Immunity-inducing agent comprising antigen peptide-adjuvant nucleotide conjugate and pharmaceutical composition comprising same
Inventors
Mochizuki, Shinichi • Koizumi, Makoto • Morita, Koji
Assignees
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Publication Number
US-12589148-B2
Publication Date
2026-03-31
Expiration Date
Abstract
The present invention provides an immunity-inducing agent comprising, as an active component, a polynucleotide/peptide conjugate in which a single-chain polynucleotide or polynucleotide derivative comprising a CpG motif, and an antigenic peptide are bound via a spacer, wherein the spacer is covalently bound at one end thereof to the polynucleotide or polynucleotide derivative and covalently bound at the other end thereof to the antigenic peptide, as well as a pharmaceutical composition comprising said immunity-inducing agent.
Core Innovation
The invention relates to an immunity-inducing agent having, as an active component, a conjugate comprising a single-chain polynucleotide or a single-chain polynucleotide derivative comprising a CpG motif and an antigenic peptide bound thereto via a spacer. The spacer is covalently bound at one end to the single-chain polynucleotide or derivative comprising a CpG motif and covalently bound at the other end to the antigenic peptide, and the single-chain polynucleotide or derivative comprising a CpG motif is not complexed with β-1,3-glucan.
The antigenic peptide and the spacer are bound together via a disulfide bond produced by a reaction between a thiol group of a cysteine residue at the N-terminus of the antigenic peptide and a thiol group of the spacer. The spacer comprises a repeating unit represented by a formula in which X represents an oxygen atom or a sulfur atom, and R represents (CH2)pO, (CH2)qNH, or (CH2CH2O)m, with m, p, q, and n each representing a natural number not more than 10.
The disclosure also describes preferred spacer structures and reactive chemistries for covalently linking a phosphorothioate CpG DNA(S) to an antigenic peptide. Example CpG DNA(S)-peptide conjugates are reported, and the conjugate induces peptide-specific cytotoxic T lymphocyte responses in mice, with activity dependent on CpG nucleotide length, CpG motif multiplicity, and antigenic peptide length.
Claims Coverage
Three inventive features are identified across the independent claims: a covalently spacer-linked CpG-motif single-chain polynucleotide and antigenic peptide conjugate, a spacer repeating-unit structure, and a pharmaceutical composition comprising the same conjugate. The claims also require that the CpG-motif single-chain polynucleotide is not complexed with β-1,3-glucan and that the peptide-spacer connection is formed by a disulfide bond via a cysteine thiol and a spacer thiol.
Conjugate with CpG-motif single-chain polynucleotide and spacer-linked antigenic peptide via disulfide bond
A conjugate of a single-chain polynucleotide or derivative comprising a CpG motif and an antigenic peptide bound via a spacer, where the spacer is covalently bound at one end to the CpG-motif single-chain polynucleotide and covalently bound at the other end to the antigenic peptide, the CpG-motif single-chain polynucleotide is not complexed with β-1,3-glucan, and the antigenic peptide and the spacer are bound together via a disulfide bond produced by a reaction between a thiol group of a cysteine residue at the N-terminus of the antigenic peptide and a thiol group of the spacer.
Spacer repeating unit structure for CpG-motif conjugate
The spacer comprises a repeating unit represented by a formula with X representing an oxygen atom or a sulfur atom, and R representing any of (CH2)pO, (CH2)qNH, and (CH2CH2O)m, where m, p, and q each independently represent a natural number of not more than 10, and n represents a natural number of not more than 10.
Pharmaceutical composition including the specified conjugate
A pharmaceutical composition comprising the conjugate of a single-chain polynucleotide or derivative comprising a CpG motif and an antigenic peptide bound thereto via a spacer, with the same end-to-end covalent attachment arrangement, non-complexation with β-1,3-glucan, disulfide bond produced by a reaction between the thiol group of a cysteine residue at the N-terminus of the antigenic peptide and a thiol group of the spacer, and the same spacer repeating unit structure.
Overall claim coverage is centered on a covalently connected CpG-motif single-chain polynucleotide–spacer–antigenic peptide conjugate, with peptide–spacer linkage formed by a disulfide bond via a N-terminal cysteine thiol and a spacer repeating-unit structure defined by the formula. The independent claims further require that the CpG-motif single-chain polynucleotide is not complexed with β-1,3-glucan, and extend the conjugate to a pharmaceutical composition.
Stated Advantages
High immunostimulatory activity.
Easier production and design flexibility.
Induces peptide-specific cytotoxic T lymphocyte responses in mice.
Documented Applications
Tumor treatment by administering an effective amount of the pharmaceutical composition comprising the conjugate.
Use as a tumor-treatment pharmaceutical composition.
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