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1. 发明申请

WO02052040A3 METHOD FOR THE SIMULTANEOUS AMPLIFICATION OF MULTIPLE SEQUENCES IN A PCR REACTION AND MARKING THEREOF 审中-公开
标题翻译：程序对于许多序列在PCR反应与他们的印记同步放大
公开(公告)号：WO02052040A3
公开(公告)日：2003-12-11
申请号：PCT/DE0104951
申请日：2001-12-22
申请人： EPIGENOMICS AG , DISTLER JUERGEN , BERLIN KURT , OLEK ALEXANDER
发明人： DISTLER JUERGEN , BERLIN KURT , OLEK ALEXANDER
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , C12Q2537/143 , C12Q2525/155
摘要： A method for the amplification of nucleic acids is disclosed, whereby the section for amplification is first hybridised with at least two primer oligonucleotides, comprising two domains, of which the sequence-specific domain at the 3' terminus on the section to be amplified is hybridised and the generic domain at the 5' terminus is not hybridised. Then an amplification reaction is carried out using a polymerase, a marked primer oligonucleotide is hybridised on the obtained amplification product, which binds to the generic domain of the first primer. In the final step the sequence of the amplification product is checked.
摘要翻译：公开了一种用于在NUC-leinsäuren的扩增，其中第一杂交到扩增的部分与至少两个寡核苷酸引物，其具有两个结构域，其中杂交位于3“末端的序列特异性域被放大部分，而一个方法在位于5“端，通用域不杂交。随后，Amplifikationsreak-和灰是通过聚合酶来进行和标记的杂交静静nachfol-PRI-meroligonukleotid至所得的扩增子，其结合所述第一引物的通用域名。在最后的步骤中，所述扩增子在其序列中的术语进行分析。

2. 发明申请

WO02061124A3 ANALYSIS OF METHYLATION PATTERNS IN GENOMIC DNA USING BISULFITE TREATMENT AND FLUORESCENCE POLARISATION ASSAY TECHNIQUES 审中-公开
标题翻译：使用双相处理和荧光偏振测定技术分析基因组DNA中的甲基化模式
公开(公告)号：WO02061124A3
公开(公告)日：2003-09-04
申请号：PCT/EP0200923
申请日：2002-01-29
申请人： EPIGENOMICS AG , BERLIN KURT , DISTLER JUERGEN
发明人： BERLIN KURT , DISTLER JUERGEN
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6858 , C12Q2561/119 , C12Q2523/125
摘要： A method for the analysis of the methylation of cytosine bases in genomic DNA samples, comprising the following steps:(a) the genomic DNA is chemically treated in such a manner that cytosine is converted into uracil or a similar base regarding the base pairing behaviour in the DNA duplex, 5 methylcytosine however remains unchanged;(b) the chemically treated DNA is amplified using of at least one species of oligonucleotide (type A) as a primer in a polymerase reaction;(c) the amplificate is left in solution with one or more species of fluorophore labelled nucleotides and one or more species of oligonucleotide (type B) , wherein the type B oligonucleotide hybridises under appropriate conditions with its 3' end directly on or up to 10 bases from the position to be examined, and wherein said type B oligonucleotide is at least partly nuclease resistant;(d) the hybridised oligonucleotide (type B) is extended by means of a polymerase by at least one nucleotide, whereby the extension is dependant upon the methylation status of the respective cytosine position in the genomic DNA sample;(e) the solution is incubated with a phosphodiesterase, which is capable of digesting nucleic acids, however incompletely digests the type B oligonucleotides and its extension products;(f) the fluorescence polarisation of the solution is measured whereby for each fluorescent label used one determines the degree of polarisation.
摘要翻译：一种用于分析基因组DNA样品中胞嘧啶碱基甲基化的方法，包括以下步骤：（a）基因组DNA以如下方式化学处理，即将胞嘧啶转化为尿嘧啶或类似的碱基，与碱基配对行为相关然而，DNA双链体5甲基胞嘧啶保持不变;（b）在聚合酶反应中使用至少一种寡核苷酸（A型）作为引物扩增化学处理的DNA;（c）将扩增体与溶液中的一个置于一个或更多种荧光团标记的核苷酸和一种或多种寡核苷酸（B型），其中B型寡核苷酸在适当条件下与其3'端直接在待检查的位置上或多达10个碱基杂交，并且其中所述 B型寡核苷酸至少部分具有核酸酶抗性;（d）通过聚合酶将杂交的寡核苷酸（B型）延伸至少一个核苷酸，由此延伸是依赖的（e）将该溶液与能够消化核酸的磷酸二酯酶一起温育，然而不完全消化B型寡核苷酸及其延伸产物;（f）测量溶液的荧光偏振，由此使用的每个荧光标记物决定偏振度。

