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12. 发明申请

WO2011149909A2 CLASS I MHC PHOSPHOPEPTIDES FOR CANCER IMMUNOTHERAPY AND DIAGNOSIS 审中-公开
标题翻译：第一类MHC磷酸化酶对于癌症的免疫和诊断
公开(公告)号：WO2011149909A2
公开(公告)日：2011-12-01
申请号：PCT/US2011/037699
申请日：2011-05-24
申请人： HUNT, Donald F. , SHABANOWITZ, Jeffrey , COTTINE, Jennifer , ENGLISH, Ann M. , NORRIS, Andrew , ENGELHARD, Victor H. , COBBOLD, Mark , CUMMINGS, Kara L. , ZARLING, Angela , OBENG, Rebecca C.
发明人： HUNT, Donald F. , SHABANOWITZ, Jeffrey , COTTINE, Jennifer , ENGLISH, Ann M. , NORRIS, Andrew , ENGELHARD, Victor H. , COBBOLD, Mark , CUMMINGS, Kara L. , ZARLING, Angela , OBENG, Rebecca C.
IPC分类号： C07K14/74 , C07K7/00 , C07K16/20 , A61K38/17 , A61K39/395 , G01N33/68 , A61P35/00
CPC分类号： C07K7/06 , A61K38/00 , A61K39/0011 , C07K7/08 , C07K14/70539 , C07K16/18 , G01N33/5743 , G01N33/57492 , G01N33/6893 , G01N2333/70539 , G01N2440/14
摘要： A set of phosphorylated peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of melanoma cells. They have the potential to (a) stimulate an immune response to the cancer, (b) to function as immunotherapeutics in adoptive T-cell therapy or as a vaccine, (c) to facilitate antibody recognition of the tumor boundaries in surgical pathology samples, and (d) act as biomarkers for early detection of the disease. Phosphorylated peptides are also presented for other cancers.
摘要翻译：一组磷酸化肽由黑素瘤细胞表面上的HLA A * 0101，A * 0201，A * 0301，B * 4402，B * 2705，B * 1402和B * 0702呈现。它们具有（a）刺激对癌症的免疫应答的潜力，（b）在过继性T细胞治疗或疫苗中用作免疫治疗剂，（c）促进手术病理样品中肿瘤边界的抗体识别，和（d）作为早期检测疾病的生物标志物。磷酸化肽也可用于其他癌症。

13. 发明申请

WO2011112901A2 HYPERMETHYLATION BIOMARKERS FOR DETECTION OF CERVICAL CANCER 审中-公开
标题翻译：用于检测宫颈癌的超临床生物标志物
公开(公告)号：WO2011112901A2
公开(公告)日：2011-09-15
申请号：PCT/US2011/028045
申请日：2011-03-11
申请人： THE JOHNS HOPKINS UNIVERSITY , GUERRERO-PRESTON, Rafael, Enrique , SIDRANSKY, David , BREBI-MIEVILLE, Priscilla
发明人： GUERRERO-PRESTON, Rafael, Enrique , SIDRANSKY, David , BREBI-MIEVILLE, Priscilla
IPC分类号： C12Q1/68 , C12N15/12
CPC分类号： C12Q1/6886 , C12Q1/6869 , C12Q2600/106 , C12Q2600/154 , C12Q2600/156 , C12Q2523/125
摘要： Pap smears and HPV infection tests do not distinguish between lesions that will progress to an invasive carcinoma and those that will not. We aimed to identify epigenetic biomarkers for diagnosis and progression monitoring of premalignant lesions in cervical cancer. Hypermethylated genes were identified as potential biomarkers after validation by MSP, including GGTLA4 and ZNF516. The methylation frequency for these two genes was higher in tumor: GGTLA4 (100%) and ZNF516 (96%); than in normal samples: GGTLA4 (12%) and ZNF516 (16%). The methylation status of GGTLA4 showed a progression in methylation frequency from normal samples to invasive carcinoma. The immunohistochemical expression was lower in tumor for both: GGTLA4 (50.8%) and ZNF516 (66.2%); than in normal samples: GGTLA4 (71.2%) and ZNF516 (88.1%) (p
摘要翻译：巴氏涂片和HPV感染测试不区分将进展为浸润性癌症的病变和不会侵犯癌症的病变。我们旨在确定子宫颈癌前期病变的诊断和进展监测的表观遗传学生物标志物。超甲基化基因在MSP验证后被鉴定为潜在的生物标志物，包括GGTLA4和ZNF516。这两个基因的甲基化频率在肿瘤中较高：GGTLA4（100％）和ZNF516（96％）; 比正常样品：GGTLA4（12％）和ZNF516（16％）。 GGTLA4的甲基化状态显示甲基化频率从正常样本到侵袭性癌的进展。肿瘤组织中GGTLA4（50.8％）和ZNF516（66.2％）的免疫组织化学表达均较低。比正常样品：GGTLA4（71.2％）和ZNF516（88.1％）（p <0.05）。总之，我们确定了甲基化生物标志物进行子宫颈癌的分子筛选和表征。

