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1. 发明授权

US07731953B2 Methods for use of TSLP and agonists and antagonists thereof 有权
标题翻译：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。

2. 发明申请

US20050249712A1 Methods for use of TSLP and agonists and antagonists thereof 审中-公开
标题翻译：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。

3. 发明申请

US20070237787A1 METHODS FOR USE OF TSLP AND AGONISTS AND ANTAGONISTS THEREOF 有权
标题翻译：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。

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