Patents Assigned to Syntaxin Limited
-
Publication number: 20120189610Abstract: 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 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, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translation 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.Type: ApplicationFiled: January 27, 2012Publication date: July 26, 2012Applicants: ALLERGAN, INC., SYNTAXIN LIMITEDInventors: Keith Foster, John Chaddock, Philip Marks, Patrick Stancombe, Kei Roger Aoki, Joseph Francis, Lance Steward
-
Publication number: 20120149084Abstract: 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.Type: ApplicationFiled: January 20, 2012Publication date: June 14, 2012Applicant: SYNTAXIN, LIMITEDInventors: Keith Alan FOSTER, John CHADDOCK, Philip MARKS, Patrick STANCOMBE, Lyndsey DUROSE
-
Publication number: 20120128649Abstract: 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.Type: ApplicationFiled: December 16, 2009Publication date: May 24, 2012Applicant: SYNTAXIN LIMITEDInventors: John Andrew Chaddock, Keith Alan Foster
-
Publication number: 20120128700Abstract: A non-toxic polypeptide, for delivery of a therapeutic agent to a neuronal cell, comprises a binding domain that binds to the neuronal cell, and a translocation domain that translocates the therapeutic agent into the neuronal cell, wherein the translocation domain is not a HN domain of a clostridial toxin and is not a fragment or derivative of a HN domain of a clostridial toxin.Type: ApplicationFiled: February 1, 2012Publication date: May 24, 2012Applicant: SYNTAXIN LIMITEDInventors: Clifford Charles SHONE, John Mark SUTTON, Nigel SILMAN
-
Publication number: 20120101027Abstract: 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.Type: ApplicationFiled: January 6, 2012Publication date: April 26, 2012Applicant: SYNTAXIN LIMITEDInventors: Keith Alan FOSTER, John Andrew CHADDOCK, Conrad Padraig QUINN, John Robert PURKISS
-
Patent number: 8158132Abstract: 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.Type: GrantFiled: September 26, 2005Date of Patent: April 17, 2012Assignee: Syntaxin LimitedInventors: Keith Alan Foster, Michael John Duggan, Clifford Charles Shone
-
Patent number: 8124405Abstract: 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.Type: GrantFiled: September 11, 2007Date of Patent: February 28, 2012Assignee: Syntaxin LimitedInventors: Keith Alan Foster, John Chaddock, Philip Marks, Patrick Stancombe, Lyndsey Durose
-
Patent number: 8124074Abstract: 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.Type: GrantFiled: December 1, 2005Date of Patent: February 28, 2012Assignee: Syntaxin LimitedInventors: Keith Alan Foster, John Chaddock, Philip Marks, Patrick Stancombe, Lyndsey Durose
-
Publication number: 20110262423Abstract: 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.Type: ApplicationFiled: November 17, 2009Publication date: October 27, 2011Applicant: SYNTAXIN LIMITEDInventors: Frederic Madec, Philip Lecane, Philip Mark, Keith Foster
-
Patent number: 8017134Abstract: 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.Type: GrantFiled: January 27, 2009Date of Patent: September 13, 2011Assignees: Syntaxin Limited, The Health Protection AgencyInventors: Clifford Charles Shone, Conrad Padraig Quinn, Keith Alan Foster, John Chaddock, Philip Marks, John Sutton, Patrick Stancombe, Jonathan Wayne
-
Patent number: 8012479Abstract: 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 surType: GrantFiled: March 6, 2009Date of Patent: September 6, 2011Assignees: Health Protection Agency, Syntaxin LimitedInventors: Clifford Charles Shone, Conrad Padraig Quinn, Keith Alan Foster, John Chaddock, Philip Marks, J. Mark Sutton, Patrick Stancombe, Jonathan Wayne
-
Publication number: 20110177056Abstract: The present invention relates to fusion proteins comprising a non-cytotoxic protease and a EGF mutein ligand. The EGF mutein provides improved EGF receptor activation for the claimed fusion proteins. Also provided is the use of said polypeptides as therapeutics for suppressing mucus hypersecretion, inflammation, endocrine neoplasia and/or neuroendocrine disorders, neuroendocrine tumours, for suppressing cancers such as colorectal cancer, prostate cancer, breast cancer, and lung cancer.Type: ApplicationFiled: August 19, 2009Publication date: July 21, 2011Applicant: SYNTAXIN LIMITEDInventors: Aimee Cossins, Ian Birch-Machin, Patrick Stancombe
-
Publication number: 20110171191Abstract: 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.Type: ApplicationFiled: June 11, 2009Publication date: July 14, 2011Applicant: SYNTAXIN LIMITEDInventors: Stephen Johnstone, Philip Marks, Keith Foster
-
Publication number: 20110165137Abstract: 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.Type: ApplicationFiled: June 11, 2009Publication date: July 7, 2011Applicant: SYNTAXIN LIMITEDInventors: Frederic Madec, Phil Lecane, Philip Marks, Keith Foster
-
Publication number: 20110158973Abstract: 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.Type: ApplicationFiled: December 16, 2010Publication date: June 30, 2011Applicant: SYNTAXIN LIMITEDInventors: Frederic MADEC, Phil LECANE, Philip MARKS, Keith FOSTER
-
Publication number: 20110160135Abstract: 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 receptor a 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 tumour cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.Type: ApplicationFiled: December 16, 2010Publication date: June 30, 2011Applicant: SYNTAXIN LIMITEDInventors: Stephen JOHNSTONE, Philip MARKS, Keith FOSTER
-
Publication number: 20110152174Abstract: 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.Type: ApplicationFiled: February 7, 2011Publication date: June 23, 2011Applicant: SYNTAXIN LIMITEDInventors: Keith Alan FOSTER, John Andrew CHADDOCK, Conrad Padraig QUINN, John Robert PURKISS
-
Publication number: 20110091437Abstract: 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 dynorphin 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 dynorphin 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.Type: ApplicationFiled: August 25, 2010Publication date: April 21, 2011Applicants: SYNTAXIN LIMITED, ALLERGAN, INC.Inventors: Keith Foster, John Chaddock, Philip Marks, Patrick Stancombe, Kei Roger Aoki, Joseph Francis, Lance Steward
-
Patent number: 7674470Abstract: 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 surType: GrantFiled: March 11, 2005Date of Patent: March 9, 2010Assignees: Health Protection Agency, Syntaxin LimitedInventors: Charles Clifford Shone, Conrad Padraig Quinn, Keith Alan Foster, John Chaddock, Philip Marks, J. Mark Sutton, Patrick Stancombe, Jonathan Wayne
-
Publication number: 20100034802Abstract: 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.Type: ApplicationFiled: June 1, 2007Publication date: February 11, 2010Applicants: SYNTAXIN LIMITED, ALLERGAN, INC.Inventors: Keith Foster, John Chaddock, Philip Marks, Patrick Stancombe, K. Roger Aoki, Joseph Francis, Lance Steward