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公开(公告)号：US09072736B2
公开(公告)日：2015-07-07
申请号：US13360565
申请日：2012-01-27
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , K. Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , K. Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is a single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo 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 Targeting Moiety; and a translation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent.
摘要翻译： 用于治疗特定疼痛病症的治疗分子的用途，其中所述治疗分子是单链多肽融合蛋白，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可以切割蛋白质或蛋白酶片段的蛋白质 伤害性感觉传入的胞外融合装置; 可以结合伤害性感觉传入物上的结合位点的靶向物质，其结合位点可以进行内吞作用以掺入伤害性感觉传入体内的内体; 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或其片段与靶向部位之间; 以及可以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的翻译结构域。
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公开(公告)号：US20100034802A1
公开(公告)日：2010-02-11
申请号：US12303078
申请日：2007-06-01
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , K. Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , K. Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is 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 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 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.
摘要翻译： 用于治疗特定疼痛病症的治疗分子的用途，其中所述治疗分子是单链多肽融合蛋白，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器的蛋白质; 能够结合伤害性感觉传入的结合位点的靶向部位，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，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或其片段与靶向部位之间; 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。
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公开(公告)号：US09243301B2
公开(公告)日：2016-01-26
申请号：US13419381
申请日：2012-03-13
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
IPC分类号： A61K38/00 , C12N9/52 , C12N15/62 , C07K14/665
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo 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, which is located between the non-cytotoxic protease and the Targeting Moiety; and a translocation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the 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：非细胞毒性蛋白酶或其片段，所述蛋白酶或蛋白酶片段可以切割伤害性感觉传入的胞外融合装置的蛋白质; 可以结合伤害性感觉传入物上的结合位点的靶向物质，其结合位点可以进行内吞作用以掺入伤害性感觉传入体内的内体; 蛋白酶切割位点，位于融合蛋白可被位于非细胞毒性蛋白酶和靶向部位之间的蛋白酶切割; 以及易位区域，其可以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; 其中靶向部分是BAM，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。 还描述了编码融合蛋白的核酸序列，其制备方法及其用途。
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公开(公告)号：US20100247509A1
公开(公告)日：2010-09-30
申请号：US11792210
申请日：2005-12-01
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C07K14/575 , A61K31/711 , A61K38/4893 , A61K47/64 , A61K47/6415 , C07K14/33 , C07K2319/00 , C07K2319/01 , C07K2319/33 , C12N9/6489 , C12N15/62 , C12Y304/24069
摘要： 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 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 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.
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，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或其片段与靶向部位之间; 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。
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公开(公告)号：US08399401B2
公开(公告)日：2013-03-19
申请号：US13239573
申请日：2011-09-22
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C07K14/575 , A61K31/711 , A61K38/4893 , A61K47/64 , A61K47/6415 , C07K14/33 , C07K2319/00 , C07K2319/01 , C07K2319/33 , C12N9/6489 , C12N15/62 , C12Y304/24069
摘要： 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 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 Targeting Moiety; 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 acids encoding the 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，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或其片段与靶向部位之间; 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的易位结构域。 还描述了编码融合蛋白的核酸，其制备方法及其用途。
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公开(公告)号：US20120230975A1
公开(公告)日：2012-09-13
申请号：US13419381
申请日：2012-03-13
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo 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, which is located between the non-cytotoxic protease and the Targeting Moiety; and a translocation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the 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：非细胞毒性蛋白酶或其片段，所述蛋白酶或蛋白酶片段可以切割伤害性感觉传入的胞外融合装置的蛋白质; 可以结合伤害性感觉传入物上的结合位点的靶向物质，该结合位点可以进行内吞作用以掺入伤害性感觉传入体内的内体; 蛋白酶切割位点，位于融合蛋白可被位于非细胞毒性蛋白酶和靶向部位之间的蛋白酶切割; 以及易位区域，其可以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; 其中靶向部分是BAM，β-内啡肽，缓激肽，物质P，强啡肽和/或伤害感受肽。 还描述了编码融合蛋白的核酸序列，其制备方法及其用途。
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公开(公告)号：US08067200B2
公开(公告)日：2011-11-29
申请号：US11792210
申请日：2005-12-01
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C07K14/575 , A61K31/711 , A61K38/4893 , A61K47/64 , A61K47/6415 , C07K14/33 , C07K2319/00 , C07K2319/01 , C07K2319/33 , C12N9/6489 , C12N15/62 , C12Y304/24069
摘要： 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 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 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.
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，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或其片段与靶向部位之间; 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。
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公开(公告)号：US20120189610A1
公开(公告)日：2012-07-26
申请号：US13360565
申请日：2012-01-27
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is a single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo 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 Targeting Moiety; and a translation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent.
摘要翻译： 用于治疗特定疼痛病症的治疗分子的用途，其中所述治疗分子是单链多肽融合蛋白，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可以切割蛋白质或蛋白酶片段的蛋白质 伤害性感觉传入的胞外融合装置; 可以结合伤害性感觉传入物上的结合位点的靶向物质，其结合位点可以进行内吞作用以掺入伤害性感觉传入体内的内体; 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或其片段与靶向部位之间; 以及可以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的翻译结构域。
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公开(公告)号：US20110091437A1
公开(公告)日：2011-04-21
申请号：US12868510
申请日：2010-08-25
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C12Y304/24069 , A61K38/00 , A61K38/1709 , A61K38/482 , A61K38/4886 , A61K38/4893 , A61K47/6415 , A61K47/65 , C07K14/665 , C07K2319/055 , C07K2319/06 , C07K2319/50 , C12N9/52 , C12N15/62
摘要： 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.
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。
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公开(公告)号：US08399400B2
公开(公告)日：2013-03-19
申请号：US12862948
申请日：2010-08-25
申请人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
发明人： Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC分类号： C12N9/96 , A61K38/00 , A61K47/64 , C07K2319/01 , C07K2319/33 , C07K2319/50 , C12N9/50
摘要： 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.
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