公开(公告)号：EP3332797A3

公开(公告)日：2018-08-01

申请号：EP18153508.9

申请日：2008-02-11

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： ALKON, Daniel L. ,  ZOHAR, Ofer

IPC分类号： A61K38/18 ,  A61K31/00 ,  A61K31/05 ,  A61K31/335 ,  A61K31/35 ,  A61K31/365 ,  A61K31/395 ,  A61K31/4015 ,  A61K45/00 ,  A61P25/00 ,  A61P25/28

CPC分类号： A61K38/1825 ,  A61K31/00 ,  A61K31/05 ,  A61K31/335 ,  A61K31/35 ,  A61K31/365 ,  A61K31/395 ,  A61K31/4015 ,  A61K38/00

摘要： The invention provides for the use of protein kinase activators or boosters of nerve growth factor (NGF), brainderived neurotrophic factor (BDNF) or other neurotrophic factors to treat head trauma. Specifically, the present invention provides methods of treating head trauma comprising the steps of identifying a subject having suffered a head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator or 4-methylcatechol acetic acid (MCBA) and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma.

公开(公告)号：EP3010500A1

公开(公告)日：2016-04-27

申请号：EP14723585.7

申请日：2014-03-15

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： ALKON, Daniel L.

IPC分类号： A61K31/365 ,  G01N33/48 ,  G01N33/53 ,  A61P25/28

CPC分类号： G01N33/5008 ,  A61K31/365 ,  C12Q1/485 ,  C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5005 ,  G01N33/573 ,  G01N2333/912 ,  G01N2500/04 ,  G01N2500/10 ,  G01N2500/20

摘要： The present disclosure is directed to methods of identifying neuroprotective PKC activators comprising analyzing candidate PKC activators to determine if they are non-tumorigenic, non-toxic, accessible to the brain, have α and ε specificity, result in minimal down regulation of the ε isozyme, are synapatogenic, and are anti-apoptotic. The methods disclosed herein may further comprise analyzing candidate PKC activators to determine whether they are neuroprotective against ASPD, protect against
in vivo neurodegeneration, enhance learning and memory in normal animal modesl, induce downstream synaptogenic biochemical events, activate Α-β degrading enzymes, inhibit GSK-3β, and/or activate alpha-secretase.

公开(公告)号：EP2959914A1

公开(公告)日：2015-12-30

申请号：EP15002036.0

申请日：2008-02-11

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： Alkon, Daniel ,  Zohar, Ofer

IPC分类号： A61K38/18 ,  A61K31/00 ,  A61K31/05 ,  A61K31/335 ,  A61K31/35 ,  A61K31/365 ,  A61K31/395 ,  A61K31/4015 ,  A61K45/00 ,  A61P25/00 ,  A61P25/28

CPC分类号： A61K38/1825 ,  A61K31/00 ,  A61K31/05 ,  A61K31/335 ,  A61K31/35 ,  A61K31/365 ,  A61K31/395 ,  A61K31/4015 ,  A61K38/00

摘要： The invention provides for the use of protein kinase activators or boosters of nerve growth factor (NGF), brainderived neurotrophic factor (BDNF) or other neurotrophic factors to treat head trauma. Specifically, the present invention provides methods of treating head trauma comprising the steps of identifying a subject having suffered a head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator or 4-methylcatechol acetic acid (MCBA) and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma.

摘要翻译： 本发明提供了使用蛋白激酶活化剂或神经生长因子（NGF）的助推器，brainderived神经营养因子（BDNF）或其他神经营养因子来治疗头部创伤。 具体而言，本发明提供了治疗头部创伤包括识别对象的步骤遭受一个头部创伤和向所述受试者施用一种药物组合物的量的包含蛋白激酶C（PKC）活化剂或4-甲基儿茶酚乙酸的方法（ MCBA）和有效药学上可接受的载体来治疗头部创伤的至少一种症状。

公开(公告)号：EP2539709B1

公开(公告)日：2015-05-20

申请号：EP11745005.6

申请日：2011-02-22

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： KHAN, Tapan, K. ,  ALKON, Daniel, L.

IPC分类号： G01N33/48 ,  G01N33/53

CPC分类号： C12Q1/485 ,  C12Q1/68 ,  C12Q1/6883 ,  G01N33/573 ,  G01N33/6896 ,  G01N2333/912 ,  G01N2800/2821

公开(公告)号：EP2780316A1

公开(公告)日：2014-09-24

申请号：EP12795194.5

申请日：2012-11-13

申请人： Blanchette Rockefeller Neurosciences Institute ,  Alkon, Daniel L. ,  Nelson, Thomas, J.

发明人： ALKON, Daniel, L. ,  NELSON, Thomas, J.

IPC分类号： C07C69/608 ,  C07D493/00 ,  C07J9/00 ,  A61P25/00 ,  A61K31/56 ,  A61K31/35 ,  A61K31/22

摘要： The present disclosure relates to esters of 8-[2-(2-pentyl-cyclopropylmethyl)cyclopropyl]-octanoic acid (“DCPLA”). The disclosure further relates to compositions, kits, and methods for treatment using the esters.

摘要翻译： 本公开涉及8- [2-（2-戊基 - 环丙基甲基）环丙基] - 辛酸（“DCPLA”）的酯。 本公开还涉及用酯处理的组合物，试剂盒和方法。

公开(公告)号：EP2764120A1

公开(公告)日：2014-08-13

申请号：EP12780586.9

申请日：2012-10-05

申请人： Blanchette Rockefeller Neurosciences Institute ,  Alkon, Daniel L. ,  Khan, Tapan Kumar

发明人： ALKON, Daniel, L. ,  KHAN, Tapan, K.

