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    METHODS AND COMPOSITIONS FOR THE SYNERGISTIC ACTIVATION OF LATENT HIV
    2.
    发明申请
    METHODS AND COMPOSITIONS FOR THE SYNERGISTIC ACTIVATION OF LATENT HIV 有权
    艾滋病知识脉络协同激活的方法与组成

    公开(公告)号：US20100168004A1

    公开(公告)日：2010-07-01

    申请号：US12297034

    申请日：2007-04-17

    申请人： Samuel A.F. Williams ,  Warner C. Greene

    发明人： Samuel A.F. Williams ,  Warner C. Greene

    IPC分类号： A61K31/216 ,  A61K38/16 ,  A61P31/18

    CPC分类号： A61K45/06 ,  A61K31/165 ,  A61K31/19 ,  A61K31/22 ,  C12N2740/16011 ,  A61K2300/00

    摘要： The present invention provides methods and compositions useful for the elimination of latent HIV reservoirs that persist despite HAART. The methods and compositions overcome this latent barrier by inducing the replication of HIV in latently infected T cells while preventing the spread of the newly produced virions to uninfected cells by providing HAART simultaneously. Compositions of the invention comprise an activator of latent HIV expression, such as prostratin, and an inhibitor of histone deacetylase, such as TSA. A surprising finding of this invention is that the inhibitor of the histone deacetylase synergizes the effect of prostratin thus, allowing administering to a patient a lower, non-toxic dose of prostratin.

    摘要翻译： 本发明提供了用于消除尽管HAART持续存在的潜伏性HIV储库的方法和组合物。 方法和组合物通过在潜伏感染的T细胞中诱导HIV的复制来克服这种潜在的障碍，同时通过同时提供HAART来防止新产生的病毒粒子扩散到未感染的细胞。 本发明的组合物包含潜伏的HIV表达的激活剂，例如前列腺素和组蛋白脱乙酰酶抑制剂，例如TSA。 本发明的令人惊奇的发现是，组蛋白脱乙酰酶的抑制剂可促进前列腺素的作用，从而允许给予患者较低的无毒剂量的前列腺素。

    Inhibitor of the inflammatory response induced by the TNFA and IL-1
    3.
    发明授权
    Inhibitor of the inflammatory response induced by the TNFA and IL-1 有权
    由TNFA和IL-1诱导的炎症反应的抑制剂

    公开(公告)号：US06265538B1

    公开(公告)日：2001-07-24

    申请号：US09257703

    申请日：1999-02-25

    申请人： Warner C. Greene ,  Xin Lin ,  Romas Gelezuinas

    发明人： Warner C. Greene ,  Xin Lin ,  Romas Gelezuinas

    IPC分类号： A61K3800

    CPC分类号： C12N9/1205

    摘要： The present invention provides the molecular basis for cytokine induction of NF-&kgr;B-dependent immune and inflammatory responses, emphasizing a role for both NIK-NIK and NIK-IKK protein-protein interactions. A relatively small region of NIK selectively impairs the NIK-IKK interaction. The present invention provides a highly specific method for modulating NF-&kgr;B-dependent immune, inflammatory, and anti-apoptotic responses, based on interruption of the critical protein-protein interaction of NIK and IKK. The present invention provides methods for inhibiting NF-&kgr;B-dependent gene expression, using mutant NIK proteins. One embodiment of the present invention provides kinase-deficient NIK mutant proteins that inhibit activation of IKK. Another embodiment of the invention provides N-terminus NIK mutant proteins that bind IKK, thus inhibiting NIK/IKK interaction.

    摘要翻译： 本发明提供NF-κB依赖性免疫和炎症反应的细胞因子诱导的分子基础，强调NIK-NIK和NIK-IKK蛋白质 - 蛋白质相互作用的作用。 NIK相对较小的区域选择性地损害NIK-IKK相互作用。 本发明基于NIK和IKK的关键蛋白质 - 蛋白质相互作用的中断，提供了调节NF-κB依赖性免疫，炎症和抗凋亡反应的高度特异性方法。 本发明提供使用突变NIK蛋白抑制NF-κB依赖性基因表达的方法。 本发明的一个实施方案提供抑制IKK活化的激酶缺陷型NIK突变蛋白。 本发明的另一个实施方案提供结合IKK的N末端NIK突变蛋白，从而抑制NIK / IKK相互作用。

    Methods and compositions for the synergistic activation of latent HIV
    5.
    发明授权
    Methods and compositions for the synergistic activation of latent HIV 有权
    潜伏HIV协同激活的方法和组合物

    公开(公告)号：US08247613B2

    公开(公告)日：2012-08-21

    申请号：US12297034

    申请日：2007-04-17

    申请人： Samuel A. F. Williams ,  Warner C. Greene

    发明人： Samuel A. F. Williams ,  Warner C. Greene

    IPC分类号： C07C45/00 ,  A61K38/00 ,  A61K38/12

    CPC分类号： A61K45/06 ,  A61K31/165 ,  A61K31/19 ,  A61K31/22 ,  C12N2740/16011 ,  A61K2300/00

    摘要： The present invention provides methods and compositions useful for the elimination of latent HIV reservoirs that persist despite HAART. The methods and compositions overcome this latent barrier by inducing the replication of HIV in latently infected T cells while preventing the spread of the newly produced virions to uninfected cells by providing HAART simultaneously. Compositions of the invention comprise an activator of latent HIV expression, such as prostratin, and an inhibitor of histone deacetylase, such as TSA. A surprising finding of this invention is that the inhibitor of the histone deacetylase synergizes the effect of prostratin thus, allowing administering to a patient a lower, non-toxic dose of prostratin.

