公开(公告)号：US08158132B2

公开(公告)日：2012-04-17

申请号：US11234250

申请日：2005-09-26

Applicant: Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

Inventor： Keith Alan Foster ,  Michael John Duggan ,  Clifford Charles Shone

IPC: C07K14/33 ,  C07K14/48 ,  C07K14/70 ,  C07K19/00 ,  C12N15/62

CPC classification number: C07K14/48 ,  A61K38/4886 ,  A61K38/4893 ,  A61K47/62 ,  C07K14/33 ,  C07K2319/00 ,  Y10S424/832

Abstract: This invention describes a novel agent for the targeted control of a mammalian cell activity, in particular the agent is used to control the interaction of particular cell types with their external environment. The agent has applications as a pharmaceutical for the treatment of a variety of disorders. An agent according to the invention comprises three Domains B, T and E linked together in the following manner: Domain B-Domain T-Domain E where Domain B is the Binding Domain which binds the agent to a Binding Site on the cell which undergoes endocytosis to produce an endosome, Domain T is the Translocation Domain which translocates the agent (with or without the Binding Site) from within the endosome across the endosomal membrane into the cytosol of the cell, Domain E is the Effector Domain which inhibits the ability of the Recyclable Membrane Vesicles to transport the Integral Membrane Proteins to the surface of the cell.

Abstract translation: 本发明描述了用于靶向控制哺乳动物细胞活性的新型试剂，特别是该试剂用于控制特定细胞类型与其外部环境的相互作用。 该试剂具有用作治疗各种疾病的药物的应用。 根据本发明的药剂包含以下列方式连接在一起的三个B，T和E域：域B结构域T域E，其中B区是绑定结构域，该结合域将该试剂结合到经历内吞作用的细胞上的结合位点 为了产生内体，结构域T是易位区域，其将试剂（具有或不具有结合位点）从内体内穿过内体膜转移到细胞的细胞溶质中，域E是效应区，其抑制 可循环膜囊将整体膜蛋白转运至细胞表面。

公开(公告)号：US20110171191A1

公开(公告)日：2011-07-14

申请号：US12996643

申请日：2009-06-11

Applicant: Stephen Johnstone ,  Philip Marks ,  Keith Foster

Inventor： Stephen Johnstone ,  Philip Marks ,  Keith Foster

IPC: A61K38/48 ,  C12N9/96 ,  C07H21/00 ,  A61K31/7088 ,  A61P35/00 ,  A61P35/04 ,  A61P3/00 ,  A61P9/12 ,  A61P1/12 ,  A61P1/00

CPC classification number: C12N9/6489 ,  A61K38/4893 ,  A61K47/6415 ,  C07K2319/035 ,  C07K2319/06

Abstract: The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumour cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptora melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalised and inhibits secretion—from said tumourcell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract translation: 本发明涉及抑制神经内分泌疾病的方法。 该疗法使用非细胞毒性蛋白酶，其优选通过生长抑素或皮质抑素受体，GHRH受体，生长素释放肽受体，铃蟾肽受体，泌尿生长因受体α黑素浓缩激素受体1靶向神经内分泌肿瘤细胞; KiSS-1受体或催乳素释放肽受体。 当这样传递时，蛋白酶被内化并且抑制分泌 - 从所述的肿瘤。 本发明还涉及用于所述方法的多肽和核酸。

公开(公告)号：US20110158973A1

公开(公告)日：2011-06-30

申请号：US12969826

申请日：2010-12-16

Applicant: Frederic MADEC ,  Phil LECANE ,  Philip MARKS ,  Keith FOSTER

Inventor： Frederic MADEC ,  Phil LECANE ,  Philip MARKS ,  Keith FOSTER

IPC: A61K38/48 ,  C12N9/52 ,  C07H21/00 ,  A61P35/00 ,  C12N9/96

CPC classification number: C07K14/33 ,  A61K38/00 ,  C07K2319/035 ,  C07K2319/06 ,  C12N9/50

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.

