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1. 发明申请

US20120028889A1 INTEGRASE COFACTOR 审中-公开
标题翻译：整合剂
公开(公告)号：US20120028889A1
公开(公告)日：2012-02-02
申请号：US13168114
申请日：2011-06-24
申请人： Zeger DEBYSER , Petr Cherepanov , Erik De Clercq
发明人： Zeger DEBYSER , Petr Cherepanov , Erik De Clercq
IPC分类号： A61K38/18 , A61P31/18 , A61P31/14 , C12Q1/70 , A61P31/12 , A61K31/7088 , C12N9/12
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/475 , C12N5/0641 , C12N9/22 , C12N2740/16222
摘要： The present invention provides nucleic acid molecules which include a region specifically interacting with the nucleic acid encoding the LEDGF/P75 protein or the nucleic acid encoding a fragment of a LEDGF/P75 protein and methods and uses of such nucleic acid molecules.
摘要翻译：本发明提供了核酸分子，其包括与编码LEDGF / P75蛋白的核酸特异性相互作用的区域或编码LEDGF / P75蛋白片段的核酸以及这种核酸分子的方法和用途。

2. 发明授权

US08008470B2 Integrase cofactor 有权
标题翻译：整合酶辅因子
公开(公告)号：US08008470B2
公开(公告)日：2011-08-30
申请号：US12392680
申请日：2009-02-25
申请人： Zeger Debyser , Petr Cherepanov , Erik De Clercq
发明人： Zeger Debyser , Petr Cherepanov , Erik De Clercq
IPC分类号： C07H21/04
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/475 , C12N5/0641 , C12N9/22 , C12N2740/16222
摘要： The present invention provides nucleic acid molecules which include a region specifically interacting with the nucleic acid encoding the LEDGF/P75 protein or the nucleic acid encoding a fragment of a LEDGF/P75 protein and methods and uses of such nucleic acid molecules.
摘要翻译：本发明提供了核酸分子，其包括与编码LEDGF / P75蛋白的核酸特异性相互作用的区域或编码LEDGF / P75蛋白片段的核酸以及这种核酸分子的方法和用途。

3. 发明授权

US07514233B2 Integrase cofactor 有权
标题翻译：整合酶辅因子
公开(公告)号：US07514233B2
公开(公告)日：2009-04-07
申请号：US10529508
申请日：2003-09-26
申请人： Zeger Debyser , Petr Cherepanov , Erik De Clercq
发明人： Zeger Debyser , Petr Cherepanov , Erik De Clercq
IPC分类号： A61K39/385 , A61K39/21 , G01N33/53 , C12Q1/70 , G01N33/569
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/475 , C12N5/0641 , C12N9/22 , C12N2740/16222
摘要： The present invention provides integrase interacting proteins including cofactors which promote strand transfer activity of viral integrase, more particularly HIV integrase, and methods and uses relating thereto. The present invention also relates to methods of identifying molecules interacting with integrase interacting protein and their use as an antiviral.
摘要翻译：本发明提供了整合酶相互作用蛋白，包括促进病毒整合酶的链转移活性，更特别是HIV整合酶的辅因子及其相关的方法和用途。本发明还涉及鉴定与整合酶相互作用蛋白相互作用的分子及其作为抗病毒剂的用途的方法。

4. 发明申请

US20090247610A1 INTEGRASE COFACTOR 有权
标题翻译：整合剂
公开(公告)号：US20090247610A1
公开(公告)日：2009-10-01
申请号：US12392680
申请日：2009-02-25
申请人： Zeger DEBYSER , Petr Cherepanov , Erik De Clercq
发明人： Zeger DEBYSER , Petr Cherepanov , Erik De Clercq
IPC分类号： A61K31/7052 , C07H21/00 , A61P31/12 , A61P31/18
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/475 , C12N5/0641 , C12N9/22 , C12N2740/16222
摘要： The present invention provides nucleic acid molecules which include a region specifically interacting with the nucleic acid encoding the LEDGF/P75 protein or the nucleic acid encoding a fragment of a LEDGF/P75 protein and methods and uses of such nucleic acid molecules.
摘要翻译：本发明提供了核酸分子，其包括与编码LEDGF / P75蛋白的核酸特异性相互作用的区域或编码LEDGF / P75蛋白片段的核酸以及这种核酸分子的方法和用途。

