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31. 发明申请

US20120094922A1 SCREENING ASSAYS FOR AGENTS THAT ALTER INHIBITOR OF APOPTOSIS (IAP) PROTEIN REGULATION OF CASPASE ACTIVITY 审中-公开
标题翻译：用于杀虫剂（IAP）蛋白抑制剂对CASPASE活性的抑制剂的筛选测定
公开(公告)号：US20120094922A1
公开(公告)日：2012-04-19
申请号：US13287979
申请日：2011-11-02
申请人： John C. Reed , Quinn Deveraux , Guy S. Salvesen , Ryosuke Takahashi , Natalie Roy
发明人： John C. Reed , Quinn Deveraux , Guy S. Salvesen , Ryosuke Takahashi , Natalie Roy
IPC分类号： A61K38/02 , A61P35/00 , A61P25/28 , C12Q1/37 , G01N33/573
CPC分类号： G01N33/5011 , C12Q1/37 , G01N33/573 , G01N2333/96466 , G01N2500/00 , G01N2500/10 , G01N2510/00
摘要： The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7 or a pro-caspase such as pro-caspase-9, or that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP. The invention further provides methods of reducing the severity of a pathologic condition in an individual by administering to the individual an agent that alters the caspase inhibitory activity of an IAP.
摘要翻译：本发明涉及凋亡抑制剂（IAP）蛋白和细胞死亡蛋白酶半胱天冬酶家族的成员之间的作用，例如，X染色体连接的IAP（XIAP）和半胱天冬酶-3的相互作用，半胱天冬酶-7或胱天蛋白酶-9，其中IAP调节胱天蛋白酶的活性。本发明提供用于鉴定改变IAP如XIAP，c-IAP-1或c-IAP-2和胱天蛋白酶如半胱天冬酶-3或半胱天冬酶-7或前半胱天冬酶的特异性关联的筛选试验， pro-caspase-9，或者在IAP存在下调节胱天蛋白酶的活性，并且通过IAP调节前半胱天冬酶的活化。本发明还提供了通过向个体施用改变IAP的半胱天冬酶抑制活性的试剂来降低个体病理状况的严重性的方法。

32. 发明授权

US08071315B2 Detecting Bcl-B expression in cancer and uses thereof 失效
标题翻译：检测癌症中的Bcl-B表达及其用途
公开(公告)号：US08071315B2
公开(公告)日：2011-12-06
申请号：US12433481
申请日：2009-04-30
申请人： John C. Reed , Maryla Krajewska
发明人： John C. Reed , Maryla Krajewska
IPC分类号： G01N33/53
CPC分类号： G01N33/57484 , C12Q1/6886 , C12Q2600/106 , C12Q2600/118
摘要： Provided herein are compositions and methods of detecting Bcl-B expression in cancer cells to prognose, monitor, or select therapies for cancers such as breast cancer, prostate cancer, lung cancer, or gastric cancer.
摘要翻译：本文提供检测癌细胞中Bcl-B表达以预测，监测或选择癌症如乳腺癌，前列腺癌，肺癌或胃癌的疗法的组合物和方法。

33. 发明申请

US20110183358A1 METHODS AND COMPOSITIONS FOR DEREPRESSION OF IAP-INHIBITED CASPASE 审中-公开
标题翻译：用于抑制IAP抑制CASPASE的方法和组合物
公开(公告)号：US20110183358A1
公开(公告)日：2011-07-28
申请号：US11886385
申请日：2006-03-17
申请人： John C. Reed , Richard A. Houghten , Adel Nefzi , John M. Ostresh , Kate Welsh , Clemencia Pinilla
发明人： John C. Reed , Richard A. Houghten , Adel Nefzi , John M. Ostresh , Kate Welsh , Clemencia Pinilla
IPC分类号： G01N33/53
CPC分类号： C07D207/09 , A61K38/00
摘要： The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.
摘要翻译：本发明提供了具有新化学结构并且作为IAP抑制剂抑制半胱天冬酶具有优异活性的分离剂。本发明还提供了一种去抑制IAP抑制的半胱天冬酶的方法。本发明还提供了使用本发明的标记化合物，特别是荧光标记的化合物的测定方法。

