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1. 发明授权

US06358507B1 Transgene expression systems 失效
标题翻译：转基因表达系统
公开(公告)号：US06358507B1
公开(公告)日：2002-03-19
申请号：US09416673
申请日：1999-10-12
申请人： Johanne Kaplan , Donna Armentano , Richard J. Gregory
发明人： Johanne Kaplan , Donna Armentano , Richard J. Gregory
IPC分类号： A61K4800
CPC分类号： C12N15/86 , A61K38/1709 , A61K48/00 , C12N2710/10322 , C12N2710/10343
摘要： The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E40RF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or “E4 cassette”) includes E40RF3 and at least one other portion selected from E40RF4, E40RF6/7 and E40RF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.
摘要翻译：本发明涉及转基因表达系统，包含转基因表达系统的相关组合物，以及制备和使用它们的方法。优选的系统使用腺病毒转基因表达载体，其包含编码转基因的DNA，所述转基因编码与表达控制序列可操作地连接的所需产物，以及腺病毒E3区域的至少一部分和E4区域的某些部分。 E4部分包括被称为E40RF3的开放阅读框序列和E4的至少一个其他部分。优选地，载体（或“E4盒”）的E4部分包括E40RF3和至少一个选自E40RF4，E40RF6 / 7和E40RF3 / 4的其它部分。本发明具有许多重要特征，包括改善所需宿主细胞中转基因表达的持续性。本发明的转基因表达系统可用于各种应用，包括在体外和体内提供转基因的持续细胞表达。

2. 发明授权

US06485720B2 Transgene expression systems 失效
公开(公告)号：US06485720B2
公开(公告)日：2002-11-26
申请号：US09924925
申请日：2001-08-08
申请人： Johanne Kaplan , Donna Armentano , Richard J. Gregory
发明人： Johanne Kaplan , Donna Armentano , Richard J. Gregory
IPC分类号： A61K4800
CPC分类号： C12N15/86 , A61K38/1709 , A61K48/00 , C12N2710/10322 , C12N2710/10343
摘要： The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or “E4 cassette”) includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

3. 发明授权

US6100086A Transgene expression systems 失效
标题翻译：转基因表达系统
公开(公告)号：US6100086A
公开(公告)日：2000-08-08
申请号：US839679
申请日：1997-04-14
申请人： Johanne Kaplan , Donna Armentano , Richard J. Gregory
发明人： Johanne Kaplan , Donna Armentano , Richard J. Gregory
IPC分类号： C12N15/09 , A61K35/76 , A61K38/17 , A61K48/00 , A61P11/00 , C12N15/861 , C12N15/86 , C07J9/00
CPC分类号： C12N15/86 , A61K38/1709 , A61K48/00 , C12N2710/10322 , C12N2710/10343
摘要： The present invention relates to transgene expression systems, related pharmaceutical compositions, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA sequence encoding a transgene which codes for a desired product, expressibly contained within an adenovirus vector containing at least a portion of the E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or "E4 cassette") includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.
摘要翻译：本发明涉及转基因表达系统，相关药物组合物及其制备和使用方法。优选的系统采用腺病毒转基因表达载体，其包含编码所需产物的转基因的DNA序列，其表达地包含在含有E3区的至少一部分和E4区的某些部分的腺病毒载体中。 E4部分包括被称为E4ORF3的开放阅读框序列和E4的至少一个其他部分。优选地，载体（或“E4盒”）的E4部分包括E4ORF3和至少一个选自E4ORF4，E4ORF6 / 7和E4ORF3 / 4的其它部分。本发明具有许多重要特征，包括改善所需宿主细胞中转基因表达的持续性。本发明的转基因表达系统可用于各种应用，包括在体外和体内提供转基因的持续细胞表达。

4. 发明授权

US5877011A Chimeric adenoviral vectors 失效
标题翻译：嵌合腺病毒载体
公开(公告)号：US5877011A
公开(公告)日：1999-03-02
申请号：US752760
申请日：1996-11-20
申请人： Donna Armentano , Richard J. Gregory , Alan E. Smith
发明人： Donna Armentano , Richard J. Gregory , Alan E. Smith
IPC分类号： C12N15/09 , A61K48/00 , C07K14/075 , C12N15/861 , C12N15/86
CPC分类号： C12N15/86 , C07K14/005 , C12N2710/10322 , C12N2710/10343 , C12N2810/6018
摘要： A chimeric adenoviral vector is provided that comprises nucleotide sequence of a first adenovirus, wherein at least one gene of said first adenovirus encoding a protein that facilitates binding of said vector to a target mammalian cell, or internalization thereof within said cell, is replaced by the corresponding gene from a second adenovirus belonging to subgroup D, said vector further comprising a transgene operably linked to a eucaryotic promoter to allow for expression therefrom in a mammalian cell. Additionally, a method of delivering transgenes to target mammalian cells, particularly airway epithelial cells, is provided.
摘要翻译：提供了包含第一腺病毒的核苷酸序列的嵌合腺病毒载体，其中编码促进所述载体与靶哺乳动物细胞结合的蛋白质的所述第一腺病毒的至少一个基因或其在所述细胞内的内化被替换为来自属于亚组D的第二腺病毒的相应基因，所述载体还包含可操作地连接到真核启动子以在哺乳动物细胞中从其中表达的转基因。另外，提供了将转基因递送至靶哺乳动物细胞，特别是气道上皮细胞的方法。

