Abstract: This disclosure provides a method of treating urologic and related disorders, for example, urinary incontinence, in women through the administration of a composition comprising a neurotoxin and DMSO. Methods for making and using the described compositions are also provided.

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. This conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.

Abstract: Agents for treating pain, methods for producing the agents and methods for treating pain by administration to a patient of a therapeutically effective amount of the agent. The agent can include a clostridial neurotoxin, or a component or fragment or derivative thereof, attached to a targeting moiety, wherein the targeting moiety is selected from a group consisting of transmission compounds which can be released from neurons upon the transmission of pain signals by the neurons, and compounds substantially similar to the transmission compounds.

Abstract: Animal product free (APF) media and processes for the culture and fermentation of botulinum toxin producing Clostridium botulinum bacteria. The botulinum toxin obtained can be used for formulating and compounding botulinum toxin pharmaceutical compositions. The APF media can contain significantly reduced levels of meat or dairy by-products and use non-animal based products instead of the animal-derived products. Preferably, the APF media used are substantially free or free of animal derived products.

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: A headache can be treated more effectively by co-administration of a botulinum toxin and a triptan drug to a patient and/or the effectiveness of a triptan medication can be increased. The botulinum toxin can be botulinum toxin type A and the botulinum toxin can be administered to or to the vicinity of where a patient experiences or is predisposed to experience pain or a headache.

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: A composition for treating a subject is provided. The composition includes dimeric or polymeric secretory IgA therapeutic. Formulating agents are mixed with the dimeric or polymeric secretory IgA to yield a dosing form of a capsule, tablet, and a suppository. A process for manufacturing a medicament for the treatment of C. difficile associated disease in a human is also provided wherein dimeric or polymeric IgA is modified with secretory component to form a dimeric or polymeric secretory IgA therapeutic. The dimeric or polymeric secretory IgA therapeutic is then mixed with formulating agents to create a capsule, tablet, or suppository dosing form. The therapeutic is amenable to enrobement directly through microencapsulation or the dosing form is coated with an enteric coating. A method of C. difficile treatment with the therapeutic is also provided that is amenable to supplementation with concurrent or prior antibiotic administration.

Abstract: The present invention relates to a composition comprising: at least one botulinum neurotoxin, and at least one opiate derivative or its salt. The invention also relates to a product comprising at least one botulinum neurotoxin and at least one opiate derivative or its salt, as a combination product for simultaneous, separate or sequential therapeutic use in the treatment or prevention of pain and of neuromuscular disorders.

Abstract: Methods for treating a coronary risk factor (such as hypertension, diabetes, hyperlipidemia and obesity) and/or a respiratory disorder (such as asthma, chronic obstructive pulmonary disease and bronchitis) and/or arthritis by local administration of a botulinum neurotoxin to at least one of a head, neck or shoulder location (for example, by subdermal, subcutaneous or intramuscular administration of the botulinum neurotoxin) of a patient with a coronary risk factor, respiratory disorder or arthritis.

Abstract: Compositions and a method for sensitizing a cancer for treatment by cytotoxic therapy is disclosed. The method includes the step of administering to the cancerous tissue or cells a pharmaceutical composition containing a Botulinum toxin, BT.

Abstract: The non-toxic proteolytic C fragment of tetanus toxin (TTC peptide) has the same ability to bind nerve cells and be retrogradely transported through a synapse as the native toxin. A hybrid protein encoded by the lacZ-TTC gene fusion retains the biological functions of both proteins in vivo, i.e. retrograde transynaptic transport of the TTC fragment and -gal enzymatic activity. After intramuscular injection, enzymatic activity could be detected in motoneurons and connected neurons of the brainstem areas. This strategy is useful for the delivery of a biological activity to neurons from the periphery to the central nervous system. Such a hybrid protein can also be used to map synaptic connections between neural cells.

Abstract: Methods of treating a urethral stricture in a patient. The methods can include the step of administering an therapeutically effective amount of a botulinum toxin directly to a urethra of the patient, for example by use of a stent from which the botulinum toxin can elute or diffuse, thereby treating the urethra stricture.

