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    Arginine deiminase mutant and preparation and application thereof
    1.
    发明授权
    Arginine deiminase mutant and preparation and application thereof 有权
    精氨酸脱亚氨酶突变体及其制备及应用

    公开(公告)号：US08663967B2

    公开(公告)日：2014-03-04

    申请号：US13214398

    申请日：2011-08-22

    申请人： Yanshan Huang ,  Jiwan Qiu ,  Xiaoyu Fu ,  Min Fan ,  Yujiao Wang ,  Yefei Wang

    发明人： Yanshan Huang ,  Jiwan Qiu ,  Xiaoyu Fu ,  Min Fan ,  Yujiao Wang ,  Yefei Wang

    IPC分类号： C12N11/02 ,  C12N11/08 ,  C12N9/00 ,  C12N9/78 ,  C12N1/20 ,  C12N15/00 ,  C07H21/04

    CPC分类号： C12N9/78 ,  A61K38/00 ,  C12Y305/03006

    摘要： The present invention relates to an arginine deiminase mutant with partial lysine-deficient and preparation and application thereof. The arginine deiminase mutant of the present invention has enzymatic activity of degrading arginine into citruline; compared with the arginine deiminase with the amino acid sequence of SEQ ID NO: 1, the amino acid sequence comprises one or more of K9N, T, K59Q, K66R, A, K93E, A, Q, K111R, A, K119Q, L, M, K121Q, I, K122E, L, K126E, S, R, K178I, E, D, K196I, R, K209G, T, D, K243E, V, R, K249D, Q, K263N, Q, K279Y, T, K293R, H, E, K325V, I, K380T, R, E, and K406E, D, S substitutions. Compared with PEG modified natural derived arginine deiminase, the PEG modified arginine deiminase mutant of the present invention retain better bioactivity; and because the quantity of lysine in arginine deiminase is reduced, the PEG modified products are more uniform and can be applied to clinical treatment of hepatoma, melanoma and the like.

    摘要翻译： 本发明涉及具有部分赖氨酸缺陷型及其制备及应用的精氨酸脱亚胺酶突变体。 本发明的精氨酸脱亚胺酶突变体具有将精氨酸降解成柠檬酸的酶活性; 与具有SEQ ID NO：1的氨基酸序列的精氨酸脱亚氨酶相比，氨基酸序列包含K9N，T，K59Q，K66R，A，K93E，A，Q，K111R，A，K119Q，L， M，K121Q，I，K122E，L，K126E，S，R，K178I，E，D，K196I，R，K209G，T，D，K243E，V，R，K249D，Q，K263N，Q，K279Y， K293R，H，E，K325V，I，K380T，R，E和K406E，D，S取代。 与PEG改性天然衍生的精氨酸脱亚胺酶相比，本发明的PEG修饰的精氨酸脱亚氨酶突变体保持较好的生物活性; 并且由于精氨酸去酰亚胺酶中赖氨酸的量减少，PEG改性产物更均匀，可用于肝癌，黑素瘤等的临床治疗。

    ARGININE DEIMINASE MUTANT AND PREPARATION AND APPLICATION THEREOF
    2.
    发明申请
    ARGININE DEIMINASE MUTANT AND PREPARATION AND APPLICATION THEREOF 有权
    ARGININE DEIMINASE突变体及其制备及应用

    公开(公告)号：US20130052179A1

    公开(公告)日：2013-02-28

    申请号：US13214398

    申请日：2011-08-22

    申请人： Yanshan HUANG ,  Jiwan Qiu ,  Xiaoyu Fu ,  Min Fan ,  Yujiao Wang ,  Yefei Wang

    发明人： Yanshan HUANG ,  Jiwan Qiu ,  Xiaoyu Fu ,  Min Fan ,  Yujiao Wang ,  Yefei Wang

    IPC分类号： A61K38/46 ,  C12N11/02 ,  C12N11/10 ,  C12N11/08 ,  C12N15/55 ,  A61P35/00 ,  C12N1/21 ,  C12N1/19 ,  C12N5/10 ,  A61P31/12 ,  A61P25/28 ,  C12N9/78 ,  C12N15/63

    CPC分类号： C12N9/78 ,  A61K38/00 ,  C12Y305/03006

    摘要： The present invention relates to an arginine deiminase mutant with partial lysine-deficient and preparation and application thereof. The arginine deiminase mutant of the present invention has enzymatic activity of degrading arginine into citruline; compared with the arginine deiminase with the amino acid sequence of SEQ ID NO: 1, the amino acid sequence comprises one or more of K9N, T, K59Q, K66R, A, K93E, A, Q, K111R, A, K119Q, L, M, K121Q, I, K122E, L, K126E, S, R, K178I, E, D, K196I, R, K209G, T, D, K243E, V, R, K249D, Q, K263N, Q, K279Y, T, K293R, H, E, K325V, I, K380T, R, E, and K406E, D, S substitutions. Compared with PEG modified natural derived arginine deiminase, the PEG modified arginine deiminase mutant of the present invention retain better bioactivity; and because the quantity of lysine in arginine deiminase is reduced, the PEG modified products are more uniform and can be applied to clinical treatment of hepatoma, melanoma and the like.

