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1. 发明申请

US20090130660A1 Single Nucelotide Polymorphism (SNP) 审中-公开
标题翻译：单核苷酸多态性（SNP）
公开(公告)号：US20090130660A1
公开(公告)日：2009-05-21
申请号：US11792772
申请日：2005-12-05
申请人： Malek Faham , Soren Germer , Hywel Bowden Jones , Delphine Lagarde , Mitchell Lee Martin , Martin Emilio Moorhead , Erik Roy Rasmussen , Brian Kent Rhees , James Andrew Rosinski
发明人： Malek Faham , Soren Germer , Hywel Bowden Jones , Delphine Lagarde , Mitchell Lee Martin , Martin Emilio Moorhead , Erik Roy Rasmussen , Brian Kent Rhees , James Andrew Rosinski
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , C12Q2600/172
摘要： Association of Type 2 diabetes with single nucleotide polymorphisms and haplotypes are disclosed. Also disclosed are diagnostic applications in identifying those who have Type 2 diabetes or are at risk of developing Type 2 diabetes, and discovery of therapeutic agents and methods of treatment.
摘要翻译：公开了2型糖尿病与单核苷酸多态性和单体型的关联。还公开了用于鉴定具有2型糖尿病或具有发展为2型糖尿病风险的患者的诊断应用，以及治疗剂和治疗方法的发现。

2. 发明授权

US08980563B2 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：US08980563B2
公开(公告)日：2015-03-17
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： 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。

3. 发明申请

US20140255944A1 MONITORING TREATMENT-RESISTANT CLONES IN LYMPHOID AND MYELOID NEOPLASMS BY RELATIVE LEVELS OF EVOLVED CLONOTYPES 审中-公开
标题翻译：通过相对级别的革兰阳性监测淋巴细胞和髓磷脂细胞中的治疗抗性克隆
公开(公告)号：US20140255944A1
公开(公告)日：2014-09-11
申请号：US14197615
申请日：2014-03-05
申请人： Victoria Carlton , Malek Faham
发明人： Victoria Carlton , Malek Faham
IPC分类号： C12Q1/68
CPC分类号： C12Q1/686 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156
摘要： The invention is directed to a method of monitoring or detecting treatment-resistant clones in a patient being treated for a lymphoid or myeloid neoplasm from which patient-specific correlating clonotypes have been identified. In some embodiments, such method includes the steps of obtaining a sample from the patient comprising T-cells and/or B-cells; amplifying molecules of nucleic acid from the T-cells and/or B-cells of the sample, the molecules of nucleic acid comprising recombined DNA sequences from T-cell receptor genes or immunoglobulin genes; sequencing the amplified molecules of nucleic acid to form a clonotype profile; determining from the clonotype profile a level of each correlating clonotype and clonotypes clonally evolved therefrom; and correlating a presence of a treatment-resistant clone of the neoplasm with a change in relative levels of the correlating clonotypes and clonotypes clonally evolved therefrom. In part, the invention permits one to distinguish between cases where treatment is effective but insufficiently intense and cases where a cancer clone arises that is resistant to a current treatment approach.
摘要翻译：本发明涉及一种监测或检测被治疗的患者的治疗抗性克隆的方法，所述治疗抗性克隆被治疗用于已经鉴定了患者特异性相关克隆型的淋巴或骨髓瘤。在一些实施方案中，这种方法包括从包括T细胞和/或B细胞的患者获得样品的步骤; 从样品的T细胞和/或B细胞扩增核酸分子，所述核酸分子包含来自T细胞受体基因或免疫球蛋白基因的重组DNA序列; 测序扩增的核酸分子以形成克隆型谱; 从克隆型分析确定每个相关克隆型和从其中克隆进化的克隆型的水平; 并将肿瘤的治疗抗性克隆的存在与从其克隆进行的相关克隆型和克隆型的相对水平的变化相关联。部分地，本发明允许区分治疗有效但不充分的情况，以及出现对当前治疗方法有抗性的癌症克隆的情况。

4. 发明授权

US08748103B2 Monitoring health and disease status using clonotype profiles 有权
公开(公告)号：US08748103B2
公开(公告)日：2014-06-10
申请号：US13100365
申请日：2011-05-04
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 , 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.

5. 发明授权

US08628927B2 Monitoring health and disease status using clonotype profiles 有权
标题翻译：使用克隆型概况监测健康和疾病状态
公开(公告)号：US08628927B2
公开(公告)日：2014-01-14
申请号：US13763978
申请日：2013-02-11
申请人： Malek Faham , Thomas Willis
发明人： Malek Faham , Thomas Willis
IPC分类号： C12P19/34 , 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.
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。

6. 发明授权

US08236503B2 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：US08236503B2
公开(公告)日：2012-08-07
申请号：US12615263
申请日：2009-11-09
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。

7. 发明申请

US20080199916A1 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：US20080199916A1
公开(公告)日：2008-08-21
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： 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。

8. 发明申请

US20050239080A1 Mismatch repair detection 审中-公开
标题翻译：不匹配修复检测
公开(公告)号：US20050239080A1
公开(公告)日：2005-10-27
申请号：US10728122
申请日：2003-12-03
申请人： David Cox , Malek Faham , Siamak Baharloo
发明人： David Cox , Malek Faham , Siamak Baharloo
IPC分类号： C12N1/21 , C12N15/74 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6897 , C12Q2600/156
摘要： Mismatch Repair Detection (MRD), a novel method for DNA-variation detection, utilizes bacteria to detect mismatches by a change in expression of a marker gene. DNA fragments to be screened for variation are cloned into two MRD plasmids, and bacteria are transformed with heteroduplexes of these constructs. Resulting colonies express the marker gene in the absence of a mismatch, and lack expression in the presence of a mismatch. MRD is capable of detecting a single mismatch within 10 kb of DNA. In addition, MRD can analyze many fragments simultaneously, offering a powerful method for high-throughput genotyping and mutation detection.
摘要翻译：用于DNA变异检测的新方法的不匹配修复检测（MRD）利用细菌通过标记基因的表达变化来检测错配。将待筛选的DNA片段克隆到两个MRD质粒中，并用这些构建体的异源双链体转化细菌。得到的菌落在不存在错配的情况下表达标记基因，并且在存在失配的情况下缺乏表达。 MRD能够检测DNA的10 kb内的单一错配。此外，MRD可以同时分析许多片段，为高通量基因分型和突变检测提供了强大的方法。

9. 发明授权

US06406847B1 Mismatch repair detection 失效
公开(公告)号：US06406847B1
公开(公告)日：2002-06-18
申请号：US09271055
申请日：1999-03-17
申请人： David R. Cox , Malek Faham , Siamak Baharloo
发明人： David R. Cox , Malek Faham , Siamak Baharloo
IPC分类号： C12Q168
CPC分类号： C12Q1/6827 , C12Q1/6897 , C12Q2600/156
摘要： Mismatch Repair Detection (MRD), a novel method for DNA-variation detection, utilizes bacteria to detect mismatches by a change in expression of a marker gene. DNA fragments to be screened for variation are cloned into two MRD plasmids, and bacteria are transformed with heteroduplexes of these constructs. Resulting colonies express the marker gene in the absence of a mismatch, and lack expression in the presence of a mismatch. MRD is capable of detecting a single mismatch within 10 kb of DNA. In addition, MRD can analyze many fragments simultaneously, offering a powerful method for high-throughput genotyping and mutation detection.

10. 发明申请

US20130005584A1 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：US20130005584A1
公开(公告)日：2013-01-03
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： 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.
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。

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