RU2672585C2 - Применение эрибулина и ленватиниба в качестве комбинированной терапии для лечения рака - Google Patents
Применение эрибулина и ленватиниба в качестве комбинированной терапии для лечения рака Download PDFInfo
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- RU2672585C2 RU2672585C2 RU2016102158A RU2016102158A RU2672585C2 RU 2672585 C2 RU2672585 C2 RU 2672585C2 RU 2016102158 A RU2016102158 A RU 2016102158A RU 2016102158 A RU2016102158 A RU 2016102158A RU 2672585 C2 RU2672585 C2 RU 2672585C2
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- Prior art keywords
- cancer
- pharmaceutically acceptable
- acceptable salt
- eribulin
- lenvatinib
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| CN102036962B (zh) | 2008-01-29 | 2013-08-07 | 卫材R&D管理有限公司 | 血管生成抑制剂和紫杉烷的组合使用 |
| SG10201500552PA (en) | 2010-01-26 | 2015-03-30 | Eisai R&D Man Co Ltd | Furo [3, 2 -b] pyrane derivatives useful in the synthesis of halichondrin b analogs |
| KR101677790B1 (ko) | 2010-06-25 | 2016-11-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 키나제 저해 작용을 갖는 화합물의 병용에 의한 항종양제 |
| US20120077837A1 (en) | 2010-09-24 | 2012-03-29 | Eisai R&D Management Co., Ltd. | Anti-tumor agent |
| WO2012129100A1 (en) | 2011-03-18 | 2012-09-27 | Eisai R&D Management Co., Ltd. | Methods and compositions for predicting response to eribulin |
| KR101762999B1 (ko) * | 2011-04-18 | 2017-07-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양 치료제 |
| WO2012154935A1 (en) | 2011-05-12 | 2012-11-15 | Eisai R&D Management Co., Ltd. | Biomarkers that are predictive of responsiveness or non-responsiveness to treatment with lenvatinib or a pharmaceutically acceptable salt thereof |
| CN106029070A (zh) | 2014-03-03 | 2016-10-12 | 卫材R&D管理有限公司 | 艾日布林和mTOR抑制剂作为治疗癌症的联合疗法的用途 |
| MX2016015378A (es) | 2014-05-28 | 2017-12-04 | Eisai R&D Man Co Ltd | Uso de eribulina en el tratamiento de cancer. |
| US10238630B2 (en) | 2014-05-28 | 2019-03-26 | Eisai R&D Management Co., Ltd. | Use of eribulin and poly (ADP ribose) polymerase (PARP) inhibitors as combination therapy for the treatment of cancer |
| JP6644479B2 (ja) | 2014-06-24 | 2020-02-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | がん治療のための併用療法としてのエリブリンとｓ−１（もしくは５−ｆｕ）の使用 |
-
2014
- 2014-06-26 WO PCT/JP2014/067723 patent/WO2014208774A1/en not_active Ceased
- 2014-06-26 AU AU2014299699A patent/AU2014299699B2/en active Active
- 2014-06-26 ES ES14739971T patent/ES2705698T3/es active Active
- 2014-06-26 JP JP2015562231A patent/JP6404242B2/ja active Active
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- 2014-06-26 CN CN201480036218.0A patent/CN105338977B/zh active Active
- 2014-06-26 KR KR1020167001713A patent/KR102265952B1/ko active Active
-
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- 2015-11-01 IL IL242386A patent/IL242386B/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012119077A1 (en) * | 2011-03-02 | 2012-09-07 | Morphotek Inc. | Co -administration of eribulin and farletuzumab for the treatment of breast cancer |
| WO2012166899A2 (en) * | 2011-06-03 | 2012-12-06 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
Non-Patent Citations (1)
| Title |
|---|
| Харкевич Д.А. Фармакология / Учебник, 2010, 10-е издание, стр.72-82. Микуляк Н.И. и др. Изучение противоопухолевого и антиметастатического эффектов противоопухолевых антибиотиков при раздельном и совместном применении с мексидолом / Известия ВУЗов. Поволжский регион. Медицинские науки. 2007. Хирургическая онкология / surgery.su, 2009, URL: http://oncosurgery.surgery.su/. * |
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| Publication number | Publication date |
|---|---|
| KR102265952B1 (ko) | 2021-06-16 |
| BR112015029386B1 (pt) | 2023-11-14 |
| US20150005343A1 (en) | 2015-01-01 |
| US9549922B2 (en) | 2017-01-24 |
| BR112015029386A2 (pt) | 2017-07-25 |
| EP3013335A1 (en) | 2016-05-04 |
| JP2016528162A (ja) | 2016-09-15 |
| AU2014299699A1 (en) | 2015-12-10 |
| BR112015029386A8 (pt) | 2020-03-17 |
| CN105338977B (zh) | 2018-10-16 |
| EP3013335B1 (en) | 2018-11-07 |
| IL242386B (en) | 2019-06-30 |
| WO2014208774A1 (en) | 2014-12-31 |
| ES2705698T3 (es) | 2019-03-26 |
| CA2915005A1 (en) | 2014-12-31 |
| CN105338977A (zh) | 2016-02-17 |
| KR20160023816A (ko) | 2016-03-03 |
| CA2915005C (en) | 2021-12-28 |
| JP6404242B2 (ja) | 2018-10-10 |
| AU2014299699B2 (en) | 2019-10-10 |
| RU2016102158A (ru) | 2017-07-31 |
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