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公开(公告)号：US06627739B1
公开(公告)日：2003-09-30
申请号：US09724566
申请日：2000-11-28
申请人： John P. Anderson , Guriqbal Basi , Minh Tam Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
发明人： John P. Anderson , Guriqbal Basi , Minh Tam Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
IPC分类号： C07K1640
CPC分类号： C12N9/6478 , A01K2217/075 , A61K38/00
摘要： Disclosed are various forms of an active, isolated &bgr;-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (&bgr;-APPwt and &bgr;-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate &bgr;-secretase. Inhibitors of &bgr;-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.
摘要翻译： 公开了各种形式的纯化和重组形式的活性，分离的β-分泌酶。 这种酶涉及积聚在患有阿尔茨海默病的个体的脑中的淀粉样蛋白斑块成分的产生。 产生该酶的重组细胞单独或与其一些天然底物（β-APPwt和β-APPsw）组合也被公开，以及针对这种蛋白质的抗体。 这些组合物可用于选择调节β-分泌酶的化合物的方法。 β-分泌酶的抑制剂涉及作为治疗神经变性疾病如阿尔茨海默病的治疗剂。
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公开(公告)号：US20050164294A1
公开(公告)日：2005-07-28
申请号：US11090866
申请日：2005-03-25
申请人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
发明人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
IPC分类号： A61K38/00 , C12N9/64 , H01Q1/36 , H01Q1/38 , H01Q3/44 , H01Q5/00 , H01Q9/04 , H01Q15/02 , C12Q1/68 , C07H21/04
CPC分类号： C12N9/6478 , A01K2217/075 , A61K38/00 , H01Q1/364 , H01Q1/38 , H01Q3/44 , H01Q9/0407 , H01Q9/0442 , H01Q15/02
摘要： Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (β-APPwt and β-APPsw-) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.
摘要翻译： 公开了各种形式的纯化和重组形式的活性，分离的β-分泌酶。 这种酶涉及积聚在患有阿尔茨海默病的个体的脑中的淀粉样蛋白斑块成分的产生。 也公开了单独或与其一些天然底物（β-APPwt和β-APPsw-）组合产生该酶的重组细胞，以及针对这种蛋白质的抗体。 这些组合物可用于选择调节β-分泌酶的化合物的方法。 β-分泌酶的抑制剂涉及作为治疗神经变性疾病如阿尔茨海默病的治疗剂。
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公开(公告)号：US20050177888A1
公开(公告)日：2005-08-11
申请号：US11090872
申请日：2005-03-25
申请人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
发明人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
IPC分类号： A61K38/00 , C12N9/64 , H01Q1/36 , H01Q1/38 , H01Q3/44 , H01Q5/00 , H01Q9/04 , H01Q15/02 , C12Q1/68 , A01K67/027 , C07H21/04 , G01N33/53 , G01N33/567
CPC分类号： C12N9/6478 , A01K2217/075 , A61K38/00 , H01Q1/364 , H01Q1/38 , H01Q3/44 , H01Q9/0407 , H01Q9/0442 , H01Q15/02
摘要： Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (β-APPwt and β-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.
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公开(公告)号：US20050196839A1
公开(公告)日：2005-09-08
申请号：US11090399
申请日：2005-03-25
申请人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
发明人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
IPC分类号： A61K38/00 , C12N9/64 , H01Q1/36 , H01Q1/38 , H01Q3/44 , H01Q5/00 , H01Q9/04 , H01Q15/02 , C07H21/04
CPC分类号： C12N9/6478 , A01K2217/075 , A61K38/00 , H01Q1/364 , H01Q1/38 , H01Q3/44 , H01Q9/0407 , H01Q9/0442 , H01Q15/02
摘要： Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (β-APPwt and β-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.
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公开(公告)号：US20050170489A1
公开(公告)日：2005-08-04
申请号：US11069377
申请日：2005-02-28
申请人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
发明人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
CPC分类号： C12N9/6478 , A01K2217/075 , A61K38/00 , H01Q1/364 , H01Q1/38 , H01Q3/44 , H01Q9/0407 , H01Q9/0442 , H01Q15/02
摘要： Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (β-APPwt and β-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.
摘要翻译： 公开了各种形式的纯化和重组形式的活性，分离的β-分泌酶。 这种酶涉及积聚在患有阿尔茨海默病的个体的脑中的淀粉样蛋白斑块成分的产生。 产生该酶的重组细胞单独或与其一些天然底物（β-APPwt和β-APPsw）组合也被公开，以及针对这种蛋白质的抗体。 这些组合物可用于选择调节β-分泌酶的化合物的方法。 β-分泌酶的抑制剂涉及作为治疗神经变性疾病如阿尔茨海默病的治疗剂。
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公开(公告)号：US20050164327A1
公开(公告)日：2005-07-28
申请号：US11089918
申请日：2005-03-25
申请人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
发明人： John Anderson , Guriqbal Basi , Minh Doan , Normand Frigon , Varghese John , Michael Power , Sukanto Sinha , Gwen Tatsuno , Jay Tung , Shuwen Wang , Lisa McConlogue
IPC分类号： A61K38/00 , C12N9/64 , H01Q1/36 , H01Q1/38 , H01Q3/44 , H01Q5/00 , H01Q9/04 , H01Q15/02 , C12Q1/37
CPC分类号： C12N9/6478 , A01K2217/075 , A61K38/00 , H01Q1/364 , H01Q1/38 , H01Q3/44 , H01Q9/0407 , H01Q9/0442 , H01Q15/02
摘要： Disclosed are various forms of an active, isolated β-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (β-APPwt and β-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate β-secretase. Inhibitors of β-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.
