公开(公告)号：US20100034802A1

公开(公告)日：2010-02-11

申请号：US12303078

申请日：2007-06-01

Applicant: Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  K. Roger Aoki ,  Joseph Francis ,  Lance Steward

Inventor： Keith Foster ,  John Chaddock ,  Philip Marks ,  Patrick Stancombe ,  K. Roger Aoki ,  Joseph Francis ,  Lance Steward

IPC: A61K38/48 ,  C12N9/48 ,  A61P25/00

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: 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.

Abstract translation: 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。

公开(公告)号：US20090291457A1

公开(公告)日：2009-11-26

申请号：US12534740

申请日：2009-08-03

Applicant: Keith Foster ,  John Chaddock ,  Charles Penn

Inventor： Keith Foster ,  John Chaddock ,  Charles Penn

IPC: C12N9/52 ,  C12N9/50 ,  G01N33/567

CPC classification number: C12N9/52 ,  A61K47/64 ,  A61K47/642

Abstract: The present invention provides a method for designing a re-targeted toxin conjugate for use in treating a medical condition or disease. Also provided, is the use of said conjugates in the manufacture of a medicament for treating medical conditions or diseases. The conjugates include a Targeting Moiety, which directs the conjugate to a desired target cell, and are characterised by a Targeting Moiety that increases exocytic fusion in the target cell. The present invention also provides methods for identifying agonists suitable for use as Targeting Moieties, and methods for preparing conjugates comprising said Targeting Moieties.

Abstract translation: 本发明提供了一种用于设计用于治疗医学病症或疾病的再靶向毒素缀合物的方法。 还提供了所述缀合物在制备用于治疗医学病症或疾病的药物中的用途。 缀合物包括将缀合物引导至期望的靶细胞的靶向部位，其特征在于靶细胞增加靶细胞中的胞外融合。 本发明还提供了用于鉴定适合用作靶向部分的激动剂的方法，以及制备包含所述靶向部分的缀合物的方法。

公开(公告)号：US20090004174A1

公开(公告)日：2009-01-01

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 ,  C07K14/00 ,  C12N15/11 ,  C12N15/62 ,  C12P21/02 ,  A61K38/48 ,  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。

公开(公告)号：US08852603B2

公开(公告)日：2014-10-07

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

IPC: A61K39/08 ,  C07K14/54 ,  C07K14/50 ,  C07K14/33 ,  C07K14/48 ,  A61K38/18 ,  A61K47/48 ,  C07K16/12 ,  A61K38/48

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。

公开(公告)号：US20130315888A1

公开(公告)日：2013-11-28

申请号：US13867740

申请日：2013-04-22

Applicant: Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

Inventor： Andreas Rummel ,  Tanja Weil ,  Aleksandrs Gutcaits

IPC: C12N9/52

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.

公开(公告)号：US20130115682A1

公开(公告)日：2013-05-09

申请号：US13738235

申请日：2013-01-10

Applicant: SYNTAXIN, LIMITED

Inventor： Keith Alan FOSTER ,  John CHADDOCK ,  Philip MARKS ,  Patrick STANCOMBE ,  Lyndsey DUROSE

IPC: C12N9/50

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。

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

IPC: A61K38/48 ,  C12N9/52 ,  A61P25/00 ,  C12N15/63 ,  A61P29/00 ,  C12N9/50 ,  C12N15/62

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。

公开(公告)号：US20120128649A1

公开(公告)日：2012-05-24

申请号：US13202696

申请日：2009-12-16

Applicant: John Andrew Chaddock ,  Keith Alan Foster

Inventor： John Andrew Chaddock ,  Keith Alan Foster

IPC: C12N9/96 ,  A61K8/66 ,  A61P21/00 ,  C07H21/04 ,  A61K38/48

CPC classification number: A61K38/4893 ,  A61K38/00 ,  C07K2319/06 ,  C07K2319/33 ,  C07K2319/50 ,  C12N9/50 ,  C12N9/52 ,  C12Y304/24069

Abstract: The present invention relates to a modified polypeptide comprising a non-cytotoxic protease, a translocation domain, a destructive protease cleavage site and a Targeting Moiety that binds to a Binding Site on a nerve cell, wherein after cleavage of the destructive cleavage site the polypeptide has reduced potency. The destructive cleavage site is recognised and cleaved by a protease present at or in an off-site target cell, and, in one embodiment, the polypeptide is a modified clostridial neurotoxin. The present invention also relates to the use of said polypeptides for treating a range of conditions, and to nucleic acids encoding said polypeptides.

Abstract translation: 本发明涉及包含非细胞毒性蛋白酶，易位结构域，破坏性蛋白酶切割位点和与神经细胞上的结合位点结合的靶向部位的修饰多肽，其中在所述破坏性切割位点切割后，所述多肽具有 功效降低 破坏性切割位点被存在于位点外靶点细胞上或位于外部靶细胞中的蛋白酶识别和切割，并且在一个实施方案中，多肽是经修饰的梭菌神经毒素。 本发明还涉及所述多肽用于治疗一系列病症的用途，以及编码所述多肽的核酸。

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。

公开(公告)号：US20110262423A1

公开(公告)日：2011-10-27

申请号：US13125407

申请日：2009-11-17

Applicant: Frederic Madec ,  Philip Lecane ,  Philip Mark ,  Keith Foster

Inventor： Frederic Madec ,  Philip Lecane ,  Philip Mark ,  Keith Foster

IPC: A61K38/48 ,  A61P35/00 ,  C07H21/04 ,  C12N9/48 ,  C07H21/00

CPC classification number: C12N9/50 ,  A61K38/4893 ,  A61K47/60 ,  A61K47/6415 ,  C07K14/33 ,  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。