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1. 发明申请

WO2010118016A2 DIGITAL QUANTIFICATION OF DNA METHYLATION 审中-公开
标题翻译： DNA甲基化的数字量化
公开(公告)号：WO2010118016A2
公开(公告)日：2010-10-14
申请号：PCT/US2010/030084
申请日：2010-04-06
申请人： THE JOHNS HOPKINS UNIVERSITY , CASE WESTERN RESERVE UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , LI, Meng , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , LI, Meng , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/52
CPC分类号： C12Q1/6816 , C12Q1/6886 , C12Q2600/154 , C12Q2565/501 , C12Q2527/125 , C12Q2523/125
摘要： Abnormal DNA methylation can be used as a biomarker in cancer patients. For such purposes, it is important to determine precisely the fraction of methylated molecules in an analyzed sample. A technology we term Methyl-BEAMing achieves this goal. Individual bisulfite-treated DNA molecules can be PCR-amplified within aqueous nanocompartments containing beads, resulting in a population of beads each containing thousands of copies of the template molecule. After hybridization with probes specific for methylated sequences, the beads can be analyzed by flow cytometry. This approach enables detection and enumeration of one methylated molecule in a population of ~5000 unmethylated molecules. Methyl-BEAMing provides digital quantification of rare methylation events and is generally applicable to the assessment of methylated genes in clinical samples.
摘要翻译： DNA甲基化异常可用作癌症患者的生物标志物。为此目的，重要的是精确测定分析样品中甲基化分子的分数。我们称之为甲基BEAMing的技术实现了这一目标。单独的亚硫酸氢盐处理的DNA分子可以在含有珠粒的含水纳米间隔内进行PCR扩增，导致每个珠粒群含有数千份拷贝的模板分子。与特异于甲基化序列的探针杂交后，可以通过流式细胞术分析珠粒。这种方法能够检测和计数一个约5000个非甲基化分子的一个甲基化分子。甲基BEAMing提供罕见甲基化事件的数字量化，通常适用于临床样品中甲基化基因的评估。

2. 发明授权

EP2417270B1 DIGITAL QUANTIFICATION OF DNA METHYLATION 有权
标题翻译： DNA甲基化的数字量化
公开(公告)号：EP2417270B1
公开(公告)日：2017-09-20
申请号：EP10762298.7
申请日：2010-04-06
申请人： The Johns Hopkins University , Case Western Reserve University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , LI, Meng , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/52
CPC分类号： C12Q1/6816 , C12Q1/6886 , C12Q2600/154 , C12Q2565/501 , C12Q2527/125 , C12Q2523/125

3. 发明公开

EP2417270A2 DIGITAL QUANTIFICATION OF DNA METHYLATION 有权
标题翻译： DNA甲基化的定量数字
公开(公告)号：EP2417270A2
公开(公告)日：2012-02-15
申请号：EP10762298.7
申请日：2010-04-06
申请人： The Johns Hopkins University , Case Western Reserve University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , LI, Meng , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/52
CPC分类号： C12Q1/6816 , C12Q1/6886 , C12Q2600/154 , C12Q2565/501 , C12Q2527/125 , C12Q2523/125
摘要： Abnormal DNA methylation can be used as a biomarker in cancer patients. For such purposes, it is important to determine precisely the fraction of methylated molecules in an analyzed sample. A technology we term Methyl-BEAMing achieves this goal. Individual bisulfite-treated DNA molecules can be PCR-amplified within aqueous nanocompartments containing beads, resulting in a population of beads each containing thousands of copies of the template molecule. After hybridization with probes specific for methylated sequences, the beads can be analyzed by flow cytometry. This approach enables detection and enumeration of one methylated molecule in a population of ~5000 unmethylated molecules. Methyl-BEAMing provides digital quantification of rare methylation events and is generally applicable to the assessment of methylated genes in clinical samples.

5. 发明公开

EP3327139A1 DIGITAL QUANTIFICATION OF DNA METHYLATION 审中-公开
公开(公告)号：EP3327139A1
公开(公告)日：2018-05-30
申请号：EP17191835.2
申请日：2010-04-06
申请人： The Johns Hopkins University , Case Western Reserve University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth , LI, Ming , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/52
CPC分类号： C12Q1/6816 , C12Q1/6886 , C12Q2600/154 , C12Q2565/501 , C12Q2527/125 , C12Q2523/125
摘要： Abnormal DNA methylation can be used as a biomarker in cancer patients. For such purposes, it is important to determine precisely the fraction of methylated molecules in an analyzed sample. A technology we term Methyl-BEAMing achieves this goal. Individual bisulfite-treated DNA molecules can be PCR-amplified within aqueous nanocompartments containing beads, resulting in a population of beads each containing thousands of copies of the template molecule. After hybridization with probes specific for methylated sequences, the beads can be analyzed by flow cytometry. This approach enables detection and enumeration of one methylated molecule in a population of ∼5000 unmethylated molecules. Methyl-BEAMing provides digital quantification of rare methylation events and is generally applicable to the assessment of methylated genes in clinical samples.

