The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of human obesity protein (leptin) to result in leptin proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.