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1.发明授权公开(公告)号：US08722641B2
公开(公告)日：2014-05-13
申请号：US13575492
申请日：2011-01-28
申请人： Michael B. Kastan , Jing Chen
发明人： Michael B. Kastan , Jing Chen
IPC分类号： C07H21/04
CPC分类号： C12N15/1135 , C12N2310/11 , C12N2310/351
摘要： The present invention relates to novel oligonucleotides which comprise p53 5′-UTR sequence TCCCTGG (SEQ ID NO: 1) or the complementary p53 3′-UTR sequence CCAGGGA (SEQ ID NO: 2) and their use for such therapeutic applications as protection of normal tissues from the toxicities of chemical or radiation exposure; reducing tissue damage in hypoxia-reperfusion injury, neurodegenerative disorders, oxidative stress, injuries, hyperthermia; preventing aging; preservation of tissues and organs prior to transplanting, etc.
摘要翻译： 本发明涉及包含p53 5'-UTR序列TCCCTGG（SEQ ID NO：1）或互补p53 3'-UTR序列CCAGGGA（SEQ ID NO：2）的新型寡核苷酸及其在治疗应用中的用途， 正常组织从化学或辐射暴露的毒性; 减少缺氧再灌注损伤中的组织损伤，神经变性障碍，氧化应激，损伤，高热; 防止老化; 移植前保存组织和器官等
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2.发明申请公开(公告)号：US20120302628A1
公开(公告)日：2012-11-29
申请号：US13575492
申请日：2011-01-28
申请人： Michael B. Kastan , Jing Chen
发明人： Michael B. Kastan , Jing Chen
IPC分类号： A61K31/7088 , C12N5/071 , C07H21/04
CPC分类号： C12N15/1135 , C12N2310/11 , C12N2310/351
摘要： The present invention relates to novel oligonucleotides which comprise p53 5′-UTR sequence TCCCTGG (SEQ ID NO: 1) or the complementary p53 3′-UTR sequence CCAGGGA (SEQ ID NO: 2) and their use for such therapeutic applications as protection of normal tissues from the toxicities of chemical or radiation exposure; reducing tissue damage in hypoxia-reperfusion injury, neurodegenerative disorders, oxidative stress, injuries, hyperthermia; preventing aging; preservation of tissues and organs prior to transplanting, etc.
摘要翻译： 本发明涉及包含p53 5'-UTR序列TCCCTGG（SEQ ID NO：1）或互补p53 3'-UTR序列CCAGGGA（SEQ ID NO：2）的新型寡核苷酸及其在治疗应用中的用途， 正常组织从化学或辐射暴露的毒性; 减少缺氧再灌注损伤中的组织损伤，神经变性障碍，氧化应激，损伤，高热; 防止老化; 移植前保存组织和器官等
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公开(公告)号：US08933043B2
公开(公告)日：2015-01-13
申请号：US12063463
申请日：2006-09-28
IPC分类号： C12N15/11 , A61K48/00 , C12N15/113
CPC分类号： C12N15/1135 , C12N2310/11 , C12N2310/12 , C12N2310/14 , C12N2310/15
摘要： The present invention relates to novel methods for modulating the activity of p53 tumor suppressor protein by affecting p53 translational regulation. More specifically, the invention relates to novel methods for modulating p53 mRNA translation in a cell by affecting a function of a p53 5′-untranslated region (5′UTR), including its interaction with proteins such as Ribosomal Protein L26 (RPL26), nucleolin, and p53. The invention also relates to the use of these methods for treating cancer, neurodegenerative disorders and minimizing the negative effects of cellular stresses.
