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81. 发明申请

US20110059435A1 Methods for Beaming 有权
标题翻译： Beaming方法
公开(公告)号：US20110059435A1
公开(公告)日：2011-03-10
申请号：US12091395
申请日：2006-02-06
申请人： Bert Vogelstein , Frank Diehl , Kenneth W. Kinzler , Ming Li
发明人： Bert Vogelstein , Frank Diehl , Kenneth W. Kinzler , Ming Li
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6858 , G01R31/025 , G01R31/3277 , C12Q2565/537 , C12Q2563/155 , C12Q2527/125
摘要： Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.
摘要翻译：用于BEAMing的基本方法的改进提高了灵敏度并提高了信噪比。这些改进允许确定各种DNA聚合酶的固有错误率，并允许检测从癌症患者血浆中分离的DNA中罕见且微妙的突变。

82. 发明授权

US07785564B2 Design and synthesis of renal dipeptidase inhibitors 有权
标题翻译：肾二肽酶抑制剂的设计与合成
公开(公告)号：US07785564B2
公开(公告)日：2010-08-31
申请号：US11175478
申请日：2005-07-07
申请人： Saeed R. Khan , Bert Vogelstein , Kenneth W. Kinzler , Hallur Gurulingappa , Phillip Buckhaults
发明人： Saeed R. Khan , Bert Vogelstein , Kenneth W. Kinzler , Hallur Gurulingappa , Phillip Buckhaults
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07F9/303 , A61K51/0489 , C07B59/004 , C07B2200/05
摘要： Aminophosphinic acid derivatives were synthesized as potential inhibitors of renal dipeptidase, an enzyme overexpressed in benign and malignant colon tumors. Several compounds showed potent enzyme-inhibitory activity. These compounds can be used therapeutically and diagnostically for treatment and detection of tumors.
摘要翻译：合成氨基次膦酸衍生物作为肾二肽酶的潜在抑制剂，其是在良性和恶性结肠肿瘤中过表达的酶。几种化合物显示出有效的酶抑制活性。这些化合物可用于治疗和诊断用于治疗和检测肿瘤。

83. 发明申请

US20100136560A1 Integrated Analyses of Breast and Colorectal Cancers 审中-公开
标题翻译：乳腺癌和结肠直肠癌综合分析
公开(公告)号：US20100136560A1
公开(公告)日：2010-06-03
申请号：US12619726
申请日：2009-11-17
申请人： Bert Vogelstein , Kenneth W. Kinzler , Rebecca J. Leary , Victor E. Velculescu
发明人： Bert Vogelstein , Kenneth W. Kinzler , Rebecca J. Leary , Victor E. Velculescu
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes—deletion of all copies or amplification of at least twelve copies per cell—averaged thirteen per tumor. These data were integrated with previous mutation analyses of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.
摘要翻译：使用可以可靠地检测纯合缺失和扩增的方法对乳腺和结肠直肠肿瘤的拷贝数变化进行全基因组分析。通过主要拷贝数变化改变的基因数量 - 全部拷贝的缺失或每个细胞至少12个拷贝的扩增，平均每个肿瘤13个。这些数据与这些相同肿瘤类型中的参考序列基因的先前突变分析相结合，以鉴定受拷贝数变化和点改变影响的基因和细胞途径。富含遗传改变的途径包括控制细胞粘附，细胞内信号转导，DNA拓扑变化和细胞周期控制的途径。这些分析提供了在全基因组范围内的拷贝数和排序变化的综合视图，并确定了可用于癌症诊断和治疗的基因和途径。

84. 再颁专利

USRE40948E1 APC antibodies 有权
标题翻译： APC抗体
公开(公告)号：USRE40948E1
公开(公告)日：2009-10-27
申请号：US09983543
申请日：2001-10-24
申请人： Bert Vogelstein , Kenneth W. Kinzler , Hans Albertsen , Rakesh Anand , Mary Carlson , Joanna Groden , Philip Hedge , Geoff Joslyn , Alexander Fred Markham , Yusuke Nakumura , Andrew Thliveris , Raymond White
发明人： Bert Vogelstein , Kenneth W. Kinzler , Hans Albertsen , Rakesh Anand , Mary Carlson , Joanna Groden , Philip Hedge , Geoff Joslyn , Alexander Fred Markham , Yusuke Nakumura , Andrew Thliveris , Raymond White
IPC分类号： C07K16/30 , A61K39/395
摘要： A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.
摘要翻译：公开了一种称为APC的人类基因。提供了用于评估人类组织和身体样品中APC基因突变的方法和试剂盒。家族性腺瘤性息肉病患者以及散发性结肠直肠癌患者发现APC突变。 APC在大多数正常组织中表达。这些结果表明APC是肿瘤抑制因子。

