Abstract: Provided herein are methods and compositions for stabilization of active agents. The active agents are distributed, mixed or embedded in a silk fibroin matrix, thereby retaining the bioactivity of the active agents upon storage and/or transportation. In some embodiments, the storage-stable vaccine-silk compositions are also provided herein.

Abstract: Chromatographic processes and systems for purifying a botulinum toxin from an APF fermentation medium.

Abstract: The present invention relates to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.

Abstract: Effective devices and methods using a chemical denervation agent are provided for treating chronic back pain. The devices and methods comprise a chemical denervation agent to degrade or to shrink at least a portion of a nerve associated with back pain e.g. basivertebral nerve of the lumbar. In some embodiments, the methods and devices are configured to immediately release an effective amount of the chemical denervation agent within 24 hours and provide sustained release of the chemical denervation agent or other therapeutic agent over a period of up to one year to treat chronic back pain.

Abstract: Methods of using tetanus toxin to modulate or control neural functions or nonneural cellular activities at selected sites in animals, particularly in mammals, and more particularly in humans, are provided. Pharmaceutical formulations to modulate neural functions or non-neural cellular activities of an animal at selected sites in animals, particularly in mammals, and more particularly in humans are also provided. Uses of tetanus toxin in preparation of medicaments for methods of treating clinical disorders or symptoms of animals, particularly mammals and more particularly humans are also provided.

Abstract: A vaccine composition comprising at least one antigen and one adjuvant, characterized in that the adjuvant comprises sterile-filterable nanoparticles comprising pseudo-boehmite and polyacrylate.

Abstract: The disclosure provides a method of preparing an immunologically-active adjuvant-bound freeze dried vaccine composition. A specific embodiment provides a stable vaccine composition comprising an aluminum-salt adjuvant, a recombinant Clostridium botulinum neurotoxin protein and a glass-forming agent. These vaccine compositions are useful in the treatment of humans and other animals at risk of infection from Clostridium botulinum neurotoxin.

Abstract: The present invention relates to a treatment method. This method involves contacting a subject with an isolated, physiologically active, atoxic derivative of a Clostridial neurotoxin. Contacting is carried out to treat the subject. The derivative of a Clostridial neurotoxin does not possess a cargo attachment peptide sequence at its N-terminus.

Abstract: The present invention relates to at least one botulinum neurotoxin for treatment of prevention of pain associated with diabetic neuropathy wherein said botulinum neurotoxin is prepared for local administration, wherein the local administration is not in the central nervous system (CNS), and wherein pain is treated at a site distant to the site of administration.

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 wherein the Targeting Moiety is selected from the group consisting of BAM, ?-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

Abstract: An isolated polypeptide comprising an amino acid sequence selected from amino acids 506-582 of SV2A, wherein position 573 is N and is glycosylated, or amino acids 449-525 of SV2B, wherein position 516 is N and is glycosylated. The present invention also provides an antibody that binds specifically to the polypeptide, an isolated nucleic acid comprising a polynucleotide that encodes the polypeptide; a method for reducing BoNT/E toxicity in an animal; a method for identifying an agent that blocks or inhibits binding between BoNT/E and an SV2A or SV2B protein; a method for monitoring synaptic vesicle endo- or exocytosis, a method for specifically delivering a chemical entity to a cell which has a specific receptor to a BoNT toxin.

Abstract: The present invention relates to a compound of the following general formula (I): R1—NH—CH(R2)—P(?O)(OR3)—CH2—C(R4)(R5)—CONH—CH(R6)—COOR7 (I) or a pharmaceutically acceptable salt of the latter, an isomer or a mixture of isomers in any proportions, especially a mixture of enantiomers, and in particular a racemic mixture, for which R1 represents a —C(?O)—O—C(R8)(R9)—OC(?O)—R10 group; R2 represents an optionally substituted hydrocarbon-based chain, an aryl or heteroaryl group or a methylene group substituted by a heterocycle; R3 represents a hydrogen atom or a —C(R12)(R13)—OC(?O)—R14 group; R4 and R5 form, together with the carbon that bears them, a saturated hydrocarbon-based ring or an optionally substituted piperidine ring or R4 represents a hydrogen atom and R5 represents a phenyl or a benzyl that is optionally substituted, a heteroaromatic ring or a methylene group substituted by a heterocycle; R6 represents an optionally substituted hydrocarbon-based chain or a phenyl or a benzyl that is optionally substi

