JP2006525226A - β−アミロイド関連疾患の治療のための治療用製剤 - Google Patents
β−アミロイド関連疾患の治療のための治療用製剤 Download PDFInfo
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- JP2006525226A JP2006525226A JP2005509680A JP2005509680A JP2006525226A JP 2006525226 A JP2006525226 A JP 2006525226A JP 2005509680 A JP2005509680 A JP 2005509680A JP 2005509680 A JP2005509680 A JP 2005509680A JP 2006525226 A JP2006525226 A JP 2006525226A
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2005020882A1 (ja) * | 2003-08-29 | 2006-10-26 | 小野薬品工業株式会社 | Ｓ１ｐ受容体結合能を有する化合物およびその医薬用途 |
| JP2007516939A (ja) * | 2003-06-23 | 2007-06-28 | ニューロケム （インターナショナル） リミテッド | アミロイド関連疾患を治療するための方法および組成物 |
| WO2010140704A1 (ja) * | 2009-06-04 | 2010-12-09 | 住友化学株式会社 | Ｓ－（３－アミノプロピル）チオ硫酸またはその金属塩の使用 |
| JP2018529648A (ja) * | 2015-08-10 | 2018-10-11 | アルジオン， インコーポレイテッド | 神経変性疾患を治療および予防するための組成物および方法 |
| JP2022092910A (ja) * | 2020-12-11 | 2022-06-23 | 国立研究開発法人国立長寿医療研究センター | 認知症の危険性判定システムおよび認知症の危険性判定用プログラム |
Families Citing this family (115)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| EP1628663B1 (en) * | 2003-05-15 | 2009-07-29 | Roskamp Research llc | Method for producing medicaments for reducing amyloid deposition, amyloid neurotoxicity and microgliosis |
| US20070010573A1 (en) | 2003-06-23 | 2007-01-11 | Xianqi Kong | Methods and compositions for treating amyloid-related diseases |
| CA2528627A1 (en) * | 2003-06-23 | 2005-01-06 | Neurochem (International) Limited | Treatment of protein aggregation disorders |
| US20050142191A1 (en) * | 2003-06-23 | 2005-06-30 | Neurochem (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
| AU2011250847B2 (en) * | 2003-06-23 | 2013-06-20 | Bhi Limited Partnership | Methods and compositions for treating amyloid-related diseases |
| JP4696079B2 (ja) | 2003-12-17 | 2011-06-08 | ヤンセン アルツハイマー イミュノセラピー | Ａβ免疫原性ペプチド担体結合物およびそれの製造方法 |
| CN1960781A (zh) * | 2004-04-14 | 2007-05-09 | 沃尼尔·朗伯有限责任公司 | 治疗阿尔茨海默氏病的治疗组合 |
| EP1841460A2 (en) * | 2004-06-18 | 2007-10-10 | Neurochem (International) Limited | Therapeutic formulations for the treatment of beta-amyloid related diseases |
| JP4717537B2 (ja) * | 2004-08-31 | 2011-07-06 | 株式会社 資生堂 | 皮膚外用組成物 |
| EP1828111A2 (en) * | 2004-11-12 | 2007-09-05 | Neurochem (International) Limited | Methods and fluorinated compositions for treating amyloid-related diseases |
| BRPI0519243A2 (pt) * | 2004-12-22 | 2009-01-06 | Neurochem Int Ltd | mÉtodos e composiÇÕes para tratar doenÇas relacionadas a amilàide |
| TW200716088A (en) * | 2005-04-15 | 2007-05-01 | Neurochem Int Ltd | Formulations and methods for treating amyloidosis |
| US7420071B2 (en) * | 2005-05-04 | 2008-09-02 | Uchicago Argonne, Llc | Thermally stable surfactants and compositions and methods of use thereof |
| US8691224B2 (en) | 2005-11-30 | 2014-04-08 | Abbvie Inc. | Anti-Aβ globulomer 5F7 antibodies |
| HRP20140240T4 (hr) | 2005-11-30 | 2017-02-24 | Abbvie Inc. | Monoklonalna antitijela protiv amiloidnih beta proteina i njihova upotreba |
| EP1959996A2 (en) | 2005-12-12 | 2008-08-27 | AC Immune S.A. | Monoclonal antibody |
| KR101152557B1 (ko) | 2005-12-12 | 2012-09-07 | 에이씨 이뮨 에스.에이. | 치료 백신 |