摘要翻译： 本发明涉及通过影响p53翻译调节来调节p53肿瘤抑制蛋白活性的新方法。 更具体地，本发明涉及通过影响p53 5'-非翻译区（5'UTR）的功能来调节细胞中p53 mRNA翻译的新方法，包括其与诸如核糖体蛋白L26（RPL26），核仁素 ，和p53。 本发明还涉及这些方法用于治疗癌症，神经变性疾病和使细胞应激的负面影响最小化的用途。
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4.发明授权
公开(公告)号：US5616463A
公开(公告)日：1997-04-01
申请号：US288872
申请日：1994-08-10
IPC分类号： C07K14/47 , C07K16/18 , C12N5/22 , C12Q1/68 , G01N33/573 , G01N33/574 , G01N33/68 , C07H21/02
CPC分类号： C07K16/18 , C07K14/47 , C12Q1/6809 , C12Q1/6886 , G01N33/573 , G01N33/57496 , G01N33/68 , G01N33/6893 , C12Q2600/158 , G01N2333/47
摘要： The dependence of ionizing radiation-induced GADD45 mRNA expression on the presence of functional p53 in mammalian cells is disclosed. First and second oligonucleotide sequences are provided which can form a double-stranded oligomer capable of binding to functional p53 protein. The present invention demonstrates that the dependence of ionizing radiation-induced GADD45 mRNA expression on the presence of functional p53 and the binding of functional p53 to a double-stranded oligomer binding sequence can serve as the basis for methods for determining the presence of functional p53 in mammalian cell lines and tumors.
摘要翻译： 公开了电离辐射诱导的GADD45mRNA表达对哺乳动物细胞中功能性p53存在的依赖性。 提供可以形成能够结合功能性p53蛋白质的双链寡聚物的第一和第二寡核苷酸序列。 本发明证明电离辐射诱导的GADD45mRNA表达对功能性p53的存在和功能性p53与双链寡聚体结合序列的结合的依赖性可以作为确定功能性p53存在的方法的基础 哺乳动物细胞系和肿瘤。
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公开(公告)号：US07108992B2
公开(公告)日：2006-09-19
申请号：US10307077
申请日：2002-11-27
IPC分类号： C07K16/40 , G01N33/573
CPC分类号： G01N33/6812 , A61K31/4706 , A61K31/675 , C07K16/40 , C12Q1/485 , G01N33/6842 , G01N33/6893 , G01N2800/52
摘要： The present invention provides methods for detecting activation of ATM kinase, DNA damage, and DNA damaging agents. Further provided are antibodies which specifically recognize the phosphorylation state of Ataxia Telangiectasia-Mutated (ATM) kinase. Methods of identifying agents which modulate the activation and activity of ATM kinase are also provided.
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公开(公告)号：US06916627B2
公开(公告)日：2005-07-12
申请号：US10351733
申请日：2003-01-24
IPC分类号： A61K31/4706 , A61K31/675 , C07K16/40 , C12N5/071 , C12Q1/48 , G01N33/68 , C12N9/12 , G01N33/53 , G01N33/567 , G01N3/537 , G01N3/543
CPC分类号： A61K31/4706 , A61K31/675 , C07K16/40 , C12N5/0602 , C12N2501/06 , C12N2501/999 , C12Q1/485 , G01N33/6812 , G01N33/6842 , G01N33/6893 , G01N2800/52 , Y02A50/411
摘要： The present invention provides methods for detecting activation of ATM kinase, DNA damage, and DNA damaging agents. Further provided are antibodies which specifically recognize the phosphorylation state of Ataxia Telangiectasia-Mutated (ATM) kinase. Methods of identifying agents which modulate the activation and activity of ATM kinase are also provided.
摘要翻译： 本发明提供了检测ATM激酶，DNA损伤和DNA损伤剂活化的方法。 还提供了特异性识别共济失调血管扩张突变（ATM）激酶的磷酸化状态的抗体。 还提供了鉴定调节ATM激酶活化和活性的试剂的方法。
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7.发明授权Method for determining the presence of functional p53 by measuring GADD45 protein expression 失效通过测量GADD45蛋白表达来确定功能性p53的存在的方法
公开(公告)号：US5858679A
公开(公告)日：1999-01-12
申请号：US432176
申请日：1995-05-10
IPC分类号： C07K14/47 , C07K16/18 , C12N5/22 , C12Q1/68 , G01N33/573 , G01N33/574 , G01N33/68 , G01N33/53
CPC分类号： C07K16/18 , C07K14/47 , C12Q1/6809 , C12Q1/6886 , G01N33/573 , G01N33/57496 , G01N33/68 , G01N33/6893 , C12Q2600/158 , G01N2333/47
摘要： The dependence of ionizing radiation-induced GADD45 mRNA and protein expression on the presence of functional p53 in mammalian cells is disclosed. First and second oligonucleotide sequences are provided which can form a double-stranded oligomer capable of binding to functional p53 protein. The present invention demonstrates that the dependence of ionizing radiation-induced GADD45 mRNA and protein expression on the presence of functional p53 and the binding of functional p53 to a double-stranded oligomer binding sequence can serve as the bases for methods for determining the presence of functional p53 in mammalian cell lines and tumors.
