Fusion molecules of CTLA4 and IL-15
Inventors
OLSON, Clifford Anders • Soon-Shiong, Patrick • Tanaka, Shiho
Assignees
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Publication Number
US-12297247-B2
Publication Date
2025-05-13
Expiration Date
Abstract
Soluble fusion protein complexes, including domains from IL-15, IL-15 receptor, and αCTLA4 antibody for preventing, reducing the occurrence of, and/or treating cancer or an autoimmune disease or disorder in a subject are provided herein. The methods provided herein include administering to a subject a pharmaceutical composition of a soluble fusion protein complex.
Core Innovation
A soluble fusion protein complex is described that combines an interleukin-15 (IL-15) peptide with an IL-15 receptor alpha Sushi (IL15RαSu) fusion polypeptide and an αCTLA4 antibody heavy chain and light chain. The IL-15 peptide binds to the IL15RαSu peptide to form a soluble fusion protein complex, and the IL-15 peptides comprise SEQ ID NO: 17 or SEQ ID NO: 1.
The IL15RαSu fusion polypeptide includes the IL15RαSu peptide fused with an αCTLA4 antibody heavy chain having the amino acid sequence of SEQ ID NO: 10. The soluble fusion protein complex also includes an αCTLA4 antibody light chain having the amino acid sequence of SEQ ID NO: 3. The described fusion configurations include TxM-A, TxM-B, and TxM-C, as well as non-TxM IL-15/αCTLA4 orientations.
The document further describes therapeutic uses for modulating immune responses, including preventing or reducing cancer and autoimmune diseases. It also describes injectable pharmaceutical formulations using pharmaceutically acceptable carriers and parenteral injection routes.
Claims Coverage
The independent claim is clm-00001 and defines a soluble fusion protein complex with three domain components in which IL-15 binding to an IL15RαSu fusion domain forms a soluble complex; it includes two selectable IL-15 sequence options and specific αCTLA4 heavy and light chain sequences. Dependent claims refine the specific IL-15 sequence, fusion-polypeptide/linker placement, and defined fusion polypeptide sequences, and they also cover pharmaceutical formulations and a melanoma treatment method.
Soluble fusion complex with IL-15 binding to IL15RαSu
A soluble fusion protein complex wherein an IL-15 peptide binds to the IL15RαSu peptide of a second domain to form a soluble fusion protein complex.
IL-15 peptide domain defined by SEQ ID NO: 17 or SEQ ID NO: 1
A first domain comprising an IL-15 peptide wherein the IL-15 peptide comprises SEQ ID NO: 17 or SEQ ID NO: 1.
IL15RαSu fused to αCTLA4 heavy chain defined by SEQ ID NO: 10
A second domain comprising a fusion polypeptide comprising an IL15RαSu peptide and an αCTLA4 antibody heavy chain having the amino acid sequence of SEQ ID NO: 10.
αCTLA4 light chain defined by SEQ ID NO: 3
A third domain comprising an αCTLA4 antibody light chain having the amino acid sequence of SEQ ID NO: 3.
Pharmaceutical composition for parenteral injection
A pharmaceutical composition for parenteral injection with pharmaceutically acceptable carriers.
Method of treating melanoma by administering the soluble fusion protein complex
A method of treating melanoma in a subject by administering the soluble fusion protein complex.
Overall claim coverage centers on a soluble fusion protein complex built from an IL-15 peptide domain that binds an IL15RαSu fusion domain, together with an αCTLA4 antibody heavy chain and αCTLA4 antibody light chain with specified sequence identifiers. The dependent coverage further restricts IL-15 and fusion details and extends to injectable pharmaceutical composition and melanoma treatment by administration of the complex.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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