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: 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: 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: This invention relates to compositions including Clostridium difficile toxins and/or toxoids and corresponding methods. The compositions of the invention include one or more excipients that increase stability and/or decrease aggregation of the toxins.

Abstract: The specification discloses modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; polynucleotide molecules encoding modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; and method of producing modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain.

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

Abstract: The invention relates to a complexing system comprising two polypeptide helices derived from a SNAP protein; one polypeptide helix derived from syntaxin; one polypeptide helix derived from synaptobrevin or a homolog thereof; and one or more cargo moieties attached to the polypeptide helices, wherein the four polypeptide helices can form a stable SNARE complex. The invention also relates to a method of producing the complexing system and the use of the complexing system.

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: The invention relates to polypeptide carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines are particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: This invention relates to botulinum toxin formulations that are stabilized without the use of any proteinaceous excipients. The invention also relates to methods of preparing and using such botulinum toxin formulations.

Abstract: A method for treating a mammary gland disorder, including hyperplastic, hypertonic, cystic and/or neoplastic mammary gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted breast tissue.

Abstract: A method of temporarily elevating the eyebrow position and softening undesirable glabellar muscle activity to affect a more desirable appearance. In a broad aspect the invention comprises injecting small quantities of botulinum toxin (BTX) equivalent in activity to 0.001 to 1.0 Units of botulinum toxin A, dissolved in 10 to 50 microliters microdroplets of injectable saline carrier, and injected 0.5 to 1.0 millimeters below the skin surface to treat the septal and orbital orbicularis oculi muscles, on each side of a patient's face. In sufficient numbers, injected microdroplets of BTX are able to selectively weaken these muscles. This method preferably also includes using microdroplets of BTX to treat: a) the depressor supercilii muscle, on each side; b) the procerus muscle; c) the corrugator supercilii muscle, on each side; and d) the inferior limit of the frontalis muscle where it meets the superior aspect of the orbital portion of the orbicularis oculi muscle.

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

Abstract: The invention provides methods for treating epilepsy, mental disorders and/or deficits in sensory organ by administering to patients therapeutically effective amounts of AMPA receptor antagonists in combination with one or more other active ingredients useful for treating epilepsy, mental disorders and/or deficits in sensory organ. The invention also provides pharmaceutical combinations, kits, and pharmaceutical compositions comprising therapeutically effective amounts of AMPA receptor antagonists, and optionally, one or more other active ingredients that are useful for treating epilepsy, mental disorders and/or deficits in sensory organ.

Abstract: An injectable amino-acid composition acts naturally to fuel collagen synthesis, which retards aging and helps to clear cellular decay while accelerating the cell division that promotes healthy, younger looking skin. The amino-acid composition includes carnosine. The composition is injected into the dermis of patients. The composition can be used in conjunction with botulinum toxin and fillers to enhance their effectiveness and extend their usefulness.

Abstract: The invention provides compositions comprising an antigenic botulinum neurotoxin serotype E (BoNT/E) peptide, wherein the peptide has improved solubility and thus improved ability to stimulate an immune response against BoNT/E holotoxin. The composition may be used as part of a multivalent vaccine regimen via coordinated use with non-serotype E BoNT peptides, such as one or more BoNT/A and/or BoNT/B peptides. It further provides processes for manufacturing said BoNT/E peptide. It also provides methods of stimulating an immune response in a mammal, comprising administering to the mammal an effective amount of a BoNT/E and optionally one or more non-serotype E BoNT peptides such as one or more BoNT/A and/or BoNT/B peptides.

Abstract: A method for treating a mammary gland disorder, including hyperplastic, hypertonic, cystic and/or neoplastic mammary gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted breast tissue.

Abstract: The invention relates to the use of a pre-synaptic neuromuscular blocking substance for preparing a medicament intended to treat a gland, organ or duct obstructed by a naturally formed stone. This method can be applied notably for salivary gland, gall bladder, kidney or pancreas stones.

Abstract: Methods for treating diverse cancers by local administration of a botulinum toxin to or to the vicinity of the cancer.

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

Abstract: The present invention relates to new 1-methylpyrazole modulators of substance P release, calcitonin gene-related peptide activity, adrenergic receptor activity, and/or 5-HT receptor activity, pharmaceutical compositions thereof, and methods of use thereof.

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: Methods and compositions for immediately immunizing an individual against any molecule or compound are provided. The present invention is directed to an immunity linker with at least two sites; (1) at least one first binding site that binds to an immune response component in an individual, and (2) at least one second binding site that binds specifically to a desired compound or molecule, the target. The second binding sites are preferably thiolated aptamers that have the benefit of increased stability, resistance to degradation and longer circulating half life. Methods of making and using pharmaceutical compositions including immunity linker molecules having a thiolated aptamer are also provided.

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: The present invention includes a method of treating pain caused by neuralgia comprising administering botulinum toxin to an afflicted area of a patient. The pain may be caused by trigeminal neuralgia or be associated with dental extraction or reconstruction, and may be facial pain. The neuralgia may be associated with compressive forces on a sensory nerve, intrinsic nerve damage, demyelinating disease, a genetic disorder, a metabolic disorder, central neurologic vascular disease, or trauma. The present invention also includes a method of treating post-operative incisional wound pain comprising administering botulinum toxin to an afflicted area of a patient.

