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    Method of inducing a cell to proliferate using a chimeric receptor comprising janus kinase
    1.
    发明授权
    Method of inducing a cell to proliferate using a chimeric receptor comprising janus kinase 失效
    使用包含janus激酶的嵌合受体诱导细胞增殖的方法

    公开(公告)号：US5837544A

    公开(公告)日：1998-11-17

    申请号：US485293

    申请日：1995-06-07

    申请人： Daniel J. Capon ,  Huan Tian ,  Douglas H. Smith ,  Genine A. Winslow ,  Miriam Siekevitz

    发明人： Daniel J. Capon ,  Huan Tian ,  Douglas H. Smith ,  Genine A. Winslow ,  Miriam Siekevitz

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K14/715 ,  C07K14/73 ,  C12N9/12 ,  C12N15/12 ,  C12N5/10 ,  C12N1/38

    CPC分类号： C12N9/1205 ,  C07K14/705 ,  C07K14/70514 ,  C07K14/7155 ,  A61K38/00 ,  C07K2319/00

    摘要： The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide. In yet a third category, a novel hybrid chimeric protein receptor is contemplated that contains an intracellular or extracellular inducer domain, a transmembrane domain, a proliferation signaling domain and an effector signaling domain in a single chain molecule. Whether the binding domain is intracellular or extracellular, the binding of inducer to these novel chimeric receptor proteins induces the clustering of the binding domains to each other and further signals the cell to proliferate, and optionally, signal an effector function. The present invention further relates to expression vectors containing the nucleic acids encoding the novel chimeric receptors, cells expressing the novel chimeric receptors and therapeutic methods of using cells expressing these novel receptors for the treatment of cancer, infectious disease and autoimmune diseases, for example.

    摘要翻译： 本发明涉及嵌合增殖受体蛋白和编码这些蛋白的DNA序列，其中嵌合蛋白的特征在于三个一般类别。 在一个类别中，新型嵌合蛋白质包含至少三个结构域，即能够结合将信号传递给增殖信号转导域的细胞外诱导物 - 响应性聚簇结构域，跨膜结构域和增殖信号转导域， 宿主细胞分裂。 在第二类中，新的嵌合蛋白包含至少两个结构域，即能够结合细胞内诱导物的细胞内诱导物 - 响应聚簇结构域和信号细胞分裂的增殖信号转导域。 在三分之一类别中，预期在单链分子中含有细胞内或细胞外诱导物结构域，跨膜结构域，增殖信号结构域和效应子信号结构域的新型杂合嵌合蛋白受体。 结合结构域是细胞内还是细胞外，诱导物与这些新型嵌合受体蛋白的结合诱导结合结构域彼此聚集，并进一步使细胞信号增殖，并且任选地发送效应子功能。 本发明还涉及含有编码新型嵌合受体的核酸，表达新型嵌合受体的细胞和使用表达这些新受体的细胞治疗癌症，感染性疾病和自身免疫疾病的治疗方法的表达载体。

    Chimeric receptors comprising janus kinase for regulating cellular pro liferation
    2.
    发明授权
    Chimeric receptors comprising janus kinase for regulating cellular pro liferation 失效
    包含janus激酶调节细胞增殖的嵌合受体

    公开(公告)号：US5741899A

    公开(公告)日：1998-04-21

    申请号：US481003

    申请日：1995-06-07

    申请人： Daniel J. Capon ,  Huan Tian ,  Douglas H. Smith ,  Genine A. Winslow ,  Miriam Siekevitz

    发明人： Daniel J. Capon ,  Huan Tian ,  Douglas H. Smith ,  Genine A. Winslow ,  Miriam Siekevitz

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K14/715 ,  C07K14/73 ,  C12N9/12 ,  C12N15/12 ,  C12N15/62 ,  C07K19/00 ,  C12N5/10

    CPC分类号： C12N9/1205 ,  C07K14/705 ,  C07K14/70514 ,  C07K14/7155 ,  A61K38/00 ,  C07K2319/00

    摘要： The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide. In yet a third category, a novel hybrid chimeric protein receptor is contemplated that contains an intracellular or extracellular inducer domain, a transmembrane domain, a proliferation signaling domain and an effector signaling domain in a single chain molecule. Whether the binding domain is intracellular or extracellular, the binding of inducer to these novel chimeric receptor proteins induces the clustering of the binding domains to each other and further signals the cell to proliferate, and optionally, signal an effector function. The present invention further relates to expression vectors containing the nucleic acids encoding the novel chimeric receptors, cells expressing the novel chimeric receptors and therapeutic methods of using cells expressing these novel receptors for the treatment of cancer, infectious disease and autoimmune diseases, for example.

