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1. 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。

2. 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。

3. 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。

4. 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.

5. 发明申请

US20050084480A1 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：US20050084480A1
公开(公告)日：2005-04-21
申请号：US10951102
申请日：2004-09-27
申请人： Abraham Bout , Menzo Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Havenga , Ronald Vogels
IPC分类号： A61K48/00 , C12N5/02 , C12N5/10 , C12N7/00 , C12N15/00 , C12N15/09 , C12N15/35 , C12N15/63 , C12N15/70 , C12N15/74 , C12N15/861
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： The invention provides a gene delivery vehicle and a gene of interest comprising at least one Ad35 element or a functional equivalent thereof, responsible for avoiding or diminishing neutralizing activity against adenoviral elements by the host to which the gene is to be delivered. A functional equivalent/homologue of an Ad35 (element) includes an adenovirus (element) which, like adenovirus 35, encounters pre-existing immunity in less than about 10% of the hosts to which it is administered for the first time, or which is capable in more than about 90% of the hosts to which it is administered of avoiding or diminishing the immune response.
摘要翻译：本发明提供了一种基因递送载体和目标基因，其包含至少一种Ad35元件或其功能等同物，负责避免或减少基因将被递送的宿主对腺病毒元件的中和活性。 Ad35（元件）的功能等同物/同系物包括腺病毒（元件），其像腺病毒35一样在首次施用的宿主的少于约10％的宿主中遇到预先存在的免疫，或者是能够超过约90％的给予它的宿主避免或减少免疫反应。

6. 发明授权

US07749493B2 Chimeric adenoviruses 失效
标题翻译：嵌合腺病毒
公开(公告)号：US07749493B2
公开(公告)日：2010-07-06
申请号：US11207626
申请日：2005-08-18
申请人： Menzo Havenga , Ronald Vogels , Abraham Bout
发明人： Menzo Havenga , Ronald Vogels , Abraham Bout
IPC分类号： A61K48/00 , C12N15/00 , C12N15/09 , C12N15/11 , C12N15/34
CPC分类号： C12N15/86 , C07K14/005 , C12N2710/10322 , C12N2710/10344 , C12N2760/20134
摘要： The present invention provides methods and vector systems for the generation of chimeric recombinant adenoviruses. These hybrid adenoviruses contain a genome that is derived from different adenovirus serotypes. In particular, novel hybrid adenoviruses are disclosed with improved properties for gene therapy purposes. These properties include: a decreased sensitivity towards neutralizing antibodies, a modified host range, a change in the titer to which adenovirus can be grown, the ability to escape trapping in the liver upon in vivo systemic delivery, and absence or decreased infection of antigen presenting cells (APC) of the immune system, such as macrophages or dendritic cells. These chimeric adenoviruses thus represent improved tools for gene therapy and vaccination since they overcome the limitations observed with the currently used serotype subgroup C adenoviruses.
摘要翻译：本发明提供用于产生嵌合重组腺病毒的方法和载体系统。这些杂合腺病毒含有衍生自不同腺病毒血清型的基因组。特别地，公开了具有改进的用于基因治疗目的的性质的新型杂合腺病毒。这些性质包括：对中和抗体的降低的敏感性，修饰的宿主范围，可以生长腺病毒的滴度的变化，在体内全身递送时逃避捕获在肝脏中的能力，以及抗原呈递的不存在或减少的感染免疫系统的细胞（APC），例如巨噬细胞或树突状细胞。因此，这些嵌合腺病毒代表了用于基因治疗和疫苗接种的改进工具，因为它们克服了目前使用的血清型亚型C腺病毒所观察到的限制。

7. 发明申请

US20080171018A1 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：US20080171018A1
公开(公告)日：2008-07-17
申请号：US11980222
申请日：2007-10-29
申请人： Abraham Bout , Menzo Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Havenga , Ronald Vogels
IPC分类号： A61K48/00
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。

8. 发明申请

US20050169891A1 Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells 审中-公开
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：US20050169891A1
公开(公告)日：2005-08-04
申请号：US11018669
申请日：2004-12-20
申请人： Ronald Vogels , Menzo Havenga , Abraham Bout
发明人： Ronald Vogels , Menzo Havenga , Abraham Bout
IPC分类号： A61K38/00 , A61K48/00 , C07K14/075 , C12N15/861
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。

9. 发明授权

US07270811B2 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：US07270811B2
公开(公告)日：2007-09-18
申请号：US10951102
申请日：2004-09-27
申请人： Abraham Bout , Menzo Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Havenga , Ronald Vogels
IPC分类号： A01N63/00 , A61K48/00 , C12N15/00
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： The invention provides a gene delivery vehicle and a gene of interest comprising at least one Ad35 element or a functional equivalent thereof, responsible for avoiding or diminishing neutralizing activity against adenoviral elements by the host to which the gene is to be delivered. A functional equivalent/homologue of an Ad35 (element) includes an adenovirus (element) which, like adenovirus 35, encounters pre-existing immunity in less than about 10% of the hosts to which it is administered for the first time, or which is capable in more than about 90% of the hosts to which it is administered of avoiding or diminishing the immune response.
摘要翻译：本发明提供了一种基因递送载体和目标基因，其包含至少一种Ad35元件或其功能等同物，负责避免或减少基因将被递送的宿主对腺病毒元件的中和活性。 Ad35（元件）的功能等同物/同系物包括腺病毒（元件），其像腺病毒35一样在首次施用的宿主的少于约10％的宿主中遇到预先存在的免疫，或者是能够超过约90％的给予它的宿主避免或减少免疫反应。

10. 发明授权

US06913922B1 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：US06913922B1
公开(公告)日：2005-07-05
申请号：US09573740
申请日：2000-05-18
申请人： Abraham Bout , Menzo Havenga , Ronald Vogels
发明人： Abraham Bout , Menzo Havenga , Ronald Vogels
IPC分类号： A61K48/00 , C12N5/02 , C12N5/10 , C12N7/00 , C12N15/00 , C12N15/09 , C12N15/35 , C12N15/63 , C12N15/70 , C12N15/74 , C12N15/861
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。

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