Cyclic peptides for protection against respiratory syncytial virus
Inventors
Ghasparian, Arin • Zuniga, Armando • Marrero Nodarse, Aniebrys • RASSEK, OLIVER • Robinson, John A. • Möhle, Kerstin
Assignees
VIROMETIX AG • Zurich Universitaet Institut fuer Medizinische Virologie
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Publication Number
US-11680085-B2
Publication Date
2023-06-20
Expiration Date
Abstract
The present invention relates to a cyclic peptide, a conjugate comprising said cyclic peptide and a lipopeptide building block, a bundle of said conjugates, a synthetic virus-like particle comprising at least one bundle of conjugates and pharmaceutical compositions comprising the same. The present invention further relates to said cyclic peptide, said conjugate said bundle of conjugates, said synthetic virus-like particle and said pharmaceutical compositions for use as a medicament, preferably for use in a method for preventing of an infectious disease or reducing the risk of an infectious disease, more preferably for use in a method for preventing or reducing the risk of an infectious disease associated with or caused by a respiratory syncytial virus.
Core Innovation
The invention provides a cyclic peptide comprising an amino acid sequence (I) defined by SEQ ID NO: 1, with fixed residues at P12, I13, T14, N15, D16, Q17, K18-K19, and L20, and variable positions X1, X2, X3, X5, X6, X7, X9, X10, X11, X22, X23, X24, X26, X27, X28, and X29, where X30 is an amino acid or a deletion. The cyclic peptide is characterized by cysteines at C4, C8, C21, and C25, with C4 and C25 forming a first disulfide bond and C8 and C21 forming a second disulfide bond.
The cyclic peptide scope includes cystine-stabilized cyclic-peptide embodiments arranged to form a helical hairpin and/or helix-turn-helix conformation, together with enumerated sequence identities including SEQ ID NOs 2-5, 16-36, and 39-57. The sequence design space also includes extensive residue substitutions, D/L stereochemistry, and cyclic peptides of at most 80, at most 60, at most 40, and at most 30 amino acids.
The invention further defines linker and conjugate architectures in which the cyclic peptide is connected directly or via a linker to a lipopeptide building block comprising a coiled-coil peptide chain segment and a lipid moiety with two or three hydrocarbons chains. The resulting conjugates are assembled into bundles of conjugates to form synthetic virus-like particles (SVLPs). Pharmaceutical and vaccine compositions include such SVLPs for preventing or reducing respiratory syncytial virus (RSV) infection risk.
Claims Coverage
The independent claim coverage centers on a cyclic peptide defined by the SEQ ID NO: 1 pattern with two disulfide bonds. The remaining claim coverage extends to cyclic peptide length limits, enumerated sequence embodiments, linker structures, lipopeptide building blocks, synthetic virus-like particles, and pharmaceutical compositions.
Cyclic peptide with two disulfide bonds
A cyclic peptide comprising an amino acid sequence (I) having X1-X2-X3-C4-X5-X6-X7-C8-X9-X10-X11-P12-I13-T14-N15-D16-Q17-K18-K19-L20-C21-X22-X23-X24-C25-X26-X27-X28-X29-X30 (SEQ ID NO: 1), where the variable positions are independently an amino acid, C4, C8, C21 and C25 are cysteine, P12 is proline, I13 is isoleucine, T14 is threonine, N15 is asparagine, D16 is aspartic acid, Q17 is glutamine, K18 and K19 are lysine, L20 is leucine, and X30 is an amino acid or a deletion; C4 and C25 form a first disulfide bond and C8 and C21 form a second disulfide bond.
Lipopeptide building block conjugate with cyclic peptide
A conjugate including a lipopeptide building block made of a peptide moiety with at least one coiled coil peptide chain segment and a lipid moiety with two or three hydrocarbons chains, wherein the cyclic peptide is connected directly or via a linker to the lipopeptide building block.
Synthetic virus-like particles from conjugates
Synthetic virus-like particles formed by bundling conjugates of the cyclic peptide with the lipopeptide building block.
Pharmaceutical composition with immunologically effective amount of SVLP
A pharmaceutical composition that includes an immunologically effective amount of the synthetic virus-like particle plus a pharmaceutically acceptable diluent, carrier, or excipient.
Constrained cyclic peptide length
The cyclic peptide has an amino acid sequence length selected from embodiments of at most 80 amino acids, at most 60 amino acids, at most 40 amino acids, and at most 30 amino acids.
Enumerated cyclic peptide sequence identities
The cyclic peptide has an amino acid sequence selected from SEQ ID NO: 2, 3, 4, 5, 16 to 36, or 39 to 57.
Linker selection with linker parameter n
A cyclic peptide conjugate defined with a linker selected from provided linker chemical structures, where n is an integer from 1 to 45 and the wavy line indicates the attachment site to an amino acid sequence (I).
The claim set focuses on a cystine-stabilized cyclic peptide sequence defined by SEQ ID NO: 1 with two disulfide bonds and variable positions, and extends to conjugates using a lipopeptide building block, bundling into synthetic virus-like particles, and pharmaceutical compositions. Additional claim features include sequence enumerations, length thresholds, and optional linker structures.
Stated Advantages
Presentation of multiple copies of the cyclic peptide on a non-lipophilic surface while lipid moieties aggregate in an internal core.
SVLP formation by self-assembly/bundling of cyclic-peptide–lipopeptide conjugates using coiled-coil α-helical bundle domains.
Provision of vaccine/pharmaceutical compositions for RSV with an immunologically effective amount.
Prevents or reduces respiratory syncytial virus (RSV) infection risk.
Enables multivalent surface display of cyclic peptides on synthetic virus-like particles (SVLPs).
Provides an immune rationale for RSV vaccination.
Documented Applications
Vaccine and medicament use for RSV, including compositions containing an immunologically effective amount and pharmaceutically acceptable diluent, carrier, or excipient, optionally with an adjuvant and route/dosing concepts.
Pharmaceutical and vaccine compositions that include synthetic virus-like particles for preventing or reducing RSV infection risk.
Vaccination use, including RSV vaccination, using a pharmaceutical composition and optionally an adjuvant for an immunologically effective amount.
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