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1. 发明授权

US6153436A Method of gene delivery using wildtype adeno associated viral (AAV) vectors with insertions 失效
标题翻译：使用具有插入的野生型腺相关病毒（AAV）载体的基因递送方法
公开(公告)号：US6153436A
公开(公告)日：2000-11-28
申请号：US4877
申请日：1998-01-09
申请人： Paul L. Hermonat , J. Gerald Quirk , Brian Bishop , Han Li
发明人： Paul L. Hermonat , J. Gerald Quirk , Brian Bishop , Han Li
IPC分类号： A61K48/00 , C12N15/864 , C12N15/86
CPC分类号： C12N15/86 , A61K48/00 , C12N2750/14143
摘要： The present invention provides a method of human gene therapy using AAV vectors with essentially wildtype phenotype. Genes of 900 bases or less can be inserted into wildtype AAV and still allow the resulting vector to have a largely wildtype phenotype. For example, several antisense genes could be inserted and still allow packaging. Such wildtype vectors have several advantages. First, high titers of such vectors is easy to accomplish. Second, the vectors, since they include the Rep78 gene, integrate specifically into human chromosome 19. Third, such vectors, being wildtype, spread after their initial introduction. Another method for use of large wildtype AAV genomes is as complementors for fully defective AAV vectors. Such complementors can be delivered by virus infection and, be introduced easily into 100% of the cells used to produce virus. Viral infection is superior to synthetic techniques for introducing DNA into tissue culture producer cells. When large essentially wildtype AAV complementor virus are used in conjunction with AAV vector virus allowing for the introduction of both vectors into all cells, high titers of recombinant AAV virus is achieved.
摘要翻译：本发明提供使用基本上野生型表型的AAV载体的人基因治疗方法。将900个碱基以下的基因插入到野生型AAV中，并且仍然允许所得载体具有很大的野生型表型。例如，可以插入几个反义基因并仍然允许包装。这种野生型载体具有几个优点。首先，这种载体的高滴度很容易完成。第二，载体，因为它们包括Rep78基因，特异性整合入人染色体19。第三，这种载体，野生型，在其初次引入后扩散。使用大型野生型AAV基因组的另一种方法是完全缺陷的AAV载体的补体。这样的补体可以通过病毒感染递送，并且容易地引入用于产生病毒的100％的细胞中。病毒感染优于将DNA引入组织培养生产细胞的合成技术。当大的基本野生型AAV补体病毒与AAV载体病毒结合使用时，允许将两种载体引入所有细胞，实现了高效价的重组AAV病毒。

2. 发明授权

US5139941A AAV transduction vectors 失效
标题翻译： AAV转导载体
公开(公告)号：US5139941A
公开(公告)日：1992-08-18
申请号：US785224
申请日：1991-10-25
申请人： Nicholas Muzyczka , Paul L. Hermonat , Kenneth I. Berns , Richard J. Samulski
发明人： Nicholas Muzyczka , Paul L. Hermonat , Kenneth I. Berns , Richard J. Samulski
IPC分类号： C12N15/864
CPC分类号： C12N15/86 , C12N2750/14143
摘要： A hybrid gene vector suitable for introducing foreign DNA into a mammalian cell comprising the foreign DNA ligated to an AAV genome; a method of constructing the hybrid gene vector; a method of transducing foreign DNA into mammalian cells comprising infecting the cells with the above hybrid gene vector and a method of rescuing foreign DNA from mammalian cells utilizing helper virus.
摘要翻译：一种适用于将外源DNA引入哺乳动物细胞的杂交基因载体，其包含与AAV基因组连接的外源DNA; 构建杂交基因载体的方法; 将外源DNA转导入哺乳动物细胞的方法，包括用上述杂交基因载体感染细胞，以及利用辅助病毒从哺乳动物细胞中拯救外来DNA的方法。