5. 发明授权

US5670488A Adenovirus vector 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：US5670488A
公开(公告)日：1997-09-23
申请号：US136742
申请日：1993-10-13
申请人： Richard J. Gregory , Donna Armentano , Larry A. Couture , Alan E. Smith
发明人： Richard J. Gregory , Donna Armentano , Larry A. Couture , Alan E. Smith
IPC分类号： A61K38/00 , A61K48/00 , C07K14/47 , C12N15/861 , C12N15/00
CPC分类号： C12N15/86 , A61K48/00 , C07K14/4712 , A61K38/00 , C12N2710/10343 , C12N2830/42 , C12N2840/203
摘要： Gene Therapy vectors, which are especially useful for cystic fibrosis, and methods for using the vectors are disclosed.
摘要翻译：公开了对囊性纤维化特别有用的基因治疗载体和使用载体的方法。

6. 发明授权

US5981275A Transgene expression system for increased persistence 失效
标题翻译：转基因表达系统增加持久性
公开(公告)号：US5981275A
公开(公告)日：1999-11-09
申请号：US839552
申请日：1997-04-14
申请人： Donna Armentano , John Marshall , Nelson S. Yew , Seng H. Cheng , Richard J. Gregory
发明人： Donna Armentano , John Marshall , Nelson S. Yew , Seng H. Cheng , Richard J. Gregory
IPC分类号： C12N15/09 , A61K35/76 , A61K48/00 , A61P11/00 , C07K14/47 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/861 , C12N15/00
CPC分类号： C12N15/86 , C07K14/4712 , A61K48/00 , C12N2710/10343 , C12N2830/00 , C12N2830/15 , C12N2830/42 , C12N2830/60 , C12N2830/85
摘要： The invention is directed to a transgene expression system comprising a transcription unit which contains a transgene operably linked to expression control sequences, preferably the CMV promoter, and which is delivered simultaneously with all or part of the adenovirus E4 genomic region to a cell in order to facilitate persistent expression of the transgene. The components of the transgene expression system can be delivered by vectors including plasmids and/or viruses and may be complexed with cationic amphiphiles to facilitate entry into a cell. The invention is also directed to methods for the production of the transgene expression system. The invention is further directed to compositions that contain the transgene expression system and to methods for the use of such compositions to deliver transgenes encoding biologically active proteins to cells.
摘要翻译：本发明涉及包含转录单元的转基因表达系统，该转录单元含有可操作地连接到表达调控序列，优选CMV启动子的转基因，并且其与全部或部分腺病毒E4基因组区域同时递送至细胞，以便促进转基因的持续表达。转基因表达系统的组分可以通过包括质粒和/或病毒的载体递送，并且可以与阳离子两亲物复合以便于进入细胞。本发明还涉及生产转基因表达系统的方法。本发明还涉及含有转基因表达系统的组合物以及使用这种组合物将编码生物活性蛋白质的转基因递送至细胞的方法。

7. 发明授权

US6093567A Gene therapy for cystic fibrosis 有权
标题翻译：基因治疗囊性纤维化
公开(公告)号：US6093567A
公开(公告)日：2000-07-25
申请号：US248026
申请日：1999-02-10
申请人： Richard J. Gregory , Donna Armentano , Larry A. Couture , Alan E. Smith
发明人： Richard J. Gregory , Donna Armentano , Larry A. Couture , Alan E. Smith
IPC分类号： A61K38/00 , A61K48/00 , C07K14/47 , C12N15/861
CPC分类号： C12N15/86 , A61K48/00 , C07K14/4712 , A61K38/00 , C12N2710/10343 , C12N2830/42 , C12N2840/203
摘要： Gene Therapy vectors, which are especially useful for cystic fibrosis, and methods for using the vectors are disclosed.
摘要翻译：公开了对囊性纤维化特别有用的基因治疗载体和使用载体的方法。

