Revance Therapeutics, Inc.

Nektar Therapeutics

Other

Stewart A Thompson

Jacob M Waugh

Curtis L Ruegg

Mei-chang Kuo

Zhihao Fang

Mary J Bossard

Tacey Viegas

Derek Hudson

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.

Albumin-free botulinum toxin formulations

This invention relates totoxin formulations that are stabilized without the use of any proteinaceous excipients. The invention also relates to methods of preparing and using suchtoxin formulations.

Conjugates of a GLP-1 moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-1 polymer conjugate may include a GLP-1 moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-1 polymer conjugate may include a GLP-1 moiety covalently attached to a water-soluble polymer, wherein the GLP-1 moiety possesses an N-methyl substituent.

Polymer conjugates of GLP-1

Conjugates of a GLP-I moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-I polymer conjugate may include a GLP-I moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached to a water-soluble polymer, wherein the GLP-I moiety possesses an N-methyl substituent. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached at a polymer attachment site to a water-soluble polymer, wherein the GLP-I moiety is glycosylated at a site separate from the polymer attachment site.

A method is provided which facilitates and enables the production of a wide range of complex conjugates composed of similar or dissimilar units linked together by amide bonds. Said method for the production of acylthio derivatives, R&prime;&mdash;CO&mdash;SA, involves reaction of a carboxylate, R&prime;&mdash;CO&mdash;O,(or carboxylic acid R&prime;&mdash;CO&mdash;OH) with an iso-thiouronium derivative (bearing SA) in the presence of base. Nucleophilic counterion forms of the iso-thiouronium salts confer significant rate enhancement. The processes are simple, generally applicable, efficient, and do not require the employment of noxious reagents. The production of complex protein-like products by the intermediary of acylthio esters generated by the process of this invention, provides a method which is compatible with mild methods of chain assembly; and is preferably applied when the second component in the ligation bears an amino terminal cysteine residue.

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Burlingame, CA, United States of America

Stewart A Thompson