Fluorocarbon-linked peptide formulation
The invention provides an aqueous acidic formulation suitable for use as in the preparation of a pharmaceutically acceptable fluorocarbon-linked peptide formulation, which aqueous formulation comprises a first fluorocarbon-linked peptide, wherein: the peptide linked to the fluorocarbon is at least 20 amino acid residues long, comprises at least 50% hydrophobic amino acid residues and has an isoelectric point greater than or equal to 7; and the fluorocarbon-linked peptide is present in micelles.
1. An aqueous acidic formulation for use in the preparation of a pharmaceutically acceptable fluorocarbon-linked peptide formulation, the aqueous acidic formulation comprising a first fluorocarbon-linked peptide, wherein:
the peptide linked to the fluorocarbon is 20 to 50 amino acid residues long, comprises at least 50% hydrophobic amino acid residues and has an isoelectric point greater than or equal to 7, but does not comprise a contiguous sequence of 20 amino acid residues comprising more than 80% hydrophobic amino acid residues; and
(ii) the fluorocarbon-linked peptide is present in micelles.
2. The aqueous acidic formulation according to claim 1 , further comprising acetic acid.
3. The aqueous acidic formulation according to claim 1 , further comprising one or more fluorocarbon-linked peptides that:
(i) are 20 to 50 amino acid residues long;
(ii) comprise at least 50% hydrophobic amino acid residues; and/or
(iii) have an isoelectric point greater than or equal to 7; and/or
the first fluorocarbon-linked peptide and/or one or more of the further fluorocarbon-linked peptides comprises a peptide that:
(iv) comprises a positively charged amino acid in the last 15 contiguous amino acids distal to the fluorocarbon; and/or
(v) does not comprise a contiguous sequence of 20 amino acid residues comprising more than 80% hydrophobic amino acid residues.
4. A The aqueous acidic formulation according to claim 1 , wherein the formulation does not comprise a fluorocarbon-linked peptide in which the peptide linked to the fluorocarbon:
(i) has an isoelectric point of less than 7; and/or
(ii) does not comprise a positively charged amino acid in the last 15 contiguous amino acids distal to the fluorocarbon.
5. A The aqueous acidic formulation according to claim 1 , wherein the peptide linked to the fluorocarbon is an immunogenic peptide derived from a pathogen, autologous protein or tumor cell.
6. A method for obtaining a pharmaceutically acceptable fluorocarbon-linked peptide formulation, said method comprising:
(i) solubilising a fluorocarbon-linked peptide in acetic acid;
(ii) filter-sterilising the solubilised fluorocarbon-linked peptide; and
(iii) drying the filter-sterilised fluorocarbon-linked peptide.
7. The method according to claim 6 , wherein the peptide linked to the fluorocarbon is at least 20 amino acid residues long and comprises at least 50% hydrophobic amino acid residues and has an isoelectric point greater than or equal to 7.
8. The method according to claim 6 , wherein:
(i) a mixture of the fluorocarbon-linked peptide and one or more further fluorocarbon-linked peptides are solubilised in acetic acid; and/or
(ii) the method further comprises blending the solubilised fluorocarbon-linked peptide with one or more further solubilised fluorocarbon-linked peptides.
9. The method according to claim 6 , wherein the peptide linked to the fluorocarbon is an immunogenic peptide derived from a pathogen, autologous protein or tumor cell.
10. The aqueous acidic formulation according to claim 1 , wherein the formulation has a pH of 5 or less.
11. The aqueous acidic formulation according to claim 1 further comprising one or more additional fluorocarbon-linked peptides present in micelles with a diameter of less than 0.22 μm.
12. The aqueous acidic formulation according to claim 1 , wherein at least 80% of the fluorocarbon-linked peptide micelles have a diameter of less than 100 nm.
13. The aqueous acidic formulation according to claim 1 , wherein the aqueous acidic formulation comprises six fluorocarbon-linked peptides, wherein each of the peptides have the sequences set out in SEQ ID NOs: 1 to 6 and wherein the aqueous acidic formulation comprises no other fluorocarbon-linked peptides.