Abstract: The present invention relates to polypeptides transiently activating Ras homolog gene family member A (RhoA) GTPase, polynucleotides encoding said polypeptides and pharmaceutical compositions comprising said polypeptides or said polynucleotides. The present invention further relates to the use of said polypeptides, said polynucleotides or said pharmaceutical compositions for long-term treatment of damage of the peripheral or central nervous system.

Abstract: Methods for preventing or treating neuropsychiatric disorder and/or a neurological disorder including a neurological disorder mediated by the thalamus. Neuropsychiatric disorders and/or a neurological disorders, including a thalamically mediated disorder can be treated by peripheral administration of a botulinum toxin to or to the vicinity of a trigeminal sensory nerve, thereby preventing or treating a neurological disorder and/or a neuropsychiatric disorder.

Abstract: The invention is a method for reducing the symptoms of vertigo. The method is performed by delivering a therapeutically effective amount of presynaptic neurotoxin, such as Botulinum Toxin A, in a pharmaceutically safe form to suitable locations around the head and neck.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

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: Disclosed herein are methods of using extracellular matrix digesting enzymes and neurotoxins, such as a Clostridial neurotoxins, to treat various medical conditions, such as overactive bladder, benign prostatic hyperplasia, hyperhidrosis, for example.

Abstract: The present invention relates to the field of vaccines for protecting against tetanus, and in particular processes for the production of vaccines comprising tetanus toxoid adsorbed onto aluminium salts. Processes are provided whereby tetanus toxoid is absorbed onto aluminium salt adjuvant having defined characteristics for optimal results.

Abstract: A botulinum toxin pharmaceutical formulation comprising a botulinum toxin and a low molecular weight recombinant or native gelatin fragment suitable for administration to a human patient, and methods for treating patients with various diseases and afflictions using the formulation.

Abstract: The invention provides an agent for preventing or treating a condition characterised by the presence of unwanted cells, the agent comprising: (i) a targeting moiety that is capable of targeting to the unwanted cells; and (ii) a T cell antigen, wherein the T cell antigen can be released from the targeting moiety by selective cleavage of a cleavage site in the agent in the vicinity of the unwanted cells.

Abstract: Disclosed herein is a liquid pharmaceutical composition of botulinum toxin which is improved in stability. It comprises botulinum toxin, polysorbate 20, and methionine and optionally isoleucine. Employing, instead of the animal-derived protein albumin or gelatin, a combination of polysorbate 20 and methionine and optionally isoleucine as botulinum toxin stabilizers, the liquid pharmaceutical composition eliminates the risk of contaminating the body with serum-derived pathogens or microorganisms and can be administered safely to the body. Also, the composition is convenient for use as a direct injection for patients. Superior to conventional compositions employing either detergents or amino acids in terms of the storage stability of botulinum toxin at 25˜370C as well as at refrigerated temperatures, the liquid pharmaceutical composition of the present invention is very useful for storing botulinum toxin under an emergency condition such as an environment without maintaining low temperature.

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: A method for treating a patient with migraine headache includes administering to the patient a therapeutically effective amount of an invertebrate presynaptic neurotoxin in a pharmaceutically safe form. The administration includes extramuscular injection of the neurotoxin to emerging nerve points including foraminal sites for enabling neurotoxin access to concentrated nerve bundles at exit points of the foramina.

Abstract: The present invention utilizes patient-specific landmarks in order to treat headache pain. In one aspect, the present invention relates to the administration of Clostridial toxins, such as a botulinum neurotoxin, to a patient suffering from a headache pain, where the location of administration of the botulinum toxin is based upon at least one suture line of the patient's skull.

