Neuroprotection in demyelinating diseases 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2011100589 A1 2011-08-18 [WO2011100589] / 2011-08-18
申请号/申请日
2011WO-US24594 / 2011-02-11
发明人
GOELZ SUSAN;DAWSON KATE;LINKER RALF;GOLD RALF;
申请人
BIOGEN IDEC;
主分类号
IPC分类号
A01N-037/34A61K-031/275
摘要
(WO2011100589) Methods of treating neurological disorders, e.g., those characterized by demyelination and/or axonal loss (e.g., MS), are provided.  The methods comprise administration of a therapeutically effective amount of at least one compound of Formula I: (I) wherein R1 and R2 are independently selected from OH, O", and (C1-6)alkoxy, or a pharmaceutically acceptable salt thereof; and either glatiramer acetate or interferon-beta.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2010US-61304325 2010-02-12 2010US-61321486 2010-04-06
主权利要求
(WO2011100589) 1. WHAT IS CLAIMED IS: 1. A method of treating a subject having multiple sclerosis (MS), the method comprising administering to the subject: (a) a therapeutically effective amount of at least one compound of Formula I:  1 2 wherein R and R are independently selected from OH, 0\ and (Ci-6)alkoxy, or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of glatiramer acetate. 2. The method of claim 1, wherein the MS is selected from relapsing remitting MS, secondary progressive MS, primary progressive MS, progressive relapsing MS, and clinically isolated syndrome. 3. The method of claim 1, wherein the subject has a progressive form of MS. 4. The method of claim 3, wherein the subject exhibits at least a 1 -point increase on the Enhanced Disability Status Scale (EDSS) over a period of about one year prior to the administering the compound of Formula I and the glatiramer acetate. 5. The method of claim 3, wherein the subject exhibits at least a 25% increase in Tl lesion load over a period of about one year prior to the administering the compound of Formula I and the glatiramer acetate. 6. The method of claim 1, wherein the subject has an EDSS score of at least about 3. 7. The method of claim 1, wherein the subject has more than about 10 hypointense Tl lesions. The method of claim 1, wherein the compound of Formula I and the glatiramer acetate present in a single pharmaceutical formulation. 9. The method of claim 1, wherein the at least one compound of Formula I is chosen from dimethyl fumarate (DMF), monomethyl fumarate (MMF), and combinations thereof. 10. The method of claim 9, wherein the at least one compound of Formula I is DMF. 1 1. The method of claim 10, wherein about 120 mg of DMF is administered to the subject at one time. 12. The method of claim 1 1 , wherein the DMF is administered to the subject three times per day (TID) equivalent to a total daily dose of about 360 mg/day. 13. The method of claim 10, wherein about 240 mg of DMF is administered to the subject at one time. 14. The method of claim 13, wherein the DMF is administered to the subject three times per day (TID) equivalent to a total daily dose of about 720 mg/day. 15. The method of claim 13, wherein the DMF is administered to the subject two times per day (BID) equivalent to a total daily dose of about 480 mg/day. 16. The method of claim 10, wherein the DMF is administered at least about one hour before, or at least about one hour after food is consumed by the subject. 17. The method of claim 1, wherein about 20 mg/day of glatiramer acetate is administered to the subject. 18. The method of claim 1 , wherein less than about 20 mg/day of glatiramer acetate is administered to the subject. 19. The method of claim 1, wherein the compound of Formula I and the glatiramer acetate are administered in amounts and for periods of time sufficient to reduce a relapse rate in the subject. 20. The method of claim 1 , wherein the compound of Formula I and the glatiramer acetate are administered in amounts and for periods of time sufficient to reduce demyelination and/or axonal death in the subject. 21. A method of treating a subject having multiple sclerosis (MS), the method comprising administering to the subject: (a) a therapeutically effective amount of at least one compound of Formula I:  wherein R1and R2are independently selected from OH, O", and (Q^alkoxy, or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of interferon-beta. 22. The method of claim 21, wherein the MS is selected from relapsing remitting MS, secondary progressive MS, primary progressive MS, progressive relapsing MS, and clinically isolated syndrome. 23. The method of claim 21, wherein the subject has a progressive form of MS. 24. The method of claim 23, wherein the subject exhibits at least a 1 -point increase on the Enhanced Disability Status Scale (EDSS) over a period of about one year prior to the administering the compound of Formula I and the interferon-beta. 25. The method of claim 23, wherein the subject exhibits at least a 25% increase in Tl lesion load over a period of about one year prior to the administering the compound of Formula I and the interferon-beta. 26. The method of claim 21, wherein the subject has an EDSS score of at least 3. 27. The method of claim 21, wherein the subject has more than about 10 hypointense Tl lesions. 28. The method of claim 21, wherein the at least one compound of Formula I is chosen from dimethyl fumarate (DMF), monomethyl fumarate (MMF), and combinations thereof. 29. The method of claim 28, wherein the at least one compound of Formula I is DMF. 30. The method of claim 29, wherein about 120 mg of DMF is administered to the subject at one time. 31. The method of claim 30, wherein the DMF is administered to the subject three times per day (TID) equivalent to a total daily dose of about 360 mg per day. 32. The method of claim 29, wherein about 240 mg of DMF is administered to the subject at one time. 33. The method of claim 32, wherein the DMF is administered to the subject three times per day (TID) equivalent to a total daily dose of about 720 mg per day. 34. The method of claim 32, wherein the DMF is administered to the subject two times per day (BID) equivalent to a total daily dose of about 480 mg per day. 35. The method of claim 29, wherein the DMF is administered at least about one hour before or at least about one hour after food is consumed by the subject. 36. The method of claim 21, wherein the compound of Formula I and the interferon-beta are administered in amounts and for periods of time sufficient to reduce demyelination and/or axonal death in the subject. 37. The method of claim 21, wherein the compound of Formula I and the interferon-beta are administered in amounts and for periods of time sufficient to reduce accumulation of disability in the subject. 38. The method of claim 21, wherein the compound of Formula I and the interferon-beta are administered in amounts and for periods of time sufficient to reduce a relapse rate in the subject. 39. The method of claim 21, wherein the interferon-beta is selected from interferon-beta la and interferon-beta lb. 40. The method of claim 39, wherein the interferon-beta is interferon-beta la. 41. The method of claim 40, wherein the interferon-beta has an amino acid sequence essentially identical to amino acid sequence of human interferon-beta l a. 42. The method of claim 40, wherein the interferon-beta la is administered at a dose of about 5 meg to about 80 meg at one time. 43. The method of claim 42, wherein the interferon-beta la is administered at a dose of about 20 meg to about 46 meg at one time. 44. The method of claim 43, wherein the interferon-beta la is administered once a week. 45. The method of claim 44, wherein the interferon-beta la is administered at a dose of about 30 meg once a week. 46. The method of claim 44, wherein the interferon-beta la is administered at a dose of less than about 30 meg once a week. 47. The method of claim 43, wherein the interferon-beta la is administered twice a week equivalent to a total dose of from about 40 meg to about 92 meg per week. 48. The method of claim 43, wherein the interferon-beta la is administered three times a week equivalent to a total dose of from about 60 meg to about 138 meg per week. 49. The method of claim 39, wherein the interferon-beta is interferon-beta lb. 50. The method of claim 49, wherein the interferon-beta has an amino acid sequence essentially identical to amino acid sequence of human interferon-beta lb.
