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1. 发明公开

EP0812204A1 CODOMINANCE-MEDIATED TOXINS 失效
标题翻译：共显性控制毒素
公开(公告)号：EP0812204A1
公开(公告)日：1997-12-17
申请号：EP96907881.0
申请日：1996-02-28
申请人： Varshavsky, Alexander
发明人： Varshavsky, Alexander
IPC分类号： C12N15 , A61K38 , A61K48 , A61P35 , C07K19
CPC分类号： C07K19/00 , C07K2319/09 , C07K2319/55 , C07K2319/95 , C12N15/62
摘要： Disclosed is a new class of therapeutic reagents referred to as codominance-mediated toxins. These reagents include (1) an effector domain; (2) a first codominant signaling moiety located proximately to a binding domain for a first protein; and (3) a second codminant signaling moiety located proximately to a binding domain for a second protein. The ability to mask and unmask the signaling moiety by the binding of intracellurar reagents, and the codominance of signaling moieties are exploited to design a novel class of reagents having previously unattainable selectivity.

2. 发明公开

EP0812204A4 CODOMINANCE-MEDIATED TOXINS 失效
标题翻译：共显性控制毒素
公开(公告)号：EP0812204A4
公开(公告)日：2000-05-03
申请号：EP96907881
申请日：1996-02-28
申请人： VARSHAVSKY ALEXANDER
发明人： VARSHAVSKY ALEXANDER
IPC分类号： C12N15/09 , A61K38/43 , A61K48/00 , A61P35/00 , C07K19/00 , C12N15/62 , A61K38/00 , C07H17/00 , C07K14/00 , C12N5/00 , C12N15/00 , C12P21/06
CPC分类号： C07K19/00 , C07K2319/09 , C07K2319/55 , C07K2319/95 , C12N15/62
摘要： Disclosed is a new class of therapeutic reagents referred to as codominance-mediated toxins. These reagents include (1) an effector domain; (2) a first codominant signaling moiety located proximately to a binding domain for a first protein; and (3) a second codminant signaling moiety located proximately to a binding domain for a second protein. The ability to mask and unmask the signaling moiety by the binding of intracellurar reagents, and the codominance of signaling moieties are exploited to design a novel class of reagents having previously unattainable selectivity.

3. 发明申请

WO2003079999A3 MODULATION OF ANGIOGENESIS THROUGH TARGETING OF ARGINYL TRANSFERASE (ATE1) 审中-公开
公开(公告)号：WO2003079999A3
公开(公告)日：2003-10-02
申请号：PCT/US2003/009061
申请日：2003-03-21
申请人： CALIFORNIA INSTITUTE OF TECHNOLOGY , KWON, Young, Tae , KASHINA, Anna, S. , VARSHAVSKY, Alexander
发明人： KWON, Young, Tae , KASHINA, Anna, S. , VARSHAVSKY, Alexander
IPC分类号： A61K339/38
摘要： The invention provides methods and compositions for modulating angiogenesis in a subject. The methods of modulating angiogenesis in a subject include administering to the subject a modulator of N-terminal arginylation activity. The invention also provides a method of identifying such a modulator and a method of in vitro screening for modulators of N-terminal arginylation activity. Additionally, the invention provides a method of treating an angiogenesis-related disorder.

