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31. 发明授权

US07510829B2 Multiplex PCR 有权
标题翻译：多重PCR
公开(公告)号：US07510829B2
公开(公告)日：2009-03-31
申请号：US10300285
申请日：2002-11-19
申请人： Malek Faham , Eugeni Anatolyevich Namsaraev , Thomas Daniel Willis
发明人： Malek Faham , Eugeni Anatolyevich Namsaraev , Thomas Daniel Willis
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/04
CPC分类号： C12Q1/6853 , C12Q1/6855 , C12Q2537/143 , C12Q2525/161 , C12Q2521/325 , C12Q2521/307
摘要： Compositions and methods for nucleic acid amplification are provided that minimize the formation and amplification of spurious products, particularly in multiplex amplification reactions. Linear amplification molecules are provided. A first embodiment comprises a first common primer sequence, a first template homology region, a cleavable site, a second common primer sequence and a second template homology region. Methods employing the linear amplification molecules for nucleic acid amplification are also provided. A first embodiment comprises a template-specific hybridization, a linear amplification, a template-specific intramolecular hybridization, a strand cleavage, a second linear amplification and an exponential amplification using common primers.
摘要翻译：提供用于核酸扩增的组合物和方法，其使杂散产物的形成和扩增最小化，特别是在多重扩增反应中。提供线性扩增分子。第一实施方案包括第一共同引物序列，第一模板同源区，可切割位点，第二共同引物序列和第二模板同源区。还提供了使用线性扩增分子进行核酸扩增的方法。第一个实施方案包括模板特异性杂交，线性扩增，模板特异性分子内杂交，链切割，第二线性扩增和使用常规引物的指数扩增。

32. 发明申请

US20070065865A1 Polymorphisms Associated with Coronary Artery Disease 审中-公开
标题翻译：与冠状动脉疾病相关的多态性
公开(公告)号：US20070065865A1
公开(公告)日：2007-03-22
申请号：US11530407
申请日：2006-09-08
申请人： Victoria Carlton , Martin Moorhead , Chunnuan Chen , Malek Faham
发明人： Victoria Carlton , Martin Moorhead , Chunnuan Chen , Malek Faham
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/156
摘要： The invention provides human polymorphisms that are associated with coronary artery disease (CAD). Polymorphisms in genes were identified that confer an increased susceptibility to CAD or a decreased susceptibility. Particular alleles of the polymorphisms were identified as being associated with differential risk. In particular an allele of CDC42 in combination with an allele of PARD3 was shown to confer increased risk of CAD.
摘要翻译：本发明提供与冠状动脉疾病（CAD）相关的人多态性。鉴定出基因多态性导致对CAD的敏感性增加或易感性降低。多态性的特定等位基因被鉴定为与差异风险相关。特别地，CDC42与PARD3的等位基因组合的等位基因被证明具有增加的CAD风险。

33. 发明授权

US09217176B2 Methods of monitoring conditions by sequence analysis 有权
标题翻译：通过序列分析监测条件的方法
公开(公告)号：US09217176B2
公开(公告)日：2015-12-22
申请号：US13459701
申请日：2012-04-30
申请人： Malek Faham , Thomas Willis
发明人： Malek Faham , Thomas Willis
IPC分类号： C12P19/34 , C12Q1/68 , C12N15/10
CPC分类号： C12Q1/6886 , C12N15/1072 , C12Q1/6809 , C12Q1/6827 , C12Q1/6869 , C12Q1/6881 , C12Q1/6883 , C12Q2600/106 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , Y02A90/26
摘要： There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.
摘要翻译：需要改进的方法来确定包括自身免疫性疾病和癌症在内的患者的诊断和预后。本文提供了使用DNA测序鉴定患有自身免疫疾病和其他病症的个体化生物标志物的方法。识别的生物标志物可用于确定具有自身免疫疾病或其他病症的受试者的疾病状态。

