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1. 发明申请

US20150197739A1 FUSION PROTEINS AND METHODS FOR TREATING, PREVENTING OR AMELIORATIONG PAIN 审中-公开
标题翻译：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
申请人： Syntaxin Limited , Allergan, Inc.
发明人： Peter James , Keith Foster , John Chaddock , Roger Kei Aoki , Lance Steward , Joseph Francis
IPC分类号： C12N9/52 , C07K14/575
摘要： 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.
摘要翻译：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。

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