14. 发明申请

WO2011112880A3 HYPERMETHYLATION BIOMARKERS FOR DETECTION OF HEAD AND NECK SQUAMOUS CELL CANCER 审中-公开
公开(公告)号：WO2011112880A3
公开(公告)日：2011-09-15
申请号：PCT/US2011/028011
申请日：2011-03-11
申请人： THE JOHNS HOPKINS UNIVERSITY , GUERRERO-PRESTON, Rafael Enrique , SIDRANSKY, David , SOUDRY, Ethan
发明人： GUERRERO-PRESTON, Rafael Enrique , SIDRANSKY, David , SOUDRY, Ethan
IPC分类号： C12Q1/68 , C12N15/12 , C40B40/08
摘要： Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

15. 发明申请

WO2011082422A2 HUMAN IMMUNODEFICIENCY VIRUS (HIV-1) HIGHLY CONSERVED AND LOW VARIANT SEQUENCES AS TARGETS FOR VACCINE AND DIAGNOSTIC APPLICATIONS 审中-公开
标题翻译：人类免疫缺陷病毒（HIV-1）高度保守和低变异序列作为疫苗和诊断应用的目标
公开(公告)号：WO2011082422A2
公开(公告)日：2011-07-07
申请号：PCT/US2011/020122
申请日：2011-01-04
申请人： THE JOHNS HOPKINS UNIVERSITY , NATIONAL UNIVERSITY OF SINGAPORE , AUGUST, J. Thomas , SIMON, Gregory George , TAN, Tin Wee , KHAN, Asif Mohammad , YONGLI, Hu
发明人： AUGUST, J. Thomas , SIMON, Gregory George , TAN, Tin Wee , KHAN, Asif Mohammad , YONGLI, Hu
IPC分类号： C07K14/16 , C12N15/49 , C12N15/63 , A61K39/21 , C12Q1/70 , A61P31/18
CPC分类号： A61K39/21 , A61K39/00 , C07K14/005 , C12N2740/16022 , C12N2740/16034
摘要： We identified regions of the HIV-1 proteome with high conservation, and low variant incidence. Such highly conserved sequences have direct relevance to the development of new-generation vaccines and diagnostic applications. The immune relevance of these sequences was assessed by their correlation to previously reported human T-cell epitopes and to recently identified human HIV- 1 T-cell epitopes (identified using HLA transgenic mice). We identified (a) sequences specific to HIV-1 with no shared identity to other viruses and organisms, and (b) sequences that are specific to primate lentivirus group, with multiclade HIV-1 conservation.
摘要翻译：我们确定了具有高度保守性和低变异发生率的HIV-1蛋白质组的区域。这种高度保守的序列与新一代疫苗和诊断应用的发展直接相关。这些序列的免疫相关性通过与先前报道的人类T细胞表位和最近鉴定的人类HIV-1 T细胞表位（使用HLA转基因小鼠鉴定）的相关性来评估。我们确定（a）HIV-1特异性序列，与其他病毒和生物体无共享身份，（b）具有多重HIV-1保护的灵长类慢病毒组特异性序列。