摘要翻译： PCT No.PCT / US93 / 11026 Sec。 371日期：1995年5月10日 102（e）日期1995年5月10日PCT提交1993年11月12日PCT公布。 公开号WO94 / 11533 日期1994年5月26日公开了电离辐射诱导的GADD45 mRNA和蛋白质表达对哺乳动物细胞中功能性p53存在的依赖性。 提供可以形成能够结合功能性p53蛋白质的双链寡聚物的第一和第二寡核苷酸序列。 本发明证明电离辐射诱导的GADD45 mRNA和蛋白质表达对功能性p53的存在的依赖性和功能性p53与双链寡聚体结合序列的结合可以作为确定功能性p53存在的方法的基础 p53在哺乳动物细胞系和肿瘤中的表达。
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公开(公告)号：US08440695B2
公开(公告)日：2013-05-14
申请号：US12093198
申请日：2006-10-31
IPC分类号： A61K31/47
CPC分类号： A61K31/4706 , A61K45/06 , Y02A50/411
摘要： The present invention provides methods and compositions for modulating certain metabolic processes and for treating a variety of disorders associated with metabolic syndrome, including insulin related disorders, ischemia, oxidative stress, atherosclerosis, hypertension, obesity, abnormal lipid metabolism, and stroke by administering an effective dose of a chloroquine compound. The invention also provides methods and compositions relating to administering an effective dose of a chloroquine compound in combination with at least a second pharmaceutically active ingredient or compound including an antihyperglycemic diabetes treatment, an antihypertensive agent, an antithrombotic agent, and/or an inhibitor of cholesterol synthesis or absorption.
摘要翻译： 本发明提供用于调节某些代谢过程和用于治疗与代谢综合征相关的多种疾病，包括胰岛素相关病症，缺血，氧化应激，动脉粥样硬化，高血压，肥胖，异常脂质代谢和中风的方法和组合物， 剂量的氯喹化合物。 本发明还提供了与至少第二药物活性成分或化合物组合施用有效剂量的氯喹化合物的方法和组合物，所述药物活性成分或化合物包括抗高血糖糖尿病治疗，抗高血压药，抗血栓形成剂和/或胆固醇抑制剂 合成或吸收。
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公开(公告)号：US20090149377A1
公开(公告)日：2009-06-11
申请号：US12063463
申请日：2006-09-28
CPC分类号： C12N15/1135 , C12N2310/11 , C12N2310/12 , C12N2310/14 , C12N2310/15
摘要： The present invention relates to novel methods for modulating the activity of p53 tumor suppressor protein by affecting p53 translational regulation. More specifically, the invention relates to novel methods for modulating p53 mRNA translation in a cell by affecting a function of a p53 5′-untranslated region (5′UTR), including its interaction with proteins such as Ribosomal Protein L26 (RPL26), nucleolin, and p53. The invention also relates to the use of these methods for treating cancer, neurodegenerative disorders and minimizing the negative effects of cellular stresses.
摘要翻译： 本发明涉及通过影响p53翻译调节来调节p53肿瘤抑制蛋白活性的新方法。 更具体地，本发明涉及通过影响p53 5'-非翻译区（5'UTR）的功能来调节细胞中p53 mRNA翻译的新方法，包括其与诸如核糖体蛋白L26（RPL26），核仁素 ，和p53。 本发明还涉及这些方法用于治疗癌症，神经变性疾病和使细胞应激的负面影响最小化的用途。
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公开(公告)号：US07279290B2
公开(公告)日：2007-10-09
申请号：US11285841
申请日：2005-11-23
CPC分类号： A61K31/4706 , A61K31/675 , C07K16/40 , C12N5/0602 , C12N2501/06 , C12N2501/999 , C12Q1/485 , G01N33/6812 , G01N33/6842 , G01N33/6893 , G01N2800/52 , Y02A50/411
摘要： The present invention provides methods for detecting activation of ATM kinase, DNA damage, and DNA damaging agents. Further provided are antibodies which specifically recognize the phosphorylation state of Ataxia Telangiectasia-Mutated (ATM) kinase. Methods of identifying agents which modulate the activation and activity of ATM kinase are also provided.
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