3. 发明申请

WO2006009870A3 COMPOSITIONS AND METHODS FOR PREVENTING CARRY-OVER CONTAMINATION IN NUCLEIC ACID AMPLIFICATION REACTIONS 审中-公开
标题翻译：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：WO2006009870A3
公开(公告)日：2006-06-22
申请号：PCT/US2005021525
申请日：2005-06-17
申请人： EPIGENOMICS AG , TETZNER REIMO , BERLIN KURT , DISTLER JUERGEN
发明人： TETZNER REIMO , BERLIN KURT , DISTLER JUERGEN
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：特定方面提供了在存在来自先前扩增实验的潜在污染PCR产物的情况下特异性扩增模板DNA的方法，但是其中基于使用特定的污染物降解使污染的在先反应扩增物（遗留污染物）变得不可扩增以及使用至少一种与任何污染性在先反应扩增核酸完全互补但包含与样品模板核酸的相应序列错配的引物。另外的方面提供了用于在潜在的双链结转产物的存在下特异性扩增单链样品模板DNA的方法。其它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DNA聚合酶以及脱氧核苷酸以提供嵌合扩增物的方法。用RNase消化后，任何污染的嵌合扩增物，RNA酶都会失活。这些方面是称为UNG系统的结转保护系统以及其他本领域公认的方法的出乎意料的有效替代方案。

4. 发明申请

WO2004067775A3 METHOD FOR THE DETECTION OF CYTOSINE METHYLATION PATTERNS WITH HIGH SENSITIVITY 审中-公开
标题翻译：用于检测具有高灵敏度的胞嘧啶甲基化模式的方法
公开(公告)号：WO2004067775A3
公开(公告)日：2004-12-09
申请号：PCT/EP2004000856
申请日：2004-01-30
申请人： EPIGENOMICS AG , BERLIN KURT
发明人： BERLIN KURT
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/686 , C12Q2527/137 , C12Q2523/125 , C12Q2535/125 , C12Q2525/185
摘要： The present invention concerns a method for the detection of cytosine methylation in DNA samples, in which the following steps are conducted: a genomic DNA sample which comprises target DNA and background DNA is chemically treated such that all unmethylated cytosine bases are converted to uracil, while the 5-methylcytosine bases remain unchanged; the chemically treated DNA sample is amplified with the use of at least 2 primer oligonucleotides as well as a polymerase and a nucleotide mixture, the composition of which leads to a preference for the target DNA over the background DNA as the template; and the methylation state in the target DNA is concluded from the presence of an amplificate or its quantity.
摘要翻译：本发明涉及检测DNA样品中胞嘧啶甲基化的方法，其中进行以下步骤：将包含靶DNA和背景DNA的基因组DNA样品进行化学处理，使得所有未甲基化胞嘧啶碱基转化成尿嘧啶，同时 5-甲基胞嘧啶碱基保持不变; 使用至少2个引物寡核苷酸以及聚合酶和核苷酸混合物扩增化学处理的DNA样品，其组合导致在背景DNA上作为模板的靶DNA优先选择; 并且目标DNA中的甲基化状态从扩增子或其量的存在得出。

5. 发明申请

WO0202808A3 METHOD AND NUCLEIC ACIDS FOR THE ANALYSIS OF ASTROCYTOMAS 审中-公开
标题翻译：方法和核酸分析ASTROCYTOMAS
公开(公告)号：WO0202808A3
公开(公告)日：2003-09-04
申请号：PCT/EP0107538
申请日：2001-07-02
申请人： EPIGENOMICS AG , OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
发明人： OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
IPC分类号： G01N27/62 , C07K14/47 , C07K14/82 , C12M1/00 , C12M1/34 , C12N15/09 , C12Q1/68 , G01N33/53 , G01N33/58 , G01N37/00 , B01J19/00 , C07K14/48 , G01N33/483
CPC分类号： C07K14/82 , C07K14/4703 , C12Q1/6883 , C12Q1/6886 , C12Q2523/125 , C12Q2600/154 , C12Q2600/156
摘要： The present invention relates to chemically modified genomic sequences, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genomic DNA, as well as to a method for ascertaining genetic and/or epigenetic parameters of genes for use in the characterisation, classification, differentiation, grading, staging, treatment and/or diagnosis of astrocytomas, or the predisposition to astrocytomas.
摘要翻译：本发明涉及用于检测基因组DNA的胞嘧啶甲基化状态的寡核苷酸和/或PNA寡聚体的化学修饰基因组序列，以及用于确定用于表征的基因的遗传和/或表观遗传参数的方法，星形细胞瘤的分类，分化，分级，分期，治疗和/或诊断，或星形细胞瘤的倾向。

