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1. 发明授权

US4714899A Frequency synthesizer 失效
标题翻译：频率合成器
公开(公告)号：US4714899A
公开(公告)日：1987-12-22
申请号：US913426
申请日：1986-09-30
申请人： Gary Kurtzman , Joseph P. Heck , Kenneth A. Hansen , Ralph Enderby , Bronis Vidugiris
发明人： Gary Kurtzman , Joseph P. Heck , Kenneth A. Hansen , Ralph Enderby , Bronis Vidugiris
IPC分类号： H03C3/09 , H03L7/193 , H03L7/06 , H03L7/10
CPC分类号： H03C3/0991 , H03C3/0925 , H03C3/0933 , H03L7/193
摘要： A programmable frequency synthesizer is disclosed having most components implemented on a single large scale integration (LSI) chip, which facilitates rapid frequency acquisition. Provision is made by the present invention to configure the frequency synthesizer for use in either a receiver or a transmitter. In the transmitter mode, modulation cancelling allows modulation down to approximate DC. A serial programming protocol is provided to program the frequency synthesizer.
摘要翻译：公开了一种可编程频率合成器，其中大多数组件实现在单个大规模集成（LSI）芯片上，这有助于快速频率采集。本发明提出了配置用于接收机或发射机的频率合成器。在发射机模式下，调制消除允许调制到近似直流。提供串行编程协议来对频率合成器进行编程。

2. 发明申请

US20060099185A1 Methods of treating anemia using recombinant adeno-associated virus virions 审中-公开
标题翻译：使用重组腺相关病毒粒子治疗贫血的方法
公开(公告)号：US20060099185A1
公开(公告)日：2006-05-11
申请号：US11305629
申请日：2005-12-15
申请人： Gregory Podsakoff , Gary Kurtzman
发明人： Gregory Podsakoff , Gary Kurtzman
IPC分类号： A61K48/00
CPC分类号： C12N15/86 , A01K2217/05 , A61K38/1816 , A61K38/47 , A61K48/00 , A61K48/0058 , A61K48/0075 , C07K14/505 , C12N9/2402 , C12N2750/14143 , C12N2830/42 , C12N2840/44 , C12Y302/0102 , C12Y302/01023 , Y10S514/814 , Y10S514/815
摘要： The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue in the treatment of anemia is disclosed, The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of a delivered nucleotide sequence encoding erythropoietin, and for in vivo secretion thereof from transduced muscle cells such that systemic delivery is achieved.
摘要翻译：公开了使用重组腺相关病毒（AAV）病毒粒子将DNA分子递送到肌肉细胞和组织以治疗贫血症。本发明允许将重组AAV病毒体直接体内注射入肌肉组织，例如，通过肌内注射，以及肌肉细胞的体外转导，随后可以将其引入受试者进行治疗。本发明提供了编码促红细胞生成素的递送核苷酸序列的持续高水平表达，以及用于体内从转导的肌肉细胞分泌，从而实现全身递送。

3. 发明授权

US5843742A Adeno-associated derived vector systems for gene delivery and integration into target cells 失效
标题翻译：用于基因递送和整合入靶细胞的腺相关衍生载体系统
公开(公告)号：US5843742A
公开(公告)日：1998-12-01
申请号：US525835
申请日：1995-09-08
申请人： Georges Natsoulis , Gary Kurtzman
发明人： Georges Natsoulis , Gary Kurtzman
IPC分类号： C12N15/09 , C07K14/755 , C12N5/10 , C12N15/864 , C12N15/10
CPC分类号： C12N15/86 , C07K14/755 , C12N2750/14143
摘要： A novel nucleotide sequence integration and targeting system is described. The system employs adeno-associated virus (AAV) derived vectors which include a selected nucleotide sequence bounded by AAV inverted terminal repeats (ITRs). An AAV rep coding region is also provided, enabling the targeted integration of the selected nucleotide sequence into the genome of a suitable target cell. The nucleotide sequence integration system of the present invention can deliver and integrate large segments of DNA into the genome of target cells. Further, the subject integration system provides the advantage of site-specific integration of the selected nucleotide sequences in a target cell genome, thereby avoiding insertional mutagenesis events experienced with prior systems.
摘要翻译：描述了一种新的核苷酸序列整合和靶向系统。该系统使用腺相关病毒（AAV）衍生载体，其包括由AAV反向末端重复（ITR）限定的选定核苷酸序列。还提供了AAV代码编码区，使得能够将选择的核苷酸序列靶向整合到合适的靶细胞的基因组中。本发明的核苷酸序列整合体系可以将大片段的DNA递送并整合到靶细胞的基因组中。此外，受试者整合系统提供了选择的核苷酸序列在靶细胞基因组中的位点特异性整合的优点，从而避免了现有系统经历的插入突变事件。