3. 发明申请

US20110213018A1 COMPOSITIONS AND METHODS FOR REGULATION OF SMOOTH MUSCLE CELLS AND BLOOD PRESSURE 有权
标题翻译：用于调节平滑肌细胞和血压的组合物和方法
公开(公告)号：US20110213018A1
公开(公告)日：2011-09-01
申请号：US13051508
申请日：2011-03-18
申请人： Sung W. Rhee , Paul L. Hermonat , Nancy J. Rusch
发明人： Sung W. Rhee , Paul L. Hermonat , Nancy J. Rusch
IPC分类号： A61K31/7088 , C12N15/85 , C12N15/861 , A61P9/00 , A61P7/00
CPC分类号： C07K14/705 , A61K48/005 , A61K48/0058 , C12N15/86 , C12N2750/14143 , C12N2830/008
摘要： The invention encompasses a composition for regulating smooth muscle cells. In particular, the invention encompasses a vector comprising a smooth muscle promoter operably-linked to a nucleic acid encoding a calcium-activated potassium channel.
摘要翻译：本发明包括用于调节平滑肌细胞的组合物。特别地，本发明包括载体，其包含与编码钙激活的钾通道的核酸可操作地连接的平滑肌促进剂。

4. 发明申请

US20080199434A1 COMPOSITIONS AND METHODS FOR THE TREATMENT OF CARDIOVASCULAR CONDITIONS 审中-公开
标题翻译：用于治疗心血管病症的组合物和方法
公开(公告)号：US20080199434A1
公开(公告)日：2008-08-21
申请号：US11938992
申请日：2007-11-13
申请人： Jawahar L. Mehta , Paul L. Hermonat , Jiawei Chen , Chang-Ping Hu , Abhijit Dandapat , Yong Liu
发明人： Jawahar L. Mehta , Paul L. Hermonat , Jiawei Chen , Chang-Ping Hu , Abhijit Dandapat , Yong Liu
IPC分类号： A61K48/00 , A61P9/10 , C12Q1/68 , G01N33/53 , A61K31/711 , A61K31/7105
CPC分类号： A61K31/7105 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0375 , A61K31/711 , A61K48/0058 , C07K14/705 , C07K14/723 , C12N15/8509 , C12N2799/025 , C12N2830/008 , G01N33/6893 , G01N2333/705 , G01N2800/32
摘要： The present invention provides methods and compositions for treating a cardiovascular condition. In particular, provided is a method comprising administering to a subject an agent that increases the level and/or activity of angiotensin II type 2 receptors. Also provided is a method for evaluating the risk of having or developing a cardiovascular condition
摘要翻译：本发明提供了治疗心血管病症的方法和组合物。特别地，提供了一种方法，其包括向受试者施用增加血管紧张素II 2型受体的水平和/或活性的试剂。还提供了评估患有或发展心血管疾病的风险的方法

5. 发明授权

US08227445B2 Methods of treating hypertension 有权
标题翻译：治疗高血压的方法
公开(公告)号：US08227445B2
公开(公告)日：2012-07-24
申请号：US13051508
申请日：2011-03-18
申请人： Sung W. Rhee , Paul L. Hermonat , Nancy J. Rusch
发明人： Sung W. Rhee , Paul L. Hermonat , Nancy J. Rusch
IPC分类号： A01K43/04 , A61K31/715 , A61K48/00 , A01N63/00
CPC分类号： C07K14/705 , A61K48/005 , A61K48/0058 , C12N15/86 , C12N2750/14143 , C12N2830/008
摘要： The invention encompasses a composition for regulating smooth muscle cells. In particular, the invention encompasses a vector comprising a smooth muscle promoter operably-linked to a nucleic acid encoding a calcium-activated potassium channel.
摘要翻译：本发明包括用于调节平滑肌细胞的组合物。特别地，本发明包括载体，其包含与编码钙激活的钾通道的核酸可操作地连接的平滑肌促进剂。

