By Donald Zuhn —

The United States Patent and Trademark Office recently issued U.S. Patent No. 7,179,484 to Azaya Therapeutics, Inc.  The ‘484 patent, which relates to protein-stabilized liposomal formulations for the delivery of pharmaceutical agents, is the first U.S. patent to be awarded to the San Antonio-based pharmaceutical company.

After receiving a Notice of Allowance in November 2006, Azaya announced that the ‘484 patent would allow the company to fully utilize its proprietary Protein Stabilized Liposome (PSL®) nanotechnology, which allows for the production of uniform liposomal particles of less than 200 nm in size in a single-step manufacturing process.  According to Azaya, the strength of its PSL® nanotechnology is that it can be used to encapsulate a large array of water insoluble drugs.

Azaya has described the ‘484 patent as a "core technology patent" that will allow the company to further develop its lead product candidate, ATI-1123.  ATI-1123 is a PSL® formulation of Aventis’ Taxotere, which is a poorly water-soluble semi-sythetic taxane analog used in the treatment of non-small cell lung, prostrate, and breast cancer.  Prior to the development of Azaya’s PSL® nanotechnology, Taxotere’s poor water-solubility had been overcome by formulating the compound with a toxic carrier, Tween 80.

In addition, Azaya has been using its PSL® nanotechnology to develop a secondary product candidate, ATI-1153.  ATI-1153 is PSL® formulation of SN-38, which is an active metabolite of Pfizer’s drug CAMPTOSAR® for use in treating colorectal cancer.  While SN-38 has proven to be more potent than alternative therapeutics, absent PSL® encapsulation, it cannot be administered directly to patients due to its water insolubility and high systemic toxicity.

The ‘484 patent issued from U.S. Application No. 10/703,187 and claims the benefit of U.S. Provisional Application No. 60/424,230, which was filed on November 6, 2002.  Representative independent Claim 1 recites:

1.  A method of preparing protein-stabilized liposome nanoparticles containing at least one lipophilic pharmaceutical agent, the method comprising:
    (a)  preparing an oil-in-water emulsion by a process comprising
        i)  preparing an organic solution comprising one or more phospholipids;
        ii)  mixing the at least one lipophilic pharmaceutical agent into said organic solution;
        iii)  infusing said organic mixture into an aqueous solution comprising an emulsion-forming protein, wherein said emulsion-forming protein comprises from about 0.1% to about 20% (w/v) of the aqueous solution, to form a the oil-in-water emulsion; and
    (b)  removing organic solvent from said emulsion to form the protein-stabilized liposome nanoparticles, wherein said liposome nanoparticles have sizes below 400 nm and said emulsion-forming protein adsorbed onto their surface.

Dependent claim 30 recites:

30.  A protein-stabilized lipid formulation comprising protein-stabilized liposome nanoparticles and a lipophilic pharmaceutical agent, the formulation prepared by a process selected from the group of processes consisting of those processes set forth in any one of claims 1, 2-9 and 10-29.

Additional information concerning Azaya’s PSL® liposome nanoparticles and manufacturing process, including an animated simulation, can be found here.