42 results about "Botulinum neurotoxin" patented technology

The present invention relates to aqueous saline solutions comprising dantrolene and optionally at least one additional active ingredient, such as botulinum neurotoxin, and their use for various therapeutic and / or aesthetic purposes. The solutions can be administered in any suitable manner, but have the advantage of being particularly well-suited for intramuscular injection.

The present invention relates to a method for preparing a composition comprising (A) a cross-linked material comprising one or more polysaccharide moieties covalently cross-linked with each other through ester bonds using one or more triazine-based activating agents, and (B) at least one botulinum toxin. Furthermore, the present invention relates to the composition obtainable by said method, and therapeutic and aesthetic uses of such composition.

The present invention relates to a novel alternative material to botulinum neurotoxin and a method for producing the same, specifically, to a myricetin acetyl derivative that has a dramatically improved stability of the substance, including stability in the body, and has the ability to inhibit the formation of the SNARE complex and thereby inhibit acetylcholine secretion, and a method for producing the same.

The present invention relates to methods of treating headache disorders with Botulinum neurotoxin type A (BoNT / A).

The present invention relates to aqueous compositions comprising dantrolene and optionally also at least one additional active principle, such as botulinum neurotoxin, and their use for various therapeutic and / or aesthetic / cosmetic purposes. The compositions can be administered in any suitable way but are advantageous in that they are particularly well adapted to intramuscular injection, subcutaneous injection and / or intradermal injection.

Products, pharmaceutical compositions, methods of use, and kits are provided for treating a patient suffering from botulinum neurotoxin intoxication. Featured are single-domain variable heavy-chain (VHH) polypeptides (antibodies) that target and neutralize the light chain (LC) protease domains of botulinum neurotoxin (BoNT), i.e., BoNT LC / A and BoNT LC / B, and that advantageously provide late and post-exposure therapy for botulism patients. The LC / A toxin-binding and LC / B toxin-binding VHH polypeptides, which can be recombinantly produced, specifically bind to the LCs of the botulinum neurotoxins to inhibit toxin activity and treat intoxication.

Disclosed herein are methods of treatment of moderate to severe and very severe glabellar lines and lateral canthal lines using liquid botulinum neurotoxin compositions. Also disclosed are liquid compositions of botulinum neurotoxin.

Form-specific cell based assays for the characterization of Clostridia botulinum neurotoxins and genetically modified cells utilized in such assays are described. Such assays and genetically modified cells can discriminate between complexed and non-complexed forms of botulinum neurotoxin having the same serotype, for example serotype E. Methods are also provided for generating and identifying cell lines that can be utilized in such cell based assays.

The present invention is directed inter alia to the treatment of pain. For example, there is provided a chimeric clostridial neurotoxin for use in treating pain by inhibiting the release of a pain mediator from a neuron comprising an Aδ nerve fiber or a C nerve fiber, wherein the chimeric clostridial neurotoxin binds to the neuron comprising the Aδ nerve fiber or the C nerve fiber, respectively, and wherein the chimeric clostridial neurotoxin comprises a botulinum neurotoxin A (BoNT / A) light-chain and translocation domain (HN domain), and a BoNT / B receptor binding domain (HC domain). Also provided are methods, uses, kits, and unit dosage forms.

Provided are a composition for stabilizing botulinum neurotoxin, a botulinum neurotoxin formulation including the same, and a polypeptide for use therein.

Methods for the isolation and purification of a botulinum neurotoxin protein (BONT) or a polypeptide comprising a BONT receptor-binding domain from a solution are disclosed here. The method comprises contacting the solution containing the protein or polypeptide with a matrix bound to it by a non-toxic non-hemagglutinin (NTNHA) under appropriate conditions for binding, washing the matrix to remove unbound materials, and eluting the protein or polypeptide with a solution that dissociates the bound protein from the NTNHA. Appropriate conditions for binding are a pH less than 7.5 (e.g., 6). Appropriate conditions for dissociation are a pH greater than or equal to 7.5 (e.g., 8). Specific compositions for the methods are also described.

The present invention is directed inter alia to the treatment of pain. For example, there is provided a chimeric clostridial neurotoxin for use in treating pain by inhibiting release of a pain mediator from a neuron comprising an Aδ nerve fiber or a C nerve fiber, wherein the chimeric clostridial neurotoxin binds to the neuron comprising the Aδ nerve fiber or the C nerve fiber, respectively, and wherein the chimeric clostridial neurotoxin comprises a botulinum neurotoxin A (BoNT / A) light-chain and translocation domain (HN domain), and a BoNT / B receptor binding domain (HC domain). Also provided are methods, uses, kits, and unit dosage forms.

