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1. 发明公开

EP4090344A1 METHODS OF TREATING FRAGILE X SYNDROME WITH REELIN 审中-实审
公开(公告)号：EP4090344A1
公开(公告)日：2022-11-23
申请号：EP21741738.5
申请日：2021-01-19
申请人： University of South Florida , Weeber, Edwin
发明人： NASH, Kevin R. , LI, Qingyou , MORRILL, Nicole , WEEBER, Edwin
IPC分类号： A61K35/761 , A61P25/00 , A61P25/28

2. 发明申请

WO2019006107A1 MODIFIED UBE3A GENE FOR A GENE THERAPY APPROACH FOR ANGELMAN SYNDROME 审中-公开
公开(公告)号：WO2019006107A1
公开(公告)日：2019-01-03
申请号：PCT/US2018/039980
申请日：2018-06-28
申请人： NASH, Kevin Ron , WEEBER, Edwin John , UNIVERSITY OF SOUTH FLORIDA
发明人： NASH, Kevin Ron , WEEBER, Edwin John
IPC分类号： A61K31/711 , C12N15/85 , C12P19/34
摘要： A novel vector, composition and method of treating a neurological disorder characterized by deficient UBE3A is presented. The UBE3A gene, which encodes for E6-AP, a ubiquitin ligase, was found to be responsible for Angelman syndrome (AS). A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. A UBE3A protein construct was generated with additional sequences that allow the secretion from cells and uptake by neighboring neuronal cells. This UBE3A vector may be used in gene therapy to confer a functional E6-AP protein into the neurons and rescue disease pathology.

3. 发明申请

WO2018027037A2 REELIN COMPOSITIONS FOR TREATMENT OF NEUROLOGICAL DISORDERS 审中-公开
公开(公告)号：WO2018027037A2
公开(公告)日：2018-02-08
申请号：PCT/US2017/045307
申请日：2017-08-03
申请人： UNIVERSITY OF SOUTH FLORIDA , WEEBER, Edwin, J.
发明人： WEEBER, Edwin, J.
IPC分类号： A61K38/16
摘要： Changes in Reelin levels as well as Reelin signaling alter cognitive function. This can be accomplished by administering a therapeutically effective amount of a repeat fragment of Reelin, or a construct formed from fragment repeats of Reelin to a patient or subject. Changes to Reelin levels can be used to treat various neurodegenerative diseases, neuronal insults, or stroke, such as fragile X syndrome, William's syndrome, Rett syndrome, Down's syndrome, Angelman syndrome, autism, ischemia, hypoxia, Alzheimer's disease, and schizophrenia. Reelin can also be used to alter dendritic spine density, diminished long-term potentiation, and diminished synaptic plasticity and associative learning deficits. Constructs formed from repeat region 3 of full length Reelin and repeat region 5 of full length Reelin, or repeat region 3 of full length Reelin and repeat region 6 of full length Reelin have been found particularly useful.

4. 发明申请

WO2012103543A2 OPTICAL NEURON STIMULATION PROSTHETIC USING SIC (SILICON CARBIDE) 审中-公开
标题翻译：使用SIC（碳化硅）的光学神经元刺激假体
公开(公告)号：WO2012103543A2
公开(公告)日：2012-08-02
申请号：PCT/US2012/023131
申请日：2012-01-30
申请人： UNIVERSITY OF SOUTH FLORIDA , REGISTER, Joseph , SADDOW, Stephen , FREWIN, Christopher , WEEBER, Edwin
发明人： REGISTER, Joseph , SADDOW, Stephen , FREWIN, Christopher , WEEBER, Edwin
IPC分类号： A61N1/05 , A61N1/36 , A61F2/00 , A61L27/02 , A61N1/378
CPC分类号： A61N5/0622 , A61L31/02 , A61L2400/18 , A61L2430/32 , A61N2005/0612 , A61N2005/0651 , Y10T29/49826
摘要： The microfabricated prosthetic device uses local, direct, and wavelength-specific optical stimulation to achieve an action potential from a single or small group of neurons within the central nervous system (CNS). The device is biocompatible, mechanically flexible, and optically transparent. The device can also use integrated electrodes for additional input/output (IO) locations, signal verification, feedback, wireless communication, and characterization of the electrochemically-evoked potential received from the activated neuron. The purpose of the device is to act as a neural interface prosthetic. The prosthetic is designed as the central component of a Brain machine interface (BMI).
摘要翻译：微型制造的假体装置使用局部，直接和波长特异性光刺激来实现来自中枢神经系统（CNS）内的单个或一小组神经元的动作电位。该装置具有生物相容性，机械灵活性和光学透明性。该设备还可以使用集成电极用于额外的输入/输出（IO）位置，信号验证，反馈，无线通信以及从激活的神经元接收到的电化学诱发电位的表征。该设备的目的是充当神经界面假体。假体被设计为脑机接口（BMI）的核心组件。

