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101. 发明授权

US5756455A Amplification of human MDM2 gene in human tumors 失效
公开(公告)号：US5756455A
公开(公告)日：1998-05-26
申请号：US390515
申请日：1995-02-17
申请人： Kenneth W. Kinzler , Bert Vogelstein
发明人： Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12N15/09 , A61K38/00 , A61K38/17 , A61K48/00 , C07H21/04 , C07K14/47 , C07K16/18 , C12N1/19 , C12Q1/68 , G01N33/50 , G01N33/574 , G01N33/68 , C07K14/435
CPC分类号： G01N33/57484 , A61K38/1709 , C07K14/47 , C07K16/18 , C12Q1/6886 , C12Q1/6897 , G01N33/5011 , G01N33/57407 , G01N33/68 , G01N33/6872 , A61K48/00 , C12Q2600/136 , G01N2500/10 , Y10S436/813
摘要： A human gene has been discovered which is genetically altered in human tumor cells. The genetic alteration is gene amplification and leads to a corresponding increase in gene products. Detecting that the gene, designated hMDM2, has become amplified or detecting increased expression of gene products is diagnostic of tumorigenesis. Human MDM2 protein binds to human p53 and allows the cell to escape from p53-regulated growth.

102. 发明授权

US5750352A Mono-allelic mutation analysis for identifying germline mutations 失效
公开(公告)号：US5750352A
公开(公告)日：1998-05-12
申请号：US519059
申请日：1995-08-23
申请人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos
IPC分类号： C12Q1/68 , G01N33/50 , G01N33/68 , G01N33/567
CPC分类号： G01N33/68 , C12Q1/6827 , G01N33/5005
摘要： A diagnostic strategy for detection of inherited diseases caused by germline mutations is based on somatic cell hybridization. Each allele of a human gene involved in the inherited disease is isolated in a somatic cell hybrid. The products of the isolated human allele are then observed in the absence of the other allele of the human.

103. 发明授权

US5736338A Method of diagnosing Neoplastic disease by detecting increased expression of human MDM2 protein 失效
标题翻译：通过检测人MDM2蛋白表达增加来诊断肿瘤病的方法
公开(公告)号：US5736338A
公开(公告)日：1998-04-07
申请号：US390517
申请日：1995-02-17
申请人： Marilee Burrell , David E. Hill , Kenneth W. Kinzler , Bert Vogelstein
发明人： Marilee Burrell , David E. Hill , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12N15/09 , A61K38/00 , A61K38/17 , A61K48/00 , C07H21/04 , C07K14/47 , C07K16/18 , C12N1/19 , C12Q1/68 , G01N33/50 , G01N33/574 , G01N33/68 , G01N33/53 , C07K16/00 , C12N5/00
CPC分类号： G01N33/57484 , A61K38/1709 , C07K14/47 , C07K16/18 , C12Q1/6886 , C12Q1/6897 , G01N33/5011 , G01N33/57407 , G01N33/68 , G01N33/6872 , A61K48/00 , C12Q2600/136 , G01N2500/10 , Y10S436/813
摘要： In certain human tumor cells, the gene encoding MDM2 protein is amplified and expression of MDM2 protein is elevated. Since human MDM2 protein binds to human p53, excess MDM2 protein apparently releases a cell from p53-regulated growth. Detection of elevated amounts of human MDM2 protein thus can be used to diagnose neoplastic disease in a human.
摘要翻译：在某些人肿瘤细胞中，编码MDM2蛋白的基因被扩增，并且MDM2蛋白的表达升高。由于人类MDM2蛋白与人类p53结合，过量的MDM2蛋白质明显释放出p53调节生长的细胞。因此，人类MDM2蛋白质的升高量的检测可用于诊断人类的肿瘤性疾病。