6. 发明申请

US20080269159A1 COMPOSITIONS AND METHODS FOR REGULATION OF SMOOTH MUSCLE CELLS AND BLOOD PRESSURE 审中-公开
标题翻译：用于调节平滑肌细胞和血压的组合物和方法
公开(公告)号：US20080269159A1
公开(公告)日：2008-10-30
申请号：US12109756
申请日：2008-04-25
申请人： Sung W. Rhee , Paul L. Hermonat , Nancy J. Rusch
发明人： Sung W. Rhee , Paul L. Hermonat , Nancy J. Rusch
IPC分类号： A61K31/70 , C12N15/00 , A61P9/00
CPC分类号： C07K14/705 , A61K48/005 , A61K48/0058 , C12N15/86 , C12N2750/14143 , C12N2830/008
摘要： The invention encompasses a composition for regulating smooth muscle cells. In particular, the invention encompasses a vector comprising a smooth muscle promoter operably-linked to a nucleic acid encoding a calcium-activated potassium channel.
摘要翻译：本发明包括用于调节平滑肌细胞的组合物。特别地，本发明包括载体，其包含与编码钙激活的钾通道的核酸可操作地连接的平滑肌促进剂。

7. 发明授权

US06506600B2 Secreting products from skin by adeno-associated virus (AAV) gene transfer 失效
公开(公告)号：US06506600B2
公开(公告)日：2003-01-14
申请号：US09813937
申请日：2001-03-22
申请人： Paul L. Hermonat , Michael Mane , Yong Liu
发明人： Paul L. Hermonat , Michael Mane , Yong Liu
IPC分类号： C12N502
CPC分类号： C12N15/86 , C12N2750/14143
摘要： The present invention utilizes AAV as a vector to transfect epithelial cells with an AAV/heterologous gene containing/Neo vector, to form a heterologous protein secreting culture of epithelial cells. This culture is useful for preparing recombinant skin using the organotypic epithelial raft culture system. The sheets of epithelial cells is composed of a stratified sqaumous epithelium composed of a lower layer of immature basal cells and an upper layer of mature keratinized epithelium. The rAAV virus stock prepared without wild type AAV is useful in expressing heterologous protein, however, the maximum production of the heterologous protein was achieved; when the rAAV virus stock contained wild type AAV. This invention discloses that AAV is appropriate for genetically altering skin to secrete new proteins to treat diseases and skin disorders or conditions.

8. 发明申请

US20080145339A1 Adeno-associated virus AAV Rep78 major regulatory protein mutants thereof and uses thereof 审中-公开
公开(公告)号：US20080145339A1
公开(公告)日：2008-06-19
申请号：US10969248
申请日：2004-10-21
申请人： Paul L. Hermonat
发明人： Paul L. Hermonat
IPC分类号： A61K35/76 , C12N7/01 , A61K38/00 , C12N15/00 , C12N15/09 , C12Q1/68 , A61P31/12 , A61K31/70 , C07H21/00 , C07K14/005
CPC分类号： C12N15/86 , A61K38/00 , A61K48/00 , A61K2121/00 , C07K14/005 , C07K2319/00 , C12N2740/16322 , C12N2740/16334 , C12N2750/14122 , C12N2750/14143
摘要： AAV Rep78 mutants comprising a modified AAV Rep78 protein that possesses different biochemical and biological functions as compared to the wild-type AAV Rep78 protein are disclosed. Particularly, the AAV Rep78 mutants that bind to at least one of a papillomavirus DNA or an AAV DNA or an oncogene or HIV DNA differently as compared to the wild-type AAV Rep78 protein, assays to select such mutants, and pharmaceutical compositions containing the AAV Rep78 mutants are disclosed. The present invention further discloses DNA sequences encoding at least one AAV Rep78 mutant that possesses different biochemical and biological functions as compared to the wild-type AAV Rep78 protein and pharmaceutical compositions comprising the DNA sequences. The present invention additionally is directed to a method of inhibiting papillomavirus associated diseases comprising administering pharmaceutical compositions containing AAV Rep78 mutants or the DNA sequences encoding the mutants. Also discloses are DNA sequences comprising the full length AAV genome modified to where the AAV Rep78 protein is replaced with an AAV Rep mutant that binds weakly or not at all to a papillomavirus DNA or an AAV DNA or both differently as compared to the wild-type AAV Rep78 protein and its use in producing recombinant AAV at increased levels production over wild-type levels of production. Further disclosed is a method of inhibiting papillomavirus-associated diseases, cancer, and HIV-associated diseases comprising administering a pharmaceutical composition comprising a wild-type AAV Rep78 or a mutant thereof to a patient afflicted with a papillomavirus-associated disease, cancer, or HIV-associated diseases. Particularly, useful in treating papillomavirus-associated diseases are the AAV Rep78 or mutant thereof that binds to nucleotides 14-56 of p97 of HPV-16 and inhibits expression of HPV oncoproteins. An AAV Rep78 regulation element of a DNA sequence comprising about nucleotides 14-56 of the nucleotide sequence of FIG. 2 and an AAV Rep78 regulatable promoter comprising the regulation element and a promoter sequence except for the HPV-16 p97 promoter.

