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公开(公告)号：US07344883B2
公开(公告)日：2008-03-18
申请号：US11165697
申请日：2005-06-24
IPC分类号： C12N5/10 , C12N5/08 , C12N7/00 , C12N15/861
CPC分类号： C12N15/86 , C12N7/00 , C12N7/025 , C12N15/861 , C12N2710/10041 , C12N2710/10051 , C12N2710/10343 , C12N2710/10352 , C12N2830/00 , C12N2840/20
摘要： A packaging cell line that complements recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line is preferably derived from primary, diploid human cells that are transformed by adenovirus E1 sequences either operatively linked on one DNA molecule or located on two separate DNA molecules, the sequences being operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also disclosed is a cell line derived from PER.C6 that expresses functional Ad35 E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter or a heterologous promoter and terminated by a heterologous poly-adenylation signal. The cell lines are useful for producing recombinant adenoviruses designed for gene therapy and vaccination. The cell lines can also be used for producing human recombinant therapeutic proteins such as human growth factors and human antibodies. Also, the cell lines are useful for producing human viruses other than adenovirus such as influenza virus, herpes simplex virus, rotavirus, and measles virus.
摘要翻译： 一种包装细胞系，其基于来自亚组B，优选腺病毒35的血清型补充重组腺病毒。细胞系优选衍生自通过腺病毒E1序列转化的原代二倍体人细胞，所述腺病毒E1序列可操作地连接在一个DNA分子上或位于两个 分离的DNA分子，该序列可操作地连接到能够转录和翻译编码蛋白质的调控序列。 还公开了衍生自表达功能性Ad35 E1B序列的PER.C6的细胞系。 Ad35-E1B序列由E1B启动子或异源启动子驱动，并通过异源多聚腺苷酸化信号终止。 细胞系可用于生产设计用于基因治疗和疫苗接种的重组腺病毒。 细胞系也可以用于生产人重组治疗蛋白质，例如人生长因子和人抗体。 此外，细胞系可用于生产除了腺病毒如流感病毒，单纯疱疹病毒，轮状病毒和麻疹病毒之外的人类病毒。
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公开(公告)号：US20080199433A1
公开(公告)日：2008-08-21
申请号：US11786409
申请日：2007-04-11
CPC分类号： C12N15/86 , C12N7/00 , C12N7/025 , C12N15/861 , C12N2710/10041 , C12N2710/10051 , C12N2710/10343 , C12N2710/10352 , C12N2830/00 , C12N2840/20
摘要： A packaging cell line that complements recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line is preferably derived from primary, diploid human cells that are transformed by adenovirus E1 sequences either operatively linked on one DNA molecule or located on two separate DNA molecules, the sequences being operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also disclosed is a cell line derived from PER.C6 that expresses functional Ad35 E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter or a heterologous promoter and terminated by a heterologous poly-adenylation signal. The cell lines are useful for producing recombinant adenoviruses designed for gene therapy and vaccination. The cell lines can also be used for producing human recombinant therapeutic proteins such as human growth factors and human antibodies. Also, the cell lines are useful for producing human viruses other than adenovirus such as influenza virus, herpes simplex virus, rotavirus, and measles virus.
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公开(公告)号：US08114637B2
公开(公告)日：2012-02-14
申请号：US12804179
申请日：2010-07-14
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/38
摘要： In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. Provided are means and methods for reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.
摘要翻译： 在重组腺病毒载体和包装细胞基因组之间不存在实质的序列重叠的情况下，可以以低频形成辅助依赖性的含有E1的颗粒（HDEP）。 提供减少或防止HDEP产生的手段和方法。 为此，提供了新颖的包装电池及其制造方法。
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公开(公告)号：US08052967B2
公开(公告)日：2011-11-08
申请号：US11899572
申请日：2007-09-05
CPC分类号： C12N15/86 , A61K2039/5256 , C12N2710/10343 , C12N2840/20 , C12N2840/44
摘要： Provided are methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B-55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.
摘要翻译： 提供了通过在腺病毒包装细胞中过表达pIX，通过在重组腺病毒载体中保留至少一部分E1B-55K区域或通过调节pIX来提高重组腺病毒的稳定性和/或包装能力的方法和手段 与异源启动子。 本发明还涉及在补体细胞系上产生这种腺病毒的方法和装置，其中编码核酸的早期区域4开放阅读框6（E4-orf6）存在于腺病毒中，其中E4-orf6基因产物是 与补体细胞中E1基因产物的一种或多种产物相容，使得腺病毒载体可以通过补体细胞有效产生。
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公开(公告)号：US20100311172A1
公开(公告)日：2010-12-09
申请号：US12804179
申请日：2010-07-14
IPC分类号： C12N15/87
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/38
摘要： In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. Provided are means and methods for reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.
