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1.发明申请METHOD FOR THE PRODUCTION OF CONJUGATES OF INSULIN-LIKE GROWTH FACTOR-1 AND POLY(ETHYLENE GLYCOL) 审中-公开产生胰岛素样生长因子-1和聚（乙二醇）的方法公开(公告)号：US20100035817A1
公开(公告)日：2010-02-11
申请号：US12576266
申请日：2009-10-09
申请人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
发明人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
CPC分类号： C07K14/65 , A61K47/60 , C07K2319/21 , C07K2319/50
摘要： The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.
摘要翻译： 本发明涉及包含IGF-I或与前肽的C-末端N末端连接的IGF-1变体的融合蛋白。 本发明还涉及涉及在制备赖氨酸 - PEG化IGF-I或IGF-I变体中使用上述融合蛋白的方法。 该方法包括以下步骤：培养包含含有编码融合蛋白的核酸的表达载体的原核宿主细胞，并使细胞表达融合蛋白，回收聚乙二醇化所述融合蛋白，用IgA蛋白酶切割所述聚乙二醇化融合蛋白，以及 回收赖氨酸 - PEG化IGF-I或IGF-I变体。 本发明还涉及使用上述方法制备的赖氨酸 - 聚乙二醇化IGF-I或IGF-I变体。 此外，本发明涉及使用赖氨酸PEG化IGF-I或IGF-1变体和包含赖氨酸 - PEG化IGF-I或IGF-I变体的组合物治疗神经变性疾病如阿尔茨海默病的方法。
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2.发明申请METHOD FOR THE PRODUCTION OF CONJUGATES OF INSULIN-LIKE GROWTH FACTOR-1 AND POLY(ETHYLENE GLYCOL) 有权产生胰岛素样生长因子-1和聚（乙二醇）的方法公开(公告)号：US20080119409A1
公开(公告)日：2008-05-22
申请号：US11846857
申请日：2007-08-29
申请人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
发明人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
CPC分类号： C07K14/65 , A61K47/60 , C07K2319/21 , C07K2319/50
摘要： The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.
摘要翻译： 本发明涉及包含IGF-I或与前肽的C-末端N末端连接的IGF-1变体的融合蛋白。 本发明还涉及涉及在制备赖氨酸 - PEG化IGF-I或IGF-I变体中使用上述融合蛋白的方法。 该方法包括以下步骤：培养包含含有编码融合蛋白的核酸的表达载体的原核宿主细胞，并使细胞表达融合蛋白，回收聚乙二醇化所述融合蛋白，用IgA蛋白酶切割所述聚乙二醇化融合蛋白，以及 回收赖氨酸 - PEG化IGF-I或IGF-I变体。 本发明还涉及使用上述方法制备的赖氨酸 - 聚乙二醇化IGF-I或IGF-I变体。 此外，本发明涉及使用赖氨酸PEG化IGF-I或IGF-1变体和包含赖氨酸 - PEG化IGF-I或IGF-I变体的组合物治疗神经变性疾病如阿尔茨海默病的方法。
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3.发明申请METHOD FOR THE PRODUCTION OF CONJUGATES OF INSULIN-LIKE GROWTH FACTOR-1 AND POLY(ETHYLENE GLYCOL) 有权产生胰岛素样生长因子-1和聚（乙二醇）的方法公开(公告)号：US20130065831A1
公开(公告)日：2013-03-14
申请号：US13590549
申请日：2012-08-21
申请人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
发明人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
CPC分类号： C07K14/65 , A61K47/60 , C07K2319/21 , C07K2319/50
摘要： The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.
摘要翻译： 本发明涉及包含IGF-I或与前肽的C-末端N末端连接的IGF-1变体的融合蛋白。 本发明还涉及涉及在制备赖氨酸 - PEG化IGF-I或IGF-I变体中使用上述融合蛋白的方法。 该方法包括以下步骤：培养包含含有编码融合蛋白的核酸的表达载体的原核宿主细胞，并使细胞表达融合蛋白，回收聚乙二醇化所述融合蛋白，用IgA蛋白酶切割所述聚乙二醇化融合蛋白;以及 回收赖氨酸 - PEG化IGF-I或IGF-I变体。 本发明还涉及使用上述方法制备的赖氨酸 - 聚乙二醇化IGF-I或IGF-I变体。 此外，本发明涉及使用赖氨酸PEG化IGF-I或IGF-1变体和包含赖氨酸 - PEG化IGF-I或IGF-I变体的组合物治疗神经变性疾病如阿尔茨海默病的方法。
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4.发明申请公开(公告)号：US20100210547A1
公开(公告)日：2010-08-19
申请号：US12767829
申请日：2010-04-27
申请人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
发明人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
CPC分类号： C07K14/65 , A61K47/60 , C07K2319/21 , C07K2319/50
摘要： The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.
