LONG-ACTING CYTOKINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM

摘要

Cytokine derivatives are provided bearing functional groups sensitive to mild basic conditions such as fluorenylmethoxycarbonyl (Fmoc) and 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) and pharmaceutical compositions comprising them. Preferred derivates are those in which amino groups of the cytokine are substituted with FMS, for example FMS7-IFN- alpha 2 and FMS3-IL-2. These cytokine derivatives can be administered as inactive or slightly active prodrugs and are capable of undergoing spontaneous regeneration into the parent bioactive drugs under in vivo physiological conditions and in a hom egenous fashion. The cytokine prodrugs present higher metabolic stability and augmented bioavailability.