5. 发明申请

WO2011066552A3 CUBIC SILICON CARBIDE IMPLANTABLE NEURAL PROSTHETIC 审中-公开
公开(公告)号：WO2011066552A3
公开(公告)日：2011-06-03
申请号：PCT/US2010/058376
申请日：2010-11-30
申请人： UNIVERSITY OF SOUTH FLORIDA , FREWIN, Christopher, Leroy , SADDOW, Stephen, E. , WEEBER, Edwin
发明人： FREWIN, Christopher, Leroy , SADDOW, Stephen, E. , WEEBER, Edwin
IPC分类号： A61N1/05 , A61B5/0478 , C01B31/36 , C04B35/565
摘要： An implantable neuronal prosthetic and method of manufacture thereof includes at least one elongated electrode shank adapted for arrangement in the brain having at least one electrode contact disposed on its surface and arranged to electrically couple with said brain. The at least one elongated electrode shank is formed form a single crystal cubic silicon carbide. An insulation layer of amorphous, polycrystalline, or single crystal silicon carbide is disposed over the elongated electrode shank; the insulation layer of amorphous, polycrystalline, or single crystal silicon carbide is removed from the at least one electrode contact. Signal control electronics are attached to the at least one elongated electrode shank and are in electrical communication with the at least one electrode contact. In an embodiment, a plurality of the at least one elongated electrode shanks are arranged into a matrix.

6. 发明申请

WO2018027037A3 REELIN COMPOSITIONS FOR TREATMENT OF NEUROLOGICAL DISORDERS 审中-公开
标题翻译： REELIN组合物治疗神经系统疾病
公开(公告)号：WO2018027037A3
公开(公告)日：2018-02-08
申请号：PCT/US2017/045307
申请日：2017-08-03
申请人： UNIVERSITY OF SOUTH FLORIDA , WEEBER, Edwin, J.
发明人： WEEBER, Edwin, J.
IPC分类号： A61K38/17 , A61K39/395 , A61P25/18 , A61P25/28 , A61P25/00 , A61K38/48
摘要： Changes in Reelin levels as well as Reelin signaling alter cognitive function. This can be accomplished by administering a therapeutically effective amount of a repeat fragment of Reelin, or a construct formed from fragment repeats of Reelin to a patient or subject. Changes to Reelin levels can be used to treat various neurodegenerative diseases, neuronal insults, or stroke, such as fragile X syndrome, William's syndrome, Rett syndrome, Down's syndrome, Angelman syndrome, autism, ischemia, hypoxia, Alzheimer's disease, and schizophrenia. Reelin can also be used to alter dendritic spine density, diminished long-term potentiation, and diminished synaptic plasticity and associative learning deficits. Constructs formed from repeat region 3 of full length Reelin and repeat region 5 of full length Reelin, or repeat region 3 of full length Reelin and repeat region 6 of full length Reelin have been found particularly useful.
摘要翻译： Reelin水平的变化以及Reelin信号改变了认知功能。这可以通过向患者或受试者施用治疗有效量的Reelin的重复片段或由Reelin的片段重复形成的构建体来实现。 Reelin水平的变化可用于治疗各种神经退行性疾病，神经元损伤或中风，如脆性X综合征，威廉氏综合征，雷特综合征，唐氏综合征，安格曼综合征，自闭症，局部缺血，缺氧，阿尔茨海默病和精神分裂症。 Reelin也可以用来改变树突棘密度，减少长时程增强，减少突触可塑性和联想学习障碍。已经发现由全长Reelin的重复区域3和全长Reelin的重复区域5或全长Reelin的重复区域3和全长Reelin的重复区域6形成的构建体是特别有用的。

7. 发明申请

WO2016179584A1 MODIFIED UBE3A GENE FOR A GENE THERAPY APPROACH FOR ANGELMAN SYNDROME 审中-公开
标题翻译：改良的UBE3A基因治疗阿格尼曼综合症的基因治疗方法
公开(公告)号：WO2016179584A1
公开(公告)日：2016-11-10
申请号：PCT/US2016/031468
申请日：2016-05-09
申请人： UNIVERSITY OF SOUTH FLORIDA , NASH, Kevin Ron , WEEBER, Edwin John
发明人： NASH, Kevin Ron , WEEBER, Edwin John
IPC分类号： A61K48/00 , C12N9/00 , C12N15/52 , C12N15/85
CPC分类号： A61K48/005 , A61K48/00 , C07K2319/01 , C07K2319/02 , C07K2319/036 , C07K2319/10 , C12N9/104 , C12N9/93 , C12N15/52 , C12N15/85 , C12Y203/02 , C12Y603/02019
摘要： Angelman Syndrome (AS) is a genetic disorder occurring in one in every 15,000 births. It is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. We have generated a Ube3a protein with additional sequences that should allow the secretion from cells and uptake by neighboring neuronal cells. This would confer a functional E6-AP protein into the neurons and rescue disease pathology.
摘要翻译：安格曼综合征（AS）是一种遗传性疾病，每15 000例出生一次。其特征是严重的精神发育迟滞，癫痫发作，言语困难和共济失调。发现AS的基因是UBE3A，编码E6-AP，泛素连接酶。该基因的独特之处在于它以神经元特异性方式进行母体印记。在大多数AS病例中，在母亲遗传的UBE3A基因中存在突变或缺失，尽管其他病例是母体基因的单亲二倍体或错配乙基化的结果。虽然以严重精神发育迟滞为特征的大多数人类疾病涉及大脑结构异常，但并不存在与AS相关的重大解剖学变化。我们已经产生了一种具有额外序列的Ube3a蛋白，其应该允许细胞分泌和相邻神经元细胞摄取。这将赋予功能性E6-AP蛋白进入神经元并拯救疾病病理学。

