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1. 发明申请

WO2002061143A2 COMPARATIVE ANALYSIS OF NUCLEIC ACIDS USING POPULATION TAGGING 审中-公开
标题翻译：使用人口标签对核酸进行比较分析
公开(公告)号：WO2002061143A2
公开(公告)日：2002-08-08
申请号：PCT/US2002/003097
申请日：2002-01-31
申请人： AMBION, INC. , WINKLER, Matthew, M. , BROWN, David
发明人： WINKLER, Matthew, M. , BROWN, David
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , C12Q2531/143 , C12Q2525/161 , C12Q2525/155
摘要： Disclosed are methods that allow one or more nucleic acid targets to be compared across two or more nucleic acid samples. Nucleic acid tags are appended to the samples to be assessed, such that each sample has a unique tag. The tagged nucleic acids are then mixed, and the targets within the mixture are amplified. The amplification products are distinguished using the unique tag domains to reveal the abundance of the amplification products derived from each sample, which correlates to the relative abundance of the target in the samples.
摘要翻译：公开了允许在两个或多个核酸样品之间比较一个或多个核酸靶标的方法。将核酸标签附加到待评估的样品上，使得每个样品具有唯一的标记。然后将标记的核酸混合，并扩增混合物内的靶。使用独特的标签结构区分扩增产物，以揭示衍生自每个样品的扩增产物的丰度，其与样品中靶标的相对丰度相关。

2. 发明申请

WO2002064835A3 METHODS FOR NUCLEIC ACID FINGERPRINT ANALYSIS 审中-公开
公开(公告)号：WO2002064835A3
公开(公告)日：2002-08-22
申请号：PCT/US2002/003168
申请日：2002-01-31
申请人： AMBION, INC. , BROWN, David , WINKLER, Matthew, M. , LAWRENCE, Frank , SHELTON, Jeffrey
发明人： BROWN, David , WINKLER, Matthew, M. , LAWRENCE, Frank , SHELTON, Jeffrey
IPC分类号： C12Q1/68
摘要： Methods are provided for generating nucleic acid fingerprints from complex nucleic acid populations. The methods rely on the addition of a nucleic acid tag with at least two functional domains to members of the complex population being assessed. Primers specific to the appended tag and arbitrary or adapter-specific primers are used to amplify subsets of the complex population. The amplified population is then used to generate labeled products for comparative expression analysis using the functional domain of the appended tag sequence that was not used for amplification. The separation of amplification and labeling substantially reduces the number of false positives common in amplification fingerprinting experiments by removing all amplification products from the analysis that do not derive from the anchored ends of the nucleic acid population.

3. 发明申请

WO2002064835A2 METHODS FOR NUCLEIC ACID FINGERPRINT ANALYSIS 审中-公开
标题翻译：核酸指纹分析方法
公开(公告)号：WO2002064835A2
公开(公告)日：2002-08-22
申请号：PCT/US2002/003168
申请日：2002-01-31
申请人： AMBION, INC. , BROWN, David , WINKLER, Matthew, M. , LAWRENCE, Frank , SHELTON, Jeffrey
发明人： BROWN, David , WINKLER, Matthew, M. , LAWRENCE, Frank , SHELTON, Jeffrey
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , C12Q2539/113 , C12Q2525/191 , C12Q2525/179
摘要： Methods are provided for generating nucleic acid fingerprints from complex nucleic acid populations. The methods rely on the addition of a nucleic acid tag with at least two functional domains to members of the complex population being assessed. Primers specific to the appended tag and arbitrary or adapter-specific primers are used to amplify subsets of the complex population. The amplified population is then used to generate labeled products for comparative expression analysis using the functional domain of the appended tag sequence that was not used for amplification. The separation of amplification and labeling substantially reduces the number of false positives common in amplification fingerprinting experiments by removing all amplification products from the analysis that do not derive from the anchored ends of the nucleic acid population.
摘要翻译：提供了从复杂核酸群体产生核酸指纹的方法。所述方法依赖于将正在评估的复合群体的成员添加具有至少两个功能结构域的核酸标签。用于附加标签和任意或接头特异性引物特异性的引物用于扩增复合群体的子集。然后使用扩增的群体产生用于比较表达分析的标记产物，其使用未用于扩增的附加标签序列的功能域。扩增和标记的分离大大减少了扩增指纹图谱实验中常见的假阳性数目，其中从分析中除去不是从核酸群体的锚定末端得到的所有扩增产物。

