The present invention concerns molecules and a process in which one or
more biologically active peptides are incorporated into an Fc domain. In
this invention, pharmacologically active compounds may be prepared by a
process comprising (a) selecting at least one peptide that modulates the
activity of a protein of interest; and (b) preparing a pharmacologic
agent comprising an amino acid sequence of the selected peptide in a loop
region of an Fc domain. This process may be employed to modify an Fc
domain that is already linked through an N- or C-terminus or sidechain to
a peptide or to a polypeptide (e.g., etanercept). This process may also
be employed to modify an Fc domain that is part of an antibody (e.g.,
adalimumab, epratuzumab, infliximab, Herceptin.RTM., and the like). In
this way, different molecules can be produced that have additional
functionalities, such as a binding domain to a different epitope or an
additional binding domain to the precursor molecule's existing epitope.
The peptide can be selected, for example, by phage display, E. coli
display, ribosome display, RNA-peptide screening, yeast-based screening,
chemical-peptide screening, rational design, or protein structural
analysis.