Human ApoB100 epitopes, methods and uses for modulating inflammatory responses, and treating adverse cardiovascular events, disease and atherosclerosis
Inventors
Ley, Klaus • Sette, Alessandro
Assignees
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Publication Number
US-12448433-B2
Publication Date
2025-10-21
Expiration Date
Abstract
Provided herein are composition comprising novel epitopes of ApoB100, as well as sub-sequences, portions and modifications thereof, and uses thereof for treating adverse cardiovascular events, cardiovascular disease, atherosclerosis and certain liver disorders.
Core Innovation
The invention relates to novel ApoB100-derived T cell epitopes comprising peptides with specific amino acid sequences that bind one or more MHC-II molecules. The peptides are defined by amino acid sequences set forth in SEQ ID NOs included in the document and are described as ApoB100-derived T cell epitopes.
The problem addressed is immune-mediated adverse cardiovascular events and cardiovascular disease, including atherosclerosis, and also liver disorders, where modulation of immune and inflammatory responses is needed. The disclosed peptides are described as being able to modulate immune and inflammatory responses through binding to MHC-II molecules, thereby providing therapeutic and/or prophylactic effects.
The document further describes multiple use modes centered on the MHC-II-binding ApoB100-derived peptides, including vaccination for protection and reduced risk, treatment of subjects, and immune-cell binding assays for detecting ApoB-specific CD4 T cells and related immune status. Nucleic acids, cells expressing peptide, and pharmaceutical compositions/vaccines with adjuvants are described, with optional inclusion of statins as part of the broader approaches.
Claims Coverage
The independent claims provide peptide-level coverage and method-level coverage, each grounded on administering or using ApoB100-derived peptides defined by specific SEQ ID NO options that bind one or more MHC-II molecules. Across the independent claims, there are three main inventive feature groupings: an MHC-II-binding peptide defined by SEQ IDs, a protection method using the same peptide sequences, and a treatment method using the same peptide sequences.
MHC-II-binding ApoB-derived peptide set forth in specified SEQ IDs
A peptide consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, 16, 17, 19 and 20, wherein the peptide binds to one or more major histocompatibility complex II (MHC-II) molecules.
Administering an MHC-II-binding peptide to provide protection
A method of providing a subject with protection against an adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage, comprising administering to the subject an amount of a peptide consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, 16, 17, 19 and 20, sufficient to provide the subject with protection against the adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage, wherein the peptide binds to one or more major histocompatibility complex II (MHC-II) molecules.
Administering an MHC-II-binding peptide to treat adverse cardiovascular/liver conditions
A method of treating a subject for an adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage, the method comprising administering to the subject an amount of a peptide consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 10, 11, 16, 17, 19 and 20, sufficient to treat the subject for the adverse cardiovascular event or cardiovascular disease, atherosclerosis or liver disease, disorder or damage, wherein the peptide binds to one or more major histocompatibility complex II (MHC-II) molecules.
Overall, the claims focus on peptides defined by specific SEQ ID NOs that bind MHC-II molecules, and on providing protection and treating adverse cardiovascular events/diseases, atherosclerosis, and liver disease/disorder/damage by administering those peptides in an amount sufficient for the stated protective or therapeutic effect.
Stated Advantages
Provides protection against an adverse cardiovascular event or cardiovascular disease, including atherosclerosis, and against liver disease, disorder or damage.
Treats a subject for an adverse cardiovascular event or cardiovascular disease, including atherosclerosis, and for liver disease, disorder or damage.
Includes prophylactic vaccination for protection against or reduction of risk of adverse cardiovascular events or cardiovascular disease, atherosclerosis, or liver disease, disorder, or damage.
Documented Applications
Vaccination/prophylaxis to protect against or reduce the risk of adverse cardiovascular events or cardiovascular disease, atherosclerosis, and liver-related disorders, as supported by an atherosclerosis/liver-protective vaccine model described in the document.
Treatment of a subject for an adverse cardiovascular event or cardiovascular disease, atherosclerosis, and/or liver disease, disorder, or damage, via administration of the disclosed peptides as described in the document.
Immune-cell binding assays using an ApoB peptide tetramer to identify and characterize ApoB-specific CD4 T cells in patient PBMCs, supporting detection/characterization of immune status relevant to ApoB vaccination or disease status.
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