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公开(公告)号：US07718413B2
公开(公告)日：2010-05-18
申请号：US12341336
申请日：2008-12-22
申请人： John Anderson , Lisa McConlogue , Guriqbal Basi , Sukanto Sinha
发明人： John Anderson , Lisa McConlogue , Guriqbal Basi , Sukanto Sinha
CPC分类号： C12N9/6478
摘要： Human BACE polypeptides having modifications to the N-linked glycosylation sites including one or more of the following amino acid substitutions: S174I, N223A, N153Q and N354S. DNA sequences, vectors, and host cells for producing the polypeptides. Crystalline protein compositions formed from the purified polypeptides. Methods of screening for compounds that inhibit Aβ using the polypeptides.
摘要翻译： 具有N连接糖基化位点修饰的人BACE多肽包括一个或多个以下氨基酸取代：S174I，N223A，N153Q和N354S。 DNA序列，载体和用于产生多肽的宿主细胞。 由纯化的多肽形成的结晶蛋白质组合物。 筛选抑制A＆bgr的化合物的方法 使用多肽。
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公开(公告)号：US20090286281A1
公开(公告)日：2009-11-19
申请号：US12341336
申请日：2008-12-22
申请人： John Anderson , Lisa McConlogue , Guriqbal Basi , Sukanto Sinha
发明人： John Anderson , Lisa McConlogue , Guriqbal Basi , Sukanto Sinha
CPC分类号： C12N9/6478
摘要： Human BACE polypeptides having modifications to the N-linked glycosylation sites including one or more of the following amino acid substitutions: S174I, N223A, N153Q and N354S. DNA sequences, vectors, and host cells for producing the polypeptides. Crystalline protein compositions formed from the purified polypeptides. Methods of screening for compounds that inhibit Aβ using the polypeptides.
摘要翻译： 具有N连接糖基化位点修饰的人BACE多肽包括一个或多个以下氨基酸取代：S174I，N223A，N153Q和N354S。 DNA序列，载体和用于产生多肽的宿主细胞。 由纯化的多肽形成的结晶蛋白质组合物。 筛选使用多肽抑制Abeta的化合物的方法。
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公开(公告)号：US07482136B2
公开(公告)日：2009-01-27
申请号：US10837021
申请日：2004-04-30
申请人： John Anderson , Lisa McConlogue , Guriqbal Basi , Sukanto Sinha
发明人： John Anderson , Lisa McConlogue , Guriqbal Basi , Sukanto Sinha
CPC分类号： C12N9/6478
摘要： Human BACE polypeptides having modifications to the N-linked glycosylation sites including one or more of the following amino acid substitutions: S174I, N223A, N153Q and N354S. DNA sequences, vectors, and host cells for producing the polypeptides. Crystalline protein compositions formed from the purified polypeptides. Methods of screening for compounds that inhibit Aβ using the polypeptides.
摘要翻译： 具有N连接糖基化位点修饰的人BACE多肽包括一个或多个以下氨基酸取代：S174I，N223A，N153Q和N354S。 DNA序列，载体和用于产生多肽的宿主细胞。 由纯化的多肽形成的结晶蛋白质组合物。 筛选使用多肽抑制Abeta的化合物的方法。
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公开(公告)号：US09067981B1
公开(公告)日：2015-06-30
申请号：US12608869
申请日：2009-10-29
IPC分类号： C07K16/18 , A61K39/395
CPC分类号： C07K16/18 , A61K39/3955 , C07K2299/00 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/60
摘要： The present invention provides crystals including amino acids 1-7 of SEQ ID NO:1 and a Fab fragment of 12A11, 12B4, 10D5 or 3D6, as well as of amino acids 1-40 of SEQ ID NO:1 and a Fab fragment of 12A11 or 3D6, as well as methods for preparing the crystals. The present invention also provides a computer implemented method for analyzing binding of a candidate antibody fragment to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, a method for identifying an antibody fragment that can mimic the Fab fragment of 12A11, a method for identifying an antibody fragment that can mimic the Fab fragment of 3D6, a method for identifying a candidate antibody fragment that binds to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, and a method for designing a humanized antibody that binds to a peptide comprising an epitope of amino acids 1-7 of SEQ ID NO:1.
摘要翻译： 本发明提供了包含SEQ ID NO：1的氨基酸1-7和12A11,12B4,10D5或3D6的Fab片段以及SEQ ID NO：1的氨基酸1-40的晶体和包含SEQ ID NO： 12A11或3D6，以及制备晶体的方法。 本发明还提供了一种用于分析候选抗体片段与包含SEQ ID NO：1的氨基酸1-7的表位的肽的结合的计算机实施方法，用于鉴定可以模拟SEQ ID NO：1的Fab片段的抗体片段的方法 12A11，鉴定可以模拟3D6的Fab片段的抗体片段的方法，鉴定与包含SEQ ID NO：1的氨基酸1-7的表位的肽结合的候选抗体片段的方法，以及方法 用于设计与包含SEQ ID NO：1的氨基酸1-7的表位的肽结合的人源化抗体。
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