Present invention provides a stable pharmaceutical composition comprising botulinum neurotoxin, anesthetic in a buffer. Present invention also provides a process for the preparation of the stable pharmaceutical composition. The botulinum neurotoxin is stabilized by the formation of complex between the toxin and anesthetic. The present invention further provides a method for treating wrinkles using the said pharmaceutical composition.

The present invention includes a composition and method of allosterically potentiating the activity of neurolysin comprising contacting the neurolysin with an amount of a histidine-containing dipeptide that is an allosteric that increases the activity of neurolysin.

Disclosed herein is a method of enhancing the ubiquitin proteasome system (“UPS”) in a subject in need thereof, comprising administering an effective amount of a composition comprising neprilysin and a cell targeting moiety, wherein administration of the composition delivers the composition into the intracellular space of one or more cells of the subject and wherein the subject suffers from a condition associated with a UPS deficiency.

Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH.sub.4.sup.+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R.sup.58, R.sup.56 and K.sup.57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.

The invention provides compositions and methods for treating celiac sprue.

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Disclosed herein are systems and methods for manufacturing botulinum neurotoxin serotype E (BoNT/E) with improved yield and purity of BoNT/E. Disclosed herein are systems and methods for manufacturing BoNT/E drug substance.

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Compositions and methods for treating type II diabetes in a feline are provided. A viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding a feline GLP-1 receptor agonist.