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 presently disclosed invention is broadly directed to therapeutic micro- and/or nanoparticles designed to target an immune cell with an active agent. More particularly, the particles have a predetermined geometry and a broadest dimension of less than about 10 ?m. The immune cell-targeted micro and/or nanoparticles may additionally comprise a biocompatible polymer.

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: The present invention provides methods of inducing an immune response against Clostridium species in birds, for protecting birds from Clostridium infection, and/or for protecting birds from related disorders such as necrotic enteritis. The methods can be practiced in ovo and/or post-hatch. The invention further provides compositions and methods for delivery of a composition of this invention in ovo directly to the embryo body.

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: Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Abstract: Methods for treating obsessions and compulsions by local administration of a Clostridial toxin. The obsessions or compulsions can be eye poking, body rocking, finger biting, counting, checking and related disorders treated by low dose, intramuscular administration of a botulinum toxin.

Abstract: The present invention provides methods of inducing an immune response against Clostridium species in birds, for protecting birds from Clostridium infection, and/or for protecting birds from related disorders such as necrotic enteritis. The methods can be practiced in ovo and/or post-hatch. The invention further provides compositions and methods for delivery of a composition of this invention in ovo directly to the embryo body.

Abstract: Disclosed are vaccines and vaccine adjuvants useful in the treatment and/or prevention of infection and diseases associated with infectious pathogens, such as tetanus, as well as diseases associated with biological toxins. Also provided are methods of preparing an adjuvant and the vaccine containing the adjuvant. Methods are also provided for vaccinating/immunizing an animal against infection and diseases associated with infectious pathogens, such as tetanus, and other diseases associated with biological toxins. Adjuvant materials are presented that are prepared from an extracellular matrix material. The adjuvants are demonstrated to enhance the immunogenicity of an infectious pathogen antigen or biological toxin antigen of interest, as well as to enhance the survival of an immunized animal.

Abstract: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

Abstract: A stabilizing composition that also enhances permeation is provided for the topical or transdermal administration of an active ingredient. The composition preferably comprises collagen, elastin, sphingoside and cerebroside. Also provided are pharmaceutical or cosmetic formulations comprising an effective amount of an active agent and the stabilizing composition as well as methods of administering active agents topically or transdermally.

Abstract: Described herein are methods of preventing, modulating and treating spasticity and maladaptive neuronal plasticity in patients having upper motor neuron lesions or have had a traumatic central nervous system event by early intervention methods. The methods comprise the step of administering a therapeutically effective amount of a botulinum toxin or derivative thereof to least a portion of a 1A sensory afferent of at least one muscle prior to development of spasticity or maladaptive neuronal plasticity becomes clinically apparent. The therapeutically effective amount of botulinum toxin administered to the 1A afferent of the muscle does not substantially affect the Golgi tendons therein.

Abstract: Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Abstract: The present invention relates to pharmaceutical compositions of activated botulinum holotoxin type B (150 kD). In particular, the present invention relates to botulinum toxin type B pharmaceutical compositions wherein at least 90% of said botulinum toxin type B is activated (i.e., “nicked”), and wherein at least 99% said nicked botulinum toxin type B is a 150 kD holotoxin (i.e., “stripped”). The invention also relates to a process of activating and stripping botulinum toxin type B wherein at least 90% of said botulinum toxin type B is nicked, and wherein at least 99% of said nicked botulinum toxin type B is stripped. The invention further relates to methods for the treatment of a variety of neuromuscular diseases, pain, inflammatory and cutaneous disorders comprising administering a pharmaceutical composition of activated botulinum holotoxin type B (150 kD) wherein at least 90% of said botulinum toxin type B is nicked, and wherein at least 99% of said nicked botulinum toxin type B is stripped.

Abstract: The present invention relates to pharmaceutical compositions of activated botulinum toxin type B. In particular, the present invention relates to botulinum toxin type B pharmaceutical compositions wherein at least 90% of said botulinum toxin type B is activated—i.e., “nicked”. The invention also relates to a process of activating botulinum toxin type B wherein at least 90% of said botulinum toxin type B is nicked. The invention further relates to methods for the treatment of a variety of overactive or neuromuscular diseases, pain, inflammatory and cutaneous disorders comprising administering a pharmaceutical composition of activated botulinum toxin type B wherein at least 90% of said botulinum toxin type B is nicked.

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: Botulinum toxin is increasingly being injected into visceral smooth muscle for a variety of indications. The present invention discloses intragastric administration of botulinum toxin to delay gastric emptying with the aim of inducing satiety and promoting weight-loss. The present invention also discloses the effects of intragastric administration of Botulinum toxin in reducing post-prandial hyperglycemia in patients suffering from Diabetes Mellitus.

