Abingdon, United Kingdom
Abingdon, United Kingdom

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Patent
Syntaxin and Allergan, Inc. | Date: 2014-06-10

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, -endorphin, bradykinin, substance P, dynorphin and/or nociceptin.


Patent
Allergan, Inc. and Syntaxin | Date: 2013-07-17

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.


Patent
Syntaxin | Date: 2014-08-05

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.


Patent
Syntaxin | Date: 2014-06-04

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.


Patent
Syntaxin | Date: 2014-04-11

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.


Patent
Syntaxin | Date: 2014-04-11

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.


The invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum. The protein binds specifically to nerve cells with a higher affinity as the native neurotoxin. The invention also relates to a method for the production of transport protein, the nucleic acids coding for the transport protein, the transport protein containing pharmaceutical and cosmetic compositions and use thereof.


Patent
Syntaxin | Date: 2014-04-16

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.


Patent
Syntaxin | Date: 2014-08-14

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.


Grant
Agency: GTR | Branch: BBSRC | Program: | Phase: Research Grant | Award Amount: 731.57K | Year: 2014

CONTEXT OF THE RESEARCH: An ability to deliver biologically active molecules (drugs, DNA and proteins) to specified cells either in the lab or the body would impact on many branches of biology and medicine. Imagine being able to selectively find and destroy diseased cells; or simply to test the effectiveness of a new drug inside a range of cells before animal and human trials? Unfortunately, there is no general solution to this problem of delivering bioactive molecules within cells, and even bespoke true solutions are few and far between. The problem is not straightforward, and is best illustrated by how biology has evolved viruses to do this. Viruses are astonishing natural nanoscale packages, usually termed virions. Though they come in many types, all virions perform three functions: (1) they recognise often specific cell types, which they do by presenting molecules on their surfaces to recognize molecules on the target cells; (2) they penetrate the outer barriers of the cell; and (3) they deliver a payload, which is the genetic information to make more virus in the host cell. Functions (1) and (2) are performed by the viral coats, or capsids. Not surprisingly, many people have tried to mimic these structures to deliver payloads other than RNA and DNA. AIMS, OBJECTIVES AND ASPIRATIONS OF THE RESEARCH: The overall ambition of the proposed work is to produce hollow, cage-like particles that have the diameter of about one hundredth the width of a human hair, so-called SAGE particles. We will do this in a modular way, using small versions of proteins called peptides. Each peptide module will have a specific function to mimic one the properties of virions: one set will be made to recognize specific cell types; another will be used to construct the casing of the particles; and the third set will carry the biologically active payloads. On their own, these modules would not be useful at all. However, if combined correctly they could assemble into virus-like particles, but without the (deadly) RNA and DNA cargo, instead they would contain drugs or useful proteins. To do this we will build on a multidisciplinary team of chemists, biochemists, cell biologists and molecular modellers that has delivered the SAGE particles. The physical scientists will work together to design and make the assemblies of molecules, and then work with the biologists to test and visualise how they interact with cells and deliver their payloads. POTENTIAL APPLICATIONS AND BENEFITS: Throughout the research, we will work with a company, Syntaxin, interested in targeting and killing particular diseased cell types in the body. As well as providing reagents and know-how, this partnership will encourage real-life applications, and thus clear and practical end points for our research. In this way, we will explore both the fundamentals of SAGE assembly and engineering, and potential applications of functional SAGEs in cell biology and medicine. Broadly speaking, this modular and systematic approach to constructing complex biological molecules, assemblies and systems is called synthetic biology. The aim and spirit of synthetic biology is to make the engineering of biological systems easier (that is, systematic, quick, and predictable) and ultimately to make useful functions and products. For example, synthetic biology is being recognised as increasingly important to generate new medicines, biofuels and fine chemicals. It is being invested in by Government and Research Councils, with the aim of developing the field sufficiently to be of direct benefit to the UK (biotech) industry and economy. One of the key aspects of our proposal is that it fits with this spirit and these aspirations: we aim to make a toolkit of different modules for each of the above three properties; in this way, modules could be combined rapidly, reliably and with predictable outcomes to generate different particles for targeting and tackling different cells and diseases.

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