| MX2008008213A (es) | 2005-12-22 | 2008-09-03 | Neurochem Int Ltd | Tratamiento de trastornos renales, nefropatia diabetica y dislipidemias. |
| CA2675230A1 (en) * | 2006-01-10 | 2008-07-26 | Pipex, Inc. | Pharmaceutical compositions and methods to achieve and maintain a targeted and stable copper status and prevent and treat copper-related central nervous system diseases |
| MY153248A (en) | 2006-07-14 | 2015-01-29 | Ac Immune Sa | Humanized antibody against amyloid beta |
| EP2046833B9 (en) | 2006-07-14 | 2014-02-19 | AC Immune S.A. | Humanized antibody against amyloid beta |
| DK2089417T3 (en) * | 2006-10-12 | 2015-03-23 | Bhi Ltd Partnership | Methods, Compounds, Compositions and Vehicles for Delivery of 3-Amion-1-Propanesulfonic Acid |
| US8188046B2 (en) | 2006-10-16 | 2012-05-29 | University Of South Florida | Amyloid beta peptides and methods of use |
| KR101450356B1 (ko) | 2006-11-24 | 2014-10-15 | 에이씨 이뮨 에스.에이. | 알츠하이머와 같은 아밀로이드 또는 아밀로이드-유사 단백질과 관련된 질환의 치료를 위한 ｎ-(메틸)-1ｈ-피라졸-3-아민, ｎ-(메틸)-피리딘-2-아민 및 ｎ-(메틸)-티아졸-2-아민 유도체 |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| GB0701970D0 (en) * | 2007-02-01 | 2007-03-14 | Wilson Stuart | Treatment of protein aggregation diseases |
| US8895004B2 (en) | 2007-02-27 | 2014-11-25 | AbbVie Deutschland GmbH & Co. KG | Method for the treatment of amyloidoses |
| US7618944B2 (en) * | 2007-03-01 | 2009-11-17 | Intezyne Technologies, Inc. | Encapsulated amyloid-beta peptides |
| WO2008142560A2 (en) * | 2007-05-24 | 2008-11-27 | Simone Arca | Method for the production of binary clathrate hydrates of hydrogen |
| US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
| ES2529174T3 (es) | 2007-06-12 | 2015-02-17 | Ac Immune S.A. | Anticuerpos humanizados para amiloide beta |
| NZ581835A (en) | 2007-06-12 | 2012-09-28 | Ac Immune Sa | Monoclonal anti beta amyloid antibody |
| US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
| EP2182978A4 (en) | 2007-07-20 | 2012-03-21 | Sanomune Inc | TISSUE KALLIKREIN FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID PROTEIN |
| EP2044951A1 (en) | 2007-10-02 | 2009-04-08 | Merz Pharma GmbH & Co. KGaA | The use of substances for the treatment of loss of eyesight in humans with glaucoma and other degenerative eye diseases |
| NZ584729A (en) | 2007-10-05 | 2012-12-21 | Alzheimer S Inst Of America Inc | Method for reducing amyloid deposition, amyloid neurotoxicity, and microgliosis with (-)-nilvadipine enantiomer |
| AU2008311367B2 (en) | 2007-10-05 | 2014-11-13 | Ac Immune S.A. | Use of anti-amyloid beta antibody in ocular diseases |
| BRPI0818623A2 (pt) | 2007-10-05 | 2017-05-23 | Ac Immune Sa | composição farmacêutica, e, métodos para reduzir a carga da placa na camada de célula de gânglio retinal de um animal, para reduzir a quantidade de placas na camada de célula de gânglio retinal de um animal, para diminuir a quantidade total de amilóide-beta solúvel na camada de célula de gânglio retinal de um animal, para prevenir, tratar e/ou aliviar os efeitos de uma doença ocular associada com anormalidades patológicas/mudanças no tecido do sistema visual, para monitorar doença ocular residual mínima associada com anormalidades patológicas/mudanças nos tecidos do sistema visual, para predizer responsividade de um paciente, e para reter ou diminuir a pressão ocular nos olhos de um animal |
