利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

33 条记录 (耗时 0.045 秒)

    Manipulation of non-terminally differentiated cells using the Notch pathway
    21.
    发明申请
    Manipulation of non-terminally differentiated cells using the Notch pathway 审中-公开
    使用Notch途径操纵非终末分化细胞

    公开(公告)号：US20050158859A1

    公开(公告)日：2005-07-21

    申请号：US10746237

    申请日：2003-12-22

    申请人： Spyridon Artavanis-Tsakonas ,  Mark Fortini ,  Kenji Matsuno

    发明人： Spyridon Artavanis-Tsakonas ,  Mark Fortini ,  Kenji Matsuno

    IPC分类号： A61K35/12 ,  A61K38/00 ,  C07K14/47 ,  C12N5/00 ,  C12N5/07 ,  A61K48/00 ,  C12N5/08 ,  C12N15/85

    CPC分类号： C07K14/47 ,  A61K35/12 ,  A61K38/00 ,  C12N5/0018 ,  C12N5/0601 ,  C12N2501/42

    摘要： The present invention is directed to methods for the expansion of non-terminally differentiated cells (“precursor cells”) using agonists of Notch function, by inhibiting the differentiation of the cells without inhibiting proliferation (mitotic activity) such that an expanded population of non-terminally differentiated cells is obtained. The cells are preferably stem or progenitor cells. These expanded cells can be used in cell replacement therapy to provide desired cell populations and help in the regeneration of diseased and/or injured tissues. The expanded cell populations can also be made recombinant and used for gene therapy, or can be used to supply functions associated with a particular precursor cell or its progeny cell.

    摘要翻译： 本发明涉及使用Notch功能的激动剂来扩增非终末分化的细胞（“前体细胞”）的方法，通过抑制细胞的分化而不抑制增殖（有丝分裂活性），使得扩增的非 - 得到终末分化的细胞。 细胞优选是干细胞或祖细胞。 这些扩展的细胞可用于细胞替代疗法以提供所需的细胞群体并有助于患病和/或损伤组织的再生。 扩增的细胞群体也可以重组并用于基因治疗，或可用于提供与特定前体细胞或其后代细胞相关的功能。

    Activated forms of notch and methods based thereon
    22.
    发明授权
    Activated forms of notch and methods based thereon 失效
    基于此的活化形式的缺口和方法

    公开(公告)号：US06692919B1

    公开(公告)日：2004-02-17

    申请号：US09121457

    申请日：1998-07-23

    申请人： Spyridon Artavanis-Tsakonas ,  Huilin Qi ,  Matthew D. Rand

    发明人： Spyridon Artavanis-Tsakonas ,  Huilin Qi ,  Matthew D. Rand

    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。

    Activated forms of notch and methods based thereon
    23.
    发明授权
    Activated forms of notch and methods based thereon 失效
    基于此的活化形式的缺口和方法

    公开(公告)号：US06436650B1

    公开(公告)日：2002-08-20

    申请号：US08899232

    申请日：1997-07-23

    申请人： Spyridon Artavanis-Tsakonas ,  Huilin Qi

    发明人： Spyridon Artavanis-Tsakonas ,  Huilin Qi

    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。

    Nucleotide and protein sequences of vertebrate delta genes and methods based thereon
    24.
    发明授权
    Nucleotide and protein sequences of vertebrate delta genes and methods based thereon 失效
    脊椎动物δ基因的核苷酸和蛋白质序列及其基础的方法

    公开(公告)号：US06262025B1

    公开(公告)日：2001-07-17

    申请号：US08981392

    申请日：1998-04-07

    申请人： David Ish-Horowicz ,  Domingos Manuel Pinto Henrique ,  Julian Hart Lewis ,  Spyridon Artavanis-Tsakonas ,  Grace E. Gray

    发明人： David Ish-Horowicz ,  Domingos Manuel Pinto Henrique ,  Julian Hart Lewis ,  Spyridon Artavanis-Tsakonas ,  Grace E. Gray

    IPC分类号： C07K1400

    CPC分类号： C07K14/47 ,  A61K38/00 ,  C07K14/705 ,  C07K2319/00

    摘要： The present invention relates to nucleotide sequences of vertebrate Delta genes, and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof. In a specific embodiment, the vertebrate Delta protein is a human protein. The invention further relates to fragments (and derivatives and analogs thereof) of Delta which comprise one or more domains of the Delta protein, including but not limited to the intracellular domain, extracellular domain, DSL domain, domain amino-terminal to the DSL domain, transmembrane region, or one or more EGF-like repeats of a Delta protein, or any combination of the foregoing. Antibodies to Delta, its derivatives and analogs, are additionally provided. Methods of production of the Delta proteins, derivatives and analogs, e.g., by recombinant means, are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are provided. In specific examples, isolated Delta genes, from Xenopus, chick, mouse, and human, are provided.

