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Publication Number
US-11932674-B2
Publication Date
2024-03-19
Expiration Date
Abstract
The invention relates to proteins having multi-specific binding abilities by fusion of an OB-fold variant, in particular from the Sac7d family, to the light or heavy chain of an antibody.
Core Innovation
The invention provides multi-specific engineered proteins formed by genetically fusing an OB-fold variant to an antibody heavy or light chain. The OB-fold variant is defined as a variant OB-fold polypeptide having an amino acid sequence set forth in SEQ ID NO: 35 and is configured to bind to IL17. The engineered format enables multi-specific binding by combining the OB-fold binding activity with antibody binding activity in a single polypeptide.
The engineered proteins include symmetrical and asymmetrical bi-specific and multi-specific architectures, with multiple OB-fold variants fused within the constructs. The OB-fold variants are derived from a Sac7d-family protein, and certain embodiments specify quantitative constraints for residue mutations in Sac7d-derived OB-fold binding residues. The fusion is defined as being at the N-terminus or C-terminus of an antibody heavy or light chain, using genetic fusion constructs.
Genetic constructs, vectors, and host cells are described for producing the engineered multi-specific proteins, including eukaryotic production systems and engineered bacterial systems. The constructs can further be extended to conjugation with an organic molecule and are described for diagnostic and therapeutic uses involving relevant targets.
Claims Coverage
The independent claims cover, at a minimum, four inventive features: a defined IL17-binding OB-fold variant polypeptide, antibody fusion architectures, production by genetically transformed cells, and conjugation to an organic molecule. The coverage centers on the SEQ ID NO: 35 OB-fold variant, multi-specific antibody/OB-fold fusion formats, and genetic construct and recovery features.
IL17-binding variant OB-fold polypeptide defined by SEQ ID NO: 35
A polypeptide comprising a variant OB-fold polypeptide having the amino acid sequence set forth in SEQ ID NO: 35, wherein the variant OB-fold polypeptide binds to IL17.
Antibody heavy-chain or light-chain fusion at the 3′ or 5′ end
A genetic construct made from a selected DNA sequence encoding either an antibody heavy-chain or light-chain polypeptide fused at the 3′ or 5′ end to the polypeptide specified in claim 1.
Producing the polypeptide by culturing genetically transformed cells and recovering the polypeptide
Producing the polypeptide by culturing genetically transformed cells that carry a DNA construct encoding the polypeptide, followed by recovering the polypeptide.
Polypeptide conjugated to an organic molecule
A polypeptide conjugated to an organic molecule.
The independent claim scope is directed to a defined SEQ ID NO: 35 OB-fold variant polypeptide that binds IL17, fusion with antibody heavy or light chains at defined orientations via genetic constructs, production in genetically transformed cells with subsequent recovery, and conjugation to an organic molecule. Dependent claim refinements further narrow mutation constraints for Sac7d-derived OB-fold binding residues and specify example antibody binding targets including TNFα, IL23, IL12, IL4, IL13, IL31, the IL31 receptor, or a tumor specific antigen.
Stated Advantages
Maintained or increased recovery yield versus naked antibodies.
Documented Applications
Diagnostic and therapeutic uses involving binding targets described in the document, including TNFα, IL17, IL23, IL12, IL4, IL13, IL31, the IL31 receptor, and tumor-associated antigens.
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