| WO2009059239A2 (en) * | 2007-11-02 | 2009-05-07 | Mayo Foundation For Medical Education And Research | REDUCING Aβ42 LEVELS AND Aβ AGGREGATION |
| EP2149380A1 (en) * | 2008-07-29 | 2010-02-03 | Medivet Pharma, S.L. | Veterinary immunotherapy compositions for the Aged Related Cognitive Dysfunction. |
| US8846315B2 (en) | 2008-08-12 | 2014-09-30 | Zinfandel Pharmaceuticals, Inc. | Disease risk factors and methods of use |
| WO2010042603A1 (en) * | 2008-10-08 | 2010-04-15 | Cingulate Neuro Therapeutics, Llc | Amyloid and depression |
| HUE055739T2 (hu) | 2009-03-18 | 2021-12-28 | Ac Immune Sa | Eljárás terápiás alkalmazásra |
| UA107571C2 (xx) | 2009-04-03 | 2015-01-26 | Фармацевтична композиція | |
| EP2311823A1 (en) | 2009-10-15 | 2011-04-20 | AC Immune S.A. | 2,6-Diaminopyridine compounds for treating diseases associated with amyloid proteins or for treating ocular diseases |
| US8987419B2 (en) | 2010-04-15 | 2015-03-24 | AbbVie Deutschland GmbH & Co. KG | Amyloid-beta binding proteins |
| AU2011239966B2 (en) | 2010-04-16 | 2014-05-08 | Ac Immune S.A. | Novel compounds for the treatment of diseases associated with amyloid or amyloid-like proteins |
| EP2377860A1 (en) | 2010-04-16 | 2011-10-19 | AC Immune S.A. | Novel compounds for the treatment of diseases associated with amyloid or amyloid-like proteins |
| EP2598882B1 (en) | 2010-07-30 | 2017-07-26 | AC Immune S.A. | Safe and functional humanized antibodies for use in treating an amyloidosis |
| EP3533803B1 (en) | 2010-08-14 | 2021-10-27 | AbbVie Inc. | Anti-amyloid-beta antibodies |
| MY164376A (en) | 2010-10-07 | 2017-12-15 | Univ Leuven Kath | Phosphospecific antibodies recognizing tau |
| JP6027011B2 (ja) | 2010-10-26 | 2016-11-16 | エーシー イミューン ソシエテ アノニム | 疎水性部分によって修飾されたペプチドを含むリポソームベースの構築物 |
| US20120328605A1 (en) * | 2010-10-27 | 2012-12-27 | Daniel Larocque | Compositions and uses |
| EA201391017A1 (ru) | 2011-01-10 | 2014-04-30 | Зинфандел Фармасьютикалз, Инк. | Способы и готовые лекарственные формы для лечения болезни альцгеймера |
| WO2013009799A1 (en) * | 2011-07-11 | 2013-01-17 | Beth Israel Deaconess Medical Center, Inc. | Vitamin d receptor agonists and uses thereof |
| CA2811188C (en) | 2011-09-23 | 2020-04-28 | Andrea Pfeifer | Vaccine therapy |
| KR101981351B1 (ko) | 2011-10-07 | 2019-09-02 | 에이씨 이뮨 에스.에이. | 타우를 인식하는 포스포특이적 항체 |
| RU2644242C2 (ru) | 2012-04-05 | 2018-02-08 | Ац Иммуне С.А. | Гуманизированное тау-антитело |
| US20130315891A1 (en) | 2012-05-25 | 2013-11-28 | Matthew Charles | Formulations of human tissue kallikrein-1 for parenteral delivery and related methods |
| US20130323222A1 (en) | 2012-06-04 | 2013-12-05 | Matthew Charles | Human tissue kallikrein 1 glycosylation isoforms |
| CA3132310C (en) * | 2012-08-07 | 2024-01-09 | Children's Medical Center Corporation | Potassium channel openers for treating neurodegenerative diseases |
