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: Sympathetic nerves run through the adventitia surrounding renal arteries and are critical in the modulation of systemic hypertension. Hyperactivity of these nerves can cause renal hypertension, a disease prevalent in 30-40% of the adult population. Hypertension can be treated with neuromodulating agents (such as angiotensin converting enzyme inhibitors, angiotensin II inhibitors, or aldosterone receptor blockers), but requires adherence to strict medication regimens and often does not reach target blood pressure threshold to reduce risk of major cardiovascular events. A minimally invasive solution is presented here to reduce the activity of the sympathetic nerves surrounding the renal artery by locally delivering neurotoxic or nerve-blocking agents into the adventitia. Extended elution of these agents may also be accomplished in order to tailor the therapy to the patient.

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: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: Various improvements to vaccines that include a serogroup C meningococcal conjugate antigen, including: (a) co-administration with acellular B. pertussis antigen; (b) co-administration with an inactivated poliovirus antigen; (c) supply in a kit together with a separate pneumococcal conjugate component, which may be in a liquid form; and (d) use in combination with a pneumococcal conjugate antigen but without an aluminium phosphate adjuvant. A kit may have: (a) a first immunogenic component that comprises an aqueous formulation of a conjugated capsular saccharide from Streptococcus pneumoniae; and (b) a second immunogenic component that comprises a conjugated capsular saccharide from Neisseria meningitidis serogroup C.

Abstract: The present invention provides modified multi-chain and multi-subunit proteins and methods for making them. In some protease embodiments the proteins are modified AB5 toxins in which a compound of interest is attached to the A1 chain.

Abstract: The present invention provides compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such 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 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.

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

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: 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: A pharmaceutical preparation comprising one of the botulinum neurotoxins from Clostridium botulinum of types A, B, C, D, E, F or G or a mixture of two or more of these neurotoxins, wherein the neurotoxin or the mixture of neurotoxins is free of the complexing proteins which naturally form the botulinum neurotoxin complexes together with the neurotoxins.

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: 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, and cholecystitis for example.

Abstract: Methods for prevention, treatment or inhibition of the growth or metastasis of cancer cells in a subject are disclosed. One method comprises the step of administering to the subject a therapeutically effective amount of tumor associated antigen binding ligand-coated planetary ball milled (PBM) nanoparticles containing a cytotoxic agent.

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 pertains to pharmaceutical compositions which comprise a botulinum neurotoxin from Clostridium botulinum, the neurotoxin being free of the complexing proteins naturally present in the botulinum neurotoxin complex or being chemically modified or being modified by genetic manipulation. Moreover the pharmaceutical compositions of the instant invention have good stability and are advantageously formulated free of human serum albumin.

Abstract: The present invention provides a chimeric protein capable of killing or modifying a cell expressing abnormally high levels of a ligand of a receptor of the TNF/NGF family, comprising the amino acid sequence of at least one polypeptide consisting of an extracellular portion of said receptor connected to an effector molecule. In addition the invention provides pharmaceutical compositions comprising said chimeric protein and use thereof.

Abstract: Various improvements to vaccines that include a serogroup C meningococcal conjugate antigen, including: (a) co-administration with acellular B. pertussis antigen; (b) co-administration with an inactivated poliovirus antigen; (c) supply in a kit together with a separate pneumococcal conjugate component, which may be in a liquid form; and (d) use in combination with a pneumococcal conjugate antigen but without an aluminum phosphate adjuvant. A kit may have: (a) a first immunogenic component that comprises an aqueous formulation of a conjugated capsular saccharide from Streptococcus pneumoniae; and (b) a second immunogenic component that comprises a conjugated capsular saccharide from Neisseria meningitidis serogroup C.

Abstract: The present invention relates to methods and systems for administering antibody therapeutic agents. The methods include administering one or more (e.g., two or three) binding agents, wherein each of the binding agents has one or more monomers that have a binding region that is specific to a portion of a disease agent and one or more copies of a tag. The binding agents can be specific to one or more portions of the same or different disease agents. The tag is the same for each of the binding agents. The methods include administering an anti-tag antibody, wherein the anti-tag antibody has an anti-tag region that is specific to the tag, and can have an immunoglobulin (e.g., IgA, IgD, IgE, IgG, and IgM). Disease agents include bacteria, bacterial proteins, viruses, viral proteins, cancer cells, and proteins or toxins produced therefrom or from other sources such as snakes, insects, plants, etc.

