Abstract: The present invention relates to new pharmaceutical compositions comprising benzoquinoline compounds, and methods to inhibit vesicular monoamine transporter 2 (VMAT2) activity in a subject for the treatment of chronic hyperkinetic movement disorders.

Abstract: The present invention relates to a pharmaceutical composition for treating a foot pain disease, including botulinum toxin and hyaluronic acid, and a foot pain disease treatment method using the same. More specifically, the composition according to the present invention can exhibit a synergistic action of increasing both anti-inflammatory and anti-pain activity through an inflammation-inhibiting effect on a foot pain disease such as pain arising from plantar fasciitis, foot fasciitis, Achilles tendon damage, flat feet, diabetes, and gout. Thus, the composition according to the present invention is expected to be able to be usefully used subcutaneously in the foot as a liquid injection agent that exhibits an effect of treating or alleviating a foot pain disease.

Abstract: Rapid, animal protein free, chromatographic processes and systems for obtaining high potency, high yield botulinum neurotoxin for research, therapeutic and cosmetic use.

Abstract: A proteolytically active polypeptide comprising an acid sequence having at least 50% sequence identity with the sequence of SEQ ID NO: 1 with the proviso that the polypeptide does not comprise the amino acid sequence of SEQ ID NO: 1. A nucleic acid encoding the polypeptide. An antibody specifically binding to the polypeptide. A method for the manufacture of a proteolytically processed polypeptide comprising contacting a first polypeptide having at least 50% sequence identity to SEQ ID NO: 1 with a second polypeptide that is susceptible to proteolysis by said first polypeptide.

Abstract: A method of treating ASD (autism) in a patient in need thereof comprises administering a botulinum toxin to the patient. The botulinum toxin may be administered by subcutaneous/intradermal injection. The subcutaneous/intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, and a sacral nerve of the patient. In infants or toddlers—from about 1 to 5 year old, it is used to prevent or minimize damage to the developing brain; in older children and adult Autism Spectrum Disorder (ASD) patients, it will be used to reduce or eliminate their symptoms.

Abstract: Methods are disclosed for treating post traumatic stress disorder (PTSD) in a subject. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilii and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilii and/or a procerus muscle in the subject, thereby treating PTSD. The neurotoxin can be Botulinum toxin A, such as at a dose of about 20 to about 50 units of Botulinum toxin A.

Abstract: The present invention relates to methods for treating diseases and disorders by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition is devoid of any other protein of the Clostridium botulinum toxin complex and wherein the composition is administered at short intervals and/or in high doses.

Abstract: The present invention discloses an extended release oral liquid pharmaceutical composition comprising eslicarbazepine or its pharmaceutically acceptable esters, salts, solvates, polymorphs, enantiomers or mixtures thereof in a pharmaceutically acceptable carrier. The extended release liquid compositions are in the form of ready-to-use liquid compositions or reconstituted liquid compositions. It also relates to processes for the preparation of said extended release liquid compositions. The prior art discloses immediate release oral liquid dosage form. The prepared novel test formulations exhibited desired pharmaceutical technical attributes.

Abstract: Provided are processes for the prevention or treatment of infection by SARS-CoV-2. Some aspects provide administration of a sphingoid compound, optionally sphingosine, an active ingredient that activates generation of a sphingoid base, optionally of sphingosine; or an active agent that inhibits the degradation of a sphingoid base, optionally of sphingosine, to a subject such as a human. By increasing the local concentration of sphingosine in a subject or an area of a subject to which the composition is administered such as the airways, nose or interior of the nose or portion thereof, the ability or SARS-CoV-2 to infect the subject or cells thereof is reduced thereby treating of preventing infection by the virus.

Abstract: A stable liquid composition comprising a botulinum toxin as an active ingredient is described, which is ready-to-use without the need for a reconstitution process, and thus, it is possible to improve user's convenience, and reduce a deviation of botulinum toxin activity due to dilution errors in the reconstitution process. Further, the liquid composition efficiently prevents the botulinum toxin from aggregating even at a low botulinum toxin concentration to thereby have extremely excellent storage stability, and efficiently prevents adsorption of the botulinum toxin to a container, thereby constantly maintaining an activity of the botulinum toxin for each batch or for each liquid vial.

Abstract: A method for treating chronic obstructive pulmonary disease (COPD) in a patient in need thereof comprises administering botulinum toxin to the patient. The botulinum toxin may be administered by subcutaneous or intradermal injection. The subcutaneous or intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, and/or a sacral nerve of the patient.

