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1. 发明申请

US20110257036A1 Methods and Compositions for the Diagnosis of Cancer Susceptibilities and Defective DNA Repair Mechanisms and Treatment Thereof 审中-公开
标题翻译：用于诊断癌症易感性和缺陷DNA修复机制及其治疗的方法和组合
公开(公告)号：US20110257036A1
公开(公告)日：2011-10-20
申请号：US12749419
申请日：2010-03-29
申请人： Alan D. D'Andrea , Toshiyasu Taniguchi , Cynthia Timmers , Markus Grompe , Edward A. Fox
发明人： Alan D. D'Andrea , Toshiyasu Taniguchi , Cynthia Timmers , Markus Grompe , Edward A. Fox
IPC分类号： C40B30/06 , G01N33/566 , C12N5/071 , C07K14/47 , C12Q1/02
CPC分类号： G01N33/5011 , A01K2217/05 , A01K2217/075 , C07K14/47 , C07K16/18 , C12Q1/025 , C12Q1/6886 , C12Q2600/156 , C12Q2600/158 , G01N33/5091 , G01N33/574 , G01N33/57484 , G01N33/6893 , G01N2333/47 , G01N2500/00 , G01N2800/52
摘要： Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.
摘要翻译：提供了用于诊断癌症易感性，缺陷DNA修复机制及其治疗的方法和组合物。在这里提供的序列中，已经鉴定了FANCD2基因，并提供了探针和引物，用于筛选基因型测试中的患者和诊断范康尼贫血和癌症。可以在体内靶向FANCD2基因，以制备用于筛选用于治疗涉及有缺陷的DNA修复的病症的新治疗剂的实验小鼠模型。 FANCD2多肽已被测序，已被证明存在于被鉴定为FANCD2-S的两种同种型和单配FANCD-L形式中。已经制备了包括多克隆和单克隆抗体的抗体，其区分两种同种型并且已经用于诊断测试以确定受试者是否具有完整的范可尼贫血/ BRCA途径。

2. 发明授权

US07858331B2 Compositions and methods for the treatment of cancer 有权
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：US07858331B2
公开(公告)日：2010-12-28
申请号：US11441289
申请日：2006-05-24
申请人： Alan D. D'Andrea , Toshiyasu Taniguchi
发明人： Alan D. D'Andrea , Toshiyasu Taniguchi
IPC分类号： G01N33/574
CPC分类号： G01N33/5011 , A01K2217/05 , A01K2217/075 , C07K14/47 , C07K16/18 , C12Q1/6886 , C12Q2600/156 , C12Q2600/158 , G01N33/5091 , G01N33/574 , G01N33/57484 , G01N2500/00 , G01N2500/02
摘要： Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention discloses inhibitors of the Fanconi anemia pathway and methods using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
摘要翻译：本文公开了用于治疗癌症的方法和组合物。特别地，本发明公开了范可尼贫血途径的抑制剂及其使用方法。这样的抑制剂可用于抑制DNA损伤修复，并且可用于例如治疗癌症。

3. 发明授权

US08597900B2 Compositions and methods for the treatment of cancer 有权
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：US08597900B2
公开(公告)日：2013-12-03
申请号：US12950419
申请日：2010-11-19
申请人： Alan D. D'Andrea , Toshiyasu Taniguchi
发明人： Alan D. D'Andrea , Toshiyasu Taniguchi
IPC分类号： G01N33/574
CPC分类号： G01N33/5011 , A01K2217/05 , A01K2217/075 , C07K14/47 , C07K16/18 , C12Q1/6886 , C12Q2600/156 , C12Q2600/158 , G01N33/5091 , G01N33/574 , G01N33/57484 , G01N2500/00 , G01N2500/02
摘要： Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention discloses inhibitors of the Fanconi anemia pathway and methods using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
摘要翻译：本文公开了用于治疗癌症的方法和组合物。特别地，本发明公开了范可尼贫血途径的抑制剂及其使用方法。这样的抑制剂可用于抑制DNA损伤修复，并且可用于例如治疗癌症。

4. 发明申请

US20110151487A1 Compositions And Methods For The Treatment Of Cancer 有权
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：US20110151487A1
公开(公告)日：2011-06-23
申请号：US12950419
申请日：2010-11-19
申请人： Alan D. D'Andrea , Toshiyasu Taniguchi
发明人： Alan D. D'Andrea , Toshiyasu Taniguchi
IPC分类号： G01N33/53 , G01N33/566
CPC分类号： G01N33/5011 , A01K2217/05 , A01K2217/075 , C07K14/47 , C07K16/18 , C12Q1/6886 , C12Q2600/156 , C12Q2600/158 , G01N33/5091 , G01N33/574 , G01N33/57484 , G01N2500/00 , G01N2500/02
摘要： Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention discloses inhibitors of the Fanconi anemia pathway and methods using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
摘要翻译：本文公开了用于治疗癌症的方法和组合物。特别地，本发明公开了范可尼贫血途径的抑制剂及其使用方法。这样的抑制剂可用于抑制DNA损伤修复，并且可用于例如治疗癌症。

