JP5449774B2 - αｖβ６ペプチドリガンド及びその活用 - Google Patents
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- JP5449774B2 JP5449774B2 JP2008534069A JP2008534069A JP5449774B2 JP 5449774 B2 JP5449774 B2 JP 5449774B2 JP 2008534069 A JP2008534069 A JP 2008534069A JP 2008534069 A JP2008534069 A JP 2008534069A JP 5449774 B2 JP5449774 B2 JP 5449774B2
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- C07K7/04—Linear peptides containing only normal peptide links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| GB0520068.8 | 2005-10-03 | ||
| GB0520068A GB0520068D0 (en) | 2005-10-03 | 2005-10-03 | av peptide ligand |
| PCT/GB2006/003673 WO2007039728A2 (en) | 2005-10-03 | 2006-10-03 | AVß6 PEPTIDE LIGANDS AND THEIR USES |
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| JP2009509562A JP2009509562A (ja) | 2009-03-12 |
| JP2009509562A5 JP2009509562A5 (enExample) | 2009-11-12 |
| JP5449774B2 true JP5449774B2 (ja) | 2014-03-19 |
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| JP2008534069A Active JP5449774B2 (ja) | 2005-10-03 | 2006-10-03 | αｖβ６ペプチドリガンド及びその活用 |
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| JP (1) | JP5449774B2 (enExample) |
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| ES (1) | ES2638439T3 (enExample) |
| GB (1) | GB0520068D0 (enExample) |
| WO (1) | WO2007039728A2 (enExample) |
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| GB0520068D0 (en) | 2005-10-03 | 2005-11-09 | Cancer Res Technology | av peptide ligand |
| JP5362563B2 (ja) | 2006-08-03 | 2013-12-11 | アストラゼネカ・アクチエボラーグ | αＶβ６に対する抗体およびその使用 |
| GB0718843D0 (en) | 2007-09-26 | 2007-11-07 | Cancer Rec Tech Ltd | Materials and methods relating to modifying the binding of antibodies |
| JP2013520173A (ja) * | 2010-02-18 | 2013-06-06 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | インテグリンαｖβ８中和抗体 |
| WO2013025261A2 (en) * | 2011-04-06 | 2013-02-21 | Georgia Tech Research Corporation | Fluorogenic peptide probes and assays |
| WO2013078250A2 (en) | 2011-11-22 | 2013-05-30 | The Board Of Trustees Of The Leland Stanford Junior University | Cystine knot peptides that bind alpha-v-beta-6 integrin |
| US9403877B2 (en) | 2012-01-24 | 2016-08-02 | Inter-K Pty Limited | Peptide agents for cancer therapy |
| US9027086B2 (en) * | 2013-02-01 | 2015-05-05 | Vidder, Inc. | Securing organizational computing assets over a network using virtual domains |
| GB201311031D0 (en) * | 2013-06-20 | 2013-08-07 | Queen Mary & Westfield College | Method |
| JP6789823B2 (ja) * | 2014-04-15 | 2020-11-25 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 両末端ｐｅｇ化インテグリン結合性ペプチドおよびその使用方法 |
| GB201513540D0 (en) | 2015-07-31 | 2015-09-16 | King S College London | Therapeutic agents |
| CA3027364A1 (en) | 2016-06-13 | 2017-12-21 | The Regents Of The University Of California | Alpha(v)beta(6) integrin-binding peptides and methods of use thereof |
| BR112018076184A2 (pt) * | 2016-06-16 | 2019-03-26 | The University Of Liverpool | composição sólida, composição farmacêutica ou veterinária na forma injetável, formulação intramuscularmente injetável, formulação subcutaneamente injetável, dispersão aquosa, dispersão oleosa, processos para preparar uma composição sólida, uma dispersão aquosa e uma dispersão oleosa, métodos para tratar e/ou prevenir uma infecção parasítica ou fúngica e para prevenir malária, e, kit para preparação de uma formulação líquida estéril de nanopartículas de atovaquona para injeção. |