Abstract: A method for treating asthma in a patient in need thereof comprises administering botulinum toxin to the patient. The botulinum toxin may be administered by subcutaneous or intradermal injection. The subcutaneous or intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, a sacral nerve, or a combination thereof of the patient.

Abstract: The present invention is directed to topical compositions containing botulinum toxin, benzoyl peroxide, salicylic acid or a mixture of benzoyl peroxide and salicylic acid. The present invention is further directed to methods of treating acne or reducing rhytides with these topical compositions.

Abstract: The present specification discloses a retargeted endopeptidase pharmaceutical wherein the activity has been determined by the methods disclosed.

Abstract: Method for preparing botulinum neurotoxin and nanoparticle thereof are provided. The method includes fermenting bacteria Clostridium botulinum in a fermentation media free of animal-derived ingredients and contacting the fermentation media with an anion exchange media slurry and obtaining a supernatant including the botulinum neurotoxin by centrifugation. The method further includes dialyzing the supernatant and collecting a dialyzed solution including the botulinum neurotoxin, contacting the dialyzed solution with an anion exchange chromatography column, contacting an elute collected from the anion exchange chromatography column with a cation exchange chromatography column, and collecting an elute. The nanoparticle includes multi-layer including an innermost water phase core including biomolecules encapsulated by an oil phase layer, thereby forming a water-in-oil structure, water phase layers; oil phase layers; and an outmost cream layer.

Abstract: One subject of the present invention is the use of a combination of a polyol (i) consisting of 12 carbon atoms and of a polyol (ii) consisting of 4 to 6 carbon atoms, as protein stabilizer. Another subject of the present invention is protein compositions comprising such a combination. A final subject of the present invention is a process for preparing protein compositions using such a combination.

Abstract: The present invention relates to methods for treating diseases and disorders by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition is devoid of any other protein of the Clostridium botulinum toxin complex and wherein the composition is administered at short intervals and/or in high doses.

Abstract: Methods for a cell-based assay for Botulinum neurotoxin are provided in which a transfected cell that produces a reporting peptide is contacted with a Botulinum neurotoxin in media having a sub-physiological osmolarity and a temperature that is above physiological temperature. This combination provides an unexpected synergistic effect in reducing the EC50 of the cell-based assay relative to an analogous cell-based assay performed at physiological osmolarity and temperature.

Abstract: A method of tolerance to narcotics in a patient in need thereof comprises administering a botulinum toxin to the patient. The botulinum toxin is selected from the group consisting of botulinum toxin type A, botulinum toxin type B, botulinum toxin type C, botulinum toxin type D, botulinum toxin type E, botulinum toxin type F and botulinum toxin type G, a fragment thereof, a hybrid thereof, a chimera thereof, and a combination thereof. The botulinum toxin may be administered by subcutaneous/intradermal injection. The subcutaneous/intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, and a sacral nerve of the patient. The therapeutically effective amount of the botulinum toxin administered is between about 1 unit and about 150 units.

Abstract: A method of treating ASD (autism) in a patient in need thereof comprises administering a botulinum toxin to the patient. The botulinum toxin may be administered by subcutaneous/intradermal injection. The subcutaneous/intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, and a sacral nerve of the patient. In infants or toddlers—from about 1 to 5 year olds, it is used to prevent or minimize damage to the developing brain; in older children and adult Autism Spectrum Disorder (ASD) patients, it will be used to reduce or eliminate their symptoms.

Abstract: The present invention relates to the construction of a new class of Targeted Secretion Inhibitors (TSIs), which comprise a non-cytotoxic protease, translocation peptide and a targeting moiety peptide, wherein the targeting moiety peptide has a free N-terminal domain and a free C-terminal domain; to a single-chain fusion protein precursor thereof, and to a method of activating said single-chain fusion protein precursor.

Abstract: The present invention relates to a process for preparing a highly pure neurotoxic component of a botulinum toxin by cultivating Clostridium botulinum under conditions that allow production of a botulinum toxin, and isolating the neurotoxic component from the botulinum toxin. In addition, the present invention relates to a highly pure neurotoxic component of a botulinum toxin obtainable by the process of the present invention and uses thereof.

