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31. 发明授权

EP2326735B1 GENETIC ALTERATIONS IN ISOCITRATE DEHYDROGENASE AND OTHER GENES IN MALIGNANT GLIOMA 有权
标题翻译：异柠檬酸脱氢酶基因变异并在恶性胶质瘤的其他基因
公开(公告)号：EP2326735B1
公开(公告)日：2016-11-16
申请号：EP09792198.5
申请日：2009-09-03
申请人： The Johns Hopkins University , Duke University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PARSONS, D. Williams , ZHANG, Xiaosong , LIN, Jimmy Cheng-Ho , LEARY, Rebecca J. , ANGENENDT, Philipp , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , JONES, Sian , YAN, Hai , BIGNER, Darell , KUAN, Chien-Tsun , RIGGINS, Gregory J.
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/156

32. 发明公开

EP2326734A2 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 有权
标题翻译：胰腺肿瘤的发生和遗传PANKREASKREBSGEN信号通路
公开(公告)号：EP2326734A2
公开(公告)日：2011-06-01
申请号：EP09812193.2
申请日：2009-09-03
申请人： The Johns Hopkins University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , PARSONS, D., Williams , JONES, Sian , ZHANG, Xiaosong , LIN, Jimmy Chang-Ho , LEARY, Rebecca J. , ANGENENDT, Philipp , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison
IPC分类号： C12Q1/68
CPC分类号： G01N33/57438 , C12Q1/6886 , C12Q2600/156 , G01N2800/50
摘要： There are currently few therapeutic options for patients with pancreatic cancers and new insights into the pathogenesis of this lethal disease are urgently needed. To this end, we performed a comprehensive analysis of the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying ~one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies. We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70 % to 100 % of the samples. The data suggest that dysregulation of this core set of pathways is responsible for the major features of pancreatic tumorigenesis.

33. 发明授权

EP2326734B1 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 有权
标题翻译：胰腺肿瘤的发生和遗传PANKREASKREBSGEN信号通路
公开(公告)号：EP2326734B1
公开(公告)日：2016-11-09
申请号：EP09812193.2
申请日：2009-09-03
申请人： The Johns Hopkins University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , PARSONS, Donald William , JONES, Sian , ZHANG, Xiaosong , LIN, Jimmy Chang-Ho , LEARY, Rebecca J. , ANGENENDT, Philipp , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison
IPC分类号： C12Q1/68
CPC分类号： G01N33/57438 , C12Q1/6886 , C12Q2600/156 , G01N2800/50

34. 发明公开

EP2326735A1 GENETIC ALTERATIONS IN ISOCITRATE DEHYDROGENASE AND OTHER GENES IN MALIGNANT GLIOMA 有权
标题翻译：异柠檬酸脱氢酶基因变异并在恶性胶质瘤的其他基因
公开(公告)号：EP2326735A1
公开(公告)日：2011-06-01
申请号：EP09792198.5
申请日：2009-09-03
申请人： The Johns Hopkins University , Duke University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PARSONS, D. Williams , ZHANG, Xiaosong , LIN, Jimmy Chang-Ho , LEARY, Rebecca J. , ANGENENDT, Philipp , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , JONES, Sian , YAN, Hai , BIGNER, Darell , KUAN, Chien-Tsun
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/156
摘要： We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

35. 发明公开

EP1730303A2 MUTATIONS OF THE PIK3CA GENE IN HUMAN CANCERS 有权转让
标题翻译： PIK3CA基因在癌症突变在人类
公开(公告)号：EP1730303A2
公开(公告)日：2006-12-13
申请号：EP05723277.9
申请日：2005-02-18
申请人： THE JOHNS-HOPKINS UNIVERSITY
发明人： SAMUELS, Yardena , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the P13K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the P13K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.

36. 发明申请

WO2022140386A1 DETECTION OF LUNG CANCER USING CELL-FREE DNA FRAGMENTATION 审中-公开
公开(公告)号：WO2022140386A1
公开(公告)日：2022-06-30
申请号：PCT/US2021/064613
申请日：2021-12-21
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VELCULESCU, Victor , SCHARPF, Robert B. , MATHIOS, Dimitrios , PHALLEN, Jillian A. , BRUHM, Daniel , CRISTIANO, Stephen
IPC分类号： G06N5/04 , G16B25/10 , C12Q1/6874
摘要： Cell free DNA (cfDNA) fragmentation for lung cancer detection is combined with current imaging-based screening methods and biomarkers.

