Amino Acid and Peptide Conjugates and Uses Thereof
OwnerMargaret Anne Brimble, Peter Roderick Dunbar +2inventors
InventorsMargaret Anne Brimble, Peter Roderick Dunbar, Geoffrey Martyn Williams, Daniel Verdon
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Abstract
The present invention relates to peptides, and amino acid and peptide conjugates, methods for making amino acid and peptide conjugates, conjugates produced by the methods, pharmaceutical compositions comprising the peptides and conjugates, methods of eliciting immune responses in a subject and methods of vaccinating a subject, uses of the peptides and conjugates for the same, and uses of the peptides and conjugates in the manufacture of medicaments for the same.
Claims95
A method for making a peptide conjugate, the method comprising
- providing a lipididated amino acid or peptide, and
- coupling the lipidated amino acid or peptide to one or more amino acids or peptides to provide a peptide conjugate, and wherein the peptide conjugate comprises one or more EBV LMP2 epitopes.
A compound of the formula (V):
- wherein
- m is an integer from 0 to 4;
- n is 1 or 2;
- R1 and R2 at each instance of m are each independently hydrogen, C1-6alkyl, or C3-6cycloalkyl;
- R3, R4, R5, R8, and R9 are each independently hydrogen, C1-6alkyl, or C3-6cycloalkyl;
- or R9 is an amino protecting group, L3-C(O), or A2;
- R6 and R7 at each instance of n are each independently hydrogen, C1-6alkyl, or C3-6cycloalkyl,
- L1 is C5-21alkyl or C4-20heteroalkyl;
- L3 is C1-6alkyl or C3-6cycloalkyl;
- A1 and A2 are each independently an amino acid or a peptide;
- or A1 is OH or OP1, wherein P1 is a carboxyl protecting group, and wherein A1 or A2 comprise one or more EBV LMP2 epitopes, or wherein A1, A2 or both A1 and A2 comprise one or more peptides selected from the group consisting of SEQ ID NOs:
- 1-101;
- wherein any alkyl, cycloalkyl or heteroalkyl present in any of R1, R2, R3, R4, R5, R6, R7, R8, R9, L1, and L3 is optionally substituted, and or a pharmaceutically acceptable salt or solvate thereof.
The compound of claim 72, wherein R9 is independently hydrogen, C1-6alkyl, or C3-6cycloalkyl;
- or R9 is L3-C(O) or A2;
- and
- A1 and A2 are each independently a peptide;
- or A1 is OH;
- provided that:
- at least one of A1 and A2 comprises an EBV LMP2 epitope;
- and
- when R9 is not A2, A1 is a peptide.
The compound of claim 72 or 73, wherein L1 is as defined in claim 49 or 50.
The compound of any one of claims 72 to 74, wherein m is as defined in claim 42 or 43.
The compound of any one of claims 72 to 75, wherein m is 0.
The compound of any one of claims 72 to 76, wherein R1 and R2 at each instance of m are each independently hydrogen.
The compound of any one of claims 72 to 77, wherein R3 is hydrogen.
The compound of any one of claims 72 to 78, wherein R4 and R5 are each hydrogen.
The compound of any one of claims 72 to 79, wherein R6 and R7 are each hydrogen.
The compound of any one of claims 72 to 80, wherein R8 is hydrogen and R9 is hydrogen, an amino protecting group, L3-C(O), or A2.
The compound of any one of claims 72 to 81, wherein A1 is a OP1 or OH and R9 is hydrogen, an amino protecting group or L3-C(O).
The compound of any one of claims 72 to 82, wherein L3 is Me.
The compound of any one of claims 72 to 83, wherein A1 and/or A2 is an amino acid or a peptide.
The compound of any one of claims 72 to 84, wherein the peptide comprises an epitope selected from the group consisting of the amino acid sequence of any one of SEQ ID NOs:
- 76-101.
The compound of any one of claims 72 to 81 and 83 to 85, wherein A1 is serine or a peptide comprising serine as the first N-terminal amino acid residue.
The compound of any one of claims 72 to 81 and 83 to 86, wherein A1 and/or A2 is a peptide comprising a solubilising group comprising an amino acid sequence comprising two or more hydrophilic amino acid residues in the peptide chain.
An isolated, purified, or recombinant peptide comprising, consisting of, or consisting essentially of an amino acid sequence selected from the group consisting of any one of SEQ ID NOs:
- 1-75.
A method for making a peptide conjugate, the method comprising reacting
- a lipid-containing conjugation partner, and
- an amino acid-comprising conjugation partner,
- under conditions effective to conjugate the lipid-containing conjugation partner to the amino acid-comprising conjugation partner by the hydrothiolation of a carbon-carbon double bond with a thiol,
- the method further comprising coupling the amino acid of the amino acid conjugate to an amino acid or a peptide to provide a peptide conjugate, and wherein the peptide conjugate comprises one or more EBV LMP2 epitopes.
A method for making a peptide conjugate, the method comprising reacting
- a lipid-containing conjugation partner, and
- a peptide-comprising conjugation partner, wherein the peptide-comprising partner comprises one or more EBV LMP2 epitopes,
- under conditions effective to conjugate the lipid-containing conjugation partner to the peptide-comprising conjugation partner by the hydrothiolation of a carbon-carbon double bond with a thiol.
Dependencies are inferred from the claim text.