this invention relates to the fields of immunology and protein therapeutics . the therapeutic proteins are polypeptides to be administered especially to humans . the polypeptides are modified whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject . the invention therefor provides methods for the development of therapeutic polypeptides that are less immunogenic than any non - modified counterpart when used in vivo . the modifications used according to this invention relate , for example , to the introduction of protease cleavage sites , attachment of different molecules or insertion of non - natural amino acids .