4. 发明申请

WO2003079999A2 MODULATION OF ANGIOGENESIS THROUGH TARGETING OF ARGINYL TRANSFERASE (ATE1) 审中-公开
标题翻译：通过ARGINYL转移靶向调节血管生成（ATE1）
公开(公告)号：WO2003079999A2
公开(公告)日：2003-10-02
申请号：PCT/US2003/009061
申请日：2003-03-21
申请人： CALIFORNIA INSTITUTE OF TECHNOLOGY , KWON, Young, Tae , KASHINA, Anna, S. , VARSHAVSKY, Alexander
发明人： KWON, Young, Tae , KASHINA, Anna, S. , VARSHAVSKY, Alexander
IPC分类号： A61K
CPC分类号： C12Q1/48 , G01N2333/515 , G01N2500/00 , G01N2500/04 , G01N2500/10
摘要： The invention provides methods and compositions for modulating angiogenesis in a subject. The methods of modulating angiogenesis in a subject include administering to the subject a modulator of N-terminal arginylation activity. The invention also provides a method of identifying such a modulator and a method of in vitro screening for modulators of N-terminal arginylation activity. Additionally, the invention provides a method of treating an angiogenesis-related disorder.
摘要翻译：本发明提供了调节受试者血管生成的方法和组合物。调节受试者血管生成的方法包括向受试者施用N-末端精氨酰化活性的调节剂。本发明还提供鉴定这种调节剂的方法和一种体外筛选N-末端精氨酰化活性调节剂的方法。另外，本发明提供了治疗血管发生相关病症的方法。

5. 发明申请

WO2011088421A3 DISCOVERY AND APPLICATIONS OF THE PROTEOLYTIC FUNCTION OF N-TERMINAL ACETYLATION OF CELLULAR PROTEINS 审中-公开
标题翻译：细胞蛋白N-末端乙酰化蛋白质功能的发现与应用
公开(公告)号：WO2011088421A3
公开(公告)日：2011-11-10
申请号：PCT/US2011021432
申请日：2011-01-14
申请人： CALIFORNIA INST OF TECHN , HWANG CHEOL-SANG , SHEMORRY ANNA , VARSHAVSKY ALEXANDER
发明人： HWANG CHEOL-SANG , SHEMORRY ANNA , VARSHAVSKY ALEXANDER
IPC分类号： C12Q1/48 , C12N9/10
CPC分类号： C12Q1/48 , G01N2333/91045 , G01N2500/02 , G01N2500/10
摘要： Screening assays that allow for the identification of agents that modulate the activity of N -terminal acetylation of a polypeptide arid the Doa10 branch of the N-end rule pathway are provided. Also provided are methods of using an agent that modulates the activity of N- terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway to increase or decrease protein degradation in a cell, and to modulate physiologic and pathologic associated with N-terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway.
摘要翻译：提供了允许鉴定调节多肽的N-端乙酰化活性和N端规则途径的Doa10分支的试剂的筛选试验。还提供了使用调节多肽的N末端乙酰化活性和N末端规则途径的Doa10分支的活性剂以增加或减少细胞中的蛋白质降解以及调节与N 多肽的N-末端乙酰化和N-末端规则途径的Doa10分支。

6. 发明申请

WO2011088421A2 DISCOVERY AND APPLICATIONS OF THE PROTEOLYTIC FUNCTION OF N-TERMINAL ACETYLATION OF CELLULAR PROTEINS 审中-公开
标题翻译：蛋白质N-末端乙酰化的蛋白质功能的发现和应用
公开(公告)号：WO2011088421A2
公开(公告)日：2011-07-21
申请号：PCT/US2011/021432
申请日：2011-01-14
申请人： CALIFORNIA INSTITUTE OF TECHNOLOGY , HWANG, Cheol-Sang , SHEMORRY, Anna , VARSHAVSKY, Alexander
发明人： HWANG, Cheol-Sang , SHEMORRY, Anna , VARSHAVSKY, Alexander
CPC分类号： C12Q1/48 , G01N2333/91045 , G01N2500/02 , G01N2500/10
摘要： Screening assays that allow for the identification of agents that modulate the activity of N -terminal acetylation of a polypeptide arid the Doa10 branch of the N-end rule pathway are provided. Also provided are methods of using an agent that modulates the activity of N- terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway to increase or decrease protein degradation in a cell, and to modulate physiologic and pathologic associated with N-terminal acetylation of a polypeptide and the Doa10 branch of the N-end rule pathway.
摘要翻译：提供了允许鉴定调节多肽的N-末端乙酰化活性的试剂的筛选试验，以及N端规则途径的Doa10分支。还提供了使用调节多肽的N-末端乙酰化活性和N端规则途径的Doa10分支以增加或减少细胞中的蛋白质降解并调节与N相关的生理和病理学的试剂的方法 - 末端乙酰化多肽和N端规则途径的Doa10分支。