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: The present invention features methods for selecting a patient with an enhanced therapeutic response to a botulinum toxin treatment of a headache. In some embodiments, the methods comprise the step of identifying a patient who is not using a prophylactic headache pain medication, a patient who is overusing an acute pain medication, a patient who suffers four or more hours of headache pain per headache, a patient who has a chronic daily headache for twenty or more years, and/or a patient who has twenty or more headache days out of a 30-day-month.

Abstract: Pharmaceutical compositions for transdermal administration of neurotoxins to a patient include a neurotoxin, such as a botulinum toxin, and an enhancing agent that facilitates absorption of the neurotoxin through the skin of the patient and does not eliminate the bioactivity associated with the neurotoxin. The pharmaceutical compositions are topically applied on a patient, and may be provided in a transdermal patch.

Abstract: Methods of treating an eye disorder are disclosed. Particular methods comprise a step of locally administering a Clostridial toxin to the eye of a patient to treat the disorder.

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: The purpose of the present invention is to provide micro- or mili-capsules and film preparations having not only sustained-release function but also targeting and adhesive functions with approximately 100% loading efficiency of the objective substance. The present invention provides a parenteral preparation having three layers structure of; basement layer composed of polymer; carrying layer that contains objective substances selected from drugs, aroma chemicals, mosquito propellant, dyes, cells or antigens; and surface layer, and in which the carrying layer is sandwiched between the basement layer and the surface layer.

Abstract: An effective, long lasting, non-systemic drug administration protocol for preventing vascular vasospasm and vessel thrombosis in free tissue transplantation. In a free flap procedure, after the recipient vein and artery (vascular pedicle) are divided, the recipient artery and vein are pretreated with a local injection of botulinum toxin. The vein and artery from the flap (vascular pedicle) are anastomosed (connected) to the vein and artery identified using microsurgery. The free flap is sutured to the prepared area, and the donor site is sutured closed. Then, a relatively long term, non-systemic local administration neurotoxin administration protocol is effected in conjunction with a periodic monitoring program to ensure the blood vessels remain patent (i.e. the vessels have good blood flow). The botulinum post-treatment alone or in combination with the botulinum pretreatment can proactively prevent vascular vasospasm and vessel thrombosis after the free tissue transplantation.

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: The present invention provides improved formulations of botulinum toxin that increase delivery of the botulinum toxin to neural and associated tissues and exhibit a higher specific neurotoxicity and higher potency (in LD50 Units) than available formulations of botulinum toxins. These improved formulations enable physicians to treat a wide variety of pathological conditions with a lower toxin load that reduces the risk of inducing an immune response against the toxin and its associated proteins that may ultimately lead to the development of toxin resistance. These benefits are particularly important in the treatment of conditions that require high-dose or chronic administration of botulinum toxin. Additionally, the decreased in LD50 Unit doses of inventive formulations allows for controlled administration limits diffusion. The present invention also provides methods of treating neuromuscular diseases and pain, using low-dose botulinum toxin.

Abstract: The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, a multivalent Streptococcus pneumoniae immunogenic composition is provided with various conjugated capsular saccharides from different S. pneumoniae serotypes conjugated to 2 or more different carrier proteins, where the composition comprises serotype 19F capsular saccharide conjugated to diphtheria toxoid (DT) or CRM197, optionally wherein 19F is the only saccharide in the composition conjugated to diphtheria toxoid (DT) or CRM197.

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: 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: Methods and compositions for improving skin quality are disclosed. The methods include applying a solution of about 20-30% pre-wetting agent, such as hyaluronic acid, and/or Botulinum toxin to a skin surface with concurrent particle-free dermabrasion treatment, such as particle-free microdermabrasion treatment. These methods lead to significant improvement in the treatment of skin aging. Compositions for improving skin quality are also disclosed. These compositions comprise a pre-wetting agent and a Botulinum toxin agent.

Abstract: Aqueous dispersions of chemically and physically stable particles for use in delivery of active pharmaceutical ingredients and processes for their production and use to enhance a biological response to an active pharmaceutical ingredient and prophylactically or therapeutically treat a subject are provided. Vaccines, wherein the active pharmaceutical ingredient is a solution of subunit vaccine antigen mixed with a colloidal dispersion of electrically charged particles and use of such vaccines in immunization are also provided.

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

Abstract: Antigenic compositions are provided comprising a single chain polypeptide comprising first and second domains, wherein said first domain is a clostridial neurotoxin light chain or a fragment or a variant thereof and is capable of cleaving one or more vesicle or plasma membrane associated proteins essential to exocytosis; and said second domain is a clostridial neurotoxin heavy chain HN portion or a fragment or a variant thereof, wherein said second domain is capable of (i) translocating the polypeptide into a cell or (ii) increasing the solubility of the polypeptide compared to the solubility of the first domain on its own or (iii) both translocating the polypeptide into a cell and increasing the solubility of the polypeptide compared to the solubility of the first domain on its own; and wherein the second domain lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell sur

Abstract: The present invention provides for a pharmaceutical composition that includes tetrabenazine and a release-retarding agent; and a method of treating a hyperkinetic movement disorder (e.g., Huntington's disease, chorea associated with Huntington's disease, hemiballismus, senile chorea, tic disorders, tardive dyskinesia, myoclonlus, dystoniia and/or Tourette's syndrome). The method includes administering an effective amount of the pharmaceutical composition, for a period of time effective to treat the hyperkinetic movement disorder.