34. 发明授权

US07927816B2 Methods for identifying modulators of apoptosis 失效
标题翻译：识别凋亡调节剂的方法
公开(公告)号：US07927816B2
公开(公告)日：2011-04-19
申请号：US12206670
申请日：2008-09-08
申请人： John C. Reed , Bin Guo
发明人： John C. Reed , Bin Guo
IPC分类号： G01N33/53 , A61K38/00 , C07K14/00
CPC分类号： G01N33/5011 , G01N33/5008 , G01N33/502 , G01N33/5079 , G01N33/5091 , G01N33/566 , G01N2510/00
摘要： The invention provides a method of identifying an effective compound that modulates the binding of Humanin to Bax or Bid. The invention also provides a method of identifying an effective compound that modulates an activity of Bax or Bid. In addition, the invention provides a method of identifying a Humanin-like compound that binds to Bax or Bid or modulates an activity of Bax or Bid, or inhibits the apoptotic activity of Bax or Bid. The invention further provides an isolated polypeptide containing a mitochondrial-derived form of Humanin (SEQ ID NO:3) or a functional fragment thereof where the fragment contains the methionine at position 16 of SEQ ID NO:3.
摘要翻译：本发明提供了鉴定调节人源蛋白与Bax或Bid的结合的有效化合物的方法。本发明还提供了鉴定调节Bax或Bid的活性的有效化合物的方法。此外，本发明提供了鉴定结合Bax或Bid或调节Bax或Bid的活性或抑制Bax或Bid的凋亡活性的人类素样化合物的方法。本发明还提供了含有线粒体衍生形式的人源（SEQ ID NO：3）或其功能片段的分离的多肽，其中该片段含有SEQ ID NO：3的16位的甲硫氨酸。

35. 发明申请

US20110059465A1 SCREENING ASSAYS FOR AGENTS THAT ALTER INHIBITOR OF APOPTOSIS (IAP) PROTEIN REGULATION OF CASPASE ACTIVITY 失效
标题翻译：用于杀虫剂（IAP）蛋白抑制剂对CASPASE活性的抑制剂的筛选测定
公开(公告)号：US20110059465A1
公开(公告)日：2011-03-10
申请号：US12848936
申请日：2010-08-02
申请人： John C. Reed , Quinn Deveraux , Guy S. Salvesen , Ryosuke Takahashi , Natalie Roy
发明人： John C. Reed , Quinn Deveraux , Guy S. Salvesen , Ryosuke Takahashi , Natalie Roy
IPC分类号： G01N33/573 , C12Q1/37
CPC分类号： G01N33/5011 , C12Q1/37 , G01N33/573 , G01N2333/96466 , G01N2500/00 , G01N2500/10 , G01N2510/00
摘要： The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7. The invention also provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a pro-caspase such as pro-caspase-9. In addition, the invention also provides methods for identifying agents that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP. The invention further provides methods of reducing the severity of a pathologic condition in an individual by administering to the individual an agent that alters the caspase inhibitory activity of an IAP. In addition, the invention provides methods of modulating the ability of a population of cells to survive ex vivo by contacting the cells with an agent that alters the caspase inhibitory activity of an IAP in the cells.
摘要翻译：本发明涉及凋亡抑制剂（IAP）蛋白和细胞死亡蛋白酶半胱天冬酶家族的成员之间的作用，例如，X染色体连接的IAP（XIAP）和半胱天冬酶-3的相互作用，半胱天冬酶-7或胱天蛋白酶-9，其中IAP调节胱天蛋白酶的活性。本发明提供用于鉴定改变IAP（诸如XIAP，c-IAP-1或c-IAP-2）和半胱天冬酶（例如半胱天冬酶-3或半胱天冬酶-7）的IAP的特异性缔合的试剂的筛选试验。本发明还提供用于鉴定改变IAP如XIAP，c-IAP-1或c-IAP-2和前半胱天冬酶如前半胱天冬酶-9的特异性关联的试剂的筛选试验。此外，本发明还提供了鉴定在IAP存在下调节半胱天冬酶的活性并且通过IAP调节前半胱天冬酶的活化的试剂的方法。本发明还提供了通过向个体施用改变IAP的半胱天冬酶抑制活性的试剂来降低个体病理状况的严重性的方法。此外，本发明提供了通过使细胞与改变细胞中IAP的半胱天冬酶抑制活性的试剂接触来调节细胞群体离体存活的能力的方法。

36. 发明授权

US07812058B2 Methods and compounds useful to induce apoptosis in cancer cells 有权
标题翻译：用于诱导癌细胞凋亡的方法和化合物
公开(公告)号：US07812058B2
公开(公告)日：2010-10-12
申请号：US10877781
申请日：2004-06-25
申请人： John C. Reed , Maurizio Pellecchia
发明人： John C. Reed , Maurizio Pellecchia
IPC分类号： A01N29/00 , A01N43/00 , A61K31/655
CPC分类号： A61K31/05 , A61K31/02 , A61K31/075 , A61K31/11 , A61K31/216 , A61K31/225 , A61K31/352 , A61K31/52 , A61K45/06 , G01N2500/02 , Y02A50/471 , A61K2300/00
摘要： The present invention provides a method for treating cancer in a mammal comprising contacting the cancer cells with a compound which is a apogossypol, derivative.
摘要翻译：本发明提供了一种用于治疗哺乳动物癌症的方法，包括使癌细胞与作为脱乙酰壳多糖衍生物的化合物接触。

