The present invention concerns molecules and a process in which one or morebiologically active peptides are incorporated into an Fc domain. In thisinvention, pharmacologically active compounds may be prepared by a processcomprising (a) selecting at least one peptide that modulates the activity of aprotein of interest； and (b) preparing a pharmacologic agent comprising anamino 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 linkedthrough 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 domainthat is part of an antibody (e.g., adalimumab, epratuzumab, infliximab,Herceptin~, and the like). In this way, different molecules can be producedthat have additional functionalities, such as a binding domain to a differentepitope or an additional binding domain to the precursor molecule's existingepitope. The peptide can be selected, for example, by phage display, E. colidisplay, ribosome display, RNA-peptide screening, yeast-based screening,chemical-peptide screening, rational design, or protein structural analysis.