4. 发明申请

US20080069803A1 Methods for delivering DNA to muscle cells using recombinant adeno-associated virus virions vectors 审中-公开
标题翻译：使用重组腺相关病毒载体向DNA递送肌肉细胞的方法
公开(公告)号：US20080069803A1
公开(公告)日：2008-03-20
申请号：US11980214
申请日：2007-10-30
申请人： Gregory Podsakoff , Paul Kessler , Barry Byrne , Gary Kurtzman
发明人： Gregory Podsakoff , Paul Kessler , Barry Byrne , Gary Kurtzman
IPC分类号： A61K48/00 , C12N15/63 , C12N15/861 , C12N5/00 , C12N7/01
CPC分类号： C12N15/86 , A01K2217/05 , A61K38/1816 , A61K38/47 , A61K48/00 , A61K48/0075 , C07K14/505 , C12N9/2408 , C12N2750/14143 , C12N2799/025 , C12N2830/42 , C12N2840/44 , C12Y302/0102 , C12Y302/01023
摘要： The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of the delivered gene and for in vivo secretion of the therapeutic protein from transduced muscle cells such that systemic delivery is achieved.
摘要翻译：公开了使用重组腺相关病毒（AAV）病毒颗粒将DNA分子递送至肌肉细胞和组织。本发明允许将重组AAV病毒体直接，体内注射到肌肉组织中，例如通过肌内注射，以及肌肉细胞的体外转导，随后可将其导入受试者进行治疗。本发明提供所传递的基因的持续高水平表达以及用于体内分泌来自转导的肌细胞的治疗性蛋白质，从而实现全身递送。

5. 发明申请

US20060216274A1 Induction of immune response to antigens expressed by recombinant adeno-associated virus 审中-公开
公开(公告)号：US20060216274A1
公开(公告)日：2006-09-28
申请号：US11199903
申请日：2005-08-09
申请人： Gary Kurtzman , Edgar Engelman , Greg Podsakoff , Dirk Brockstedt
发明人： Gary Kurtzman , Edgar Engelman , Greg Podsakoff , Dirk Brockstedt
IPC分类号： A61K48/00 , A61K39/21
CPC分类号： C12N15/86 , A61K39/0008 , A61K39/0011 , A61K2039/5256 , A61K2039/53 , A61K2039/57 , C12N2750/14143 , C12N2840/44
摘要： The present invention relates generally to immunization methods using recombinant viral vectors. In particular, the invention relates to methods and compositions for immunizing a subject with a nucleic acid molecule encoding an antigen of interest, wherein the nucleic acid molecule is delivered to the subject via a recombinant AAV virion.

6. 发明授权

US6027931A High-efficiency AA V helper functions 失效
标题翻译：高效AA V辅助功能
公开(公告)号：US6027931A
公开(公告)日：2000-02-22
申请号：US107708
申请日：1998-06-30
申请人： George Natsoulis , Peter Colosi , Gary Kurtzman
发明人： George Natsoulis , Peter Colosi , Gary Kurtzman
IPC分类号： C07K14/015 , C12N5/10 , C12N7/04 , C12N15/864 , C12N7/01 , C12N15/86
CPC分类号： C12N15/86 , C07K14/005 , C12N7/00 , C07K2319/00 , C12N2750/14122 , C12N2750/14143 , C12N2750/14152 , C12N2750/14162 , C12N2800/30 , C12N2840/20
摘要： The present invention provides methods and compositions for producing high titer preparations of recombinant AAV ("rAAV") virions. The compositions of the present invention include AAV helper function systems and host cells. The present invention also includes methods of using AAV helper function vectors that effect the production of only small amounts of the long forms of Rep protein, and rAAV virions produced by such methods.
摘要翻译：本发明提供了用于生产重组AAV（“rAAV”）病毒粒子的高效价制剂的方法和组合物。本发明的组合物包括AAV辅助功能体系和宿主细胞。本发明还包括使用影响仅产生少量Rep形式的Rep蛋白的AAV辅助功能载体的方法和通过这些方法产生的rAAV病毒体。

7. 发明申请

US20060099184A1 Methods for delivering DNA to muscle cells using recombinant adeno-associated virus virions vectors 审中-公开
标题翻译：使用重组腺相关病毒载体向DNA递送肌肉细胞的方法
公开(公告)号：US20060099184A1
公开(公告)日：2006-05-11
申请号：US11303896
申请日：2005-12-15
申请人： Gregory Podsakoff , Paul Kessler , Barry Byrne , Gary Kurtzman
发明人： Gregory Podsakoff , Paul Kessler , Barry Byrne , Gary Kurtzman
IPC分类号： A61K48/00 , C12N15/861
CPC分类号： C12N15/86 , A01K2217/05 , A61K38/1816 , A61K38/47 , A61K48/00 , A61K48/0075 , C07K14/505 , C12N9/2408 , C12N2750/14143 , C12N2799/025 , C12N2830/42 , C12N2840/44 , C12Y302/0102 , C12Y302/01023
摘要： The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of the delivered gene and for in vivo secretion of the therapeutic protein from transduced muscle cells such that systemic delivery is achieved.
摘要翻译：公开了使用重组腺相关病毒（AAV）病毒颗粒将DNA分子递送至肌肉细胞和组织。本发明允许将重组AAV病毒体直接，体内注射到肌肉组织中，例如通过肌内注射，以及肌肉细胞的体外转导，随后可将其导入受试者进行治疗。本发明提供所传递的基因的持续高水平表达以及用于体内分泌来自转导的肌细胞的治疗性蛋白质，从而实现全身递送。

