Abstract: 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. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

Abstract: 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. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

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: A non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said 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 said 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.

Abstract: A non-cytotoxic protein conjugate for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell, comprising: (i) a Targeting Moiety (TM), wherein said TM is an agonist of a receptor present on said nociceptive sensory afferent cell, and wherein said 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 said 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.

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, to re-target a toxin to a cell of therapeutic interest. In particular, the present invention describes a method for designing a toxin conjugate, and describes therapeutic applications of said conjugates to inhibit or reduce cellular processes.

Abstract: (?)-4-Amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one, its pharmaceutically acceptable derivatives, pharmaceutical formulations thereof, methods for its preparation and its use as an antiviral agent are described.

Abstract: Toilet paper, paper towel and facial tissue products (10) are presented. Information may be placed, through printing or embossing, on the toilet paper, paper towels and facial tissues. The information (62) may comprise advertisements, coupons, prizes (such as stickers and crossword puzzles), games or other promotional materials. In addition, information (62) may be placed on a sheet separate from the toilet paper and/or paper towels and/or facial tissues. The information sheet may be then be placed in conjunction with the toilet paper, paper towel or facial tissue by rolling or by interleaving (16) the information sheet with the toilet paper, paper towel or facial tissue. In another aspect, different information may be place on two or more sheets to convey a story (39) or other information. The information (72) may, for example, be used to help potty train children, or to teach children numbers or the alphabet.

Abstract: An antigenic pharmaceutical composition is provided comprising Protective Antigen (PA) and Lethal Factor (LF), wherein said PA and/or LF lacks a functional binding site, thereby preventing said PA and LF from binding together via said binding site or thereby preventing said PA from binding to a native PA cell receptor via said binding site, and wherein said composition is substantially non-toxic to animal cells. The composition is for preventing or minimising anthrax toxicity in mammals, preferably in humans. Also provided are DNA and RNA based vaccines encoding the antigenic components of said pharmaceutical composition. The present specification also describes antibodies that bind to at least one of PA, LF or EF, which binding thereby prevents:—(i) PA from binding to LF or EF, or to a native PA cell receptor; or (ii) LF from binding to PA; or (iii) EF from binding to PA.

Abstract: A system, method, and computer program product for configuring a stochastic simulation model. According to the method of the present invention, an arbitrarily complex functional expression is created from a library of functional expression components. A proxy/adapter object is also created. The proxy/adapter object serves as an intermediary between the arbitrarily complex functional expression and a target domain object within the stochastic simulation model so as to modify a property of the target domain object in accordance with the arbitrarily complex functional expression at runtime.

Abstract: Toilet paper, paper towel and facial tissue products (10) are presented. Information may be placed, through printing or embossing, on the toilet paper, paper towels and facial tissues. The information (62) may comprise advertisements, coupons, prizes (such as stickers and crossword puzzles), games or other promotional materials. In addition, information (62) may be placed on a sheet separate from the toilet paper and/or paper towels and/or facial tissues. The information sheet may be then be placed in conjunction with the toilet paper, paper towel or facial tissue by rolling or by interleaving (16) the information sheet with the toilet paper, paper towel or facial tissue. In another aspect, different information may be place on two or more sheets to convey a story (39) or other information. The information (72) may, for example, be used to help potty train children, or to teach children numbers or the alphabet.