ES3010545T3 - Bicyclic peptide-toxin conjugates specific for mt1-mmp - Google Patents
Bicyclic peptide-toxin conjugates specific for mt1-mmp Download PDFInfo
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- ES3010545T3 ES3010545T3 ES17723745T ES17723745T ES3010545T3 ES 3010545 T3 ES3010545 T3 ES 3010545T3 ES 17723745 T ES17723745 T ES 17723745T ES 17723745 T ES17723745 T ES 17723745T ES 3010545 T3 ES3010545 T3 ES 3010545T3
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- peptide
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- amino acid
- formula
- bicyclic
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Landscapes
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| PCT/GB2017/051250 WO2017191460A1 (en) | 2016-05-04 | 2017-05-04 | Bicyclic peptide-toxin conjugates specific for mt1-mmp |
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| GB201607827D0 (en) | 2016-05-04 | 2016-06-15 | Bicycle Therapeutics Ltd | Bicyclic peptide-toxin conjugates specific for MT1-MMP |
| WO2018096365A1 (en) * | 2016-11-27 | 2018-05-31 | Bicyclerd Limited | Methods for treating cancer |
| CN110603261A (zh) | 2016-12-23 | 2019-12-20 | 拜斯科阿迪有限公司 | 具有新型键结构的肽衍生物 |
| US10624968B2 (en) | 2017-01-06 | 2020-04-21 | Bicyclerd Limited | Compounds for treating cancer |
| NZ756012A (en) | 2017-01-17 | 2025-10-31 | Michael David Forrest | Therapeutic inhibitors of the reverse mode of atp synthase |
| SI3592393T1 (sl) | 2017-03-10 | 2022-04-29 | Quiapeg Pharmaceuticals Ab | Sprostljivi konjugati |
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| US10899798B2 (en) | 2017-06-26 | 2021-01-26 | Bicyclerd Limited | Bicyclic peptide ligands with detectable moieties and uses thereof |
| WO2019012149A1 (en) | 2017-07-13 | 2019-01-17 | Forrest Michael David | THERAPEUTIC MODULATORS OF THE INVERSE MODE OF ATP SYNTHASE |
| JP7670481B2 (ja) | 2017-08-04 | 2025-04-30 | バイスクルテクス・リミテッド | Ｃｄ１３７に対して特異的な二環式ペプチドリガンド |
| EP3668550A1 (en) * | 2017-08-14 | 2020-06-24 | Bicyclerd Limited | Bicyclic peptide ligand prr-a conjugates and uses thereof |
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| JP2021514953A (ja) * | 2018-02-23 | 2021-06-17 | バイスクルテクス・リミテッド | 多量体二環式ペプチドリガンド |
| TW202003044A (zh) | 2018-03-09 | 2020-01-16 | 瑞典商奎亞培格製藥公司 | 可釋放之抗體結合物 |
| GB201810316D0 (en) | 2018-06-22 | 2018-08-08 | Bicyclerd Ltd | Peptide ligands for binding to EphA2 |
| GB201810320D0 (en) | 2018-06-22 | 2018-08-08 | Bicycletx Ltd | Peptide ligands for binding to CD38 |
| GB201810329D0 (en) | 2018-06-22 | 2018-08-08 | Bicycletx Ltd | Peptide ligands for binding to integrin avB3 |
| GB201810327D0 (en) | 2018-06-22 | 2018-08-08 | Bicycletx Ltd | Peptide ligands for binding to IL-17 |
| US11180531B2 (en) | 2018-06-22 | 2021-11-23 | Bicycletx Limited | Bicyclic peptide ligands specific for Nectin-4 |
| AU2019340472A1 (en) | 2018-09-12 | 2021-04-01 | Quiapeg Pharmaceuticals Ab | Releasable GLP-1 conjugates |
| WO2020084305A1 (en) | 2018-10-23 | 2020-04-30 | Bicycletx Limited | Bicyclic peptide ligands and uses thereof |
| SG11202106081YA (en) * | 2018-12-13 | 2021-07-29 | Bicycletx Ltd | Bicyclic peptide ligands specific for mt1-mmp |
| GB201820325D0 (en) | 2018-12-13 | 2019-01-30 | Bicyclerd Ltd | Bicyclic peptide ligands specific for psma |
| GB201820288D0 (en) | 2018-12-13 | 2019-01-30 | Bicycle Tx Ltd | Bicycle peptide ligaands specific for MT1-MMP |
| GB201820295D0 (en) | 2018-12-13 | 2019-01-30 | Bicyclerd Ltd | Bicyclic peptide ligands specific for MT1-MMP |
| EP3897850A1 (en) * | 2018-12-21 | 2021-10-27 | Bicyclerd Limited | Bicyclic peptide ligands specific for pd-l1 |
| EP3897849A1 (en) * | 2018-12-21 | 2021-10-27 | BicycleTx Limited | Bicyclic peptide ligands specific for pd-l1 |
| GB201900526D0 (en) * | 2019-01-15 | 2019-03-06 | Bicyclerd Ltd | Bicyclic peptide ligands specific for caix |
