公开(公告)号：US20110129852A1

公开(公告)日：2011-06-02

申请号：US12834628

申请日：2010-07-12

申请人： Christophe Barthe ,  Pascale Cony-Makhoul ,  Amie Corbin ,  Sven De Vos ,  Brian Jay Druker ,  Harald Gschaidmeier ,  Michael Hallek ,  Andreas Hochhaus ,  Dieter Hoelzer ,  Wolf-Karsten Hofmann ,  Phillip Koeffler ,  Sebastian Kreil ,  Francois-Xavier Mahon ,  Martin Müller ,  Oliver Gerhard Ottmann ,  Markus Warmuth

发明人： Christophe Barthe ,  Pascale Cony-Makhoul ,  Amie Corbin ,  Sven De Vos ,  Brian Jay Druker ,  Harald Gschaidmeier ,  Michael Hallek ,  Andreas Hochhaus ,  Dieter Hoelzer ,  Wolf-Karsten Hofmann ,  Phillip Koeffler ,  Sebastian Kreil ,  Francois-Xavier Mahon ,  Martin Müller ,  Oliver Gerhard Ottmann ,  Markus Warmuth

IPC分类号： C12N9/12 ,  C07H21/04 ,  G01N33/53 ,  C12N15/63 ,  C12N5/10

CPC分类号： C12Q1/6886 ,  C07K14/82 ,  C12N9/12 ,  C12Q1/485 ,  C12Q2600/106 ,  G01N33/57426 ,  G01N2333/82

摘要： The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, 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.

摘要翻译： 本发明涉及分离的多肽，其包含由突变的功能性Ab1激酶结构域组成的氨基酸序列，所述突变的功能性激酶结构域对N- [4-甲基-3-（4-吡啶基） 吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺或其盐，用于筛选抑制酪氨酸激酶的化合物 这种多肽的活性，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及这种核酸分子在制备这些多肽中的用途，用于筛选抑制酪氨酸激酶的化合物 这些多肽的活性。

公开(公告)号：US20090191606A1

公开(公告)日：2009-07-30

申请号：US12337322

申请日：2008-12-17

申请人： Christophe Barthe ,  Pascale Cony-Makhoul ,  Amie Corbin ,  Sven De Vos ,  Brian Jay Druker ,  Harald Gschaidmeier ,  Michael Hallek ,  Andreas Hochhaus ,  Dieter Hoelzer ,  Wolf-Karsten Hofmann ,  Phillip Koeffler ,  Sebastian Kreil ,  Francois-Xavier Mahon ,  Martin Muller ,  Oliver Gerhard Ottmann ,  Markus Warmuth

发明人： Christophe Barthe ,  Pascale Cony-Makhoul ,  Amie Corbin ,  Sven De Vos ,  Brian Jay Druker ,  Harald Gschaidmeier ,  Michael Hallek ,  Andreas Hochhaus ,  Dieter Hoelzer ,  Wolf-Karsten Hofmann ,  Phillip Koeffler ,  Sebastian Kreil ,  Francois-Xavier Mahon ,  Martin Muller ,  Oliver Gerhard Ottmann ,  Markus Warmuth

IPC分类号： C12N9/12 ,  C07H21/00 ,  C12N15/63 ,  C12N5/10

CPC分类号： C12Q1/6886 ,  C07K14/82 ,  C12N9/12 ,  C12Q1/485 ,  C12Q2600/106 ,  G01N33/57426 ,  G01N2333/82

摘要： The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, 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.

摘要翻译： 本发明涉及分离的多肽，其包含由突变的功能性Ab1激酶结构域组成的氨基酸序列，所述突变的功能性激酶结构域对N- [4-甲基-3-（4-吡啶基） 吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺或其盐，用于筛选抑制酪氨酸激酶的化合物 这种多肽的活性，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及这种核酸分子在制备这些多肽中的用途，用于筛选抑制酪氨酸激酶的化合物 这些多肽的活性。

公开(公告)号：US20060148058A1

公开(公告)日：2006-07-06

申请号：US11343891

申请日：2006-01-31

申请人： Christophe Barthe ,  Pascale Cony-Makhoul ,  Amie Corbin ,  Sven De Vos ,  Brian Druker ,  Harald Gschaidmeier ,  Michael Hallek ,  Andreas Hochhaus ,  Dieter Hoelzer ,  Wolf-Karsten Hofmann ,  Phillip Koeffler ,  Sebastian Kreil ,  Francois-Xavier Mahon ,  Martin Muller ,  Oliver Ottmann ,  Markus Warmuth

发明人： Christophe Barthe ,  Pascale Cony-Makhoul ,  Amie Corbin ,  Sven De Vos ,  Brian Druker ,  Harald Gschaidmeier ,  Michael Hallek ,  Andreas Hochhaus ,  Dieter Hoelzer ,  Wolf-Karsten Hofmann ,  Phillip Koeffler ,  Sebastian Kreil ,  Francois-Xavier Mahon ,  Martin Muller ,  Oliver Ottmann ,  Markus Warmuth

