Abstract: Methods for treating or alleviating symptoms associated with femoroacetabular impingement (FAI) by local administration of a clostridial derivative, such as a botulinum toxin, to the hip capsule and surrounding muscle.

Abstract: The present invention relates to pharmaceutical compositions suitable for the treatment of chronic diseases associated with the presence of abnormal or an abnormal distribution of microflora in the gastrointestinal tract of a mammalian host, which compositions comprise viable non-pathogenic or attenuated pathogenic Clostridia. The compositions further comprise one or more additional viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Bacteroides, Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobic cocci, Ruminococcus, E. coli, Gemmiger, Desulfomonas, Peptostreptococcus, and fungi. The present invention also provides pharmaceutical compositions suitable for the treatment of the same chronic diseases comprising viable non-pathogenic or attenuated pathogenic Escherichia coli, at least one strain of viable non-pathogenic or attenuated pathogenic Bacteroides and at least one strain of viable non-pathogenic or attenuated pathogenic microorganism.

Abstract: The invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum. The protein binds specifically to nerve cells with a higher affinity as the native neurotoxin. The invention also relates to a method for the production of transport protein, the nucleic acids coding for the transport protein, the transport protein containing pharmaceutical and cosmetic compositions and use thereof.

Abstract: Methods of using botulinum toxin based pharmaceuticals are disclosed. The methods cause vasodilatation and decreased flow resistance of certain vascular beds for the purpose of increasing blood flow to a region in order to positively impact deterioration from a number of diseases.

Abstract: A novel type A botulinum toxin preparation is provided. A neuromuscular transmission blocking agent comprising as an active ingredient a highly purified type A botulinum toxin from Clostridium botulinum as infant botulism pathogen and a medicament for treating a disease with a muscle overactivity comprising as an active ingredient said toxin. In particular, the medicament of the present invention, as compared to the conventional known botulinum toxin preparations, has rapid efficacy of potential and is less diffusive and thus, having a broader safety margin, may be used as therapeutic medicament for decreasing local, muscle overactivity in a disease with a muscle overactivity.

Abstract: Phycotoxins are purified from a mixture of phycotoxins produced in a continuous process. Cyanobacteria are produced in a continuous culture, then lyzed, the cells pelleted and extracted, and the extract purified using an organic solvent-aqueous mixture and repeated passage through a diatomaceous earth column. The column is washed with acetic acid, then the neosaxitoxin extracted with an alcohol-water mixture. The eluate is passed through activated charcoal columns, which are washed with distilled water to remove the retained pigments and impurities, the further purified by HPLC. In one embodiment, the process produces only neosaxitoxin and saxitoxin. In another embodiment, the process produces only GTX2/3.

Abstract: The invention includes Clostridial neurotoxin derivatives containing at least two light chain endopeptidase domains, and nucleic acids encoding such Clostridial neurotoxin derivatives. In preferred embodiments, the invention includes methods and compositions for the treatment of inflammatory disorders (such as arthritis); chronic pain, such as neuropathic pain and inflammatory pain through the use of such Clostridial neurotoxin derivatives, including those derived from an intact BoNT/A having an LC/E-derived endopeptidase joined to the LC/A endopeptidase.

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

Abstract: There are provided a lyophilized preparation of botulinum toxin without a protein stabilizer derived from animals. The lyophilized preparation of botulinum toxin according to the present invention can maintain an activity of botulinum toxin, and also exhibit excellent long-term storage stability even under conditions of high temperature, which may occur when botulinum toxin is stored, delivered, and processed.

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

Abstract: A headache can be treated effectively by administration of a botulinum toxin to a patient at specific muscles using specific doses.

Abstract: There is provided a method for supporting soft tissue in a mammal. The method may in aspects treat acutely or chronically injured soft tissue in an animal or human, the method comprising administering a therapeutically effective amount of HA and botulinum toxin in combination around the injured soft tissue. The method is useful for the treatment of sprain and strain in an animal such as a human.

Abstract: An extended duration pharmaceutical composition including a botulinum neurotoxin, an adhesive agent, and a stabilizing macromolecule. The composition effectively has all the properties to cause chemodenervation through a facial muscle, or other muscle, that predecessor botulinum toxin preparations have had as well as agents which create a fibrotic adhesion on the under surface of facial muscles (or other muscles) to the facial bone (or other bones) so that the facial bone tethers the under surface of the facial muscle, thereby causing fibrosis to the underlying fat pad. The composition can be used to treat various disorders. Methods of modifying facial contour for functional or cosmetic purposes in a human patient are disclosed which involve injecting a therapeutically effective amount of the disclosed compositions. A method of quantifying the extended duration of the compositions is also disclosed.

