Immune inducer containing polynucleotide-peptide conjugate and pharmaceutical composition containing same

Inventors

Mochizuki, Shinichi • Koizumi, Makoto • Morita, Koji

Assignees

Kitakyushu, University of • Daiichi Sankyo Co Ltd

Abstract

The present invention provides an immunity-inducing agent comprising a polynucleotide-peptide conjugate or a pharmaceutically acceptable salt thereof as an active component, wherein the polynucleotide-peptide conjugate consists of: a single-chain polynucleotide or polynucleotide derivative comprising a CpG motif; a peptide; and a spacer which is covalently bonded at one end thereof to the polynucleotide or polynucleotide derivative and covalently bonded at the other end thereof to the peptide, wherein the peptide is a peptide modified by substituting one or more contiguous amino acids at the N-terminus of an MHC-binding peptide with an amino acid having a reactive functional group which allows for the formation of a covalent bond with the spacer, wherein the one or more contiguous amino acids contain no anchor residues for MHC binding.

Core Innovation

The invention provides an immunity-inducing agent composition comprising a polynucleotide-peptide conjugate or a pharmaceutically acceptable salt thereof. The polynucleotide-peptide conjugate includes a single-chain polynucleotide or polynucleotide derivative comprising a CpG motif and a peptide, with a spacer covalently bonded at one end to the polynucleotide or polynucleotide derivative and covalently bonded at the other end to the peptide.

The peptide is an MHC-binding peptide modified by substituting one or more contiguous amino acids at the N-terminus with an amino acid having a reactive functional group that allows formation of a covalent bond with the spacer, and the one or more contiguous amino acids contain no anchor residues for MHC binding. The amino acid having the reactive functional group is cysteine or an analogue thereof having a side chain containing thiol.

The polynucleotide derivative includes a modification for increasing nuclease resistance. The disclosure characterizes CpG DNA(S)-peptide conjugates with cysteine-based linkages, disulfide linkages, and spacer variants connecting CpG DNA(S) to MHC-binding peptides.

Claims Coverage

The claims present 4 inventive features across independent claim scopes: a CpG motif-containing single-chain polynucleotide covalently linked to an MHC-binding peptide through a spacer, N-terminal substitution of non-anchor residues in the peptide to enable covalent bonding, a cysteine or thiol-containing analogue for spacer coupling, and a nuclease-resistance modification in the polynucleotide derivative.

The claim coverage focuses on a CpG motif-containing single-chain polynucleotide covalently connected through a spacer to an MHC-binding peptide, with N-terminal contiguous amino acid substitutions lacking MHC anchor residues and bearing cysteine or a thiol-containing analogue for covalent spacer bonding, together with a nuclease-resistance modification in the polynucleotide derivative.

Stated Advantages

Documented Applications