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1.发明授权Assays using amyloid precursor proteins with modified β-secretase cleavage sites to monitor β-secretase activity 失效测定使用具有修饰的β-分泌酶切割位点的淀粉样蛋白前体蛋白以监测β-分泌酶活性公开(公告)号：US07196163B2
公开(公告)日：2007-03-27
申请号：US10427208
申请日：2003-04-30
申请人： Daria Jean Hazuda , Elizabeth Chen Dodson , Ming-Tain Lai , Min Xu , Xiao-Ping Shi , Adam J. Simon , Guoxin Wu , Yueming Li , Bruce Register
发明人： Daria Jean Hazuda , Elizabeth Chen Dodson , Ming-Tain Lai , Min Xu , Xiao-Ping Shi , Adam J. Simon , Guoxin Wu , Yueming Li , Bruce Register
CPC分类号： C07K7/06 , A01K2217/05 , A01K2267/0306 , A61K38/00 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K14/4711 , C07K16/18 , C12P21/06 , C12Q1/37 , G01N33/5088 , G01N33/6896 , G01N2500/00 , G01N2800/52
摘要： Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.
摘要翻译： 提供了鉴定使用修饰的β-分泌酶底物的β-分泌酶抑制剂的方法。 修饰的β-分泌酶底物具有从野生型改变的β-分泌酶切割位点。 改变的β-分泌酶切割位点的氨基酸序列在β-分泌酶切割位点的至少一个位置P2-P1-P1'-P2'中含有不同的氨基酸。 许多修饰的β-分泌酶底物比具有野生型序列的相应底物更有效的β-分泌酶底物，也就是说，这些修饰的底物更易受β-分泌酶的酶分解。 提供了编码经修饰的β-分泌酶底物的重组多核苷酸分子。 提供了识别修饰的β-分泌酶底物的切割产物的抗体。 提供了表达改良的β-分泌酶底物的稳定细胞系。 提供了表达改良的β-分泌酶底物的转基因动物。
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2.发明申请公开(公告)号：US20070219354A1
公开(公告)日：2007-09-20
申请号：US11714985
申请日：2007-03-07
申请人： Daria Hazuda , Elizabeth Chen Dodson , Ming-Tain Lai , Min Xu , Xiao-Ping Shi , Adam Simon , Guoxin Wu , Yueming Li , Bruce Register
发明人： Daria Hazuda , Elizabeth Chen Dodson , Ming-Tain Lai , Min Xu , Xiao-Ping Shi , Adam Simon , Guoxin Wu , Yueming Li , Bruce Register
CPC分类号： C07K7/06 , A01K2217/05 , A01K2267/0306 , A61K38/00 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K14/4711 , C07K16/18 , C12P21/06 , C12Q1/37 , G01N33/5088 , G01N33/6896 , G01N2500/00 , G01N2800/52
摘要： Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.
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公开(公告)号：US08128930B2
公开(公告)日：2012-03-06
申请号：US12828411
申请日：2010-07-01
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William L. Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William L. Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
IPC分类号： A61K39/395 , C07K16/18 , G01N33/53
CPC分类号： G01N33/5058 , C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , G01N2800/2814 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLs, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本发明的抗体还阻断ADDL与神经元的结合，ADDL的组装和tau磷酸化，并且在预防和治疗与淀粉样蛋白的可溶性低聚物相关的疾病的方法中是有用的。 1-42。
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公开(公告)号：US07811563B2
公开(公告)日：2010-10-12
申请号：US11577426
申请日：2005-10-21
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Elizabeth Chen Dodson , Gene Kinney , William L Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola , Lei Chang
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Elizabeth Chen Dodson , Gene Kinney , William L Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola , Lei Chang
IPC分类号： A61K39/395 , C07K16/18 , G01N33/53
CPC分类号： G01N33/5058 , C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , G01N2800/2814 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLs, and tauphosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本抗体还阻断ADDL与神经元的结合，ADDL的组装和酪氨酸磷酸化，并且在用于预防和治疗与淀粉样蛋白和可溶性蛋白的可溶性低聚物相关的疾病的方法中是有用的。 1-42。
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公开(公告)号：US20080175835A1
公开(公告)日：2008-07-24
申请号：US11577426
申请日：2005-10-21
申请人： Paul Acton , Zhigiang An , Andrew J. Bett , Robert Breese , Elizabeth Chen Dodson , Gene Kinney , William L. Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola , Lei Chang