Abstract: The present composition combines an RNAIII-inhibiting peptide (RIP) with an antimicrobial peptide, such as a cathelicidin, that is capable of binding and neutralizing lipidic and polyanionic components of bacterial cell envelope. In another embodiment, the RIP is combined with an antibiotic, with or without an antimicrobial peptide. The present composition is advantageously used in a method of treatment of bacterial sepsis.

Abstract: The present invention relates to methods for enhancing the therapeutic effects of a neurotoxin, e.g., a botulinum toxin, where the methods comprise a “wash-down” (e.g., a decreased intake) of a current pain medication and an administration of a neurotoxin. In some embodiments, the present inventions relates to methods for enhancing the therapeutic effects of a neurotoxin for treating pain, e.g., headache pain.

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: 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: Botulinum toxin, or other neuromuscular inhibitors, injected into the lower leg muscle of infants, less than a year old, with idiopathic clubfoot is shown to be an effective therapy in correcting this physical deformity. Following a protocol of manipulations, castings, and injections, clubfoot is effectively treated, and surgical treatment procedures can be avoided.

Abstract: Herein disclosed are methods for treating headache, such as a chronic migraine for example, by administration of botulinum toxin to fixed specific locations of a patient at a fixed amount, as well as optionally administering additional botulinum toxin to a subset of the fixed specific locations of a patient to treat the headache.

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 is directed to multivalent Clostridial toxin comprising more than one binding domain directed to a cell surface molecule of a target cell. Such modified toxins 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: Method for alleviating testicular pain in a patient in need thereof. The method can comprise the step of locally administering a neurotoxin (e.g., a botulinum toxin) to at least one anatomical site selected from the group consisting of a testicle and a tissue associated with the testicle of the patient.

Abstract: The present invention discloses attenuated Clostridium perfringens organisms that express a substantially nontoxic alpha-toxin. The expressed alpha-toxin is a deletion mutein that relative to the alpha-toxin of the mature alpha-toxin of Clostridium perfringens strain 13, is missing at least nine consecutive amino acid residues including His68. The present invention also discloses attenuated organisms that encode the muteins, as well as the use of such attenuated organisms as vaccines.

Abstract: A composition for treating a subject is provided. The composition includes a pentameric secretory IgM therapeutic. Formulating agents are mixed with the pentameric secretory IgM 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 that the modification of pentameric IgM with secretory component to form a pentameric secretory IgM therapeutic. The pentameric secretory IgM 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 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: A Clostridial toxin pharmaceutical composition comprising a Clostridial toxin, such as a botulinum toxin and a polysaccharide, such as a hydroxyethyl starch, wherein the pharmaceutical composition has a reduced toxicity. The Clostridial toxin pharmaceutical composition can be essentially free of any blood or serum derived proteins, filtrates or fractions.

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 a method of treating a cancer using a neurotoxin, preferably Botulinum toxin (“BTX”). The application of a neurotoxin around a cancer acts to decrease the contractile forces of the muscles surrounding a neoplasm which normally squeeze cancer cells through efferent channels leaving the cancer vicinity to distant sites. Also, the application of the toxin at sites distant from the cancer enhances cellular and humoral immunologic functions which further contributes to cancer cell death and spread. Following administration of botulinum toxin around and distant to a cancer, it is noticed that local, regional, and distant spread is reduced or eliminated. Immunomodulation with botulinum toxin is also valuable in treating other disease that may or may not be associated with cancers, such as viral-induced growths, viral conditions, fungal disease, chronic wounds, graft versus host disease, autoimmune disease, and HIV.

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: 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: 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: The present invention provides a method of treating a neoplasm using a neurotoxin, preferably botulinum toxin. Neurotoxin administered around a neoplasm acts to decrease the contractile forces of the muscles surrounding a neoplasm which normally squeeze neoplastic cells through efferent channels leaving the neoplasm to distant sites. The present invention also provides a method of administering botulinum toxin at sites distant from the neoplasm, thereby enhancing cellular and humoral immunologic functions, which further contribute to neoplastic cell death. Following administration of botulinum toxin around or distant to a neoplasm as described herein, local, regional, and distant spread of neoplastic cells is reduced or eliminated. Immunomodulation with botulinum toxin is also valuable in treating other diseases that may or may not be associated with cancers, such as viral-induced growths, viral conditions, fungal disease, chronic wounds, graft versus host disease, autoimmune disease, and HIV.

Abstract: Botulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the sphenopalatine ganglion. Exemplary delivery is carried out by way of injection.

Abstract: 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: A method of facilitating intracellular uptake or transcellular transport of cargo comprising: contacting target cells with a composition comprising an effective amount of cargo incorporated in a nanocarrier having a surface, wherein the nanocarrier surface comprises integrin-specific ligands having a surface density of approximately 5 to 50,000 integrin-specific ligands per ?m2, and maintaining contact between the composition and the target cells for a period of time sufficient to permit intracellular uptake or transcellular transport of the cargo.

Abstract: A method of improving muscle movement, contraction and/or tone in an animal is provided. The method is carried out by administering tetanus toxin to the muscle of an animal has already been vaccinated against tetanus toxin. The toxin is administered in an amount sufficient to improve muscle movement, contraction and/or tone. The method may be used to treat patients with impaired muscle function, e.g due to compromise of the central nervous system (for example, due to stroke or spinal cord injury) or due to muscle atrophy (for example, due to immobilization after an injury). A regimen for dosage escalation of tetanus toxin is also provided.

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