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公开(公告)号:US20070184070A1
公开(公告)日:2007-08-09
申请号:US11717713
申请日:2007-03-14
Applicant: Clifford Shone , Conrad Quinn , Keith Foster , John Chaddock , Philip Marks , J. Sutton , Patrick Stancombe , Jonathan Wayne
Inventor: Clifford Shone , Conrad Quinn , Keith Foster , John Chaddock , Philip Marks , J. Sutton , Patrick Stancombe , Jonathan Wayne
CPC classification number: C12N15/62 , A61K38/00 , A61K39/00 , A61K39/08 , A61K47/6415 , A61K47/646 , A61K2039/505 , A61K2039/53 , A61K2039/627 , C07K14/33 , C07K14/475 , C07K14/65 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , Y02A50/469 , Y10S530/825
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
Abstract translation: 提供了包含第一和第二结构域的单个多肽。 第一结构域使多肽能够切割一种或多种与胞吐作用相关的囊泡或质膜相关的蛋白质,而第二结构域使多肽易位于靶细胞或增加多肽或两者的溶解度。 因此,该多肽结合梭菌毒素如肉毒杆菌或破伤风毒素的有用性质,而不与天然分子相关的毒性。 多肽还可以含有将其靶向特定细胞的第三结构域,使得多肽可用于抑制靶细胞中的胞吐作用。 还提供了包含多肽的融合蛋白,编码多肽的核酸和制备该多肽的方法。 多肽的受控活化是可能的,并且多肽可以并入疫苗和毒素测定中。
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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
Applicant: Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
Inventor: Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC classification number: C07K14/575 , A61K31/711 , A61K38/4893 , A61K47/64 , A61K47/6415 , C07K14/33 , C07K2319/00 , C07K2319/01 , C07K2319/33 , C12N9/6489 , C12N15/62 , C12Y304/24069
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 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.
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
Applicant: Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
Inventor: Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC classification number: 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
Abstract: 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.
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:US08124074B2
公开(公告)日:2012-02-28
申请号:US11792076
申请日:2005-12-01
Applicant: Keith Alan Foster , John Chaddock , Philip Marks , Patrick Stancombe , Lyndsey Durose
Inventor: Keith Alan Foster , John Chaddock , Philip Marks , Patrick Stancombe , Lyndsey Durose
IPC: C12N9/50 , C12N15/11 , C12N15/62 , C07K14/00 , A61K38/48 , C12P21/02 , A61P37/00 , A61P19/00 , A61P9/00 , A61P1/00
CPC classification number: C12N9/50 , A61K38/00 , C07K14/33 , C07K2319/06 , C07K2319/50 , C12N15/62
Abstract: The invention provides 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 target cell; a Targeting Moiety that is capable of binding to a Binding Site on the target cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endocome within the target cell; a protease cleaving site at which site the fusion protein is cleavable by the protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and the 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 target cell.
Abstract translation: 本发明提供了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靶细胞的胞外融合装置的蛋白质; 能够结合靶细胞上的结合位点的靶向物质,所述结合位点能够经历内吞作用以掺入靶细胞内的内皮细胞; 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; 以及能够将位于内体内的蛋白酶或蛋白酶片段穿过体内膜并进入靶细胞的胞质溶胶的易位结构域。
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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
Applicant: Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
Inventor: Keith Foster , John Chaddock , Philip Marks , Patrick Stancombe , Kei Roger Aoki , Joseph Francis , Lance Steward
CPC classification number: C07K14/575 , A61K31/711 , A61K38/4893 , A61K47/64 , A61K47/6415 , C07K14/33 , C07K2319/00 , C07K2319/01 , C07K2319/33 , C12N9/6489 , C12N15/62 , C12Y304/24069
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 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.
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:US08017134B2
公开(公告)日:2011-09-13
申请号:US12360470
申请日:2009-01-27
Applicant: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , John Sutton , Patrick Stancombe , Jonathan Wayne
Inventor: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , John Sutton , Patrick Stancombe , Jonathan Wayne
CPC classification number: C12N15/62 , A61K38/00 , A61K39/00 , A61K39/08 , A61K47/6415 , A61K47/646 , A61K2039/505 , A61K2039/53 , A61K2039/627 , C07K14/33 , C07K14/475 , C07K14/65 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , Y02A50/469 , Y10S530/825
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
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公开(公告)号:US08012491B2
公开(公告)日:2011-09-06
申请号:US12369341
申请日:2009-02-11
Applicant: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
Inventor: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC classification number: C07K14/65 , A61K38/00 , A61K39/00 , A61K47/6415 , A61K47/646 , A61K2039/505 , C07K14/33 , C07K14/475 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , C12N15/62 , Y10S530/825
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
Abstract translation: 提供了包含第一和第二结构域的单个多肽。 第一结构域使多肽能够切割一种或多种与胞吐作用相关的囊泡或质膜相关的蛋白质,而第二结构域使多肽易位于靶细胞或增加多肽或两者的溶解度。 因此,该多肽结合梭菌毒素如肉毒杆菌或破伤风毒素的有用性质,而不与天然分子相关的毒性。 多肽还可以含有将其靶向特定细胞的第三结构域,使得多肽可用于抑制靶细胞中的胞吐作用。 还提供了包含多肽的融合蛋白,编码多肽的核酸和制备多肽的方法。 多肽的受控活化是可能的,并且多肽可以并入疫苗和毒素测定中。
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公开(公告)号:US07897158B2
公开(公告)日:2011-03-01
申请号:US11717713
申请日:2007-03-14
Applicant: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
Inventor: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
IPC: A61K39/38 , A61K39/08 , A61K39/085 , A61K39/40 , A61K39/02 , A61K38/00 , C07K1/00 , C07K2/00 , C07K4/00 , C07K14/00 , C07K17/00
CPC classification number: C12N15/62 , A61K38/00 , A61K39/00 , A61K39/08 , A61K47/6415 , A61K47/646 , A61K2039/505 , A61K2039/53 , A61K2039/627 , C07K14/33 , C07K14/475 , C07K14/65 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , Y02A50/469 , Y10S530/825
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
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公开(公告)号:US20080064092A1
公开(公告)日:2008-03-13
申请号:US11853517
申请日:2007-09-11
Applicant: Keith FOSTER , John CHADDOCK , Philip MARKS , Patrick STANCOMBE , Lyndsey DUROSE
Inventor: Keith FOSTER , John CHADDOCK , Philip MARKS , Patrick STANCOMBE , Lyndsey DUROSE
CPC classification number: C12N9/50 , A61K38/00 , C07K14/33 , C07K2319/06 , C07K2319/50 , C12N15/62
Abstract: The invention provides 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 target cell; a Targeting Moiety that is capable of binding to a Binding Site on the target cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the target cell; 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 target cell.
Abstract translation: 本发明提供了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靶细胞的胞外融合装置的蛋白质; 能够结合目标细胞上的结合位点的靶向物质,所述结合位点能够经历内吞作用以掺入靶细胞内的内体; 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; 以及能够将位于内体内的蛋白酶或蛋白酶片段穿过体内膜并进入靶细胞的胞质溶胶的易位结构域。
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