公开(公告)号：EP1268765B1

公开(公告)日：2008-08-13

申请号：EP01907187.7

申请日：2001-02-12

申请人： THE JOHNS HOPKINS UNIVERSITY ,  Morphotek, Inc.

发明人： NICOLAIDES, Nicholas, C. ,  SASS, Philip, M. ,  GRASSO, Luigi ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： C12N15/10 ,  C12N1/20

CPC分类号： C12N15/1024 ,  C12N15/01 ,  C12N15/102

摘要： Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficinecy and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch reparir activity to the bacteria.

公开(公告)号：EP1430123A2

公开(公告)日：2004-06-23

申请号：EP01935403.4

申请日：2001-05-14

申请人： The Johns Hopkins University ,  Morphotek Inc. ,  Nicolaides, Nicholas, C. ,  Sass, Philip, M. ,  Grasso, Luigi ,  Vogelstein, Bert ,  Kinzler, Kenneth

发明人： NICOLAIDES, Nicholas, C. ,  SASS, Philip, M. ,  GRASSO, Luigi ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： C12N15/10 ,  C12N15/01 ,  C12Q1/68 ,  A01K67/027

摘要： PROBLEM TO BE SOLVED: To provide a method for rendering cells hypermutable, and hypermutable cell lines altered genetically and phenotypically.SOLUTION: The invention relates to use of dominant negative alleles of human mismatch repair genes to generate hypermutable cells and organisms; the use of introducing genes into cells and transgenic animals by which new cell lines and animal varieties with new and useful properties can be prepared more efficiently than by relying on the natural rate of mutation; and use of mutagens for enhancing a rate of further augmented mutation.

摘要翻译： 要解决的问题：提供一种使细胞变性可变的方法，以及基因和表型改变的超可变细胞系。解决方案：本发明涉及人错配修复基因的显性阴性等位基因用于产生超可变细胞和生物体; 将基因导入细胞和转基因动物中，通过其可以比通过依赖于自然的突变率更有效地制备具有新的和有用的性质的新的细胞系和动物品种; 并使用诱变剂提高进一步增强突变率。

公开(公告)号：EP1430123B1

公开(公告)日：2018-01-03

申请号：EP01935403.4

申请日：2001-05-14

申请人： The Johns Hopkins University ,  Morphotek, Inc. ,  Nicolaides, Nicholas, C. ,  Sass, Philip, M. ,  Grasso, Luigi ,  Vogelstein, Bert ,  Kinzler, Kenneth

发明人： NICOLAIDES, Nicholas, C. ,  SASS, Philip, M. ,  GRASSO, Luigi ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： C12N15/10 ,  C12N15/01 ,  C12Q1/68 ,  A01K67/027 ,  C07K14/47

摘要： PROBLEM TO BE SOLVED: To provide a method for rendering cells hypermutable, and hypermutable cell lines altered genetically and phenotypically.SOLUTION: The invention relates to use of dominant negative alleles of human mismatch repair genes to generate hypermutable cells and organisms; the use of introducing genes into cells and transgenic animals by which new cell lines and animal varieties with new and useful properties can be prepared more efficiently than by relying on the natural rate of mutation; and use of mutagens for enhancing a rate of further augmented mutation.

公开(公告)号：EP1259628B1

公开(公告)日：2007-01-17

申请号：EP01911013.9

申请日：2001-02-21

申请人： THE JOHNS HOPKINS UNIVERSITY ,  Morphotek, Inc.

发明人： NICOLAIDES, Nicholas, C. ,  SASS, Philip, M. ,  GRASSO, Luigi ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： C12N15/81 ,  C12N5/10 ,  C12N15/01

CPC分类号： C12N15/81

摘要： Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.

