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21. 发明申请

US20090233809A1 RESEQUENCING METHODS FOR IDENTIFICATION OF SEQUENCE VARIANTS 审中-公开
标题翻译：用于识别序列变量的测度方法
公开(公告)号：US20090233809A1
公开(公告)日：2009-09-17
申请号：US12398177
申请日：2009-03-04
申请人： Malek Faham , Jianbiao Zheng
发明人： Malek Faham , Jianbiao Zheng
IPC分类号： C40B30/04 , C40B40/08
CPC分类号： C12Q1/6827 , C12Q1/6874 , C12Q2565/513 , C12Q2535/131
摘要： Methods for detection of variant alleles are disclosed. In preferred aspects variants are detected by hybridization patterns to arrays of probes that are contain a single mismatch to a reference sequence, thus reducing the number of probes needed for resequencing by hybridization. The target capture method used is Target Amplification by Capture and Ligation (TACL), and is capable of amplifying many thousands of loci together. Mismatch Repair Detection (MRD) is used as an allele enrichment method to efficiently sort variant and non-variant alleles in thousands of loci simultaneously.
摘要翻译：公开了用于检测变异等位基因的方法。在优选的方面，通过与参考序列单个错配的探针阵列的杂交模式检测变体，从而减少通过杂交重排序所需的探针的数量。所采用的靶捕获方法是通过捕获和连接（TACL）进行靶向扩增，并且能够将数千个位点放在一起。使用不匹配修复检测（MRD）作为等位基因富集方法，以有效地对数千个位点中的变异和非变异等位基因进行同时分选。

22. 发明申请

US20150247201A1 PREDICTING RELAPSE OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED BY ALLOGENEIC STEM CELL TRANSPLANTATION 审中-公开
标题翻译：慢性淋巴细胞移植治疗慢性淋巴细胞白血病患者预后的相关性
公开(公告)号：US20150247201A1
公开(公告)日：2015-09-03
申请号：US14404435
申请日：2013-05-30
申请人： Malek Faham , Victoria Carlton , Martin Moorhead , Francois Pepin
发明人： Malek Faham , Victoria Carlton , Martin Moorhead , Francois Pepin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to a prognostic indicator for CLL patients who have undergone an allogeneic stem cell transplant (SCT). The indicator is based on a method of monitoring levels and changes in levels of correlating clonotypes of the CLLs at successive time points. The prognostic indicator applies to patients who have survived for at least one year from an allogeneic SCT and includes criteria based on the following two measurements: (a) frequency of CLL correlating clonotypes (e.g. in terms of number per 106 clonotypes) in an initial clonotype profile (from peripheral blood), and (b) fold change in such CLL correlating clonotype number between such initial measurement and a successively measured clonotype profile.
摘要翻译：本发明涉及经历同种异体干细胞移植（SCT）的CLL患者的预后指标。该指标基于在连续时间点监测CLL相关性克隆型水平和水平变化的方法。预后指标适用于从同种异体SCT生存至少一年的患者，并包括基于以下两个测量的标准：（a）CLL相关克隆型（例如，以106个克隆型的数目）在初始克隆型中的频率（来自外周血），和（b）在这种初始测量和连续测量的克隆型分布之间的这种CLL相关克隆型号的倍数变化。

23. 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。

24. 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。

25. 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。

26. 发明申请

US20130196328A1 RARE CLONOTYPES AND USES THEREOF 有权
标题翻译：罕见的克隆及其用途
公开(公告)号：US20130196328A1
公开(公告)日：2013-08-01
申请号：US13834794
申请日：2013-03-15
申请人： Francois Pepin , Malek Faham , Martin Moorhead
发明人： Francois Pepin , Malek Faham , Martin Moorhead
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6883 , C12Q2600/158
摘要： The invention is directed to a method of selecting disease-correlated clonotypes that have a reduced likelihood of producing a false positive signal of relapse when, used to monitor minimal residual disease. In accordance with the invention, candidate correlating clonotype are obtained from a patient, the rarity of each is determined either by comparison with a clonotype database or a clonotype model, and one or more of the rarest of such clonotypes are used to monitor the minimal residual disease.
摘要翻译：本发明涉及一种选择疾病相关性克隆型的方法，所述疾病相关性克隆型在用于监测最小残留疾病时具有降低的产生假阳性信号的可能性。根据本发明，从患者获得候选相关克隆型，通过与克隆型数据库或克隆型模型比较来确定每个的罕见性，并且使用一种或多种最稀有的这种克隆型来监测最小残留疾病。

27. 发明申请

US20130136799A1 MONITORING HEALTH AND DISEASE STATUS USING CLONOTYPE PROFILES 有权
公开(公告)号：US20130136799A1
公开(公告)日：2013-05-30
申请号：US13763978
申请日：2013-02-11
申请人： Malek Faham
发明人： Malek Faham
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6881 , C12Q1/6883 , 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.

28. 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。

29. 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。

30. 发明申请

US20110124052A1 Multiplex Targeted Amplification Using Flap Nuclease 有权
标题翻译：使用翼片核酸酶进行多重靶向扩增
公开(公告)号：US20110124052A1
公开(公告)日：2011-05-26
申请号：US12972208
申请日：2010-12-17
申请人： Jianbiao Zheng , Li Weng , Malek Faham
发明人： Jianbiao Zheng , Li Weng , Malek Faham
IPC分类号： 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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