8. 发明申请

WO2010091399A2 REELIN RESCUES COGNITIVE FUNCTION 审中-公开
标题翻译：重新评估认知功能
公开(公告)号：WO2010091399A2
公开(公告)日：2010-08-12
申请号：PCT/US2010/023615
申请日：2010-02-09
申请人： UNIVERSITY OF SOUTH FLORIDA , VANDERBILT UNIVERSITY , WEEBER, Edwin , ZHAO, Lisa , PETERS, Melinda
发明人： WEEBER, Edwin , ZHAO, Lisa , PETERS, Melinda
CPC分类号： A61K38/1709 , A61K38/53
摘要： Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.
摘要翻译：公开了通过增加和/或防止对Reelin水平以及Reelin信令的干扰来影响和增强认知功能的方法。在有需要的受试者中，通过向受试者施用治疗有效量的Reelin，Reelin特异性调节剂或脂蛋白受体激动剂来改善认知功能。脂蛋白受体可以选自ApoER2和VLDLR等候选物质。如本文所公开的，用于本发明方法的脂蛋白受体的激动剂包括APC，Sep和Fc-RAP。除了施用外源Reelin之外，可以使用Reelin特异性调节剂如重组Reelin片段来增加Reelin水平和/或信号传导。

9. 发明申请

WO2012103543A3 OPTICAL NEURON STIMULATION PROSTHETIC USING SIC (SILICON CARBIDE) 审中-公开
标题翻译：光学神经元刺激使用SIC（碳化硅）
公开(公告)号：WO2012103543A3
公开(公告)日：2012-10-26
申请号：PCT/US2012023131
申请日：2012-01-30
申请人： UNIV SOUTH FLORIDA , REGISTER JOSEPH , SADDOW STEPHEN , FREWIN CHRISTOPHER , WEEBER EDWIN
发明人： REGISTER JOSEPH , SADDOW STEPHEN , FREWIN CHRISTOPHER , WEEBER EDWIN
IPC分类号： A61N1/05 , A61F2/00 , A61L27/02 , A61N1/36 , A61N1/378
CPC分类号： A61N5/0622 , A61L31/02 , A61L2400/18 , A61L2430/32 , A61N2005/0612 , A61N2005/0651 , Y10T29/49826
摘要： The microfabricated prosthetic device uses local, direct, and wavelength-specific optical stimulation to achieve an action potential from a single or small group of neurons within the central nervous system (CNS). The device is biocompatible, mechanically flexible, and optically transparent. The device can also use integrated electrodes for additional input/output (IO) locations, signal verification, feedback, wireless communication, and characterization of the electrochemically-evoked potential received from the activated neuron. The purpose of the device is to act as a neural interface prosthetic. The prosthetic is designed as the central component of a Brain machine interface (BMI).
摘要翻译：微制造假体装置使用局部，直接和波长特定的光学刺激来实现来自中枢神经系统（CNS）内的单个或小组神经元的动作电位。该设备具有生物相容性，机械灵活性和光学透明度。该装置还可以使用集成电极用于额外的输入/输出（IO）位置，信号验证，反馈，无线通信以及从激活的神经元接收的电化学诱发电位的表征。该装置的目的是作为神经接口假肢。假肢被设计为脑机界面（BMI）的中心组件。

10. 发明申请

WO2010091399A9 REELIN RESCUES COGNITIVE FUNCTION 审中-公开
标题翻译：重新评估认知功能
公开(公告)号：WO2010091399A9
公开(公告)日：2011-02-17
申请号：PCT/US2010023615
申请日：2010-02-09
申请人： UNIV SOUTH FLORIDA , UNIV VANDERBILT , WEEBER EDWIN , ZHAO LISA , PETERS MELINDA
发明人： WEEBER EDWIN , ZHAO LISA , PETERS MELINDA
IPC分类号： A61K39/395 , A61P25/00 , A61P25/28 , C07K14/47
CPC分类号： A61K38/1709 , A61K38/53
摘要： Disclosed are methods of influencing, and enhancing, cognitive function by increasing, and/or preventing interference with, Reelin levels as well as Reelin signaling. Cognitive function is improved, in a subject in need thereof, by administering a therapeutically effective amount of Reelin, a Reelin-specific modulator or an agonist of a lipoprotein receptor to the subject. The lipoprotein receptor can be selected from candidates such as ApoER2 and VLDLR. As disclosed herein, agonists of the lipoprotein receptor for use with the inventive method include APC, Sep and Fc-RAP. In addition to administering exogenous Reelin, a Reelin-specific modulator, such as a recombinant Reelin fragment, can be used to increase Reelin levels and/or signaling.

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