Abstract: The present specification discloses methods of treating a sensory disturbance disorder in an individual using Targeted Endopeptidase Modulators (TEMs), compositions comprising such TEMs, compositions comprising such TEMs and Clostridial toxins, use of such TEMs and/or Clostridial toxins in manufacturing a medicament for treating a sensory disturbance disorder, use of such TEMs and Clostridial toxins in manufacturing a medicament for treating a sensory disturbance disorder, use of such TEMs in treating a sensory disturbance disorder, and use of such TEMs and Clostridial toxins in treating a sensory disturbance disorder.

Abstract: The present invention is directed to multivalent Clostridial toxin comprising more than one binding domain directed to a cell surface molecule of a target cell. Such modified toxins are useful as therapeutic compositions to prevent exocytosis and secretion by the target cell. Conditions in which such compositions may be useful include, without limitation, disorders of the sensory or motor nervous system, acute or chronic pain, cancer, pancreatitis, hyperhydrosis, glandular disorders, viral infections, cystic fibrosis and the like. The invention is also directed to methods of using and administering such a composition, and methods of treating a given condition using such a composition.

Abstract: Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.

Abstract: The present invention relates to a method of treating or preventing pain or pains induced by an anti-neoplastic agent, comprising the step of administering an effective amount of at least one botulinum neurotoxin to a patient in need thereof.

Abstract: This invention relates to the use of a composition comprising a polysaccharide and a botulinum toxin for reducing a skin wrinkle. In some embodiments, the polysaccharide comprises disaccharides. In some embodiments, the average molecular weight of a disaccharide unit of the polysaccharide is between about 345 D and about 1,000 D.

Abstract: The present invention provides methods for treating a substance addiction- related behavior in a patient with a substance addiction, comprising the step of locally administering a therapeutically effective amount of a botulinum neurotoxin to a location on the patient's body or in the vicinity of the area which comes into contact with a smoking tool or addictive substance, thereby altering, reducing or eliminating sensations associated with behaviors associated with substance addiction. Botulinum neurotoxin may be administered to a dermal, subdermal, mucosal or submucosal location or to a muscle area or in the vicinity of the location to which a smoking tool or addictive substance contacts.

Abstract: Disclosed herein are compositions of neurotoxins and methods of their use for the treatment of sleep disordered breathing. In one embodiment of the present invention, a method of treating sleep breathing disorders comprising administering a therapeutically effective amount of Clostridia neurotoxin (CnT) or light chain thereof to a mammal in need thereof is disclosed.

Abstract: Methods and systems are described for a rapid and sustainable change in the pigment melanin content of melanocytes of the iris stroma, thereby to change the color of the eye. Also described are compositions for lightening or darkening the pigmented tissues or treating a pigmented tissue disease.

Abstract: Animal protein-free, solid-form Clostridial toxin pharmaceutical compositions comprising a Clostridial toxin active ingredient and at least two excipients.

Abstract: Botulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the nerve endings of the trigeminal nerve, the occipital nerve and the intranasal terminals of the parasympathetic fibers originating in the Sphenopalatine ganglion. The administration preferably targets the extracranial nerve endings of the trigeminal nerve in the temporal area, the extracranial occipital nerve endings in the occipital area, and the intranasal terminals of the trigeminal nerve and parasympathetic fibers originating in the Sphenopalatine ganglion. The delivery is carried out by way of injection or topically.

Abstract: Botulinum toxin, a well know systemic poison, produces favorable therapeutic effect by virtue of regionally attaching to nerves within the myoneural junction and possibly other tissues in a target region of a particular tissue. The present invention provides compositions of botulinum toxin and a sequestration agent that increase sequestration and delivery of the botulinum toxin to neural and associated tissues, as compared with available formulations of botulinum toxins, and thereby produce a beneficial clinical effect. The sequestration agents of the present invention include proteins, lipids and carbohydrates. A preferred composition of the present invention comprises a botulinum toxin and an albumin. The present invention also provides methods of treating neuromuscular diseases and pain using the disclosed compositions and methods of making the disclosed compositions.

Abstract: The present invention relates to immunogenic compositions comprising capsular polysaccharide or oligosaccharide of H. influenzae B (PRP) and methods of making such compositions.

Abstract: The invention provides therapeutics and methods to induce a mammalian host, including a human, to produce antibodies, which agonize death receptors and cause the apoptotic death of target cells within the host's body. The therapeutics are vaccine compositions, including genetic vaccines encoding death receptor antigens of the tumor necrosis factor receptor family. Also provided are means and methods for overcoming host immunological tolerance to death receptors. The vaccines are useful against cancer cells and other death receptor bearing target cells within the host, and can be used in both therapeutic and prophylactic settings. The vaccines are also useful for diagnostic testing of the immunocompetence of a host.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: This invention relates to the use of a composition comprising a polysaccharide and a botulinum toxin for reducing a skin wrinkle. In some embodiments, the polysaccharide comprises disaccharides. In some embodiments, the average molecular weight of a disaccharide unit of the polysaccharide is between about 345 D and about 1,000 D.

