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    Methods for use of TSLP and agonists and antagonists thereof
    5.
    发明授权
    Methods for use of TSLP and agonists and antagonists thereof 有权
    使用TSLP及其激动剂及其拮抗剂的方法

    公开(公告)号：US07731953B2

    公开(公告)日：2010-06-08

    申请号：US11762357

    申请日：2007-06-13

    申请人： Warren J. Leonard ,  Akhilesh Pandey ,  Amin Al-Shami ,  Rosanne Spolski

    发明人： Warren J. Leonard ,  Akhilesh Pandey ,  Amin Al-Shami ,  Rosanne Spolski

    IPC分类号： A01N63/00 ,  C12N5/071

    CPC分类号： A61K35/17 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0387 ,  A61K9/0078 ,  A61K31/7088 ,  A61K38/00 ,  A61K41/00 ,  A61K45/06 ,  A61K48/00 ,  A61K2039/505 ,  C07K14/5418 ,  C07K16/244 ,  A61K2300/00

    摘要： Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.

    摘要翻译： 本文公开了特异性诱导CD4 + T细胞增殖的方法。 该方法可用于治疗免疫缺陷，例如由免疫缺陷病毒感染产生的免疫缺陷，例如人免疫缺陷病毒（HIV）的感染。 所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素（TSLP）多肽或治疗有效量的编码TSLP多肽的核酸接触，从而诱导T细胞的增殖。 还公开了用于治疗IgE介导的病症如哮喘的方法。 所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。 本文还公开了转基因小鼠。 这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体（TSLP）基因，破坏足以抑制TSLP与其受体的相互作用，以及破坏的γc基因，破坏足以减少通过γc的信号转导 。 小鼠表现出胸腺细胞减少。 还公开了将这些小鼠用于药物筛选的方法。

    METHODS FOR USE OF TSLP AND AGONISTS AND ANTAGONISTS THEREOF
    6.
    发明申请
    METHODS FOR USE OF TSLP AND AGONISTS AND ANTAGONISTS THEREOF 有权
    使用TSLP和激动剂及其拮抗剂的方法

    公开(公告)号：US20070237787A1

    公开(公告)日：2007-10-11

    申请号：US11762357

    申请日：2007-06-13

    申请人： Warren Leonard ,  Akhilesh Pandey ,  Amin Al-Shami ,  Rosanne Spolski ,  John Kelly ,  Andrea Keane-Myers

    发明人： Warren Leonard ,  Akhilesh Pandey ,  Amin Al-Shami ,  Rosanne Spolski ,  John Kelly ,  Andrea Keane-Myers

    IPC分类号： A61K38/18 ,  A61K38/00 ,  A61K39/00 ,  A61K39/02 ,  A61K39/12 ,  C12N5/02

    CPC分类号： A61K35/17 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0387 ,  A61K9/0078 ,  A61K31/7088 ,  A61K38/00 ,  A61K41/00 ,  A61K45/06 ,  A61K48/00 ,  A61K2039/505 ,  C07K14/5418 ,  C07K16/244 ,  A61K2300/00

    摘要： Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.

    摘要翻译： 本文公开了用于特异性诱导CD4 + T细胞增殖的方法。 该方法可用于治疗免疫缺陷，例如由免疫缺陷病毒感染产生的免疫缺陷，例如人免疫缺陷病毒（HIV）的感染。 所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素（TSLP）多肽或治疗有效量的编码TSLP多肽的核酸接触，从而诱导T细胞的增殖。 还公开了用于治疗IgE介导的病症如哮喘的方法。 所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。 本文还公开了转基因小鼠。 这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体（TSLP）基因，破坏足以抑制TSLP与其受体的相互作用，以及破坏的γ基因，破坏 足以减少信号通过伽马。 小鼠表现出胸腺细胞减少。 还公开了将这些小鼠用于药物筛选的方法。

    Mutant Proteins as Cancer-Specific Biomarkers
    7.
    发明申请
    Mutant Proteins as Cancer-Specific Biomarkers 审中-公开
    突变蛋白作为癌症特异性生物标志物

