公开(公告)号：EP1476577B1

公开(公告)日：2009-04-15

申请号：EP03733833.2

申请日：2003-02-21

申请人： Morphotek, Inc.

发明人： GRASSO, Luigi ,  NICOLAIDES, Nicholas, C. ,  SASS, Philip, M.

IPC分类号： C12Q1/68 ,  C12N15/85

CPC分类号： C12N15/1024 ,  C12N15/85 ,  C12N2830/42 ,  C12N2840/203

摘要： The present invention features mammalian expression vectors that are useful for controlling DNA hypermutability in mammalian cell as well as the encoding polynucleotide sequences of vector sequences. In related aspects the invention features expression vectors and host cells comprising such polynucleotides. In other related aspects, the invention features transgenic cells expressing a mutator gene to enhance genome-wide mutagenesis, due to, for example, the presence of an exogenous mutator-encoding polynucleotide sequence. Further, the invention provides methods for using vector sequences that can remove the expression of such gene to restore DNA stability in a host cell.

公开(公告)号：EP1363930B1

公开(公告)日：2006-08-16

申请号：EP00978578.3

申请日：2000-11-14

申请人： Morphotek Inc.

发明人： NICOLAIDES, Nicholas, C. ,  GRASSO, Luigi ,  SASS, Philip, M.

IPC分类号： C07K14/47 ,  A61K39/00 ,  C12N15/00 ,  C12N15/63 ,  C12N15/85

CPC分类号： C07K14/47 ,  A61K39/00 ,  C07K2319/00

摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within genes encoding for therapeutic antigens to produce altered polypeptides with enhanced antigenic and immunogenic activity. Moreover, these methods are useful for generating effective vaccines.

公开(公告)号：EP1351565A1

公开(公告)日：2003-10-15

申请号：EP01901992.6

申请日：2001-01-15

申请人： Morphotek Inc.

发明人： NICOLAIDES, Nicholas, C. ,  GRASSO, Luigi ,  SASS, Philip, M.

IPC分类号： A01H1/06 ,  A61K31/7076 ,  A61K31/7088 ,  C12N1/00 ,  C12N5/00 ,  C12Q1/68

CPC分类号： C12N15/1024 ,  A01H3/04 ,  C12N15/01 ,  C12N15/8212 ,  G01N33/5014 ,  G01N33/5088

摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. Methods of generating mutations in genes of interest and of making various cells mismatch repari defective through the use of chemicals to block mismatch repari in in vivo are disclosed.

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：EP1551988B1

公开(公告)日：2010-11-24

申请号：EP03765839.0

申请日：2003-07-21

申请人： Morphotek, Inc.

发明人： GRASSO, Luigi ,  KLINE, J. Bradford ,  NICOLAIDES, Nicholas, C. ,  SASS, Philip, M.

IPC分类号： C12P21/00 ,  C12P21/04 ,  C12N15/00 ,  C12N15/63 ,  C12N15/87 ,  C12Q1/68 ,  C12Q1/70 ,  G01N33/53 ,  A61K48/00

CPC分类号： C12N15/1024 ,  C07K16/00 ,  C12N15/1034

摘要： The use of mismatch repair (MMR) defective antibody producer cells offers a method to generate subclone variants with elevated protein production such as antibodies. Using MMR defective cells and animals, new cell lines and animal varieties with novel and useful properties such as enhanced protein production can be generated more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within host cells to alter endogenous genes that can yield increased titer levels of protein production. By employing this method, two genes were discovered whose suppressed expression is associated with enhanced antibody production. Suppressed expression of these genes by a variety of methods leads to increased antibody production for manufacturing as well as strategies for modulating antibody production in immunological disorders. Moreover, the suppression of these two genes in host cells can be useful for generating universal high titer protein production lines.

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：EP1363930A1

公开(公告)日：2003-11-26

申请号：EP00978578.3

申请日：2000-11-14

申请人： Morphotek Inc.

发明人： NICOLAIDES, Nicholas, C. ,  GRASSO, Luigi ,  SASS, Philip, M.