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 aquatic subunit vaccine comprises an antigenic fusion protein and suitable carrier or adjuvant. The antigenic fusion protein sequence consists from its amino terminus to carboxyl terminus of a receptor binding motif and a translocation domain of Pseudomonas aeruginosa exotoxin A and has the amino acid sequence of SEQ ID No: 8; a viral antigenic protein affecting fish disease; and a signal peptide having the amino acid sequence of SEQ ID No: 10.

Abstract: This invention provides botulinum antitoxin compositions and methods of production, and methods of treating animals and humans prophylactically and also those suspected of having contacted botulism toxin. The botulinum antitoxin is prepared by inoculating an animal with a monovalent botulinum toxoid and toxin. The animal's plasma is collected and purified at a high pH by affinity chromatography. The resulting monovalent immunoglobulins are de-speciated by digestion with pepsin. Monovalent antitoxins for all seven botulinum serotypes are then combined to produce a high titered heptavalent botulinum antitoxin composition.

Abstract: The invention provides methods of modulating an immune response to a second antigen which entail administration of a first antigen and an immunostimulatory polynucleotide. Modulation of the immune response is generally manifested as stimulation of a Th1 response.

Abstract: The present invention provides methods to produce toxoid vaccines, such as ricin A chain vaccines, with reduced ability to promote vascular leak syndrome (VLS) and catalytic toxicity associated with various proteinaceous toxins, such as ribosome inactivating proteins. The invention also provides toxoids which have been mutated to lack amino acid sequences which induce VLS and toxic catalytic activity.

Abstract: The invention relates to a modified botulinum toxin comprising a natural heavy chain and a modified light chain, characterized in that the modification of the light chain resides in that it comprises (i) an extension of the chain on its N-terminus which has the structure —(C)n-(tag)m-(X)l- in the direction from the N- to the C-terminal end, wherein C represents a cysteine residue, tag represents any tag and X represents the residue of any naturally occurring amino acid, n represents an integer from 1 to 50, m represents 0 or 1, and l represents 0 or an integer from 1 to 50, and in that (ii) at least one of the cysteine residues in the extension of the chain is coupled to at least one chain of PEG.

Abstract: The present invention provides compositions including siderophore receptor polypeptides from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such compositions.

Abstract: The present invention provides compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such compositions.

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: The present invention relates to a therapeutic composition comprising a pharmaceutically active agent and a diarrheagenic agent, wherein the diarrheagenic agent induces diarrhea to reduce the harmful or undesired side effects of the pharmaceutically active agent when the pharmaceutically active agent is ingested at a dose higher than the prescribed dose.

Abstract: The invention concerns a novel method for extracting endotoxins from bacteria, and the use of said method for preparing compositions comprising endotoxins or derivatives thereof designed for human or animal use (scientific, medical usage).

Abstract: A method for using bird eggs to detect the presence of at least one botulinum toxin.

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: A method for treating allergy with a pharmaceutical composition containing a detoxified E. coli heat-labile enterotoxin, and, optionally, an allergen.

Abstract: The present invention provides methods for the treatment or prevention of allergic airways diseases, the suppression of allergic immune responses, and the induction protective immunity against allergic airways diseases wherein the methods comprise administering to subjects in need thereof an effective amount of a Streptococcus pneumoniae capsular polysaccharide and a Streptococcus pneumoniae exotoxin or exotoxoid, optionally together with one or more additional antigenic or immunomodulatory constituents, components or fractions of Streptococcus pneumoniae and/or immunopotentiators. Administration of individual components is also contemplated. Also provided are vaccine compositions suitable for use in accordance with methods disclosed herein.

Abstract: Apparatuses, compositions and methods for removing cells which interfere with regenerative processes. The apparatuses, compositions and methods selectively kill partially functional and/or non-functional cells versus functional cells while protecting functional proliferative cells to the extent that, upon removal of the killed cells by disintegration or scavenging, functional cells replace the partially- or non-functional cells.