4. 发明申请

WO2002061140A3 COMPETITIVE POPULATION NORMALIZATION FOR COMPARATIVE ANALYSIS OF NUCLEIC ACID SAMPLES 审中-公开
公开(公告)号：WO2002061140A3
公开(公告)日：2002-08-08
申请号：PCT/US2002/002892
申请日：2002-01-31
申请人： AMBION, INC. , BROWN, David , WINKLER, Matthew, M.
发明人： BROWN, David , WINKLER, Matthew, M.
IPC分类号： C12Q1/68
摘要： Methods are disclosed that convert two or more complex nucleic acid samples into a single collection of normalized target molecules that can be used to compare the abundance of each of the targets in the original samples. Multiple RNA or DNA samples are uniquely tagged and pooled to create a sample mixture. A defined set of target within the sample mixture is converted to approximately equal amounts of nucleic acid by one of several methods employing primer extension with a set of target specific primers. The concentration of target specific primers is equal and limiting for all targets, therefore an appropriate number of primer extension cycles converts all targets to similar final concentrations of product nucleic acid. The different tags appended to the sample nucleic acids from each sample population unique. These different tags are used to generate RNA or DNA , molecules for analysis that derive form each of the input samples. The disclosed methods are primarily intended to enhance gene array analysis, however, any method used to compare multiple nucleic acid targets form different samples will benefit form the invention.

5. 发明申请

WO2002061145A2 COMPETITIVE AMPLIFICATION OF FRACTIONATED TARGETS FROM MULTIPLE NUCLEIC ACID SAMPLES 审中-公开
标题翻译：来自多种核酸样品的分离目标的竞争性放大
公开(公告)号：WO2002061145A2
公开(公告)日：2002-08-08
申请号：PCT/US2002/003169
申请日：2002-01-31
申请人： AMBION, INC. , WINKLER, Matthew, M. , BROWN, David
发明人： WINKLER, Matthew, M. , BROWN, David
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6851 , C12Q2545/107
摘要： Disclosed are methods that allow one or more targets to be compared across two or more nucleic acid populations. The methods rely on first mixing sample populations that are being compared. The sample mixture is then divided into target fractions using hybridization to polynucleotides or oligonucleotides that can be separated form the sample mixture. the target fraction(s) are independently amplified such that the targets from each sample compete for amplification reagents. The amplification products are quantified in a manner that differentiates the sample from which a particular amplification product arose. The relative abundance of amplification products descended from each sample population reflects the level of target present in each of the original samples, providing a direct comparison of the abundance of the target sequences in the samples being characterized.
摘要翻译：公开了允许在两个或多个核酸群体上比较一个或多个靶标的方法。该方法依赖于第一次混合正在比较的样本群体。然后将样品混合物与可与样品混合物分离的多核苷酸或寡核苷酸杂交分成目标级分。靶分离物被独立地扩增，使得来自每个样品的靶标竞争扩增试剂。扩增产物以区分特定扩增产物产生的样品的方式进行定量。从每个样本群体下降的扩增产物的相对丰度反映了每个原始样品中存在的靶标水平，提供了正在表征的样品中靶序列丰度的直接比较。