7. 发明申请

WO2009012170A1 TARGETING THE ABSENCE: HOMOZYGOUS DNA DELETIONS AS SIGNPOSTS FOR CANCER THERAPY 审中-公开
标题翻译：指定绝食：作为癌症治疗的标志的嗜酒DNA脱氧核糖核酸
公开(公告)号：WO2009012170A1
公开(公告)日：2009-01-22
申请号：PCT/US2008/069850
申请日：2008-07-11
申请人： CALIFORNIA INSTITUTE OF TECHNOLOGY , VARSHAVSKY, Alexander
发明人： VARSHAVSKY, Alexander
IPC分类号： C12N15/09 , A61K48/00
CPC分类号： C12N15/85 , A61K48/00 , C12N2810/00 , C12Q1/6886
摘要： The present application relates to methods and compositions for targeting a homozygous DNA deletion (HD) in cells. Methods, structures, vectors and compositions for activating a payload in cells having an HD are provided. In some embodiments, the methoJ comprises administering, to a population of cells comprising at least one cell having an HD, a nucleic acid vector encoding two complementary protein fusion molecules and a payload such that the payload is selectively activated only in cells having a HD. HDs are attractive "negative" targets for cancer therapy because of their immutability and prevalence in cancer cells. Thus, in some embodiments methods of treating cancer by specifically delivering a payload, such as a toxin, to cancer cells comprising one or more particular HDs are provided.
摘要翻译：本申请涉及靶向细胞中纯合DNA缺失（HD）的方法和组合物。提供了用于激活具有HD的单元中的有效载荷的方法，结构，载体和组合物。在一些实施方案中，所述方法包括向包含至少一个具有HD的细胞的细胞群体施用编码两种互补蛋白质融合分子的核酸载体和有效载荷，使得所述有效载荷仅在具有HD的细胞中选择性地激活。 HD是癌症治疗的有吸引力的“阴性”靶标，因为它们在癌细胞中的不变性和流行性。因此，在一些实施方案中，提供了通过将包含一种或多种特定HD的癌细胞特异性递送有效载荷（例如毒素）来治疗癌症的方法。

8. 发明申请

WO0212902A3 SPLIT-UBIQUITIN BASED REPORTER SYSTEMS AND METHODS OF THEIR USE 审中-公开
标题翻译：基于分布式UBIQUITIN的报告器系统及其使用方法
公开(公告)号：WO0212902A3
公开(公告)日：2003-03-27
申请号：PCT/US0141621
申请日：2001-08-06
申请人： MAX PLANCK GESELLSCHAFT , VARSHAVSKY ALEXANDER , WITTKE SANDRA , JOHNSSON NILS , LEHMING NORBERT
发明人： VARSHAVSKY ALEXANDER , WITTKE SANDRA , JOHNSSON NILS , LEHMING NORBERT
IPC分类号： C07H21/04 , C07K14/00 , C12N9/64 , C12P21/04 , C12Q1/68 , C40B30/04 , G01N33/542 , G01N33/68 , C07K19/00 , C12N15/62 , C12N15/63 , C12Q1/00 , G01N33/53
CPC分类号： C40B30/04 , C07K14/00 , G01N33/542 , G01N33/6818 , G01N33/6845 , G01N2500/10
摘要： Methods and reagents for the detection and selection of two interacting-polypeptides, especially integral membrane proteins and transcription factors, by monitoring the reassembly of ubiquitin amino-terminal and carboxy-terminal chimeric polypeptide fragments are disclosed. Negative selection against an N-end rule-labilized marker released following ubiquiting reassembly allows direct selection of the interacting polypeptide pair. Methods to identify agonists and antagonists for certain protein-protein interactions; methods and reagents/kits for identifying proteins that binds a target protein are also provided. The dynamic and adaptable nature of the assay allows adaptation to a number of applications - such as probing the molecular environment of cellular membrane proteins in vivo.
摘要翻译：公开了通过监测泛素氨基末端和羧基末端嵌合多肽片段的重新组装来检测和选择两种相互作用多肽，特别是整合膜蛋白和转录因子的方法和试剂。在完成重组后释放的N端规则生化标记物的负选择允许直接选择相互作用的多肽对。识别某些蛋白质 - 蛋白质相互作用的激动剂和拮抗剂的方法; 还提供了用于鉴定结合靶蛋白的蛋白质的方法和试剂/试剂盒。该测定的动态和适应性质允许适应许多应用 - 例如在体内探测细胞膜蛋白的分子环境。