5. 发明授权

US08541192B2 Methods to identify USP1 deubiquitinating enzyme complex inhibitors 有权
标题翻译：鉴定USP1去泛素化酶复合物抑制剂的方法
公开(公告)号：US08541192B2
公开(公告)日：2013-09-24
申请号：US12835559
申请日：2010-07-13
申请人： Alan D. D'Andrea
发明人： Alan D. D'Andrea
IPC分类号： C12Q1/37
CPC分类号： G01N33/57496 , C12Q1/37 , G01N33/5011 , G01N2500/00
摘要： The invention provides methods used to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be identified by contacting isolated USP1 with a test compound in the presence of monoubiquitinated proliferating cell nuclear antigen (PCNA), monoubiquitinated human Fanconi anemia group D2 (FANCD2), or ubiquitin-7-amido-4-methylcoumarin, and detecting the deubiquitination of said PCNA, FANCD2, or ubiquitin-7-amido-4-methylcoumarin using an antibody or fluorescence, wherein a decrease in the deubiquitination of said PCNA, FANCD2, or ubiquitin-7-amido-4-methylcoumarin in the presence of the test compound relative to the absence of the test compound identifies said test compound as an inhibitor of USP1 deubiquitinase.
摘要翻译：本发明提供了用于鉴定USP1去泛素酶的新抑制剂的方法。可以通过在单泛素化增殖细胞核抗原（PCNA），单泛素化人范康尼贫血症组D2（FANCD2）或泛素-7-酰氨基-4-甲基香豆素）存在下将分离的USP1与测试化合物接触来鉴定抑制剂，并检测使用抗体或荧光对所述PCNA，FANCD2或泛素-7-酰氨基-4-甲基香豆素进行去泛素化，其中所述PCNA，FANCD2或泛素-7-酰氨基-4-甲基香豆素的去泛素化在测试化合物相对于不存在测试化合物，鉴定所述测试化合物作为USP1去泛素酶的抑制剂。

6. 发明申请

US20110312514A1 Method For Determination And Quantification Of Radiation Or Genotoxin Exposure 有权
标题翻译：辐射或基因毒素暴露的测定和定量方法
公开(公告)号：US20110312514A1
公开(公告)日：2011-12-22
申请号：US13023201
申请日：2011-02-08
申请人： Alan D. D'Andrea
发明人： Alan D. D'Andrea
IPC分类号： G01N33/566 , C40B30/04 , G01N21/64 , C07K16/18 , C12N1/21 , C12N1/15 , C12N1/19 , C07K2/00 , C12N15/12 , C12N5/10
CPC分类号： C07K14/47 , C07K16/18 , G01N33/5014 , G01N2800/52
摘要： The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.
摘要翻译：本发明公开了一种用于检测活体受体对基因毒物的暴露的方法，检测对遗传毒性试剂的敏感性，以及确定由暴露于药剂引起的DNA损伤的方法，包括从所述受试者收集的样品中检测含FANCD2的病灶的存在。浓缩灶的存在表明DNA损伤，并且病灶形成程度与暴露程度相关。诊断试剂含有与可检测标记物相关的人FANCD2结合的配体。用于检测生物样品中DNA损伤的试剂盒含有这样的诊断试剂和信号检测组分。本发明还公开了用于鉴定调节含FANCD2的灶的形成能力的试剂的方法。除此之外，这些试剂是潜在有用的化学增感剂或可以赋予针对由遗传毒性剂引起的损伤的保护。

7. 发明授权

US07910325B2 Method for determination and quantification of radiation or genotoxin exposure 有权
标题翻译：辐射或基因毒素暴露的测定和定量方法
公开(公告)号：US07910325B2
公开(公告)日：2011-03-22
申请号：US12315368
申请日：2008-12-01
申请人： Alan D. D'Andrea
发明人： Alan D. D'Andrea
IPC分类号： G01N33/533 , G01N33/53
CPC分类号： C07K14/47 , C07K16/18 , G01N33/5014 , G01N2800/52
摘要： The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.
摘要翻译：本发明公开了一种用于检测活体受体对基因毒物的暴露的方法，检测对遗传毒性试剂的敏感性，以及确定由暴露于药剂引起的DNA损伤的方法，包括从所述受试者收集的样品中检测含FANCD2的病灶的存在。浓缩灶的存在表明DNA损伤，并且病灶形成程度与暴露程度相关。诊断试剂含有与可检测标记物相关的人FANCD2结合的配体。用于检测生物样品中DNA损伤的试剂盒含有这样的诊断试剂和信号检测组分。本发明还公开了用于鉴定调节含FANCD2的灶的形成能力的试剂的方法。除此之外，这些试剂是潜在有用的化学增感剂或可以赋予针对由遗传毒性剂引起的损伤的保护。

