公开(公告)号：US20060247422A1

公开(公告)日：2006-11-02

申请号：US11342519

申请日：2006-01-30

申请人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

发明人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

IPC分类号： C07K14/53

CPC分类号： C07K17/08 ,  A61K38/00 ,  A61K47/60 ,  C07K14/535

摘要： The present invention provides a chemically-modified protein prepared by binding polyethylene glycol to a polypeptide characterized by being the product of expression by a host cell of an exogenous DNA sequence and substantially having the following amino acid sequence: (Het)n Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Het Glu Glu Leu Gly Het Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Het Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro (n = 0 or 1)

公开(公告)号：US5824778A

公开(公告)日：1998-10-20

申请号：US983620

申请日：1992-11-30

申请人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

发明人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

IPC分类号： A61K38/00 ,  A61K47/48 ,  C07K14/535 ,  C07K17/08 ,  C07K14/53

CPC分类号： A61K47/48215 ,  C07K14/535 ,  C07K17/08 ,  A61K38/00 ,  Y10S930/145

摘要： The present invention provides a chemically-modified protein prepared by binding polyethylene glycol to a polypeptide characterized by being the product of expression by a host cell of an exogenous DNA sequence and substantially having the following amino acid sequence: ##STR1## The chemically-modified protein according to the present invention has a much longer lasting neutrophil-increasing activity than that of the intact human G-CSF, enabling fewer numbers of administration with a lower dose.

摘要翻译： 本发明提供了一种化学修饰的蛋白质，其通过将聚乙二醇与通过宿主细胞表达外源DNA序列并且基本上具有以下氨基酸序列的产物结合的多肽制备：基本上具有以下氨基酸序列：（Met）n ThrProLeuGlyProAlaSerSerLeuProGln SerPheLeuLe​​uLysCysLeuGluGlnValArg LysIleGInGlyAspGlyAlaAlaLeuGlnGlu LysLeuCysAlaThrTyrLysLeuCysHisPro GluGluLeuValLeuLe​​uGlyHisSerLeuGly IleProTrpAlaProLeuSerSerCysProSer GlnAlaLeuGlnLeuAlaGlyCysLeuSerGln LeuHisSerGlyLeuPheLeuTyrGlnGlyLeu LeuGlnAlaLeuGluGlyIleSerProGluLeu GlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrIleTrpGlnGlnMet GluGluLeuGlyMetAlaProAlaLeuGlnPro ThrGlnGlyAlaMetProAlaPheAlaSerAla PheGlnArgArgAlaGlyGlyValLeuValAla SerHisLeuGlnSerPheLeuGluValSerTyr ArgValLeuArgHisLeuAlaGlnPro（n = 0或1）的化学修饰的蛋白质根据本发明具有比完整的人G-CSF的长得多的持续嗜中性粒细胞增加的活动，以便˚F 有较低剂量的治疗数量。

公开(公告)号：US20070219357A1

公开(公告)日：2007-09-20

申请号：US11716866

申请日：2007-03-12

申请人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

发明人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

IPC分类号： C07K14/475

CPC分类号： C07K17/08 ,  A61K38/00 ,  A61K47/60 ,  C07K14/535 ,  Y10S930/145

摘要： The present invention provides a chemically-modified protein prepared by binding polyethylene glycol to a polypeptide characterized by being the product of expression by a host cell of an exogenous DNA sequence and substantially having the following amino acid sequence: (Met)n Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro (n = 0 (SEQ ID NO: 1) or 1 (SEQ ID NO: 2)) The chemically-modified protein according to the present invention has a neutrophils-increasing activity much more lasted than that of the intact human G-CSF, enabling fewer numbers of administration with a lower dose.

公开(公告)号：US06166183A

公开(公告)日：2000-12-26

申请号：US957719

申请日：1997-10-27

申请人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

发明人： Rika Ishikawa ,  Yuji Okada ,  Makoto Kakitani

IPC分类号： C07K14/535

CPC分类号： C07K14/535

摘要： The present invention provides a chemically-modified protein prepared by binding polyethylene glycol to a polypeptide characterized by being the product of expression by a host cell of an exogenous DNA sequence and substantially having the following amino acid sequence: (Het)n - Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln - Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg - Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu - Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro - Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly - Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser - Gln Ala Leu Gln Leu Ala Cly Cys Leu Ser Gln - Leu His Ser Gly Leu Phe Leu Tyr Gln GIY Leu - Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu - Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val - Ala Asp Phe Ala Thr Tbr Ile Trp Gln Gln Het - Glu Glu Leu Gly Het Ala Pro Ala Leu Gln Pro - Thr Gln Gly Ala Het Pro Ala Phe Ala Ser Ala - Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala - Ser His Leu Gln Ser Phe Leu Glu Val Scr Tyr - Arg Val Leu Arg His Leu Ala Gln Pro (n = 0 or 1) The chemically-modified protein according to the present invention has a neutrophils-increasing activity much more lasted than that of the intact human G-CSF, enabling fewer numbers of administration with a lower dose.

摘要翻译： 本发明提供了通过将聚乙二醇与多肽结合而制备的化学修饰的蛋白质，其特征在于宿主细胞表达外源DNA序列并且基本上具有以下氨基酸序列的产物： - （Het）n - Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln - Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg - - Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu - - Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro - - Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly - - Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser - - Gln Ala Leu Gln Leu Ala Cly Cys Leu Ser Gln - - Leu His Ser Gly Leu Phe Leu Tyr Gln GIY Leu - - Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu - - Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val - - Ala Asp Phe Ala Thr Tbr Ile Trp Gln Gln Het - Glu Glu Leu Gly Het Ala Pro Ala Leu Gln Pro - - Thr Gln Gly Ala Het Pro Ala Phe Ala Ser Ala - - Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala - - Ser His Leu Gln Ser Phe Leu Glu Val Scr Ty r - Arg Val Leu Arg His Leu Ala Gln Pro - （n = 0或1） - 根据本发明的化学修饰的蛋白具有比完整的人G-CSF的中性粒细胞增加活性更多的持续时间， 使用更少剂量的较少数量的给药。