The present invention concerns a process by which a misfold in an Fc
fusion molecule can be prevented or corrected. In one embodiment, the
process comprises (a) preparing a pharmacologically active compound
comprising an Fc domain; (b) treating the fusion molecule with a copper
(II) halide; and (c) isolating the treated fusion molecule. The
pharmacologically active compound can be an antibody or a fusion molecule
comprising a pharmacologically active domain and an Fc domain. The
preferred copper (II) halide is CuCl.sub.2. The preferred concentration
thereof is at least about 10 mM for fusion molecules prepared in E. coli;
at least about 30 mM for fusion molecules prepared in CHO cells. The
process can be employed with any number of pharmacologically active
domains. Preferred pharmacologically active domains include OPG proteins,
leptin proteins, soluble portions of TNF receptors (e.g., wherein the
fusion molecule is etanercept), IL-1ra proteins, and TPO-mimetic
peptides. The Fc domain preferably has a human sequence, with an Fc
sequence derived from IgG1 most preferred. An exemplary Fc sequence is
shown in FIG. 5 hereinafter.