| PL2931276T3 (pl) * | 2012-12-13 | 2018-06-29 | H. Lundbeck A/S | Kompozycje zawierające wortioksetynę i donepezil |
| US9200068B2 (en) * | 2012-12-18 | 2015-12-01 | Regents Of The University Of Minnesota | Compositions and methods related to tauopathy |
| WO2014150877A2 (en) | 2013-03-15 | 2014-09-25 | Ac Immune S.A. | Anti-tau antibodies and methods of use |
| WO2015110263A1 (en) | 2014-01-21 | 2015-07-30 | Ac Immune Sa | Carbazole and carboline compounds for use in the diagnosis, treatment, alleviation or prevention of disorders associated with amyloid or amyolid-like proteins |
| US10314911B2 (en) * | 2014-04-08 | 2019-06-11 | Healthpartners Research & Education | Methods for protecting and treating traumatic brain injury, concussion and brain inflammation with intranasal insulin |
| KR102298676B1 (ko) * | 2014-05-09 | 2021-09-07 | 테크니메데 소시에다데 테크니코-메디시날 에스.에이. | 의약으로서 사용되기 위한 (s)-펄린돌 및 약학적으로 허용 가능한 그의 염 |
| TN2016000497A1 (en) * | 2014-05-09 | 2018-04-04 | Tecnimede Sociedade Tecnico Medicinal S | (r)-pirlindole and its pharmaceutically acceptable salts for use in medicine |
| CN107428820B (zh) | 2014-11-19 | 2022-03-22 | 阿克松神经系统科学公司 | 在阿尔茨海默氏病中的人源化tau抗体 |
| NZ775762A (en) | 2015-06-05 | 2025-02-28 | Genentech Inc | Anti-tau antibodies and methods of use |
| EP3374381A4 (en) | 2015-11-09 | 2019-05-15 | The University Of British Columbia | EPITOPES IN THE AMYLOID-BETA MEDIUM REGION AND CONFORMITY-SELECTIVE ANTIBODIES THEREOF |
| AU2016353553B2 (en) | 2015-11-09 | 2022-01-20 | The University Of British Columbia | Amyloid beta epitopes and antibodies thereto |
| KR102776187B1 (ko) | 2015-11-09 | 2025-03-07 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 아밀로이드 베타에서의 n-말단 에피토프 및 이에 형태적으로-선택적인 항체 |
| ITUA20161679A1 (it) | 2016-03-15 | 2017-09-15 | Neuraxpharm Italy S P A | Composizione per prevenire e trattare patologie neurodegenerative e disturbi cognitivi |
| CN109476729A (zh) | 2016-07-18 | 2019-03-15 | 英属哥伦比亚大学 | 淀粉样蛋白β的抗体 |
| WO2018038973A1 (en) * | 2016-08-20 | 2018-03-01 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Neuroprotective beta amyloid core peptides and peptidomimetic derivatives |
| US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
| MX2019006330A (es) | 2016-12-07 | 2019-09-26 | Genentech Inc | Anticuerpos anti-tau y metodos de uso. |
| UA128383C2 (uk) | 2016-12-07 | 2024-07-03 | Дженентек, Інк. | Антитіло до тау-білка та спосіб його застосування |
| AU2018230478B2 (en) | 2017-03-09 | 2025-01-23 | Diamedica Inc. | Dosage forms of tissue kallikrein 1 |
| EP3601337A1 (en) | 2017-03-28 | 2020-02-05 | Genentech, Inc. | Methods of treating neurodegenerative diseases |
| AU2018260628A1 (en) * | 2017-04-25 | 2019-12-12 | Temple Otorongo Llc | Pharmaceutical composition comprising tryptophan and phyllokinin derivative for use in treating psychiatric and psychological conditions |
| KR101917128B1 (ko) | 2017-04-28 | 2018-11-09 | 강원대학교산학협력단 | 산양삼 추출물을 포함하는 알츠하이머병의 예방 또는 치료용 약학 조성물 |
| WO2019018445A1 (en) * | 2017-07-17 | 2019-01-24 | Maxwell Biosciences, Inc. | POLYTHERAPY MODULATING THE MODULATION OF CATHELICIDINE GENE EXPRESSION FOR THE TREATMENT OF ALZHEIMER'S DISEASE AND OTHER DISEASES |
