149 results about "Botulinum neurotoxin" patented technology

Methods for treating a coronary risk factor (such as hypertension, diabetes, hyperlipidemia and obesity) and/or a respiratory disorder (such as asthma, chronic obstructive pulmonary disease and bronchitis) and/or arthritis by local administration of a botulinum neurotoxin to at least one of a head, neck or shoulder location (for example, by subdermal, subcutaneous or intramuscular administration of the botulinum neurotoxin) of a patient with a coronary risk factor, respiratory disorder or arthritis.

The invention provides methods and devices for the delivery of therapeutic or biologically active agents to tissue, for example by facilitating the transport of said agents through the skin of a human or animal. Therapeutic agents include various botulinum neurotoxin (BoNT) and other biologically active agents, which can be delivered across the skin and into the dermis using multiple strategies including microneedle drug delivery, transport moieties, or penetration enhancers such as extracellular matrix-digestive enzymes.

This invention is directed to preparation and expression of synthetic genes encoding polypeptides containing protective epitopes of botulinum neurotoxin (BoNT). The invention is also directed to production of immunogenic peptides encoded by the synthetic genes, as weel as recovery and purification of the immunogenic peptides from recombinant organisms. The invention is also directed to methods of vaccination against botulism using the expressed peptides.

The present invention provides a nucleic acid molecule which contains a nucleotide sequence encoding a SNAP-25 substrate which includes (i) a green fluorescent protein; (ii) a first partner of an affinity couple; and (iii) a portion of SNAP-25 that includes a BoNT/A, BoNT/C1 or BoNT/E recognition sequence containing a cleavage site, where the cleavage site intervenes between the green fluorescent protein and the first partner of the affinity couple. Further provided herein is a nucleic acid molecule which contains a nucleotide sequence encoding a tagged toxin substrate which includes (i) a fluorescent protein; (ii) a first partner of an affinity couple; and (iii) a clostridial toxin recognition sequence containing a cleavage site, where the cleavage site intervenes between the fluorescent protein and the first partner of the affinity couple.

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.

A method of targeting therapeutic molecules to motor neurons is disclosed. In one embodiment, this method comprises the steps of (a) synthesizing a prodrug comprising a therapeutic molecule covalently bound to a polymeric delivery vehicle, and (b) conjugating the prodrug to a botulinum neurotoxin heavy chain.

A molecular construct comprises a donor label, an acceptor label, a linker peptide disposed between the donor and the acceptor, the linker having a cleavage site sequence, and a spacer between at least one of (a) the donor and the cleavage site sequence and (b) the acceptor and the cleavage site sequence. Preferably, the construct is selected from the group consisting of CFP-(SGLRSRA)-SNAP-25-(SNS)-YFP, and CFP-(SGLRSRA)-synaptobrevin-(SNS)-YFP. In preferred embodiments, the linker peptide is a substrate of a botulinum neurotoxin selected from the group consisting of synaptobrevin (VAMP), syntaxin and SNAP-25, or a fragment thereof that can be recognized and cleaved by the botulinum neurotoxin. Advantageously, the spacer increases the electronic coupling between the donor label and the acceptor label relative to a corresponding construct without the spacer.

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.

Antibodies for binding epitopes of BoNT/A and hybridomas which produce such antibodies are described. The antibodies of the present invention can be used in a method for detecting BoNT/A in a sample and/or in a method for purifying BoNT/A from an impure solution. In addition, the antibodies can be used for passive immunization against BoNT/A intoxication or as intoxication therapy. Another aspect of the invention is a kit for detecting BoNT/A in a sample.

This disclosure provides antibodies that specifically bind to and typically neutralize botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/E, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies 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.

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.

This invention provides antibodies that specifically bind to and typically neutralize botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/E, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies 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.

This invention provides antibodies that specifically bind to botulinum neurotoxin type A (BoNT/A) and/or botulinum neurotoxin type B (BoNT/B) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies 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. Also included in the invention are diagnostic and therapeutic assays directed to botulinum neurotoxins.

Methods for treating rhinitis in a subject are provided herein. The methods of the present invention comprise intranasal administration of a topical composition comprising a purified botulinum neurotoxin, a carrier and a viscosity modifier to one or more inner surfaces of the nose. The methods disclosed herein provide alternative methods for delivery of botulinum neurotoxin to the nasal anatomy for the treatment of rhinitis.

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. The methods of the present invention are adapted for cell based screening to monitor the catalytic activity of a BoNT in living cells and to identify molecules that inhibit the catalytic activity of a BoNT in living cells. 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.

A remedy for muscle hyperactivity, comprising a purified botulinum neurotoxin as an active ingredient.

A novel subtype of type A botulinum neurotoxin (BoNT/A) is disclosed in the application. Methods to purify the neurotoxin as well as uses thereof are also disclosed.