JP2016540729A - 酢酸グラチラマーへの応答を予測する遺伝子マーカー - Google Patents
酢酸グラチラマーへの応答を予測する遺伝子マーカー Download PDFInfo
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| PT1592384E (pt) | 2003-01-21 | 2013-01-28 | Yeda Res & Dev | Cop-1 para o tratamento de doenças inflamatórias do intestino |
| CA2518079A1 (en) | 2003-03-04 | 2004-10-28 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and alphacalcidol for the treatment of multiple sclerosis |
| HRP20140524T1 (hr) | 2003-05-14 | 2014-12-19 | Teva Pharmaceutical Industries Ltd. | Kombinacijska terapija glatiramer acetatom i mitoksantronom za lijeäśenje multiple skleroze |
| US20050064483A1 (en) | 2003-08-28 | 2005-03-24 | Baylor College Of Medicine | Gene expression profiling technology for treatment evaluation of multiple sclerosis |
| EA200600877A1 (ru) | 2003-10-31 | 2006-12-29 | Тева Фармасьютикал Индастриз, Лтд. | Наночастицы для доставки лекарств |
| CA2558380A1 (en) | 2004-03-03 | 2005-09-15 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and riluzole |
| WO2006004749A2 (en) | 2004-06-25 | 2006-01-12 | Id Biomedical Corporation Of Quebec | Compositions and methods for treating neurological disorders |
| CA2579038A1 (en) | 2004-09-02 | 2006-03-16 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and n-acetylcysteine for the treatment of multiple sclerosis |
| KR101317131B1 (ko) | 2004-09-09 | 2013-10-10 | 테바 파마슈티컬 인더스트리즈 리미티드 | 정제된 브롬화 수소산을 이용한 폴리펩타이드류의 혼합물의제조방법 |
| HRP20160455T1 (hr) | 2004-09-09 | 2016-07-15 | Yeda Research And Development Co., Ltd. | Smjese polipeptida, sastavi koji ih sadrže i postupci za njihovu pripremu, te njihove primjene |
| WO2006083608A1 (en) | 2005-02-02 | 2006-08-10 | Teva Pharmaceutical Industries, Ltd. | Process for producing polypeptide mixtures using hydrogenolysis |
| US20100167983A1 (en) | 2007-10-22 | 2010-07-01 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and rasagiline for the treatment of multiple sclerosis |
| US20080261894A1 (en) | 2005-02-17 | 2008-10-23 | Rivka Kreitman | Combination Therapy with Glatiramer Acetate and Rasagiline for the Treatment of Multiple Sclerosis |
| CA2606194A1 (en) | 2005-04-25 | 2006-11-02 | Yeda Research And Development Company | Markers associated with the therapeutic efficacy of glatiramer acetate |
| WO2007030573A2 (en) | 2005-09-09 | 2007-03-15 | Yeda Research And Development Co. Ltd. | Polypeptides useful for molecular weight determinations |
| WO2007081975A2 (en) | 2006-01-11 | 2007-07-19 | Teva Pharmaceutical Industries, Ltd. | Method of treating multiple sclerosis |
| US20080118553A1 (en) | 2006-06-12 | 2008-05-22 | Anton Frenkel | Tannate salt form of polypeptide mixtures, their preparation and use |
| US20080131887A1 (en) * | 2006-11-30 | 2008-06-05 | Stephan Dietrich A | Genetic Analysis Systems and Methods |
| US20090149541A1 (en) | 2007-11-28 | 2009-06-11 | Yafit Stark | Method of delaying the onset of clinically definite multiple sclerosis |
| US20100105627A1 (en) * | 2008-09-17 | 2010-04-29 | Paul Salama | Pharmaceutical compositions and related methods of delivery |
| EP2406396A2 (en) * | 2009-03-12 | 2012-01-18 | Brainco Biopharma, S.L. | A genotyping tool for improving the prognostic and clinical management of ms patients |
| NZ577731A (en) * | 2009-06-16 | 2010-08-27 | Innate Therapeutics Ltd | Compositions and methods for treatment of multiple sclerosis |
| CA2697570C (en) | 2009-07-15 | 2011-11-01 | Teva Pharmaceutical Industries, Ltd. | Reduced volume formulation of glatiramer acetate and methods of administration |