5. 发明申请

US20070259358A1 INTEGRASE COFACTOR 审中-公开
标题翻译：整合剂
公开(公告)号：US20070259358A1
公开(公告)日：2007-11-08
申请号：US11675507
申请日：2007-02-15
申请人： Zeger DEBYSER , Petr CHEREPANOV , Erik DE CLERCQ
发明人： Zeger DEBYSER , Petr CHEREPANOV , Erik DE CLERCQ
IPC分类号： C12Q1/68 , C07H21/00 , C07K16/00 , C07K2/00 , G01N33/53 , C12N1/00 , C12N15/63 , C12N9/00
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/475 , C12N5/0641 , C12N9/22 , C12N2740/16222
摘要： In a study of HIV-1 integrase (IN) complexes derived from nuclei of human cells stably expressing the viral protein from a synthetic gene it was demonstrated that in the nuclear extracts IN exists as part of a large distinct complex with apparent Stokes radius of 61 Å, which dissociates upon dilution yielding a core molecule of 41 Å. The IN complexes were isolated from cells expressing FLAG-tagged IN. By present invention it was demonstrated that the 41 Å core is tetramer of IN, whereas 61 Å molecules are composed of IN tetramers associated with a cellular protein with an apparent molecular weight of 76 kDa. This integrase interacting protein (Inip76) was found to be identical to LEDGF/DFS70/p75 a protein implicated in regulation of gene expression and cellular stress-response. HIV-1 IN and Inip76 co-localized in the nuclei of human cells stably expressing IN. Furthermore, it has been demonstrated by present invention that recombinant Inip76 strongly promoted strand-transfer activity of HIV-1 IN in vitro. Our findings reveal that the minimal IN molecule in human cells is a tetramer and clearly demonstrates that Inip76 is plays a role in retroviral integration. Therefore the present invention provides integrase interacting proteins and more particularly cofactors which promote strand transfer activity of viral integrase, more particularly HIV integrase, and methods and uses relating thereto. The present invention relates to a cellular protein that associates with integrase (integrase interacting protein-Inip), to molecules interacting with Inip and their use as an antiviral. The present invention also relates to antibodies, RNA interference, antigen therapy, gene silencing or antisense inhibition of said integrase interacting protein. The novel integrase interaction protein is a target for HIV replication prevention or inhibition.
摘要翻译：在从合成基因稳定表达病毒蛋白质的人细胞核衍生的HIV-1整合酶（IN）复合物的研究中，证明在核提取物IN中存在作为具有明显的斯托克斯半径61的大的不同复合物的一部分 Å在稀释时解离，得到41的核心分子。从表达FLAG标记的IN的细胞中分离IN复合物。通过本发明，证明41核心是IN的四聚体，而61A分子由与表观分子量为76kDa的细胞蛋白质相关的IN四聚体组成。发现该整合酶相互作用蛋白（Inip76）与涉及基因表达和细胞应激反应调节的蛋白质与LEDGF / DFS70 / p75相同。 HIV-1IN和Inip76共同定位在稳定表达IN的人细胞核中。此外，本发明已经证明，重组Inip76在体外强烈促进HIV-1IN的链转移活性。我们的研究结果表明，人类细胞中的最小IN分子是四聚体，并且清楚地表明Inip76在逆转录病毒整合中起作用。因此，本发明提供了整合酶相互作用蛋白，更具体地说是促进病毒整合酶的链转移活性，尤其是HIV整合酶的辅因子及其相关的方法和用途。本发明涉及与整合酶（整合酶相互作用蛋白-inip），与Inip相互作用的分子及其用作抗病毒剂的细胞蛋白。本发明还涉及所述整合酶相互作用蛋白的抗体，RNA干扰，抗原治疗，基因沉默或反义抑制。该新型整合酶相互作用蛋白是HIV复制预防或抑制的靶标。

