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公开(公告)号:US09006395B2
公开(公告)日:2015-04-14
申请号:US12900214
申请日:2010-10-07
申请人: Clifford Charles Shone , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
IPC分类号: A61K38/00 , A61K39/08 , A61K47/48 , C07K14/33 , C07K16/12 , C12N9/52 , C12N15/62 , A61K39/00
CPC分类号: A61K39/08 , A61K38/00 , A61K39/00 , A61K47/6415 , A61K47/646 , A61K2039/505 , A61K2039/53 , A61K2039/627 , C07K14/33 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , C12N15/62 , Y10S530/825
摘要: 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.
摘要翻译: 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:US08012479B2
公开(公告)日:2011-09-06
申请号:US12399542
申请日:2009-03-06
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC分类号: 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
摘要: Antigenic compositions are provided comprising a single chain polypeptide comprising first and second domains, wherein said first domain is a clostridial neurotoxin light chain or a fragment or a variant thereof and is capable of cleaving one or more vesicle or plasma membrane associated proteins essential to exocytosis; and said second domain is a clostridial neurotoxin heavy chain HN portion or a fragment or a variant thereof, wherein said second domain is capable of (i) translocating the polypeptide into a cell or (ii) increasing the solubility of the polypeptide compared to the solubility of the first domain on its own or (iii) both translocating the polypeptide into a cell and increasing the solubility of the polypeptide compared to the solubility of the first domain on its own; and wherein the second domain lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell surface receptors to which native clostridial neurotoxin binds. Antibodies that bind to the polypeptides, and compositions comprising these antibodies, are also provided, as are DNA vaccines comprising polynucleotides that encode these polypeptides.The antigenic and antibody compositions, and the DNA vaccine compositions, can be used in methods of immunising against, or treating, clostridial neurotoxin poisoning in a subject by administering to that subject a therapeutically effective amount of the composition.
摘要翻译: 提供抗原组合物,其包含包含第一和第二结构域的单链多肽,其中所述第一结构域是梭菌神经毒素轻链或其片段或变体,并且能够切割一种或多种与胞吐作用必需的相关蛋白或质膜相关蛋白; 并且所述第二结构域是梭菌神经毒素重链HN部分或其片段或变体,其中所述第二结构域能够(i)将多肽转位到细胞中,或(ii)与溶解度相比增加多肽的溶解度 或(iii)将多肽转移到细胞中并且与第一结构域本身的溶解度相比增加多肽的溶解度; 并且其中所述第二结构域缺少称为HC的梭菌神经毒素重链的功能性C-末端部分,从而使所述多肽不能结合作为天然梭菌神经毒素结合的天然细胞表面受体的细胞表面受体。 还提供了结合多肽的抗体和包含这些抗体的组合物,DNA疫苗也包括编码这些多肽的多核苷酸。 抗原和抗体组合物和DNA疫苗组合物可用于通过向该受试者施用治疗有效量的组合物来免疫或治疗受试者的梭菌神经毒素中毒的方法。
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公开(公告)号:US20100022751A1
公开(公告)日:2010-01-28
申请号:US12369341
申请日:2009-02-11
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC分类号: 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
摘要: 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.
摘要翻译: 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:US20090246827A1
公开(公告)日:2009-10-01
申请号:US12174896
申请日:2008-07-17
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC分类号: 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
摘要: 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.
摘要翻译: 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:US08012491B2
公开(公告)日:2011-09-06
申请号:US12369341
申请日:2009-02-11
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC分类号: 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
摘要: 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.
摘要翻译: 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
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
IPC分类号: A61K39/38 , A61K39/08 , A61K39/085 , A61K39/40 , A61K39/02 , A61K38/00 , C07K1/00 , C07K2/00 , C07K4/00 , C07K14/00 , C07K17/00
CPC分类号: 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
摘要: 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:US07192596B2
公开(公告)日:2007-03-20
申请号:US10241596
申请日:2002-09-12
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
CPC分类号: A61K39/08 , A61K38/00 , A61K39/00 , A61K47/6415 , A61K47/646 , A61K2039/505 , A61K2039/53 , A61K2039/627 , C07K14/33 , C07K2319/00 , C07K2319/20 , C07K2319/23 , C07K2319/50 , C07K2319/55 , C07K2319/705 , C07K2319/75 , C12N9/52 , C12N15/62 , Y10S530/825
摘要: 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:US20090148888A1
公开(公告)日:2009-06-11
申请号:US12360470
申请日:2009-01-27
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
IPC分类号: C12P21/04 , C07K14/195 , C12N15/11
CPC分类号: 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
摘要: 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:US08017134B2
公开(公告)日:2011-09-13
申请号:US12360470
申请日:2009-01-27
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , John Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , John Sutton , Patrick Stancombe , Jonathan Wayne
CPC分类号: 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
摘要: 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:US08454976B2
公开(公告)日:2013-06-04
申请号:US12174896
申请日:2008-07-17
申请人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , John Sutton , Patrick Stancombe , Jonathan Wayne
发明人: Clifford Charles Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , John Sutton , Patrick Stancombe , Jonathan Wayne
IPC分类号: A61K39/40 , A61K39/02 , A61K39/08 , A61K38/00 , C07K14/00 , C07K16/00 , C07K17/00 , C07K2/00 , C07K4/00 , C07K5/00 , C07K7/00
CPC分类号: 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
摘要: 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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