| US8920373B2 (en) | 2009-07-15 | 2014-12-30 | Teva Pharmaceutical Industries, Ltd. | Reduced volume formulation of glatiramer acetate and methods of administration |
| HUE031282T2 (hu) | 2009-08-20 | 2017-06-28 | Yeda Res & Dev | Alacsony gyakoriságú glatiramer acetát terápia |
| US8759302B2 (en) | 2010-03-16 | 2014-06-24 | Teva Pharmaceutical Industries, Ltd. | Methods of treating a subject afflicted with an autoimmune disease using predictive biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis |
| NZ703122A (en) | 2010-10-11 | 2016-06-24 | Teva Pharma | Cytokine biomarkers as predictive biomarkers of clinical response for glatiramer acetate |
| WO2013005683A1 (ja) * | 2011-07-01 | 2013-01-10 | 日本ゼオン株式会社 | 二次電池用多孔膜、製造方法、及び用途 |
| KR20140101730A (ko) * | 2011-10-10 | 2014-08-20 | 테바 파마슈티컬 인더스트리즈 리미티드 | 글라티라머 아세테이트에 대한 임상 반응을 예측하는 데 유용한 단일 뉴클레오티드 다형성 |
| HK1213830A1 (zh) | 2012-10-10 | 2016-07-15 | Teva Pharmaceutical Industries Ltd. | 用於预测醋酸格拉替雷临床反应的生物标志物 |
| KR20150111919A (ko) | 2012-12-21 | 2015-10-06 | 테바 파마슈티컬 인더스트리즈 리미티드 | 글라티라머 아세테이트의 경구 경점막 전달 |
| JP2016503803A (ja) | 2012-12-21 | 2016-02-08 | テバ ファーマシューティカル インダストリーズ リミティド | 酢酸グラチラマーの経粘膜送達 |
| EA201591251A1 (ru) | 2013-01-04 | 2016-05-31 | Тева Фармасьютикал Индастриз Лтд. | Характеризация лекарственного продукта, родственного ацетату глатирамера |
| EA201591687A1 (ru) | 2013-03-12 | 2016-07-29 | Тева Фармасьютикал Индастриз Лтд. | Индукционная терапия ритуксимабом с последующим лечением с использованием глатирамера ацетата |
| CN103169670B (zh) * | 2013-03-22 | 2016-07-06 | 深圳翰宇药业股份有限公司 | 一种醋酸格拉替雷微球及其制备方法 |
| UY35790A (es) | 2013-10-21 | 2015-05-29 | Teva Pharma | Marcadores genéticos que predicen la respuesta al acetato de glatiramer |
| US9155775B1 (en) | 2015-01-28 | 2015-10-13 | Teva Pharmaceutical Industries, Ltd. | Process for manufacturing glatiramer acetate product |
-
2014
- 2014-10-20 UY UY0001035790A patent/UY35790A/es not_active Application Discontinuation
- 2014-10-21 WO PCT/US2014/061647 patent/WO2015061367A1/en not_active Ceased
- 2014-10-21 JP JP2016522037A patent/JP2016540729A/ja not_active Withdrawn
- 2014-10-21 TW TW103136383A patent/TW201610166A/zh unknown
- 2014-10-21 AU AU2014340247A patent/AU2014340247A1/en not_active Abandoned
- 2014-10-21 CN CN201480058055.6A patent/CN105658818A/zh active Pending
- 2014-10-21 US US14/520,280 patent/US9702007B2/en active Active
- 2014-10-21 EP EP14855499.1A patent/EP3060681A4/en not_active Withdrawn
- 2014-10-21 MX MX2016005003A patent/MX2016005003A/es unknown
- 2014-10-21 EA EA201690759A patent/EA201690759A1/ru unknown
- 2014-10-21 KR KR1020167013482A patent/KR20160098199A/ko not_active Withdrawn
- 2014-10-21 CA CA2926724A patent/CA2926724A1/en not_active Abandoned
-
2016
- 2016-03-28 IL IL244783A patent/IL244783A0/en unknown
-
2017
- 2017-01-19 US US15/410,091 patent/US20180002753A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20180002753A1 (en) | 2018-01-04 |
| UY35790A (es) | 2015-05-29 |
| EP3060681A4 (en) | 2017-06-07 |
| CA2926724A1 (en) | 2015-04-30 |
| CN105658818A (zh) | 2016-06-08 |
| US20150110733A1 (en) | 2015-04-23 |
| US9702007B2 (en) | 2017-07-11 |
| AU2014340247A1 (en) | 2016-06-02 |
| KR20160098199A (ko) | 2016-08-18 |
| TW201610166A (zh) | 2016-03-16 |
| EA201690759A1 (ru) | 2017-01-30 |
| MX2016005003A (es) | 2016-08-03 |
| EP3060681A1 (en) | 2016-08-31 |
| WO2015061367A1 (en) | 2015-04-30 |
| IL244783A0 (en) | 2016-04-21 |
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