37. 发明授权

US07785900B1 Glutathione beads and GST fusion proteins 有权
标题翻译：谷胱甘肽和GST融合蛋白
公开(公告)号：US07785900B1
公开(公告)日：2010-08-31
申请号：US11652432
申请日：2007-01-11
申请人： Peter C. Simons , Larry A. Sklar , Eric R. Prossnitz , Angela Wandinger-Ness , Mathewos Z. Tessema , John C. Reed , Dayong Zhai
发明人： Peter C. Simons , Larry A. Sklar , Eric R. Prossnitz , Angela Wandinger-Ness , Mathewos Z. Tessema , John C. Reed , Dayong Zhai
IPC分类号： G01N33/543 , G01N33/53
CPC分类号： G01N33/54393 , G01N33/543
摘要： The present invention relates generally to glutathione derivatized beads which are adapted for use in conjunction with glutathione-S-transferase fusion proteins (generally, GST fusion proteins, which contain a fluorescent label such as fluorescent green protein) for use in flow cytometry. The present invention also relates to methods for detecting and/or quantifying interactions between a GST fusion protein and their binding partners, in particular, labeled binding partners such as fluorescently labeled binding partners. By creating glutathione beads with an appropriate high or increased site density, disadvantages often associated with low affinity systems and quick off-rates in solution may be resolved to provide a workable system and method. Methods of identifying potential agonists, antagonists and regulator compounds of proteins fused to GST from libraries of compounds represents another aspect of the present invention.
摘要翻译：本发明一般涉及适用于与流式细胞术中使用的谷胱甘肽-S-转移酶融合蛋白（通常为含有荧光标记如荧光绿蛋白的GST融合蛋白）结合使用的谷胱甘肽衍生化珠粒。本发明还涉及用于检测和/或定量GST融合蛋白与其结合配偶体，特别是标记的结合配偶体如荧光标记的结合配偶体之间的相互作用的方法。通过产生具有适当的高或增加的位点密度的谷胱甘肽珠，可以解决通常与低亲和力系统相关的缺点和解决方案中的快速关闭速率，以提供可行的系统和方法。从化合物文库鉴定与GST融合的蛋白质的潜在激动剂，拮抗剂和调节剂化合物的方法代表本发明的另一方面。

38. 发明申请

US20100028892A1 YEAST BASED EXPRESSION OF PROTEASES AND METHODS OF USE 审中-公开
标题翻译：基于YEAST的表达及其使用方法
公开(公告)号：US20100028892A1
公开(公告)日：2010-02-04
申请号：US12504600
申请日：2009-07-16
申请人： John C. Reed , Hideki Hayashi , Michael Cuddy
发明人： John C. Reed , Hideki Hayashi , Michael Cuddy
IPC分类号： C12Q1/68
CPC分类号： C12N15/1055 , C12N15/1086 , C12N15/81
摘要： This disclosure generally relates to components and methods of using a high throughput screening (HTS) systems for intracellular proteases, using Caspases as a prototype. Genetic systems are disclosed for monitoring exogenous caspase activation pathways in the yeast, Saccharomyces cerevisiae. The yeast-based cellular systems permit facile expression of proteases (e.g., caspase) and protease-activating proteins in combinations that reconstitute entire mammalian pathways in these simple eukaryotes. Among the assay methods integrated into the yeast system are cleavable reporter gene activators, in which protease-mediated cleavage activates a transcription factor. Exemplary systems rely, singly or in concert, on exogenous recombinant caspases and exogenous upstream activators of caspases to cleave a chimeric protein giving rise to a transcription factor which induces the expression of the LacZ and LEU2 genes. The activities of these genes result in colored cultures and impart the ability of the yeast to grow in leucine deficient media. The intensity of the color is measured by colorimetry and quantified with OD units. The OD units are directly proportional to the activity of the caspase in the system. The method of quantification is referred to as the “readout”.
摘要翻译：本公开通常涉及使用胱天蛋白酶作为原型的细胞内蛋白酶的高通量筛选（HTS）系统的组件和方法。公开了用于监测酵母，酿酒酵母中的外源半胱天冬酶活化途径的遗传系统。基于酵母的细胞系统允许在这些简单真核生物中重组整个哺乳动物途径的组合，容易地表达蛋白酶（例如胱天蛋白酶）和蛋白酶活化蛋白。整合到酵母系统中的测定方法中是可裂解的报告基因激活因子，其中蛋白酶介导的切割激活转录因子。示例性系统单独或一致地依赖于外源重组胱天蛋白酶和胱天蛋白酶的外源上游激活剂以切割嵌合蛋白，产生诱导LacZ和LEU2基因表达的转录因子。这些基因的活性导致有色培养物，并赋予酵母在亮氨酸缺乏培养基中生长的能力。通过比色法测量颜色的强度并用OD单位定量。 OD单位与系统中半胱天冬酶的活性成正比。定量方法被称为“读出”。

