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    Method of treatment using a soluble human delta protein fragment
    2.
    发明授权
    Method of treatment using a soluble human delta protein fragment 失效
    使用可溶性人类δ蛋白片段的治疗方法

    公开(公告)号：US08415303B2

    公开(公告)日：2013-04-09

    申请号：US11546583

    申请日：2006-10-10

    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： A61K38/16 ,  A61K38/18

    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。

    Manipulation of tissue of organ type using the notch pathway
    3.
    发明授权
    Manipulation of tissue of organ type using the notch pathway 失效
    使用缺口途径操纵器官类型的组织

    公开(公告)号：US08084258B2

    公开(公告)日：2011-12-27

    申请号：US10751908

    申请日：2004-01-05

    申请人： Walter Gehring ,  Spyridon Artavanis-Tsakonas

    发明人： Walter Gehring ,  Spyridon Artavanis-Tsakonas

    IPC分类号： C12N5/00

    CPC分类号： A01K67/0339 ,  A61K38/1709 ,  G01N33/6872 ,  G01N2500/00

    摘要： The present invention is directed to methods for altering the fate of a cell, tissue or organ type by altering Notch pathway function in the cell. The invention is further directed to methods for altering the fate of a cell, tissue or organ type by simultaneously changing the activation state of the Notch pathway and one or more cell fate control gene pathways. The invention can be utilized for cells of any differentiation state. The resulting cells may be expanded and used in cell replacement therapy to repopulate lost cell populations and help in the regeneration of diseased and/or injured tissues. The resulting cell populations can also be made recombinant and used for gene therapy or as tissue/organ models for research. The invention is directed to methods for of treating macular degeneration comprising altering Notch pathway function in retinal pigment epithelium cells or retinal neuroepithelium or both tissues. The present invention is also directed to kits utilizing the methods of the invention to generate cells, tissues or organs of altered fates. The invention also provides methods for screening for agonists or antagonists of Notch or cell fate control gene pathway functions.

    摘要翻译： 本发明涉及通过改变细胞中Notch途径功能来改变细胞，组织或器官类型的命运的方法。 本发明还涉及通过同时改变Notch途径的活化状态和一种或多种细胞命运控制基因途径来改变细胞，组织或器官类型的命运的方法。 本发明可用于任何分化状态的细胞。 所得细胞可以扩增并用于细胞替代疗法以重新填充损失的细胞群并有助于患病和/或损伤组织的再生。 所得细胞群也可以重组并用于基因治疗或用作研究的组织/器官模型。 本发明涉及治疗黄斑变性的方法，包括改变视网膜色素上皮细胞或视网膜神经上皮细胞或两种组织中的Notch途径功能。 本发明还涉及利用本发明的方法产生改变命运的细胞，组织或器官的试剂盒。 本发明还提供筛选Notch或细胞命运控制基因途径功能的激动剂或拮抗剂的方法。

    Nucleotide and protein sequences of vertebrate delta genes and methods based thereon
    6.
    发明授权
    Nucleotide and protein sequences of vertebrate delta genes and methods based thereon 有权
    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：US07928071B2

    公开(公告)日：2011-04-19

    申请号：US11492497

    申请日：2006-07-24

    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： A61K38/17 ,  C07K14/705 ,  C07K16/28

    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。

    Manipulation of non-terminally differentiated cells using the notch pathway
    7.
    发明申请
    Manipulation of non-terminally differentiated cells using the notch pathway 审中-公开
    使用缺口途径操纵非终末分化细胞

    公开(公告)号：US20070166824A1

    公开(公告)日：2007-07-19

    申请号：US11605536

    申请日：2006-11-28

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

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

    IPC分类号： C12N5/08

    CPC分类号： C12N5/0623 ,  A61K35/12 ,  A61K38/00 ,  C07K14/47 ,  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。

    Therapeutic and diagnostic methods and compositions based on notch proteins and nucleic acids
    8.
    发明申请
    Therapeutic and diagnostic methods and compositions based on notch proteins and nucleic acids 审中-公开
    基于缺口蛋白和核酸的治疗和诊断方法和组合物

    公开(公告)号：US20050112121A1

    公开(公告)日：2005-05-26

    申请号：US10781060

    申请日：2004-02-17

    申请人： Spyridon Artavanis-Tsakonas ,  Richard Fehon ,  Panayiotis Zagouras ,  Christine Blaumueller

    发明人： Spyridon Artavanis-Tsakonas ,  Richard Fehon ,  Panayiotis Zagouras ,  Christine Blaumueller

    IPC分类号： A01N37/18 ,  A61K38/00 ,  A61K38/17 ,  A61K39/395 ,  C07K14/435 ,  C07K14/705 ,  C12N15/62 ,  G01N33/574

    CPC分类号： C07K14/43581 ,  C07K14/705 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/20 ,  C07K2319/23 ,  C07K2319/70 ,  C07K2319/95 ,  C12N15/62

    摘要： The present invention relates to therapeutic and diagnostic methods and compositions based on Notch proteins and nucleic acids. The invention provides for treatment of disorders of cell fate or differentiation by administration of a therapeutic compound of the invention. Such therapeutic compounds (termed herein “Therapeutics”) include Notch proteins and analogs and derivatives (including fragments) thereof, antibodies thereto, nucleic acids encoding the Notch proteins, analogs, or derivatives, Notch antisense nucleic acids, as well as toporythmic proteins and derivatives which bind to or otherwise interact with Notch proteins and their encoding nucleic acids and antibodies. In a preferred embodiment, a Therapeutic of the invention is administered to treat a cancerous condition, or to prevent progression from a pre-neoplastic or non-malignant state into a neoplastic or a malignant state. In other embodiments, a Therapeutic is administered to treat a nervous system disorder or to promote tissue regeneration and repair. In one embodiment, Therapeutics which antagonize, or inhibit, Notch function (hereinafter “Antagonist Therapeutics”) are administered for therapeutic effect. In another embodiment, Therapeutics which promote Notch function (hereinafter “Agonist Therapeutics”) are administered for therapeutic effect. Diagnostic methods and methods of inhibiting Notch expression are also provided.

    摘要翻译： 本发明涉及基于Notch蛋白和核酸的治疗和诊断方法和组合物。 本发明提供了通过施用本发明的治疗化合物治疗细胞命运或分化的病症。 此类治疗化合物（本文称为“治疗学”）包括Notch蛋白及其类似物和衍生物（包括其片段），其抗体，编码Notch蛋白，类似物或衍生物的核酸，Notch反义核酸以及拓扑蛋白和衍生物 其与Notch蛋白质及其编码核酸和抗体结合或以其它方式相互作用。 在优选的实施方案中，施用本发明的治疗剂以治疗癌症状况，或预防从肿瘤前或非恶性状态进展为肿瘤或恶性状态。 在其它实施方案中，施用治疗剂以治疗神经系统疾病或促进组织再生和修复。 在一个实施方案中，施用拮抗或抑制Notch功能的治疗剂（以下称为“拮抗剂治疗剂”）用于治疗效果。 在另一个实施方案中，施用促进Notch功能的治疗剂（以下称为“激动剂治疗剂”）用于治疗效果。 还提供了抑制Notch表达的诊断方法和方法。

    Nucleotide and protein sequences of vertebrate delta genes and methods based thereon
    9.
    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：US06783956B2

    公开(公告)日：2004-08-31

    申请号：US09908322

    申请日：2001-07-17

    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： C12P2106

    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。