| CA3036232C (en) | 2016-09-29 | 2025-11-18 | The Regents Of The University Of California | Neutralizing antibodies directed against the Integrin Alpha V Beta 8 complex for immunotherapy |
| CN109952376B (zh) * | 2016-11-01 | 2023-09-05 | 箭头药业股份有限公司 | αvβ6整联蛋白配体及其应用 |
| GB201706472D0 (en) * | 2017-04-24 | 2017-06-07 | Cancer Res Tech Ltd | Tumour-targeting peptide variants |
| IL274300B2 (en) | 2017-11-01 | 2024-09-01 | Arrowhead Pharmaceuticals Inc | Alpha v beta 6 integrin ligands, compositions comprising same and uses thereof |
| GB201802539D0 (en) * | 2018-02-16 | 2018-04-04 | Univ College Cardiff Consultants Ltd | Modified adenoviruses |
| EP3846858A4 (en) * | 2018-09-07 | 2022-10-19 | The Regents of the University of California | Alpha(v)beta(6) integrin-binding peptides and methods of use thereof |
| US20220348609A1 (en) * | 2019-10-25 | 2022-11-03 | University Of Washington | Computational design of alpha(v) beta (6) integrin binding proteins |
| US20220402980A1 (en) * | 2019-11-15 | 2022-12-22 | Ospedale San Raffaele S.R.L. | Chromogranin a-derived peptides and uses thereof |
| KR20230167082A (ko) | 2021-04-08 | 2023-12-07 | 애로우헤드 파마슈티컬스 인코포레이티드 | 진행성 당화 최종 산물에 대한 수용체의 발현을 억제하기 위한 RNAi 작용제, 그의 조성물, 및 사용 방법 |
| WO2022221144A1 (en) * | 2021-04-12 | 2022-10-20 | University Of Washington | Engineered peptides for αvβ6 integrin binding and related methods of use and synthesis |
| CN115010949B (zh) * | 2022-07-12 | 2024-02-13 | 华熙生物科技股份有限公司 | 促渗物、护肤品组合物以及化妆品 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8301928D0 (en) | 1983-01-24 | 1983-02-23 | Nicholson B H | Process for producing polypeptides |
| JPS60103596A (ja) * | 1983-11-11 | 1985-06-07 | Toshiba Corp | サンプル・ホ−ルド回路 |
| AUPM411994A0 (en) * | 1994-02-25 | 1994-03-24 | Deakin Research Limited | Epitopes |
| JP2002533064A (ja) * | 1998-12-19 | 2002-10-08 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | インテグリンαｖβ６阻害剤 |
| DE19929410A1 (de) * | 1999-06-26 | 2000-12-28 | Merck Patent Gmbh | Inhibitoren des Integrins avß6 |
| DE19933173A1 (de) * | 1999-07-15 | 2001-01-18 | Merck Patent Gmbh | Cyclische Peptidderivate als Inhibitoren des Integrins alpha¶v¶beta¶6¶ |
| AU2001258638A1 (en) * | 2000-05-26 | 2001-12-03 | Glaxo Group Limited | Methods for identifying modulators of the interaction between lap (latency associated peptide) and intergrin alpha.v.beta.3 and medical use thereof |
| US20030031648A1 (en) * | 2000-11-28 | 2003-02-13 | Virogene Ltd. | Vectors for expressing heterologous peptides at the amino-terminus of potyvirus coat protein, methods for use thereof, plants infected with same and methods of vaccination using same |
| GB0520068D0 (en) | 2005-10-03 | 2005-11-09 | Cancer Res Technology | av peptide ligand |
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| WO2007039728A3 (en) | 2007-09-20 |
| US8927501B2 (en) | 2015-01-06 |
| EP1957522A2 (en) | 2008-08-20 |
| CA2624618C (en) | 2016-03-29 |
| WO2007039728A2 (en) | 2007-04-12 |
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