8. 发明授权

US5882877A Adenoviral vectors for gene therapy containing deletions in the adenoviral genome 失效
标题翻译：用于在腺病毒基因组中含有缺失的基因治疗的腺病毒载体
公开(公告)号：US5882877A
公开(公告)日：1999-03-16
申请号：US895194
申请日：1997-07-16
申请人： Richard J. Gregory , Donna Armentano , Larry A. Couture , Alan E. Smith
发明人： Richard J. Gregory , Donna Armentano , Larry A. Couture , Alan E. Smith
IPC分类号： A61K38/00 , A61K48/00 , C07K14/47 , C12N15/861 , C12N15/00 , C12N15/86
CPC分类号： C12N15/86 , A61K48/00 , C07K14/4712 , A61K38/00 , C12N2710/10343 , C12N2830/42 , C12N2840/203
摘要： Adenoviral vectors which contain deletions of the early regions and/or late genes provide efficient delivery and expression of foreign nucleic acids of interest to patients. These vectors have a particular use in the treatment of cystic fibrosis patients. Furthermore, PAV vectors provide for a second generation of adenoviral vectors that contain the 5' ITR's, the packaging signal and the E1A enhancer. Other adenoviral vectors contain a deletion of the E1 region or a deletion of E4 but retain orf3 or orf6, and can either retain or delete the E3 region.
摘要翻译：含有早期区域和/或晚期基因缺失的腺病毒载体提供对患者感兴趣的外来核酸的有效递送和表达。这些载体在囊性纤维化患者的治疗中具有特别的用途。此外，PAV载体提供含有5'ITR，包装信号和E1A增强子的第二代腺病毒载体。其他腺病毒载体含有E1区的缺失或E4的缺失，但保留orf3或orf6，并且可以保留或删除E3区。

9. 发明申请

US20090082289A1 Adenoviral vectors having a protein IX deletion 审中-公开
标题翻译：具有蛋白质IX缺失的腺病毒载体
公开(公告)号：US20090082289A1
公开(公告)日：2009-03-26
申请号：US11800036
申请日：2007-05-02
申请人： Richard J. Gregory , Ken N. Wills , Daniel C. Maneval
发明人： Richard J. Gregory , Ken N. Wills , Daniel C. Maneval
IPC分类号： A61K48/00 , A61P35/00
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10332 , C12N2710/10343 , C12N2830/008 , C12N2830/85
摘要： This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention.Thus, for example, the adenoviral vector of this invention- can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).
摘要翻译：本发明提供一种重组腺病毒表达载体，其特征在于部分或完全缺失腺病毒蛋白IX DNA并具有编码外来蛋白或其功能片段或突变体的基因。转化的宿主细胞和生产重组蛋白和基因治疗的方法也包括在本发明的范围内。因此，例如，本发明的腺病毒载体可以含有外源基因，用于表达有效调节细胞周期的蛋白质，例如p53，Rb或mitosin，或诱导细胞死亡，例如有条件的自杀基因胸苷激酶。（后者必须与胸苷激酶代谢物结合使用才能有效）。

10. 发明授权

US06432927B1 Compositions and methods for inducing gene expression 有权
标题翻译：诱导基因表达的组合物和方法
公开(公告)号：US06432927B1
公开(公告)日：2002-08-13
申请号：US09579897
申请日：2000-05-26
申请人： Richard J. Gregory , Karen Vincent
发明人： Richard J. Gregory , Karen Vincent
IPC分类号： A61K3170
CPC分类号： C12N15/85 , A61K38/00 , A61K48/00 , C07K14/4702 , C07K14/52 , C07K2319/00 , C07K2319/71 , C07K2319/80 , C12N2799/022
摘要： The present invention provides recombinant nucleic acid molecules encoding a chimeric transactivator protein including a DNA binding domain of a DNA binding protein and a protein domain capable of transcriptional activation. The present invention also provides recombinant viral and non-viral vectors that are able to infect and/or transfect and sustain expression of a biologically active chimeric transactivator proteins in mammalian cells. Also provided are host cell lines and non-human transgenic animals capable of expressing biologically active chimeric transactivator proteins. In another aspect, compositions and methods for treating or preventing ischemic damage associated with hypoxia-related disorders are provided.
摘要翻译：本发明提供了编码嵌合反式激活因子蛋白的重组核酸分子，其包括DNA结合蛋白的DNA结合结构域和能够转录激活的蛋白质结构域。本发明还提供能够感染和/或转染和维持哺乳动物细胞中生物活性嵌合反式激活因子蛋白表达的重组病毒和非病毒载体。还提供了能够表达生物活性嵌合反式激活蛋白的宿主细胞系和非人转基因动物。在另一方面，提供了用于治疗或预防与缺氧相关疾病相关的缺血性损伤的组合物和方法。

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