ES2987670T3 - Métodos novedosos para actuar sobre células madre cancerosas - Google Patents
Métodos novedosos para actuar sobre células madre cancerosas Download PDFInfo
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- ES2987670T3 ES2987670T3 ES11757135T ES11757135T ES2987670T3 ES 2987670 T3 ES2987670 T3 ES 2987670T3 ES 11757135 T ES11757135 T ES 11757135T ES 11757135 T ES11757135 T ES 11757135T ES 2987670 T3 ES2987670 T3 ES 2987670T3
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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| CN107666906A (zh) | 2015-04-17 | 2018-02-06 | 波士顿生物医药有限公司 | 用于治疗癌症的方法 |
| CN107708700A (zh) | 2015-04-17 | 2018-02-16 | 波士顿生物医药有限公司 | 用于治疗癌症的方法 |
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| US20050049207A1 (en) | 2003-09-03 | 2005-03-03 | Kaufmann Doug A. | Method of treating and preventing cancer |
| WO2005033048A2 (en) | 2003-09-29 | 2005-04-14 | The Johns Hopkins University | Wnt pathway antagonists |
| US7745468B2 (en) | 2003-12-11 | 2010-06-29 | Board of Regents, University of Texas Systems The | Compounds for treatment of cell proliferative diseases |
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| RU2007123675A (ru) | 2004-11-24 | 2008-12-27 | Новартис АГ (CH) | Комбинации ингибиторов jak |
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| WO2007115269A2 (en) | 2006-03-31 | 2007-10-11 | The Board Of Regents Of The University Of Texas System | Orally bioavailable caffeic acid related anticancer drugs |
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| WO2008094321A2 (en) | 2006-10-04 | 2008-08-07 | Universtiy Of South Florida | Akt sensitization of cancer cells |
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-
2011
- 2011-03-21 RU RU2012144420/15A patent/RU2591823C2/ru active
- 2011-03-21 JP JP2013500247A patent/JP2013522326A/ja active Pending
- 2011-03-21 EP EP11757135.6A patent/EP2547205B1/en active Active
- 2011-03-21 SM SM20240193T patent/SMT202400193T1/it unknown
- 2011-03-21 CA CA2946890A patent/CA2946890A1/en not_active Abandoned
- 2011-03-21 AU AU2011227023A patent/AU2011227023B2/en active Active
- 2011-03-21 HR HRP20240658TT patent/HRP20240658T1/hr unknown
- 2011-03-21 BR BR112012023660A patent/BR112012023660B8/pt active IP Right Grant
- 2011-03-21 DK DK11757135.6T patent/DK2547205T3/da active
- 2011-03-21 LT LTEPPCT/US2011/029283T patent/LT2547205T/lt unknown
- 2011-03-21 FI FIEP11757135.6T patent/FI2547205T3/fi active
- 2011-03-21 RS RS20240574A patent/RS65536B1/sr unknown
- 2011-03-21 ES ES11757135T patent/ES2987670T3/es active Active
- 2011-03-21 WO PCT/US2011/029283 patent/WO2011116399A1/en not_active Ceased
- 2011-03-21 PL PL11757135.6T patent/PL2547205T3/pl unknown
- 2011-03-21 CN CN2011800233152A patent/CN103025159A/zh active Pending
- 2011-03-21 US US13/634,694 patent/US9730909B2/en not_active Expired - Fee Related
- 2011-03-21 CA CA2793527A patent/CA2793527A1/en not_active Abandoned
- 2011-03-21 SI SI201132110T patent/SI2547205T1/sl unknown
-
2017
- 2017-07-05 US US15/642,105 patent/US20170319537A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2012144420A (ru) | 2014-04-27 |
| BR112012023660B8 (pt) | 2021-05-25 |
| CN103025159A (zh) | 2013-04-03 |
| AU2011227023A1 (en) | 2012-09-27 |
| SI2547205T1 (sl) | 2024-08-30 |
| WO2011116399A1 (en) | 2011-09-22 |
| RS65536B1 (sr) | 2024-06-28 |
| CA2793527A1 (en) | 2011-09-22 |
| EP2547205A4 (en) | 2013-08-14 |
| DK2547205T3 (da) | 2024-05-27 |
| US20130028944A1 (en) | 2013-01-31 |
| EP2547205A1 (en) | 2013-01-23 |
| RU2591823C2 (ru) | 2016-07-20 |
| JP2013522326A (ja) | 2013-06-13 |
| US9730909B2 (en) | 2017-08-15 |
| CA2946890A1 (en) | 2011-09-22 |
| SMT202400193T1 (it) | 2024-07-09 |
| EP2547205B1 (en) | 2024-03-20 |
| AU2011227023B2 (en) | 2015-05-28 |
| US20170319537A1 (en) | 2017-11-09 |
| PL2547205T3 (pl) | 2024-07-08 |
| BR112012023660B1 (pt) | 2021-05-18 |
| BR112012023660A2 (pt) | 2015-09-15 |
| LT2547205T (lt) | 2024-06-10 |
| HRP20240658T1 (hr) | 2024-08-16 |
| FI2547205T3 (fi) | 2024-05-27 |
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