公开(公告)号：EP0813545A1

公开(公告)日：1997-12-29

申请号：EP96911262

申请日：1996-03-07

申请人： UNIV YALE ,  IMP CANCER RES TECH

发明人： ISH-HOROWICZ DAVID ,  HENRIQUE DOMINGOS M P ,  LEWIS JULIAN H ,  MYAT ANNA M ,  ARTAVANIS-TSAKONAS SPYRIDON ,  MANN ROBERT S ,  GRAY GRACE

IPC分类号： C12N15/09 ,  A61K31/70 ,  A61K38/00 ,  A61K39/395 ,  A61K48/00 ,  A61P25/00 ,  A61P35/00 ,  C07K14/435 ,  C07K14/46 ,  C07K14/465 ,  C07K14/47 ,  C07K14/705 ,  C07K16/18 ,  C07K19/00 ,  C12N5/10 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/53 ,  G01N33/577 ,  C07K14/00 ,  A01N37/18 ,  A01N43/04 ,  C07H17/00 ,  C12N5/00 ,  C12P21/06

CPC分类号： C07K14/465 ,  A61K38/00 ,  C07K14/43504 ,  C07K14/43581 ,  C07K14/46 ,  C07K14/463 ,  C07K14/705

摘要： The present invention relates to nucleotide sequences of vertebrate Serrate genes, and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof. In a specific embodiment, the Serrate protein is a human protein. The invention further relates to fragments (and derivatives and analogs thereof) of a vertebrate Serrate which comprise one or more domains of the Serrate protein, including but not limited to the intracellular domain, extracellular domain, DSL domain, cysteine rich domain, transmembrane region, membrane-associated region, or one or more EGF-like repeats of a Serrate protein, or any combination of the foregoing. Antibodies to vertebrate Serrate, its derivatives and analogs, are additionally provided. Methods of production of the vertebrate Serrate proteins, derivatives and analogs, e.g., by recombinant means, are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are provided.In specific examples, isolated Serrate genes, from chick, mouse, Xenopus and human, are provided.

公开(公告)号：EP0576623A4

公开(公告)日：1995-01-18

申请号：EP92911557

申请日：1992-05-01

申请人： UNIV YALE ,  INDIANA UNIVERSITY FOUNDATION

发明人： ARTAVANIS-TSAKONAS SPYRIDON ,  MUSKAVITCH MARC ALAN TELANDER ,  FEHON RICHARD GRANT ,  REBAY ILARIA ,  BLAUMUELLER CHRISTINE MARIE ,  SHEPARD SCOTT BROCKEWELL

IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K14/47 ,  C07K14/485 ,  C07K14/52 ,  C07K14/705 ,  C07K16/00 ,  C07K16/18 ,  C07K19/00 ,  C12N5/10 ,  C12N15/12 ,  C12P21/02 ,  C12P21/08 ,  C12R1/91 ,  C07K13/00 ,  C12N15/63 ,  C12P21/00

CPC分类号： C07K16/18 ,  A61K38/00 ,  C07K14/705 ,  C07K2319/00 ,  Y10S530/839

摘要： The present invention relates to nucleotide sequences of the human Notch and Delta genes, and amino acid sequences of their encoded proteins, as well as fragments thereof containing an antigenic determinant or which are functionally active. The invention is also directed to fragments (termed herein "adhesive fragments"), and the sequences thereof, of the proteins ("toporythmic proteins") encoded by toporythmic genes which mediate homotypic or heterotypic binding to toporythmic proteins. Toporythmic genes, as used herein, refers to the genes Notch, Delta and Serrate, as well as other members of the Delta/Serrate family which may be identified, e.g., by the methods described herein. Antibodies to human Notch and to adhesive fragments are additionally provided.

公开(公告)号：EP0948348A4

公开(公告)日：2002-05-22

申请号：EP96933960

申请日：1996-09-27

申请人： UNIV YALE

发明人： ARTAVANIS-TSAKONAS SPYRIDON ,  FORTINI MARK E ,  MATSUNO KENJI

IPC分类号： C12N15/09 ,  A61K31/00 ,  A61K35/12 ,  A61K38/00 ,  A61K39/395 ,  A61K45/00 ,  A61K48/00 ,  A61P43/00 ,  C07K14/47 ,  C12N5/00 ,  C12N5/07 ,  C12N5/0797 ,  C12N5/10 ,  C12P21/02 ,  C12N5/08 ,  A61K38/17

CPC分类号： C12N5/0623 ,  A61K35/12 ,  A61K38/00 ,  C07K14/47 ,  C12N5/0018 ,  C12N5/0601 ,  C12N2501/42

摘要： The present invention is directed to methods for the expansion of non-terminally differentiated cells ("precursor cells") using agonists of Notch function, by inhibiting the differentiation of the cells without inhibiting proliferation (mitotic activity) such that an expanded population of non-terminally differentiated cells is obtained. The cells are preferably stem or progenitor cells. These expanded cells can be used in cell replacement therapy to provide desired cell populations and help in the regeneration of diseased and/or injured tissues. The expanded cell populations can also be made recombinant and used for gene therapy, or can be used to supply functions associated with a particular precursor cell or its progeny cell.