IPC分类号： C12N9/12

CPC分类号： C12Q1/6886 ,  C07K14/82 ,  C12N9/12 ,  C12Q1/485 ,  C12Q2600/106 ,  G01N33/57426 ,  G01N2333/82

摘要： The tides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, 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 they 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 molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

摘要翻译： 包含由突变的功能性Ab1激酶结构域组成的氨基酸序列的所述突变体，所述突变的功能性激酶结构域对N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺或其盐，用于筛选抑制这些多肽的酪氨酸激酶活性的化合物， 涉及编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及这些核酸分子在产生此类多肽中的用途，用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。

公开(公告)号：US20100021920A1

公开(公告)日：2010-01-28

申请号：US12545113

申请日：2009-08-21

申请人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thlbaut Leguay ,  Francois-Xavier Mahon ,  Gèrald Marit ,  Martin Müller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thlbaut Leguay ,  Francois-Xavier Mahon ,  Gèrald Marit ,  Martin Müller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

IPC分类号： C12Q1/68 ,  C12N9/12 ,  C07H21/00 ,  C12N15/63 ,  C12N1/00

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：US20100021921A1

公开(公告)日：2010-01-28

申请号：US12545133

申请日：2009-08-21

申请人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

IPC分类号： C12Q1/68 ,  C12N9/12 ,  C07H21/00 ,  C12N15/63 ,  C12N1/00

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.

摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，所述功能性激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 或其盐使用这样的多肽筛选抑制这种多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及使用其 核酸分子 生产这样的多肽用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。

公开(公告)号：US20090117641A1

公开(公告)日：2009-05-07

申请号：US12165217

申请日：2008-06-30

申请人： Christophe Barthe ,  Susan Bradford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francios-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Bradford ,  Amie Corbin ,  Brian Jay Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francios-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Christian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

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.

摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，所述功能性激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 或其盐使用这样的多肽筛选抑制这种多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及使用其 核酸分子 生产这样的多肽用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。

公开(公告)号：US20050202519A1

公开(公告)日：2005-09-15

申请号：US10491603

申请日：2002-10-04

申请人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Chriatian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

发明人： Christophe Barthe ,  Susan Branford ,  Amie Corbin ,  Brian Druker ,  Justus Duyster ,  Andreas Hochhaus ,  Timothy Hughes ,  Sebastian Kreil ,  Thibaut Leguay ,  Francois-Xavier Mahon ,  Gerald Marit ,  Martin Muller ,  Chriatian Peschel ,  Claude Preudhomme ,  Catherine Roche Lestienne ,  Zbigniew Rudzki

IPC分类号： C12N15/09 ,  C07H21/04 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/12 ,  C12Q1/48

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.

摘要翻译： 本发明涉及分离的多肽，其包含功能性激酶结构域，所述功能性激酶结构域包含天然人Abl激酶结构域的氨基酸序列或其基本相似的序列，其中至少一种选自Met244，Leu248，Gly250，Glu252，Tyr253， Val256，Glu258，Phe311，Ile313，Phe317，Met318，Met351，Glu355，Glu359，Ile360，His361，Leu370，Asp381，Phe382，His396，Ser417，Glu459和Phe486被另一个氨基酸取代，所述突变的功能性激酶结构域对 通过N- [4-甲基-3-（4-吡啶-3-基 - 嘧啶-2-基氨基） - 苯基] -4-（4-甲基 - 哌嗪-1-基甲基） - 苯甲酰胺抑制其酪氨酸激酶活性 或其盐使用这样的多肽筛选抑制这种多肽的酪氨酸激酶活性的化合物，编码这种多肽的核酸分子，重组载体和包含此类核酸分子的宿主细胞，以及使用其 核酸分子 生产这样的多肽用于筛选抑制这些多肽的酪氨酸激酶活性的化合物。

公开(公告)号：US20090306094A1

公开(公告)日：2009-12-10

申请号：US12225125

申请日：2007-03-16

申请人： Francis Y. Lee ,  Andreas Hochhaus ,  Martin Müller

发明人： Francis Y. Lee ,  Andreas Hochhaus ,  Martin Müller

IPC分类号： A61K31/496 ,  C12Q1/68 ,  A61P35/00

CPC分类号： C12Q1/485 ,  G01N33/574

摘要： The present invention relates to mutant BCR-ABL kinase proteins, and to diagnostic and therapeutic methods and compositions useful in the management of disorders, for example cancers, involving cells that express such mutant BCR-ABL kinase proteins.

摘要翻译： 本发明涉及突变型BCR-ABL激酶蛋白，以及可用于治疗病症（例如涉及表达这种突变型BCR-ABL激酶蛋白的细胞）的癌症的诊断和治疗方法和组合物。