104. 发明授权

US5492808A Means for detecting familial colon cancer (FCC) 失效
标题翻译：用于检测家族性结肠癌（FCC）的方法
公开(公告)号：US5492808A
公开(公告)日：1996-02-20
申请号：US56546
申请日：1993-05-05
申请人： Albert de la Chapelle , Bert Vogelstein , Kenneth W. Kinzler
发明人： Albert de la Chapelle , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12N15/09 , A61K38/00 , C07K14/82 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/683 , C07K14/82 , C12Q1/6886 , A61K38/00 , C12Q2600/112 , C12Q2600/156 , C12Q2600/172
摘要： Markers on chromosome 2 are associated with cancer predisposition, as shown by linkage analysis, in a significant fraction of families with a history of colon and other cancers. Tumors from these patients progressed through the same series of accumulated mutations in oncogenes and tumor suppressor genes found in non-familial cases, but showed no losses of heterozygosity for the linked chromosome 2 markers. DNA from the tumors (but not normal tissues) in most familial cases revealed a consistent and distinct abnormality: rearrangements in short repeated sequences throughout their genomes. This abnormality suggests that a large number of replication errors had occurred during tumor development. Methods are presented for detecting the presence of the gene which predisposes people to have colon and other tumors and for utilizing this information for diagnostic, prognostic, and preventive purposes. DNA markers useful for such methods are also described.
摘要翻译：染色体2上的标记与癌症倾向相关，如通过连锁分析所显示的，具有结肠和其他癌症病史的家族的很大一部分。来自这些患者的肿瘤通过在非家族性病例中发现的致癌基因和肿瘤抑制基因的相同序列的累积突变进行，但是对于连锁的2号染色体标记物，没有显示出杂合性的损失。在大多数家族性病例中，来自肿瘤（但不是正常组织）的DNA显示出一致和明显的异常：在整个基因组中重复序列的重新排列。这种异常表明在肿瘤发展过程中发生了大量的复制错误。提出了用于检测易患人群具有结肠和其他肿瘤的基因的存在以及用于诊断，预后和预防目的的这种信息的方法。还描述了对这些方法有用的DNA标记。

105. 发明授权

US08859206B2 Digital amplification 有权
标题翻译：数字放大
公开(公告)号：US08859206B2
公开(公告)日：2014-10-14
申请号：US13071105
申请日：2011-03-24
申请人： Bert Vogelstein , Kenneth W. Kinzler
发明人： Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q1/6818 , C12Q1/6851 , C12Q1/686 , C12Q1/6874 , C12Q2600/156 , C12Q2600/158
摘要： The identification of pre-defined mutations expected to be present in a minor fraction of a cell population is important for a variety of basic research and clinical applications. The exponential, analog nature of the polymerase chain reaction is transformed into a linear, digital signal suitable for this purpose. Single molecules can be isolated by dilution and individually amplified; each product is then separately analyzed for the presence of pre-defined mutations. The process provides a reliable and quantitative measure of the proportion of variant sequences within a DNA sample.
摘要翻译：预期存在于细胞群体的较小部分中的预定义突变的鉴定对于各种基础研究和临床应用是重要的。聚合酶链反应的指数模拟性质被转化为适合于此目的的线性数字信号。单分子可以通过稀释和单独扩增分离; 然后分别分析每种产品是否存在预先定义的突变。该过程提供了DNA样品中变体序列比例的可靠和定量测量。

106. 发明申请

US20140154683A1 Enrichment of Nucleic Acids by Complimentary Capture 有权
标题翻译：通过免费捕获富集核酸
公开(公告)号：US20140154683A1
公开(公告)日：2014-06-05
申请号：US14130007
申请日：2012-06-28
申请人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian WU
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian WU
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6806 , C12Q2535/122 , C12Q2563/131 , C12Q2563/149 , C12Q2565/518
摘要： Assays can be used to detect mutations found in neoplasms of the pancreas, as well as for other neoplasms and other uses. Nucleic acids can be captured from body fluids such as cyst fluids. Thousands of oligonucleotides can be synthesized in parallel, amplified and ligated together. The ligated products can be further amplified. The amplified, ligated products are used to capture complementary DNA sequences, which can be analyzed, for example by massively parallel sequencing.
摘要翻译：检测可用于检测胰腺肿瘤中发现的突变，以及其他肿瘤和其他用途。核酸可以从体液如囊液中捕获。数千个寡核苷酸可以并行合成，扩增并连接在一起。连接的产物可以进一步扩增。扩增的连接产物用于捕获互补DNA序列，其可以例如通过大规模并行测序来分析。

107. 发明授权

US08613917B2 Combination bacteriolytic therapy for the treatment of tumors 有权
标题翻译：联合溶菌治疗肿瘤治疗
公开(公告)号：US08613917B2
公开(公告)日：2013-12-24
申请号：US13198850
申请日：2011-08-05
申请人： Long Dang , Chetan Bettegowda , Kenneth W. Kinzler , Bert Vogelstein
发明人： Long Dang , Chetan Bettegowda , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： A61K35/00 , A01N63/00 , A01N63/02 , C12N1/20 , C12N3/00
CPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06 , Y10S435/842 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane, docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sporulated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
摘要翻译：目前用于治疗癌症的方法在一定程度上受到药物不能影响肿瘤血管不足的区域的限制。我们已经发现，厌氧细菌的孢子与与微管相互作用的药物组合可能导致肿瘤的血管和非血管性腔室的破坏。发现两类微管抑制剂发挥显着不同的作用。抑制微管合成的一些药物，如长春瑞滨，当与孢子结合使用时，引起快速，大规模的出血性坏死。相比之下，稳定微管（如紫杉烷，多西紫杉醇）的药物导致肿瘤消退缓慢，导致大多数肿瘤细胞死亡。肿瘤不良灌注区域的剩余细胞可以被孢子细菌消灭。机理研究表明，微管不稳定剂，而不是微管稳定剂，从根本上减少了流向肿瘤的血液，从而扩大了孢子可以发芽的缺氧生态位。在没有过量毒性的情况下，单次静脉注射孢子加选择的微管相互作用剂能够引起几种肿瘤的回归。