Abstract: Disclosed herein are apparatuses and methods for treating a neurological disorder associated with excessive neuronal excitability (e.g., epilepsy). Methods disclosed herein comprise administering to a subject in need of such treatment an antiepileptic drug solution comprising a therapeutically effective amount of an antiepileptic drug (e.g., a toxin that inhibits the exocytosis of neurotransmifters, excitotoxins, etc.) using convection-enhanced delivery (CED).

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: The invention concerns the use or a fragment of botulinum toxin having said toxin activity for preparing a medicine for reversibly desensitizing an area of the skin, said skin area being designed to receive injections. Said injections can be related, for example, to repeated delivery of insulin, growth hormones or other medicines in injectable form.

Abstract: Animal product free (APF) media and processes for the culture and fermentation of botulinum toxin producing Clostridium botulinum bacteria. The botulinum toxin obtained can be used for formulating and compounding botulinum toxin pharmaceutical compositions. The APF media can contain significantly reduced levels of meat or dairy by-products and use non-animal based products instead of the animal-derived products. Preferably, the APF media used are substantially free or free of animal derived products.

Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located within the di-chain loop region; polynucleotide molecules encoding such modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located in the di-chain loop region; and method of producing modified Clostridial toxins comprising Clostridial toxin substrate cleavage site located within the di-chain loop region.

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: Methods of diagnosis, prognosis, and treatment of breast cancer, and of metastatic brain cancer, are provided The diagnostic and prognostic methods involve the immunohistochemical detection of the level of expression of the proteins claudin 1, 3, 4, and 7 in tissue or cell samples. Claudins 1 and 7 are underexpressed in the majority of breast cancers, and claudins 3 and 4 are overexpressed. The methods of treatment involve the use of Clostridium perfringens enterotoxin (or a variant thereof) to lyse metastatic cancer cells in the brain and bone that overexpress claudins 3 and 4.

Abstract: Improved dermal filler formulation comprising a hyaluronic acid and a botulinum toxin.

Abstract: Pharmaceutical application of a chemodenervating agent, particularly botulinum toxin, reduces inflammatory response and serves as an anti-inflammatory agent without systemic side effects and with long duration action, on the order of 12-24 weeks. In one embodiment, the effective dosage for allergy provoked inflammation reduction is an order of magnitude less than dosages associated with treatment of regional movement diseases, since the agent works to reduce inflammation by reducing histamine and other preformed mediator releases associated with mast cell degranulation.

Abstract: Improved vaccine compositions and methods of use thereof are described that elicit production of antibodies in an individual to the individual's own endogenous cholesteryl ester transfer protein (CETP).

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

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 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: An isolated, biologically active 33 kDa Hemagglutinin purified from the type A Clostridium botulinum neurotoxin complex and its uses are described.

Abstract: The present specification discloses modified Clostridial toxins, compositions comprising such toxins and methods of treating urogenital-neurological disorders in a mammal using such modified Clostridial toxins and compositions.

Abstract: The present specification discloses modified Clostridial toxins, compositions comprising such toxins and methods of treating chronic neurogenic inflammation in a mammal using such modified Clostridial toxins and compositions.

Abstract: The present invention is directed to multivalent Clostridial neurotoxin derivatives having more than one binding domain directed to a cell surface feature of a target cell. Such modified neurotoxins are useful as therapeutic compositions to prevent exocytosis and secretion by the target cell. Conditions in which such compositions man 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 provides methods of treating an eye disorder. The methods comprise a step of locally administering a Clostridial toxin to the eye of a patient to treat the disorder. The eye disorder may be associated with an inflammation of the eye, including for example, bacterial conjunctivitis, fungal conjunctivitis, viral conjunctivitis, uveitis, keratic precipitates, macular edema, and inflammation response after intra-ocular lens implantation. The Clostridial toxin may be produced by a Clostridial beratti, a Clostridia butyricum, a Clostridial tetani bacterium and/or a Clostridial botulinum.

Abstract: Improved formulations for transdermal delivery of botulinum toxin are disclosed. The formulations include, for example, botulinum toxin non-covalently associated with a positively charged backbone having branching or efficiency groups. The formulations also include a partitioning agent, oligo-bridge, or polyanion bridge, and may optionally contain a viscosity modifying agent. The formulations are designed for topical application onto the skin of a patient and may be used to treat wrinkles, hyperhidrosis, and other health-related problems. Kits for administration are also described.

