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：EP1556508A4

公开(公告)日：2006-10-04

申请号：EP03754530

申请日：2003-09-12

申请人： MORPHOTEK INC ,  NICOLAIDES NICHOLAS E ,  SASS PHILIP M

发明人： GRASSO LUIGI

IPC分类号： C07K16/00 ,  C12N15/01 ,  C12N15/10 ,  C12Q1/68

CPC分类号： C12N15/01 ,  C07K16/00 ,  C07K16/4291 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/92 ,  C12N15/1024

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 immunoglobulins 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. The invention also provides methods for increasing the affinity of monoclonal antibodies and monoclonal antibodies with increased affinity.

公开(公告)号：EP1259628A1

公开(公告)日：2002-11-27

申请号：EP01911013.9

申请日：2001-02-21

申请人： The Johns Hopkins UNiversity School of Medicine ,  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： C12N15/81 ,  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：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：EP1556508A2

公开(公告)日：2005-07-27

申请号：EP03754530.8

申请日：2003-09-12

申请人： Morphotek Inc. ,  Nicolaides, Nicholas E. ,  Sass, Philip, M.

发明人： GRASSO, Luigi

IPC分类号： C12Q1/68 ,  C07K16/00

CPC分类号： C12N15/01 ,  C07K16/00 ,  C07K16/4291 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/92 ,  C12N15/1024

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 immunoglobulins 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. The invention also provides methods for increasing the affinity of monoclonal antibodies and monoclonal antibodies with increased affinity.