16. 发明申请

WO2011046996A2 CONSENSUS SEQUENCE FOR INFLUENZA A VIRUS 审中-公开
标题翻译： INFLUZZA病毒的一致性序列
公开(公告)号：WO2011046996A2
公开(公告)日：2011-04-21
申请号：PCT/US2010/052432
申请日：2010-10-13
申请人： THE JOHNS HOPKINS UNIVERSITY , NATIONAL UNIVERSITY OF SINGAPORE , AUGUST, J. Thomas , TAN, Paul ThiamJoo , TAN, Tin Wee , KHAN, Asif Mohammad
发明人： AUGUST, J. Thomas , TAN, Paul ThiamJoo , TAN, Tin Wee , KHAN, Asif Mohammad
IPC分类号： C07K14/11 , C12N15/44 , C12N7/01 , A61K39/145 , A61P31/16
CPC分类号： A61K39/145 , A61K39/12 , A61K2039/5154 , A61K2039/5156 , A61K2039/70 , C07K14/005 , C07K2319/00 , C12N2760/16122 , C12N2760/16134
摘要： Pandemic A(H1N1) continues its global spread, and vaccine production is a serious problem. Protection by current vaccines is limited by the mutational differences that rapidly accumulate in the circulating strains, especially in the virus surface proteins. New vaccine strategies are focusing at conserved regions of the viral internal proteins to produce T cell epitope-based vaccines. T cell responses have been shown to reduce morbidity and promote recovery in mouse models of influenza challenge. We previously reported 54 highly conserved sequences of NP, Ml and the polymerases of all human H1N1, H3N2, H1N2, and H5N1, and avian subtypes over the past 30 years. Sixty-three T cell epitopes elicited responses in HLA transgenic mice (A2, A24, B7, DR2, DR3 and DR4). These epitopes were compared to the 2007-2009 human H1N1 sequences to identify conserved and variant residues. Seventeen T cell epitopes of PB1, PB2, and M1 were selected as vaccine targets by analysis of sequence conservation and variability, functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. The vaccines composed of these epitopes, being highly conserved and temporally stable, would be useful for any avian or human influenza A virus.
摘要翻译：甲型H1N1流感继续其全球蔓延，疫苗生产是一个严重的问题。目前疫苗的保护受到流行株中特别是病毒表面蛋白中迅速积累的突变差异的限制。新疫苗策略集中于病毒内部蛋白质的保守区域以产生基于T细胞表位的疫苗。已显示T细胞应答降低发病率并促进流感攻击的小鼠模型中的恢复。我们以前报道过去30年中54种高度保守的NP，M1和所有人类H1N1，H3N2，H1N2和H5N1以及禽类亚型的聚合酶。 63个T细胞表位在HLA转基因小鼠（A2，A24，B7，DR2，DR3和DR4）中引发应答。将这些表位与2007-2009年人类H1N1序列进行比较以鉴定保守和变体残基。通过分析序列保守性和变异性，功能亲合力，与人类肽的非同一性，聚簇定位和对多个HLA等位基因的混杂性，选择PB1，PB2和M1的17个T细胞表位作为疫苗靶标。由这些表位组成的疫苗高度保守且时间稳定，可用于任何禽流感或人流感病毒。

