Fusion constructs and methods of using thereof

Inventors

Sabzevari, Helen • METENOU, Simon • Chen, Chang Hung • Shah, Rutul

Assignees

Precigen Inc

Abstract

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF-β trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

Core Innovation

The invention describes a fusion protein that includes a first component and a second component configured as a cytokine trap. The first component comprises a V_L region comprising the sequence of any one of SEQ ID NOs: 417-428 and a V_H region comprising the sequence of any one of SEQ ID NOs: 390-403. The second component is a cytokine trap comprising the sequence of any one of SEQ ID NOs: 14, 141, and 142.

In the described embodiments, PD-1/PD-L1 blockade is combined with cytokine-trap activity within fusion protein formats, including anti-PD-1–TGFβRII fusion proteins and anti-PD-1–ADA2 fusion proteins. The core concept links an inhibitory immune checkpoint targeting component to a cytokine trap that neutralizes TGF-β or an adenosine-deaminase activity that affects adenosine-mediated suppression. Engineered T-cell contexts and combination regimens are also described to support the immunotherapy concept.

The document further describes functional characterization of the fusion formats, including PD-1/PD-L1 blockade potency and cytokine-related activity such as TGF-β neutralization and adenosine deaminase functionality. Reported results include binding and functional assay readouts together with comparisons to related fusion formats and combination settings, including engineered T-cell synergy contexts.

Claims Coverage

The provided independent claim covers a class of fusion proteins defined by specific selectable immunoglobulin-derived V_L and V_H sequence sets in a first component and selectable cytokine-trap sequence sets in a second component. Inventive features are anchored to the chosen SEQ ID groups for each component; additional dependents further specify linker connectivity, particular SEQ ID selections, and claim scope for encoding polynucleotides and pharmaceutical compositions.

Overall, the claim coverage is centered on fusion proteins defined by selectable V_L and V_H region sequence sets paired with selectable cytokine-trap sequence sets. Dependent coverage further narrows the fusion by specifying linker sequence options, particular VL/VH combinations, and a particular cytokine-trap SEQ ID, and extends to polynucleotide and pharmaceutical composition embodiments.

Stated Advantages

Documented Applications