34. 发明申请

US20150167080A1 METHOD OF DETERMINING CLONOTYPES AND CLONOTYPE PROFILES 有权
标题翻译：确定克隆和克隆型材的方法
公开(公告)号：US20150167080A1
公开(公告)日：2015-06-18
申请号：US13196885
申请日：2011-08-02
申请人： Martin Moorhead , Malek Faham , Thomas Willis
发明人： Martin Moorhead , Malek Faham , Thomas Willis
IPC分类号： C12Q1/68 , C40B20/00
CPC分类号： C12Q1/6881 , C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , G06F19/14 , G06F19/22
摘要： The invention is directed to methods for determining clonotypes and clonotype profiles in assays for analyzing immune repertoires by high throughput nucleic acid sequencing of somatically recombined immune molecules. In one aspect, the invention comprises generating a clonotype profile from an individual by generating sequence reads from a sample of recombined immune molecules; forming from the sequence reads a sequence tree representing candidate clonotypes each having a frequency; coalescing with a highest frequency candidate clonotype any lesser frequency candidate clonotypes whenever such lesser frequency is below a predetermined value and whenever a sequence difference therebetween is below a predetermined value to form a clonotype. After such coalescence, the candidate clonotypes is removed from the sequence tree and the process is repeated. This approach permits rapid and efficient differentiation of candidate clonotypes with genuine sequence differences from those with experimental or measurement errors, such as sequencing errors.
摘要翻译：本发明涉及用于通过体细胞重组的免疫分子的高通量核酸测序分析免疫谱的测定中的克隆型和克隆型谱的方法。在一个方面，本发明包括通过从重组的免疫分子的样品产生序列读数来从个体产生克隆型谱; 从序列形成读取表示每个具有频率的候选克隆型的序列树; 每当这样较小的频率低于预定值，并且每当它们之间的序列差异低于预定值以形成克隆型时，以最高频率候选克隆型任何较低频率候选克隆型聚合。在这样的聚结之后，从序列树中移除候选克隆型，并重复该过程。这种方法允许用具有实验或测量误差（例如测序错误）的那些具有真正序列差异的候选克隆型的快速和有效的分化。

35. 发明授权

US09043160B1 Method of determining clonotypes and clonotype profiles 有权
标题翻译：确定克隆型和克隆型谱的方法
公开(公告)号：US09043160B1
公开(公告)日：2015-05-26
申请号：US13196885
申请日：2011-08-02
申请人： Martin Moorhead , Malek Faham , Thomas Willis
发明人： Martin Moorhead , Malek Faham , Thomas Willis
IPC分类号： G06F7/00 , G06F19/14
CPC分类号： C12Q1/6881 , C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , G06F19/14 , G06F19/22
摘要： The invention is directed to methods for determining clonotypes and clonotype profiles in assays for analyzing immune repertoires by high throughput nucleic acid sequencing of somatically recombined immune molecules. In one aspect, the invention comprises generating a clonotype profile from an individual by generating sequence reads from a sample of recombined immune molecules; forming from the sequence reads a sequence tree representing candidate clonotypes each having a frequency; coalescing with a highest frequency candidate clonotype any lesser frequency candidate clonotypes whenever such lesser frequency is below a predetermined value and whenever a sequence difference therebetween is below a predetermined value to form a clonotype. After such coalescence, the candidate clonotypes is removed from the sequence tree and the process is repeated. This approach permits rapid and efficient differentiation of candidate clonotypes with genuine sequence differences from those with experimental or measurement errors, such as sequencing errors.
摘要翻译：本发明涉及用于通过体细胞重组的免疫分子的高通量核酸测序分析免疫谱的测定中的克隆型和克隆型谱的方法。在一个方面，本发明包括通过从重组的免疫分子的样品产生序列读数来从个体产生克隆型谱; 从序列形成读取表示每个具有频率的候选克隆型的序列树; 每当这样较小的频率低于预定值，并且每当它们之间的序列差异低于预定值以形成克隆型时，以最高频率候选克隆型任何较低频率候选克隆型聚合。在这样的聚结之后，从序列树中移除候选克隆型，并重复该过程。这种方法允许用具有实验或测量误差（例如测序错误）的那些具有真正序列差异的候选克隆型的快速和有效的分化。

36. 发明授权

US08795970B2 Methods of monitoring conditions by sequence analysis 有权
标题翻译：通过序列分析监测条件的方法
公开(公告)号：US08795970B2
公开(公告)日：2014-08-05
申请号：US13468323
申请日：2012-05-10
申请人： Malek Faham , Thomas Willis
发明人： Malek Faham , Thomas Willis
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6886 , C12N15/1072 , C12Q1/6809 , C12Q1/6827 , C12Q1/6869 , C12Q1/6881 , C12Q1/6883 , C12Q2600/106 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , Y02A90/26
摘要： There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.
摘要翻译：需要改进的方法来确定包括自身免疫性疾病和癌症在内的患者的诊断和预后。本文提供了使用DNA测序鉴定患有自身免疫疾病和其他病症的个体化生物标志物的方法。识别的生物标志物可用于确定具有自身免疫疾病或其他病症的受试者的疾病状态。

