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    NOVEL RECOMBINANT PROTEINS WITH N-TERMINAL FREE THIOL
    1.
    发明申请
    NOVEL RECOMBINANT PROTEINS WITH N-TERMINAL FREE THIOL 审中-公开
    新型重组蛋白与N-末端免费THIOL

    公开(公告)号：US20090239790A1

    公开(公告)日：2009-09-24

    申请号：US12476268

    申请日：2009-06-02

    申请人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

    发明人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

    IPC分类号： A61K38/22 ,  C07K14/61

    CPC分类号： C07K1/1075 ,  C07K1/1077 ,  C07K14/505

    摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO   (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position -1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of -1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

    摘要翻译： 本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可通过重组方法制备并准备进一步化学衍生化。 特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的红细胞生成素缀合物化合物。 更具体地，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：<？in-line-formula description =“In-line Formulas”end =“lead”→（M）nXA-cys-EPO（I） 其中EPO是选自红细胞生成素或促红细胞生成素变体的红细胞生成素，其具有不同于野生型人EPO的至少一种氨基酸，其中，“=”在线公式“end =”tail“ 或其具有引起骨髓细胞增加红细胞产生的生物学特性的任何药物可接受的衍生物; cys代表氨基酸半胱氨酸并且发生在相对于促红细胞生成素部分的氨基酸序列的位置-1; A表示用于将X化学连接到-1Cys的硫醇基上的残留部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其它聚合物; M是增加构建体的循环半衰期的有机分子（包括肽和蛋白质） N为0〜15的整数。

    Novel recombinant proteins with N-terminal free thiol
    2.
    发明申请
    Novel recombinant proteins with N-terminal free thiol 审中-公开
    具有N-末端游离硫醇的新型重组蛋白

    公开(公告)号：US20050170457A1

    公开(公告)日：2005-08-04

    申请号：US11021516

    申请日：2004-12-23

    申请人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

    发明人： Chadler Pool ,  Juliane Mills ,  Mark Cunningham

    IPC分类号： C07H21/04 ,  C07K1/00 ,  C07K1/107 ,  C07K14/505 ,  C12N9/96 ,  C12N15/85 ,  C12P21/02

    CPC分类号： C07K1/1075 ,  C07K1/1077 ,  C07K14/505

    摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO   (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position −1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of −1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

    摘要翻译： 本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可通过重组方法制备并准备进一步化学衍生化。 特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的红细胞生成素缀合物化合物。 更具体地，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：<？in-line-formula description =“In-line Formulas”end =“lead”？>（M） -XA-cys-EPO（I）<？in-line-formula description =“In-line Formulas”end =“tail”？>其中EPO是选自促红细胞生成素或具有至少一个氨基酸的促红细胞生成素变体的红细胞生成部分 不同于野生型人EPO，或其具有引起骨髓细胞增加红细胞产生的生物学特性的任何药物可接受的衍生物; cys代表氨基酸半胱氨酸并且发生在相对于促红细胞生成素部分的氨基酸序列的位置-1; A表示用于将X化学连接到-1Cys的硫醇基上的残留部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其它聚合物; M是增加构建体的循环半衰期的有机分子（包括肽和蛋白质） N为0〜15的整数。