85. 发明申请

US20090117546A1 Disease detection by digital protein truncation assays 有权
标题翻译：通过数字蛋白截断检测进行疾病检测
公开(公告)号：US20090117546A1
公开(公告)日：2009-05-07
申请号：US11703821
申请日：2007-02-08
申请人： C. Giovanni Traverso , Kenneth W. Kinzler , Bert Vogelstein
发明人： C. Giovanni Traverso , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156 , G01N33/68
摘要： Genetic diseases can be diagnosed by detection of mutations in causative genes. Protein truncation assays can be used to detect gene products of truncation-type mutations. However, the sensitivity of the assays is often insufficient to detect mutations present in a sample of DNA at a low frequency. Sensitivity can be increased by dividing samples so that the signal generated by a mutant allele comprises a larger fraction of the total alleles than prior to dividing. Thus a previously undetectable signal generated by the mutant allele can become detectable in the assay. Such increased sensitivity permits detection at early stages and in samples having high levels of other alleles.
摘要翻译：可以通过检测致病基因突变来诊断遗传疾病。蛋白质截短测定可用于检测截短型突变的基因产物。然而，测定的灵敏度通常不足以在低频下检测DNA样品中存在的突变。可以通过分割样本来增加灵敏度，使得由突变等位基因产生的信号包含总分子数之前比分裂前的更大部分。因此，在测定中可以检测到由突变等位基因产生的以前不可检测的信号。这种增加的灵敏度允许早期检测和具有高水平其他等位基因的样品。

86. 发明申请

US20080241830A1 Digital amplification 有权
标题翻译：数字放大
公开(公告)号：US20080241830A1
公开(公告)日：2008-10-02
申请号：US11709742
申请日：2007-02-23
申请人： Bert Vogelstein , Kenneth W. Kinzler
发明人： Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12Q1/68
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。

87. 发明授权

US07358351B2 Endothelial cell expression patterns 有权
公开(公告)号：US07358351B2
公开(公告)日：2008-04-15
申请号：US10979159
申请日：2004-11-03
申请人： Brad St. Croix , Bert Vogelstein , Kenneth W. Kinzler
发明人： Brad St. Croix , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C07H21/04 , C12P19/34
CPC分类号： C07K16/30 , A61K2039/505
摘要： To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

88. 发明授权

US07045352B2 Converting diploidy to haploidy for genetic diagnosis 失效
公开(公告)号：US07045352B2
公开(公告)日：2006-05-16
申请号：US10210066
申请日：2002-08-02
申请人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Hai Yan
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Hai Yan
IPC分类号： C12N5/12 , C12Q1/00 , C12N15/06 , C12N15/87
CPC分类号： C12N5/166 , C12Q1/6886 , C12Q2600/156
摘要： Detection of mutations associated with hereditary diseases is complicated by the diploid nature of mammalian cells. Mutations present in one allele are often masked by the wild-type sequence of the other allele. Individual alleles can be isolated from every chromosome within somatic cell hybrids generated from a single fusion. Nucleic acids from the hybrids can be analyzed for mutations in an unambiguous manner. This approach was used to detect two cancer-causing mutations that had previously defied genetic diagnosis. One of the families studied, Warthin Family G, was the first kindred with a hereditary colon cancer syndrome described in the biomedical literature.

89. 发明授权

US06825038B2 Method for generating hypermutable organisms 有权
标题翻译：产生超可变生物体的方法
公开(公告)号：US06825038B2
公开(公告)日：2004-11-30
申请号：US09853646
申请日：2001-05-14
申请人： Nicholas C. Nicolaides , Philip M. Sass , Luigi Grasso , Bert Vogelstein , Kenneth W. Kinzler
发明人： Nicholas C. Nicolaides , Philip M. Sass , Luigi Grasso , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12N1500
CPC分类号： C12N15/1024 , C07K14/47 , C12N15/01 , C12N15/102
摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. The enhanced rate of mutation can be further augmented using mutagens. Moreover, the hypermutability of mismatch repair deficient cells can be remedied to stabilize cells or mammals with useful mutations.
摘要翻译：人类错配修复基因的主要阴性等位基因可用于产生超可变细胞和生物体。通过将这些基因引入细胞和转基因动物，可以比通过依赖于突变的自然速率更有效地制备具有新颖和有用性质的新细胞系和动物品种。使用诱变剂可以进一步增强突变率的增强。此外，错配修复缺陷细胞的高度易失性可以补救以稳定具有有用突变的细胞或哺乳动物。

90. 发明授权

US06740523B2 14-3-3&sgr; arrests the cell cycle 有权
标题翻译： 14-3-3sigma阻止细胞周期
公开(公告)号：US06740523B2
公开(公告)日：2004-05-25
申请号：US09939581
申请日：2001-08-28
申请人： Heiko Hermeking , Bert Vogelstein , Kenneth W. Kinzler
发明人： Heiko Hermeking , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C07H2104
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00
摘要： Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a growth arrest, with cells blocked in both the G1 and G2 phases of the cell cycle. The G1 block has been shown to be due to the p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3&sgr; is strongly induced by &ggr;-irradiation and other DNA-damaging agents. The induction of 14-3-3&sgr; is mediated by a p53-responsive element located 1.815 kb upstream of its transcription start site. Exogenous introduction of 14-3-3&sgr; into cycling cells results in a G2 block similar to that observed following irradiation. These results document a molecular mechanism for G2/M control that is regulated in human cells by p53.
摘要翻译：结直肠癌（CRC）细胞暴露于电离辐射导致生长停滞，细胞在细胞周期的G1期和G2期都被阻断。已经显示G1阻断是由于p53介导的细胞周期蛋白依赖性激酶抑制剂p21 的诱导，但G2阻滞的基础是未知的。通过对CRC细胞系中基因表达模式的定量分析，我们发现14-3-3sigma被γ辐射和其他DNA损伤剂强烈诱导。 14-3-3sigma的诱导是由位于其转录起始位点上游1.815kb的p53反应元件介导的。外源性引入14-3-3sigma进入循环细胞导致G2块与照射后观察到的相似。这些结果记录了p53在人细胞中调控的G2 / M对照的分子机制。

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