37. 发明申请

WO2018005276A1 NEOANTIGENS AS TARGETS FOR IMMUNOTHERAPY 审中-公开
标题翻译： NEOANTIGENS作为免疫治疗的靶点
公开(公告)号：WO2018005276A1
公开(公告)日：2018-01-04
申请号：PCT/US2017/038942
申请日：2017-06-23
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VELCULESCU, Victor , ANAGNOSTOU, Valsamo
IPC分类号： C12Q1/68 , G01N33/68 , C07K16/30
CPC分类号： A61K35/17 , A61K39/39 , A61P35/00 , C07K14/70539 , C12Q1/68 , C12Q1/6869 , C12Q1/6881 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , G01N33/56977 , G01N33/57484
摘要： Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have observed the emergence of acquired resistance in non-small cell lung cancer patients that were initially responsive to immune checkpoint blockade. Resistance occurred 4-11 months after the initiation of immunotherapy and both clinical response and therapeutic resistance were associated with changes in T cell clonality but not with changes in expression of PD-L1. Genomic analyses of responsive and resistant tumors from the same patients identified loss of 7 to 18 mutation-associated putative neoantigens in resistant clones that were predicted to have high MHC binding affinity. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations. These analyses provide insights into the mechanisms of evasion to immune checkpoint blockade and immune therapies that target tumor neoantigens.
摘要翻译：免疫检查点抑制剂已显示针对含有增加的突变相关新抗原负荷的肿瘤的显着治疗反应。我们观察到最初对免疫检查点阻断有反应的非小细胞肺癌患者中获得性耐药的出现。免疫治疗开始后4-11个月发生抗药性，临床反应和治疗抵抗均与T细胞克隆性变化相关，但与PD-L1表达变化无关。来自相同患者的响应性和抗性肿瘤的基因组分析鉴定出在预测具有高MHC结合亲和力的抗性克隆中缺失7至18个突变相关的推定新抗原。新抗原丢失通过消除肿瘤亚克隆或通过删除含有躯干改变的染色体区域而发生。这些分析提供了针对免疫检查点阻断和针对肿瘤新抗原的免疫疗法的逃避机制的见解。

38. 发明公开

EP3266879A1 GENETIC ALTERATIONS IN ISOCITRATE DEHYDROGENASE AND OTHER GENES IN MALIGNANT GLIOMA 有权转让
标题翻译：异常脱氧核糖核酸酶及其他基因在恶性脑胶质瘤中的遗传学改变
公开(公告)号：EP3266879A1
公开(公告)日：2018-01-10
申请号：EP17168866.6
申请日：2009-09-03
申请人： The Johns Hopkins University , Duke University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , JONES, Sian , YAN, Hai , BIGNER, Darell , KUAN, Chien-Tsun , RIGGINS, Gregory , PARSONS, Williams , ZHANG, Xiaosong , LIN, Jimmy Cheng-Ho , LEARY, Rebecca , ANGENENDT, Philipp
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/156
摘要： We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.
摘要翻译：我们在大多数II级和III级星形细胞瘤以及少突胶质细胞瘤以及从这些低级病变发展而来的胶质母细胞瘤中发现异柠檬酸脱氢酶1（IDH1）的R132残基突变。没有IDH1突变的那些肿瘤通常在密切相关的IDH2基因的类似R172残基处具有突变。这些发现对于恶性神经胶质瘤的发病机制和诊断具有重要意义。

39. 发明授权

EP2536854B1 PERSONALIZED TUMOR BIOMARKERS 有权
标题翻译：个性化肿瘤生物标志物
公开(公告)号：EP2536854B1
公开(公告)日：2017-07-19
申请号：EP11745196.3
申请日：2011-02-17
申请人： The Johns Hopkins University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , DIAZ, Luis , LEARY, Rebecca J.
IPC分类号： C12Q1/68 , C12N15/11 , C40B40/06
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers revealed an average of nine rearranged sequences (range 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.
摘要翻译：人类癌症的临床管理依赖于准确监测残留和复发性肿瘤。我们开发了一种称为重排末端的个性化分析（PARE）的方法，可以识别实体瘤中的易位。对四个结直肠癌和两个乳腺癌的分析显示每个肿瘤平均有9个重排序列（范围4-15）。使用跨越断点的引物进行的聚合酶链式反应能够检测到存在的水平低于0.001％的突变DNA分子，并且易于鉴定患者血浆样品中的突变循环DNA。这种方法为开发个性化生物标志物以提高癌症患者的临床管理提供了一种非常灵敏和广泛适用的方法。

40. 发明授权

EP1730303B1 MUTATIONS OF THE PIK3CA GENE IN HUMAN CANCERS 有权转让
标题翻译： PIK3CA基因在癌症突变在人类
公开(公告)号：EP1730303B1
公开(公告)日：2013-07-31
申请号：EP05723277.9
申请日：2005-02-18
申请人： THE JOHNS-HOPKINS UNIVERSITY
发明人： SAMUELS, Yardena , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the P13K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the P13K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.

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