The invention relates to the technical field of bioengineering, in particular to recombinant botulinum toxin and a preparation method thereof. The nucleotide sequence of the coding gene of the recombinant botulinum neurotoxin is as shown in SEQ ID NO: 1; the amino acid sequence of the toxin is as shown in SEQ ID NO: 2. The clostridium botulinum neurotoxin sequence optimization method realizes soluble expression of clostridium botulinum neurotoxin protein by escherichia coli; meanwhile, the purity of the botulinum neurotoxin protein is improved by a novel purification process technology, and the double-chain botulinum neurotoxin with relatively high biological activity is obtained; according to the method, the process operation steps of the botulinum neurotoxin are reduced, the biological safety risk is remarkably reduced, industrial production amplification of the botulinum neurotoxin is facilitated, a solid foundation is provided for large-scale production of the botulinum neurotoxin, and the method can be effectively applied to preparation of medical, beauty and health-care products.

A botulinum neurotoxin serotype E (BoNT / E) for use in treating a disorder or a cosmetic condition, wherein the BoNT / E provides a maximum inhibition of neurotransmitter secretion from a target cell or tissue 13 days or less after administration to a human subject and the inhibition is reduced but is greater than 25% at day 14 following administration. A method for treating a disorder or a cosmetic condition, the method comprising administering the aforementioned BoNT / E.

The present invention is directed to a modified botulinum neurotoxin A (BoNT / A) for use in treating a facial dystonia, including blepharospasm and hemifacial spasm, wherein the unit dose of the modified BoNT / A is at least 240 pg of modified BoNT / A, wherein the modified BoNT / A is administered by intramuscular injection to an affected muscle of a subject, wherein the total dose administered during the treatment is greater than 24,000 pg and up to 82,500 pg (e.g. up to 75,000 pg) of the modified BoNT / A, and wherein the modified BoNT / A comprises a BoNT / A light-chain and translocation domain (HN), and a BoNT / B receptor binding domain (HC domain).

This invention provides libraries of Botulinum neurotoxin A (BoNT / A) protease variants for stepwise evolution of the enzyme to generate BoNT / A variants that can specifically cleave a desired cleavage site in a target protein. Related methods for performing stepwise evolution of BoNT / A with the BoNT / A variant libraries and simultaneous stepwise evolution of a desired substrate sequence in a target protein are also provided by the disclosure. Additionally provided in the disclosure are specifically evolved BoNT / A variant enzymes and conjugate proteins that specifically degrade intrinsically disordered proteins (IDPs) that are involved in human deceases, e.g., a-Synuclein. Polynucleotide sequences encoding the engineered BoNT / A proteases, expression vectors and related pharmaceutical compositions are also provided in this disclosure. Further encompassed by the invention are therapeutic methods that utilize the engineered BoNT / A enzymes in the treatment of various synucleinopathies.

The present invention discloses a detection method and application for type B botulinum neurotoxin. The method of the present invention has a short detection time and is highly sensitive as a qualitative detection method, reaching the picogram level, and has obvious advantages in detecting trace toxin samples. Compared with the animal method using antiserum detection, the use of monoclonal antibodies has high detection specificity, which is conducive to accurate decision-making whether it is used for scientific research detection and food hygiene inspection, and has a small error compared to the animal method. In addition, the characteristic peak of the botulinum neurotoxin double antibody sandwich reaction produced by the present invention can be used for the stability detection of botulinum neurotoxin, and plays a role that cannot be replaced by other methods in the production of botulinum toxin products, quality control, new product development, quality control and monitoring of calibration standards, and market supervision. Therefore, the present invention can be used to guide the establishment of toxin immunoassay standard substances and promote capillary immunoassay technology to become a new standard method for botulinum toxin detection.

Provided herein are solid compositions comprising Clostridium botulinum neurotoxin serotype A (BoNT / A) and human serum albumin (HSA), wherein the solid compositions comprise a low amount of HSA aggregates. Further provided herein are methods of producing solid compositions comprising BoNT / A and HSA by drying a solution comprising BoNT / A in a manner such that the solution does not undergo freezing during drying.

The present invention belongs to the field of biotechnology, and specifically relates to a mutant of botulinum neurotoxin serotype A (BoNT / A) and its application. Compared with the wild-type BoNT / A having the amino acid sequence shown in SEQ ID NO:1, the mutant has at least one amino acid difference. In view of the defects of the prior art, through the screening of various sequences, the present invention provides an optimized BoNT / A sequence. Through codon optimization of the sequence and partial sequence replacement, not only high-purity soluble expression is achieved, but also the recombinantly expressed BoNT / A can mimic the natural post-translational modification process. Therefore, the optimized BoNT / A sequence provided by the present invention has broad prospects in the industrial production of BoNT / A.

