Amino acid and peptide conjugates and conjugation process
Inventors
Brimble, Margaret Anne • WRIGHT, Thomas Hugh • DUNBAR, Peter Roderick • Williams, Geoffrey Martyn
Assignees
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Publication Number
US-10576144-B2
Publication Date
2020-03-03
Expiration Date
Abstract
The present invention relates to amino acid and peptide conjugates, methods for making amino acid and peptide conjugates, conjugates produced by the methods, pharmaceutical compositions comprising the conjugates, methods of eliciting immune responses in a subject and methods of vaccinating a subject, uses of the conjugates for the same, and uses of the conjugates in the manufacture of medicaments for the same.
Core Innovation
The disclosure provides lipid-peptide conjugate structures described by representative compound formulae (IV) and (V), including variable linker lengths and substituents identified as L1-L3, R3, and R9, and peptide-related moieties identified as A1 and A2. Embodiments include cases where at least one peptide segment contains an epitope, and the conjugates include peptide-related features used as amino-acid or peptide conjugation partners within the overall lipid-peptide architecture.
The disclosure describes a thiol-ene conjugation framework for attaching a lipid-containing conjugation partner bearing an alkene to amino-acid/peptide conjugation partners containing thiol functionality. The conjugation proceeds through a free radical mechanism using thermal or photochemical radical initiation, together with optional additives described to suppress dimerization or polymerization.
The disclosure also provides peptide sequence embodiments selected from SEQ ID NO:1-20 and variants, and defines compound structure rules that include amino-acid/peptide substitutions and constraints on which epitope-containing peptides are used. It frames peptide construction and conjugate formulation concepts in the context of preparing immunogenic compositions and vaccine-related embodiments, including administration of the peptide conjugates optionally without extrinsic adjuvant to elicit immune responses in subjects.
Claims Coverage
The independent claims center on formula-defined lipid-peptide conjugate compounds with epitope-containing peptide segments and optional solubilising cationic peptide features, together with use claims directed to vaccinating or eliciting an immune response by administration of the peptide compound.
Formula (V) peptide-epitope conjugate scaffold
A compound of formula (V) with defined values for m, n, R1-R9, L1, and L3, including the option where A1 is a peptide comprising an epitope or R9 is A2 and A2 is a peptide comprising an epitope; the compound is also provided as a pharmaceutically acceptable salt or solvate.
Peptide sequences comprising epitope
The compound of formula (V) is defined such that the peptide comprises or consists of an amino acid sequence selected from SEQ ID NO:1-20 or variants, including sequences having 8 or more contiguous amino acid residues with optionally absent or substituted positions.
Solubilising peptide group with two or more cationic residues
The compound of formula (V) is defined such that A1 and/or A2 is a peptide containing a solubilising group made up of an amino acid sequence with two or more cationic amino acid residues in the peptide chain.
Vaccination / immune-response administration of peptide compound
A method of vaccinating or eliciting an immune response in a subject by administering an effective amount of the peptide compound, optionally in a pharmaceutical composition with a pharmaceutically acceptable carrier.
Across the provided claim scope, the claims center on a formula-defined lipid-peptide conjugate incorporating peptide/epitope elements and optional solubilising cationic peptide features, with further scope directed to vaccinating or eliciting immune responses via administration of the peptide compound.
Stated Advantages
Elicits immune responses in a subject upon vaccination or administration of the peptide conjugates.
Can be administered optionally without extrinsic adjuvant.
Upregulation of human monocyte CD80 associated with TLR2 agonism.
Peptide conjugates maintain or improve antigen processing and presentation on antigen-presenting cells for CD8+ and CD4+ clones.
Documented Applications
Vaccination of a subject to elicit an immune response by administering an effective amount of the peptide compound, optionally as a pharmaceutical composition with a pharmaceutically acceptable carrier.
Immune-elicitation applications described in connection with systemic immunity and mucosal immunity, including booster vaccination and specified routes of administration.
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