摘要翻译： 在重组腺病毒载体和包装细胞基因组之间不存在实质的序列重叠的情况下，可以以低频形成辅助依赖性的含有E1的颗粒（HDEP）。 提供减少或防止HDEP产生的手段和方法。 为此，提供了新颖的包装电池及其制造方法。
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公开(公告)号：US08609402B2
公开(公告)日：2013-12-17
申请号：US13134206
申请日：2011-05-31
申请人： Menzo Jans Emco Havenga , Ronald Vogels , Jerald C. Sadoff , David Hone , Yasir Abdul Wahid Skeiky , Katarina Rado{hacek over (s)}evic
发明人： Menzo Jans Emco Havenga , Ronald Vogels , Jerald C. Sadoff , David Hone , Yasir Abdul Wahid Skeiky , Katarina Rado{hacek over (s)}evic
IPC分类号： C12N15/00 , C12N15/09 , C12N15/48 , C12N15/52 , C12N15/867
CPC分类号： A61K39/04 , A61K35/761 , A61K2039/523 , A61K2039/5256 , A61K2039/53 , A61K2039/55544 , C07K14/35 , C07K2319/00 , C12N2710/10343
摘要： The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Further described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
摘要翻译： 本发明涉及包含重组载体例如重组腺病毒的疫苗。 载体包含编码来自一种或多种结核分枝杆菌的至少两种抗原的异源核酸。 还描述了连接抗原的特异性蛋白酶识别位点的使用，通过该抗原，编码的抗原在切割时被分离。 在切割后，抗原以单独的方式有助于免疫应答。 重组载体可以包含编码切割接头并分离抗原的蛋白酶的核酸。 进一步描述了由重组载体编码的遗传佐剂的用途，其中此类遗传佐剂也可通过存在可切割连接子和特异性蛋白酶来切割。
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公开(公告)号：US08221971B2
公开(公告)日：2012-07-17
申请号：US11980222
申请日：2007-10-29
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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公开(公告)号：US20110281347A1
公开(公告)日：2011-11-17
申请号：US13134190
申请日：2011-05-31
申请人： Menzo Jans Emco Havenga , Ronald Vogels , Jerald C. Sadoff , David Hone , Yasir Abdul Wahid Skeiky , Katarina Radosevic
发明人： Menzo Jans Emco Havenga , Ronald Vogels , Jerald C. Sadoff , David Hone , Yasir Abdul Wahid Skeiky , Katarina Radosevic
IPC分类号： C12N15/63
CPC分类号： A61K39/04 , A61K35/761 , A61K2039/523 , A61K2039/5256 , A61K2039/53 , A61K2039/55544 , C07K14/35 , C07K2319/00 , C12N2710/10343
摘要： Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Also described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
摘要翻译： 描述了包含重组载体例如重组腺病毒的疫苗。 载体包含编码来自一种或多种结核分枝杆菌的至少两种抗原的异源核酸。 还描述了连接抗原的特异性蛋白酶识别位点的使用，通过该抗原，编码的抗原在切割时被分离。 在切割后，抗原以单独的方式有助于免疫应答。 重组载体可以包含编码切割接头并分离抗原的蛋白酶的核酸。 还描述了由重组载体编码的遗传佐剂的用途，其中这种遗传佐剂也可以通过可切割接头和特异性蛋白酶的存在来切割。
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公开(公告)号：US07816104B2
公开(公告)日：2010-10-19
申请号：US11384850
申请日：2006-03-20
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/38
摘要： In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. The invention provides means and methods reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.
摘要翻译： 在重组腺病毒载体和包装细胞基因组之间不存在实质的序列重叠的情况下，可以以低频形成辅助依赖性的含有E1的颗粒（HDEP）。 本发明提供减少或防止HDEP产生的方法和方法。 为此，提供了新颖的包装电池及其制造方法。
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公开(公告)号：US20090123438A1
公开(公告)日：2009-05-14
申请号：US11667975
申请日：2005-11-15
申请人： Menzo Jans Emco Havenga , Ronald Vogels , Jerald C. Sadoff , David Hone , Yasir Abdul Wahid Skeiky , Katarina Radosevic
发明人： Menzo Jans Emco Havenga , Ronald Vogels , Jerald C. Sadoff , David Hone , Yasir Abdul Wahid Skeiky , Katarina Radosevic
IPC分类号： A61K48/00 , A61K39/04 , C12N15/861 , C12N7/01
CPC分类号： A61K39/04 , A61K35/761 , A61K2039/523 , A61K2039/5256 , A61K2039/53 , A61K2039/55544 , C07K14/35 , C07K2319/00 , C12N2710/10343
摘要： The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. The invention also relates to the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. The invention furthermore relates to the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
摘要翻译： 本发明涉及包含重组载体例如重组腺病毒的疫苗。 载体包含编码来自一种或多种结核分枝杆菌的至少两种抗原的异源核酸。 本发明还涉及连接抗原的特异性蛋白酶识别位点的用途，通过该抗原将经编码的抗原在切割后分离。 在切割后，抗原以单独的方式有助于免疫应答。 重组载体可以包含编码切割接头并分离抗原的蛋白酶的核酸。 本发明还涉及由重组载体编码的遗传佐剂的用途，其中这种遗传佐剂也可以通过存在可切割接头和特异性蛋白酶来切割。
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