8. 发明申请

US20060003453A1 High-efficiency AAV helper functions 审中-公开
公开(公告)号：US20060003453A1
公开(公告)日：2006-01-05
申请号：US11222108
申请日：2005-09-08
申请人： Georges Natsoulis , Gary Kurtzman , Peter Colosi
发明人： Georges Natsoulis , Gary Kurtzman , Peter Colosi
IPC分类号： C12N7/02 , C12N15/861
CPC分类号： C12N15/86 , C07K14/005 , C07K2319/00 , C12N7/00 , C12N2750/14122 , C12N2750/14143 , C12N2750/14152 , C12N2750/14162 , C12N2800/30 , C12N2840/20
摘要： The present invention provides methods and compositions for producing high titer preparations of recombinant AAV (“rAAV”) virions. The compositions of the present invention include AAV helper function systems and host cells. The present invention also includes methods of using AAV helper function vectors that effect the production of only small amounts of the long forms of Rep protein, and rAAV virions produced by such methods.

9. 发明申请

US20070030034A1 Wide linear range peak detector 有权
标题翻译：宽线性范围峰值检测器
公开(公告)号：US20070030034A1
公开(公告)日：2007-02-08
申请号：US11199493
申请日：2005-08-08
申请人： Gary Kurtzman , Steven Hoggarth
发明人： Gary Kurtzman , Steven Hoggarth
IPC分类号： H03K5/153
CPC分类号： G01R19/04
摘要： A wide linear range peak detector including first and second peak detectors and a compensation circuit. The first peak detector receives an input signal and has an output providing a first peak signal approximation which approximates a peak level of the input signal. The first peak signal approximation includes a non-linear portion which is a function of the peak level of the input signal. The second peak detector also receives the input signal and has an output providing a second peak signal approximation. The compensation circuit uses the second peak signal approximation to provide a compensation signal which compensates the non-linear portion of the first peak signal approximation. In particular, the second peak signal is used to generate the compensation signal to approximate and cancel the non-linear portion.
摘要翻译：宽线性范围峰值检测器，包括第一和第二峰值检测器和补偿电路。第一峰值检测器接收输入信号并具有提供近似输入信号的峰值电平的第一峰值信号近似的输出。第一峰值信号近似包括作为输入信号的峰值电平的函数的非线性部分。第二峰值检测器还接收输入信号并具有提供第二峰值信号近似的输出。补偿电路使用第二峰值信号近似来提供补偿第一峰值信号近似的非线性部分的补偿信号。特别地，第二峰值信号用于产生补偿信号以近似和消除非线性部分。

10. 发明授权

US07115391B1 Production of recombinant AAV using adenovirus comprising AAV rep/cap genes 失效
标题翻译：使用包含AAV rep / cap基因的腺病毒生产重组AAV
公开(公告)号：US07115391B1
公开(公告)日：2006-10-03
申请号：US10089394
申请日：2000-09-29
申请人： Haifeng Chen , Gary Kurtzman
发明人： Haifeng Chen , Gary Kurtzman
IPC分类号： C12P21/06 , C12N15/63 , C12N15/64 , A61K39/12 , A01N63/00
CPC分类号： C12N15/86 , A61K2039/5256 , C12N2710/10344 , C12N2750/14143 , C12N2830/002 , C12N2830/42 , C12N2830/75 , C12N2840/20 , C12N2840/203
摘要： This invention relates to novel adenoviruses useful in the production of high titers of recombinant adeno-associated virus (rAAV) comprising a foreign DNA insert and methods of making these adenoviruses. The adenovirus comprises the AAV rep gene in which the p5 promoter is replaced by a minimal promoter or by no promoter. The invention also provides methods of producing high levels of rAAV as a substantially homogenous preparation and composition of rAAV.
摘要翻译：本发明涉及可用于生产包含外源DNA插入片段的重组腺相关病毒（rAAV）的高滴度的新型腺病毒和制备这些腺病毒的方法。腺病毒包含AAV rep基因，其中p5启动子被最小启动子或无启动子替代。本发明还提供了生产高水平rAAV作为rAAV的基本上均匀的制剂和组成的方法。

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