39. 发明授权

US07638324B2 Bcl-G polypeptides, encoding nucleic acids and methods of use 失效
标题翻译： Bcl-G多肽，编码核酸和使用方法
公开(公告)号：US07638324B2
公开(公告)日：2009-12-29
申请号：US09738396
申请日：2000-12-14
申请人： John C. Reed , Adam Godzik , Bin Guo
发明人： John C. Reed , Adam Godzik , Bin Guo
IPC分类号： C07H21/02 , C07H21/04 , C12Q1/68 , C12N5/00 , A61K31/70
CPC分类号： C07K7/08 , C07K7/06 , C07K14/4747 , C07K2319/00
摘要： The invention provides Bcl-G polypeptides and encoding nucleic acids. Bcl-G polypeptides include Bcl-GL and Bcl-GS. The invention also provides mouse Bcl-G. The invention also provides vectors containing Bcl-G nucleic acids, host cells containing such vectors, Bcl-G anti-sense nucleic acids and related compositions. The invention additionally provides Bcl-G oligonucleotides that can be used to hybridize to or amplify a Bcl-G nucleic acid. Anti-Bcl-G specific antibodies are also provided. Further provided are kits containing Bcl-G nucleic acids or Bcl-G specific antibodies. Such kits and reagents can be used to diagnose cancer, monitor response to therapy, or predict the prognosis of a cancer patient. The invention additionally provides methods of modulating apoptosis using Bcl-G polypeptides, encoding nucleic acids, or compounds that modulate the activity or expression of Bcl-G polypeptides. The methods for modulating apoptosis can be used to treat diseases such as cancer.
摘要翻译：本发明提供了Bcl-G多肽和编码核酸。 Bcl-G多肽包括Bcl-GL和Bcl-GS。本发明还提供了小鼠Bcl-G。本发明还提供含有Bcl-G核酸的载体，含有这些载体的宿主细胞，Bcl-G反义核酸和相关组合物。本发明另外提供可用于与Bcl-G核酸杂交或扩增的Bcl-G寡核苷酸。还提供抗Bcl-G特异性抗体。还提供了含有Bcl-G核酸或Bcl-G特异性抗体的试剂盒。这样的试剂盒和试剂可用于诊断癌症，监测对治疗的反应或预测癌症患者的预后。本发明另外提供了使用调节Bcl-G多肽的活性或表达的Bcl-G多肽，编码核酸或化合物来调节凋亡的方法。调节凋亡的方法可用于治疗癌症等疾病。

40. 发明申请

US20080233638A1 PAAD domain-containing polypeptides, encoding nucleic acids, and methods of use 审中-公开
标题翻译：含PAAD结构域的多肽，编码核酸和使用方法
公开(公告)号：US20080233638A1
公开(公告)日：2008-09-25
申请号：US11977647
申请日：2007-10-24
申请人： John C. Reed , Adam Godzik
发明人： John C. Reed , Adam Godzik
IPC分类号： C12N5/06 , C07H21/04 , C12N15/00 , C12N5/00 , C07K14/435 , C07K16/18
CPC分类号： C07H21/04 , C07K14/4747 , Y10T436/143333
摘要： The invention provides isolated nucleic acid molecules encoding PAAD-domain containing polypeptides and functional fragments thereof, including fragments containing PAAD domains, NACHT domains and ARED domains, encoded polypeptides, and antibodies. Also provided are methods of identifying polypeptides and agents that associate with a PAAD-domain containing polypeptide or fragment thereof, or that alter an association of a PAAD domain-containing polypeptides. Further provided are methods of identifying agents that modulate PAAD domain-mediated inhibition of NFκB activity, or modulate an activity of a NACHT domain of a PAAD domain-containing polypeptide. Also provided are methods of modulating NFκB transcriptional activity in a cell, and methods of altering expression of a PAAD domain-containing polypeptide in a cell.
摘要翻译：本发明提供编码含有PAAD结构域的多肽及其功能片段的分离的核酸分子，包括含有PAAD结构域，NACHT结构域和ARED结构域，编码多肽和抗体的片段。还提供了鉴定与含PAAD结构域的多肽或其片段缔合的多肽和试剂的方法，或改变含PAAD结构域的多肽的缔合。还提供了鉴定调节PAAD结构域介导的NFκB活性抑制或调节含有PAAD结构域的多肽的NACHT结构域的活性的试剂的方法。还提供了调节细胞中NFκB转录活性的方法，以及改变细胞中含有PAAD结构域的多肽的表达的方法。

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