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

Abstract: The present invention encompasses methods and compositions for alleviating pruritis. The compositions may comprise an analgesic agent.

Abstract: The present invention relates to pharmaceutical compositions suitable for the treatment of chronic diseases associated with the presence of abnormal or an abnormal distribution of microflora in the gastrointestinal tract of a mammalian host, which compositions comprise viable non-pathogenic or attenuated pathogenic Clostridia. The compositions further comprise one or more additional viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Bacteroides, Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobic cocci, Ruminococcus, E. Coli, Gemmiger, Desulfamonas, Peptostreptococcus, and fungi. The present invention also provides pharmaceutical compositions suitable for the treatment of the same chronic diseases comprising viable non-pathogenic or attenuated pathogenic Escherichia coli, at least one strain of viable non-pathogenic or attenuated pathoenic Bacteroides and at least one strain of viable non-pathogenic or attenuated pathogenic microorganism.

Abstract: The present invention describes vaccines that comprise C. perfringens Type alpha toxoids, antigenic fragments thereof, inactivated antigenic fragments of C. perfringens Type alpha toxins, or any combination thereof. The present invention further describes methods of using with these vaccines to protect animals against clostridial diseases. The present invention also describes methods of making these vaccines.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Abstract: The present disclosure provides immunogenic compositions, such as vaccines, including DNA vaccines, and uses thereof, e.g., to suppress or prevent an immune response and/or to treat or prevent an autoimmune disease.

Abstract: The present invention is directed to analgesic Clostridial neurotoxin derivatives comprising polypeptides having a long-lasting SNARE protein-selective endopeptidase activity. These derivatives selectively bind to and are internalized by non-neuronal cells secreting cytokines or sensory neurons in preference to motor neurons or autonomic neurons. The invention is also directed to nucleic acid constructs encoding such polypeptides, and methods of making such derivatives and nucleic acid constructs, and methods of treating pain, such as chronic pain, by administering such derivatives to a patient suffering from, or at risk of suffering from such pain.

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: The present invention relates to methods and compositions for use in modulating, including inhibiting the growth and/or reducing the virulence of gram-positive bacteria. The present invention provides methods and compositions for disrupting the cell wall and/or cell membrane in gram-positive bacteria such that cell wall or cell membrane target(s) are rendered exposed or accessible and sensitive to a modulation thereof. Methods for modulation of one or more gram-positive bacterial cell wall or cell membrane targets in a gram-positive bacteria are provided comprising disrupting the cell wall such that the cell wall or cell membrane target, which is particularly a sortase, is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, which is particularly an antibody or fragment thereof, wherein the cell wall or cell membrane target is inaccessible or relatively insensitive to the modifying, modulating or binding agent in the absence of cell wall disruption.

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. Also provided are novel stable cell lines that express the botulinum toxin substrate complex and viral vectors capable of efficiently expressing an active light chain of the BoNT within mammalian cells.

Abstract: The present invention relates to methods of treating esophageal spasms using botulinum toxins.

Abstract: This invention relates to isolated Clostridium botulinum propeptides and neurotoxins, isolated nucleic acid molecules encoding Clostridium botulinum propeptides and neurotoxins, methods of expression, treatment methods, and methods of detecting neurotoxin trafficking. The isolated Clostridium botulinum propeptides have a light chain region; a heavy chain region, where the light and heavy chain regions are linked by a disulfide bond; an intermediate region connecting the light and heavy chain regions and comprising a highly specific protease cleavage site; and an S6 peptide sequence according to SEQ ID NO:2 positioned upstream from, but not attached directly to, the N-terminus of the neurotoxin propeptide at the light chain region to enable site specific attachment of cargo.

Abstract: The present invention describes vaccines that comprise C. perfringens Type alpha toxoids, antigenic fragments thereof, inactivated antigenic fragments of C. perfringens Type alpha toxins, or any combination thereof. The present invention further describes methods of using with these vaccines to protect animals against clostridial diseases. The present invention also describes methods of making these vaccines.

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: The present invention relates to the therapeutic use of the carboxy-terminal domain of the heavy chain of the tetanus toxin for the treatment of amyotrophic lateral sclerosis (ALS).

Abstract: The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.

Abstract: Disclosed is a method for decreasing depression in a patient by local administration of a botulinum neurotoxin to the frontalis, corrugator, procereus, occipitalis, temporalis, trapezius and cervical paraspinal muscles.

