Disclosed herein are methods for the isolation and purification of a botulinum neurotoxin (BoNT) protein, or a polypeptide comprising a receptor binding domain of BoNT, from a solution. The method comprises contacting the solution containing the protein or polypeptide to a matrix which has attached thereto a non-toxic non-hemagglutinin (NTNHA) under conditions appropriate for binding, washing the matrix to thereby remove unbound materials, and eluting the protein or polypeptide with a solution that dissociates the bound protein from the NTNHA. Conditions appropriate for binding are a pH of less than 7.5 (e.g, 6). Conditions appropriate for dissociation are a pH greater than or equal to 7.5 (e.g., 8). Compositions specific to the methods are also disclosed.

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

The present invention relates to methods for reducing facial lines or wrinkles of the skin or of removing facial asymmetries by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition may be 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.

Described herein are methods and compositions for treating and/or preventing a microbial infection. Aspects of the invention relate to administering to a subject an agent that inhibits CGRP release and CGRP receptors. In some embodiments of any of the aspects, a subject has been diagnosed with having, or is at risk of having, a microbial infection.

Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified BoNT/B4 receptor binding domain (B4-H.sub.C) having amino acid mutations that modify the binding of the BoNT to the human SytII receptor. Specific mutations and combinations of mutations are disclosed. Isolated modified H.sub.Cs, polypeptides comprising such modified H.sub.Cs, 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 provides a method for treating a patient for migraine headache, including symptoms associated with migraine head ache, such as migraine associated vertigo, which comprises administering to the patient a therapeutically effective amount of an invertebrate presynaptic neurotoxin, e.g. Botulinum toxin in a pharmaceutically safe form.

Methods, compositions, and devices for enhancing transdermal delivery and/or bioavailability of large agents.

The invention provides a method for alleviating discogenic pain by administering a therapeutic agent that disrupts neuronal and/or vascular elements in the disc, which is typically a degenerated disc. Disruption of neuronal elements in the disk includes destroying nerve endings without substantially affecting the central body of the nerve, suppressing activation of the nerve endings, and inhibiting the growth of nerve endings into the disk. Disruption of vascular elements includes causing the vascular extensions to retract from the disk, or suppressing the formation of such extensions. The therapeutic agent may be administered locally via an interbody pump, a bolus or a depot, or may be administered systemically.

Disclosed herein is a cosmetic composition including novel cell penetrating peptides, cell penetrating botulinum toxin recombinant proteins in which the cell-penetrating peptide and botulinum toxin are fused, polynucleotides encoding the cell penetrating botulinum toxin recombinant proteins, recombinant expression vector comprising the polynucleotides, and the cell penetrating botulinum toxin recombinant protein as active ingredients.

Chromatographic processes and systems for purifying a botulinum toxin from an APF fermentation medium.