Il-12 stability variants

IL-12 stability variants, engineered to lack the native disulfide bond and featuring a furin-cleavable linker, address the systemic toxicity and efficacy challenges of IL-12 therapies by ensuring localized activity and reduced systemic exposure, enhancing immune stimulation and tumor targeting.

WO2025006797A1PCT designated stage expired Publication Date: 2025-01-02LYELL IMMUNOPHARMA INC +1
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Patent Information

Application Number
PCT/US2024/035900
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-06-27
Filing Date
2024-06-27
Publication Date
2025-01-02

AI Technical Summary

Technical Problem

Current IL-12 therapies face challenges due to systemic toxicity and limited efficacy, particularly because IL-12 activates proinflammatory signaling at low concentrations and is restrained by the immunosuppressive tumor microenvironment, necessitating a safer and more effective form for immune stimulation.

Method used

Development of IL-12 stability variants lacking the native disulfide bond between the p40 and p35 subunits, with mutations such as C177S and C74S, and optionally a furin-cleavable linker, which rapidly inactivate after secretion, allowing local activity without systemic toxicity.

Benefits of technology

The IL-12 stability variants achieve localized immune modulation and enhanced tumor killing by T and NK cells, reducing systemic toxicity and maintaining biological activity, thus providing a safer and more effective immune stimulation.

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Abstract

The present disclosure provides IL-12 stability variants, nucleic acids encoding the variants, vectors comprising the nucleic acids, pharmaceutical compositions comprising the variants, therapeutic cells expressing the variants, and methods or uses of the same for the treatment or prevention of a disease or disorder.
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Citation Information

Patent Citations

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