9. 发明申请

WO1996026733A1 CODOMINANCE-MEDIATED TOXINS 审中-公开
标题翻译：编码介导的毒素
公开(公告)号：WO1996026733A1
公开(公告)日：1996-09-06
申请号：PCT/US1996002271
申请日：1996-02-28
申请人： VARSHAVSKY, Alexander
IPC分类号： A61K38/00
CPC分类号： C07K19/00 , C07K2319/09 , C07K2319/55 , C07K2319/95 , C12N15/62
摘要： Disclosed is a new class of therapeutic reagents referred to as codominance-mediated toxins. These reagents include (1) an effector domain; (2) a first codominant signaling moiety located proximately to a binding domain for a first protein; and (3) a second codminant signaling moiety located proximately to a binding domain for a second protein. The ability to mask and unmask the signaling moiety by the binding of intracellurar reagents, and the codominance of signaling moieties are exploited to design a novel class of reagents having previously unattainable selectivity.
摘要翻译：公开了一类称为共价介导毒素的治疗试剂。这些试剂包括（1）效应结构域; （2）位于第一蛋白质的结合结构域附近的第一共显性信号传导部分; 和（3）位于第二蛋白质的结合结构域附近的第二传染性信号传导部分。通过胞内试剂的结合掩蔽和揭示信号传导部分的能力以及信号传导部分的共同性被开发以设计具有先前无法获得的选择性的新一类试剂。

10. 发明申请

WO2006071717A1 APPARATUS AND METHOD FOR ANALYZING CROSS-ENTERPRISE RADIO FREQUENCY TAG INFORMATION 审中-公开
标题翻译：用于分析跨企业无线电频率标签信息的装置和方法
公开(公告)号：WO2006071717A1
公开(公告)日：2006-07-06
申请号：PCT/US2005/046547
申请日：2005-12-22
申请人： T3C, INC. , SWAN, Richard, James , MOHAN, Shantha , SUN, David , VARSHAVSKY, Alexander , MOHANRAM, Karthik
发明人： SWAN, Richard, James , MOHAN, Shantha , SUN, David , VARSHAVSKY, Alexander , MOHANRAM, Karthik
IPC分类号： G06Q30/00
CPC分类号： G06Q10/08
摘要： A computer readable medium including executable instructions to analyze radio frequency (RF) tag information includes executable instruction to access cross-enterprise RF tag information, identify a product transition based upon the cross-enterprise RF tag information, and define a new product path based upon the product transition, where the new product path defines product pedigree information. Additional executable instructions authenticate a user, secure product information, supply product pedigree information corresponding to the product information, and verify the pedigree of the product based upon the product pedigree information.
摘要翻译：包括用于分析射频（RF）标签信息的可执行指令的计算机可读介质包括访问跨企业RF标签信息的可执行指令，基于跨企业RF标签信息识别产品转换，并且基于产品过渡，新产品路径定义产品血统信息。额外的可执行指令验证用户，安全的产品信息，提供与产品信息相对应的产品系谱信息，并根据产品血统信息验证产品的血统。

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