Abstract: The present invention provides a new means of restoring the immune system in aging and immunocompromised individuals using an antioxidant nutraceutical. The nutraceutical stimulates the aging immune system through the Nrf2 master gene regulatory pathway. The invention is based in part on the discovery that the Nrf2 has antioxidant and immune restorative activity. The nutraceutical improves function of both the innate and adaptive immune systems.

Abstract: Antibodies that specifically bind to toxins of C. difficile, antigen binding portions thereof, and methods of making and using the antibodies and antigen binding portions thereof are provided herein.

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: The application relates to Clostridium difficile cell surface polysaccharides, compositions comprising Clostridium difficile cell surface polysaccharides, and includes kits, methods and uses thereof.

Abstract: The invention is a method for reducing the symptoms of vertigo. The method is performed by delivering a therapeutically effective amount of presynaptic neurotoxin, such as Botulinum Toxin A, in a pharmaceutically safe form to suitable locations around the head and neck.

Abstract: The present invention relates to the isolation of polypeptides derived from the Clostridium botulinum neurotoxin and the use thereof as immunogens for the production of vaccines and antitoxins, as well as research and drug development applications. Clostridium botulinum is responsible for food bone botulism, a severe and often deadly disease. Botulinum neurotoxin binds to neural cells and are translocated into the cytosol. The toxin then prevents neurotransmitter release by cleaving a SNARE protein. A double mutant E224A/E262 full length botulinum neurotoxin Type A holo form was successfully cloned and purified, which lacks the endopeptidase activity involved in the toxic action of the BoNT, and thus leading to its detoxification (DR BoNT/A). This new molecule can be used as an antidote against botulism, and also as a vaccine candidate for botulism. Due to the poor availability and extreme toxicity of native holo-toxin, a nontoxic form of the holo-toxin is highly desired for research and vaccine development.

Abstract: This invention relates to a composition of botulinum based pharmaceuticals used for therapeutic and cosmetic treatment. This invention offers an improvement on the prior art by eliminating the potential of blood-borne contamination with botulinum based pharmaceuticals. Recombinant serum albumin is taught for use in the place of human serum albumin as a stabilizing or enhancing agent.

Abstract: The invention provides for the use of any form of botulinum toxin, or any enzymatically active derivative thereof, to cause temporary paralysis of the muscles of the lips of the mouth to promote smoking cessation.

Abstract: Provided herein are methods for generating dry vaccine powder formulations. Dry vaccine powder formulations can be used for intranasal delivery. Also provided are methods for stimulating local mucosal and systemic immunity by intranasal vaccine delivery.

Abstract: The present invention relates to methods for treating diseases and disorders by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition is devoid of any other protein of the Clostridium botulinum toxin complex and wherein the composition is administered at short intervals and/or in high doses.

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: The present invention relates to a combination vaccine comprising a mixture of antigens for protection against diseases such as diphtheria, tetanus, acellular pertussis, and infections caused by Haemophilus influenzae and polio viruses. The present invention also relates to inclusion of antigens for protection against infections caused Hepatitis virus and other pathogens, such that administration of the vaccine can simultaneously immunize a subject against more than one pathogen. The invention in particular relates to a fully liquid stable combination vaccine comprising the antigens as indicated above and the methods for manufacturing the same.

Abstract: Compositions useful for detecting Clostridial toxin activity comprising a cell that comprises a membrane-associated Clostridial toxin substrate comprising a first member of a fluorescence resonance energy transfer pair; and a Clostridial toxin recognition sequence including a cleavage site; and a membrane-associated second member of the FRET pair and methods useful for determining Clostridial toxin activity using such Clostridial toxin substrates.

Abstract: Methods for treating melanin related afflictions by local administration of a Clostridial toxin, such as a botulinum toxin, to a patient with a melanin related affliction.

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 sphenopalatine ganglion. Exemplary delivery is carried out by way of injection.

Abstract: A formulation free of protein which stabilizes pharmaceutical active proteins, peptides, or mixtures thereof in large scale production processes comprising a mixture of a hydrophilic polymer and a non-ionic detergent, and a mixture of a polyalcohol and a sugar. In some embodiments the polyalcohol is absent.

