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1. 发明申请

WO2004022779A3 METHOD FOR THE DETECTION OF NUCLEIC ACID SEQUENCES BY MEANS OF CRACKABLE PROBE MOLECULES 审中-公开
标题翻译：通过可纺固体分子检测核酸序列的方法
公开(公告)号：WO2004022779A3
公开(公告)日：2004-06-03
申请号：PCT/DE0302936
申请日：2003-09-01
申请人： EPIGENOMICS AG , SCHATZ PHILIPP , SCHUSTER MATTHIAS , BERLIN KURT
发明人： SCHATZ PHILIPP , SCHUSTER MATTHIAS , BERLIN KURT
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6816 , C12Q2563/167
摘要： The invention relates to a method for detecting nucleic acid sequences, which is characterized by the fact that the following steps are carried out: a) at least one nucleic acid is bound onto a solid phase; b) probe molecules which are provided with a crackable bond and a probe molecule-specific mass marker are hybridized in a sequence-specific manner to the nucleic acid; c) the probe molecules that are not hybridized are removed; d) the hybridized probe molecules are brought into contact with a matrix which cracks said crackable bonds and is used as a matrix in a MALDI mass spectrometer; e) the mass markers are detected in the positions in which the nucleic acid is bound.
摘要翻译：本发明描述了用于检测核酸序列的方法，其特征在于进行以下步骤：a）至少一种核酸与固相结合; b）探针分子与核酸序列特异性杂交，其中探针分子具有可剪切键和对探针分子特异的质量标签; c）去除未杂交的探针分子; d）使杂交的探针分子与裂解所述可裂解键的基质接触，同时用作MALDI质谱仪中的基质; e）检测核酸结合位置的质量标签。

2. 发明申请

WO2006039563A2 METHOD FOR PROVIDING DNA FRAGMENTS DERIVED FROM AN ARCHIVED SAMPLE 审中-公开
标题翻译：用于提供从存档样品衍生的DNA片段的方法
公开(公告)号：WO2006039563A2
公开(公告)日：2006-04-13
申请号：PCT/US2005035317
申请日：2005-09-30
申请人： EPIGENOMICS AG , BALLHAUSE MATTHIAS , BERLIN KURT , DIETRICH DIMO , KLUTH ANTJE , SCHUSTER MATTHIAS , WAGNER UTE , WASSERKORT REINHOLD , ZIEBARTH HEIKE
发明人： BALLHAUSE MATTHIAS , BERLIN KURT , DIETRICH DIMO , KLUTH ANTJE , SCHUSTER MATTHIAS , WAGNER UTE , WASSERKORT REINHOLD , ZIEBARTH HEIKE
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6806 , C12N15/1003 , C12Q2527/127 , C12Q2523/125 , C12Q2521/531 , C12Q2547/107
摘要： Aspects of the present invention relate to compositions and methods for providing DNA fragments from an archived sample (e.g., paraffin-embedded and/or fixed-tissue biopsies, etc). Particular aspects provide methods whereby high yields of DNA are isolated as well as a substantial portion of the DNA consists of long DNA fragments, and where the isolated genomic DNA is free of associated or cross-linked contaminants like proteins, peptides, amino acids or RNA. The methods are facile, cost-effective, an are characterized by high reproducibility and reliability. Particular aspects provide methods for providing DNA fragments derived from an archived sample, wherein the yield of DNA before, for example, an amplification step is at least 20%, and amplicons up to a length of about 1,000 base pairs are amplifiable.
摘要翻译：本发明的方面涉及从归档样品（例如石蜡包埋和/或固定组织活组织检查等）提供DNA片段的组合物和方法。具体方面提供了分离DNA的高产率以及大部分DNA由长DNA片段组成并且分离的基因组DNA不含相关或交联的污染物如蛋白质，肽，氨基酸或RNA的方法。这些方法是容易的，具有成本效益的，其特征在于重现性和可靠性高。特定方面提供用于提供衍生自归档样品的DNA片段的方法，其中在例如扩增步骤之前的DNA的产量为至少20％，并且可扩增至约1000个碱基对的扩增子。

3. 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。

4. 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。

5. 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。

6. 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。

7. 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。

8. 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。

9. 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。

10. 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。

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