    公开(公告)号：US20140051105A1

    公开(公告)日：2014-02-20

    申请号：US13980005

    申请日：2012-01-17

    申请人： Bert Vogelstein ,  Qing Wang ,  Akhilesh Pandey ,  Kenneth W. Kinzler ,  Nickolas Papadopoulos

    发明人： Bert Vogelstein ,  Qing Wang ,  Akhilesh Pandey ,  Kenneth W. Kinzler ,  Nickolas Papadopoulos

    IPC分类号： G01N33/68

    CPC分类号： G01N33/6893 ,  G01N33/574 ,  G01N33/6848

    摘要： Altered protein products resulting from somatic mutations are directly identified and quantified by mass spectrometry. The peptides expressed from normal and mutant alleles are detected by Selected Reaction Monitoring (SRM) of their productions using a triple quadrupole mass spectrometer. As a prototypical example of this approach, we quantify the number and fraction of mutant Ras protein present in cancer cell lines. There were an average of 1.3 million molecules of Ras protein per cell and the ratio of mutant to normal Ras proteins ranged from 0.49 to 5.6. Similarly, we detected and quantified mutant Ras proteins in clinical specimens such as colorectal and pancreatic tumor tissues as well as in pre-malignant pancreatic cyst fluids. These methods are useful for diagnostic applications.

    摘要翻译： 通过质谱直接鉴定和定量由体细胞突变产生的改变的蛋白质产物。 从正常和突变等位基因表达的肽通过使用三重四极杆质谱仪的选择反应监测（SRM）进行检测。 作为这种方法的典型例子，我们量化癌细胞系中存在的突变型Ras蛋白的数量和分数。 每个细胞平均含有130万分子的Ras蛋白，突变体与正常Ras蛋白的比例范围为0.49-5.6。 类似地，我们检测和定量临床标本中的突变体Ras蛋白，如结肠直肠和胰腺肿瘤组织以及恶性前期胰腺囊肿液。 这些方法对于诊断应用是有用的。

    Methods for use of TSLP and agonists and antagonists thereof
    8.
    发明申请
    Methods for use of TSLP and agonists and antagonists thereof 审中-公开
    使用TSLP及其激动剂及其拮抗剂的方法

    公开(公告)号：US20050249712A1

    公开(公告)日：2005-11-10

    申请号：US11084408

    申请日：2005-03-18

    申请人： Warren Leonard ,  Akhilesh Pandey ,  Amin Al-Shami ,  Rosanne Spolski ,  John Kelly ,  Andrea Keane-Myers

    发明人： Warren Leonard ,  Akhilesh Pandey ,  Amin Al-Shami ,  Rosanne Spolski ,  John Kelly ,  Andrea Keane-Myers

    IPC分类号： A61K31/7088 ,  A61K35/17 ,  A61K35/18 ,  A61K38/18 ,  A61K38/19 ,  A61K38/20 ,  A61K39/00 ,  A61K41/00 ,  A61K45/00

    CPC分类号： A61K35/17 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0387 ,  A61K9/0078 ,  A61K31/7088 ,  A61K38/00 ,  A61K41/00 ,  A61K45/06 ,  A61K48/00 ,  A61K2039/505 ,  C07K14/5418 ,  C07K16/244 ,  A61K2300/00

    摘要： Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.

    摘要翻译： 本文公开了用于特异性诱导CD4 + T细胞增殖的方法。 该方法可用于治疗免疫缺陷，例如由免疫缺陷病毒感染产生的免疫缺陷，例如人免疫缺陷病毒（HIV）的感染。 所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素（TSLP）多肽或治疗有效量的编码TSLP多肽的核酸接触，从而诱导T细胞的增殖。 还公开了用于治疗IgE介导的病症如哮喘的方法。 所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。 本文还公开了转基因小鼠。 这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体（TSLP）基因，破坏足以抑制TSLP与其受体的相互作用，以及破坏的γ基因，破坏 足以减少信号通过伽马。 小鼠表现出胸腺细胞减少。 还公开了将这些小鼠用于药物筛选的方法。