Abstract: The present invention relates to engineered Clostridium difficile type IV pilin (tfp) genes, type IV pilin proteins which can serve as a diagnostic marker for identification of patients infected with C. difficile, and vaccines comprising type IV pilin proteins, antigenic fragments and variants thereof for therapeutic interventions.

Abstract: This invention relates to novel compositions of botulinum toxin that can be applied topically for various therapeutic, aesthetic and/or cosmetic purposes. The compositions may include botulinum toxin complexes, wherein the amounts of hemagglutinin, non-toxin non-hemagglutinin and/or exogenous albumin are selectively and independently reduced compared to conventional commercially available botulinum toxin. The compositions may further contain molecules that are not native to botulinum toxin and that bind non-covalently to the botulinum toxin complexes, thereby acting as skin-tropic “adhesion molecules” to improve the ability of the toxin complexes to adhere to and to penetrate the skin epithelium. The compositions have an improved safety profile compared to existing botulinum-containing compositions that are injected subcutaneously. Methods for the use of such compositions are also contemplated by this invention.

Abstract: A method is provided for treating a neuromuscular defect in a subject. One step of the method includes locating a target nerve. After locating the target nerve, a treatment probe is provided. The treatment probe includes an elongated body member having a proximal end portion and a distal end portion. The distal end portion includes an energy delivery mechanism for stimulating or ablating the target nerve, a monitoring mechanism, and a fluid aspiration/delivery mechanism. Next, the target nerve is verified as an appropriate target for ablation by stimulating and then monitoring the target nerve via the energy delivery mechanism and the monitoring mechanism, respectively. After verifying the target nerve, a tumescent fluid is injected into the tissue surrounding the target nerve. An electric current is then delivered to the energy delivery mechanism to substantially ablate the target nerve.

Abstract: A novel dosing regimen for the administration of botulinum toxin based on the pattern, quantity, and location of neuromuscular junctions in the target tissue. Because the number of neuromuscular junctions in a target tissue remains generally stable throughout life and because the pharmacological effect of botulinum toxin is localized at the neuromuscular junction, dosing efficacy is unaffected by muscle mass, age of the patient, or body weight.

Abstract: A composition for topical application of a botulinum toxin (including botulinum toxin derivatives) comprises a botulinum toxin and a carrier comprising a polymeric backbone comprising a long-chain polypeptide or nonpeptidyl polymer having attached positively charged branching or “efficiency” groups. The invention also relates to methods for reducing muscle paralysis and other conditions that may be treated with a botulinum toxin, particularly paralysis of subcutaneous, and most particularly, facial, muscles, by topically applying an effective amount of the botulinum toxin and carrier, in conjunction, to the subject's skin or epithelium. Kits for administration are also described.

Abstract: Disorders such as headaches can be treated by administration of a botulinum toxin to a patient suffering therefrom, such as a migraine headache. A combined a fixed site/fixed dose and an optional follow the pain variable dosage and injection site paradigm is disclosed for optimizing clinical effectiveness of botulinum toxin administration for patients suffering headache, particularly chronic migraine.

Abstract: Biodegradable neurotoxin implants and methods of making and using such implants are provided. Biodegradable neurotoxin implants include a neurotoxin, a biodegradable polymer component, and an acidity regulating component. The biodegradable polymer component is effective in controlling the release of the neurotoxin from the implant when the implant is located in a patient's body. The acidity regulating component is effective in maintaining a pH of the implant in a desired range that may be effective in stabilizing the neurotoxin as the implant biodegrades when the implant is located in a patient's body. In one embodiment, an implant includes a botulinum toxin, a biodegradable polymer, and either monomers from which a biodegradable polymer is derived or oligomers including monomeric units substantially identical to a monomer from which a biodegradable polymer is derived, or a combination of such monomers and oligomers. The oligomers and biodegradable polymer may be derived from a single type of monomer.

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: Methods are disclosed herein for treating depression in the subject. A method includes the use of Botulinum toxin to cause paralysis of a facial muscle, such as the depressor anguli oris, procerus, frontalis, orbicularis oculi, or corrugator supercilii muscle to treat depression in the subject.