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5.发明授权公开(公告)号：US08476232B2
公开(公告)日：2013-07-02
申请号：US13590549
申请日：2012-08-21
申请人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
发明人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
CPC分类号： C07K14/65 , A61K47/60 , C07K2319/21 , C07K2319/50
摘要： The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.
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6.发明授权Method for the production of conjugates of insulin-like growth factor-1 and poly(ethylene glycol) 有权生产胰岛素样生长因子-1和聚（乙二醇）共轭物的方法公开(公告)号：US07625996B2
公开(公告)日：2009-12-01
申请号：US11846857
申请日：2007-08-29
申请人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
发明人： Stephan Fischer , Friederike Hesse , Hendrik Knoetgen , Kurt Lang , Friedrich Metzger , Joerg Thomas Regula , Christian Schantz , Andreas Schaubmar , Hans-Joachim Schoenfeld
CPC分类号： C07K14/65 , A61K47/60 , C07K2319/21 , C07K2319/50
摘要： The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.
摘要翻译： 本发明涉及包含IGF-I或与前肽的C-末端N末端连接的IGF-1变体的融合蛋白。 本发明还涉及涉及在制备赖氨酸 - PEG化IGF-I或IGF-I变体中使用上述融合蛋白的方法。 该方法包括以下步骤：培养包含含有编码融合蛋白的核酸的表达载体的原核宿主细胞，并使细胞表达融合蛋白，回收聚乙二醇化所述融合蛋白，用IgA蛋白酶切割所述聚乙二醇化融合蛋白，以及 回收赖氨酸 - PEG化IGF-I或IGF-I变体。 本发明还涉及使用上述方法制备的赖氨酸 - 聚乙二醇化IGF-I或IGF-I变体。 此外，本发明涉及使用赖氨酸PEG化IGF-I或IGF-1变体和包含赖氨酸 - PEG化IGF-I或IGF-I变体的组合物治疗神经变性疾病如阿尔茨海默病的方法。
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7.发明申请公开(公告)号：US20120322732A1
公开(公告)日：2012-12-20
申请号：US13551648
申请日：2012-07-18
申请人： Beat Amrein , Stefan Foser , Kurt Lang , Friedrich Metzger , Joerg Regula , Andreas Schaubmar , Friederike Hesse , Klaus-Peter Kuenkele , Martin Lanzendoerfer
发明人： Beat Amrein , Stefan Foser , Kurt Lang , Friedrich Metzger , Joerg Regula , Andreas Schaubmar , Friederike Hesse , Klaus-Peter Kuenkele , Martin Lanzendoerfer
CPC分类号： A61K47/60 , C07K14/475 , C07K14/65
摘要： A conjugate consisting of an insulin-like growth factor-1 (IGF-I) variant and one or two poly(ethylene glycol) group(s), characterized in that said IGF-I variant has an amino acid alteration at up to three amino acid positions 27, 37, 65, 68 of the wild-type IGF-I amino acid sequence so that one or two of said amino acids is/are lysine and amino acid 27 is a polar amino acid but not lysine, is conjugated via the primary amino group(s) of said lysine(s) and said poly(ethylene glycol) group(s) have an overall molecular weight of from 20 to 100 kDa is disclosed. This conjugate is useful for the treatment of neurodegenerative disorders like Alzheimer's Disease.
摘要翻译： 由胰岛素样生长因子-1（IGF-I）变体和一个或两个聚（乙二醇）基团组成的缀合物，其特征在于所述IGF-1变体在至多三个氨基酸处具有氨基酸改变 野生型IGF-I氨基酸序列的酸性位置27,37,65,68，使得一个或两个所述氨基酸是赖氨酸，氨基酸27是极性氨基酸而不是赖氨酸，通过 公开了所述赖氨酸和所述聚（乙二醇）基团的伯氨基的总分子量为20至100kDa。 该缀合物可用于治疗神经变性疾病如阿尔茨海默病。
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8.发明申请公开(公告)号：US20060154865A1
公开(公告)日：2006-07-13
申请号：US11313101
申请日：2005-12-20
申请人： Beat Amrein , Stefan Foser , Kurt Lang , Friedrich Metzger , Joerg Regula , Andreas Schaubmar , Friederike Hesse , Klaus-Peter Kuenkele , Martin Lanzendoerfer
发明人： Beat Amrein , Stefan Foser , Kurt Lang , Friedrich Metzger , Joerg Regula , Andreas Schaubmar , Friederike Hesse , Klaus-Peter Kuenkele , Martin Lanzendoerfer
CPC分类号： A61K47/60 , C07K14/475 , C07K14/65
摘要： A conjugate consisting of an insulin-like growth factor-1 (IGF-I) variant and one or two poly(ethylene glycol) group(s), characterized in that said IGF-I variant has an amino acid alteration at up to three amino acid positions 27, 37, 65, 68 of the wild-type IGF-I amino acid sequence so that one or two of said amino acids is/are lysine and amino acid 27 is a polar amino acid but not lysine, is conjugated via the primary amino group(s) of said lysine(s) and said poly(ethylene glycol) group(s) have an overall molecular weight of from 20 to 100 kDa is disclosed. This conjugate is useful for the treatment of neurodegenerative disorders like Alzheimer's Disease.