| US12286469B2 (en) | 2017-07-18 | 2025-04-29 | The University Of British Columbia | Humanized antibodies binding to amyloid-beta (A-beta) |
| US12459965B2 (en) | 2017-10-09 | 2025-11-04 | Compass Pathfinder Limited | Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use |
| GB2571696B (en) | 2017-10-09 | 2020-05-27 | Compass Pathways Ltd | Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced |
| US20200330592A1 (en) * | 2017-10-09 | 2020-10-22 | Keith Black | Compositions and methods of treating alzheimer's and other amyloid related diseases |
| CN111787942B (zh) | 2017-10-25 | 2024-03-29 | 杨森制药公司 | 磷酸化Tau肽的组合物及其用途 |
| PE20211090A1 (es) | 2018-01-05 | 2021-06-14 | Ac Immune Sa | Derivados de 1,3,4,5-tetrahidro-2h-pirido[4,3-b]indol para el tratamiento, alivio o prevencion de trastornos asociados con los agregados de tau |
| SG11202008098TA (en) | 2018-03-28 | 2020-10-29 | Axon Neuroscience Se | Antibody-based methods of detecting and treating alzheimer's disease |
| CN112351984B (zh) | 2018-06-04 | 2024-01-02 | Ac免疫有限公司 | 用于治疗、缓解或预防与Tau聚集物相关病症的四氢苯并呋喃并[2.3-c]吡啶和β-咔啉化合物 |
| CN112313230B (zh) | 2018-06-04 | 2024-03-15 | Ac免疫有限公司 | 用于治疗、缓解或预防与Tau聚集体相关的病症的新型化合物 |
| KR20200086198A (ko) | 2019-01-08 | 2020-07-16 | 주식회사 솔고 바이오메디칼 | 수소 흡장 금속을 포함하는 치매 예방 또는 치료용 조성물 |
| WO2020150423A1 (en) * | 2019-01-16 | 2020-07-23 | Yumanity Therapeutics, Inc. | Methods for the treatment of neurological disorders |
| MY206596A (en) | 2019-02-08 | 2024-12-25 | Janssen Pharmaceuticals Inc | Method of safe administration of phosphorylated tau peptide vaccine |
| JP7232931B2 (ja) | 2019-03-01 | 2023-03-03 | エイシー イミューン ソシエテ アノニム | タウ凝集体に関連する障害の治療、緩和、または予防のための新規化合物 |
| US12377112B2 (en) | 2019-04-17 | 2025-08-05 | Compass Pathfinder Limited | Methods of treating neurocognitive disorders, chronic pain and reducing inflammation |
| JP7327788B2 (ja) * | 2019-08-06 | 2023-08-16 | 学校法人福岡大学 | 糖化産物生成抑制剤及び医薬組成物 |
| US12352719B2 (en) | 2019-09-20 | 2025-07-08 | KYCERA AVX Components Corporation | Somatic cell-based electrical biosensor |
| WO2021067850A2 (en) * | 2019-10-02 | 2021-04-08 | Washington University | METHODS OF DETECTING circRNA |
| ES2821599A1 (es) | 2019-10-24 | 2021-04-26 | Univ Del Pais Vasco / Euskal Herriko Unibertsitatea | Compuestos y metodos para el tratamiento de la enfermedad de alzheimer |
| CN112939823A (zh) * | 2019-12-10 | 2021-06-11 | 中国石油天然气股份有限公司 | 泥页岩抑制剂制备方法及抑制剂的应用 |
| KR20210133603A (ko) | 2020-04-29 | 2021-11-08 | 정지영 | 굼벵이를 포함하는 치매 예방 또는 치료용 조성물 |
| WO2021231566A1 (en) * | 2020-05-12 | 2021-11-18 | Massachusetts Institute Of Technology | The use of choline supplementation as therapy for apoe4-related disorders |
| AR123730A1 (es) | 2020-10-15 | 2023-01-04 | Ac Immune Sa | Compuestos novedosos |
| KR102598904B1 (ko) * | 2022-12-16 | 2023-11-06 | 닥터노아바이오텍 주식회사 | 콜린에스터라제 억제제의 부작용 예방 또는 치료용 조성물 |
| JP2024534151A (ja) | 2021-08-27 | 2024-09-18 | ジェネンテック， インコーポレイテッド | タウ病態の治療方法 |
| CN115624555A (zh) * | 2022-02-24 | 2023-01-20 | 中国药科大学 | 猪去氧胆酸在制备抗抑郁药物中的应用 |
| CN118871989A (zh) | 2022-03-14 | 2024-10-29 | 基因泰克公司 | 基于语音分析来预测神经退行性疾病 |
