Interleukin-2 fusion proteins and uses thereof
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Publication Number
US-11680090-B2
Publication Date
2023-06-20
Expiration Date
Abstract
The present invention relates to interleukin-2 fusion proteins. More specifically, the invention provides, in part, fusion proteins that include a interleukin-2 protein moiety joined to a Bcl-2 family member protein moiety.
Core Innovation
The patent describes fusion proteins and related compositions for therapeutic modulation of cells expressing an interleukin-2 receptor (IL-2R). The fusion protein comprises interleukin-2 (IL-2) fused to a Bcl-2 family polypeptide, linking IL-2 signaling with Bcl-2 family-mediated regulation of apoptosis and cell survival.
The IL-2 used in the fusion proteins may be circularly permuted and/or may be IL-2Rβ- or IL-2Rγ-selective/mutant variants, including circularly permuted IL-2 constructs (cpIL-2; cpProS2). Example fusion constructs include proS2-Bad, cpProS2-Bcl-xL, and proS2-Bcl-xL, with optional linker elements such as GS, ubiquitin, or protease-cleavable regions.
The patent positions the fusion proteins as therapeutics that can either enhance survival/proliferation or induce apoptosis/death in IL-2R-expressing target cells, depending on the Bcl-2 family polypeptide selected. The patent also describes nucleic acid molecules encoding the fusion proteins, vectors comprising the nucleic acids, and pharmaceutical compositions comprising these fusion proteins.
Claims Coverage
The independent claim is directed to a method that combines contacting an IL-2R-expressing target cell with an IL-2/Bcl-2 family fusion protein or nucleic acid/vector encoding it to drive either enhanced survival/proliferation or inhibition of cell death/apoptosis. The claim set centers on three inventive features.
Enhancing cell survival or proliferation or inhibiting cell death or apoptosis with IL-2/Bcl-2 family fusion
A method of enhancing cell survival or proliferation, or inhibiting cell death or apoptosis of a target cell expressing an interleukin-2 receptor (IL-2R) by contacting the target cell with a fusion protein, a nucleic acid molecule encoding the fusion protein or a vector comprising the nucleic acid molecule, wherein the fusion protein comprises interleukin-2 (IL-2) and a Bcl-2 family polypeptide.
IL-2 selected from SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4
A method wherein the IL-2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4.
Anti-apoptotic Bcl-xL comprising SEQ ID NO:7
A method wherein the Bcl-2 family polypeptide is an anti-apoptotic Bcl-2 family polypeptide Bcl-xL comprising the amino acid sequence of SEQ ID NO:7.
Overall, the claim coverage centers on contacting IL-2R-expressing target cells with an IL-2/Bcl-2 family fusion or encoding nucleic acid/vector using IL-2 amino acid sequences selected from SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4 and an anti-apoptotic Bcl-xL polypeptide comprising SEQ ID NO:7, to enhance survival/proliferation or inhibit apoptosis/cell death.
Stated Advantages
Enhances cell survival or proliferation of a target cell expressing an interleukin-2 receptor (IL-2R).
Inhibits cell death or apoptosis of a target cell expressing an interleukin-2 receptor (IL-2R).
Documented Applications
Therapeutic modulation of IL-2R-expressing target cells in contexts including cancer and autoimmune disorders, as described in the patent’s therapeutic use discussion.
Targeting natural killer (NK) cells and regulatory T cells (Tregs), as described in the patent’s therapeutic use discussion.
Use in immune modulation approaches including adoptive cell transfer therapy and CAR-T therapy, as described in the patent’s therapeutic use discussion.
Pharmaceutical compositions comprising the fusion proteins, as described in the patent’s composition discussion.
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