Abstract: The invention features a polypeptide complex synthesized by bacteria of the genus Clostridia that contains the serotype E botulinum neurotoxin and five neurotoxin associated polypeptides having molecular weights of about 118, 80, 65, 40, and 18 kDa, respectively. The complex is useful in the treatment of diseases or conditions that are caused by excessive release of acetylcholine from presynaptic nerve terminals.

Abstract: Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.

Abstract: Modified neurotoxin comprising neurotoxin including structural modification, wherein the structural modification alters the biological persistence, such as the biological half-life and/or a biological activity of the modified neurotoxin relative to an identical neurotoxin without the structural modification. In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In another embodiment, methods of using the modified neurotoxin to treat conditions include treating various disorders, neuromuscular aliments and pain.

Abstract: Pharmaceutical compositions for the treatment of nasal congestion, wherein the pharmaceutical compositions comprise low concentrations of a super-selective subclass of selective ?-2 adrenergic receptor agonists. Methods of using the compositions for the treatment of nasal congestion, cerebrovascular disease or systemic conditions, and as delivery vehicles to deliver other active agents to treat systemic or cerebrovascular diseases or conditions.

Abstract: Methods of using clostridial toxins and other biological agents to treat skin cosmesis in humans is provided. The disclosed methods provide beneficial effects in humans.

Abstract: Botulinum neurotoxin formulated with a hyaluronic acid carrier with increased residency time of the botulinum toxin at a subdermal location and fewer botulinum toxin induced complications or side effects.

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: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of botulinum toxin types A, B, C, D, E, F and G.

Abstract: This disclosure relates to materials and methods for inhibiting Botulinum neurotoxin, and more particularly to materials and methods for inhibiting the zinc endopeptidase of Botulinum neurotoxin serotypes A, D and/or E (BoNTA, BoNTD and/or BoNTE).

Abstract: Methods of using clostridial toxins and other biological agents to control holocrine gland dysfunction in humans is provided. In preferred embodiments the methods provide beneficial effects in humans.

Abstract: The invention includes liquid formulations of botulinum toxin that are stable to storage in liquid form at standard refrigerator temperatures for at least 1-2 years and to storage at higher temperatures for at least 6 months. The invention also includes methods of treatment using such formulations for various therapeutic and cosmetic purposes.

Abstract: This invention relates to botulinum toxin formulations that are stabilized without the use of any proteinaceous excipients. The invention also relates to methods of preparing and using such botulinum toxin formulations.

Abstract: The present invention relates to the pharmaceutical field. Specifically, it contemplates a polynucleotide encoding a neurotoxin polypeptide exhibiting a reduced duration of the biological effect in a subject, wherein the polypeptide comprises at least one degradation signal in the light chain of the neurotoxin polypeptide as well as vectors and host cells comprising the polynucleotide, polypeptides encoded thereby and antibodies specifically binding to the polypeptides. Moreover, the invention relates to medicaments comprising the polynucleotides and polypeptides, as well as specific therapeutic applications thereof. Furthermore, the present invention contemplates methods for the manufacture of the polypeptides and medicaments.

Abstract: The present invention pertains to a formulation comprising a hydrophilic polymer, a mixture of a polyalcohol and a sugar, wherein the weight ratio of polyalcohol to sugar is between 2:1 to 5:1 (wt-%), a detergent, and wherein the formulation is free of stabilizing proteins.

Abstract: Methods of treating one or more autoimmune disorders include a step of administering a Clostridial neurotoxin, such as a botulinum toxin, to a patient that has an autoimmune disorder. In one aspect, a method includes a step of administering the neurotoxin to the thymus gland or near the thymus gland of the patient. In another aspect, a method includes a step of administering the neurotoxin in combination with administering a cytokine inhibitor to the patient. Compositions are also described.

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: Methods of using clostridial toxins and other biological agents to treat rosacea in humans is provided. The disclosed methods provide beneficial effects in humans.

Abstract: Methods for prolongation of climax time in a patient in need thereof are presented, as are methods for treating premature ejaculation by local administration of a Clostridial neurotoxin, such a botulinum neurotoxin, to the patient, are provided.

Abstract: The present invention provides BoNT/A peptides as well as methods of predicting or determining immunoresistance to botulinum toxin therapy in an individual using BoNT/A peptides.

Abstract: A polypeptide having ?/? type SASP activity, for use as a medicament.

Abstract: Methods and apparatus are provided for applying an fragment of a neurotoxin such as the active light chain (LC) of the botulinum toxin (BoNT), such as one of the serotype A, B, C, D, E, F or G botulinum toxins, via permeabilization of targeted cell membranes to enable translocation of the botulinum neurotoxin light chain (BoNT-LC) molecule across the targeted cell membrane to the cell cytosol where a therapeutic response is produced in a mammalian system. The methods and apparatus include use of catheter based delivery systems, non-invasive delivery systems, and transdermal delivery systems.

Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and an enhanced Clostridial toxin binding domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.

Abstract: Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.

Abstract: A method for treating uterine disorders, including hyperplasic, hypertonic, cystic and/or neoplastic uterine gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted uterine tissue.

Abstract: The present invention provides a novel modified BoNT/E catalytic domain and methods of use thereof. In one embodiment, the light chain residue 224, or a residue corresponding to residue 224, of the modified BoNT/E catalytic domain has been altered to be aspartic acid or glutamic acid. The modified catalytic domain cleaves SNAP23 but does not cleave SNAP29 or SNAP47, providing novel methods of treating diseases including without limitation, asthma, CF, chronic obstructive pulmonary, gastric acid efflux and inflammation, immune disorders with a cytokine component or cancers with a cytokine component.

Abstract: A method is provided for improving the solubility of proteins, for example, bacterial toxins. In one embodiment, solubility is improved by introducing point mutations that replace cysteine residues capable of forming intermolecular disulfide bonds with other amino acid residues that do not form such bonds. By abrogating the ability of the cysteine residues to form inter-molecular disulfide bonds, aggregation of the protein is reduced, thereby improving the solubility of the protein. In another embodiment, solubility of the protein is improved by producing truncated forms of the protein that express the LHN domain and a fragment of the Hc domain. Proteins made according to the method of the invention are useful, for example, as immunodiagnostic agents and vaccine components.

Abstract: Methods of treating one or more autoimmune disorders include a step of administering a Clostridial neurotoxin, such as a botulinum toxin, to a patient that has an autoimmune disorder. In one aspect, a method includes a step of administering the neurotoxin to the thymus gland or near the thymus gland of the patient. In another aspect, a method includes a step of administering the neurotoxin in combination with administering a cytokine inhibitor to the patient. Compositions are also described.

Abstract: The present invention relates to an isolated Clostridial neurotoxin propeptide having a light chain region, a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond, and an intermediate region connecting the light and heavy chain regions. An isolated nucleic acid molecule encoding a Clostridial neurotoxin propeptide is also disclosed. Also disclosed is an isolated, physiologically active Clostridial neurotoxin produced by cleaving a Clostridial neurotoxin propeptide, a vaccine or antidote thereof, and methods of immunizing against or treating for toxic effects of Clostridial neurotoxins. Methods of expressing recombinant physiologically active Clostridial neurotoxins are also disclosed. Also disclosed is a chimeric protein having a heavy chain region of a Clostridial neurotoxin and a protein with therapeutic functionality. A treatment method is also disclosed.

Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

Abstract: A system and method for identifying a botulinum neurotoxin inhibitor employing a botulinum neurotoxin substrate complex having a peptide substrate, preferably SNAP-25, a reporter domain on one side of said peptide substrate and an immobilization domain on the opposite side of said peptide substrate. The botulinum neurotoxin inhibitor is identified by its ability to decrease the relative amount of cleaved complex, detected through measuring a decrease in complex bound to a solid support. The method of the present invention also utilizes novel cells that express a botulinum neurotoxin substrate complex. The methods of the present invention are adapted for cell based screening to monitor the catalytic activity of a BoNT in living cells and to identify molecules that inhibit the catalytic activity of a BoNT in living cells.

Abstract: The invention relates to novel DNA and protein vaccines against Clostridium botulinum. The DNA vaccine includes a DNA molecule that includes a first segment encoding a fragment of a heavy chain region of a Clostridium botulinum neurotoxin, wherein the first segment is codon-enhanced to improve expression of the isolated DNA molecule in a mammalian host, and preferably a second segment that encodes a secretion signal peptide. The chimeric protein of the present invention includes the secretion signal peptide linked N-terminal of the fragment of a heavy chain region of a Clostridium botulinum neurotoxin. Use of these materials to raise antibodies, and to impart resistance against Clostridium botulinum to a mammal is also disclosed.

Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

Abstract: An isolated polypeptide comprising a botulinum neurotoxin C1 light chain having a modified amino acid sequence relative to the sequence of a wild-type botulinum neurotoxin C1 light chain is disclosed. The modified botulinum neurotoxin C1 light chain is capable of selectively cleaving syntaxin protein, but has substantially reduced or no activity against SNAP-25 as compared to wild type botulinum neurotoxin C1 light chain, and is thus useful as a research tool and in medical treatment.

Abstract: A method for skin antiaging treatment comprising administering Botulinum toxin to an area of facial and/or neck skin, combined with the administration of a cosmetic or pharmaceutical composition comprising a cosmetically or pharmaceutically effective amount of at least one peptide derived from the SNAP-25 protein and/or at least one enkephalin-derived peptide, and at least one cosmetically or pharmaceutically acceptable excipient or adjuvant.