IPC分类号： C07H21/04 ,  C12N15/00 ,  C12N15/63 ,  C12N15/85

CPC分类号： C07K14/47 ,  A61K39/00 ,  C07K2319/00

摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within genes encoding for therapeutic antigens to produce altered polypeptides with enhanced antigenic and immunogenic activity. Moreover, these methods are useful for generating effective vaccines.

公开(公告)号：EP1345495A1

公开(公告)日：2003-09-24

申请号：EP00977014.0

申请日：2000-11-07

申请人： Morphotek Inc.

发明人： NICOLAIDES, Nicholas, C. ,  GRASSO, Luigi ,  SASS, Philip, M.

IPC分类号： A01N63/00 ,  A61K39/395 ,  A61K48/00 ,  C07H21/04 ,  C12N5/00 ,  C12N15/00 ,  C12P21/06

CPC分类号： C12N15/1024 ,  A01K2217/05 ,  C07K16/4291 ,  C07K2317/92

摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production.

公开(公告)号：EP2972376A1

公开(公告)日：2016-01-20

申请号：EP14762325.0

申请日：2014-03-15

申请人： Morphotek, Inc.

发明人： O'SHANNESSY, Daniel, John ,  NICOLAIDES, Nicholas, C. ,  SOMERS, Elizabeth, B.

IPC分类号： G01N33/574 ,  G01N1/30 ,  G01N33/48

CPC分类号： G01N33/57419 ,  G01N2333/4742 ,  G01N2333/71 ,  G01N2333/78

摘要： Provided herein are methods for determining the risk that a subject diagnosed with colorectal cancer will develop a recurrence of colorectal cancer and methods of predicting clinical outcome for a subject diagnosed with colorectal cancer by a) determining the level of expression for each marker of a panel of markers in a panel of tumor compartments in a tumor tissue sample from the subject, wherein the panel of markers comprises at least two of TEM1, HIF2α, CAIX, PDGFRβ, fibronectin, collagen I, collagen IV, and CD31 and wherein the panel of tumor compartments comprises at least three tumor compartments of pure stroma, tumor, stromal vessel, and tumor vessel; b) determining the TAPPS score for said subject; and c) comparing the TAPPS score of the subject to the TAPPS score of a population of subjects diagnosed with colorectal cancer. Also provided are related computer-implemented methods and systems, kits, and tumor microarrays.

摘要翻译： 本文提供了确定被诊断患有结肠直肠癌的受试者将发展为结肠直肠癌复发的风险的方法以及通过以下方法确定被诊断患有结肠直肠癌的受试者的临床结果的方法：a）确定一组患者的每个标记物的表达水平 标记物在来自受试者的肿瘤组织样品中的一组肿瘤区室中，其中所述标记物组包含TEM1，HIF2α，CAIX，PDGFR和bgr;纤连蛋白，胶原I，胶原IV和CD31中的至少两种，并且其中 肿瘤室包含至少三个纯基质肿瘤区，肿瘤，基质血管和肿瘤血管; b）确定所述受试者的TAPPS得分; 和c）将受试者的TAPPS得分与诊断为结肠直肠癌的受试者群体的TAPPS评分进行比较。 还提供了相关的计算机实现的方法和系统，试剂盒和肿瘤微阵列。

公开(公告)号：EP2310416A1

公开(公告)日：2011-04-20

申请号：EP09774273.8

申请日：2009-06-30

申请人： Morphotek, Inc.

发明人： NICOLAIDES, Nicholas, C. ,  SASS, Philip, M. ,  GRASSO, Luigi ,  EBEL, Wolfgang ,  ROUTHIER, Eric ,  YAO, Jun ,  ZHOU, Yuhong ,  ZUO, Xun

IPC分类号： C07K16/30 ,  A61K39/395 ,  A61P35/00

CPC分类号： C07K16/3084 ,  C07K2317/21 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/92

摘要： Described herein are antibodies that specifically bind ganglioside GD2. Also described are nucleotides encoding such antibodies, cells expressing such antibodies, methods of use for such antibodies, and methods for using the antibodies to treat diseases associated with ganglioside GD2. In addition, tissue culture media supplements are described as are methods of use for the supplements. Described herein are albumin-ganglioside conjugates and corresponding methods for producing such conjugates. Methods of purifying or isolating antibodies are also described.