CA2843432A1 - Treatment of multiple sclerosis with combination of laquinimod and interferon-beta - Google Patents
Treatment of multiple sclerosis with combination of laquinimod and interferon-beta Download PDFInfo
- Publication number
- CA2843432A1 CA2843432A1 CA2843432A CA2843432A CA2843432A1 CA 2843432 A1 CA2843432 A1 CA 2843432A1 CA 2843432 A CA2843432 A CA 2843432A CA 2843432 A CA2843432 A CA 2843432A CA 2843432 A1 CA2843432 A1 CA 2843432A1
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- Prior art keywords
- laquinimod
- interferon
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- multiple sclerosis
- beta
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| US201161512817P | 2011-07-28 | 2011-07-28 | |
| US61/512,817 | 2011-07-28 | ||
| PCT/US2012/048689 WO2013016686A1 (en) | 2011-07-28 | 2012-07-27 | Treatment of multiple sclerosis with combination of laquinimod and interferon-beta |
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| CA2843432A Abandoned CA2843432A1 (en) | 2011-07-28 | 2012-07-27 | Treatment of multiple sclerosis with combination of laquinimod and interferon-beta |
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| JP (2) | JP2014521659A (enExample) |
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| WO2009082471A1 (en) | 2007-12-20 | 2009-07-02 | Teva Pharmaceutical Industries, Ltd. | Stable laquinimod preparations |
| KR20130006640A (ko) * | 2010-03-03 | 2013-01-17 | 테바 파마슈티컬 인더스트리즈 리미티드 | 라퀴니모드를 이용한 루푸스 신장염의 치료 |
| EA201290860A1 (ru) | 2010-03-03 | 2013-04-30 | Тева Фармасьютикал Индастриз Лтд. | Лечение ревматоидного артрита комбинацией лаквинимода и метотрексата |
| SG11201401330YA (en) | 2011-10-12 | 2014-05-29 | Teva Pharma | Treatment of multiple sclerosis with combination of laquinimod and fingolimod |
| WO2013116657A1 (en) | 2012-02-03 | 2013-08-08 | Teva Pharmaceutical Industries Ltd. | USE OF LAQUINIMOD FOR TREATING CROHN'S DISEASE PATIENTS WHO FAILED FIRST-LINE ANTI-TNFα THERAPY |
| MX2014009889A (es) | 2012-02-16 | 2014-11-13 | Teva Pharma | N-etil-n-fenil-1,2-dihidro-4,5-di-hidroxi-1-metil-2-oxo-3-quinoli ncarboxamida, preparacion y usos de los mismos. |
| FR2988058B1 (fr) | 2012-03-15 | 2014-10-03 | A Fermetures As | Dispositif de calage a quai de vehicule de transport de marchandises |
| TW201350467A (zh) | 2012-05-08 | 2013-12-16 | Teva Pharma | Ｎ－乙基－４－羥基－１－甲基－５－（甲基（２，３，４，５，６－五羥基己基）胺基）－２－側氧－ｎ－苯基－１，２－二氫喹啉－３－甲醯胺 |
| TW201400117A (zh) | 2012-06-05 | 2014-01-01 | Teva Pharma | 使用拉喹莫德治療眼發炎疾病 |
| AR091706A1 (es) * | 2012-07-11 | 2015-02-25 | Teva Pharma | Formulaciones de laquinimod sin agentes alcalinizantes |
| TW201410244A (zh) | 2012-08-13 | 2014-03-16 | Teva Pharma | 用於治療ｇａｂａ媒介之疾病之拉喹莫德（ｌａｑｕｉｎｉｍｏｄ） |
| EA201590788A1 (ru) | 2012-11-07 | 2015-12-30 | Тева Фармасьютикал Индастриз Лтд. | Аминные соли лахинимода |
| KR20150119227A (ko) * | 2013-02-15 | 2015-10-23 | 테바 파마슈티컬 인더스트리즈 리미티드 | 라퀴니모드에 의한 다발성 경화증의 진행형 형태의 치료 |
| JP2016514162A (ja) | 2013-03-14 | 2016-05-19 | 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 | ラキニモドナトリウムの結晶およびその製造のための改善された方法 |
| EP3027187A4 (en) * | 2013-08-01 | 2017-03-29 | Teva Pharmaceutical Industries Ltd. | Treatment of multiple sclerosis by alemtuzumab induction followed by laquinimod therapy |
| HK1231413A1 (zh) | 2014-04-29 | 2017-12-22 | Teva Pharmaceutical Industries Ltd. | 用於治疗具有高残疾状况的复发-缓解型多发性硬化症(rrms)的患者的拉喹莫德 |
| WO2016196621A1 (en) * | 2015-06-01 | 2016-12-08 | Biogen Ma Inc. | Manganese supplementation for control of glycosylation in mammalian cell culture process |