公开(公告)号：EP0813545A4

公开(公告)日：2002-04-24

申请号：EP96911262

申请日：1996-03-07

申请人： UNIV YALE ,  IMP CANCER RES TECH

发明人： ISH-HOROWICZ DAVID ,  HENRIQUE DOMINGOS M P ,  LEWIS JULIAN H ,  MYAT ANNA M ,  ARTAVANIS-TSAKONAS SPYRIDON ,  MANN ROBERT S ,  GRAY GRACE E

IPC分类号： C12N15/09 ,  A61K31/70 ,  A61K38/00 ,  A61K39/395 ,  A61K48/00 ,  A61P25/00 ,  A61P35/00 ,  C07K14/435 ,  C07K14/46 ,  C07K14/465 ,  C07K14/47 ,  C07K14/705 ,  C07K16/18 ,  C07K19/00 ,  C12N5/10 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/53 ,  G01N33/577 ,  C07K14/00 ,  A01N37/18 ,  A01N43/04 ,  C07H17/00 ,  C12N5/00 ,  C12P21/06

CPC分类号： C07K14/465 ,  A61K38/00 ,  C07K14/43504 ,  C07K14/43581 ,  C07K14/46 ,  C07K14/463 ,  C07K14/705

公开(公告)号：EP0861261A4

公开(公告)日：2001-08-29

申请号：EP96924334

申请日：1996-06-28

申请人： IMP CANCER RES TECH ,  UNIV YALE

发明人： ISH-HOROWICZ DAVID ,  HENRIQUE DOMINGO M P ,  LEWIS JULIAN H ,  ARTAVANIS-TSAKONAS SPYRIDON ,  GRAY GRACE E

IPC分类号： C12N15/09 ,  A61K31/70 ,  A61K38/00 ,  A61K39/395 ,  A61K48/00 ,  A61P25/00 ,  A61P35/00 ,  C07K14/46 ,  C07K14/47 ,  C07K14/705 ,  C07K16/18 ,  C12N5/10 ,  C12P21/02 ,  C12R1/91 ,  C07H17/00 ,  C07K14/00 ,  C12N5/00 ,  C12N15/00 ,  C12P21/06

CPC分类号： C07K14/47 ,  A61K38/00 ,  C07K14/705 ,  C07K2319/00

公开(公告)号：EP0662827A4

公开(公告)日：1997-12-03

申请号：EP93923752

申请日：1993-09-30

申请人： UNIV YALE

发明人： ARTAVANIS-TSAKONAS SPYRIDON ,  FEHON RICHARD GRANT ,  ZAGOURAS PANAYIOTIS ,  BLAUMUELLER CHRISTINE MARIE DE

IPC分类号： G01N33/53 ,  A01N37/18 ,  A61K31/70 ,  A61K38/00 ,  A61K38/17 ,  A61K39/395 ,  A61K48/00 ,  A61P1/16 ,  A61P17/00 ,  A61P25/00 ,  A61P35/00 ,  A61P43/00 ,  C07H21/04 ,  C07K14/435 ,  C07K14/47 ,  C07K14/705 ,  C12N1/21 ,  C12N15/09 ,  C12N15/62 ,  C12P21/02 ,  C12R1/19 ,  G01N33/574 ,  G01N33/68 ,  A61K31/00 ,  A61K39/44

CPC分类号： A61K31/70 ,  A61K38/00 ,  C07K14/43581 ,  C07K14/47 ,  C07K14/705 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/20 ,  C07K2319/23 ,  C07K2319/70 ,  C07K2319/95 ,  C12N15/62 ,  G01N33/57411 ,  G01N33/57415 ,  G01N33/57419 ,  G01N33/57484 ,  G01N33/6893 ,  Y10S436/811 ,  Y10S436/813 ,  Y10S436/815

摘要： The present invention relates to therapeutic and diagnostic methods and compositions based on Notch proteins and nucleic acids. Figure 17 displays the sequences of human Notch DNA and the encoded human Notch protein. The invention provides for treatment of disorders of cell fate or differentiation by administration of a therapeutic compound of the invention. Such therapeutic compounds (termed herein 'Therapeutics') include Notch proteins and analogs and derivatives (including fragments) thereof, antibodies thereto, nucleic acids encoding the Notch proteins, analogs, or derivatives, Notch antisense nucleic acids, as well as toporythmic proteins and derivatives which bind to or otherwise interact with Notch proteins, their encoding nucleic acids or antibodies. In a preferred embodiment, a Therapeutic of the invention is administered to treat a cancerous condition, or to prevent progression from a pre-neoplastic or non-malignant state into a neoplastic or a malignant state.