KR20040081431A - 운동신경 질환의 치료용 백신 및 치료 방법 - Google Patents
운동신경 질환의 치료용 백신 및 치료 방법 Download PDFInfo
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- KR20040081431A KR20040081431A KR10-2004-7008780A KR20047008780A KR20040081431A KR 20040081431 A KR20040081431 A KR 20040081431A KR 20047008780 A KR20047008780 A KR 20047008780A KR 20040081431 A KR20040081431 A KR 20040081431A
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| WO2004060265A2 (en) * | 2003-01-07 | 2004-07-22 | Yeda Research And Development Co. Ltd. | Eye-drop vaccine containing copolymer 1 for therapeutic immunization |
| CA2546077C (en) | 2003-11-12 | 2016-07-05 | Yeda Research And Development Co. Ltd. | Vaccine and method for treatment of neurodegenerative diseases |
| DK1701730T3 (da) | 2003-12-09 | 2013-11-25 | Yeda Res & Dev | Fremgangsmåde og vaccine omfattende copolymer 1 til behandling af psykiatriske forstyrrelser |
| EP1778286A4 (en) * | 2004-03-03 | 2009-04-08 | Teva Pharma | COMBINATION THERAPY WITH ACETATE OF GLATIRAMER AND RILUZOLE |
| US7655221B2 (en) | 2004-05-07 | 2010-02-02 | Peptimmune, Inc. | Methods of treating disease with random copolymers |
| CA2565819A1 (en) * | 2004-05-07 | 2005-12-01 | Peptimmune, Inc. | Methods of treating disease with random copolymers |
| JP5241012B2 (ja) * | 2005-07-15 | 2013-07-17 | ノバルティス アーゲー | Pamps、病原体関連分子パターン |
| CN100448481C (zh) * | 2006-06-22 | 2009-01-07 | 中国科学院遗传与发育生物学研究所 | xCT蛋白及其编码基因的新用途 |
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| USRE49251E1 (en) | 2010-01-04 | 2022-10-18 | Mapi Pharma Ltd. | Depot systems comprising glatiramer or pharmacologically acceptable salt thereof |
| 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 |
| EA025780B1 (ru) | 2010-10-11 | 2017-01-30 | Тева Фармасьютикал Индастриз Лтд. | Цитокиновые биомаркеры в качестве биомаркеров, прогнозирующих клинический ответ на глатирамер ацетат |
| ES2601892T3 (es) | 2011-04-21 | 2017-02-16 | Mapi Pharma Limited | Pentapolímero aleatorio para el tratamiento de enfermedades autoinmunes |
| MX2014004309A (es) | 2011-10-10 | 2015-07-06 | Teva Pharma | Polimorfismos de nucleotidos individuales utiles para predecir una respuesta clinica para el acetato de glatiramer. |
| US9861686B2 (en) * | 2011-12-05 | 2018-01-09 | Ben-Gurion University Of The Negev Research & Development Authority | Diagnostic and therapeutic methods and their application in amyotrophic lateral sclerosis (ALS) |
| KR20140145173A (ko) * | 2012-03-26 | 2014-12-22 | 예다 리서치 앤드 디벨럽먼트 캄파니 리미티드 | 알츠하이머 질병 진단 및 알츠하이머 질병 진행 진단용 세포 마커 |
| EP2892353A4 (en) | 2012-09-10 | 2016-10-26 | Yeda Res & Dev | INDIVIDUALIZED IMMUNOMODULATION THERAPY FOR NEURODEGENERATIVE ILLNESSES, CNS LESIONS AND AGGREGATIVE DEMENTIA |
| US12097292B2 (en) | 2016-08-28 | 2024-09-24 | Mapi Pharma Ltd. | Process for preparing microparticles containing glatiramer acetate |
| AU2017319728B2 (en) | 2016-08-31 | 2024-09-05 | Mapi Pharma Ltd | Depot systems comprising glatiramer acetate |
| IL316573A (en) | 2017-03-26 | 2024-12-01 | Mapi Pharma Ltd | Storage systems containing glatiramer acetate for the treatment of multiple sclerosis |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL36670A (en) * | 1971-04-21 | 1974-09-10 | Sela M | Therapeutic basic copolymers of amino acids |
| US3849650A (en) | 1973-03-29 | 1974-11-19 | Picker Corp | Automatic x-ray inspection system |
| IL113812A (en) | 1994-05-24 | 2000-06-29 | Yeda Res & Dev | Copolymer-1 pharmaceutical compositions containing it and its use |
| SE505316C2 (sv) * | 1995-10-17 | 1997-08-04 | Kenneth G Haglid | Användning av proteinet S-100b för framställning av läkemedel för nervceller |
| RU2211697C2 (ru) * | 1996-09-27 | 2003-09-10 | Гилфорд Фармасьютикалз Инк. | Способ лечения глутаматных расстройств |
| JP2002503658A (ja) * | 1998-02-13 | 2002-02-05 | オートイミューン インク | COP−1及びTh−2促進性サイトカインを使用した、多発性硬化症の治療 |
| US20030108528A1 (en) | 1998-05-19 | 2003-06-12 | Michal Eisenbach-Schwartz | Activated t-cells, nervous system-specific antigens and their uses |
| US20020072493A1 (en) | 1998-05-19 | 2002-06-13 | Yeda Research And Development Co. Ltd. | Activated T cells, nervous system-specific antigens and their uses |
| WO1999060021A2 (en) | 1998-05-19 | 1999-11-25 | Yeda Research And Development Co. Ltd. | Use of activated t cells, nervous system-specific antigens for treating disorders of the nevrous system |
| EP1039929A1 (en) | 1998-07-21 | 2000-10-04 | YEDA RESEARCH AND DEVELOPMENT Co. Ltd. | Activated t-cells and their uses |
| JP2003521448A (ja) | 1998-07-23 | 2003-07-15 | ザ・プレジデント・アンド・フェローズ・オブ・ハーバード・カレッジ | 合成ペプチドおよび自己免疫疾患治療のための使用方法 |
| RU2155063C1 (ru) * | 1999-10-20 | 2000-08-27 | Санкт-Петербургская общественная организация "Институт биорегуляции и геронтологии" | Тетрапептид, стимулирующий функциональную активность нейронов, фармакологическое средство на его основе и способ его применения |
| HK1054507B (zh) * | 2000-01-20 | 2008-10-31 | 耶达研究及发展有限公司 | 共聚物1和相关肽和多肽及其处理过的t细胞在神经保护性治疗中的用途 |
| DE60116467T2 (de) | 2000-06-07 | 2006-11-02 | Yeda Research And Development Co., Ltd. | Verwendung des Copolymer-1 Peptids sowie von damit verwandten Peptiden und Polypeptiden und von damit behandelten T-Zellen zur Neuroprotektion gegen die Toxizität von Glutamat |
| WO2002076503A1 (en) * | 2000-06-20 | 2002-10-03 | Mayo Foundation For Medical Education And Research | Treatment of central nervous system diseases by antibodies against glatiramer acetate |
| US6835711B2 (en) * | 2001-06-28 | 2004-12-28 | Yeda Research And Development Co. Ltd. | Use of poly-Glu,Tyr for neuroprotective therapy |
| US7399740B2 (en) * | 2001-06-28 | 2008-07-15 | Yeda Research And Development Co. Ltd. | Poly-Glu,Tyr for neuroprotective therapy |
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