Novel interferon variants and bifunctional fusion molecules thereof

Abstract

The present invention relates to bifunctional fusion molecules comprising a mutated polypeptide ligand (e.g., mutated IFN-α) having reduced biological activity attached to a disease tissue targeting biologic or a tumor associated antigen (TAA)-targeting biologic (e.g., anti-PD-L1 antibody), wherein the targeting biologic or TAA-targeting biologic directs the mutated ligands to cells that express on their surfaces the antigens to which said targeting biologic binds, as well as receptors for said ligands. Importantly, because the mutated polypeptide ligands have reduced biological activity, the resultant fusion molecule have reduced off-target activity/toxicity. More importantly, the targeting of the mutated ligand by the targeting biologic restores the activity of the mutated ligand, with the degree of activity restoration apparently correlated with the level of targeting biologic on the cells. As such, the fusion molecules of the present invention advance the state of art by providing bifunctional fusion molecules having a greater therapeutic window than those previously described. The invention further relates to methods of treating cancer in a patient and in particular, patients with refractory and/or recurrent cancers involving the use of these bifunctional fusion molecules. The invention also relates to methods of treating infectious disease, including but not limited to chronic hepatitis B and C infections in a patient involving the use of these bifunctional fusion molecules.

Dependencies are inferred from the claim text.