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1. 发明申请

WO2009074328A2 METHODS AND NUCLEIC ACIDS FOR ANALYSES OF CELL PROLIFERATIVE DISORDERS 审中-公开
标题翻译：方法和细胞增殖性疾病分析的核酸
公开(公告)号：WO2009074328A2
公开(公告)日：2009-06-18
申请号：PCT/EP2008/010549
申请日：2008-12-11
申请人： EPIGENOMICS AG , DIETRICH, Dimo , LIEBENGERG, Volker , TETZNER, Reimo , DISTLER, Jürgen , LEWIN, Jörn , SCHLEGEL, Thomas
发明人： DIETRICH, Dimo , LIEBENGERG, Volker , TETZNER, Reimo , DISTLER, Jürgen , LEWIN, Jörn , SCHLEGEL, Thomas
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16
摘要： The invention provides methods, nucleic acids and kits for detecting lung carcinoma. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供了用于检测肺癌的方法，核酸和试剂盒。本发明公开了基因组序列，其甲基化模式可用于改善所述病症的检测，从而能够改善患者的诊断和治疗。

2. 发明申请

WO2008087040A2 METHODS AND NUCLEIC ACIDS FOR ANALYSES OF CELL PROLIFERATIVE DISORDERS 审中-公开
标题翻译：方法和核酸分析细胞增殖性疾病
公开(公告)号：WO2008087040A2
公开(公告)日：2008-07-24
申请号：PCT/EP2008/000384
申请日：2008-01-18
申请人： EPIGENOMICS AG , LIEBENBERG, Volker , DISTLER, Jürgen , LEWIN, Jörn , MODEL, Fabian , TETZNER, Reimo , CORTESE, Rene
发明人： LIEBENBERG, Volker , DISTLER, Jürgen , LEWIN, Jörn , MODEL, Fabian , TETZNER, Reimo , CORTESE, Rene
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/156
摘要： The invention provides methods, nucleic acids and kits for detecting cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供了用于检测细胞增殖性病症的方法，核酸和试剂盒。本发明公开了其甲基化模式可用于改善对所述病症的检测的基因组序列，从而能够改善对患者的诊断和治疗。

3. 发明申请

WO2008061801A1 METHODS AND NUCLEIC ACIDS FOR THE ANALYSIS OF GENE EXPRESSION ASSOCIATED WITH THE DEVELOPMENT OF PROSTATE CELL PROLIFERATIVE DISORDERS 审中-公开
标题翻译：与前列腺细胞增殖性疾病相关的基因表达分析的方法和核酸
公开(公告)号：WO2008061801A1
公开(公告)日：2008-05-29
申请号：PCT/EP2007/010257
申请日：2007-11-26
申请人： EPIGENOMICS AG , SLEDZIEWSKI, Andrew , LOFTON-DAY, Catherine , TETZNER, Reimo , DISTLER, Jürgen , MODEL, Fabian , PAYNE, Shannon , DIETRICH, Dimo
发明人： SLEDZIEWSKI, Andrew , LOFTON-DAY, Catherine , TETZNER, Reimo , DISTLER, Jürgen , MODEL, Fabian , PAYNE, Shannon , DIETRICH, Dimo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , C12Q1/6886 , C12Q2523/125 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , C12Q2600/156 , C12Q2600/158
摘要： The invention provides methods, nucleic acids and kits for detecting prostate cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of said disorder, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供用于检测前列腺细胞增殖性疾病的方法，核酸和试剂盒。本发明公开了基因组序列，其甲基化模式可用于改善所述病症的检测，从而能够改善患者的诊断和治疗。

