CN105832733A - 高剂量拉喹莫德(laquinimod)用于治疗多发性硬化症的用途 - Google Patents
高剂量拉喹莫德(laquinimod)用于治疗多发性硬化症的用途 Download PDFInfo
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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| US201261641389P | 2012-05-02 | 2012-05-02 | |
| US61/641,389 | 2012-05-02 | ||
| CN201380022530.XA CN104284663A (zh) | 2012-05-02 | 2013-05-01 | 高剂量拉喹莫德(laquinimod)用于治疗多发性硬化症的用途 |
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| CN201380022530.XA Pending CN104284663A (zh) | 2012-05-02 | 2013-05-01 | 高剂量拉喹莫德(laquinimod)用于治疗多发性硬化症的用途 |
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| EP (1) | EP2844255A4 (https=) |
| JP (2) | JP2015515985A (https=) |
| KR (1) | KR20150013658A (https=) |
| CN (2) | CN105832733A (https=) |
| AR (1) | AR090885A1 (https=) |
| AU (1) | AU2013256352A1 (https=) |
| BR (1) | BR112014027010A2 (https=) |
| CA (1) | CA2870684A1 (https=) |
| CL (1) | CL2014002935A1 (https=) |
| EA (1) | EA201492010A1 (https=) |
| HK (1) | HK1206246A1 (https=) |
| IL (1) | IL235337A0 (https=) |
| MX (1) | MX2014013039A (https=) |
| PE (1) | PE20150161A1 (https=) |
| PH (1) | PH12014502447A1 (https=) |
| SG (1) | SG11201406594UA (https=) |
| TW (2) | TW201347762A (https=) |
| UY (1) | UY34775A (https=) |
| WO (1) | WO2013166166A1 (https=) |
| ZA (1) | ZA201408820B (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2851525A1 (en) | 2011-10-12 | 2013-04-18 | Teva Pharmaceutical Industries Ltd. | Treatment of multiple sclerosis with combination of laquinimod and fingolimod |
| CN104093310A (zh) | 2012-02-03 | 2014-10-08 | 泰华制药工业有限公司 | 拉喹莫德用于治疗一线抗TNFα疗法失败的克罗恩氏病患者的用途 |
| JP6215238B2 (ja) | 2012-02-16 | 2017-10-18 | 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 | Ｎ−エチル−ｎ−フェニル−１，２−ジヒドロ−４，５−ジ−ヒドロキシ−１−メチル−２−オキソ−３−キノリンカルボキサミド、その製剤、および使用 |
| US20130259856A1 (en) * | 2012-03-27 | 2013-10-03 | Teva Pharmaceutical Industries, Ltd. | Treatment of multiple sclerosis with combination of laquinimod and dimethyl fumarate |
| TW201400117A (zh) | 2012-06-05 | 2014-01-01 | Teva Pharma | 使用拉喹莫德治療眼發炎疾病 |
| 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） |
| BR112015007782A2 (pt) * | 2012-10-12 | 2017-07-04 | Teva Pharma | laquinimod para reduzir danos talâmicos na esclerose múltipla |
| EP2916915A4 (en) | 2012-11-07 | 2016-06-22 | Teva Pharma | LAQUINIMOD AMINE SALTS |
| BR112015019564A2 (pt) * | 2013-02-15 | 2017-07-18 | Teva Pharma | tratamento de esclerose múltipla com laquinimod |
| US20160046582A1 (en) | 2013-03-14 | 2016-02-18 | Teva Pharmaceutical Industries Ltd. | Crystals of laquinimod sodium and improved process for the manufacture thereof |
| AR098924A1 (es) * | 2013-12-23 | 2016-06-22 | Teva Pharma | Tratamiento de la esclerosis múltiple con una combinación de laquinimod y teriflunomida |
| WO2015168103A1 (en) * | 2014-04-29 | 2015-11-05 | Teva Pharmaceutical Industries Ltd. | Laquinimod for the treatment of relapsing-remitting multiple sclerosis (rrms) patients with a high disability status |
| WO2017027512A1 (en) * | 2015-08-13 | 2017-02-16 | Teva Pharmaceutical Industries Ltd. | Use of laquinimod to treat traumatic brain injury |
| US20190108912A1 (en) * | 2017-10-05 | 2019-04-11 | Iquity, Inc. | Methods for predicting or detecting disease |
| ES3009670T3 (en) * | 2018-07-20 | 2025-03-31 | Merck Patent Gmbh | A substituted amino-pyrimidine compound for use in a method for treatment and prevention of multiple sclerosis |
