Abstract: Compositions and methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form using a yeast host cell as the expression system are provided. Compositions of the invention are nucleotide sequences encoding a signal peptide sequence for a yeast secreted protein, an optional leader peptide sequence for a yeast secreted protein, a native propeptide leader sequence for a mature protein of interest, and a sequence for the mature protein of interest, all operably linked to a yeast promoter. Each of these elements is associated with a processing site recognized in vivo by a yeast proteolytic enzyme. Any or all of these processing sites may be a preferred processing site that has been modified or synthetically derived for more efficient cleavage in vivo. The compositions are useful in methods for expression of heterologous mammalian proteins and their secretion in the biologically active mature form.

Abstract: Stabilized pharmaceutical formulations comprising IFN-? and highly purified mannitol are provided. The highly purified mannitol stabilizes the compositions by reducing the formation of IFN-? adducts in comparison with IFN-? formulated with mannitol that has not been highly purified. Methods for increasing the stability of IFN-? or a variant thereof in a liquid or lyophilized composition and for increasing storage stability of such a composition are also provided.