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1. 发明授权

US09012195B2 Non-cytotoxic protein conjugates 有权
标题翻译：非细胞毒性蛋白偶联物
公开(公告)号：US09012195B2
公开(公告)日：2015-04-21
申请号：US13944427
申请日：2013-07-17
申请人： Syntaxin Ltd. , Allergan Inc.
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： C07K14/665 , C12N9/96 , A61K47/48 , A61K38/48
CPC分类号： C12N9/96 , A61K38/482 , A61K38/4893 , A61K47/48246 , A61K47/64 , C07K14/665 , C07K2319/00
摘要： The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.
摘要翻译：本发明涉及用于抑制或减少伤害性感觉传入细胞中的胞外融合的非细胞毒性蛋白质缀合物。所述蛋白质缀合物包含：（i）强啡肽靶向剂量（TM），其中所述TM是感受伤害感觉传入细胞上存在的受体的激动剂，并且其中所述受体经受内吞作用以掺入伤害性感觉传入物内的内体细胞; （ii）非细胞毒性蛋白酶或其片段，其中所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入细胞的胞外融合装置的蛋白质; 易位结构域（Translocation Domain），其中易位域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细胞的胞质溶胶中。还描述了编码蛋白质缀合物的核酸序列，其制备方法及其用途。

2. 发明授权

US10619146B2 Non-cytotoxic protein conjugates 有权
公开(公告)号：US10619146B2
公开(公告)日：2020-04-14
申请号：US15258282
申请日：2016-09-07
申请人： Ipsen Bioinnovation Ltd. , Allergan Inc.
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： C12N9/64 , C12N15/62 , A61K38/48 , C07K14/665 , A61K47/66 , A61K47/65 , A61K47/64 , A61K38/22 , C12N9/96 , A61K38/00
CPC分类号： C12N9/6432 , A61K38/22 , A61K38/48 , A61K47/64 , A61K47/65 , A61K47/67 , C07K14/665 , C12N9/96 , C12N15/62 , C12Y304/00 , C12Y304/21006 , A61K38/00 , C07K2319/00 , C07K2319/01 , C07K2319/21 , C07K2319/55
摘要： The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

3. 发明授权

US09474807B2 Non-cytotoxic protein conjugates 有权
标题翻译：非细胞毒性蛋白偶联物
公开(公告)号：US09474807B2
公开(公告)日：2016-10-25
申请号：US14300746
申请日：2014-06-10
申请人： IPSEN BIOINNOVATION LTD. , Allergan Inc.
发明人： Keith Foster , John Chaddock , Charles Penn , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： A61K47/48 , A61K38/48 , C12N15/62 , C07K14/665 , A61K38/22
CPC分类号： C12N9/6432 , A61K38/00 , A61K38/22 , A61K38/48 , A61K47/48246 , A61K47/48338 , A61K47/48361 , A61K47/64 , A61K47/65 , A61K47/67 , C07K14/665 , C07K2319/00 , C07K2319/01 , C07K2319/21 , C07K2319/55 , C12N9/96 , C12N15/62 , C12Y304/00 , C12Y304/21006
摘要： The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.
摘要翻译：本发明涉及用于抑制或减少伤害性感觉传入细胞中的胞外融合的非细胞毒性蛋白质缀合物。所述蛋白质缀合物包含：（i）靶向部分（TM），其中所述TM是存在于伤害性感觉传入细胞上的受体的激动剂，并且其中所述受体经受内吞作用以掺入伤害性感觉传入细胞内的内体 ; （ii）非细胞毒性蛋白酶或其片段，其中所述蛋白酶或蛋白酶片段能够切割伤害性感觉传入细胞的胞外融合装置的蛋白质; 易位结构域，其中易位域将内体内的蛋白酶或蛋白酶片段转移穿过内体膜，并转移到伤害性感觉传入细胞的胞质溶胶中，其中靶向部分选自BAM ，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。

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