公开(公告)号：EP1436384A2

公开(公告)日：2004-07-14

申请号：EP02782829.2

申请日：2002-10-04

申请人： Novartis AG ,  Université Victor Segalen Bordeaux 2 ,  Technische Universität München ,  Oregon Health & Science University ,  Universität Heidelberg ,  CHRU DE LILLE,centre Hospitalier Regional Universitaire de Lille ,  MEDVET SCIENCE PTY. LTD.

发明人： BARTHE, Christophe ,  BRANFORD, Susan ,  CORBIN, Amie ,  DRUKER, Brian, Jay ,  DUYSTER, Justus ,  HOCHHAUS, Andreas ,  HUGHES, Timothy ,  KREIL, Sebastian ,  LEGUAY, Thibaut ,  MAHON, François-Xavier ,  MARIT, Gérald ,  MÜLLER, Martin ,  PESCHEL, Christian ,  PREUDHOMME, Claude ,  ROCHE LESTIENNE, Catherine ,  RUDZKI, Zbigniew

IPC分类号： C12N9/12

CPC分类号： C12N9/1205

摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

公开(公告)号：EP1436384B1

公开(公告)日：2009-06-17

申请号：EP02782829.2

申请日：2002-10-04

申请人： NOVARTIS AG ,  Université Victor Segalen Bordeaux 2 ,  Technische Universität München ,  Oregon Health & Science University ,  Universität Heidelberg ,  CHRU DE LILLE, centre Hospitalier Regional Universitaire de Lille ,  MEDVET SCIENCE PTY. LTD.

发明人： BARTHE, Christophe ,  BRANFORD, Susan ,  CORBIN, Amie ,  DRUKER, Brian, Jay ,  DUYSTER, Justus ,  HOCHHAUS, Andreas ,  HUGHES, Timothy ,  KREIL, Sebastian ,  LEGUAY, Thibaut ,  MAHON, François-Xavier ,  MARIT, Gérald ,  MÜLLER, Martin ,  PESCHEL, Christian ,  PREUDHOMME, Claude ,  ROCHE LESTIENNE, Catherine ,  RUDZKI, Zbigniew

IPC分类号： C12N9/12

CPC分类号： C12N9/1205

摘要： The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.