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1. 发明授权

US06929946B1 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells 有权
标题翻译：为平滑肌细胞和/或内皮细胞提供组织嗜性的基因递送载体
公开(公告)号：US06929946B1
公开(公告)日：2005-08-16
申请号：US09444284
申请日：1999-11-19
申请人： Ronald Vogels , Menzo J. E. Havenga , Abraham Bout
发明人： Ronald Vogels , Menzo J. E. Havenga , Abraham Bout
IPC分类号： A61K38/00 , A61K48/00 , C07K14/075 , C12N15/861 , C12N15/00 , A01N63/00 , C07H21/04 , C12N15/63
CPC分类号： C07K14/005 , A61K38/00 , A61K48/00 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/6018
摘要： A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and/or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprises a tissue tropism determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing said gene delivery vehicles. Further, a method of delivering nucleic acid to cells such as smooth muscle cells and/or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular construct are also disclosed.
摘要翻译：具有至少一种选自平滑肌细胞，内皮细胞和/或肝细胞的细胞的组织嗜性的基因递送载体。组织向性通常由病毒衣壳提供，例如包含来自至少两种不同病毒的蛋白质片段的病毒衣壳，例如两种不同的腺病毒，包括亚组C或亚组B的腺病毒（例如，腺病毒16）。蛋白质片段可以包含衍生自亚组B腺病毒的纤维蛋白质的组织向性确定片段。此外，用于产生这种基因递送载体的细胞和含有所述基因递送载体的药物组合物。此外，将核酸递送到诸如平滑肌细胞和/或内皮细胞的细胞的方法，其涉及向细胞施用具有来自至少两种不同腺病毒的蛋白质的腺病毒衣壳，并且其中至少一种纤维蛋白质的组织向性确定片段来源于亚组B腺病毒。还公开了特定的构建体。

2. 发明授权

US07968087B2 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells 有权
标题翻译：为平滑肌细胞和/或内皮细胞提供组织嗜性的基因递送载体
公开(公告)号：US07968087B2
公开(公告)日：2011-06-28
申请号：US12455086
申请日：2009-05-28
申请人： Ronald Vogels , Menzo J. E. Havenga , Abraham Bout
发明人： Ronald Vogels , Menzo J. E. Havenga , Abraham Bout
IPC分类号： A01N63/00 , A61K48/00 , C12N15/00 , C12N15/63 , C07H21/04
CPC分类号： C07K14/005 , A61K38/00 , A61K48/00 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/6018
摘要： A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and/or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprise a tissue tropism-determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing these gene delivery vehicles are provided. Further, a method is disclosed for delivering nucleic acid to cells such as smooth muscle cells and/or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism-determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular constructs are also disclosed.
摘要翻译：具有至少一种选自平滑肌细胞，内皮细胞和/或肝细胞的细胞的组织嗜性的基因递送载体。组织向性通常由病毒衣壳提供，例如包含来自至少两种不同病毒的蛋白质片段的病毒衣壳，例如两种不同的腺病毒，包括亚组C或亚组B的腺病毒（例如，腺病毒16）。蛋白质片段可以包含衍生自亚组B腺病毒的纤维蛋白质的组织向性决定片段。此外，提供了用于产生这种基因递送载体的细胞和含有这些基因递送载体的药物组合物。此外，公开了一种用于将核酸递送至诸如平滑肌细胞和/或内皮细胞的细胞的方法，其涉及向细胞施用具有来自至少两种不同腺病毒的蛋白质的腺病毒衣壳，并且其中至少一种组织向性确定片段纤维蛋白源自B亚型腺病毒亚组。还公开了特定的构建体。

3. 发明申请

US20090253207A1 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells 有权
标题翻译：为平滑肌细胞和/或内皮细胞提供组织嗜性的基因递送载体
公开(公告)号：US20090253207A1
公开(公告)日：2009-10-08
申请号：US12455086
申请日：2009-05-28
申请人： Ronald Vogels , Menzo J. E. Havenga , Abraham Bout
发明人： Ronald Vogels , Menzo J. E. Havenga , Abraham Bout
IPC分类号： C12N15/86
CPC分类号： C07K14/005 , A61K38/00 , A61K48/00 , C07K2319/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/6018
摘要： A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and/or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprise a tissue tropism-determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing these gene delivery vehicles are provided. Further, a method is disclosed for delivering nucleic acid to cells such as smooth muscle cells and/or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism-determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular constructs are also disclosed.
摘要翻译：具有至少一种选自平滑肌细胞，内皮细胞和/或肝细胞的细胞的组织嗜性的基因递送载体。组织向性通常由病毒衣壳提供，例如包含来自至少两种不同病毒的蛋白质片段的病毒衣壳，例如两种不同的腺病毒，包括亚组C或亚组B的腺病毒（例如，腺病毒16）。蛋白质片段可以包含衍生自亚组B腺病毒的纤维蛋白质的组织向性决定片段。此外，提供了用于产生这种基因递送载体的细胞和含有这些基因递送载体的药物组合物。此外，公开了一种用于将核酸递送至诸如平滑肌细胞和/或内皮细胞的细胞的方法，其涉及向细胞施用具有来自至少两种不同腺病毒的蛋白质的腺病毒衣壳，并且其中至少一种组织向性确定片段纤维蛋白源自B亚型腺病毒亚组。还公开了特定的构建体。