    摘要翻译： 本发明涉及脊椎动物Delta基因的核苷酸序列，及其编码的蛋白质的氨基酸序列以及衍生物（例如片段）及其类似物。 在具体实施方案中，脊椎动物Delta蛋白是人蛋白质。 本发明还涉及包含Delta蛋白的一个或多个结构域的Delta的片段（及其衍生物和类似物），包括但不限于细胞内结构域，细胞外结构域，DSL结构域，DSL结构域的氨基末端， 跨膜区域，或Delta蛋白质的一种或多种EGF样重复序列或前述的任何组合。 额外提供了抗体对Delta，其衍生物和类似物。 还提供了通过重组方法生产Delta蛋白质，衍生物和类似物的方法。 提供了治疗和诊断方法和药物组合物。 在具体实例中，提供了来自爪蟾，小鸡，小鼠和人的孤立的Delta基因。

    Human Notch and Delta binding domains in toporythmic proteins, and methods based thereon
    26.
    发明授权
    Human Notch and Delta binding domains in toporythmic proteins, and methods based thereon 失效
    拓扑学蛋白质中的人类Notch和Delta结合结构域，以及基于此的方法

    公开(公告)号：US5648464A

    公开(公告)日：1997-07-15

    申请号：US264534

    申请日：1994-06-23

    申请人： Spyridon Artavanis-Tsakonas ,  Richard Grant Fehon ,  Ilaria Rebay ,  Christine Marie Blaumueller

    发明人： Spyridon Artavanis-Tsakonas ,  Richard Grant Fehon ,  Ilaria Rebay ,  Christine Marie Blaumueller

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K16/18 ,  C07K14/435

    CPC分类号： C07K16/18 ,  C07K14/705 ,  A61K38/00 ,  C07K2319/00 ,  Y10S530/839

    摘要： The present invention relates to nucleotide sequences of the human Notch and Delta genes, and amino acid sequences of their encoded proteins, as well as fragments thereof containing an antigenic determinant or which are functionally active. The invention is also directed to fragments (termed herein "adhesive fragments"), and the sequences thereof, of the proteins ("toporythmic proteins") encoded by toporythmic genes which mediate homotypic or heterotypic binding to toporythmic proteins. Toporythmic genes, as used herein, refers to the genes Notch, Delta, and Serrate, as well as other members of the Delta/Serrate family which may be identified, e.g., by the methods described herein. Analogs and derivatives of the adhesive fragments which retain binding activity are also provided. Antibodies to human Notch and to adhesive fragments are additionally provided. In specific embodiments, the adhesive fragment of Notch is that fragment comprising the Notch sequence most homologous to Drosophila Notch EGF-like repeats 11 and 12; the adhesive fragment of Delta mediating heterotypic binding is that fragment comprising the sequence most homologous to Drosophila Delta amino acids 1-230; the adhesive fragment of Delta mediating homotypic binding is that fragment comprising the sequence most homologous to Drosophila Delta amino acids 32-230; and the adhesive fragment of Serrate is that fragment comprising the sequence most homologous to Drosophila Serrate amino acids 85-283.

    摘要翻译： 本发明涉及人Notch和Delta基因的核苷酸序列及其编码蛋白质的氨基酸序列，以及其含有抗原决定簇或其功能活性的片段。 本发明还涉及由介导与拓扑蛋白质的同型或异型结合的拓扑学基因编码的蛋白质（“拓扑蛋白”）的片段（称为“粘合片段”）及其序列。 如本文所用的拓扑学基因是指Notch，Delta和Serrate基因以及Delta / Serrate家族的其他成员，例如通过本文所述的方法鉴定。 还提供了保留结合活性的粘合剂片段的类似物和衍生物。 另外提供人类Notch和粘合剂片段的抗体。 在具体实施方案中，Notch的粘合片段是包含与果蝇Notch EGF样重复序列11和12最相似的Notch序列的片段; Delta介导异型结合的粘合片段是包含与果蝇Delta氨基酸1-230最相似序列的片段; Delta介导同型结合的粘合片段是包含与果蝇三角洲氨基酸32-230最相似的序列的片段; 并且Serrate的粘合片段是包含与果糖果丝氨酸85-283最相似序列的片段。

    Activated amino- and carboxy-terminal forms of Notch
    28.
    发明授权
    Activated amino- and carboxy-terminal forms of Notch 失效
    Notch的活性氨基和羧基末端形式

    公开(公告)号：US08222213B2

    公开(公告)日：2012-07-17

    申请号：US12789148

    申请日：2010-05-27

    申请人： Spyridon Artavanis-Tsakonas ,  Huilin Qi ,  Matthew D. Rand

    发明人： Spyridon Artavanis-Tsakonas ,  Huilin Qi ,  Matthew D. Rand

    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。