6. 发明申请

WO0181620A3 METHOD FOR THE HIGHLY PARALLEL ANALYSIS OF POLYMORPHISMS 审中-公开
标题翻译：方法多态性的高度并行分析
公开(公告)号：WO0181620A3
公开(公告)日：2003-02-13
申请号：PCT/DE0101607
申请日：2001-04-25
申请人： EPIGENOMICS AG , BERLIN KURT , GUT IVO GLYNNE
发明人： BERLIN KURT , GUT IVO GLYNNE
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2565/627 , C12Q2565/501 , C12Q2523/319 , C12Q2523/107
摘要： The invention relates to a method for the highly parallel characterization of polymorphisms, especially SNPs, which can be used for the simultaneous or separate detection of DNA methylations. A set of probes that is provided with at least one detectable marking characteristic of the corresponding probe is bound to an addressed surface, the bond of the probes to the surface being photochemically, chemically or enzymatically cleavable. A nucleic acid to be analyzed is then bound to said probes, the probes are modified in an allele-specific enzymatic reaction and a part of the probes that is irrelevant for the analysis of the allele-specific reaction is removed. The allele-specific products are analyzed by means of the detectable markings and the alleles present in the analyzed nucleic acid probe are determined.
摘要翻译：公开了用于多态性，即，可用于DNA甲基化的同时或分开的检测特别SNP的高度并行的表征的方法。首先，以配合一组探针，其设置有各自的探针可检测标记中的至少一个特性，向寻址表面，光化学产生的探针的结合，化学或酶促裂解的背面到表面。然后杂交到核酸待检查到这些探针中，探针在等位基因特异性酶促反应改变，并且除去它是无关的等位基因特异性反应的分析的探针的部分。最近分析的可检测标记的基础上allelespezifischen产品和使得本由询问核酸样品中等位基因的确定。

7. 发明申请

WO0200928A3 DIAGNOSIS OF DISEASES ASSOCIATED WITH THE IMMUNE SYSTEM BY DETERMINING CYTOSINE METHYLATION 审中-公开
标题翻译：对疾病的免疫系统有关通过确定胞嘧啶甲基诊断
公开(公告)号：WO0200928A3
公开(公告)日：2002-08-01
申请号：PCT/EP0107537
申请日：2001-07-02
申请人： EPIGENOMICS AG , OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
发明人： OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
IPC分类号： G01N27/62 , C07K14/47 , C07K14/82 , C12M1/00 , C12M1/34 , C12N15/09 , C12Q1/68 , G01N33/53 , G01N33/58 , G01N37/00 , B01J19/00 , G01N33/483
CPC分类号： C07K14/82 , C07K14/4703 , C12Q1/6883 , C12Q1/6886 , C12Q2523/125 , C12Q2600/154 , C12Q2600/156
摘要： The invention relates to chemically modified genomic sequences of genes associated with the immune system, an oligonucleotide directed against said sequence and/or PNA oligomers for the detection of the methylation state of cytosine of genes associated with the immune system. The invention also relates to a method for determining genetic and/or epigenetic parameters of genes associated with the immune system.
摘要翻译：本发明涉及一种化学修饰的与免疫系统的基因相关的基因组序列，针对寡核苷酸和/或PNA寡聚物，用于检测与免疫系统的基因相关的胞嘧啶甲基化状态的序列，和用于确定遗传和/或外遗传的方法与免疫系统相关的基因的参数。