4. 发明授权

US08221971B2 Serotype of adenovirus and uses thereof 有权
标题翻译：腺病毒血清型及其用途
公开(公告)号：US08221971B2
公开(公告)日：2012-07-17
申请号：US11980222
申请日：2007-10-29
申请人： Abraham Bout , Menzo Jans Emco Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Jans Emco Havenga , Ronald Vogels
IPC分类号： C12Q3/00 , C12Q1/70 , C12N15/00 , C12N15/01 , C12N15/09 , C12N7/00
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10321 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2710/10352 , C12N2810/6018 , C12N2830/00
摘要： Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.
摘要翻译：腺病毒血清型的自然向性不同。腺病毒血清型2,4,5和7都具有与肺上皮细胞和其他呼吸组织的天然亲和关系。相比之下，血清型40和41与胃肠道具有天然的联系。所描述的血清型至少在衣壳蛋白（penton-base，hexon），负责细胞结合的蛋白质（纤维蛋白）以及涉及腺病毒复制的蛋白质中不同。血清型中对向性和衣壳蛋白的这种差异导致了许多研究工作，旨在通过修饰衣壳蛋白来重新定向腺病毒向性。

5. 发明授权

US06905678B2 Gene delivery vectors with cell type specificity for mesenchymal stem cells 有权
标题翻译：具有间充质干细胞的细胞类型特异性的基因递送载体
公开(公告)号：US06905678B2
公开(公告)日：2005-06-14
申请号：US10010645
申请日：2001-11-13
申请人： Menzo Jans Emco Havenga , Abraham Bout , Ronald Vogels
发明人： Menzo Jans Emco Havenga , Abraham Bout , Ronald Vogels
IPC分类号： C12N15/09 , A01N63/00 , A61K35/28 , A61K35/76 , A61K39/235 , A61K48/00 , A61P9/00 , A61P19/02 , A61P19/08 , A61P25/00 , C12N5/00 , C12N5/08 , C12N5/10 , C12N7/00 , C12N15/00 , C12N15/63 , C12N15/86 , C12N15/861 , C12N21/06
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343
摘要： Methods and associated materials for transducing mesenchymal stem cells with a desired nucleic acid. Mesenchymal stem cells are a recently discovered kind of stem cell for which suitable transfer vehicles are still desired. Typical gene delivery vehicles such as the adenoviruses or adeno associated viruses have no particular tropism for mesenchymal stem cells. Also disclosed is gene therapy using adenoviruses provided with tropism for mesenchymal stem cells.
摘要翻译：用所需核酸转导间充质干细胞的方法和相关材料。间充质干细胞是最近发现的干细胞，其中仍然需要合适的转运载体。典型的基因递送载体如腺病毒或腺相关病毒对间充质干细胞没有特异性的向性。还公开了使用提供间质干细胞向性的腺病毒的基因治疗。

6. 发明授权

US06803234B2 Gene delivery vectors with cell type specificity for primary human chondrocytes 有权
标题翻译：具有细胞型特异性的原代人软骨细胞的基因递送载体
公开(公告)号：US06803234B2
公开(公告)日：2004-10-12
申请号：US09928262
申请日：2001-08-10
申请人： Menzo Havenga , Ronald Vogels , Abraham Bout
发明人： Menzo Havenga , Ronald Vogels , Abraham Bout
IPC分类号： C12N1586
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2810/6018
摘要： The present invention relates to a gene delivery vehicle comprising a recombinant adenovirus having a tropism for a primary human chondrocyte. By efficiently transducing a nucleic acid of interest into a primary chondrocytes, the gene delivery vehicle is able to at least in part improve the counteraction of cartilage disease. In one embodiment the recombinant adenovirus comprises a deletion in the gene encoding for fiber protein, which is replaced by a nucleic acid sequence encoding at least part of a fiber protein of a B-type adenovirus.
摘要翻译：本发明涉及包含对于初级人软骨细胞具有向性的重组腺病毒的基因递送载体。通过将感兴趣的核酸有效地转导到原代软骨细胞中，基因递送载体能够至少部分地改善软骨疾病的反作用。在一个实施方案中，重组腺病毒在编码纤维蛋白的基因中包含缺失，其被编码B型腺病毒的纤维蛋白的至少一部分的核酸序列替代。

