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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

US5824544A Adenovirus vectors for gene therapy 失效
公开(公告)号：US5824544A
公开(公告)日：1998-10-20
申请号：US540077
申请日：1995-10-06
申请人： Donna Armentano , Helen Romanczuk , Samuel Charles Wadsworth
发明人： Donna Armentano , Helen Romanczuk , Samuel Charles Wadsworth
IPC分类号： C12N15/09 , A61K35/76 , A61K48/00 , C07K14/47 , C12N15/00 , C12N15/12 , C12N15/861 , C12R1/92
CPC分类号： C12N15/86 , C07K14/4712 , A61K48/00 , C12N2710/10343
摘要： The present invention relates to novel adenovirus vectors for use in gene therapy which are designed to prevent the generation of replication-competent adenovirus (RCA) during in vitro propagation and clinical use. The invention also provides methods for the production of the novel virus vectors. These vectors maximize safety for clinical applications in which adenovirus vectors are used to transfer genes into recipient cells for gene therapy.

3. 发明申请

US20080070297A1 REGULATORY ELEMENTS FOR DELIVERY TO THE LIVER 审中-公开
标题翻译：向肝脏递送的法规要素
公开(公告)号：US20080070297A1
公开(公告)日：2008-03-20
申请号：US11938906
申请日：2007-11-13
申请人： David SOUZA , Donna ARMENTANO , Samuel WADSWORTH
发明人： David SOUZA , Donna ARMENTANO , Samuel WADSWORTH
IPC分类号： C12N15/861 , C12N15/11
CPC分类号： C12N15/86 , A61K48/00 , A61K48/0058 , C12N15/85 , C12N2710/10343 , C12N2799/022 , C12N2830/008 , C12N2830/15 , C12N2830/85
摘要： The invention is directed to novel combinations of liver specific enhancers and promoter elements for achieving persistent transgene expression in the liver. The liver specific enhancer elements may be derived from either the human serum albumin, prothrombin, α-1microglobulin or aldolase genes in single copies or in multimerized from linked to elements derived from the cytomegalovirus intermediate early (CMV), α-1-antitrypsin or albumin promoters. In a preferred embodiment of the invention, an adenoviral vector comprising a liver specific enhancer/promoter combination operably linked to a transgene is administered to recipient cells. In other embodiments of the invention, adeno-associated viral vectors, retroviral vectors, lentiviral vectors or a plasmid comprising the liver specific enhancer/promoter combination linked to a transgene is administered to recipient cells. Also within the scope of the invention are promoter elements derived from the human prothrombin gene and the β-fibrinogen gene.
摘要翻译：本发明涉及用于实现肝脏中持续转基因表达的肝特异性增强子和启动子元件的新型组合。肝脏特异性增强子元件可以衍生自单拷贝中的人血清白蛋白，凝血酶原，α-1微球蛋白或醛缩酶基因，或与源自巨细胞病毒中间体早期（CMV），α-1-抗胰蛋白酶或白蛋白的元件连接的多聚化发起人。在本发明的优选实施方案中，向受体细胞施用包含可操作地连接到转基因的肝特异性增强子/启动子组合的腺病毒载体。在本发明的其它实施方案中，将腺相关病毒载体，逆转录病毒载体，慢病毒载体或包含与转基因连接的肝特异性增强子/启动子组合的质粒施用于受体细胞。也在本发明范围内的是源自人凝血酶原基因和β-纤维蛋白原基因的启动子元件。

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

US08758761B2 Combination therapies for treating type 1 diabetes 有权
标题翻译：用于治疗1型糖尿病的联合疗法
公开(公告)号：US08758761B2
公开(公告)日：2014-06-24
申请号：US12680614
申请日：2008-09-30
申请人： Mark A. Atkinson , Scott Eisenbeis , Donna Armentano , Abraham Scaria , Tracey Lodie
发明人： Mark A. Atkinson , Scott Eisenbeis , Donna Armentano , Abraham Scaria , Tracey Lodie
IPC分类号： A61K39/00 , A61K39/38
CPC分类号： A61K39/39541 , A61K31/436 , A61K35/28 , A61K38/193 , A61K38/26 , A61K45/06 , A61K2300/00
摘要： In accordance with the subject invention, combination therapies can be used to modulate a patient's immune response in order to prevent, delay and/or reverse type 1 diabetes.
摘要翻译：根据本发明，组合疗法可用于调节患者的免疫应答，以防止，延迟和/或逆转1型糖尿病。

