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    FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATIONG PAIN
    22.
    发明申请
    FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATIONG PAIN 审中-公开
    融合蛋白和治疗，预防或改善疼痛的方法

    公开(公告)号：US20150197739A1

    公开(公告)日：2015-07-16

    申请号：US14422574

    申请日：2013-08-27

    Applicant: Syntaxin Limited ,  Allergan, Inc.

    Inventor： Peter James ,  Keith Foster ,  John Chaddock ,  Roger Kei Aoki ,  Lance Steward ,  Joseph Francis

    IPC: C12N9/52 ,  C07K14/575

    Abstract: A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, which protease is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease and the galanin Targeting Moiety; a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; a first spacer located between the non-cytotoxic protease and the protease cleavage site, wherein said first spacer comprises an amino acid sequence of from 4 to 25 amino acid residues; and a second spacer located between the galanin Targeting Moiety and the translocation domain, wherein said second spacer comprises an amino acid sequence of from 4 to 35 amino acid residues. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

    Abstract translation: 一种单链多肽融合蛋白，其包含：非细胞毒性蛋白酶，该蛋白酶能够切割伤害性感觉传入的胞外融合装置的蛋白质; 能够结合伤害性感觉传入物的结合位点的甘丙肽靶向部位，该结合位点能够经受内吞作用以掺入伤害性感觉传入内的内体; 蛋白酶切割位点，其中融合蛋白可被蛋白酶切割，其中蛋白酶切割位点位于非细胞毒性蛋白酶和甘丙肽靶向部位之间; 能够将位于内体内的蛋白酶从内体膜转移到伤害性感觉传入体的胞质溶胶中的易位结构域; 位于所述非细胞毒性蛋白酶和所述蛋白酶切割位点之间的第一间隔物，其中所述第一间隔物包含4至25个氨基酸残基的氨基酸序列; 和位于甘丙肽靶向部位和易位结构域之间的第二间隔物，其中所述第二间隔物包含4至35个氨基酸残基的氨基酸序列。 还描述了编码多肽融合蛋白的核酸序列，其制备方法及其用途。

    Fusion proteins
    23.
    发明授权
    Fusion proteins 有权
    融合蛋白

    公开(公告)号：US08940870B2

    公开(公告)日：2015-01-27

    申请号：US13774587

    申请日：2013-02-22

    Applicant: Syntaxin Ltd. ,  Allergan Inc.

    Inventor： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  Kei Roger Aoki ,  Joseph Francis ,  Lance Steward

    IPC: C07K14/00 ,  C12N9/96 ,  A61K47/48 ,  C12N9/50 ,  A61K38/00

    CPC classification number: C12N9/96 ,  A61K38/00 ,  A61K47/64 ,  C07K2319/01 ,  C07K2319/33 ,  C07K2319/50 ,  C12N9/50

    Abstract: A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

    Abstract translation: 一种单链多肽融合蛋白，其包含：非细胞毒性蛋白酶或其片段，所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入的胞外融合装置的蛋白质; 能够结合伤害性感觉传入的结合位点的强啡肽靶向部位，该结合位点能够经历内吞作用以掺入伤害性感觉传入内的内体; 蛋白酶切割位点位于融合蛋白可被蛋白酶切割的蛋白酶切割位点，其中蛋白酶切割位点位于非细胞毒性蛋白酶或其片段与强啡肽靶向部位之间; 以及易位区域，其能够将位于内体内的蛋白酶或蛋白酶片段穿过内体膜并转移到伤害性感觉传入物的胞质溶胶中。 还描述了编码多肽融合蛋白的核酸序列，其制备方法及其用途。

    METHOD OF DETECTING CLEAVED SNAP25 IN TISSUE SAMPLES
    30.
    发明申请
    METHOD OF DETECTING CLEAVED SNAP25 IN TISSUE SAMPLES 审中-公开
    检测组织样品中的CNAP25的方法

    公开(公告)号：US20160003824A1

    公开(公告)日：2016-01-07

    申请号：US14792795

    申请日：2015-07-07

    Applicant: Allergan, Inc.

    Inventor： Ron S. Broide ,  Brian Cai ,  Ester Fernandez-Salas ,  Joseph Francis ,  Catherine Rheaume

    IPC: G01N33/573 ,  C07K16/18

    Abstract: Methods and compositions for detecting BoNT/A enzymatic activity in tissues or a tissue sample are described herein. The invention encompasses antibodies that bind preferentially to BoNT/A cleaved SNAP25 and is able to preferentially detect BoNT/A cleaved SNAP25, as compared to intact (non-cleaved) SNAP25, in a tissue sample.

    Abstract translation: 本文描述了用于检测组织或组织样品中BoNT / A酶活性的方法和组合物。 本发明包括优先结合BoNT / A切割的SNAP25的抗体，并且与组织样品中完整的（未切割的）SNAP25相比，能够优先检测BoNT / A切割的SNAP25。

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