7. 发明授权

US07906113B2 Serotype of adenovirus and uses thereof 有权
标题翻译：腺病毒血清型及其用途
公开(公告)号：US07906113B2
公开(公告)日：2011-03-15
申请号：US11586316
申请日：2006-10-25
申请人： Abraham Bout , Menzo Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Havenga , Ronald Vogels
IPC分类号： A01N63/00 , C12N15/00 , C12N15/33 , C12N15/34
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10321 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2710/10352 , C12N2810/6018 , C12N2830/00
摘要： Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.
摘要翻译：腺病毒血清型的自然向性不同。腺病毒血清型2,4,5和7都具有与肺上皮细胞和其他呼吸组织的天然亲和关系。相比之下，血清型40和41与胃肠道具有天然的联系。所描述的血清型至少在衣壳蛋白（penton-base，hexon），负责细胞结合的蛋白质（纤维蛋白）以及涉及腺病毒复制的蛋白质中不同。血清型中对向性和衣壳蛋白的这种差异导致了许多研究工作，旨在通过修饰衣壳蛋白来重新定向腺病毒向性。

8. 发明授权

US07468181B2 Means and methods for the production of adenovirus vectors 有权
标题翻译：用于产生腺病毒载体的方法和方法
公开(公告)号：US07468181B2
公开(公告)日：2008-12-23
申请号：US10512589
申请日：2003-04-24
申请人： Ronald Vogels , Abraham Bout
发明人： Ronald Vogels , Abraham Bout
IPC分类号： A01N63/00 , C12N15/00 , C12N15/11 , C12N5/00 , C12N15/34
CPC分类号： C12N15/86 , A61K48/00 , A61K2039/525 , A61K2039/5256 , C12N2710/10343 , C12N2810/6018 , C12N2830/002
摘要： The invention relates to methods and means for the production of adenoviral vectors on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenoviral vector and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products provided by the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.
摘要翻译：本发明涉及在补体细胞系上产生腺病毒载体的方法和手段，其中编码核酸的早期区域4开放阅读框6（E4-orf6）存在于腺病毒载体中，其中E4-orf6基因产物是与互补细胞提供的E1基因产物的一种或多种产物相容，使得腺病毒载体可以由补体细胞有效产生。

9. 发明申请

US20070041946A1 Serotype of adenovirus and uses thereof 有权
标题翻译：腺病毒血清型及其用途
公开(公告)号：US20070041946A1
公开(公告)日：2007-02-22
申请号：US11586316
申请日：2006-10-25
申请人： Abraham Bout , Menzo Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Havenga , Ronald Vogels
IPC分类号： A61K48/00 , C12N15/861 , C07H21/02 , C12N7/00
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10321 , C12N2710/10322 , C12N2710/10343 , C12N2710/10345 , C12N2710/10352 , C12N2810/6018 , C12N2830/00
摘要： Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.
摘要翻译：腺病毒血清型的自然向性不同。腺病毒血清型2,4,5和7都具有与肺上皮细胞和其他呼吸组织的天然亲和关系。相比之下，血清型40和41与胃肠道具有天然的联系。所描述的血清型至少在衣壳蛋白（penton-base，hexon），负责细胞结合的蛋白质（纤维蛋白）以及涉及腺病毒复制的蛋白质中不同。血清型中对向性和衣壳蛋白的这种差异导致了许多研究工作，旨在通过修饰衣壳蛋白来重新定向腺病毒向性。

10. 发明申请

US20050181507A1 Gene delivery vectors with cell type specificity for mesenchymal stem cells 审中-公开
公开(公告)号：US20050181507A1
公开(公告)日：2005-08-18
申请号：US11083590
申请日：2005-03-18
申请人： Menzo Havenga , Abraham Bout , Ronald Vogels
发明人： Menzo Havenga , Abraham Bout , Ronald Vogels
IPC分类号： C12N15/09 , A01N63/00 , A61K35/28 , A61K35/76 , A61K39/235 , A61K48/00 , A61P9/00 , A61P19/02 , A61P19/08 , A61P25/00 , C12N5/00 , C12N5/08 , C12N5/10 , C12N7/00 , C12N15/00 , C12N15/63 , C12N15/86 , C12N15/861
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343
摘要： Methods and associated materials for transducing mesenchymal stem cells with a desired nucleic acid. Mesenchymal stem cells are a recently discovered kind of stem cell for which suitable transfer vehicles are still desired. Typical gene delivery vehicles such as the adenoviruses or adeno associated viruses have no particular tropism for mesenchymal stem cells. Also disclosed is gene therapy using adenoviruses provided with tropism for mesenchymal stem cells.

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