37. 发明申请

US20130065768A1 RANDOM ARRAY SEQUENCING OF LOW-COMPLEXITY LIBRARIES 审中-公开
标题翻译：低复杂图书馆的随机阵列测序
公开(公告)号：US20130065768A1
公开(公告)日：2013-03-14
申请号：US13596581
申请日：2012-08-28
申请人： Jianbiao Zheng , Thomas Willis , Malek Faham
发明人： Jianbiao Zheng , Thomas Willis , Malek Faham
IPC分类号： C40B20/00
CPC分类号： C40B20/00 , C12Q1/6874 , C40B50/14 , C12Q2525/155 , C12Q2535/122 , C12Q2565/543
摘要： The invention is directed to a method of sequencing low-complexity amplicons randomly arrayed at high density on a surface. Methods of the invention include preparing amplicons for sequencing by a sets of primers that ensure initial signals front different amplicons on the surface will be evenly distributed among the different nucleotides being added in a sequencing by synthesis operation.
摘要翻译：本发明涉及一种排列在表面上以高密度随机排列的低复杂度扩增子的方法。本发明的方法包括通过一组引物制备用于测序的扩增子，其确保初始信号在表面上的不同扩增子前沿将通过合成操作在测序中添加的不同核苷酸之间均匀分布。

38. 发明申请

US20130017957A1 METHODS OF MONITORING CONDITIONS BY SEQUENCE ANALYSIS 有权
公开(公告)号：US20130017957A1
公开(公告)日：2013-01-17
申请号：US13468323
申请日：2012-05-10
申请人： Malek Faham , Thomas Willis
发明人： Malek Faham , Thomas Willis
IPC分类号： C40B20/00
CPC分类号： C12Q1/6886 , C12N15/1072 , C12Q1/6809 , C12Q1/6827 , C12Q1/6869 , C12Q1/6881 , C12Q1/6883 , C12Q2600/106 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , Y02A90/26
摘要： There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.

39. 发明申请

US20110151438A9 Methods of Analysis of Methylation 审中-公开
标题翻译：甲基化分析方法
公开(公告)号：US20110151438A9
公开(公告)日：2011-06-23
申请号：US11923649
申请日：2007-10-24
申请人： Shivani Nautiyal , Malek Faham
发明人： Shivani Nautiyal , Malek Faham
IPC分类号： C12Q1/68
CPC分类号： C12Q1/683 , C12Q1/6806 , C12Q1/6813
摘要： Methods for determining the methylation status of a plurality of cytosines are disclosed. In some aspects genomic DNA target sequences containing CpGs are targeted for analysis by multiplex amplification using target specific probes that can be specifically degraded prior to amplification. The targets may be modified with bisulfite prior to amplification. In another aspect targets are cut with methylation sensitive or insensitive restriction enzymes and marked with a tag using the target specific probes. The presence or absence of methylation may be determined using methylation sensitive restriction enzyme or bisulfite treatment. Detection in many embodiments employs hybridization to tag arrays, genotyping arrays or resequencing arrays.
摘要翻译：公开了确定多种胞嘧啶的甲基化状态的方法。在某些方面，含有CpG的基因组DNA靶序列靶向用于通过多重扩增进行分析，使用可在扩增前特异性降解的靶特异性探针。在扩增前可以用亚硫酸氢盐修饰靶标。在另一方面，用甲基化敏感或不敏感限制酶切割靶标，并使用靶标特异性探针用标签标记。甲基化的存在或不存在可以使用甲基化敏感的限制酶或亚硫酸氢盐处理来确定。在许多实施方案中的检测采用与标签阵列，基因分型阵列或重排序阵列的杂交。

40. 发明授权

US07862999B2 Multiplex targeted amplification using flap nuclease 有权
标题翻译：使用瓣片核酸酶进行多重靶向扩增
公开(公告)号：US07862999B2
公开(公告)日：2011-01-04
申请号：US12016195
申请日：2008-01-17
申请人： Jianbiao Zheng , Li Weng , Malek Faham
发明人： Jianbiao Zheng , Li Weng , Malek Faham
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/686 , C12Q1/6844 , C12Q1/6853 , C12Q2531/125
摘要： Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5′ or 3′ flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are hybridized to dU probes so that 5′ and 3′ flaps are generated. The flaps are cleaved using 5′ or 3′ flap endonucleases or 3′ to 5′ exonucleases. The target sequences are then ligated to common primers, the dU probes digested and the ligated targets amplified.
摘要翻译：公开了从复杂混合物多个扩增不同序列的多个靶的方法。在一个方面，使用单个环化探针对靶标进行环化，所述单个环化探针与靶区域中将要扩增的区域侧翼的两个区域互补。目标可以与环化探针杂交，从而产生5'或3'的瓣，并且公开了用于去除襟翼和使所得产物环化的方法。另一方面，目标与dU探针杂交，从而产生5'和3'瓣。使用5'或3'片段内切核酸酶或3'至5'外切核酸酶切割襟翼。然后将靶序列连接到常见引物，消化dU探针并扩增连接的靶标。

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