8. 发明申请

US20090081237A1 Prognostic, diagnostic, and cancer therapeutic uses of FANCI and FANCI modulating agents 审中-公开
标题翻译： FANCI和FANCI调节剂的预后，诊断和癌症治疗用途
公开(公告)号：US20090081237A1
公开(公告)日：2009-03-26
申请号：US12075162
申请日：2008-03-10
申请人： Alan D. D'Andrea , Patrizia Vinciguerra , Stephen J. Elledge , Shuhei Matsuoka , Agata M. Smogorzewska , Kay O. Hofmann
发明人： Alan D. D'Andrea , Patrizia Vinciguerra , Stephen J. Elledge , Shuhei Matsuoka , Agata M. Smogorzewska , Kay O. Hofmann
IPC分类号： A61K39/395 , C12Q1/68 , G01N33/53 , C07K14/00 , C07K7/08 , A61P35/00 , C07H21/04 , C12Q1/02
CPC分类号： G01N33/6875 , A61K31/713 , A61K39/3955 , A61K45/06 , C07K16/18 , C12N9/1088 , C12N15/113 , C12Q1/6886 , C12Q2600/118 , C12Q2600/136 , G01N33/5011 , G01N33/574 , G01N33/57415 , G01N2500/10 , G01N2800/50
摘要： Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention identifies and characterizes the FANCI polypeptide as a vital component of the Fanconi anemia pathway and discloses inhibitors of FANCI and methods of using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
摘要翻译：本文公开了用于治疗癌症的方法和组合物。特别地，本发明鉴定并表征FANCI多肽作为范可尼贫血途径的重要组成部分，并公开了FANCI的抑制剂及其使用方法。这样的抑制剂可用于抑制DNA损伤修复，并且可用于例如治疗癌症。

9. 发明授权

US06287858B1 DeUBiquitinating enzymes that regulate cell growth 失效
标题翻译：调节细胞生长的脱辅基酶
公开(公告)号：US06287858B1
公开(公告)日：2001-09-11
申请号：US09019095
申请日：1998-02-05
申请人： Alan D. D'Andrea , Yuan Zhu
发明人： Alan D. D'Andrea , Yuan Zhu
IPC分类号： C12N1585
CPC分类号： C12N9/1088 , A61K38/193 , A61K38/202 , A61K38/2033 , A61K48/00 , C07K2319/00 , C12N9/6472 , C12N2501/70 , Y02P20/582
摘要： The present invention relates to ubiquitin-specific thiol proteases or deubiquitinating enzymes, referred to as DUB (DeUBiquitinating) enzymes, of eukaryotic origin which are members of a superfamily of deubiquitinating enzymes and which comprise a new subfamily of deubiquitinating enzymes which are similar in size and amino acid sequence to one another. DUB enzymes of the present invention are of eukaryotic origin, such as vertebrate origin, including mammalian (e.g., murine, human) origin, as well as yeast origin. All DUB enzymes of the present invention are inducible by at least one cytokine.
摘要翻译：本发明涉及真核生物来源的泛素特异性巯基蛋白酶或脱泛素酶，其是脱辅基酶超家族的成员，并且其包含与小时相似的去泛素化酶的新亚家族氨基酸序列。本发明的DUB酶是真核来源的，例如脊椎动物来源，包括哺乳动物（例如鼠，人）来源以及酵母来源。本发明的所有DUB酶都可被至少一种细胞因子诱导。

10. 发明申请

US20130280258A1 PROGNOSTIC, DIAGNOSTIC, AND CANCER THERAPEUTIC USES OF FANCI AND FANCI MODULATING AGENTS 审中-公开
标题翻译： FANCI和FANCI调节剂的预防，诊断和癌症治疗用途
公开(公告)号：US20130280258A1
公开(公告)日：2013-10-24
申请号：US13413129
申请日：2012-03-06
申请人： Alan D. D'Andrea , Patrizia Vinciguerra , Stephen J. Elledge , Shuhei Matsuoka , Agata M. Smogorzewska , Kay O. Hofmann
发明人： Alan D. D'Andrea , Patrizia Vinciguerra , Stephen J. Elledge , Shuhei Matsuoka , Agata M. Smogorzewska , Kay O. Hofmann
IPC分类号： G01N33/68 , G01N33/50 , C07K16/18 , A61K31/713 , A61K45/06 , C12N9/10 , A61K39/395 , C12Q1/68 , C12N15/113
CPC分类号： G01N33/6875 , A61K31/713 , A61K39/3955 , A61K45/06 , C07K16/18 , C12N9/1088 , C12N15/113 , C12Q1/6886 , C12Q2600/118 , C12Q2600/136 , G01N33/5011 , G01N33/574 , G01N33/57415 , G01N2500/10 , G01N2800/50
摘要： Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention identifies and characterizes the FANCI polypeptide as a vital component of the Fanconi anemia pathway and discloses inhibitors of FANCI and methods of using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
摘要翻译：本文公开了用于治疗癌症的方法和组合物。特别地，本发明鉴定并表征FANCI多肽作为范可尼贫血途径的重要组成部分，并公开了FANCI的抑制剂及其使用方法。这样的抑制剂可用于抑制DNA损伤修复，并且可用于例如治疗癌症。

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