    摘要翻译： 本发明涉及嵌合增殖受体蛋白和编码这些蛋白的DNA序列，其中嵌合蛋白的特征在于三个一般类别。 在一个类别中，新型嵌合蛋白质包含至少三个结构域，即能够结合将信号传递给增殖信号转导域的细胞外诱导物 - 响应性聚簇结构域，跨膜结构域和增殖信号转导域， 宿主细胞分裂。 在第二类中，新的嵌合蛋白包含至少两个结构域，即能够结合细胞内诱导物的细胞内诱导物 - 响应聚簇结构域和信号细胞分裂的增殖信号转导域。 在三分之一类别中，预期在单链分子中含有细胞内或细胞外诱导物结构域，跨膜结构域，增殖信号结构域和效应子信号结构域的新型杂合嵌合蛋白受体。 结合结构域是细胞内还是细胞外，诱导物与这些新型嵌合受体蛋白的结合诱导结合结构域彼此聚集，并进一步使细胞信号增殖，并且任选地发送效应子功能。 本发明还涉及含有编码新型嵌合受体的核酸，表达新型嵌合受体的细胞和使用表达这些新受体的细胞治疗癌症，感染性疾病和自身免疫疾病的治疗方法的表达载体。

    Multispecific chimeric receptors
    3.
    发明授权
    Multispecific chimeric receptors 失效
    多特异性嵌合受体

    公开(公告)号：US6103521A

    公开(公告)日：2000-08-15

    申请号：US454098

    申请日：1995-05-30

    申请人： Daniel J. Capon ,  Douglas H. Smith ,  Huan Tian ,  Genine A. Winslow ,  Miriam Siekevitz

    发明人： Daniel J. Capon ,  Douglas H. Smith ,  Huan Tian ,  Genine A. Winslow ,  Miriam Siekevitz

    IPC分类号： A61K35/14 ,  A61K35/17 ,  A61K39/00 ,  C07K14/16 ,  C07K14/725 ,  C07K14/73 ,  C07K16/10 ,  C12N15/12 ,  C12N15/62 ,  C07K14/705

    CPC分类号： C07K14/005 ,  A61K35/17 ,  C07K14/7051 ,  C07K14/70514 ,  C07K16/1063 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C12N2740/10043 ,  C12N2740/16122

    摘要： Novel multispecific chimeric receptor DNA sequences, expression cassettes and vectors containing these sequences as well as cells containing the chimeric DNA and novel chimeric receptor proteins expressed from the sequences are provided in the present invention. The novel multispecific chimeric receptor DNA and amino acid sequences comprise at least three domains that do not naturally exist together: (1) a multispecific binding domain comprising at least two extracellular inducer-responsive clustering domains which serves to bind at least one specific inducer molecule, (2) a transmembrane domain, which crosses the plasma membrane, and (3) either a proliferation signaling domain that signals the cell to divide, or an effector function signaling domain which directs a host cell to perform its specialized function. Optionally, all the multispecific chimeric receptors may contain one or more intracellular inducer-responsive clustering domains attached to one or more of the cytoplasmic signaling domains or the transmembrane domain. The present invention also relates to novel hybrid multispecific chimeric receptors comprising at least one proliferation signaling domain and at least one effector function signaling domain together on the multispecific receptor molecule. The present invention further relates to therapeutic methods and strategies that employ the cells expressing these novel chimeric receptors for the treatment of cancer, infectious disease and autoimmune disease which may have greater therapeutic benefit over a combination of drug therapies.

    摘要翻译： 在本发明中提供了新的多特异性嵌合受体DNA序列，表达盒和含有这些序列的载体以及含有嵌合DNA的细胞和由序列表达的新型嵌合受体蛋白。 新颖的多特异性嵌合受体DNA和氨基酸序列包含至少三个不天然存在的结构域：（1）多特异性结合结构域，其包含至少两个用于结合至少一个特异性诱导物分子的细胞外诱导物反应性聚簇结构域， （2）穿越质膜的跨膜结构域，和（3）信号细胞分裂的增殖信号转导域或引导宿主细胞执行其特异功能的效应子功能信号结构域。 任选地，所有多特异性嵌合受体可以含有连接至一个或多个胞质信号结构域或跨膜结构域的一个或多个细胞内诱导物反应性聚簇结构域。 本发明还涉及在多特异性受体分子上包含至少一个增殖信号结构域和至少一个效应子功能信号结构域的新型杂合多特异性嵌合受体。 本发明还涉及使用表达这些新型嵌合受体的细胞治疗癌症，感染性疾病和自身免疫疾病的治疗方法和策略，其可以比药物疗法的组合具有更大的治疗益处。

    DNA encoding an intracellular chimeric receptor comprising Janus kinase
    4.
    发明授权
    DNA encoding an intracellular chimeric receptor comprising Janus kinase 失效
    编码包含Janus激酶的细胞内嵌合受体的DNA

    公开(公告)号：US6077947A

    公开(公告)日：2000-06-20

    申请号：US485598

    申请日：1995-06-07

    申请人： Daniel J. Capon ,  Huan Tian ,  Douglas H. Smith ,  Genine A. Winslow ,  Miriam Siekevitz