17. 发明申请

WO2011017313A1 METHOD OF ADMINISTERING NON-VIRAL NUCLEIC ACID VECTORS TO THE EYE 审中-公开
标题翻译：将非病毒核酸载体施用于眼睛的方法
公开(公告)号：WO2011017313A1
公开(公告)日：2011-02-10
申请号：PCT/US2010/044234
申请日：2010-08-03
申请人： COPERNICUS THERAPEUTICS INC. , COOPER, Mark, J.
发明人： COOPER, Mark, J.
IPC分类号： A61K48/00 , A61P27/02
CPC分类号： A61K48/0025 , A61K48/0075 , A61K48/0091
摘要： Intravitreal administration of nucleic acid vectors leads to transfection and expression of the nucleic acid vectors in retinal pigment epithelium. The nucleic acid is non-viral and may be compacted to form a unimolecular nanoparticle with a polycationic polymer. The nucleic acid vectors can be used to supply a normal copy of a gene which is defective in the recipient, to inhibit a deleterious cellular product, or to supply a beneficial product to improve the symptoms or natural history of the disease.
摘要翻译：核酸载体的玻璃体内给药导致核酸载体在视网膜色素上皮中的转染和表达。核酸是非病毒的并且可以被压实以形成具有聚阳离子聚合物的单分子纳米颗粒。核酸载体可用于提供接受者有缺陷的基因的正常拷贝，以抑制有害的细胞产物，或提供有益的产物以改善疾病的症状或自然病史。

18. 发明申请

WO2010102160A2 DIAGNOSTIC METHOD USING PALB2 审中-公开
标题翻译：诊断方法使用PALB2
公开(公告)号：WO2010102160A2
公开(公告)日：2010-09-10
申请号：PCT/US2010/026290
申请日：2010-03-05
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , PARSONS, D. Williams , JONES, Sian , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison , HIDALGO, Manuel , VELCULESCU, Victor E.
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PARSONS, D. Williams , JONES, Sian , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison , HIDALGO, Manuel , VELCULESCU, Victor E.
IPC分类号： C12Q1/68 , G01N33/68 , G01N33/574
CPC分类号： C12Q1/6886 , A61K31/407 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N2333/47
摘要： The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.
摘要翻译：本发明提供了一种检测胰腺癌患者和具有胰腺癌家族史的个体中PALB2基因突变的方法。还提供了用于诊断患有胰腺癌的倾向，用于预测患者对胰腺癌治疗的反应以及用于治疗患者胰腺癌的方法，其基于在患者体内PALB2突变或异常PALB2基因表达的存在。

19. 发明申请

WO2010028098A2 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 审中-公开
标题翻译：基于胰腺癌和胰腺癌基因的途径
公开(公告)号：WO2010028098A2
公开(公告)日：2010-03-11
申请号：PCT/US2009/055802
申请日：2009-09-03
申请人： THE JOHNS HOPKINS UNIVERSITY , 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
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.
摘要翻译：目前对胰腺癌患者几乎没有治疗方案，迫切需要对这种致死性疾病的发病机制的新见解。为此，我们对24个胰腺肿瘤中改变的基因进行了综合分析。首先，我们从这些肿瘤的DNA中确定了23,781个转录本，代表20,583个蛋白质编码基因的序列。其次，我们使用微阵列查询了每个样本中一百万个单核苷酸多态性的纯合缺失和扩增。第三，我们使用SAGE和下一代按序合成技术分析了相同样品的转录组。我们发现胰腺癌平均存在63个遗传改变，其中49个是点突变，8个是纯合缺失，6个是扩增。进一步的分析揭示了一组核心的12个调节过程或途径，在70％至100％的样品中进行了遗传改变。数据表明，这种核心途径的失调导致了胰腺肿瘤发生的主要特征。

20. 发明申请

WO2008103135A2 THE MICRORNAOME 审中-公开
标题翻译：微笑
公开(公告)号：WO2008103135A2
公开(公告)日：2008-08-28
申请号：PCT/US2007/004518
申请日：2007-02-16
申请人： THE JOHNS HOPKINS UNIVERSITY , CUMMINS, Jordan , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： CUMMINS, Jordan , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , C12N2310/141 , C12N2320/11 , C12N2330/10 , C12N2510/00 , C12Q1/6886
摘要： MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. The miRNAs are useful to diagnose and treat cancers.
摘要翻译：微小RNA（miRNA）是一类具有重要调节作用的小型非编码RNA

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