MHC class I associated hepatitis B peptides
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11191828-B2
Publication Date
2021-12-07
Expiration Date
Abstract
The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of Hepatitis B virus (HBV) infection, and discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against HBV infection. The peptide and/or proteins of the invention may be used as a therapeutic drug to stimulate the immune system to recognize and eliminate HBV infection in infected cells or as a vaccine for the prevention of disease.
Core Innovation
The invention relates to immunogenic HBV MHC class I immunogens comprising cytotoxic T lymphocyte (CTL) epitopic peptides that are naturally presented on HBV-infected cells. The identified epitopes include immunogenic CTL epitopic peptides associated with HLA-A2/HLA-A24 supertypes, and the immunogens cover breadth across HBV genotypes as peptides, polypeptides, or polynucleotides encoding immunogens.
The disclosed immunogenic CTL epitopic peptides are described as SEQ ID NO: 1-17 and include HLA-A2 and HLA-A24 epitope specificity. The patent identifies selected HLA-A2/A24-specific peptides (SEQ ID 1-8) and states that these peptides activate HBV-specific CD8+ T cells, with functional readouts including IFN-gamma ELISpot, CD107a degranulation marker, and granzyme B secretion.
The document describes an immunoproteomics workflow used to identify the HBV epitopes, including WIC molecule-specific immunoaffinity isolation followed by nano LC/MS/MS identification. Functional validation is performed with the selected peptides in vitro and in vivo using HLA-A2 and HLA-A24 transgenic mice, supporting CTL responses against HBV-infected cells.
Claims Coverage
The independent claim defines a pharmaceutical composition that includes a class I WIC allele-binding or processable immunogen and requires T lymphocyte activation, with sequence constraints relative to a specified SEQ ID. This provides one principal inventive set of features.
Sequence-constrained class I WIC-binding immunogen
A pharmaceutical composition comprising a polypeptide, oligopeptide or peptide consisting of 8 to about 30 amino acid residues and comprising a sequence that is SEQ ID NO: 4 or differs from SEQ ID NO: 4 by no more than one amino acid unit, including addition or deletion of one amino acid to or from SEQ ID NO: 4.
Binding to class I WIC alleles with T lymphocyte activation
The polypeptide, oligopeptide or peptide binds to one or more class I WIC alleles or can be processed to bind to one or more class I WIC alleles and activate a T lymphocyte.
Epitopic peptide count constraints in the immunogen
The composition further includes a polypeptide, oligopeptide, or peptide that comprises at least two epitopic peptides, at least three epitopic peptides, or at least four epitopic peptides.
Overall, the claim coverage centers on a pharmaceutical composition containing a short immunogen of 8 to about 30 amino acids defined by SEQ ID NO: 4 or a one-amino-acid difference, where the immunogen binds to or is processable to bind one or more class I WIC alleles and activates a T lymphocyte, optionally with a specified minimum number of epitopic peptides.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?