7. 发明申请

US20090162345A1 Materials and Methods for Reversing Type-1 Diabetes 审中-公开
标题翻译： 1型糖尿病逆转材料与方法
公开(公告)号：US20090162345A1
公开(公告)日：2009-06-25
申请号：US12094866
申请日：2006-11-29
申请人： Mark A. Atkinson , Gregory Simon , Clive Henry Wasserfall , Abraham Scaria , Desmond A. Schatz , Donna Armentano , Srinivas Shankara
发明人： Mark A. Atkinson , Gregory Simon , Clive Henry Wasserfall , Abraham Scaria , Desmond A. Schatz , Donna Armentano , Srinivas Shankara
IPC分类号： A61K39/395 , A61P3/10
CPC分类号： C07K16/28 , A61K39/39541 , A61K2039/505 , A61K2300/00
摘要： In accordance with the subject invention, anti-thymocyte globulin (ATG) can be used to modulate a patient's immune response in order to prevent and/or delay the onset or the progression of type 1 diabetes. ATG treatment augments CD4+CD25+ cell frequencies and their functional activities.
摘要翻译：根据本发明，抗胸腺细胞球蛋白（ATG）可用于调节患者的免疫应答，以预防和/或延缓1型糖尿病的发病或进展。 ATG治疗增加CD4 + CD25 +细胞频率及其功能活动。

8. 发明申请

US20050107318A1 Methods of treating diabetes and other blood sugar disorders 审中-公开
标题翻译：治疗糖尿病和其他血糖障碍的方法
公开(公告)号：US20050107318A1
公开(公告)日：2005-05-19
申请号：US10715976
申请日：2003-11-17
申请人： Samuel Wadsworth , Donna Armentano , Richard Gregory , Geoffrey Parsons
发明人： Samuel Wadsworth , Donna Armentano , Richard Gregory , Geoffrey Parsons
IPC分类号： A61K48/00 , C12N15/861
CPC分类号： C12N15/86 , A61K48/00 , A61K48/005 , C12N2710/10343 , C12N2830/002 , C12N2830/85
摘要： Evidence is emerging that lipid accumulation in the liver and the muscle contributes to insulin resistance in type II diabetes and the metabolic syndrome (1). This has prompted an investigation of the relationship between lipid accumulation in the liver, serum triglyceride levels, and glucose disposal. These studies demonstrate that liver fat positively correlated to fasting triglyceride levels and negatively correlated to glucose diposal (2). Therefore, strategies to prevent lipid accumulation in liver would have therapeutic value for treatment of type II diabetes, metabolic syndrome and non-alcoholic fatty liver disease. The invention described here relates to continuous administration of GLP-1 or its analogs obtained by either gene or cell therapy that results in reduction serum triglycerides and reduction of lipid accumulation in the liver for treatment of type II diabetes, the metabolic syndrome or non-alcoholic fatty liver disease.
摘要翻译：证据表明肝脏和肌肉中的脂质积累有助于II型糖尿病和代谢综合征中的胰岛素抵抗（1）。这有助于调查肝脏脂质积累，血清甘油三酯水平和葡萄糖处置之间的关系。这些研究表明，肝脏脂肪与空腹甘油三酯水平呈正相关，与葡萄糖二次分泌呈负相关（2）。因此，预防肝脏脂质积聚的策略对治疗II型糖尿病，代谢综合征和非酒精性脂肪性肝病具有治疗价值。本文描述的发明涉及通过基因或细胞疗法获得的GLP-1或其类似物的连续施用，其导致血清甘油三酯的降低和肝脏中脂质积聚的减少以用于治疗II型糖尿病，代谢综合征或非酒精性脂肪肝病。

9. 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。

10. 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。

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