Citations (1)
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| WO2011086470A1 (en) * | 2010-01-13 | 2011-07-21 | Ramot At Tel-Aviv University Ltd | Treatment of multiple sclerosis |
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| US6077851A (en) * | 1998-04-27 | 2000-06-20 | Active Biotech Ab | Quinoline derivatives |
| 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 |
| US20080118553A1 (en) * | 2006-06-12 | 2008-05-22 | Anton Frenkel | Tannate salt form of polypeptide mixtures, their preparation and use |
| JP2012530701A (ja) * | 2009-06-19 | 2012-12-06 | 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 | 多発性硬化症のラキニモドでの治療 |
| CA2851525A1 (en) * | 2011-10-12 | 2013-04-18 | Teva Pharmaceutical Industries Ltd. | Treatment of multiple sclerosis with combination of laquinimod and fingolimod |
| BR112015019564A2 (pt) * | 2013-02-15 | 2017-07-18 | Teva Pharma | tratamento de esclerose múltipla com laquinimod |
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- 2013-05-01 US US13/874,537 patent/US20130303569A1/en not_active Abandoned
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- 2013-05-01 HK HK15106789.5A patent/HK1206246A1/xx unknown
- 2013-05-01 JP JP2015510436A patent/JP2015515985A/ja not_active Withdrawn
- 2013-05-01 PE PE2014001911A patent/PE20150161A1/es not_active Application Discontinuation
- 2013-05-01 CN CN201380022530.XA patent/CN104284663A/zh active Pending
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- 2013-05-01 BR BR112014027010A patent/BR112014027010A2/pt not_active IP Right Cessation
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2014
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2015
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011086470A1 (en) * | 2010-01-13 | 2011-07-21 | Ramot At Tel-Aviv University Ltd | Treatment of multiple sclerosis |
Non-Patent Citations (4)
| Title |
|---|
| C.POLMAN等: "Treatment with laquinimod reduces development of active MRI lesions in relapsing MS", 《NEUROLOGY》 * |
| JANA PREININGEROVA: "Oral laquinimod therapy in relapsing multiple sclerosis", 《EXPERT OPIN.INVESTIG.DRUGS》 * |
| SUSAN JEFFREY: "Laquinimod Slows Progression in MS:ALLEGRO Published", 《MEDSCAPE MEDICAL NEWS》 * |
| 余永平等: "《现代实用神经病学》", 30 September 2011, 天津科学技术出版社 * |
Also Published As
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| AR090885A1 (es) | 2014-12-10 |
| KR20150013658A (ko) | 2015-02-05 |
| US20150265592A1 (en) | 2015-09-24 |
| US20130303569A1 (en) | 2013-11-14 |
| CL2014002935A1 (es) | 2015-03-06 |
| AU2013256352A1 (en) | 2014-11-27 |
| ZA201408820B (en) | 2016-06-29 |
| EP2844255A4 (en) | 2015-10-14 |
| PE20150161A1 (es) | 2015-02-22 |
| JP2015515985A (ja) | 2015-06-04 |
| EA201492010A1 (ru) | 2015-06-30 |
| HK1206246A1 (en) | 2016-01-08 |
| PH12014502447A1 (en) | 2015-01-12 |
| JP2017222691A (ja) | 2017-12-21 |
| MX2014013039A (es) | 2015-02-04 |
| EP2844255A1 (en) | 2015-03-11 |
| BR112014027010A2 (pt) | 2017-06-27 |
| IL235337A0 (en) | 2014-12-31 |
| CN104284663A (zh) | 2015-01-14 |
| TW201804997A (zh) | 2018-02-16 |
| TW201347762A (zh) | 2013-12-01 |
| WO2013166166A1 (en) | 2013-11-07 |
| UY34775A (es) | 2013-11-29 |
| SG11201406594UA (en) | 2014-11-27 |
| US20160000775A1 (en) | 2016-01-07 |
| CA2870684A1 (en) | 2013-11-07 |
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