公开(公告)号：EP0746609A4

公开(公告)日：1997-12-17

申请号：EP93901143

申请日：1992-12-17

申请人： GENPHARM INT

发明人： LONBERG NILS ,  KAY ROBERT M

IPC分类号： A01K67/027 ,  A61K38/00 ,  C07K16/00 ,  C07K16/28 ,  C07K16/30 ,  C07K16/42 ,  C07K16/44 ,  C12N5/10 ,  C12N15/02 ,  C12N15/09 ,  C12N15/85 ,  C12N15/90 ,  C12P21/08 ,  C12R1/91 ,  C12N15/00

CPC分类号： A01K67/0276 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/03 ,  A01K2267/0381 ,  A61K38/00 ,  C07K16/00 ,  C07K16/2812 ,  C07K16/3007 ,  C07K16/4291 ,  C07K16/44 ,  C07K2317/21 ,  C07K2317/24 ,  C12N15/8509 ,  C12N15/90

摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppresed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterogolous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.

公开(公告)号：EP0814159A2

公开(公告)日：1997-12-29

申请号：EP97201755

申请日：1991-08-28

申请人： GENPHARM INT

发明人： LONBERG NILS ,  KAY ROBERT

IPC分类号： A01K67/027 ,  A61K38/00 ,  A61K39/395 ,  C07K14/725 ,  C07K16/00 ,  C07K16/18 ,  C07K16/28 ,  C07K16/30 ,  C07K16/42 ,  C07K16/44 ,  C07K16/46 ,  C12N5/10 ,  C12N5/16 ,  C12N15/00 ,  C12N15/09 ,  C12N15/13 ,  C12N15/85 ,  C12N15/87 ,  C12N15/90 ,  C12P21/08 ,  C12N5/06

CPC分类号： C12N15/907 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/01 ,  A61K38/00 ,  C07K14/7051 ,  C07K16/00 ,  C07K16/2812 ,  C07K16/3007 ,  C07K16/4266 ,  C07K16/4291 ,  C07K16/44 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/56 ,  C12N5/163 ,  C12N15/00 ,  C12N15/85 ,  C12N15/8509 ,  C12N15/87 ,  C12N15/90 ,  C12N2830/008 ,  C12N2830/15 ,  C12N2830/36 ,  C12N2830/60 ,  C12N2840/44

摘要： A transgenic mouse having a genome comprising a human immunoglobulin heavy chain minilocus transgene, the transgene being capable of rearrangement and switching in the mouse, whereby two or more rearranged human heavy chain isotypes are produced.

摘要翻译： 一种具有包含人免疫球蛋白重链微型转基因的基因组的转基因小鼠，所述转基因能够在小鼠中重排和切换，由此产生两个或更多个重排的人重链同种型。

公开(公告)号：EP1237926A4

公开(公告)日：2006-04-12

申请号：EP00983939

申请日：2000-12-06

申请人： BIOSITE INC ,  GENPHARM INT

发明人： BUECHLER JOE ,  VALKIRS GUNARS ,  GRAY JEFF ,  LONBERG NILS

IPC分类号： C07K16/18 ,  C07K16/24 ,  C12N15/09 ,  G01N33/53 ,  G01N33/543 ,  C07K16/00

CPC分类号： C07K16/18 ,  C07K16/244 ,  C07K2317/21 ,  C07K2317/55 ,  G01N33/543 ,  Y10S435/962 ,  Y10S435/973 ,  Y10S436/809

摘要： The invention provides in vitro methods of detection using human antibodies. The methods are particularly useful for analyzing human samples containing HAMA or heterophilic antibodies. A human antibody can bind to an analyte in such samples without binding to HAMA or heterophilic antibodies present in the samples. The methods can be effected using a sandwich format among others.

公开(公告)号：EP0854917A4

公开(公告)日：2002-07-24

申请号：EP96941938

申请日：1996-10-10

申请人： GENPHARM INT

发明人： LONBERG NILS ,  KAY ROBERT M

IPC分类号： C12N15/02 ,  A01K67/027 ,  A61K38/00 ,  C07K14/725 ,  C07K16/00 ,  C07K16/28 ,  C07K16/30 ,  C07K16/42 ,  C07K16/44 ,  C07K16/46 ,  C12N5/00 ,  C12N5/10 ,  C12N5/16 ,  C12N15/00 ,  C12N15/09 ,  C12N15/113 ,  C12N15/85 ,  C12N15/87 ,  C12N15/90 ,  C12P21/08 ,  C12R1/91

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/0368 ,  A61K38/00 ,  C07K14/7051 ,  C07K16/00 ,  C07K16/2812 ,  C07K16/3007 ,  C07K16/4266 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/92 ,  C07K2319/00 ,  C12N5/163 ,  C12N15/00 ,  C12N15/113 ,  C12N15/85 ,  C12N15/87 ,  C12N15/90 ,  C12N15/907 ,  C12N2310/111 ,  C12N2800/206 ,  C12N2800/70 ,  C12N2830/30 ,  C12N2830/36 ,  C12N2830/85

摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

公开(公告)号：EP0754225A4

公开(公告)日：2001-01-31

申请号：EP94916581

申请日：1994-04-25

申请人： GENPHARM INT

发明人： LONBERG NILS ,  KAY ROBERT M

IPC分类号： A01K67/027 ,  A61K38/00 ,  C07K16/00 ,  C07K16/28 ,  C07K16/30 ,  C07K16/42 ,  C07K16/44 ,  C07K16/46 ,  C12N5/10 ,  C12N15/02 ,  C12N15/85 ,  C12P21/08 ,  C12N15/13 ,  A61K39/00

CPC分类号： C12N15/8509 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/01 ,  A61K38/00 ,  C07K16/00 ,  C07K16/2812 ,  C07K16/3007 ,  C07K16/4291 ,  C07K16/44 ,  C07K16/462 ,  C07K2317/24

摘要： The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.