4. 发明申请

WO2008009478A1 METHODS AND NUCLEIC ACIDS FOR ANALYSES OF CELLULAR PROLIFERATIVE DISORDERS 审中-公开
标题翻译：用于细胞增殖性疾病分析的方法和核酸
公开(公告)号：WO2008009478A1
公开(公告)日：2008-01-24
申请号：PCT/EP2007/006538
申请日：2007-07-23
申请人： EPIGENOMICS AG , TETZNER, Reimo , SLEDZIEWSKI, Andrew , LOFTON-DAY, Catherine , DISTLER, Jürgen , MODEL, Fabian , PAYNE, Shannon
发明人： TETZNER, Reimo , SLEDZIEWSKI, Andrew , LOFTON-DAY, Catherine , DISTLER, Jürgen , MODEL, Fabian , PAYNE, Shannon
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/154 , C12Q2600/158
摘要： The invention provides methods, nucleic acids and kits for detecting, or for detecting and distinguishing between or among prostate cell proliferative disorders or for detecting, or for detecting and distinguishing between or among colorectal cell proliferative disorders. The invention discloses genomic sequences the methylation patterns of which have utility for the improved detection of and differentiation between said class of disorders, thereby enabling the improved diagnosis and treatment of patients.
摘要翻译：本发明提供用于检测或检测和鉴别前列腺细胞增殖性疾病或用于检测或检测和鉴别结直肠细胞增殖性疾病之间或之中的方法，核酸和试剂盒。本发明公开了基因组序列，其甲基化模式可用于改善所述疾病类别的检测和分化，从而能够改善患者的诊断和治疗。

5. 发明申请

WO2004113567A2 IMPROVED HEAVYMETHYL ASSAY FOR THE METHYLATION ANALYSIS OF THE GSTPI GENE 审中-公开
标题翻译：改进GSTPI基因甲基化分析的重组方法
公开(公告)号：WO2004113567A2
公开(公告)日：2004-12-29
申请号：PCT/EP2004/006843
申请日：2004-06-24
申请人： EPIGENOMICS AG , TETZNER, Reimo , DISTLER, Jürgen
发明人： TETZNER, Reimo , DISTLER, Jürgen
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6827 , C12Q2600/154 , C12Q2523/125
摘要： Described herein is a method for the detection of cyto-sine methylation in DNA samples, wherein the following steps are conducted: a genomic DNA sample, which comprises the DNA to be investigated as well as background DNA is treated with bisulfite (= disulfite, hydrogen sulfite) in such a way that all of the unmethylated cytosine bases are converted to uracil, while the 5-methylcytosine bases remain un-changed; the bisulfite treated DNA sample is amplified with the use of at least 2 primer oligonucleotides as well as a polymerase, wherein the DNA to be investigated is pre-ferred over the background DNA as the template, and a control fragment is amplified simultaneously to the am-plification of the bisulfite treated DNA within the same reaction mixture the amplified products are analyzed and the methylation status in the DNA to be investigated is concluded from the presence and /or the amount of the amplified products and/or from the analysis of additional positions.
摘要翻译：本文描述了用于检测DNA样品中细胞正辛基甲基化的方法，其中进行以下步骤：将包含待研究的DNA以及背景DNA的基因组DNA样品用亚硫酸氢盐（=二亚硫酸盐，氢气亚硫酸盐），使得所有未甲基化胞嘧啶碱基转化成尿嘧啶，而5-甲基胞嘧啶碱基保持不变; 使用至少2个引物寡核苷酸和聚合酶扩增亚硫酸氢盐处理的DNA样品，其中待研究的DNA优先于背景DNA作为模板，并将对照片段同时扩增至上述在相同的反应混合物中分析亚硫酸氢盐处理的DNA，分析扩增产物，并且从待测的DNA中的甲基化状态从扩增产物的存在和/或量得出和/或从额外位置的分析得出。