公开(公告)号：US20110152174A1

公开(公告)日：2011-06-23

申请号：US13022184

申请日：2011-02-07

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

IPC: A61K38/16 ,  A61P5/00 ,  A61P19/08 ,  A61P35/00 ,  A61P3/00 ,  A61P11/06

CPC classification number: C12N9/52 ,  A61K38/1808 ,  A61K38/4886 ,  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。

公开(公告)号：US09115350B2

公开(公告)日：2015-08-25

申请号：US13867740

申请日：2013-04-22

Applicant: Syntaxin Limited

Inventor： Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

IPC: A61K39/08 ,  A61K38/48 ,  C12N9/52 ,  C07K14/33 ,  A61K38/00

CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K14/33 ,  C12Y304/24069 ,  Y02A50/469 ,  Y02A50/473

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

Abstract translation: 本发明涉及通过改变由肉毒梭菌形成的神经毒素的重链而获得的转运蛋白，其中（i）所述蛋白质以与天然神经毒素更高或更低的亲和力的神经细胞特异性结合; （ii）与天然神经毒素相比，蛋白质具有增加或减少的神经毒性，神经毒性优选在膈膜测定中确定; 和/或（iii）与天然神经毒素相比，蛋白质包含对中和抗体的较低亲和力。 本发明还涉及其制备方法及其在化妆品和药物组合物中的用途。

公开(公告)号：US20140286925A1

公开(公告)日：2014-09-25

申请号：US14295798

申请日：2014-06-04

Applicant: Syntaxin Limited

Inventor： Frederic MADEC ,  Philip LECANE ,  Philip MARKS ,  Keith FOSTER

IPC: C12N9/50

CPC classification number: C12N9/50 ,  A61K38/4893 ,  A61K47/60 ,  A61K47/6415 ,  C07K14/4756 ,  C07K14/485 ,  C07K14/495 ,  C07K14/50 ,  C07K14/503 ,  C07K14/52 ,  C07K14/522 ,  C07K14/5412 ,  C07K14/65 ,  C07K14/705 ,  C07K2319/50 ,  C07K2319/55 ,  C07K2319/74 ,  C12N9/52

Abstract: The present invention relates to polypeptides for use in suppressing cancer and cancer disorders. The treatment employs use of a non-cytotoxic protease, which is targeted to the cancer cell, and, when so delivered, the protease is internalised and inhibits secretion from the cancer cell.

Abstract translation: 本发明涉及用于抑制癌症和癌症疾病的多肽。 该治疗使用靶向癌细胞的非细胞毒性蛋白酶，并且当这样递送时，蛋白酶被内化并且抑制癌细胞的分泌。

公开(公告)号：US08796216B2

公开(公告)日：2014-08-05

申请号：US12969810

申请日：2010-12-16

Applicant: Stephen Johnstone ,  Philip Marks ,  Keith Foster

Inventor： Stephen Johnstone ,  Philip Marks ,  Keith Foster

IPC: A61K38/16 ,  C07K14/33 ,  C12P21/00

CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K2319/035 ,  C07K2319/06 ,  C12P21/06

Abstract: The present invention relates to a method for suppressing neuroendocrine disease. The therapy employs use of a non-cytotoxic protease, which is targeted to a neuroendocrine tumor cell, preferably via a somatostatin or cortistatin receptor, a GHRH receptor, a ghrelin receptor, a bombesin receptor, a urotensin receptor a melanin-concentrating hormone receptor 1; a KiSS-1 receptor or a prolactin-releasing peptide receptor. When so delivered, the protease is internalized and inhibits secretion from said tumor cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract translation: 本发明涉及抑制神经内分泌疾病的方法。 该疗法使用非细胞毒性蛋白酶，其优选靶向神经内分泌肿瘤细胞，优选通过生长抑素或皮质抑素受体，GHRH受体，生长素释放肽受体，铃蟾肽受体，泌尿生素受体，黑色素浓缩激素受体1 ; KiSS-1受体或催乳素释放肽受体。 当这样传递时，蛋白酶被内化并且抑制来自所述肿瘤细胞的分泌。 本发明还涉及用于所述方法的多肽和核酸。

公开(公告)号：US08481040B2

公开(公告)日：2013-07-09

申请号：US11919302

申请日：2006-04-26

Applicant: Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

Inventor： Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

IPC: C07K14/33

CPC classification number: C12N9/52 ,  A61K38/00 ,  C07K14/33 ,  C12Y304/24069 ,  Y02A50/469 ,  Y02A50/473

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragma assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

公开(公告)号：US08124405B2

公开(公告)日：2012-02-28

申请号：US11853517

申请日：2007-09-11

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: C07K14/00 ,  C12N15/62 ,  C12N15/63

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。

公开(公告)号：US08012479B2

公开(公告)日：2011-09-06

申请号：US12399542

申请日：2009-03-06

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: A61K39/00 ,  A61K39/38 ,  A61K39/08

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。