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公开(公告)号：US20070003983A1
公开(公告)日：2007-01-04
申请号：US10781059
申请日：2004-02-17
IPC分类号： G01N33/567 , A01K67/033
CPC分类号： G01N33/5032 , C07K14/705 , G01N33/68 , G01N2500/10
摘要： The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.
摘要翻译： 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现：Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基的异二聚体（N < SUP> EC）和约110kDa的亚基（N？TM），它们通过还原剂敏感性连接键连在一起，特别是非共价金属离子依赖性 连锁。
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公开(公告)号：US08222213B2
公开(公告)日：2012-07-17
申请号：US12789148
申请日：2010-05-27
IPC分类号： A61K38/00 , G01N33/567 , C07K1/00
CPC分类号： G01N33/5032 , C07K14/705 , G01N33/68 , G01N2500/10
摘要： The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.
摘要翻译： 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现：Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基（NEC）的异源二聚体的发现， 和约110kDa的亚基（NTM），其通过还原剂敏感性连接键连在一起，特别是非共价金属离子依赖性连接。
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公开(公告)号：US20110028383A1
公开(公告)日：2011-02-03
申请号：US12789148
申请日：2010-05-27
CPC分类号： G01N33/5032 , C07K14/705 , G01N33/68 , G01N2500/10
摘要： The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.
摘要翻译： 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现：Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基（NEC）的异源二聚体的发现， 和约110kDa的亚基（NTM），其通过还原剂敏感性连接键连在一起，特别是非共价金属离子依赖性连接。
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公开(公告)号：US07727732B2
公开(公告)日：2010-06-01
申请号：US10781059
申请日：2004-02-17
IPC分类号： G01N33/567 , A01K67/033
CPC分类号： G01N33/5032 , C07K14/705 , G01N33/68 , G01N2500/10
摘要： The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.
摘要翻译： 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现：Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基（NEC）的异源二聚体的发现， 和约110kDa的亚基（NTM），其通过还原剂敏感性连接键连在一起，特别是非共价金属离子依赖性连接。
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公开(公告)号：US06692919B1
公开(公告)日：2004-02-17
申请号：US09121457
申请日：1998-07-23
IPC分类号： G01N3353
CPC分类号： G01N33/5032 , C07K14/705 , G01N33/68 , G01N2500/10
摘要： The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.
摘要翻译： 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现：Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基的异二聚体（N < EC>）和约110kDa的亚基（N TM），其通过还原剂敏感性连接键连在一起，特别是非共价金属离子依赖性连接。
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公开(公告)号：US06436650B1
公开(公告)日：2002-08-20
申请号：US08899232
申请日：1997-07-23
IPC分类号： G01N33567
CPC分类号： G01N33/5032 , C07K14/705 , G01N33/68 , G01N2500/10
摘要： The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage.
摘要翻译： 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现：Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基（NEC）的异源二聚体的发现， 和约110kDa亚基（NTM），其通过还原剂敏感性连接物连接在一起。
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