    发明人： Daniel J. Capon ,  Huan Tian ,  Douglas H. Smith ,  Genine A. Winslow ,  Miriam Siekevitz

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K14/715 ,  C07K14/73 ,  C12N9/12 ,  C12N15/12 ,  C12N15/62 ,  C12N5/10 ,  C12N15/52 ,  C12N15/63

    CPC分类号： C12N9/1205 ,  C07K14/705 ,  C07K14/70514 ,  C07K14/7155 ,  A61K38/00 ,  C07K2319/00

    摘要： The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide. In yet a third category, a novel hybrid chimeric protein receptor is contemplated that contains an intracellular or extracellular inducer domain, a transmembrane domain, a proliferation signaling domain and an effector signaling domain in a single chain molecule. Whether the binding domain is intracellular or extracellular, the binding of inducer to these novel chimeric receptor proteins induces the clustering of the binding domains to each other and further signals the cell to proliferate, and optionally, signal an effector function. The present invention further relates to expression vectors containing the nucleic acids encoding the novel chimeric receptors, cells expressing the novel chimeric receptors and therapeutic methods of using cells expressing these novel receptors for the treatment of cancer, infectious disease and autoimmune diseases, for example.

    摘要翻译： 本发明涉及嵌合增殖受体蛋白和编码这些蛋白的DNA序列，其中嵌合蛋白的特征在于三个一般类别。 在一个类别中，新型嵌合蛋白质包含至少三个结构域，即能够结合将信号传递给增殖信号转导域的细胞外诱导物 - 响应性聚簇结构域，跨膜结构域和增殖信号转导域， 宿主细胞分裂。 在第二类中，新的嵌合蛋白包含至少两个结构域，即能够结合细胞内诱导物的细胞内诱导物 - 响应聚簇结构域和信号细胞分裂的增殖信号转导域。 在三分之一类别中，预期在单链分子中含有细胞内或细胞外诱导物结构域，跨膜结构域，增殖信号结构域和效应子信号结构域的新型杂合嵌合蛋白受体。 结合结构域是细胞内还是细胞外，诱导物与这些新型嵌合受体蛋白的结合诱导结合结构域彼此聚集，并进一步使细胞信号增殖，并且任选地发送效应子功能。 本发明还涉及含有编码新型嵌合受体的核酸，表达新型嵌合受体的细胞和使用表达这些新受体的细胞治疗癌症，感染性疾病和自身免疫疾病的治疗方法的表达载体。

    Compositions and methods for determining anti-viral drug susceptibility and resistance and anti-viral drug screening
    5.
    发明授权
    Compositions and methods for determining anti-viral drug susceptibility and resistance and anti-viral drug screening 有权
    用于确定抗病毒药物敏感性和耐药性以及抗病毒药物筛选的组合物和方法

    公开(公告)号：US07279279B2

    公开(公告)日：2007-10-09

    申请号：US10846181

    申请日：2004-05-14

    申请人： Daniel J. Capon ,  Christos J. Petropoulos

    发明人： Daniel J. Capon ,  Christos J. Petropoulos

    IPC分类号： C12Q1/68

    CPC分类号： C12N15/86 ,  C12N2740/16043 ,  C12N2830/00 ,  C12N2830/15 ,  C12N2830/60 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/206 ,  C12N2840/44 ,  C12Q1/18 ,  C12Q1/6881 ,  C12Q1/6897 ,  C12Q1/701 ,  C12Q1/703 ,  C12Q1/707 ,  C12Q2600/158 ,  G01N33/5023 ,  G01N2333/16 ,  G01N2800/52 ,  C12Q2545/113

    摘要： This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector Comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c). This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time; (b) determining anti-viral drug susceptibility of the same patient at a later time; and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient.

    摘要翻译： 本发明提供了一种用于确定抗病毒药物的易感性的方法，包括：（a）将包含患者来源区段和指示基因的抗性测试载体导入宿主细胞; （b）从（a）培养宿主细胞; （c）测量靶宿主细胞中指示基因的表达; 和（d）比较来自（c）的指示基因的表达与在不存在抗病毒药物的情况下进行步骤（a） - （c）时测量的指示基因的表达，其中测试浓度 在步骤（a） - （c）中存在抗病毒药物; 在步骤（b） - （c）; 或在步骤（c）。 本发明还提供了一种用于测定患者抗病毒药物耐药性的方法，包括：（a）使用上述敏感性试验在第一时间确定患者的抗病毒药物敏感性，其中所述患者衍生部分获自 病人约在上述时间; （b）以后确定同一病人的抗病毒药物敏感性; 和（c）比较步骤（a）和（b）中确定的抗病毒药物敏感性，其中与第一次相比后来的抗病毒药物敏感性的降低表明抗病毒药物耐药性的发展或进展 在病人身上