    摘要翻译： 本发明提供了用于消除尽管HAART持续存在的潜伏性HIV储库的方法和组合物。 方法和组合物通过在潜伏感染的T细胞中诱导HIV的复制来克服这种潜在的障碍，同时通过同时提供HAART来防止新产生的病毒粒子扩散到未感染的细胞。 本发明的组合物包含潜伏的HIV表达的激活剂，例如前列腺素和组蛋白脱乙酰酶抑制剂，例如TSA。 本发明的令人惊奇的发现是，组蛋白脱乙酰酶的抑制剂可促进前列腺素的作用，从而允许给予患者较低的无毒剂量的前列腺素。

    Inhibitor of the inflammatory response induced by TNF&agr; and IL-1
    7.
    发明授权
    Inhibitor of the inflammatory response induced by TNF&agr; and IL-1 有权
    TNFalpha和IL-1诱导的炎症反应抑制剂

    公开(公告)号：US06645728B2

    公开(公告)日：2003-11-11

    申请号：US09871889

    申请日：2001-06-01

    申请人： Warner C. Greene ,  Xin Lin ,  Romas Gelezuinas

    发明人： Warner C. Greene ,  Xin Lin ,  Romas Gelezuinas

    IPC分类号： G01N33567

    CPC分类号： C12N9/1205

    摘要： The present invention provides the molecular basis for cytokine induction of NF-&kgr;B-dependent immune and inflammatory responses, emphasizing a role for both NIK-NIK and NIK-IKK protein—protein interactions. A relatively small region of NIK selectively impairs the NIK-IKK interaction. The present invention provides a novel and highly specific method for modulating NF-&kgr;B-dependent immune, inflammatory, and anti-apoptotic responses, based on interruption of the critical protein—protein interaction of NIK and IKK. The present invention provides methods for inhibiting NF-&kgr;B-dependent gene expression, using mutant NIK proteins. One embodiment of the present invention provides kinase-deficient NIK mutant proteins that inhibit activation of IKK. Another embodiment of the invention provides N-terminus NIK mutant proteins that bind IKK, thus inhibiting NIK/IKK interaction.

    摘要翻译： 本发明提供NF-κB依赖性免疫和炎症反应的细胞因子诱导的分子基础，强调NIK-NIK和NIK-IKK蛋白质 - 蛋白质相互作用的作用。 NIK相对较小的区域选择性地损害NIK-IKK相互作用。 本发明提供了一种基于NIK和IKK的关键蛋白质 - 蛋白质相互作用中断来调节NF-κB依赖性免疫，炎症和抗凋亡反应的新型和高度特异性的方法。 本发明提供使用突变NIK蛋白抑制NF-κB依赖性基因表达的方法。 本发明的一个实施方案提供抑制IKK活化的激酶缺陷型NIK突变蛋白。 本发明的另一个实施方案提供结合IKK的N末端NIK突变蛋白，从而抑制NIK / IKK相互作用。

    Virion-based fusion assay
    10.
    发明授权
    Virion-based fusion assay 有权
    基于Virion的融合测定

    公开(公告)号：US07250251B2

    公开(公告)日：2007-07-31

    申请号：US10656803

    申请日：2003-09-04

    申请人： Warner C. Greene ,  Marielle Cavrois ,  Carlos de Noronha

    发明人： Warner C. Greene ,  Marielle Cavrois ,  Carlos de Noronha

    IPC分类号： C12Q1/70

    CPC分类号： C07K14/005 ,  C07K2319/00 ,  C12N7/00 ,  C12N2740/16322 ,  C12Q1/6897

    摘要： The present invention features methods and compositions relating to a virion-based fusion assay for detection of infection of a target cell by an enveloped retroviral virion such as HIV. The assay uses virions containing a chimeric viral protein comprising a viral accessory polypeptide (such as Vpr) fused to a reporter polypeptide (such as beta-lactamase). Fusion of the virion with a target cell membrane results in intracellular delivery of the chimeric protein to the target cell, which in turn provides for detection of a detectable signal mediated by the reporter polypeptide portion of the chimeric polypeptide. Significant detectable signal is only detected following intracellular delivery of the chimeric viral protein, thus providing for detection of productive viral entry to the exclusion of non-productive, endocytic entry of virions into the cell.

    摘要翻译： 本发明的特征在于与基于病毒体的融合测定相关的方法和组合物，用于通过包膜的逆转录病毒药物（例如HIV）检测靶细胞的感染。 该测定使用含有嵌合病毒蛋白质的病毒体，其包含与报道多肽（例如β-内酰胺酶）融合的病毒辅助多肽（例如Vpr）。 病毒粒子与靶细胞膜的融合导致嵌合蛋白质的细胞内递送至靶细胞，其又提供检测由嵌合多肽的报道多肽部分介导的可检测信号。 仅在嵌合病毒蛋白质的细胞内递送后才检测到显着的可检测信号，从而提供检测生产性病毒进入以排除病毒体进入细胞的非生产性内吞进入。