A Cd33-, Cd16- and Cd123-Specific Single Chain Triplebody

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This invention describes a nucleic acid molecule encoding a novel single-chain triplebody protein that can specifically bind to the cell surface markers CD33, CD16, and CD123. The triplebody is designed to bridge cancer cells expressing CD33/CD123 (common in acute myeloid leukemia and myelodysplastic syndromes) to immune effector cells via CD16, thereby enhancing the targeted destruction of malignant cells while limiting effects on healthy tissue. The invention covers the genetic sequence, vectors for expression, methods for production and purification, and pharmaceutical compositions for use, particularly for treating blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Use CasesContent extracted from patent full text and abstract with AI.

• Targeted immunotherapy for acute myeloid leukemia (AML), recruiting natural killer (NK) cells to efficiently eliminate leukemic cells while sparing normal cells.
• Treatment of myelodysplastic syndromes (MDS), especially by eliminating cancer stem cells to prevent disease progression or relapse.
• Maintenance therapy during remission phases in AML to eradicate minimal residual disease and prevent relapse.
• Development of new biotherapeutic drugs based on multi-specific antibody fragments for other hematological cancers or solid tumors with known surface markers.
• Potential platform technology to engineer similar multi-specific biologics against other diseases where dual or triple targeting would increase efficacy or safety.

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• Dual targeting of CD33 and CD123 allows for more precise discrimination between leukemic and normal cells, increasing efficacy while minimizing side effects.
• Engaging CD16 on NK cells enhances immune-mediated killing of cancer cells, leveraging the body’s natural defenses for better therapeutic outcomes.
• Demonstrated broad efficacy across various AML genetic subtypes and stages, with activity even against minimal residual disease and leukemia stem cells responsible for relapse.
• Improved protein engineering yields a stable, aggregation-resistant triplebody with excellent manufacturing, storage, and bioactivity characteristics suitable for clinical use.
• Production methods use standard, scalable biotechnology processes, facilitating translation to commercial scale.
• Anticipated lower systemic toxicity compared to classical chemotherapies or earlier antibody-drug conjugates due to targeted mechanism of action.
• High specificity and activity at low doses, reducing the risk of adverse reactions and potentially lowering treatment cost.
• Potential to overcome resistance mechanisms that hinder mono-target therapies due to escape variants (e.g., loss of CD33 or CD123 on some clones).

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Inventors & Applicants

Patent Abstract

The present invention relates to a nucleic acid molecule encoding a single chain triplebody capable of specifically binding to CD33, CD16 and CD123, wherein said nucleic acid molecule comprises: (a) a nucleic acid molecule encoding a protein represented by SEQ ID NO:1; (b) a nucleic acid molecule represented by SEQ ID NO:2; (c) the nucleic acid molecule of (b), wherein each thymine is replaced by uracil; (d) a nucleic acid molecule encoding a protein having at least 98% sequence identity to the protein of (a); or (e) a nucleic acid molecule that is degenerate with respect to the nucleic acid molecule of (b) or (c). The present invention further relates to a vector comprising the nucleic acid molecule of the invention, a host cell transformed or transfected with the nucleic acid molecule or the vector of the invention, as well as to a method for the production of a single chain triplebody capable of specifically binding to CD33, CD16 and CD123. Furthermore, the present invention also relates to a single chain triplebody capable of specifically binding to CD33, CD16 and CD123 encoded by the nucleic acid molecule of the invention, as well as to a composition comprising the nucleic acid molecule, the vector, the host cell and/or the single chain triplebody of the invention. Also encompassed by the present invention are the nucleic acid molecule, the vector, the single chain triplebody and/or the composition of the invention for use in the treatment of acute myeloid leukaemia and/or myelodysplastic syndrome, as well as a method of treating acute myeloid leukaemia and/or myelodysplastic syndrome.