The present disclosure provides antibodies that specifically bind to botulinum neurotoxins (e.g., BoNT / A, BoNT / B, BoNT / C, BoNT / D, BoNT / E, BoNT / F, BoNT / G, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

Disclosed herein is a botulinum neurotoxin (BoNT) polypeptide with a modified receptor binding domain (HC) having one or more amino acid mutations that modify the binding of the BoNT to the receptor. Specific mutations and combinations of mutations are also disclosed. Isolated modified HC, polypeptides comprising the modified HC, chimeric molecules, pharmaceutical compositions, and methods of making and using the same are also disclosed. Methods of identifying additional such modified receptor binding domains, are further disclosed.

The present invention relates to a method for modulating the effect of a botulinum neurotoxin composition, that is accelerating the onset of action and / or extending the duration of action and / or enhancing the intensity of action of a botulinum neurotoxin composition, comprising adding at least one postsynaptic inhibitor of cholinergic neuronal transmission to the botulinum neurotoxin composition. The invention also relates to compositions comprising at least one postsynaptic inhibitor of cholinergic neuronal transmission and a botulinum neurotoxin, and their uses for treating aesthetic or therapeutic conditions.

Described herein are Bacillus cells comprising a nucleotide sequence encoding a Botulinum neurotoxin (BoNT) and methods of producing the BoNT.

Recombinant nucleic acids encoding reporting constructs for characterizing botulinum neurotoxin protease activity and cells that incorporate such recombinant nucleic acids and that are suitable for use in cell-based assays for the neurotoxin are provided. The encoded reporting constructs are a pair of recombinant hybrid proteins that act in concert, and can include an N-terminal palmitoylation sequence. The reporting constructs are a pair of recombinant hybrid proteins that act in concert, and that include a botulinum neurotoxin protease recognition and cleavage sequence positioned to release a fluorophore upon cleavage.

The present invention is directed to a modified botulinum neurotoxin A (BoNT / A) for use in a method of treating blepharospasm in a subject, wherein the modified BoNT / A is administered by intramuscular injection at a plurality of sites of the face of the subject, the method comprising: a) administering a unit dose of the modified BoNT / A to the lateral upper orbicularis oculi muscle proximal to a first eye of the subject; b) administering a unit dose of the modified BoNT / A to the medial upper orbicularis oculi muscle proximal to the first eye of the subject; and c) administering a unit dose of the modified BoNT / A to the lateral lower orbicularis oculi muscle proximal to the first eye of the subject, wherein the unit dose of the modified BoNT / A is at least 240 pg (preferably 240 pg to 8,000 pg) of modified BoNT / A, wherein the total dose administered during the treatment is up to 24,000 pg of the modified BoNT / A, and wherein the modified BoNT / A comprises a BoNT / A light-chain and translocation domain (HN), and a BoNT / B receptor binding domain (HC domain).

The invention discloses a method and a product for detecting the binding capacity of clostridium neurotoxin and a receptor. The research discovers that the synaptic binding protein Syt1, a Syt1 mutant or Syt2 can be used for promoting glycosylation modification and membrane localization of the synaptic vesicle protein SV2, so that the binding capacity of the synaptic vesicle protein SV2 and botulinum neurotoxin or tetanus toxin is remarkably enhanced. The synaptic binding protein Syt1, Syt1 mutant or Syt2 is prepared into a product for detecting the clostridium neurotoxin, so that the synaptic vesicle protein SV2 can retain natural conformation and post-translational modification sites, and the physiological expression state is effectively simulated, thereby realizing accurate analysis of the binding capacity of the clostridium neurotoxin and the synaptic vesicle protein SV2.

The present invention is directed inter alia to a modified botulinum neurotoxin A (BoNT / A) for use in treating cervical dystonia, wherein the modified BoNT / A is administered by intramuscular injection to an affected neck muscle of a subject, wherein the modified BoNT / A is administered by way of a unit dose of greater than 17,000 pg of modified BoNT / A, wherein at least a single unit dose is administered to the affected neck muscle, wherein the total dose administered during the treatment is up to 400,000 pg of modified BoNT / A, and wherein the modified BoNT / A comprises a BoNT / A light-chain and translocation domain, and a BoNT / B receptor binding domain (HC domain). Also provided are corresponding methods, uses, unit dosage forms, and kits.

The present invention relates to aqueous saline solutions comprising dantrolene and optionally also at least one additional active principle, such as botulinum neurotoxin, and their use for various therapeutic and / or aesthetic purposes. The solutions can be administered in any suitable way, but are advantageous in that they are particularly well adapted to intramuscular injection.

The present disclosure provides antibodies that specifically bind to botulinum neurotoxins. The antibodies can be used in methods to specifically bind and, in some embodiments, neutralize, botulinum neurotoxin and are therefore also useful in the treatment of pathologies associated with botulinum neurotoxin poisoning.