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1. 发明授权

US6140087A Adenovirus vectors for gene therapy 失效
标题翻译：用于基因治疗的腺病毒载体
公开(公告)号：US6140087A
公开(公告)日：2000-10-31
申请号：US250885
申请日：1994-05-31
申请人： Frank L. Graham , Andrew Bett , Ludvik Prevec , Wael M. Haddara
发明人： Frank L. Graham , Andrew Bett , Ludvik Prevec , Wael M. Haddara
IPC分类号： C12N15/09 , C12N7/00 , C12N15/861 , C12P21/00 , C12N15/63 , C07H21/04 , C12N15/64
CPC分类号： C12N15/86 , A01K2217/05 , C12N2710/10343 , C12N2800/30
摘要： The invention comprises a series of adenovirus-based vectors having deletions in the E1 and/or E3 regions, and also insertions of pBR322 sequences, which can be used to deliver nucleic acid inserts into host cells, tissues or organisms that then can express the insert. The invention includes the use of the vectors in introducing genes into cells, in making vaccines and in gene therapy.
摘要翻译：本发明包括在E1和/或E3区域中具有缺失的一系列基于腺病毒的载体，以及pBR322序列的插入，其可用于将核酸插入物递送到宿主细胞，组织或生物体中，然后可以表达插入物。本发明包括使用载体将基因导入细胞，制备疫苗和进行基因治疗。

2. 发明授权

US07025967B2 Recombinant protein production in bovine adenovirus expression vector system 失效
公开(公告)号：US07025967B2
公开(公告)日：2006-04-11
申请号：US10046938
申请日：2002-01-14
申请人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
发明人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
IPC分类号： A61K39/235 , A61K39/295 , C12N7/01 , C12N15/861
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352
摘要： The present invention relates novel live bovine adenovirus (BAV) expression vector systems in which part or all of one or both of the early region 1 (E1) and early region 3 (E3) genes are deleted and replaced by a foreign gene or fragment thereof and novel recombinant mammalian cell lines stably transformed with BAV E1 sequences, and therefore, express E1 gene products capable of allowing replication therein of a bovine adenovirus having an E1 deletion replaced by a heterologous nucleotide sequence encoding a foreign gene or fragment thereof and their use in production of (antigenic) polypeptides or fragments thereof for the purpose of live recombinant virus or subunit vaccine or for other therapies.

3. 发明授权

US6086890A Bovine adenovirus expression vector system 失效
标题翻译：牛腺病毒表达载体系统
公开(公告)号：US6086890A
公开(公告)日：2000-07-11
申请号：US815927
申请日：1997-03-13
申请人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
发明人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
IPC分类号： A61K48/00 , C07K14/075 , C12N7/01 , C12N15/861 , A61K39/235 , C12N15/86
CPC分类号： C12N15/86 , C07K14/005 , A61K48/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352
摘要： The present invention relates novel live bovine adenovirus (BAV) expression vector systems in which part or all of one or both of the early region 1 (E1) and early region 3 (E3) genes are deleted and replaced by a foreign gene or fragment thereof and novel recombinant mammalian cell lines stably transformed with BAV E1 sequences, and therefore, express E1 gene products capable of allowing replication therein of a bovine adenovirus having an E1 deletion replaced by a heterologous nucleotide sequence encoding a foreign gene or fragment thereof and their use in production of (antigenic) polypeptides or fragments thereof for the purpose of live recombinant virus or subunit vaccine or for other therapies.
摘要翻译：本发明涉及新鲜活牛腺病毒（BAV）表达载体系统，其中早期区域1（E1）和早期区域3（E3）基因中的一个或两个的部分或全部缺失并被外源基因或其片段替代以及用BAV E1序列稳定转化的新型重组哺乳动物细胞系，因此表达能够允许在其中复制具有E1缺失的牛腺病毒的E1基因产物，其被编码外源基因或其片段的异源核苷酸序列替代，以及它们在用于活重组病毒或亚单位疫苗或用于其他疗法的（抗原性）多肽或其片段的产生。

4. 发明授权

US6001591A Recombinant bovine adenoviruses 失效
标题翻译：重组牛腺病毒
公开(公告)号：US6001591A
公开(公告)日：1999-12-14
申请号：US845623
申请日：1997-04-25
申请人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
发明人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
IPC分类号： A61K48/00 , C07K14/075 , C12N7/01 , C12N15/861 , C12N15/00 , C12N15/86
CPC分类号： C12N15/86 , C07K14/005 , A61K48/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352
摘要： The present invention provides recombinant bovine adenovirus (BAV) vectors and expression systems for introduction and expression of non-BAV sequences in mammalian cells. Methods for the preparation and use of these vectors and expression systems are also provided.
摘要翻译：本发明提供重组牛腺病毒（BAV）载体和用于在哺乳动物细胞中引入和表达非BAV序列的表达系统。还提供了用于制备和使用这些载体和表达系统的方法。