6. 发明申请

WO2006009870A2 COMPOSITIONS AND METHODS FOR PREVENTING CARRY-OVER CONTAMINATION IN NUCLEIC ACID AMPLIFICATION REACTIONS 审中-公开
标题翻译：用于防止核酸扩增反应中携带污染的组合物和方法
公开(公告)号：WO2006009870A2
公开(公告)日：2006-01-26
申请号：PCT/US2005/021525
申请日：2005-06-17
申请人： EPIGENOMICS AG , TETZNER, Reimo , BERLIN, Kurt , DISTLER, Jürgen
发明人： TETZNER, Reimo , BERLIN, Kurt , DISTLER, Jürgen
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6848 , C12Q2527/101 , C12Q2521/301
摘要： Particular aspects provide methods for the specific amplification of template DNA in the presence of potentially contaminating PCR products from previous amplification experiments, but wherein the contaminating prior reaction amplificates (carry-over contaminants) are rendered non-amplifiable, based on use of particular contaminant degradation enzmes, and use of at least one primer that is fully complementary to any contaminating prior reaction amplificate nucleic acid, but contains a mismatch with the correspond sequence of the sample template nucleic acid. Additional aspects provide a method for the specific amplification of single-stranded sample template DNA in the presence of potentially double-stranded carry-over products. Further aspects provide methods comprising use of a template-dependent thermostable DNA polymerase enzyme suitable for incorporating ribonucleotides as well as deoxy-nucleotides to provide a chimeric amplificate. After digestion with an RNase, any contaminating prior chimeric amplificate, the RNase is inactivated. These aspects are surprisingly effective alternatives to the carry over protection system known as UNG system, and other art-recognized methods.
摘要翻译：特定方面提供了在来自先前扩增实验的潜在污染性PCR产物存在下对模板DNA进行特异性扩增的方法，但其中基于使用特定的污染物降解使污染的先前的反应扩增（携带污染物）变得不可扩增并且使用与任何污染的先前反应扩增核酸完全互补的至少一个引物，但包含与样品模板核酸的相应序列不匹配的引物。另外的方面提供了在存在潜在双链携带产物的情况下单链样品模板DNA的特异性扩增的方法。另外的方面提供了包括使用适合于掺入核糖核苷酸的模板依赖性热稳定性DNA聚合酶以及脱氧核苷酸以提供嵌合扩增的方法。用RNase消化后，任何污染的先前的嵌合扩增，核糖核酸酶被灭活。这些方面对于被称为UNG系统的承载保护系统以及其他本领域公认的方法是惊人的有效的替代方案。

7. 发明申请

WO2005068648A1 METHOD FOR INVESTIGATING CYTOSINE METHYLATION IN DNA BY MEANS OF DNA REPAIR ENZYMES 审中-公开
标题翻译：通过DNA修复酶检测DNA中细胞色素甲基化的方法
公开(公告)号：WO2005068648A1
公开(公告)日：2005-07-28
申请号：PCT/EP2005/000231
申请日：2005-01-10
申请人： EPIGENOMICS AG , TETZNER, Reimo , BERLIN, Kurt , DISTLER, Jürgen
发明人： TETZNER, Reimo , BERLIN, Kurt , DISTLER, Jürgen
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2537/113 , C12Q2523/125 , C12Q2521/514
摘要： The following invention concerns a method for investigating cytosine methylation by means of DNA repair enzymes. Here, the DNA is first converted so that unmethylated cytosines are converted to uracil, while 5-methylcytosine remains unchanged. Then the DNA is hybridized to oligonucleotides, whereby hybrids will be formed with or without erroneous base pairings, in each case depending on the methylation status of the DNA. Following this, the erroneously paired hybrids will be cleaved by repair enzymes. Then the methylation status of the DNA can be determined in different ways. The method according to the invention is particularly suitable for the diagnosis and prognosis of cancer disorders and other diseases associated with a change of the methylation status as well as for predicting undesired drug effects.
摘要翻译：以下发明涉及通过DNA修复酶研究胞嘧啶甲基化的方法。这里首先转化DNA，使未甲基化的胞嘧啶转化为尿嘧啶，而5-甲基胞嘧啶保持不变。然后将DNA与寡核苷酸杂交，由此可以形成带有或没有错误碱基配对的杂交体，在每种情况下都取决于DNA的甲基化状态。之后，错误配对的杂交体将被修复酶切割。那么DNA的甲基化状态可以通过不同的方法来确定。根据本发明的方法特别适用于与甲基化状态改变相关的癌症和其它疾病的诊断和预后以及预测不期望的药物作用。