| US20190108912A1 (en) * | 2017-10-05 | 2019-04-11 | Iquity, Inc. | Methods for predicting or detecting disease |
| EP3981399A4 (en) * | 2019-06-10 | 2023-05-31 | BeiGene Switzerland GmbH | ORAL SOLID TABLET WITH A TYROSINE KINAS INHIBITOR AND METHOD OF MANUFACTURE THEREOF |
Family Cites Families (7)
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|---|---|---|---|---|
| US6077851A (en) * | 1998-04-27 | 2000-06-20 | Active Biotech Ab | Quinoline derivatives |
| EP1933860A2 (en) * | 2005-09-01 | 2008-06-25 | Ares Trading S.A. | Treatment of optic neuritis |
| CN101466379B (zh) * | 2006-06-12 | 2012-10-31 | 泰华制药工业有限公司 | 稳定的拉喹莫德的制剂 |
| EP2355660A4 (en) * | 2008-10-13 | 2012-05-02 | Biovista Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF MULTIPLE SCLEROSIS |
| NZ597378A (en) * | 2009-06-19 | 2014-08-29 | Teva Pharma | Treatment of multiple sclerosis with laquinimod |
| EP2455080A1 (en) * | 2010-11-23 | 2012-05-23 | Almirall, S.A. | S1P1 receptor agonists for use in the treatment of multiple sclerosis |
| HK1231413A1 (zh) * | 2014-04-29 | 2017-12-22 | Teva Pharmaceutical Industries Ltd. | 用於治疗具有高残疾状况的复发-缓解型多发性硬化症(rrms)的患者的拉喹莫德 |
-
2012
- 2012-07-27 HK HK14111811.8A patent/HK1198278A1/xx unknown
- 2012-07-27 US US13/560,872 patent/US20130028866A1/en not_active Abandoned
- 2012-07-27 CN CN201280043782.6A patent/CN103781355A/zh active Pending
- 2012-07-27 SG SG10201606204TA patent/SG10201606204TA/en unknown
- 2012-07-27 CA CA2843432A patent/CA2843432A1/en not_active Abandoned
- 2012-07-27 BR BR112014002092A patent/BR112014002092A2/pt not_active IP Right Cessation
- 2012-07-27 EP EP12817547.8A patent/EP2736336A4/en not_active Withdrawn
- 2012-07-27 AU AU2012286701A patent/AU2012286701A1/en not_active Abandoned
- 2012-07-27 JP JP2014523093A patent/JP2014521659A/ja not_active Withdrawn
- 2012-07-27 KR KR1020147004932A patent/KR20140054129A/ko not_active Withdrawn
- 2012-07-27 WO PCT/US2012/048689 patent/WO2013016686A1/en not_active Ceased
- 2012-07-27 MX MX2014001048A patent/MX2014001048A/es unknown
- 2012-07-27 EA EA201490378A patent/EA201490378A1/ru unknown
- 2012-10-01 UY UY0001034359A patent/UY34359A/es not_active Application Discontinuation
- 2012-10-01 TW TW105134805A patent/TW201726137A/zh unknown
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2014
- 2014-02-18 ZA ZA2014/01217A patent/ZA201401217B/en unknown
- 2014-10-29 US US14/527,199 patent/US20150056281A1/en not_active Abandoned
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2016
- 2016-02-22 US US15/050,005 patent/US20160166648A1/en not_active Abandoned
- 2016-07-13 AU AU2016204909A patent/AU2016204909A1/en not_active Abandoned
- 2016-10-26 JP JP2016209185A patent/JP2017061482A/ja not_active Withdrawn
Also Published As
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|---|---|
| CN103781355A (zh) | 2014-05-07 |
| UY34359A (es) | 2014-02-28 |
| SG10201606204TA (en) | 2016-09-29 |
| KR20140054129A (ko) | 2014-05-08 |
| MX2014001048A (es) | 2014-07-09 |
| US20150056281A1 (en) | 2015-02-26 |
| US20160166648A1 (en) | 2016-06-16 |
| ZA201401217B (en) | 2015-08-26 |
| AU2016204909A1 (en) | 2016-08-04 |
| NZ621215A (en) | 2015-11-27 |
| WO2013016686A1 (en) | 2013-01-31 |
| EP2736336A4 (en) | 2015-03-04 |
| HK1198278A1 (en) | 2015-03-27 |
| EA201490378A1 (ru) | 2014-07-30 |
| JP2014521659A (ja) | 2014-08-28 |
| BR112014002092A2 (pt) | 2017-02-21 |
| US20130028866A1 (en) | 2013-01-31 |
| JP2017061482A (ja) | 2017-03-30 |
| AU2012286701A1 (en) | 2014-03-06 |
| EP2736336A1 (en) | 2014-06-04 |
| TW201726137A (zh) | 2017-08-01 |
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