Methods for producing polypeptide with altered immunogenicity or improved
stability properties are disclosed. The methods involve
a) expressing a diversified population of nucleotide sequences encoding a
polypeptide of interest,
b) screening the polypeptides expressed in step a) for function,
immunogenicity and/or stability,
c) selecting functional polypeptides having altered immunogenicity and/or
increased stability, e.g. functional in vivo half-life as compared to the
polypeptide of interest, and
d) optionally subjecting the nucleotide sequence encoding the polypeptide
selected in step c) to one or more repeated cycles of steps a)-c). In a
further step the expressed polypeptides of step a) or c) can be
conjugated to at least one non-polypeptide moiety.