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

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: 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: 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: 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: Methods for treating conditions in an animal or human subject. The conditions may be pain, skeletal muscle conditions, smooth muscle conditions, glandular conditions and cosmetic conditions. The methods comprise the step of administering a Clostridium neurotoxin component or Clostridium neurotoxin component encoding DNA to the subject using a needleless syringe.

Abstract: Methods of treating spasticity by administering a colonically absorbable prodrug of a GABA analog having antispastic activity that is not directly mediated by the GABAB receptor, optionally in combination with an antispasticity agent or a colonically absorbable prodrug of a GABAB receptor agonist are disclosed. In particular, methods of treating spasticity by administering a colonically absorbable prodrug of gabapentin or a colonically absorbable prodrug of pregabalin, in combination with a colonically absorbable prodrug of R-baclofen are disclosed.

Abstract: The present invention relates to a method for providing a muscle relaxant at temperatures above 20° C., wherein said muscle relaxant is a solid dry composition comprising the neurotoxic component of botulinum toxin free of complexing proteins.

Abstract: The invention relates to the use of a liquid or semi-solid formulation of botulinum toxin for the preparation of a medicament intended to treat a disorder characterised by bladder spasms (e.g. urinary incontinence due to unstable bladder or unstable detrusor sphincter, voiding complications due to detrusor overactivity or unstable detrusor sphincter, urinary retention secondary to spastic sphincter or hypertrophied bladder neck and neurogenic bladder dysfunction secondary to Parkinson's disease, spinal cord injury, stroke or multiple sclerosis or characterised by a spasm reflex), wherein said medicament is for administration by infusion into the bladder or by other methods that do not involve injection into the bladder wall.

Abstract: The present invention relates to methods for treating neurogenic inflammation pain. The methods include administering an effective amount of a composition which includes a botulinum toxin component and a substance P component to a patient, thereby treating the neurogenic inflammation pain.

Abstract: Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.

Abstract: Methods for treating conditions in an animal or human subject. The conditions may be pain, skeletal muscle conditions, smooth muscle conditions, glandular conditions and cosmetic conditions. The methods comprise the step of administering a Clostridium neurotoxin component or Clostridium neurotoxin component encoding DNA to the subject using a needleless syringe.

Abstract: The present invention provides modified pore-forming protein toxins (MPPTs), capable of being used to kill cancer cells. The MPPTs according to the present invention comprise a modification of the naturally occurring activation sequence comprising one or more general cleavage sites, each of which is cleavable by general activating agent, or a plurality of specific cleavage sites, each of which is cleavable by a specific activating agent. Optional further modifications that allow specific targeting of these molecules are also described. These MPPTs may be used to treat cancer.

Abstract: The present invention relates to methods for treating neurogenic inflammation pain. The methods include administering an effective amount of a composition which includes a botulinum toxin component and a substance P component to a patient, thereby treating the neurogenic inflammation pain.

Abstract: The invention relates to methods of producing, and compositions comprising, an isolated alpha (2?8) or (2?9) oligosialic acid derivative bearing a non-reducing end enriched for one or more de-N-acetyl residues and resistant to degradation by exoneuraminidase. A representative production method involves: (i) treating an alpha (2?8) or (2?9) oligosialic acid precursor having a reducing end and a non-reducing end with sodium borohydride under conditions for de-N-acetylating the non-reducing end; and (ii) isolating alpha (2?8) or (2?9) oligosialic acid derivative having one or more de-N-acetylated residues and a non-reducing end that is resistant to degradation by exoneuraminidase. Isolated alpha (2?8) or (2?9) oligosialic acid derivatives that comprise a non-reducing end de-N-acetyl residue are provided, as well as antibodies specific for the derivatives, compositions comprising the derivatives, kits, and methods of use including protection against and detection of E. coli K1 and N.

Abstract: Agents for treating pain, methods for producing the agents and methods for treating pain by administration to a patient of a therapeutically effective amount of the agent. The agent can include a clostridial neurotoxin, or a component or fragment or derivative thereof, attached to a targeting moiety, wherein the targeting moiety is selected from a group consisting of transmission compounds which can be released from neurons upon the transmission of pain signals by the neurons, and compounds substantially similar to the transmission compounds.