6. 发明申请

WO2002061140A2 COMPETITIVE POPULATION NORMALIZATION FOR COMPARATIVE ANALYSIS OF NUCLEIC ACID SAMPLES 审中-公开
标题翻译：核酸样品比较分析的竞争性人口普查
公开(公告)号：WO2002061140A2
公开(公告)日：2002-08-08
申请号：PCT/US2002/002892
申请日：2002-01-31
申请人： AMBION, INC. , BROWN, David , WINKLER, Matthew, M.
发明人： BROWN, David , WINKLER, Matthew, M.
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , C12Q2527/143 , C12Q2525/161 , C12Q2525/143 , C12Q2525/155
摘要： Methods are disclosed that convert two or more complex nucleic acid samples into a single collection of normalized target molecules that can be used to compare the abundance of each of the targets in the original samples. Multiple RNA or DNA samples are uniquely tagged and pooled to create a sample mixture. A defined set of target within the sample mixture is converted to approximately equal amounts of nucleic acid by one of several methods employing primer extension with a set of target specific primers. The concentration of target specific primers is equal and limiting for all targets, therefore an appropriate number of primer extension cycles converts all targets to similar final concentrations of product nucleic acid. The different tags appended to the sample nucleic acids from each sample population unique. These different tags are used to generate RNA or DNA , molecules for analysis that derive form each of the input samples. The disclosed methods are primarily intended to enhance gene array analysis, however, any method used to compare multiple nucleic acid targets form different samples will benefit form the invention.
摘要翻译：公开了将两个或更多个复合核酸样品转化成归一化的靶分子的单一集合的方法，其可用于比较原始样品中每个靶的丰度。多个RNA或DNA样品被独特地标记和合并以产生样品混合物。样品混合物中定义的一组靶标通过使用一组靶特异性引物的引物延伸的几种方法之一转化为大致相等量的核酸。靶标特异性引物的浓度对于所有靶标是相同的并且是有限的，因此适当数量的引物延伸周期将所有靶标转化为产物核酸的相似终浓度。来自每个样本群体的示例核酸附加的不同标签是唯一的。这些不同的标签用于产生RNA或DNA，用于分析的分子，其从每个输入样品得到。所公开的方法主要用于增强基因阵列分析，然而，用于比较多个核酸靶标形成不同样品的任何方法将从本发明中受益。

7. 发明申请

WO2006042303A2 METHODS AND COMPOSITIONS FOR ANALYZING NUCLEIC ACIDS 审中-公开
标题翻译：分析核酸的方法和组合物
公开(公告)号：WO2006042303A2
公开(公告)日：2006-04-20
申请号：PCT/US2005/036799
申请日：2005-10-12
申请人： AMBION, INC. , WINKLER, Matthew, M. , GOLDRICK, Marianna , HARRIS, Nathan , YE, Fei
发明人： WINKLER, Matthew, M. , GOLDRICK, Marianna , HARRIS, Nathan , YE, Fei
CPC分类号： C12Q1/6844 , C12Q1/6809 , C12Q1/686 , C12Q1/6865 , C12Q2561/108 , C12Q2561/101 , C12Q2525/161 , C12Q2525/143 , C12Q2525/203 , C12Q2521/301
摘要： Methods and compositions for probe , amplification to detect, identify, quantitate, and/or analyze a targeted nucleic acid sequence. After hybridization between a probe and the targeted nucleic acid, the probe is modified to distinguish hybridized probe from unhybridized probe. Tl ereafter, the probe is amplified. Moreover, in specific embodiments, the present invention involves a chimeric probe that is particularly effective when the targeted nucleic acid sequence is short and/or has a relatively low concentration, such as with an miRNA molecule.
摘要翻译：用于探针，扩增以检测，鉴定，定量和/或分析靶向核酸序列的方法和组合物。在探针与靶向核酸杂交后，修饰探针以将杂交探针与未杂交的探针区分开。之后，探针被放大。此外，在具体实施方案中，本发明涉及当靶向的核酸序列短和/或具有相对低的浓度时，例如与miRNA分子特别有效的嵌合探针。

