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    • 12. 发明申请
      US20120003741A1 HEPATITIS C VIRUS EXPRESSING REPORTER TAGGED NS5A PROTEIN 失效
    • HEPATITIS C VIRUS EXPRESSING REPORTER TAGGED NS5A PROTEIN
    • US20120003741A1
    • 2012-01-05
    • US13121565
    • 2009-10-05
    • Judith M. Gottwein , Troels Kasper Hoyer Scheel , Jens Bukh , Jannick Prento , Tanja Bertelsen Jensen , Yiping Li , Jacob Bo Lademann
    • Judith M. Gottwein , Troels Kasper Hoyer Scheel , Jens Bukh , Jannick Prento , Tanja Bertelsen Jensen , Yiping Li , Jacob Bo Lademann
    • C12N7/01 , C12N5/10 , C12N15/85 , C12N15/51
    • C12N15/86 , A61K2039/525 , C07K14/005 , C12N7/00 , C12N2770/24222 , C12N2770/24243 , C12N2770/24251
    • The present inventors developed hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A. The inventors have identified a deletion upstream of the inserted reporter gene sequence, which conferred favourable growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. Drugs could be evaluated for their potential to prevent infection or cure infected cells. The neutralizing capacity of antibodies induced by vaccine candidates could be evaluated in order to define successful vaccination strategies. Broadly neutralizing antibodies could be identified testing engineered antibodies and antibodies derived from serum of HCV infected individuals; thus this technique could contribute to the development of immunotherapy. The developed systems could aid individualized treatment of HCV infected: Patient isolates could be tested for resistance to drugs by introduction of genome regions involved in drug resistance in the developed constructs and subsequent treatment with the drug of interest. The present inventors also developed JFH1-based intergenotypic recombinants with genotype specific homotypic 5UTR, or heterotypic 5′UTR (either of genotype 1a (strain H77) or of genotype 3a (strain S52)). The present inventors additionally developed J6/JFH1 recombinants with the 5′UTR of genotypes 1-6. These recombinants with different 5UTRs are a useful to study the function of the 5′UTR in a genotype specific manner.
    • 本发明人通过在HCV NS5A的结构域III插入报道基因，开发了通过NS2的核心通过NS2分析所有主要HCV基因型的原型分离株和分离株JFH1的剩余基因的丙型肝炎报告病毒。 发明人已经鉴定了插入的报道基因序列上游的缺失，其赋予Huh7.5细胞对这些病毒有利的生长动力学。 这些报告病毒可用于药物和疫苗候选物以及患者样品的高通量分析。 可以评估药物的潜力，以防止感染或治愈感染细胞。 可以评估疫苗候选者诱导的抗体的中和能力，以确定成功的疫苗接种策略。 可以鉴定出广泛中和抗体测试工程化抗体和源自HCV感染个体的血清的抗体; 因此这种技术可能有助于免疫治疗的发展。 开发的系统可以帮助HCV感染的个体化治疗：可以通过在开发的构建体中引入参与耐药性的基因组区域并随后用感兴趣的药物进行治疗来测试患者分离物对药物的抗药性。 本发明人还开发了具有基因型特异性同种型5UTR或异型5'UTR（基因型1a（菌株H77）或基因型3a（菌株S52））的基于JFH1的基因间重组体。 本发明人还开发了具有基因型1-6的5'UTR的J6 / JFH1重组体。 具有不同5UTR的这些重组体可用于以基因型特异性方式研究5'UTR的功能。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 14. 发明申请
      US20090029372A1 ADAM12 AS A BIOMARKER FOR BLADDER CANCER 审中-公开
    • ADAM12 AS A BIOMARKER FOR BLADDER CANCER
    • ADAM12作为刮板癌的生物标记
    • US20090029372A1
    • 2009-01-29
    • US12120544
    • 2008-05-14
    • Ulla M. Wewer
    • Ulla M. Wewer
    • C12Q1/68 , G01N33/573
    • G01N33/57407 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , G01N33/5088 , G01N33/5091
    • The present inventors have shown that the gene and protein expression profiles of ADAM8, ADAM10 and ADAM12 in different grades and stages of bladder cancer.ADAM12 gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-polymerase chain reaction (RT-PCR), quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical staining on tissue arrays of bladder cancers.The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively.Particularly ADAM12 mRNA expression was significantly upregulated in bladder cancer, as determined by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. ADAM12 protein expression correlated with tumor stage and grade. ADAM12 was present in higher levels in the urine from bladder cancer patients than in urine from healthy individuals. Significantly, following removal of tumor by surgery, in most bladder cancer cases examined the level of ADAM12 in the urine decreased and, upon recurrence of tumor, increased.