Abstract: Successful application of an engineered protein as therapeutics or in other industries would require the protein to have good expression level, good biophysical properties and often desired affinity to its target. The present invention provides s method of screening large numbers of protein candidates (PCs) in all three aspects simultaneously. PCs are fused to a protein anchor, which is captured by the target/antigen. The captured PCs are evaluated for their expression levels, biophysical properties and affinities using conventional methods.

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

Abstract: Plantar Heel Pain Syndrome can be of one or more etiologies and symptoms which refutes the mistaken tendency to categorize all plantar heel pain singularly as either plantar fasciitis or fasciosis. Recognizing that there is likely an interplay of inflammatory, degenerative and neuropathic etiologic conditions of this often-difficult malady to treat, a novel injection paradigm of botulinum toxin is explored in the treatment of 4 distinct presentations of Plantar Heel Pain Syndrome with promising results.

Abstract: The present invention refers to new glycoconjugate antigens expressing built-in multiple epitopes and to polyvalent glycoconjugate vaccines intended for the protection of mammalians, and particularly for the protection of the human population from enteropathogenic bacteria, such as the Gram-positive anaerobic bacterium Clostridium difficile and the Gram-negative bacteria Salmonella typhi, Escherichia Coli, Vibrio Cholerae, Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis, Salmonella paratyphi A, Shigella sonnei, Shigella dysenteriae, Salmonella cholerasuis, Klebsiella, Enterobacter, Pseudomonas aeruginosa and/or from viral gastrointestinal infections due to human noroviruses.

Abstract: Rapid, animal protein free, chromatographic processes and systems for obtaining high potency, high yield botulinum neurotoxin for research, therapeutic and cosmetic use.

Abstract: A method is disclosed for blocking or reducing a 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 present specification discloses a retargeted endopeptidase pharmaceutical wherein the activity has been determined by the methods disclosed.

Abstract: A preparation containing a statin-encapsulated nanoparticle obtained by encapsulating statin in a nanoparticle containing a bioabsorbable polymer is disclosed. The nanoparticle has a number average particle diameter of less than 1000 nm. The preparation is used to enhance the function of a stem cell. A stem cell with an enhanced function is disclosed. The stem cell takes up and contains the statin-encapsulated nanoparticle.

Abstract: Embodiments of the present disclosure include vaccine compositions comprising a TcdB toxin or toxoid derived therefrom. The TcdB toxin may be derived from a hypervirulent strain of C. difficile. A further embodiment is directed to a method of conferring an active immunity against a C. difficile infection in a subject by administering the vaccine composition to the subject.

Abstract: A method for treating abnormalities of the first metatarsophalangeal joint of the foot of a mammal includes administering an amount of neuromuscular toxin effective to treat the abnormalities via intramuscular injection to the extensor hallucis brevis muscle of the affected foot of the mammal. Further effectiveness can be achieved by also administering the toxin to adductor hallucis and/or the flexor hallucis brevis (lateral head) muscles of the affected foot. One of the abnormalities to be treated is hallux abductovalgus, commonly referred to as a bunion.

Abstract: Methods for modifying progression of osteoarthritis by local administration of a clostridial derivative, such as a botulinum toxin, to an arthritis-affected site are disclosed herein.

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: Described herein are methods for enhancing engraftment of hematopoietic stem and progenitor cells using compounds identified using a zebrafish model of hematopoietic cell engraftment. The compounds can be used to treat hematopoietic stem cells ex vivo prior to transplantation of the cells. Alternatively, the compounds can be administered to an individual undergoing cell transplantation.

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

Abstract: The invention provides compositions and methods for treating incontinence associated with sexual activity.

Abstract: An extended duration pharmaceutical composition including a botulinum neurotoxin, an adhesive agent, and a stabilizing macromolecule is disclosed. 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: Novel inhibitors of DXP synthase and methods of use thereof are disclosed.

Abstract: The present invention relates to a method of decreasing cholesterol or low density lipid protein in a subject in need thereof comprising: administering to said subject a pharmaceutically effective amount of a composition comprising dextromethorphan. The present invention also relates to a method of treating a subject suffered from bipolar II disorder, comprising administering to said subject a therapeutically effective amount of valproic acid and a combination of dextromethorphan and memantine, wherein the dose of dextromethorphan or memantine is a low dose not sufficient to work as a N-methyl-D-aspartate (NMDA) receptor antagonist. The present invention further relates to a composition for treating bipolar II disorder, which comprises valproic acid and a combination of dextromethorphan and memantine, wherein the dose of dextromethorphan or memantine is a low dose not sufficient to work as a N-methyl-D-aspartate (NMDA) receptor antagonist.