摘要翻译： 由胰岛素样生长因子-1（IGF-I）变体和一个或两个聚（乙二醇）基团组成的缀合物，其特征在于所述IGF-1变体在最多三个氨基酸处具有氨基酸改变 野生型IGF-I氨基酸序列的酸性位置27,37,65,68，使得一个或两个所述氨基酸是赖氨酸，氨基酸27是极性氨基酸而不是赖氨酸，通过 公开了所述赖氨酸和所述聚（乙二醇）基团的伯氨基的总分子量为20至100kDa。 该缀合物可用于治疗神经变性疾病如阿尔茨海默病。
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9.发明申请公开(公告)号：US20110009317A1
公开(公告)日：2011-01-13
申请号：US12791904
申请日：2010-06-02
申请人： Beat Amrein , Stefan Foser , Kurt Long , Friedrich Metzger , Joerg Regula , Andreas Schaubmar , Friederike Hesse , Klaus-Peter Kuenkele , Martin Lanzendoerfer
发明人： Beat Amrein , Stefan Foser , Kurt Long , Friedrich Metzger , Joerg Regula , Andreas Schaubmar , Friederike Hesse , Klaus-Peter Kuenkele , Martin Lanzendoerfer
CPC分类号： A61K47/60 , C07K14/475 , C07K14/65
摘要： A conjugate consisting of an insulin-like growth factor-1 (IGF-I) variant and one or two poly(ethylene glycol) group(s), characterized in that said IGF-I variant has an amino acid alteration at up to three amino acid positions 27, 37, 65, 68 of the wild-type IGF-I amino acid sequence so that one or two of said amino acids is/are lysine and amino acid 27 is a polar amino acid but not lysine, is conjugated via the primary amino group(s) of said lysine(s) and said poly(ethylene glycol) group(s) have an overall molecular weight of from 20 to 100 kDa is disclosed. This conjugate is useful for the treatment of neurodegenerative disorders like Alzheimer's Disease.
摘要翻译： 由胰岛素样生长因子-1（IGF-I）变体和一个或两个聚（乙二醇）基团组成的缀合物，其特征在于所述IGF-1变体在至多三个氨基酸处具有氨基酸改变 野生型IGF-I氨基酸序列的酸性位置27,37,65,68，使得一个或两个所述氨基酸是赖氨酸，氨基酸27是极性氨基酸而不是赖氨酸，通过 公开了所述赖氨酸和所述聚（乙二醇）基团的伯氨基的总分子量为20至100kDa。 该缀合物可用于治疗神经变性疾病如阿尔茨海默病。
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10.发明申请Use of PEGylated IGF-I variants for the treatment of neuromuscular disorders 审中-公开使用聚乙二醇化IGF-I变体治疗神经肌肉疾病公开(公告)号：US20090253628A1
公开(公告)日：2009-10-08
申请号：US12411673
申请日：2009-03-26
IPC分类号： A61K38/18
CPC分类号： A61K38/30 , A61K47/60 , C07K14/475
摘要： The present invention relates to a pharmaceutical composition containing a PEGylated IGF-I variant derived from the wild-type human IGF-I amino acid sequence where one or two of the lysine amino acids at positions 27, 65, and 68 are altered to be a polar amino acid other than lysine and where the PEG is attached to at least one lysine residue. The invention also relates to methods for the treatment, prevention and/or delay of progression of neuromuscular disorders, in particular amyotrophic lateral sclerosis (ALS) by administering a therapeutically effective amount of the pharmaceutical composition of the invention.
摘要翻译： 本发明涉及含有衍生自野生型人IGF-I氨基酸序列的聚乙二醇化IGF-I变体的药物组合物，其中位置27,65和68上的一个或两个赖氨酸氨基酸被改变为 除赖氨酸以外的极性氨基酸，其中PEG连接至至少一个赖氨酸残基。 本发明还涉及通过施用治疗有效量的本发明的药物组合物来治疗，预防和/或延缓神经肌肉疾病，特别是肌萎缩性侧索硬化（ALS）的进展的方法。
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