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公开(公告)号：US08372615B2
公开(公告)日：2013-02-12
申请号：US13354787
申请日：2012-01-20
Applicant: Keith Alan Foster , John Chaddock , Philip Marks , Patrick Stancombe , Lyndsey Durose
Inventor： Keith Alan 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 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.
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公开(公告)号：US20120149084A1
公开(公告)日：2012-06-14
申请号：US13354787
申请日：2012-01-20
Applicant: Keith Alan FOSTER , John CHADDOCK , Philip MARKS , Patrick STANCOMBE , Lyndsey DUROSE
Inventor： Keith Alan 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 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：US20120101027A1
公开(公告)日：2012-04-26
申请号：US13344776
申请日：2012-01-06
Applicant: Keith Alan FOSTER , John Andrew CHADDOCK , Conrad Padraig QUINN , John Robert PURKISS
Inventor： Keith Alan FOSTER , John Andrew CHADDOCK , Conrad Padraig QUINN , John Robert PURKISS
CPC classification number: C12N9/52 , A61K38/1808 , A61K38/4886 , A61K47/48246 , A61K47/64 , C07K16/1282 , C07K2319/00 , C12Y304/24069
Abstract: The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system and bone cells.
Abstract translation: 本发明涉及通过抑制细胞分泌过程，其药剂及其组合物治疗疾病，以及制备这些药剂和组合物。 本发明特别涉及依赖于内分泌细胞，外分泌细胞，炎症细胞，免疫系统细胞，心血管系统细胞和骨细胞的胞吐活性的疾病的治疗。
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Patent Agency Ranking
公开(公告)号：US20110165137A1
公开(公告)日：2011-07-07
申请号：US12996641
申请日：2009-06-11
Applicant: Frederic Madec , Phil Lecane , Philip Marks , Keith Foster
Inventor： Frederic Madec , Phil Lecane , Philip Marks , Keith Foster
CPC classification number: C12N9/50 , A61K38/00 , C07K7/086 , C07K14/33 , C07K14/48 , C07K14/575 , C07K14/57563 , C07K14/5759 , C07K14/60 , C07K14/65 , C07K14/82 , C07K2319/035 , C07K2319/06 , C07K2319/33 , C07K2319/50 , C12N9/6489
Abstract: The present invention relates to a method for suppressing or treating cancer, in particular to a method for suppressing or treating one or more of colorectal cancer, breast cancer, prostate cancer and/or lung cancer. The therapy employs use of a non-cytotoxic protease, which is targeted to a growth hormone-secreting cell such as to a pituitary cell. When so delivered, the protease is internalised and inhibits secretion/transmission of growth hormone from said cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.
Abstract translation: 本发明涉及抑制或治疗癌症的方法，特别涉及抑制或治疗结肠直肠癌，乳腺癌，前列腺癌和/或肺癌中的一种或多种的方法。 该疗法使用非细胞毒性蛋白酶，其靶向生长激素分泌细胞，例如垂体细胞。 当这样传递时，蛋白酶被内化并且抑制生长激素从所述细胞的分泌/传递。 本发明还涉及用于所述方法的多肽和核酸。
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公开(公告)号：US07674470B2
公开(公告)日：2010-03-09
申请号：US11077550
申请日：2005-03-11
Applicant: Charles Clifford Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
Inventor： Charles Clifford Shone , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
IPC: A61K39/08 , A61K39/085 , A61K39/40 , A61K39/02 , A61K38/00 , A61K39/38 , C07K14/00 , C07K17/00 , C07K2/00 , C07K4/00 , C07K1/00
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: 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.
Abstract translation: 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：US20090274708A1
公开(公告)日：2009-11-05
申请号：US12399542
申请日：2009-03-06
Applicant: Charles Clifford SHONE , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
Inventor： Charles Clifford SHONE , Conrad Padraig Quinn , Keith Alan Foster , John Chaddock , Philip Marks , J. Mark Sutton , Patrick Stancombe , Jonathan Wayne
IPC: A61K39/395 , C07K16/00 , C07K16/12
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: 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.
Abstract translation: 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相关的蛋白质或质膜相关蛋白; 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指定为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：US20090148888A1
公开(公告)日：2009-06-11
申请号：US12360470
申请日：2009-01-27
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: C12P21/04 , C07K14/195 , C12N15/11
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：US07470661B2
公开(公告)日：2008-12-30
申请号：US11062471
申请日：2005-02-22
Applicant: Clifford Charles Shone , John Mark Sutton , Bassam Hallis , Nigel Silman
Inventor： Clifford Charles Shone , John Mark Sutton , Bassam Hallis , Nigel Silman
CPC classification number: C12N9/0089 , A61K38/00 , A61K47/6415 , A61K48/00 , C07K14/33 , C07K2319/00
Abstract: A composition for delivery of superoxide dismutase to neuronal cells comprise a superoxide dismutase linked by a linker to a neuronal cell targeting component, which component comprises a first domain that binds to a neuronal cell and a second domain that translocates the superoxide dimutase into the neuronal cell. After translocation, the linker is cleaved to release superoxide dimutase from the neuronal cell targeting domain. Also described is use of the composition for treatment of oxidative damage to neuronal cells and further targeting of the composition using human mitochondrial leader sequences. A hybrid polypeptide is described that contains a bacterial superoxide dismutase plus a sequence that targets a human mitochondira.
Abstract translation: 用于将超氧化物歧化酶递送至神经元细胞的组合物包含通过接头与神经元细胞靶向组分连接的超氧化物歧化酶，该组分包含结合神经元细胞的第一结构域和将超氧化物二聚体转位到神经元细胞中的第二结构域 。 易位后，切割接头以从神经元细胞靶向结构域释放超氧化物歧化酶。 还描述了用于治疗对神经元细胞的氧化损伤的组合物的使用，并且使用人线粒体前导序列进一步靶向组合物。 描述了含有细菌超氧化物歧化酶加上靶向人线粒体的序列的杂合多肽。
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