| KR20230147988A (ko) * | 2022-04-15 | 2023-10-24 | 아주대학교산학협력단 | Rage 길항제 및 age 소거제를 포함하는 당뇨성 뇌졸중 예방 또는 치료용 약학적 조성물 |
| JP2025525371A (ja) | 2022-06-21 | 2025-08-05 | ジェネンテック， インコーポレイテッド | 音声分析に基づくアルツハイマー病（ａｄ）の長期的進行の検出 |
| WO2026037826A1 (en) | 2024-08-12 | 2026-02-19 | Ac Immune Sa | 2,4-dihydropyrazolo[3',4':4,5]pyrano[2,3-b]pyridine compounds |
| CN119570766B (zh) * | 2025-02-08 | 2025-05-16 | 上海锴泰生物科技有限公司 | 一种胶原蛋白酶突变体、基因片段、重组质粒、重组表达体系、胶原蛋白肽，及其制备方法和用途 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5840294A (en) * | 1993-03-29 | 1998-11-24 | Queen's University At Kingston | Method for treating amyloidosis |
| WO1994022437A2 (en) * | 1993-03-29 | 1994-10-13 | Queen's University At Kingston | Method for treating amyloidosis |
| WO1997021728A1 (en) * | 1995-12-12 | 1997-06-19 | Karolinska Innovations Ab | PEPTIDE BINDING THE KLVFF-SEQUENCE OF AMYLOID $g(b) |
| JPH10259126A (ja) * | 1997-01-17 | 1998-09-29 | Takeda Chem Ind Ltd | アルツハイマー病治療・予防剤 |
| CA2320224C (en) * | 1998-02-11 | 2008-08-12 | Neurochem, Inc. | Method for modulating macrophage activation |
| GB9805561D0 (en) * | 1998-03-16 | 1998-05-13 | Merck Sharp & Dohme | A combination of therapeutic agents |
| WO1999059571A1 (en) * | 1998-05-15 | 1999-11-25 | Neurochem, Inc. | Use of amyloid inhibitors for modulating neuronal cell death |
| ATE366259T1 (de) * | 1999-03-04 | 2007-07-15 | Praecis Pharm Inc | Beta-amyloid-peptidaggregation regulierende peptide mit d-aminosäuren |
| IL146143A0 (en) * | 1999-04-28 | 2002-07-25 | Univ Kingston | Compositions and methods for treating amyloidosis |
| ATE384077T1 (de) * | 1999-05-05 | 2008-02-15 | Neurochem Int Ltd | Stereoselektive antifibrillogene peptide |
| US20020094335A1 (en) * | 1999-11-29 | 2002-07-18 | Robert Chalifour | Vaccine for the prevention and treatment of alzheimer's and amyloid related diseases |
| EP1251837A2 (en) * | 1999-12-23 | 2002-10-30 | Neurochem, Inc. | Compounds and methods for modulating cerebral amyloid angiopathy |
| US20020151591A1 (en) * | 2000-10-17 | 2002-10-17 | Anabella Villalobos | Combination use of acetylcholinesterase inhibitors and GABAa inverse agonists for the treatment of cognitive disorders |
| EP1538163A3 (en) * | 2000-11-01 | 2005-06-15 | Insight Biotechnology Limited | Phosphorylated Amyloid-Beta 1-43 Protein and its use in the treatment of Alzheimer's disease |
| US20050031651A1 (en) * | 2002-12-24 | 2005-02-10 | Francine Gervais | Therapeutic formulations for the treatment of beta-amyloid related diseases |
| US20050142191A1 (en) * | 2003-06-23 | 2005-06-30 | Neurochem (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
| US20050038000A1 (en) * | 2003-06-23 | 2005-02-17 | Xianqi Kong | Methods and compositions for the treatment of amyloid-and epileptogenesis-associated diseases |
| US7253306B2 (en) * | 2003-06-23 | 2007-08-07 | Neurochem (International) Limited | Pharmaceutical drug candidates and methods for preparation thereof |
-
2003
- 2003-12-24 AU AU2003292936A patent/AU2003292936A1/en not_active Abandoned
- 2003-12-24 CA CA002511606A patent/CA2511606A1/en not_active Abandoned