法律状态
(WO2011100589) LEGAL DETAILS FOR WO2011100589  Actual or expected expiration date=2013-08-12    Legal state=DEAD    Status=LAPSED     Event publication date=2011-02-11  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2011024594  Application date=2011-02-11  Standardized application number=2011WO-US24594     Event publication date=2011-08-18  Event code=WO/A1  Event type=Examination events  Published application with search report  Publication country=WO  Publication number=WO2011100589  Publication stage Code=A1  Publication date=2011-08-18  Standardized publication number=WO2011100589     Event publication date=2013-08-12  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2012-08-13    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2012-08-13  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE  LEGAL DETAILS FOR DESIGNATED STATE DK2533634  Actual or expected expiration date=2017-02-28    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DK Corresponding appl: DK11742896  Application date in the designated or member state=2011-02-11   Application number in the designated or member state=2011DK-0742896 Corresponding cc:  Designated or member state=DK Corresponding pat: DK2533634  Publication stage code in the designated or member state=T3  Publication date in the designated or member state=2016-01-25   Publication number in the designated or member state=DK2533634T    Event publication date=2016-01-25  Event code=DK/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=DK  LEGAL DETAILS FOR DESIGNATED STATE HK1179116  Actual or expected expiration date=2031-02-11    Legal state=ALIVE    Status=GRANTED   Corresponding cc:  Designated or member state=HK Corresponding appl: HK13106428  Application date in the designated or member state=2013-05-30   Application number in the designated or member state=2013HK-0106428 Corresponding cc:  Designated or member state=HK Corresponding pat: HK1179116  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2016-04-08   Publication number in the designated or member state=HK1179116    Event publication date=2016-04-08  Event code=HK/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=HK  LEGAL DETAILS FOR DESIGNATED STATE HRP20151350  Actual or expected expiration date=2017-10-31    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=HR Corresponding appl: HRP20151350  Application date in the designated or member state=2015-12-08   Application number in the designated or member state=2015HR-0001350 Corresponding cc:  Designated or member state=HR Corresponding pat: HRP20151350  Publication stage code in the designated or member state=T1  Publication date in the designated or member state=2016-01-01   Publication number in the designated or member state=HRP20151350    Event publication date=2016-01-01  Event code=HR/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=HR  LEGAL DETAILS FOR DESIGNATED STATE RS54551  Actual or expected expiration date=2031-02-11    Legal state=ALIVE    Status=GRANTED   Corresponding cc:  Designated or member state=RS Corresponding appl: RSP20160028  Application date in the designated or member state=2011-02-11   Application number in the designated or member state=2016RS-0000028 Corresponding cc:  Designated or member state=RS Corresponding pat: RS54551  Publication stage code in the designated or member state=B1  Publication date in the designated or member state=2016-06-30   Publication number in the designated or member state=RS--54551    Event publication date=2016-06-30  Event code=RS/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=RS  LEGAL DETAILS FOR DESIGNATED STATE SI2533634  Actual or expected expiration date=2017-12-13    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=SI Corresponding appl: SI201130693  Application date in the designated or member state=2011-02-11   Application number in the designated or member state=2011SI-0030693 Corresponding cc:  Designated or member state=SI Corresponding pat: SI2533634  Publication stage code in the designated or member state=T1  Publication date in the designated or member state=2016-01-29   Publication number in the designated or member state=SI2533634T    Event publication date=2016-01-29  Event code=SI/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=SI  LEGAL DETAILS FOR DESIGNATED STATE SMT201600014  Actual or expected expiration date=2031-02-11    Legal state=ALIVE    Status=GRANTED   Corresponding cc:  Designated or member state=SM Corresponding appl: SM201600014  Application date in the designated or member state=2016-01-15   Application number in the designated or member state=2016SM-0000014T Corresponding cc:  Designated or member state=SM Corresponding pat: SMT201600014  Publication stage code in the designated or member state=B  Publication date in the designated or member state=2016-02-25   Publication number in the designated or member state=SMT201600014    Event publication date=2016-02-25  Event code=SM/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=SM
专利类型码
A1
国别省市代码
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