8. 发明申请

WO2005024056A3 VERFAHREN ZUM NACHWEIS VON CYTOSINMETHYLIERUNGEN IN DNA UNTER VERWENDUNG VON SCORPION-PRIMERN 审中-公开
公开(公告)号：WO2005024056A3
公开(公告)日：2005-03-17
申请号：PCT/DE2004/001837
申请日：2004-08-13
申请人： EPIGENOMICS AG , TETZNER, Reimo , DISTLER, Jürgen
发明人： TETZNER, Reimo , DISTLER, Jürgen
IPC分类号： C12Q1/68
摘要： Die folgende Erfindung betrifft ein Verfahren zur Untersuchung von Cytosin-Methylieurungen in DNA-Sequenzen. Dabei werden zunächst unmethylierte Cytosine in Uracil umgewandelt, während 5-Methylcytosin unverändert bleibt. Anschliessend wird die DNA mittels einer Polymerase und mindestens einem Primer amplifiziert, dessen 5‘ -Ende über einen Linker mit einer Sonde verbunden ist. Abhängig vom Methylierungsstatus der DNA erfolgt ein intramolekulare Hybridisierung der Sonde an die Amplifikate. Die Hybridisierung kann über verschiedene Detektionssystem nachgewiesen werden. Das erfindungsgemässe Verfahren eignet sich insbesondere zur Diagnose und Prognose von Krebserkrankungen und anderer mit einer Veränderung des Methylierungsstatus assozilierter Krankheiten sowie zur Vorhersage unerwünschter Arzneimittelwirkungen.

9. 发明申请

WO2004113567A3 IMPROVED HEAVYMETHYL ASSAY FOR THE METHYLATION ANALYSIS OF THE GSTPI GENE 审中-公开
公开(公告)号：WO2004113567A3
公开(公告)日：2004-12-29
申请号：PCT/EP2004/006843
申请日：2004-06-24
申请人： EPIGENOMICS AG , TETZNER, Reimo , DISTLER, Jürgen
发明人： TETZNER, Reimo , DISTLER, Jürgen
IPC分类号： C12Q1/68
摘要： Described herein is a method for the detection of cyto-sine methylation in DNA samples, wherein the following steps are conducted: a genomic DNA sample, which comprises the DNA to be investigated as well as background DNA is treated with bisulfite (= disulfite, hydrogen sulfite) in such a way that all of the unmethylated cytosine bases are converted to uracil, while the 5-methylcytosine bases remain un-changed; the bisulfite treated DNA sample is amplified with the use of at least 2 primer oligonucleotides as well as a polymerase, wherein the DNA to be investigated is pre-ferred over the background DNA as the template, and a control fragment is amplified simultaneously to the am-plification of the bisulfite treated DNA within the same reaction mixture the amplified products are analyzed and the methylation status in the DNA to be investigated is concluded from the presence and /or the amount of the amplified products and/or from the analysis of additional positions.

10. 发明申请

WO2006092339A1 VERFAHREN ZUR UNTERSUCHUNG VON CYTOSIN-METHYLIERUNGEN IN DNA 审中-公开
标题翻译：的程序对DNA甲基化的胞嘧啶
公开(公告)号：WO2006092339A1
公开(公告)日：2006-09-08
申请号：PCT/EP2006/002092
申请日：2006-03-02
申请人： EPIGENOMICS AG , LEWIN, Jörn , DISTLER, Jürgen , LESCHE, Ralf , SCHUSTER, Matthias
发明人： LEWIN, Jörn , DISTLER, Jürgen , LESCHE, Ralf , SCHUSTER, Matthias
IPC分类号： C12Q1/68
CPC分类号： C12Q1/683 , C12Q1/6848 , C12Q1/6858 , C12Q2523/125 , C12Q2521/331
摘要： Beschrieben wird ein Verfahren zum sensitiven und spezifischen Nachweis von Cytosinmethylierungen. Dabei wird die zu analysierende DNA zunächst mit Hilfe methylierungsspezifischer Restriktionsenzyme umgesetzt. Hierdurch wird die Hintergrund DNA aus dem Reaktionsansatz entfernt. Im nächsten Schritt erfolgt eine spezifische Umwandlung der nicht methylierten Cytosine, während die methylierten Cytosine unverändert bleiben. Die umgewandelte DNA kann über unterschiedliche Verfahren, insbesondere mittels Real-Time-PCR-Verfahren analysiert werden.
摘要翻译：公开了一种用于甲基化胞嘧啶的敏感和特异的检测的方法。将待分析的DNA首先用甲基化特异性限制性内切酶反应。从而，背景DNA从反应混合物中除去。下一步是非甲基化胞嘧啶的特定转化率，同时甲基化的胞嘧啶将保持不变。所述转化的DNA可以在不同的方法中特别是通过实时PCR法进行分析。

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