Fusion protein composition(s) comprising masked type i interferons (IFNA and IFNB) for use in the treatment of cancer and methods thereof

Inventors

Stover, David • MORRISON, SHERIE • VASUTHASAWAT, Alex • Trinh, Kham • Ayoub, George

Assignees

Nammi Therapeutics Inc

Abstract

Fusion Protein compositions comprising masked IFNs and methods of making masked IFNs are disclosed herein. Consequently, the masked IFNs can be fused to a Mab or binding fragment thereof and be administered to patients as a therapeutic modality and provide a method of treating cancer, immunological disorders and other disease.

Core Innovation

The invention provides masked Type-I interferon (IFNα/IFNβ) fusion proteins targeted to tumor-associated antigens using an antibody or an antibody fragment that binds a tumor associated antigen. The Type-I interferon activity is masked by an interferon mask polypeptide sequence, which suppresses Type-I interferon activity and prevents activity until unmasking occurs in a tumor-associated context.

The masked Type-I interferon is implemented as a fusion protein that includes a cleavable linker and a polypeptide mask sequence for masking Type-I IFN activity, together with an antibody for targeting a tumor-associated antigen. In the described architecture, the N-terminal of the Type-I IFN is fused to the C-terminal of the antibody heavy and/or light chain(s), and the mask polypeptide sequence is included so that it masks Type-I IFN activity in the targeted masked IFN construct.

Unmasking is associated with tumor-associated proteases, with a cleavable linker and/or tumor-associated protease cleavage site allowing reactivation of Type-I interferon at the tumor site. The document additionally lists example tumor-associated antigen targets, including CD138, CD20, mesothelin, and 5T4, and provides defined interferon mask and linker sequences (SEQ ID NO: 15 and SEQ ID NO: 16).

Claims Coverage

The partial claim set includes two independent claims. Across the independent claims, the main coverage centers on a fusion protein composition combining a cleavable linker, an interferon mask sequence that masks Type-I interferon activity, and an antibody targeting a tumor associated antigen, together with a targeted masked IFN architecture that specifies antibody/Type-I IFN fusion orientation and defined mask and linker sequences.

Together, the independent claims define targeted masked Type-I interferon constructs using a specific interferon mask sequence and a cleavable linker, combined with an antibody that binds a tumor-associated antigen, and a defined antibody/Type-I IFN fusion arrangement that places the Type-I IFN N-terminus at the antibody C-terminus.

Stated Advantages

Documented Applications