8. 发明申请

WO0236604A2 DIAGNOSIS OF DISEASES ASSOCIATED WITH THE HUMAN C-MOS GENE 审中-公开
标题翻译：与HUMOS相关疾病的诊断
公开(公告)号：WO0236604A2
公开(公告)日：2002-05-10
申请号：PCT/EP0112831
申请日：2001-11-06
申请人： EPIGENOMICS AG , OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
发明人： OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
IPC分类号： C12Q1/68 , C07H21/00
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/156
摘要： The invention relates to the chemically modified genomic sequence of the human C-mos gene, to oligonucleotides and/or PNA oligomers directed against the sequence for detecting the cytosine methylation condition of the human C-mos gene and to a method for determining genetic and/or epigenetic parameters of the human C-mos gene.
摘要翻译：本发明涉及化学修饰的抗寡核苷酸和/或PNA寡聚物用于检测基因humos的胞嘧啶甲基化状态的序列的基因humos的基因组序列，并用于确定腐殖酸的遗传和/或外遗传参数的方法基因。

9. 发明申请

WO0200927A8 DIAGNOSIS OF DISEASES ASSOCIATED WITH DEVELOPMENT GENES 审中-公开
标题翻译：诊断与发展基因相关的疾病
公开(公告)号：WO0200927A8
公开(公告)日：2002-03-21
申请号：PCT/EP0107536
申请日：2001-07-02
申请人： EPIGENOMICS AG , OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
发明人： OLEK ALEXANDER , PIEPENBROCK CHRISTIAN , BERLIN KURT
IPC分类号： G01N27/62 , C07K14/47 , C07K14/82 , C12M1/00 , C12M1/34 , C12N15/09 , C12Q1/68 , G01N33/53 , G01N33/58 , G01N37/00
CPC分类号： C07K14/82 , C07K14/4703 , C12Q1/6883 , C12Q1/6886 , C12Q2523/125 , C12Q2600/154 , C12Q2600/156
摘要： The present invention relates to the chemically modified genomic sequences of genes associated with diseases associated with development, to oligonucleotides and/or PNA/oligomers for detecting the cytosine methylation state of genes associated with diseases associated with development which are directed against the sequence, as well as to a method for ascertaining genetic and/or epigenetic parameters of genes associated with diseases associated with development.
摘要翻译：本发明涉及与发展相关疾病相关基因的化学修饰基因组序列，涉及用于检测针对该序列的与发展有关的疾病相关基因的胞嘧啶甲基化状态的寡核苷酸和/或PNA /寡聚体，以及关于确定与发展相关疾病相关基因的遗传和/或表观遗传参数的方法。

10. 发明申请

WO0127317A3 METHOD FOR DISTINGUISHING 5-POSITION METHYLATION CHANGES 审中-公开
标题翻译：区别5号位置的方法更改甲基
公开(公告)号：WO0127317A3
公开(公告)日：2002-01-17
申请号：PCT/DE0003726
申请日：2000-10-13
申请人： EPIGENOMICS AG , BERLIN KURT
发明人： BERLIN KURT
IPC分类号： G01N27/62 , C12N15/09 , C12Q1/48 , C12Q1/68 , G01N21/78 , G01N27/447 , G01N33/483 , G01N33/53 , G01N33/566 , G01N33/58
CPC分类号： C12Q1/6827 , C12Q2523/125 , C12Q2521/125
摘要： The invention relates to a method for distinguishing 5-position methylation changes of cytosine bases and cytosine-to-thymine mutations and for detecting single nucleotide polymorphisms (SNPs) or point mutations in genomic DNA, comprising the following steps: a) treating a genomic DNA-sample with sulphite or disulphite in such a way that all of the cytosine bases not methylated in the 5-position of the base are changed in such a way as to produce a different base according to the base pairing behaviour while the cytosines which are methylated in the 5-position remain unchanged; b) quantitatively methylating an aliquot of the same genomic DNA sample before chemical treatment according to a) with Sss1 or another methyltransferase; c) testing the two DNA samples treated in this way for the presence of cytosine using the same analytical methods; and d) comparing the cytosine positions that are detected with a reference DNA-sequence.
摘要翻译：描述了一种用于区分的胞嘧啶碱基和胞嘧啶到胸腺嘧啶的突变5-位甲基化的变化和用于检测单核苷酸多态性（SNP），或在基因组DNA中的点突变，一个方法，其中，魔法）与亚硫酸盐或焦亚基因组DNA样品处理，使得所有未甲基化在基胞嘧啶碱基的5位上被改变，从而使得由碱基配对行为，以不同的基发生，而甲基化在胞嘧啶的5-位上保持不变，和b）的相同基因组DNA的等分试样定量甲基化的样品之前根据与SSS1化学处理）或其他甲基，和c）将如此处理由胞嘧啶的存在与参考DNA序列确定的胞嘧啶的位置相同的分析方法，以及d）检测所述两个DNA样品匹配。

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