6. 发明申请

WO2022155409A1 METHODS OF DETECTING HIGH RISK BARRETT'S ESOPHAGUS WITH DYSPLASIA, AND ESOPHAGEAL ADENOCARCINOMA 审中-公开
公开(公告)号：WO2022155409A1
公开(公告)日：2022-07-21
申请号：PCT/US2022/012423
申请日：2022-01-14
申请人： CASE WESTERN RESERVE UNIVERSITY , THE JOHN HOPKINS UNIVERSITY
发明人： MARKOWITZ, Sanford , CHAK, Amitabh , WILLIS, Joseph , MOINOVA, Helen , VOGELSTEIN, Bert , KINZLER, Kenneth , PAPADOPOULOS, Nickolas , BETTEWGOWDA, Chetan , DOUVILLE, Christopher
IPC分类号： C12Q1/6883 , C12Q1/6844 , C12Q1/6869
摘要： A method of detecting Barrett's esophagus with low grade dysplasia, or Barrett's esophagus with high grade dysplasia, or adenocarcinoma of the esophagus, applying a Repetitive Element Aneuploidy Sequencing System (RealSeqS) methodology to a biological sample from the esophagus of the subject to detect Barrett's esophagus with low grade dysplasia, or Barrett's esophagus with high grade dysplasia, or adenocarcinoma of the esophagus.

7. 发明公开

EP2723896A2 MUTATIONS IN PANCREATIC NEOPLASMS 有权
标题翻译： PANKREAS-NEOPLASMEN中的突变体
公开(公告)号：EP2723896A2
公开(公告)日：2014-04-30
申请号：EP12802288.6
申请日：2012-06-22
申请人： The Johns Hopkins University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , WU, Jian , DIAZ, Luis , PAPADOPOULOS, Nickolas , MATTHAEI, Hanno , HRUBAN, Ralph , MAITRA, Anirban
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/156
摘要： To help reveal the pathogenesis of these lesions, we purified the DNA from Intraductal Papillary Mucinous Neoplasm (IPMN) cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. We identified recurrent mutations at codon 201 of GNAS. We found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. These data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.
摘要翻译：为了揭示这些病变的发病机制，我们从19名患者的导管内乳头状粘液性肿瘤（IPMN）囊肿液中纯化了DNA，并在人类癌症中通常改变的169种基因中进行了突变检测。我们在GNAS的201号密码子处鉴定了复发性突变。我们发现GNAS突变存在于66％的IPMNs中，KRAS或GNAS突变可以在96％中鉴定。在8例中，我们可以研究与含有GNAS突变的IPMN相关的侵袭性腺癌。在这8例中有7例中，存在于IPMNs中的GNAS突变也在侵袭性损伤中发现。在其他类型的胰腺囊性肿瘤或与IPMN无关的侵袭性腺癌中未发现GNAS突变。这些数据表明，GNAS突变可以为囊性胰腺病变患者的诊断和治疗提供依据。

8. 发明授权

EP0847450B1 MONO-ALLELIC MUTATION ANALYSIS FOR IDENTIFYING GERMLINE MUTATIONS 失效
标题翻译： MONO-等位基因突变分析及KEIMBAHMMUTATIONEN的检测
公开(公告)号：EP0847450B1
公开(公告)日：2003-11-05
申请号：EP96930551.5
申请日：1996-08-23
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , PAPADOPOULOS, Nickolas
IPC分类号： C12Q1/68 , C12P21/00 , G01N33/50 , G01N33/574 , G01N33/68
CPC分类号： G01N33/68 , C12Q1/6827 , G01N33/5005 , C12Q2561/107
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.

9. 发明申请

WO2021163546A1 METHODS AND MATERIALS FOR ASSESSING NUCLEIC ACIDS 审中-公开
公开(公告)号：WO2021163546A1
公开(公告)日：2021-08-19
申请号：PCT/US2021/017937
申请日：2021-02-12
申请人： THE JOHNS HOPKINS UNIVERSITY , PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
发明人： PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
IPC分类号： C12Q1/686
摘要： Provided herein are systems, kits, compositions and methods for sequencing library preparation and sequencing workflow (e.g., for the identification of mutations). In certain embodiments, provides herein systems and methods to identically barcode both strands of templates, and PCR-based enrichment of each strand that does not require hybridization capture.

10. 发明申请

WO2019133245A1 PREVENTING CYTOKINE RELEASE SYNDROME 审中-公开
公开(公告)号：WO2019133245A1
公开(公告)日：2019-07-04
申请号：PCT/US2018/064969
申请日：2018-12-11
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , ZHOU, Shibin , STAEDTKE, Verena , BAI, Renyuan , RIGGINS, Gregory J.
IPC分类号： A61K31/198 , A61K39/395 , A61K38/22 , A61P19/02 , A61P37/00
摘要： This document relates to methods and materials for preventing cytokine release syndrome (CRS). For example, methods and materials for using one or more catecholamine inhibitors to prevent a mammal from developing CRS are provided.

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