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21. 发明授权

US07335505B2 Materials and methods relating to protein aggregation in neurodegenerative disease 有权
标题翻译：与神经退行性疾病中的蛋白质聚集相关的材料和方法
公开(公告)号：US07335505B2
公开(公告)日：2008-02-26
申请号：US10451782
申请日：2002-01-15
申请人： Claude Michel Wischik , David Horsley , Janet Elizabeth Rickard , Charles Robert Harrington
发明人： Claude Michel Wischik , David Horsley , Janet Elizabeth Rickard , Charles Robert Harrington
IPC分类号： C12M1/20 , C12N1/14 , C12N5/06 , G01N33/53 , G01N33/567 , C12Q1/02 , A01N63/00 , A01N39/00 , A61K48/00
CPC分类号： G01N33/6896 , A61K31/00 , A61K31/5415
摘要： The present invention provides methods of proteolytically converting a precursor protein (e.g. tau) to a product fragment (e.g., a 12 kd fragment) in a stable cell line, wherein the precursor protein is associated with a disease state in which the precursor protein aggregates pathologically (e.g. a tauopathy), and the methods comprise: (a) providing a stable cell line transfected with nucleic acid encoding: (i) a template fragment of the precursor protein such that the template fragment is constitutively expressed in the cell at a level which is not toxic to the cell; and (ii) the precursor protein, which protein is inducibly expressed in the cell in response to a stimulus, whereby interaction of the template fragment with the precursor protein causes a conformational change in the precursor protein such as to cause aggregation and proteolytic processing of the precursor protein to the product fragment. The method is preferably used to screen for modulators of the aggregation process by monitoring production (or modulation of production) of the product band or bands. Also provided are materials for used in the assays, plus medicaments, and related uses and processes, based on compounds which show high activity in the assay of the invention e.g. reduced diaminophenothiazines.
摘要翻译：本发明提供了在稳定细胞系中将前体蛋白质（例如tau）蛋白水解转化成产物片段（例如，12kd片段）的方法，其中前体蛋白质与其中前体蛋白质在病理学上聚集的疾病状态相关联（例如，tau蛋白病），并且所述方法包括：（a）提供用核酸转染的稳定的细胞系，编码：（i）前体蛋白的模板片段，使得模板片段在细胞中以对细胞无毒性; 和（ii）前体蛋白质，该蛋白质响应于刺激而在细胞中可诱导表达，由此模板片段与前体蛋白质的相互作用导致前体蛋白质的构象变化，从而导致蛋白质的聚集和蛋白水解加工前体蛋白到产物片段。该方法优选用于通过监测产品带或带的生产（或调制生产）来筛选聚集过程的调制器。还提供了用于测定中的材料，以及基于在本发明的测定中显示高活性的化合物的药物以及相关用途和方法，例如。还原二氨基吩噻嗪。

22. 发明授权

US08263589B2 Inhibitors of protein aggregation 有权
标题翻译：蛋白质聚集抑制剂
公开(公告)号：US08263589B2
公开(公告)日：2012-09-11
申请号：US12294605
申请日：2007-03-28
申请人： Claude Michel Wischik , Janet Elizabeth Rickard , Charles Robert Harrington , David Horsley
发明人： Claude Michel Wischik , Janet Elizabeth Rickard , Charles Robert Harrington , David Horsley
IPC分类号： A61K31/54 , C07D279/36
CPC分类号： C07D279/20 , A61K31/5415 , A61K49/0002 , A61K49/003 , A61K51/0465 , G01N33/6896 , G01N2800/2835 , Y02A50/393 , Y02A50/411
摘要： The invention relates generally to the use of diaminophenothiazine compounds to inhibit or reverse the aggregation of synuclein, and for their use in the manufacture of medicaments for this purpose (e.g. for the treatment of Parkinson's Disease). Also provided are related methods of detecting or labelling of aggregated synuclein.
摘要翻译：本发明一般涉及二氨基吩噻嗪类化合物用于抑制或逆转突触核蛋白的聚集，并且用于制备用于此目的的药物（例如用于治疗帕金森病）。还提供了检测或标记聚集的突触核蛋白的相关方法。

