Activatable interleukin 12 polypeptides and methods of use thereof

A pharmaceutical composition comprising at least one of each of:

• a) a human interleukin 12 (IL-12) polypeptide comprising an IL-12 subunit polypeptide selected from IL-12p35 and IL-12p40;
• b) an IL-12 blocking moiety, wherein the IL-12 blocking moiety comprises a ligand-binding domain or fragment of a cognate receptor for the IL-12 polypeptide, or an antibody or antigen-binding fragment of an antibody that binds the IL-12 polypeptide;
• c) a protease-cleavable polypeptide linker;
• and
• d) a half-life extension element wherein the half-life extension element is human serum albumin, an antigen-binding polypeptide that binds human serum albumin, or an immunoglobulin Fc;
• wherein the IL-12 subunit polypeptide and the IL-12 blocking moiety are operably linked by the protease-cleavable polypeptide linker, the IL-12 polypeptide has attenuated IL-12-receptor activating activity at least about 10 fold less than the IL-12-receptor activating activity of the polypeptide that comprises the IL-12 polypeptide that is produced by cleavage of the protease-cleavable polypeptide linker, and wherein the IL-12 receptor activating activity is assessed using a using a HEK Blue reporter cell assay, with equal amounts on a mole basis of the IL-12 polypeptide and the pharmaceutical composition.