发明人： Paul Acton , Zhigiang An , Andrew J. Bett , Robert Breese , Elizabeth Chen Dodson , Gene Kinney , William L. Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola , Lei Chang
IPC分类号： A61K39/395 , C07K16/44 , G01N33/536 , C12N9/12 , G01N33/53 , A61P25/28
CPC分类号： G01N33/5058 , C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , G01N2800/2814 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLs, and tauphosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异地识别Abeta衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本抗体还阻断ADDL与神经元的结合，ADDL的组装和Tauphosphorylation，并且在用于预防和治疗与淀粉样蛋白β1-42的可溶性低聚物相关的疾病的方法中是有用的。
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公开(公告)号：US20100272714A1
公开(公告)日：2010-10-28
申请号：US12828411
申请日：2010-07-01
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
IPC分类号： A61K39/395 , C07K16/00 , C12N5/02 , G01N33/53
CPC分类号： G01N33/5058 , C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , G01N2800/2814 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLs, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本发明的抗体还阻断ADDL与神经元的结合，ADDL的组装和tau磷酸化，并且在预防和治疗与淀粉样蛋白的可溶性低聚物相关的疾病的方法中是有用的。 1-42。
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公开(公告)号：US07780963B2
公开(公告)日：2010-08-24
申请号：US11256332
申请日：2005-10-21
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola
IPC分类号： A61K39/395 , C07K16/18 , G01N33/53
CPC分类号： G01N33/5058 , C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , G01N2800/2814 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本抗体还阻断ADDL与神经元的结合，ADDLS的组装和tau磷酸化，并且在用于预防和治疗与淀粉样蛋白1-42的可溶性低聚物相关的疾病的方法中是有用的。
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公开(公告)号：US08889138B2
公开(公告)日：2014-11-18
申请号：US12901738
申请日：2010-10-11
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Elizabeth Chen Dodson , Gene Kinney , William L Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola , Lei Chang
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Elizabeth Chen Dodson , Gene Kinney , William L Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kirsten Viola , Lei Chang
IPC分类号： A61K39/395 , G01N33/50 , C07K16/18 , G01N33/68
CPC分类号： G01N33/5058 , C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , G01N2800/2814 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本抗体还阻断ADDL与神经元的结合，ADDLS的组装和tau磷酸化，并且在用于预防和治疗与淀粉样蛋白的可溶性低聚物相关的疾病的方法中是有用的。 1-42。
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公开(公告)号：US08383113B2
公开(公告)日：2013-02-26
申请号：US13368742
申请日：2012-02-08
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
IPC分类号： A61K39/395 , C07K16/18 , G01N33/53
CPC分类号： C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/5058 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本抗体还阻断ADDL与神经元的结合，ADDLS的组装和tau磷酸化，并且在用于预防和治疗与淀粉样蛋白的可溶性低聚物相关的疾病的方法中是有用的。 1-42。
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公开(公告)号：US20120171224A1
公开(公告)日：2012-07-05
申请号：US13368742
申请日：2012-02-08
申请人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
发明人： Paul Acton , Zhiqiang An , Andrew J. Bett , Robert Breese , Lei Chang , Elizabeth Chen Dodson , Gene Kinney , William Klein , Mary P. Lambert , Xiaoping Liang , Paul Shughrue , William R. Strohl , Kristen Viola
IPC分类号： A61K39/395 , C12N5/0793 , G01N33/566 , C07K16/18
CPC分类号： C07K16/18 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/5058 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
摘要翻译： 本发明涉及差异识别衍生的可扩散配体（也称为ADDL）的多维构象的抗体。 本发明的抗体可以区分阿尔茨海默病和对照人脑提取物，并且可用于检测ADDL和诊断阿尔茨海默病的方法。 本抗体还阻断ADDL与神经元的结合，ADDLS的组装和tau磷酸化，并且在用于预防和治疗与淀粉样蛋白的可溶性低聚物相关的疾病的方法中是有用的。 1-42。
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