23. 发明授权

US07893054B2 Materials and methods relating to protein aggregation in neurodegenerative disease 有权
标题翻译：与神经退行性疾病中的蛋白质聚集相关的材料和方法
公开(公告)号：US07893054B2
公开(公告)日：2011-02-22
申请号：US12010649
申请日：2008-01-28
申请人： Claude Michel Wischik , David Horsley , Janet Elizabeth Rickard , Charles Robert Harrington
发明人： Claude Michel Wischik , David Horsley , Janet Elizabeth Rickard , Charles Robert Harrington
IPC分类号： A61K31/54
CPC分类号： G01N33/6896 , A61K31/00 , A61K31/5415
摘要： The present invention is directed to methods for the treatment or prophylaxis of a tauopathy comprising administering to a patient in need thereof a medicament comprising a phenothiazine.
摘要翻译：本发明涉及治疗或预防tau病变的方法，包括向有需要的患者施用包含吩噻嗪的药物。

24. 发明授权

US07713962B2 Neurofibrillary labels 有权
标题翻译：神经原纤维标签
公开(公告)号：US07713962B2
公开(公告)日：2010-05-11
申请号：US12071693
申请日：2008-02-25
申请人： Claude Michel Wischik , Charles Robert Harrington , Janet Elizabeth Rickard , David Horsley
发明人： Claude Michel Wischik , Charles Robert Harrington , Janet Elizabeth Rickard , David Horsley
IPC分类号： A61K31/54
CPC分类号： C07D417/12 , C07D277/66 , C07D279/20 , G01N33/583 , G01N33/6896
摘要： A method for determining the Braak stage of neurofibrillary degeneration associated with a tauopathy in a subject having neurofibrillary degeneration is disclosed. The method comprises the steps of (i) administering to the subject a conjugated, chelated or detectable chemical group-associated ligand that labels aggregated paired helical filament (PHF) tau protein and is capable of crossing the blood brain barrier; (ii) determining the presence and\or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, and (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. Preferred ligands include sulphonated-benzothiazole-like compounds and diamonophenothiazines.
摘要翻译：公开了一种用于确定与具有神经原纤维变性的受试者中与tau蛋白病相关的神经原纤维变性的Braak阶段的方法。该方法包括以下步骤：（i）向受试者施用标记聚集的成对螺旋丝（PHF）tau蛋白并能够穿过血脑屏障的共轭，螯合或可检测的化学基团相关配体; （ii）确定与受试者脑内侧颞叶中细胞外聚集的PHF tau结合的配体的存在和/或数量，以及（iii）将（ii）中确定的测定结果与神经原纤维的程度相关联主题变性优选的配体包括磺化苯并噻唑类化合物和二氨基吩噻嗪。

25. 发明申请

US20100290986A1 THERAPEUTIC USE OF DIAMINOPHENOTHIAZINES 有权
标题翻译： DIAMINOPHENOTHIAZINES的治疗用途
公开(公告)号：US20100290986A1
公开(公告)日：2010-11-18
申请号：US12681511
申请日：2008-10-01
申请人： Claude Michel Wischik , Damon Jude Wischik , John Mervyn David Storey , Charles Robert Harrington
发明人： Claude Michel Wischik , Damon Jude Wischik , John Mervyn David Storey , Charles Robert Harrington
IPC分类号： A61K31/5415 , A61K51/04 , A61K49/00 , A61P25/28 , A61P7/06 , A61P25/16
CPC分类号： A61K31/5415 , A61K9/0065 , A61K31/542 , A61K45/06
摘要： The present invention relates generally to methods and materials for use in the treatment or prophylaxis of diseases, for example cognitive disorders, using diaminophenothiazines. In particular it relates to treatments having optimised pharmacokinetic properties, and dosage forms are intended to improve the relative cognitive or CNS benefits of the diaminophenothiazines, for instance compared to haematological effects.
摘要翻译：本发明一般涉及用于治疗或预防使用二氨基吩噻嗪的疾病，例如认知障碍的方法和材料。特别地，它涉及具有优化的药代动力学性质的治疗，并且剂型旨在改善二氨基吩噻嗪的相对认知或CNS益处，例如与血液学作用相比。