公开(公告)号：EP3730146A1

公开(公告)日：2020-10-28

申请号：EP20167187.2

申请日：2014-03-28

申请人： Biomed Valley Discoveries, Inc. ,  The Johns Hopkins University

发明人： SAHA, Saurabh ,  ZHOU, Shibin ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： A61K35/66 ,  A61P35/00

摘要： The present invention provides, inter alia, methods for treating or ameliorating an effect of a solid tumor present in a human. These methods include administering intratumorally to the human a unit dose of C. novyi, preferably C. novyi NT, colony forming units (CFUs), which contains about 1 x 10 3 -1 x 10 7 CFUs suspended in a pharmaceutically acceptable carrier or solution. Methods for debulking a solid tumor present in a human, methods for ablating a solid tumor present in a human, a method for microscopically precise excision of tumor cells in a human, methods for treating or ameliorating an effect of a solid tumor that has metastasized to one or more sites in a human, unit doses of C. novyi, preferably C. novyi NT, CFUs, and kits for treating or ameliorating an effect of a solid tumor present in a human are also provided.

公开(公告)号：EP3094313A1

公开(公告)日：2016-11-23

申请号：EP15737117.0

申请日：2015-01-14

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  ZHOU, Shibin ,  KINZLER, Kenneth, W. ,  SUR, Surojit

IPC分类号： A61K9/127 ,  A61K31/724 ,  A61K31/7034 ,  A61P35/00

CPC分类号： A61K9/1271 ,  A61K9/0019 ,  A61K9/1278 ,  A61K31/166 ,  A61K31/525 ,  A61K47/40 ,  A61K47/6951 ,  A61P35/00 ,  C08B37/0012

摘要： The invention provides liposome compositions comprising liposomes encapsulating cyclodextrins that both bear ionizable functional groups, such as on their solvent-exposed surfaces, and encompass therapeutic agents, as well as uses thereof.

摘要翻译： 本发明提供脂质体组合物，其包含脂质体包封环糊精，其都具有可离子化的官能团，例如在其溶剂暴露的表面上，并且包括治疗剂及其用途。

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.

公开(公告)号：EP1948816A2

公开(公告)日：2008-07-30

申请号：EP06817236.0

申请日：2006-10-20

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  DIEHL, Frank ,  KINZLER, Kenneth, W. ,  LI, Ming

IPC分类号： C12P19/34

CPC分类号： C12Q1/6858 ,  G01R31/025 ,  G01R31/3277 ,  C12Q2565/537 ,  C12Q2563/155 ,  C12Q2527/125

摘要： Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.

公开(公告)号：EP1585955A2

公开(公告)日：2005-10-19

申请号：EP02768559.3

申请日：2002-08-28

申请人： The Johns Hopkins University, School of Medicine, Office of Technology Licencing

发明人： TORRANCE, Christopher, J. ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： G01N1/00

CPC分类号： C07D257/04 ,  C07H19/16 ,  G01N33/5011 ,  G01N33/5023

摘要： A strategy for drug-screening is based on cells that are isogenic except for a gene of interest. Each cell can be tranfected with a vector that encodes a different fluorescent protein that can be differentially detected to monitor cell growth. Co-culture of both cells allows facile screening for compounds with selective toxicity towards a gene of interest. The drug screening is broadly applicable for mining therapeutic agents targeted to specific genetic alterations responsible for cancer development.

公开(公告)号：EP1320612A2

公开(公告)日：2003-06-25

申请号：EP01910499.1

申请日：2001-02-09

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  HERMEKING, Heiko

IPC分类号： C12N15/54 ,  C12N9/12 ,  C12Q1/68

CPC分类号： C12N9/1205

摘要： The prototypic oncogene c-MYC encodes a transcription factor, which can drive proliferation by promoting cell cycle re-entry. However, the mechanisms through which c-MYC achieves these effects have been unclear. Using serial analysis of gene expression (SAGE), we have identified the cyclin dependent kinase 4 (CDK4) gene as a transcriptional target of c-MYC. c-MYC induced a rapid increase in CDK4 mRNA levels through four highly conserved c-Myc binding sites (MBS) within the CDK4 promoter. Cell cycle progression is delayed in c-MYC-deficient RAT1 cells, and this delay was associated with a defect in CDK4 induction. Ectopic expression of CDK4 in these cells partially alleviated the growth defect. Thus CDK4 provides a direct link between the oncogenic effects of c-MYC and cell cycle regulation.