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: 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: Embodiments of the present invention provide processes for preparing thymus extracts and plant or fungal extracts, and more particularly provide compositions (Thyex-1-6A and -6B) produced in accordance with said processes, and methods for treatment of various conditions comprising administration of said compositions including but not limited to cancer. In preferred synergistic aspects, the inventive compositions (Thyex-1-6A and -6B) are administered in combination with a macrophage stimulating agent (e.g., beta glucan) for cancer treatment. Certain aspects relate to treating cancer, comprising: administering of a therapeutically effective amount of a thymus extract composition (Thyex-1-6A and -6B) in combination with administration of an extract of Houttuynia cordata. Further aspects comprise administration to a mammalian subject in need thereof a therapeutically effective amount of an extract of Houttuynia cordata, wherein treating or alleviating nausea is afforded. Combination or adjunctive therapies (e.

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: Mutants of cholesterol-dependent cytolysins comprising at least one amino acid substitution in at least one of Loop 1, Loop 2, or Loop 3 of Domain 4, nucleic acids, vectors, and host cells encoding such polypeptide mutants, and compositions and vaccines comprising such polypeptide mutants.

Abstract: A composition comprises a water-soluble polymer matrix in which are dispersed droplets of oil, the composition comprising an active principle. The invention includes embodiments in which the active principle is included in at least some of the oil droplets as well as embodiments in which the oil droplets are free of active principle. The oil droplets are released as the matrix containing them dissolves in an aqueous medium. In one embodiment, the oil droplets are substantially immobilized in or by the matrix and the immobilizing feature is lost as the matrix dissolves in aqueous media. In certain embodiments, the oil drops may collectively be referred to as the oil phase of the composition of the invention. The product may be in the form of mini-beads. The oil phase and/or the polymer matrix may each include a surfactant.

Abstract: Recombinant immunotoxins containing a cytotoxic RNAse fused to an antibody or antibody fragment may be produced in mammalian cell culture. Surprisingly, immunotoxins containing a cytotoxic RNAse fused to the N-terminus of one antibody variable domain can be prepared and retain the ability to specifically bind antigen. The immunotoxins may be used in a variety of therapeutic methods for treating diseases or syndromes associated with unwanted or inappropriate cell proliferation or activation.

Abstract: Devices, methods and kits are disclosed for preparing and administering less-painful formulations of Botulinum toxin. The devices, methods and kits of the present invention are comprised of or use an acidic formulation of Botulinum toxin, or, in certain embodiments, a freeze- or flash-dried composition of Botulinum toxin, having a long shelf-life which is subsequently mixed with an acid-neutralizing solution and, optionally a sequestration agent prior to administration to a patient in need thereof. The pH-neutralized formulation of Botulinum toxin is pharmaceutically acceptable for administration to a patient and is significantly less painful than acidic formulations of Botulinum toxin or formulations of Botulinum toxin having unnecessary antigens.

Abstract: The present invention provides a purified peptide comprising at least one of the sequences LKQKSSNSRKKRSTS (SEQ ID NO:1), or VKNKRTFLSPWISNI (SEQ ID NO:2) as well as a vaccine, a method to protect or treat an animal from anthrax toxin, a method of making a vaccine and the use of the peptide. The present invention also provides a monoclonal antibody that specifically binds to a peptide sequence comprising at least one of the following peptide sequences: LKQKSSNSRKKRSTS (SEQ ID NO:1), or VKNKRTFLSPWISNI (SEQ ID NO:2) as well as a method to protect or treat an animal from anthrax toxin, a method of making a vaccine, a pharmaceutical composition, a method of making a pharmaceutical composition, and the use of the monoclonal antibody.

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 methods and compositions for the stimulation of immune responses. In particular, the present invention provides immunogenic nanoemulsion compositions and methods of using the same for the induction of immune responses (e.g., innate and/or adaptive immune responses (e.g., for generation of host immunity against a bacterial species of the genus Streptococcus (e.g., Streptococcus pneumoniae))). Compositions and methods of the present invention find use in, among other things, clinical (e.g. therapeutic and preventative medicine (e.g., vaccination)) and research applications.