26. 发明授权

US09149481B2 Therapeutic use of diaminophenothiazines 有权
标题翻译：二氨基吩噻嗪的治疗用途
公开(公告)号：US09149481B2
公开(公告)日：2015-10-06
申请号：US12681511
申请日：2008-10-01
申请人： Claude Michel Wischik , Damon Jude Wischik , John Mervyn David Storey , Charles Robert Harrington
发明人： Claude Michel Wischik , Damon Jude Wischik , John Mervyn David Storey , Charles Robert Harrington
IPC分类号： A61K51/00 , A61M36/14 , A61K31/542
CPC分类号： A61K31/5415 , A61K9/0065 , A61K31/542 , A61K45/06
摘要： The present invention relates generally to methods and materials for use in the treatment or prophylaxis of diseases, for example cognitive disorders, using diaminophenothiazines. In particular it relates to treatments having optimised pharmacokinetic properties, and dosage forms are intended to improve the relative cognitive or CNS benefits of the diaminophenothiazines, for instance compared to haematological effects.
摘要翻译：本发明一般涉及用于治疗或预防使用二氨基吩噻嗪的疾病，例如认知障碍的方法和材料。特别地，它涉及具有优化的药代动力学性质的治疗，并且剂型旨在改善二氨基吩噻嗪的相对认知或CNS益处，例如与血液学作用相比。

27. 发明授权

US08895313B2 Ligands for aggregated tau molecules 有权
标题翻译：用于聚集的tau分子的配体
公开(公告)号：US08895313B2
公开(公告)日：2014-11-25
申请号：US13063525
申请日：2009-09-23
申请人： Steven John Kemp , Lynda Jane Storey , John Mervyn David Storey , Janet Rickard , Charles Robert Harrington , Claude Michel Wischik , Scott Clunas , Tobias Kerst Heinrich
发明人： Steven John Kemp , Lynda Jane Storey , John Mervyn David Storey , Janet Rickard , Charles Robert Harrington , Claude Michel Wischik , Scott Clunas , Tobias Kerst Heinrich
IPC分类号： G01N33/50 , C07D277/66 , C07D417/12 , C07D513/04 , C07D471/04 , C07D487/04 , G01N33/68
CPC分类号： G01N33/6896 , C07D277/66 , C07D417/12 , C07D471/04 , C07D487/04 , C07D513/04 , G01N2333/4709 , G01N2800/2821 , Y10T436/14 , Y10T436/147777 , Y10T436/17 , Y10T436/18
摘要： Provided are certain benzothiazole, imidazothiazole, imidazopyrimidine and imidazopyridine compounds, including, for example: formula (I) and pharmaceutically and physiologically acceptable salts, hydrates, and solvates thereof. Such compounds can be used as diagnostic ligands or labels of tau protein and PHF.
摘要翻译：提供某些苯并噻唑，咪唑并噻唑，咪唑并嘧啶和咪唑并吡啶化合物，包括例如：式（I）及其药学上和生理上可接受的盐，水合物和溶剂化物。此类化合物可用作tau蛋白和PHF的诊断配体或标记。