    • 本发明人已经表明，ADAM8，ADAM10和ADAM12在膀胱癌不同等级和阶段的基因和蛋白质表达谱。 使用定制的Affymetrix GeneChip在96例膀胱癌患者的肿瘤中评价ADAM12基因表达。 使用逆转录聚合酶链反应（RT-PCR），定量PCR和原位杂交验证膀胱癌中的基因表达。 通过免疫组织化学染色对膀胱癌组织阵列评估蛋白质表达。 癌症患者尿液中ADAM12的存在和相对量分别通过Western印迹和光密度测定法测定。 特别是ADAM12 mRNA表达在膀胱癌中显着上调，如通过微阵列分析确定的，ADAM12 mRNA的水平与疾病阶段相关。 ADAM12蛋白表达与肿瘤分期和分级相关。 ADAM12在膀胱癌患者的尿液中的含量高于来自健康个体的尿液。 重要的是，通过手术切除肿瘤后，大多数膀胱癌病例检查，尿中ADAM12的水平降低，并且在肿瘤复发时增加。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 15. 发明申请
      US20070276131A1 Continuous Process for the Assembly of Macromolecular Substances and the Subsequent Capture and Isolation of Mamacromolecular Assembly and a System Suitable for the Process 审中-公开
    • Continuous Process for the Assembly of Macromolecular Substances and the Subsequent Capture and Isolation of Mamacromolecular Assembly and a System Suitable for the Process
    • 用于大分子物质组装的连续方法以及随后的分子组装和适用于该方法的系统的捕获和分离
    • US20070276131A1
    • 2007-11-29
    • US10569372
    • 2004-08-12
    • Henrik Ferre , Dennis Hansen , Soren Buus , Timothy Hobley , Owen Thomas
    • Henrik Ferre , Dennis Hansen , Soren Buus , Timothy Hobley , Owen Thomas
    • C07K1/14 , B03C1/00 , C07H21/00
    • B03C1/002 , B03C1/288 , C07K1/113 , C07K14/70539
    • The present invention relates to a continuous process and a system for macromolecular assembly and capture (refolding or proteins (e.g. refolding of HAT human β2-microglobulin), hybridization of nucleic acid, nucleic acid analogues, and protein-nucleic acid chimera, aggregation of carbohydrates, and assembly of nanostructures/nanomaterials. The process may comprise the steps of providing fluid compositions comprising at least one of said macromolecular substances in a predominantly unassembled form, providing a dispersion comprising coated, essentially non-porous magnetic particles, combining said fluid compositions and the dispersion of magnetic particles thereby providing a continuous stream, passing said continuous stream through a first mixing device thereby forming magnetic complexes each comprising a magnetic particle and a plurality of macromolecular assembly species; passing the continuous stream through a first capture compartment of a magnetic separator thereby capturing said magnetic complexes; and separating said magnetic complexes from said continuous stream, and isolating said macromolecular assembly species.
    • 本发明涉及用于大分子装配和捕获（重折叠或蛋白质（例如HAT人β2-微球蛋白的重折叠），核酸，核酸类似物和蛋白质 - 核酸嵌合体的杂交，碳水化合物的聚集的连续方法和系统 该纳米结构/纳米材料的组装可以包括以主要组装形式提供包含至少一种所述大分子物质的流体组合物的步骤，提供包含涂覆的，基本上无孔的磁性颗粒的分散体，将所述流体组合物和 磁性颗粒的分散由此提供连续的流，使所述连续流通过第一混合装置，从而形成各自包含磁性颗粒和多个大分子组合物种的磁性复合物;使连续流通过磁选机的第一捕获隔室 从而捕获s 援助磁性复合体; 并从所述连续流中分离所述磁性复合物，并分离所述大分子组合物种。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
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