    摘要翻译： 本发明涉及具有部分赖氨酸缺陷型及其制备及应用的精氨酸脱亚胺酶突变体。 本发明的精氨酸脱亚胺酶突变体具有将精氨酸降解成柠檬酸的酶活性; 与具有SEQ ID NO：1的氨基酸序列的精氨酸脱亚氨酶相比，氨基酸序列包含K9N，T，K59Q，K66R，A，K93E，A，Q，K111R，A，K119Q，L， M，K121Q，I，K122E，L，K126E，S，R，K178I，E，D，K196I，R，K209G，T，D，K243E，V，R，K249D，Q，K263N，Q，K279Y， K293R，H，E，K325V，I，K380T，R，E和K406E，D，S取代。 与PEG改性天然衍生的精氨酸脱亚胺酶相比，本发明的PEG修饰的精氨酸脱亚氨酶突变体保持较好的生物活性; 并且由于精氨酸去酰亚胺酶中赖氨酸的量减少，PEG改性产物更均匀，可用于肝癌，黑素瘤等的临床治疗。

    Mutant G-CSF fusion protein, and preparation and use thereof
    3.
    发明授权
    Mutant G-CSF fusion protein, and preparation and use thereof 有权
    突变型G-CSF融合蛋白及其制备和应用

    公开(公告)号：US08785597B2

    公开(公告)日：2014-07-22

    申请号：US13575752

    申请日：2010-06-30

    申请人： Xiaofang Wen ,  Yiliang Wu ,  Yefei Wang ,  Zhiyu Yang ,  Min Fan ,  Yujiao Wang ,  Xiaochun Fang ,  You Lu

    发明人： Xiaofang Wen ,  Yiliang Wu ,  Yefei Wang ,  Zhiyu Yang ,  Min Fan ,  Yujiao Wang ,  Xiaochun Fang ,  You Lu

    IPC分类号： C07K1/00 ,  C12P21/04 ,  C12N15/00 ,  C12N5/00 ,  A61K38/18

    CPC分类号： C07K14/535 ,  A61K38/00 ,  C07K2319/31

    摘要： The present invention relates to a mutant G-CSF fusion protein. The mutant G-CSF fusion protein is a fusion protein having the activity of stimulating the proliferation of neutrophilic granulocytes, and having a basic structure of G-CSF/carrier protein or carrier protein/G-CSF; wherein the G-CSF moiety comprises multipoint substitutions thus resulting in changes in biological activity and binding affinity. Compared with existing products, the mutant G-CSF fusion protein in the present invention has longer half-life and higher biological activity. Administration of the pharmaceutical preparation containing this mutant G-CSF fusion protein could be used in the treating neutropenia.

    摘要翻译： 本发明涉及突变型G-CSF融合蛋白。 突变型G-CSF融合蛋白是具有刺激嗜中性粒细胞增殖活性的融合蛋白，具有G-CSF /载体蛋白或载体蛋白/ G-CSF的基本结构; 其中G-CSF部分包含多点置换，从而导致生物活性和结合亲和力的变化。 与现有产品相比，本发明的突变型G-CSF融合蛋白具有较长的半衰期和较高的生物活性。 含有该突变型G-CSF融合蛋白的药物制剂的给药可用于治疗中性粒细胞减少症。

    MUTANT G-CSF FUSION PROTEIN, AND PREPARATION AND USE THEREOF
    4.
    发明申请
    MUTANT G-CSF FUSION PROTEIN, AND PREPARATION AND USE THEREOF 有权
    突变型G-CSF融合蛋白，其制备及其用途

    公开(公告)号：US20130164251A1

    公开(公告)日：2013-06-27

    申请号：US13575752

    申请日：2010-06-30

    申请人： Xiaofang Wen ,  Yiliang Wu ,  Yefei Wang ,  Zhiyu Yang ,  Min Fan ,  Yujiao Wang ,  Xiaochun Fang ,  You Lu

    发明人： Xiaofang Wen ,  Yiliang Wu ,  Yefei Wang ,  Zhiyu Yang ,  Min Fan ,  Yujiao Wang ,  Xiaochun Fang ,  You Lu

    IPC分类号： C07K14/535 ,  C07K14/765

    CPC分类号： C07K14/535 ,  A61K38/00 ,  C07K2319/31

    摘要： The present invention relates to a mutant G-CSF fusion protein. The mutant G-CSF fusion protein is a fusion protein having the activity of stimulating the proliferation of neutrophilic granulocytes, and having a basic structure of G-CSF/carrier protein or carrier protein/G-CSF; wherein the G-CSF moiety comprises multipoint substitutions thus resulting in changes in biological activity and binding affinity. Compared with existing products, the mutant G-CSF fusion protein in the present invention has longer half-life and higher biological activity. Administration of the pharmaceutical preparation containing this mutant G-CSF fusion protein could be used in the treating neutropenia.

    摘要翻译： 本发明涉及突变型G-CSF融合蛋白。 突变型G-CSF融合蛋白是具有刺激嗜中性粒细胞增殖活性的融合蛋白，具有G-CSF /载体蛋白或载体蛋白/ G-CSF的基本结构; 其中G-CSF部分包含多点置换，从而导致生物活性和结合亲和力的变化。 与现有产品相比，本发明的突变型G-CSF融合蛋白具有较长的半衰期和较高的生物活性。 含有该突变型G-CSF融合蛋白的药物制剂的给药可用于治疗中性粒细胞减少症。