POLYMER ADJUVANT
The invention relates to an adjuvant comprising Pattern Recognition Receptor (PRR) agonist molecules linked to polymer chains that are capable of undergoing particle formation in aqueous conditions, or in aqueous conditions in response to external stimuli; and methods of treatment or prevention of disease using such an adjuvant.
1 - 34 . (canceled)
35 . An adjuvant comprising a linear unimolecular polymer chain comprising:
(a) monomer units selected from N-isopropylacrylamide (NIPAM), N-isopropylmethacrylamide (NIPMAM), N,N′-diethylacrylamide (DEAAM), N-(L)-(1-hydroxymethyl)propyl methacrylamides, N,N′-dimethylethylmethacrylate (DMEMA), N-vinyl caprolactam, acrylates, acrylamides, meth(acrylates), meth(acrylamides), N-(2-hydroxypropyl)methacrylamide (HPMA), amino acids, or a combination thereof, and
(b) Pattern Recognition Receptor agonist (PRRa) molecules, wherein said PRRa molecules comprise the formula:
wherein R is selected from
and X is selected from
and FG is selected from an amine, wherein the PRRa molecules are covalently linked to the monomer units through an amide bond at a density of between 5 mol % and 50 mol %.
36 . The adjuvant according to claim 35 , wherein the adjuvant comprises a block co-polymer.
37 . The adjuvant of claim 35 , wherein the adjuvant is in the form of particles.
38 . The adjuvant of claim 37 , wherein the particle is between 20 nm to 5,000 nm in diameter.
39 . The adjuvant of claim 35 , further comprising an antigen.
40 . The adjuvant of claim 39 , wherein the antigen comprises a protein, a peptide, a polysaccharide or a glycopeptide derived from a pathogen or a tumour.
41 . The adjuvant of claim 39 wherein the antigen is directly linked to the polymer chain.
42 . The adjuvant of claim 39 wherein the antigen is linked to the polymer chain through a linker molecule.
43 . The adjuvant of claim 42 , wherein the antigen is releasable from the polymer chain by enzymatic degradation of the linker.
44 . The adjuvant of claim 42 , wherein the antigen is linked near the end of the polymer chain.
45 . The adjuvant of claim 42 , wherein the adjuvant is in the form of particles.
46 . The adjuvant of claim 45 , wherein the particles are between 20 nm to 5,000 nm in diameter.
47 . A vaccine comprising the adjuvant of claim 35 .
48 . A method of vaccinating a patient comprising administering the vaccine of claim 47 to a patient to treat or prevent an infectious disease or cancer.
49 . A method of preparing the adjuvant of claim 35 , the method comprising the steps of:
dissolving the adjuvant of claim 35 in an organic solvent
filter sterilizing the adjuvant; and
forming particles by reconstituting the adjuvant in aqueous conditions; or, additionally providing a temperature shift from below the LCST of the polymer to above the LCST of the polymer.
50 . A method of preparing the adjuvant of claim 35 , the method comprising the steps of:
dissolving the adjuvant of claim 35 in aqueous conditions and filter sterilizing the adjuvant while the solution is at a temperature below LCST; and
forming adjuvant particles by providing a temperature shift from below the LCST of the polymer-PRRa conjugate to above the LCST of the polymer-PRR agonist conjugate.