9. 发明授权

US06884605B2 Compositions, methods and products comprising human papillomavirus for detecting and treating a cancer 失效
标题翻译：包含用于检测和治疗癌症的人乳头瘤病毒的组合物，方法和产品
公开(公告)号：US06884605B2
公开(公告)日：2005-04-26
申请号：US09927585
申请日：2001-08-09
申请人： Paul L. Hermonat , V. Suzanne Klimberg , Yong Liu
发明人： Paul L. Hermonat , V. Suzanne Klimberg , Yong Liu
IPC分类号： A61B10/00 , C12P19/34
CPC分类号： A61B10/0041 , G01N2333/025
摘要： Methods for screening a patient for a cancer wherein the methods comprise detecting an HPV in a biopsy from a patient are disclosed. Also disclosed are compositions and products for screening and for treating cancer in a patient, as well as methods of treating a patient afflicted with a cancer.
摘要翻译：公开了筛选患者癌症的方法，其中所述方法包括从患者的活组织检查中检测HPV。还公开了用于筛选和治疗患者中的癌症的组合物和产品，以及治疗患有癌症的患者的方法。

10. 发明授权

US06495361B1 Method of producing infectious papillomavirus in placental cells 失效
标题翻译：在胎盘细胞中产生感染性乳头状瘤病毒的方法
公开(公告)号：US06495361B1
公开(公告)日：2002-12-17
申请号：US09621579
申请日：2000-07-21
申请人： Paul L. Hermonat , Yong Liu
发明人： Paul L. Hermonat , Yong Liu
IPC分类号： C12N700
CPC分类号： C12Q1/708 , A61K39/00 , C12N7/00 , C12N2710/20051 , G01N2333/025
摘要： The present invention is discloses an improved method of producing infectious papillomavirus in vitro, with a method comprising (a) introducing papillomavirus or papillomavirus DNA or portions thereof necessary for replication, into an epithelial cell; and (b) providing conditions that produce papillomavirus, wherein the conditions comprise not contacting the epithelial cell a fibroblast and does not comprise an organotypic raft culture or a dermal equivalent. The present invention also discloses a papillomavirus infected non-keratinocyte epithelial cell produced by the methods of the present invention. Further, uses of the disclosed method includes detection methods, methods for screening anti-papillomavirus drugs, methods of making recombinant papillomavirus for vaccines and studying the life cycle. Additionally, a method of reducing and assessing the risk of spontaneous abortion is disclosed.
摘要翻译：本发明公开了一种在体外产生感染性乳头瘤病毒的改进方法，其方法包括（a）将乳头状瘤病毒或乳头瘤病毒DNA或其复制所必需的部分引入上皮细胞; 和（b）提供产生乳头瘤病毒的条件，其中所述条件不包括使上皮细胞与成纤维细胞接触，并且不包括器官型筏培养物或皮肤等效物。本发明还公开了通过本发明的方法生产的乳头瘤病毒感染的非角化细胞上皮细胞。此外，所公开的方法的用途包括检测方法，用于筛选抗乳头状瘤病毒药物的方法，制备用于疫苗的重组乳头瘤病毒的方法和研究生命周期。另外，公开了减少和评估自然流产风险的方法。

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