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/5023

摘要： The present disclosure is directed to methods of diagnosing a neurodegenerative condition, such as Alzheimer's disease, comprising contacting a cell sample from a subject with at least one stimulus, such as a protein and/or polysaccharide mixture, a protein kinase C activator, an Αβ oligomer, an agent, and combinations thereof; and detecting the expression of at least one gene in the cell sample. Methods may further comprise comparing the expression of the at least one gene in the cell sample to the expression of the same at least one gene in control cells; and determining whether the subject has the neurodegenerative condition (e.g., Alzheimer's disease), wherein a change in the expression of the at least one gene in the cell sample compared to the expression of the same at least one gene in the control cells indicates the subject has the neurodegenerative condition (e.g., Alzheimer's disease).

公开(公告)号：EP2669386A1

公开(公告)日：2013-12-04

申请号：EP13004274.0

申请日：2009-07-28

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： Khan, Tapan Kumar ,  Alkon, Daniel

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N2800/2821

摘要： The present invention relates to a method for diagnosing Alzheimer's Disease (AD) using PKC-elicited gene expression profiles. PKC-activation elicits different genomic profiles in AD cells, as compared with control cells, which can be used to diagnose AD and individuals at risk for developing AD.

摘要翻译： 本发明涉及使用PKC诱导的基因表达谱来诊断阿尔茨海默病（AD）的方法。 与对照细胞相比，PKC激活引起AD细胞中的不同基因组谱，可用于诊断AD和发展AD风险的个体。

公开(公告)号：EP1753511B1

公开(公告)日：2013-07-31

申请号：EP05749738.0

申请日：2005-05-18

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： SUN, Miao-Kun ,  ALKON, Daniel, L.

IPC分类号： A61P25/24 ,  A61K31/365 ,  A61K31/192 ,  A61K31/196 ,  A61K31/045 ,  A61K31/05 ,  A61K31/4164 ,  A61K31/4172

CPC分类号： A61K38/1825 ,  A61K31/045 ,  A61K31/05 ,  A61K31/192 ,  A61K31/196 ,  A61K31/365 ,  A61K31/366 ,  A61K31/4164 ,  A61K31/4172

摘要： The invention provides for the use of protein kinase C activators to treat depressive disorders.

公开(公告)号：EP2339349A1

公开(公告)日：2011-06-29

申请号：EP10011288.7

申请日：2006-09-25

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： Khan, Tapan Kumar ,  Alkon, Daniel

IPC分类号： G01N33/68

CPC分类号： G01N33/6896 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5091 ,  G01N2333/4709 ,  G01N2333/912 ,  G01N2800/2821

摘要： The present invention relates to a method for screening a test compound useful for the treatment of Alzheimer's Disease comprising (a) contacting cells isolated from a subject diagnosed with Alzheimer's Disease with an agent that is a protein kinase C activator, wherein said contacting is in the presence of the test compound; (b) measuring the ratio of a phosphorylated first MAP kinase protein to a phosphorylated second MAP kinase protein, wherein said phosphorylated first and second MAP kinase proteins are obtained from said cells after the contacting in step (a); (c) measuring the ratio of phosphorylated first MAP kinase protein to phosphorylated second MAP kinase protein in cells from said subject that have not been contacted with the test compound of step (a); (d) subtracting the ratio obtained in step (c) from the ratio obtained in step (b); and (e) identifying a test compound useful for the treatment of Alzheimer's Disease based on the difference calculated in step (d).

摘要翻译： 本发明涉及一种筛选用于治疗阿尔茨海默病的测试化合物的方法，包括（a）将从被诊断为阿尔茨海默病的受试者分离的细胞与蛋白激酶C激活剂接触，其中所述接触处于 试验化合物的存在; （b）测量磷酸化的第一MAP激酶蛋白与磷酸化的第二MAP激酶蛋白的比例，其中所述磷酸化的第一和第二MAP激酶蛋白在步骤（a）中接触后从所述细胞获得; （c）测量未与步骤（a）的测试化合物接触的来自所述受试者的细胞中磷酸化的第一MAP激酶蛋白与磷酸化的第二MAP激酶蛋白的比例; （d）从步骤（b）中获得的比率减去步骤（c）中获得的比率; 和（e）基于步骤（d）中计算出的差异鉴定用于治疗阿尔茨海默氏病的测试化合物。

公开(公告)号：EP2172246A2

公开(公告)日：2010-04-07

申请号：EP10000734.3

申请日：2003-03-07

申请人： Blanchette Rockefeller Neurosciences Institute

发明人： Alkon, Daniel L. ,  Etcheberrigaray, Rene

IPC分类号： A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  A61K31/00 ,  A61K31/366

CPC分类号： A61K31/365 ,  A61K9/0053 ,  A61K31/00 ,  A61K31/366 ,  Y02A50/406

摘要： The present invention relates to compositions to modulate alpha-secretase and/or to improve cognitive ability. The invention further relates the improved/enhanced cognitive ability in diseased individuals, particularly Alzheimer's Disease patients, and treatment thereof through increased sAPP production. In the present invention PKC activators such as compounds of bryostatin or neristatin class are used for enhancing the cognitive ability.

摘要翻译： 本发明涉及调节α-分泌酶和/或改善认知能力的组合物。 本发明进一步涉及改善/增强的患病个体，特别是阿尔茨海默病患者的认知能力，以及通过增加的sAPP产生来治疗它们。 在本发明中，PKC活化剂如苔藓抑制素或神经抑制素类化合物用于增强认知能力。