8. 发明申请

WO2005083081A1 IMPROVED NUCLEASE INHIBITOR COCKTAIL 审中-公开
标题翻译：改进的核苷酸抑制剂
公开(公告)号：WO2005083081A1
公开(公告)日：2005-09-09
申请号：PCT/US2005/006394
申请日：2005-02-25
申请人： AMBION, INC. , LATHAM, Gary, J. , WINKLER, Matthew, M. , PASLOSKE, Brittan, L. , KUDLICKI, Antoni, W.
发明人： LATHAM, Gary, J. , WINKLER, Matthew, M. , PASLOSKE, Brittan, L. , KUDLICKI, Antoni, W.
IPC分类号： C12N15/10
CPC分类号： C12N15/1003 , C07K16/40 , C12N15/1096 , C12Q1/34 , G01N33/573 , G01N2333/922
摘要： Methods and compositions for inhibiting and/or inactivating nucleases by using nuclease inhibitors are provided. The nuclease inhibitors comprise anti-nuclease antibodies and non-antibody nuclease inhibitors.
摘要翻译：提供了通过使用核酸酶抑制剂来抑制和/或灭活核酸酶的方法和组合物。核酸酶抑制剂包括抗核酸酶抗体和非抗体核酸酶抑制剂。

9. 发明授权

EP0910643B1 RIBONUCLEASE RESISTANT RNA PREPARATION AND UTILIZATION 失效
标题翻译：核糖核酸酶抗性RNA的制备和利用
公开(公告)号：EP0910643B1
公开(公告)日：2006-08-30
申请号：EP97933547.8
申请日：1997-07-02
申请人： AMBION, INC. , Cenetron Diagnostics LLC
发明人： DUBOIS, Dwight, B. , WINKLER, Matthew, M. , PASLOSKE, Brittan, L.
IPC分类号： C12N15/40 , C12N15/48 , C12N15/51 , C12N15/10 , C12N15/88 , C12N7/04 , C12Q1/68 , C12Q1/70 , C12P19/34
CPC分类号： C12N7/00 , C07K14/005 , C12N15/10 , C12N15/86 , C12N15/88 , C12N2740/16022 , C12N2740/16062 , C12N2740/16222 , C12N2770/00022 , C12N2770/00023 , C12N2770/00042 , C12N2770/34022 , C12N2770/34023 , C12N2770/34042 , C12N2770/36123 , C12N2770/36143 , C12N2795/10122 , C12N2795/10142 , C12N2795/18122 , C12N2795/18123 , C12P19/34 , C12Q1/6851 , C12Q1/702 , C12Q1/706 , C12Q1/707 , C12Q2600/158 , C12Q2545/113
摘要： The present invention relates to nuclease resistant nucleic acids in general and ribonuclease resistant RNAs in particular. Methods of making and using such nucleic acids are disclosed.
摘要翻译：本发明一般涉及核酸酶抗性核酸，特别涉及核糖核酸酶抗性RNA。公开了制造和使用这种核酸的方法。

10. 发明公开

EP1812599A2 METHODS AND COMPOSTITIONS FOR ANALYSING RIBONUCLEIC ACIDS 有权
标题翻译：方法和组合物分析核糖核酸
公开(公告)号：EP1812599A2
公开(公告)日：2007-08-01
申请号：EP05815286.9
申请日：2005-10-12
申请人： AMBION, INC.
发明人： WINKLER, Matthew, M. , GOLDRICK, Marianna , HARRIS, Nathan , YE, Fei
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6844 , C12Q1/6809 , C12Q1/686 , C12Q1/6865 , C12Q2561/108 , C12Q2561/101 , C12Q2525/161 , C12Q2525/143 , C12Q2525/203 , C12Q2521/301
摘要： Methods and compositions for probe, amplification to detect, identify, quantitate, and/or analyze a targeted nucleic acid sequence. After hybridization between a probe and the targeted nucleic acid, the probe is modified to distinguish hybridized probe from unhybridized probe. Thereafter, the probe is amplified. Moreover, in specific embodiments, the present invention involves a chimeric probe that is particularly effective when the targeted nucleic acid sequence is short and/or has a relatively low concentration, such as with an miRNA molecule.

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