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: The invention provides methods for treating primary disorders of mood and affect, including depressive disorders, anxiety and sleep disorders and CNS disorders comprising the administration of a neurotoxin.

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: Methods and compositions pertaining to botulinum neurotoxin (BoNT) light chain epitopes are provided. In particular, the methods and compositions relate to the use of real and mimetic BoNT light chain epitopes for generating an immune response in a subject, and for immunization against BoNT toxicity. Methods and compositions for detecting, isolating, and purifying BoNT epitopes and anti-BoNT antibodies are also provided.

Abstract: A mucosal vaccine for the prevention or treatment of microbial infections is described that is capable of inducing vaccine antigen-specific immune responses in an organism without the addition of a mucosal adjuvant. The mucosal vaccine comprises a composite of a nanogel comprising a hydrophilic polysaccharide having a cationic functional group and a hydrophobic cholesterol added thereto as a side chain and a vaccine antigen. The vaccine is administered via a mucosal route.

Abstract: A syringe containing a compressible porous matrix, which compressible porous matrix has in it a pharmaceutical in a soluble glass, Methods of producing and using the syringe, and compressible porous matrix inserts for insertion into a syringe barrel are also provided.

Abstract: Fraction A of Quil A can be used together with at least one other adjuvant for the preparation of an adjuvant composition, where the included adjuvant components act synergistically to enhance level of immune response and have synergistic immunomodulating activity on the co-administered antigens or immunogens. Other adjuvants can comprise saponins, naturally occurring, synthetic or semisynthetic saponin molecules; e.g. saponins and saponin fractions from Quil A, cell wall skeleton, block polymers, TDM, lipopeptides, LPS and LPS-derivatives, Lipid A from different bacterial species and derivatives thereof, e.g., monophosphoryl lipid A, CpG variants, CT and LT or fractions thereof.

Abstract: The present invention provides methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods of inducing an immune response against one or a plurality of pathogens (e.g., vaccinia virus, H5N1 influenza virus, Bacillus anthracis, C. botulinum, Y. pestis, Hepatitis B, and/or HIV, etc.) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., immunogenic composition comprising nanoemulsion and one or a plurality of pathogens (e.g., inactivated by the nanoemulsion) and/or pathogen products and/or pathogen components). 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.

Abstract: The invention relates to a method for determining the quantity of pre-synaptic neuromuscular blocking substance (notably botulinum toxin) contained in a sample. In one aspects, the method comprises the following steps: (i) determining the minimum voltage Vm needed to induce the contraction of muscle tissue, said muscle tissue being connected to an electrical stimulator through a motor nerve and preferably immersed in an oxygenated physiological buffer containing glucose; (ii) adding the sample containing the pre-synaptic neuromuscular blocking substance; (iii) electrically stimulating, at a voltage at least equal to Vm, the muscle tissue at certain time intervals; (iv) comparing the effect induced by the sample to the effect induced by a reference substance and thereby determining the quantity of the pre-synaptic neuromuscular blocking substance in the sample.

Abstract: Methods for treating skin disorders by local administration of a Clostridial toxin, such as a botulinum toxin, to a patient with a skin disorder.

Abstract: Disclosed are novel methods and compositions for combating diseases characterized by deposition of amyloid. The methods generally rely on immunization against amyloid precursor protein (APP) or beta amyloid (A?). Immunization is preferably effected by administration of analogs of autologous APP or A?, said analogs being capable of inducing antibody production against the autologous amyloidogenic polypeptides. Especially preferred as an immunogen is autologous A? which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes. Such methods and means include methods for the preparation of analogs and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

Abstract: Methods for treating a pressure sore or for preventing development of a pressure sore by local administration of a Clostridial toxin, such as a botulinum neurotoxin, to a pressure sore or to a pressure point, or to the vicinity thereof.

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

Abstract: In one aspect, the invention provides a DNA molecule. The DNA molecule includes a nucleotide sequence that encodes the receptor-binding domain of Clostridium difficile toxin A or toxin B in which at least about 10% of the in-frame codons for each amino acid residue has a higher percentage use in the human genome than the corresponding in-frame codons of C. difficile toxin A or toxin B having a known sequence. Methods for generating antibodies to Clostridium difficile toxin A or toxin B, methods for reducing the risk of a C. difficile infection, and methods for treating a C. difficile are also provided.

Abstract: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilized using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilization of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from both serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.

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

Abstract: The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system and bone cells.

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.