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- 2003-12-24 US US10/540,763 patent/US20060135403A1/en not_active Abandoned
- 2003-12-24 JP JP2005509680A patent/JP2006525226A/ja not_active Withdrawn
- 2003-12-24 BR BR0317747-5A patent/BR0317747A/pt not_active IP Right Cessation
- 2003-12-24 KR KR1020057012003A patent/KR20050101537A/ko not_active Ceased
- 2003-12-24 WO PCT/CA2003/002011 patent/WO2004058258A1/en not_active Ceased
- 2003-12-24 NZ NZ541282A patent/NZ541282A/en unknown
- 2003-12-24 CA CA002511599A patent/CA2511599A1/en not_active Abandoned
- 2003-12-24 EP EP03767368A patent/EP1585520A1/en not_active Withdrawn
- 2003-12-24 JP JP2005509679A patent/JP2006512417A/ja active Pending
- 2003-12-24 MX MXPA05006940A patent/MXPA05006940A/es active IP Right Grant
- 2003-12-24 EP EP03788737A patent/EP1581203A1/en not_active Withdrawn
- 2003-12-24 EA EA200501023A patent/EA012325B1/ru not_active IP Right Cessation
- 2003-12-24 AU AU2003291910A patent/AU2003291910B2/en not_active Ceased
-
2005
- 2005-06-22 IL IL169338A patent/IL169338A0/en unknown
- 2005-06-23 NO NO20053077A patent/NO20053077L/no not_active Application Discontinuation
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007516939A (ja) * | 2003-06-23 | 2007-06-28 | ニューロケム （インターナショナル） リミテッド | アミロイド関連疾患を治療するための方法および組成物 |
| JP2007516938A (ja) * | 2003-06-23 | 2007-06-28 | ニューロケム （インターナショナル） リミテッド | アミロイド関連疾患を治療するための方法および組成物 |
| JPWO2005020882A1 (ja) * | 2003-08-29 | 2006-10-26 | 小野薬品工業株式会社 | Ｓ１ｐ受容体結合能を有する化合物およびその医薬用途 |
| JP4947406B2 (ja) * | 2003-08-29 | 2012-06-06 | 小野薬品工業株式会社 | Ｓ１ｐ受容体結合能を有する化合物およびその医薬用途 |
| WO2010140704A1 (ja) * | 2009-06-04 | 2010-12-09 | 住友化学株式会社 | Ｓ－（３－アミノプロピル）チオ硫酸またはその金属塩の使用 |
| US8664432B2 (en) | 2009-06-04 | 2014-03-04 | Sumitomo Chemical Company, Limited | Use of S-(3-aminopropyl)thiosulfuric acid or metal salt thereof |
| JP2018529648A (ja) * | 2015-08-10 | 2018-10-11 | アルジオン， インコーポレイテッド | 神経変性疾患を治療および予防するための組成物および方法 |
| US12187668B2 (en) | 2015-08-10 | 2025-01-07 | Alzheon, Inc. | Compositions and methods for treating and preventing neurodegenerative disorders |
| JP2022092910A (ja) * | 2020-12-11 | 2022-06-23 | 国立研究開発法人国立長寿医療研究センター | 認知症の危険性判定システムおよび認知症の危険性判定用プログラム |
| JP7682515B2 (ja) | 2020-12-11 | 2025-05-26 | 国立研究開発法人国立長寿医療研究センター | 認知症の危険性判定システムおよび認知症の危険性判定用プログラム |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05006940A (es) | 2006-02-22 |
| KR20050101537A (ko) | 2005-10-24 |
| NO20053077D0 (no) | 2005-06-23 |
| CA2511599A1 (en) | 2004-07-15 |
| IL169338A0 (en) | 2007-07-04 |
| EA200501023A1 (ru) | 2005-12-29 |
| EP1581203A1 (en) | 2005-10-05 |
| NO20053077L (no) | 2005-09-22 |
| US20060135403A1 (en) | 2006-06-22 |
| EP1585520A1 (en) | 2005-10-19 |
| WO2004058239A1 (en) | 2004-07-15 |
| BR0317747A (pt) | 2005-11-22 |
| AU2003291910B2 (en) | 2009-10-01 |
| CA2511606A1 (en) | 2004-07-15 |
| NZ541282A (en) | 2009-02-28 |
| AU2003292936A1 (en) | 2004-07-22 |
| WO2004058258A1 (en) | 2004-07-15 |
| EA012325B1 (ru) | 2009-08-28 |
| AU2003291910A1 (en) | 2004-07-22 |
| JP2006512417A (ja) | 2006-04-13 |
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