5. 发明授权

US06379944B1 Mammalian cell lines expressing bovine adenovirus functions 有权
标题翻译：表达牛腺病毒功能的哺乳动物细胞系
公开(公告)号：US06379944B1
公开(公告)日：2002-04-30
申请号：US09435242
申请日：1999-11-05
申请人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk , Suresh Kumar Tikoo
发明人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk , Suresh Kumar Tikoo
IPC分类号： C12N700
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352
摘要： The present invention provides novel recombinant mammalian cell lines expressing bovine adenovirus functions. In one embodiment, mammalian cell lines stably transformed with bovine adenovirus E1 sequences express bovine adenovirus E1 gene products and are useful for the replication of bovine adenovirus vectors having deletions and/or insertions in the E1 region. Such vector/cell line combinations are useful for synthesis of recombinant polypeptides, preparation of subunit vaccines, and in gene therapy.
摘要翻译：本发明提供了表达牛腺病毒功能的新型重组哺乳动物细胞系。在一个实施方案中，用牛腺病毒E1序列稳定转化的哺乳动物细胞系表达牛腺病毒E1基因产物，并且可用于在E1区域中具有缺失和/或插入的牛腺病毒载体的复制。这样的载体/细胞系组合可用于合成重组多肽，亚单位疫苗的制备和基因治疗。

6. 发明授权

US5820868A Recombinant protein production in bovine adenovirus expression vector system 失效
公开(公告)号：US5820868A
公开(公告)日：1998-10-13
申请号：US164292
申请日：1993-12-09
申请人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
发明人： Suresh K. Mittal , Frank L. Graham , Ludvik Prevec , Lorne A. Babiuk
IPC分类号： A61K48/00 , C07K14/075 , C12N7/01 , C12N15/861 , A61K39/235 , C12N15/00
CPC分类号： C12N15/86 , C07K14/005 , A61K48/00 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352
摘要： The present invention relates novel live bovine adenovirus (BAV) expression vector systems in which part or all of one or both of the early region 1 (E1) and early region 3 (E3) genes are deleted and replaced by a foreign gene or fragment thereof and novel recombinant mammalian cell lines stably transformed with BAV E1 sequences, and therefore, express E1 gene products capable of allowing replication therein of a bovine adenovirus having an E1 deletion replaced by a heterologous nucleotide sequence encoding a foreign gene or fragment thereof and their use in production of (antigenic) polypeptides or fragments thereof for the purpose of live recombinant virus or subunit vaccine or for other therapies.

7. 发明授权

US07189561B2 Production of adenovirus vectors with reduced levels of replication competent adenovirus contamination 失效
标题翻译：生产具有降低复制水平的腺病毒载体的腺病毒载体
公开(公告)号：US07189561B2
公开(公告)日：2007-03-13
申请号：US10946484
申请日：2004-09-21
申请人： Frank L. Graham
发明人： Frank L. Graham
IPC分类号： C12N15/34 , C12N15/64 , C12N15/63 , C12N5/10 , C12N15/861 , C07H21/04
CPC分类号： C12N15/86 , C12N2710/10343 , C12N2800/30 , C12N2830/42 , C12N2840/20
摘要： Methods, cells and recombinant adenoviral vectors are disclosed that permit the production of recombinant adenoviral vector stocks with reduced levels of contamination by replication competent adenoviruses (RCA). In certain embodiments are disclosed early region 1 (E1) deficient recombinant adenoviral vectors and complementing E1 positive host cells whose sequences are designed to avoid formation of RCA by homologous recombination between sequences in the vector and E1 sequences in the cells. One aspect of the invention involves the inversion of the packaging signal in a recombinant adenoviral vector relative to an adjacent or nearby inverted terminal repeat (ITR). Methods include use of site-specific intregrase family recombinases such as Cre or FLP and recombinase recognition sites such as lox sites or frt sites.
摘要翻译：公开了方法，细胞和重组腺病毒载体，其允许通过复制性腺病毒（RCA）产生具有降低的污染水平的重组腺病毒载体原种。在某些实施方案中公开了早期区域1（E1）缺陷型重组腺病毒载体和补体E1阳性宿主细胞，其序列被设计为避免通过载体中的序列和细胞中的E1序列之间的同源重组而形成RCA。本发明的一个方面涉及重组腺病毒载体中相对于邻近或邻近倒置末端重复（ITR）的包装信号的反转。方法包括使用位点特异性整合酶家族重组酶，如Cre或FLP以及重组酶识别位点，如lox位点或frt位点。