Abstract: The present invention relates to a medium composition for production of botulinum toxin and, more particularly, to a medium composition for culture of Clostridium sp. capable of producing botulinum toxin. The medium composition of the present invention comprises at least one plant-derived peptone selected from the group consisting of a garden pea hydrolysate, a cotton seed hydrolysate and a wheat gluten hydrolysate. When the medium according to the present invention, which contains plant-derived peptones and minerals, is used for culture of Clostridium botulinum, the growth rate of the bacterium in the medium is about 1.5-2 times higher than that in the medium that is in current use. In addition, when botulinum toxin is produced by culturing the bacterium in the medium, infection with transmissible spongiform encephalopathy (TSE) or the like can be prevented by blocking introduction of animal-derived components.

Abstract: Clostridium difficile is a leading cause of antibiotic-associated infection in hospitals worldwide. There is a need for a vaccine to Clostridium difficile that can target toxic proteins, or that can elicit adequate immunity to prevent infection or reduce the severity of infection. Modified Clostridium difficile toxin A and B (TcdA and TcdB) proteins are described herein, which comprise mutations that reduce toxin A and B toxicity compared to the native toxin. The proteins described are highly similar to the native toxin of Clostridium difficile, but toxicity is reduced.

Abstract: The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.

Abstract: The present invention provides a composition for facial contouring, comprising a mixture of botulinum toxin and air, and a method of facial contouring using the same. When the mixture of botulinum toxin and air is injected into an SMAS layer, the mixture strengthens the SMAS layer and draws back the galea aponeurotica to effectively lift up the face or change the facial contour, thus effectively enhancing the effect of facial contouring.

Abstract: The described embodiments relate to methods, systems and uses for therapeutic ultrasound, and in particular, to methods, systems and uses for therapeutic ultrasound for treating or alleviating eye conditions. The described embodiments relate to methods, systems and uses that involve an ultrasound device configured for treatment of an eye condition, where the device comprises at least one ultrasound transducer for coupling to at least a portion of an eyelid to supply ultrasound waves to an area proximate to the portion of the eyelid according to treatment parameters, wherein the treatment parameters comprise a treatment frequency and a treatment period.

Abstract: Methods for treating premature ejaculation and prolongation of climax time in a patient in need thereof by local administration of a Clostridial neurotoxin, such as a botulinum toxin, are provided.

Abstract: A cell based assay for detection for protease activity is disclosed. In the assay a cell is engineered to express a protease substrate with at least one label, preferably on its C-terminus. Cleavage of the substrate by the protease that recognizes it results in a C-terminal fragment and a N-terminal fragment, where the fragment having the label is subject to ubiquitin proteasome degradation. The assay measures the disappearance of the label due to degradation of the fragment to which it is attached. A cell free assay is also described for detection of protease activity. In the cell free assay, the protease substrate is expressed in a solution that includes the elements of the ubiquitin proteasome pathway for degradation of the fragment. The assay measures the disappearance of the label attached to the fragment that results from cleavage by the protease.

Abstract: There is provided an epsilon toxin epitope polypeptide comprising a sequence of at least 10 contiguous amino acids from SEQ ID NO:3, the sequence comprising a mutation of at least one tyrosine residue compared to the equivalent sequence in SEQ ID NO:3, the polypeptide being capable of binding an antibody which binds to SEQ ID NO:5 and having reduced toxicity compared with the toxicity of SEQ ID NO:5. The polypeptide is useful in a method of vaccinating a subject against developing a disease caused by clostridium perfringens and/or caused by (or associated with the presence of) active epsilon toxin.

Abstract: The present invention relates to methods for treating diseases and disorders by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition is devoid of any other protein of the Clostridium botulinum toxin complex and wherein the composition is administered at short intervals and/or in high doses.

Abstract: One aspect of the present disclosure relates to a treatment probe comprising an elongated body member and a needle portion. The elongated body member can have a proximal end portion and a distal end portion. The needle portion can be connected to the distal end portion. The needle portion can include at least one electrode and at least one fluid port. The at least one electrode and the at least one fluid port can be configured to deliver electrical energy and a tumescent fluid, respectively, so that superficial tissue planes overlying a target nerve are protected from inadvertent heat damage as a result of application of electrical energy to a target nerve.