Abstract: Botulinum toxin has been shown to be useful for the treatment of pain when administered for cervical dystonia. Given efficacy for pain relief in regional dystonia, further expanded applications have included myofascial pain, muscle tension headaches, and other forms of headache syndromes. The application in headache practice has expanded to migraine as well as certain secondary headache syndromes. Although multiple case reports involving the use of botulinum toxin have shown promise in its utility for the treatment of primary pain syndromes, to date, controlled trials have failed to consistently and more definitively prove utility. Described herein is a method for selection of patients with headache syndromes more likely to respond to botulinum administration.

Abstract: Methods of using clostridial toxins and other biological agents to thin skin and control fine wrinkles in humans are provided. In preferred embodiments the methods provide beneficial effects in humans.

Abstract: The present invention relates to pharmaceutical compositions of activated botulinum toxin type B. In particular, the present invention relates to botulinum toxin type B pharmaceutical compositions wherein at least 75% of said botulinum toxin type B is activated—i.e., “nicked”. The invention also relates to a process of activating botulinum toxin type B wherein at least 75% of said botulinum toxin type B is nicked. The invention further relates to methods for the treatment of a variety of neuromuscular diseases, pain, inflammatory and cutaneous disorders comprising administering a pharmaceutical composition of activated botulinum toxin type B wherein at least 75% of said botulinum toxin type B is nicked.

Abstract: The present invention relates to pharmaceutical compositions of activated botulinum holotoxin type B (150 kD). In particular, the present invention relates to botulinum toxin type B pharmaceutical compositions wherein at least 75% of said botulinum toxin type B is activated (i.e., “nicked”), and wherein at least 75% said nicked botulinum toxin type B is a 150 kD holotoxin (i.e., “stripped”). The invention also relates to a process of activating and stripping botulinum toxin type B wherein at least 75% of said botulinum toxin type B is nicked, and wherein at least 75% of said nicked botulinum toxin type B is stripped. The invention further relates to methods for the treatment of a variety of neuromuscular diseases, pain, inflammatory and cutaneous disorders comprising administering a pharmaceutical composition of activated botulinum holotoxin type B (150 kD) wherein at least 75% of said botulinum toxin type B is nicked, and wherein at least 75% of said nicked botulinum toxin type B is stripped.

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: Presently descibed are methods useful in treating outer ear conditions generally associated with the secretion of cerumen. The methods comprise the step of locally administering a therapeutically effective amount of neurotoxin such as a botulinum toxin to the ear canal of a patient. The conditions to be treated are generally associated with excess secretion of cerumen or the build-up of cerumen in the ear canal of a patient. Such conditions can include, but are not limited to, conductive hearing loss, pain and cough, for example.

Abstract: Methods and systems for delivering toxin and toxin fragments to a patient's nasal cavity provide for both release of the toxin and delivery of energy which selectively porates target cells to enhance uptake of the toxin. The use of energy-mediated delivery is particularly advantageous with light chain fragment toxins which lack cell binding capacity.

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: This invention relates to novel compositions of botulinum toxin that are stabilized using HTV-TAT fragments or derivatives of HTV-TAT fragments. The composition can be administered for various therapeutic, aesthetic and/or cosmetic purposes. The invention also provides method for stabilizing botulinum toxin using HIV-TAT fragments or derivatives or HIV-TAT fragments.

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 present invention provides compositions that contain botulinum toxin and a hyaluronidase, and that lack human or recombinant serum albumin. The present invention also provides methods of administering the pharmaceutical composition to a subject in need thereof.

Abstract: A method using a pharmaceutical composition comprising botulinum toxin and a pharmacologically acceptable carrier to treat pain in the knee joint caused by saphenous nerve entrapment. The composition of the present invention is for subcutaneous injection above the medial side of the knee.

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 method of inhibiting bacterial cell growth or of treating or inhibiting a bacterial infection in a subject by administering to the subject a therapeutically effective amount of a polynucleotide encoding a polypeptide having ?/? small acid-soluble spore protein (SASP) activity in a delivery system which targets a bacterial cell.

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: A botulinum toxin pharmaceutical formulation free of animal derived proteins, comprising a botulinum toxin and a recombinant albumin, suitable for therapeutic administration to a human patient, and methods for treating patients with various diseases and afflictions with the formulation.