6. 发明申请

US20060275748A1 Integrase cofactor 有权
标题翻译：整合酶辅因子
公开(公告)号：US20060275748A1
公开(公告)日：2006-12-07
申请号：US10529508
申请日：2003-09-26
申请人： Zeger Debyser , Petr Cherepanov , Erik De Clercq
发明人： Zeger Debyser , Petr Cherepanov , Erik De Clercq
IPC分类号： C12Q1/70 , C12N9/22 , C07H21/02
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/005 , C07K14/475 , C12N5/0641 , C12N9/22 , C12N2740/16222
摘要： In a study of HIV-1 integrase (IN) complexes derived from nuclei of human cells stably expressing the viral protein from a synthetic gene it was demonstrated that in the nuclear extracts IN exists as part of a large distinct complex with apparent Stokes radius of 61 Å, which dissociates upon dilution yielding a core molecule of 41 Å. The IN complexes were isolated from cells expressing FLAG-tagged IN. By present invention it was demonstrated that the 41 Å core is tetramer of IN, whereas 61 Å molecules are composed of IN tetramers associated with a cellular protein with an apparent molecular weight of 76 kDa. This integrase interacting protein (Inip76) was found to be identical to LEDGF/DFS70/p75 a protein implicated in regulation of gene expression and cellular stress-response. HIV-1 IN and Inip76 co-localized in the nuclei of human cells stably expressing IN. Furthermore, it has been demonstrated by present invention that recombinant Inip76 strongly promoted strand-transfer activity of HIV-1 IN in vitro. Our findings reveal that the minimal IN molecule in human cells is a tetramer and clearly demonstrates that Inip76 is plays a role in retroviral integration. Therefore the present invention provides integrase interacting proteins and more particularly cofactors which promote strand transfer activity of viral integrase, more particularly HIV integrase, and methods and uses relating thereto. The present invention relates to a cellular protein that associates with integrase ( integrase interacting protein-Inip), to molecules interacting with Inip and their use as an antiviral. The present invention also relates to antibodies, RNA interference, antigen therapy, gene silencing or antisense inhibition of said integrase interacting protein. The novel integrase interaction protein is a target for HIV replication prevention or inhibition.
摘要翻译：在从合成基因稳定表达病毒蛋白质的人细胞核衍生的HIV-1整合酶（IN）复合物的研究中，证明在核提取物IN中存在作为具有明显的斯托克斯半径61的大的不同复合物的一部分 Å在稀释时解离，得到41的核心分子。从表达FLAG标记的IN的细胞中分离IN复合物。通过本发明，证明41核心是IN的四聚体，而61A分子由与表观分子量为76kDa的细胞蛋白质相关的IN四聚体组成。发现该整合酶相互作用蛋白（Inip76）与涉及基因表达和细胞应激反应调节的蛋白质与LEDGF / DFS70 / p75相同。 HIV-1IN和Inip76共同定位在稳定表达IN的人细胞核中。此外，本发明已经证明，重组Inip76在体外强烈促进HIV-1IN的链转移活性。我们的研究结果表明，人类细胞中的最小IN分子是四聚体，并且清楚地表明Inip76在逆转录病毒整合中起作用。因此，本发明提供了整合酶相互作用蛋白，更具体地说是促进病毒整合酶的链转移活性，尤其是HIV整合酶的辅因子及其相关的方法和用途。本发明涉及与整合酶（整合酶相互作用蛋白-inip），与Inip相互作用的分子及其用作抗病毒剂的细胞蛋白。本发明还涉及所述整合酶相互作用蛋白的抗体，RNA干扰，抗原治疗，基因沉默或反义抑制。该新型整合酶相互作用蛋白是HIV复制预防或抑制的靶标。

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