Pharmacia & Upjohn Company

Elan Pharmaceuticals, Inc.

Donna Paddock

Robert L Heinrikson

Alfredo Giuseppe Tomasselli

Thomas L Emmons

Ana Mildner

The invention provides methods for efficient recombinant expression, refolding, and purification of Beta-site APP cleaving enzyme (BACE) polypeptides. In various aspects, the method includes the steps of expressing a recombinant construct in bacteria, dissolving inclusion bodies with a denaturant at high pH in the presence of a reducing agent, diluting the solubilized BACE polypeptide in an aqueous solution at a temperature of about 1&#xb0; C. to 15&#xb0; C., and incubating the diluted sample at a temperature of about 4&#xb0; C. to 15&#xb0; C. until the recombinant BACE polypeptide folds into an active enzyme.

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Kalamazoo, MI, United States of America

Donna Paddock