en) | 2015-04-10 |
| IL233515A0 (en) | 2014-08-31 |
| RU2014132706A (ru) | 2016-02-27 |
| BR112014016939A2 (pt) | 2019-09-24 |
| AU2013209130A1 (en) | 2014-07-10 |
| EP2802659A1 (en) | 2014-11-19 |
| JP2015506174A (ja) | 2015-03-02 |
| SG11201403769YA (en) | 2014-07-30 |
| US20150031755A1 (en) | 2015-01-29 |
| CN104136612A (zh) | 2014-11-05 |
| WO2013104539A1 (en) | 2013-07-18 |
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