8. 发明授权

US07135187B2 System for production of helper dependent adenovirus vectors based on use of endonucleases 失效
公开(公告)号：US07135187B2
公开(公告)日：2006-11-14
申请号：US10355330
申请日：2003-01-31
申请人： Frank L. Graham , Philip Ng , Robin Parks
发明人： Frank L. Graham , Philip Ng , Robin Parks
IPC分类号： A61K39/23 , C07H21/04 , C12N7/00 , C12N15/00
CPC分类号： C12N15/86 , A01K2217/05 , A61K48/00 , C12N15/85 , C12N2710/10343 , C12N2710/10351 , C12N2800/30 , C12N2800/80 , C12N2830/38 , C12N2830/42 , C12N2840/203
摘要： The present invention relates to methods for efficient and reliable construction of adenovirus vectors which contain and express foreign DNA and are useful for gene transfer into mammalian cells, for vaccines and for gene therapy. The invention provides for the growth and purification of adenovirus vectors (helper dependent vectors or HDVs) from which all or most of the viral genes have been removed. The vector system described herein is a new method designed to eliminate helper viruses from the final HDV preparation by cleavage of the helper virus DNA with an endonuclease, alone or in combination with other methods known to limit the level of helper virus contamination of helper dependent vector preparations. The disclosed methods and compositions also provide for regulated control of gene expression.

9. 发明授权

US07045347B2 Helper dependent adenovirus vectors based on integrase family site-specific recombinases 有权
公开(公告)号：US07045347B2
公开(公告)日：2006-05-16
申请号：US10206163
申请日：2002-07-26
申请人： Frank L. Graham , Michael A. Rudnicki , Martina Anton
发明人： Frank L. Graham , Michael A. Rudnicki , Martina Anton
IPC分类号： C12N15/861 , C12N7/00 , C12N7/01 , A61K31/713 , A61K48/00
CPC分类号： C12N7/00 , A01K2217/05 , A61K48/00 , C12N9/0036 , C12N15/86 , C12N2710/10343 , C12N2710/10352 , C12N2800/30 , C12N2830/38 , C12N2830/42 , C12N2840/203
摘要： This invention provides helper-dependent adenovirus cloning vectors and helper adenoviruses, and methods for making and Using such preparations, wherein the helper adenoviruses contain recombinase target sites that are useful in reducing the level of contamination of helper virus in helper-dependent adenovirus vector preparations.

10. 发明授权

US06566128B1 Adenovirus vectors generated from helper viruses and helper-dependent vectors 失效
标题翻译：由辅助病毒和辅助因子载体产生的腺病毒载体
公开(公告)号：US06566128B1
公开(公告)日：2003-05-20
申请号：US09440809
申请日：1999-11-15
申请人： Frank L. Graham , Robin Parks , Liane Chen
发明人： Frank L. Graham , Robin Parks , Liane Chen
IPC分类号： A61K4800
CPC分类号： C12N7/00 , A01K2217/05 , C12N15/86 , C12N2710/10343 , C12N2710/10351 , C12N2800/30 , C12N2830/002 , C12N2830/38
摘要： The present invention provides an improved helper-dependent vector system for production of high capacity adenoviral cloning vectors. The invention makes use of the DNA size packaging constraints imposed on a pIX-defective Ad virion that prevent such virions from packaging DNA larger than approximately 35 kb. This constraint can be used to develop helper viruses that do not package their DNA. In one embodiment, the invention combines this methodology with the Cre-loxP helper-dependent system to decrease the quantity of contaminating helper virus in vector preparations. In another embodiment the invention is used for vector growth.
摘要翻译：本发明提供了用于产生高产量腺病毒克隆载体的改进的辅助依赖载体系统。本发明利用施加在pIX缺陷型Ad病毒粒子上的DNA大小封装限制，其阻止这种病毒粒子包装大于约35kb的DNA。该约束可用于开发不包装其DNA的辅助病毒。在一个实施方案中，本发明将该方法与Cre-loxP辅助依赖性系统相结合，以减少载体制剂中污染性辅助病毒的量。在另一个实施方案中，本发明用于载体生长。

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