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11. 发明申请

US20150065352A1 MONITORING HEALTH AND DISEASE STATUS USING CLONOTYPE PROFILES 有权
标题翻译：使用CLONOTYPE配置文件监测健康和疾病状态
公开(公告)号：US20150065352A1
公开(公告)日：2015-03-05
申请号：US14176551
申请日：2014-02-10
申请人： Malek Faham , Thomas Willis
发明人： Malek Faham , Thomas Willis
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6874 , C12Q1/6881 , C12Q1/6883 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16
摘要： There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.
摘要翻译：需要一种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，特别是淋巴瘤和白血病等淋巴样肿瘤。本文提供了使用DNA测序鉴定患有淋巴样肿瘤，自身免疫疾病和其他病症的个体化或患者特异性生物标志物的方法。识别的生物标志物可以用于确定和/或监测具有相关淋巴样病症或自身免疫疾病或其他病症的受试者的疾病状态。特别地，本发明提供了用于监测经历克隆进化的淋巴样肿瘤的敏感方法，而不需要用作用作患者特异性生物标志物的进化或突变克隆的替代性测定。

12. 发明申请

US20140356339A1 SEQUENCE-BASED MEASURES OF IMMUNE RESPONSE 审中-公开
标题翻译：基于序列的免疫应答措施
公开(公告)号：US20140356339A1
公开(公告)日：2014-12-04
申请号：US14343286
申请日：2012-08-31
申请人： Malek Faham , Martin Moorehead , Thomas Willis
发明人： Malek Faham , Martin Moorehead , Thomas Willis
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6883 , C12Q1/6886 , C12Q2600/158
摘要： The invention is directed to methods of measuring an immune response by comparing sequence-based clonotype frequency data from successively measured clonotype profiles. In particular, the invention includes immunotherapies of cancers, such as lymphomas, that include sensitive pre- and post-vaccination sequence-based measurements of changes in a patient's immune repertoire, thereby providing a sensitive measure of the likelihood of treatment success.
摘要翻译：本发明涉及通过比较来自连续测量的克隆型谱的基于序列的克隆型频率数据来测量免疫应答的方法。特别地，本发明包括诸如淋巴瘤的癌症的免疫疗法，其包括敏感的接种前和接种后基于序列的测量患者免疫谱的变化，从而提供治疗成功可能性的敏感度量。

13. 发明授权

US08691510B2 Sequence analysis of complex amplicons 有权
标题翻译：复合扩增子的序列分析
公开(公告)号：US08691510B2
公开(公告)日：2014-04-08
申请号：US13100389
申请日：2011-05-04
申请人： Malek Faham , Martin Moorhead , Thomas Willis
发明人： Malek Faham , Martin Moorhead , Thomas Willis
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6881 , C12Q1/6874 , C12Q1/6883 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to methods of generating sequence profiles of populations of nucleic acids, whose member nucleic acids contain regions of high variability, such as populations of nucleic acids encoding T cell receptors or B cell receptors. In one aspect, the invention provides pluralities of sets of primers for generating nested sets of templates from nucleic acids in such populations, thereby insuring the production of at least one template from which sequence reads are generated, despite such variability, or dispite limited lengths or quality of sequence reads. In another aspect, members of such populations are bidirectionally sequenced so that further sequence information is obtained by analyzing overlapping sequence reads in the zones of highest variability.
摘要翻译：本发明涉及产生核酸群体序列谱的方法，该核酸的成员核酸含有高度变异性的区域，例如编码T细胞受体或B细胞受体的核酸群体。在一个方面，本发明提供了多组引物，用于从这些群体中的核酸产生嵌套的模板集合，从而确保产生序列读取的至少一个模板的产生，尽管存在这种变化，或者限制长度或序列读取的质量。在另一方面，这些群体的成员被双向排序，以便通过分析最高变异性区域中的重叠序列读数来获得进一步的序列信息。

14. 发明申请

US20120135409A1 METHODS OF MONITORING CONDITIONS BY SEQUENCE ANALYSIS 审中-公开
标题翻译：通过序列分析监测条件的方法
公开(公告)号：US20120135409A1
公开(公告)日：2012-05-31
申请号：US13214111
申请日：2011-08-19
申请人： Malek Faham , Thomas Willis
发明人： Malek Faham , Thomas Willis
IPC分类号： C12Q1/68
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。

15. 发明申请

US20110207135A1 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：US20110207135A1
公开(公告)日：2011-08-25
申请号：US13100389
申请日：2011-05-04
申请人： Malek Faham , Martin Moorhead , Thomas Willis
发明人： Malek Faham , Martin Moorhead , Thomas Willis
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C12Q1/6874 , C12Q1/6883 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to methods of generating sequence profiles of populations of nucleic acids, whose member nucleic acids contain regions of high variability, such as populations of nucleic acids encoding T cell receptors or B cell receptors. In one aspect, the invention provides pluralities of sets of primers for generating nested sets of templates from nucleic acids in such populations, thereby insuring the production of at least one template from which sequence reads are generated, despite such variability, or dispite limited lenghs or quality of sequence reads. In another aspect, members of such populations are bidirectionally sequenced so that further sequence information is obtained by analyzing overlapping sequence reads in the zones of highest variability.
摘要翻译：本发明涉及产生核酸群体序列谱的方法，该核酸的成员核酸含有高度变异性的区域，例如编码T细胞受体或B细胞受体的核酸群体。在一个方面，本发明提供了多组引物，用于从这些群体中的核酸产生嵌套的模板集合，从而确保产生序列读数的至少一个模板的产生，尽管存在这种可变性，或者排除有限的长度或序列读取的质量。在另一方面，这些群体的成员被双向排序，以便通过分析最高变异性区域中的重叠序列读数来获得进一步的序列信息。

16. 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。

17. 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。

18. 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。

19. 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。

20. 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。

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