28. 发明授权

US06953794B2 Inhibition of tau-tau association 失效
标题翻译：抑制tau-tau结合
公开(公告)号：US06953794B2
公开(公告)日：2005-10-11
申请号：US10107181
申请日：2002-03-28
申请人： Claude Michel Wischik , Patricia Carol Edwards , Charles Robert Harrington , Martin Roth , Aaron Klug
发明人： Claude Michel Wischik , Patricia Carol Edwards , Charles Robert Harrington , Martin Roth , Aaron Klug
IPC分类号： G01N33/53 , A61K31/54 , A61K31/5415 , A61P25/28 , C07D279/20 , C07K14/47 , G01N33/15 , G01N33/50 , G01N33/531 , G01N33/543 , G01N33/566 , G01N33/68
CPC分类号： G01N33/502 , A61K31/54 , A61K31/5415 , C07K14/4711 , G01N33/5008 , G01N33/5058 , G01N33/6896 , G01N2333/4709 , G01N2500/00 , G01N2800/28 , G01N2800/2821
摘要： A composition and use thereof for the prophylaxis or treatment of Alzheimer's disease, motor neurone disease, Lewy body disease, Pick's disease or progressive supranuclear palsy. The composition includes an agent which modulates or inhibits tau-tau association and which does not inhibit tau-tubulin binding. In the method the agent is administered to an individual in order to achieve the desired therapeutic effect. Preferably the agent which is administered is a phenothiazine compound.
摘要翻译：用于预防或治疗阿尔茨海默病，运动神经元疾病，路易体病，皮克病或进行性核上性麻痹的组合物和用途。组合物包括调节或抑制tau-tau缔合并且不抑制tau蛋白结合的药剂。在该方法中，为了获得所需的治疗效果，向个体施用药剂。优选地，施用的药剂是吩噻嗪化合物。

29. 发明申请

US20080207604A1 Materials and methods relating to protein aggregation in neurodegenerative disease 失效
标题翻译：与神经退行性疾病中的蛋白质聚集相关的材料和方法
公开(公告)号：US20080207604A1
公开(公告)日：2008-08-28
申请号：US11979252
申请日：2007-10-31
申请人： Claude Michel Wischik , Patricia Carol Edwards , Charles Robert Harrington , Martin Roth , Aaron King
发明人： Claude Michel Wischik , Patricia Carol Edwards , Charles Robert Harrington , Martin Roth , Aaron King
IPC分类号： A61K31/54
CPC分类号： G01N33/502 , A61K31/54 , A61K31/5415 , C07K14/4711 , G01N33/5008 , G01N33/5058 , G01N33/6896 , G01N2333/4709 , G01N2500/00 , G01N2800/28 , G01N2800/2821
摘要： The present invention relates to methods for the detection of substances capable of modulating or inhibiting pathological tau-tau protein association. The methods of the present invention are particularly useful in screening substances for the prophylaxis and treatment of Alzheiemer's disease.
摘要翻译：本发明涉及检测能够调节或抑制病理性tau-tau蛋白缔合的物质的方法。本发明的方法在用于预防和治疗阿尔茨海默病的物质中特别有用。

30. 发明授权

US06376205B1 Screening methods for agents that modulate or inhibit tau association with tau or map2 失效
标题翻译：调节或抑制tau与tau或map2 tau结合的药剂的筛选方法
公开(公告)号：US06376205B1
公开(公告)日：2002-04-23
申请号：US08913915
申请日：1997-12-12
申请人： Claude Michel Wischik , Patricia Carol Edwards , Charles Robert Harrington , Martin Roth , Aaron Klug
发明人： Claude Michel Wischik , Patricia Carol Edwards , Charles Robert Harrington , Martin Roth , Aaron Klug
IPC分类号： G01N3353
CPC分类号： G01N33/502 , A61K31/54 , A61K31/5415 , C07K14/4711 , G01N33/5008 , G01N33/5058 , G01N33/6896 , G01N2333/4709 , G01N2500/00 , G01N2800/28 , G01N2800/2821
摘要： The present invention relates to methods for the detection of substances capable of modulating or inhibiting pathological tau-tau protein association. The methods of the present invention are particularly useful in screening substances for the prophylaxis and treatment of Alzheiemer's disease.
摘要翻译：本发明涉及检测能够调节或抑制病理性tau-tau蛋白缔合的物质的方法。本发明的方法在用于预防和治疗阿尔茨海默病的物质中特别有用。

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