Targeted mutant interferon-beta and uses thereof

The chimeric protein of any one of the above claims, wherein the modified IFN-β exhibits reduced affinity for IFNAR2.

The chimeric protein of any one of the above claims, wherein the one or more mutations confer reduced affinity that is restorable by attachment to one or more targeting moieties.

The chimeric protein of any one of the above claims, wherein the one or more mutations cause the modified IFN-β to have reduced binding affinity for a receptor of at least about 2-fold less to about 2,000-fold less relative to the wild type form of IFN-β.

The chimeric protein of any one of the above claims, wherein the one or more mutations cause the modified IFN-β to have reduced endogenous activity or reduced specific bioactivity of at least about 2-fold less to about 2,000-fold less relative to the wild type form of IFN-β.

The chimeric protein of any one of the above claims, wherein the targeting moiety is directed against a tumor cell.

The chimeric protein of any one of the above claims, wherein the targeting moiety is directed against an immune cell.

The chimeric protein of any one of the above claims, wherein the targeting moiety comprises a recognition domain that is a full-length antibody, a single-domain antibody, a recombinant heavy-chain-only antibody (VHH), a single-chain antibody (scFv), a shark heavy-chain-only antibody (VNAR), a microprotein (e.g. cysteine knot protein, knottin), a darpin, an anticalin, an adnectin, an aptamer, a Fv, a Fab, a Fab′, a F(ab′)2, a peptide mimetic molecule, a natural ligand for a receptor, or a synthetic molecule.

The chimeric protein of any one of the above claims, wherein the recognition domain is a single-domain antibody.

The chimeric protein of any one of the above claims, wherein the recognition domain is a VHH, humanized VHH, or camelized VHH.

The chimeric protein of any one of the above claims, wherein the recognition domain functionally modulates the antigen or receptor of interest.

The chimeric protein of any one of the above claims, wherein the recognition domain binds but does not functionally modulate the antigen or receptor of interest.

The chimeric protein of any of the above claims, comprising two or more targeting moieties.

The chimeric protein of any one of the above claims, further comprising one or more additional modified signaling agents.

The chimeric protein of any one of the above claims, wherein the chimeric protein comprises two signaling agents or two targeting moieties or two of both.

The chimeric protein of any one of the above claims, wherein the chimeric protein comprises three signaling agents or three targeting moieties or three of both.

The chimeric protein of any one of the above claims, wherein the chimeric protein is suitable for use in a patient having one or more of:

• cancer, infections, immune disorders, autoimmune diseases, cardiovascular diseases, wound, ischemia-related diseases, neurodegenerative diseases, and/or metabolic diseases.

A recombinant nucleic acid composition encoding one or chimeric proteins of any one of the above claims.

A method for treating cancer, comprising administering an effective amount of the chimeric protein of any of the above claims to a patient in need thereof.

A method for treating an autoimmune disease or disorder, comprising administering an effective amount of the chimeric protein of any of the above claims to a patient in need thereof.

A method for treating an infection, comprising administering an effective amount of the chimeric protein of any of the above claims to a patient in need thereof.