108. 发明授权

US08007782B2 Combination bacteriolytic therapy for the treatment of tumors 有权
标题翻译：联合溶菌治疗肿瘤治疗
公开(公告)号：US08007782B2
公开(公告)日：2011-08-30
申请号：US10568765
申请日：2004-10-21
申请人： Long Dang , Chetan Bettegowda , Kenneth W. Kinzler , Bert Vogelstein
发明人： Long Dang , Chetan Bettegowda , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： A01N63/00 , A01N63/02 , A61K35/00 , C12N1/20 , C12N3/00
CPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06 , Y10S435/842 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
摘要翻译：目前用于治疗癌症的方法在一定程度上受到药物不能影响肿瘤血管不足的区域的限制。我们已经发现，厌氧细菌的孢子与与微管相互作用的药物组合可能导致肿瘤的血管和非血管性腔室的破坏。发现两类微管抑制剂发挥显着不同的作用。抑制微管合成的一些药物，如长春瑞滨，当与孢子结合使用时，引起快速，大规模的出血性坏死。相比之下，稳定微管（如紫杉烷多西紫杉醇）的药物导致肿瘤消退缓慢，导致大多数肿瘤细胞死亡。肿瘤不良灌注区域中的剩余细胞可以被杂音细菌消灭。机理研究表明，微管不稳定剂，而不是微管稳定剂，从根本上减少了流向肿瘤的血液，从而扩大了孢子可以发芽的缺氧生态位。在没有过量毒性的情况下，单次静脉注射孢子加选择的微管相互作用剂能够引起几种肿瘤的回归。

109. 发明申请

US20100190153A1 SINGLE-MOLECULE PCR ON MICROPARTICLES IN WATER-IN-OIL EMULSIONS 有权
标题翻译：单分子PCR在水中乳化液中的微量元素
公开(公告)号：US20100190153A1
公开(公告)日：2010-07-29
申请号：US12305825
申请日：2007-06-19
申请人： Frank Diehl , Kenneth W. Kinzler , Bert Vogelstein
发明人： Frank Diehl , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/686 , C12Q1/6876 , C12Q2600/16 , C12Q2527/125 , C12Q2527/153 , C12Q2565/537
摘要： Modulation of the viscosity of the oil phase of a microemulsion used for amplification of DNA on a bead increases the homogeneity of product beads and the amount of amplified DNA per bead. Moreover the number of separate microemulsion populations that can be formed in parallel is increased using multi-well plates and mixer mill disruptor machines designed to lyse biological samples.
摘要翻译：用于在珠上扩增DNA的微乳液的油相的粘度的调节增加了产物珠的均匀性和每个珠的扩增DNA的量。此外，可以使用设计用于裂解生物样品的多孔板和混合机研磨破碎机来增加可以平行形成的单独的微乳液种群的数量。

110. 发明申请

US20090186339A1 Human transcriptomes 审中-公开
标题翻译：人转录组
公开(公告)号：US20090186339A1
公开(公告)日：2009-07-23
申请号：US11057194
申请日：2005-02-15
申请人： Victor E. Velculescu , Bert Vogelstein , Kenneth W. Kinzler
发明人： Victor E. Velculescu , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12Q1/68 , C07H21/00 , C12N5/10 , G01N33/53
CPC分类号： C12Q1/6886 , C12Q2600/136
摘要： Global gene expression patterns have been characterized in normal and cancerous human cells using serial analysis of gene expression (SAGE). Cancer cell-specific, cell-type specific, and ubiquitously expressed genes have been identified. This information can be used to provide combinations of cell type- and cancer-specific gene probes, as well as methods of using these probes to identify particular cell types, screen for useful drugs, reduce cancer-specific gene expression, standardize gene expression, and restore function to a diseased cell or tissue.
摘要翻译：使用基因表达（SAGE）的连续分析，在正常和癌性人类细胞中表征全球基因表达模式。已经鉴定了癌细胞特异性，细胞型特异性和普遍表达的基因。该信息可用于提供细胞类型和癌症特异性基因探针的组合，以及使用这些探针来鉴定特定细胞类型，筛选有用药物，降低癌症特异性基因表达，标准化基因表达的方法，以及恢复功能到病变细胞或组织。

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