| CA3137095A1 (en) | 2019-05-09 | 2020-11-12 | Bicycletx Limited | Bicyclic peptide ligands specific for ox40 |
| TWI869398B (zh) | 2019-05-10 | 2025-01-11 | 英商拜西克爾德有限公司 | 治療癌症之方法 |
| CN112048013B (zh) * | 2019-06-05 | 2021-11-05 | 深圳先进技术研究院 | 靶向脑胶质瘤的多肽化合物及其合成方法与应用 |
| TWI860386B (zh) | 2019-07-30 | 2024-11-01 | 英商拜西可泰克斯有限公司 | 異質雙環肽複合物 |
| EP4464721B1 (en) | 2019-10-03 | 2025-06-11 | BicycleTX Limited | Heterotandem bicyclic peptide complexes |
| CN116348476A (zh) | 2020-08-03 | 2023-06-27 | 拜斯科技术开发有限公司 | 基于肽的接头 |
| US20250186539A2 (en) | 2021-01-11 | 2025-06-12 | Bicycletx Limited | Methods for treating cancer |
| CA3206148A1 (en) | 2021-01-24 | 2022-07-28 | Michael David FORREST | Therapeutic modifiers of the reverse mode of atp synthase |
| GB202114282D0 (en) | 2021-10-06 | 2021-11-17 | Bicyclerd Ltd | Bicyclic peptide ligand drug conjugates |
| CN118103388A (zh) * | 2021-10-14 | 2024-05-28 | 西藏海思科制药有限公司 | EphA2的双环肽配体及其缀合物 |
| WO2023088236A1 (zh) * | 2021-11-16 | 2023-05-25 | 海思科医药集团股份有限公司 | Mt1-mmp的双环肽配体及其缀合物 |
| GB202214528D0 (en) | 2022-10-03 | 2022-11-16 | Owlstone Med Ltd | A compound |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2361739T3 (es) * | 2002-08-16 | 2011-06-21 | Immunogen, Inc. | Reticulantes con elevada reactividad y solubilidad y su uso en la preparación de conjugados para el suministro dirigido de fármacos de molécula pequeña. |
| EP1452868A2 (en) | 2003-02-27 | 2004-09-01 | Pepscan Systems B.V. | Method for selecting a candidate drug compound |
| JPWO2004089419A1 (ja) * | 2003-04-04 | 2006-07-06 | 国立大学法人 東京大学 | 抗ｍｔ−ｍｍｐモノクローナル抗体含有脂質膜構造体 |
| EP1844337B1 (en) | 2005-01-24 | 2013-07-03 | Pepscan Systems B.V. | Binding compounds, immunogenic compounds and peptidomimetics |
| DK2257624T5 (da) | 2008-02-05 | 2012-09-10 | Medical Res Council | Fremgangsmåder og sammensætninger |
| GB0913775D0 (en) | 2009-08-06 | 2009-09-16 | Medical Res Council | Multispecific peptides |
| GB0914110D0 (en) | 2009-08-12 | 2009-09-16 | Medical Res Council | Peptide libraries |
| JP2013518558A (ja) * | 2010-02-04 | 2013-05-23 | メディカル リサーチ カウンシル | 構造化されたペプチドプロセシング |
| CN103906865B (zh) * | 2011-10-07 | 2017-12-08 | 拜斯科医疗有限公司 | 结构化多肽特异性的调控 |
| US20140274759A1 (en) | 2013-03-15 | 2014-09-18 | Bicycle Therapeutics Limited | Modification of polypeptides |
| GB201306623D0 (en) | 2013-04-11 | 2013-05-29 | Bicycle Therapeutics Ltd | Modulation of structured polypeptide specificity |
| CN105683211B (zh) | 2013-10-28 | 2020-10-20 | 拜斯科阿迪有限公司 | 新型多肽 |
| RU2708459C2 (ru) * | 2014-10-29 | 2019-12-09 | БайсиклРД Лимитед | Бициклические пептидные лиганды, специфичные для мт1-ммр |
| GB201600911D0 (en) * | 2016-01-18 | 2016-03-02 | Bicycle Therapeutics Ltd | Stabilized peptide derivatives |
| GB201607827D0 (en) | 2016-05-04 | 2016-06-15 | Bicycle Therapeutics Ltd | Bicyclic peptide-toxin conjugates specific for MT1-MMP |
| WO2018096365A1 (en) | 2016-11-27 | 2018-05-31 | Bicyclerd Limited | Methods for treating cancer |
| JP7387440B2 (ja) | 2016-12-23 | 2023-11-28 | バイスクルテクス・リミテッド | Ｍｔ１－ｍｍｐに結合するためのペプチドリガンド |
| CN110603261A (zh) | 2016-12-23 | 2019-12-20 | 拜斯科阿迪有限公司 | 具有新型键结构的肽衍生物 |
| US10624968B2 (en) | 2017-01-06 | 2020-04-21 | Bicyclerd Limited | Compounds for treating cancer |
| GB201706477D0 (en) | 2017-04-24 | 2017-06-07 | Bicycle Therapeutics Ltd | Modification of polypeptides |
| US10857196B2 (en) | 2017-04-27 | 2020-12-08 | Bicycletx Limited | Bicyclic peptide ligands and uses thereof |
| US10899798B2 (en) | 2017-06-26 | 2021-01-26 | Bicyclerd Limited | Bicyclic peptide ligands with detectable moieties and uses thereof |
| TWI825046B (zh) | 2017-12-19 | 2023-12-11 | 英商拜西可泰克斯有限公司 | Epha2特用之雙環胜肽配位基 |
| JP2021514953A (ja) | 2018-02-23 | 2021-06-17 | バイスクルテクス・リミテッド | 多量体二環式ペプチドリガンド |
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