SYNTHETIC DERIVATIVES OF MPL AND USES THEREOF
In one aspect, the present disclosure provides compounds of formulae (I) and (II). In another aspect, a compound of formula (I) or (II) is formulated into compositions with an antigen, optionally with a vesicle. In some embodiments, compositions are administered intramuscularly.
1 . A compound of formula:
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from C x alkyl or C x+1 alkyl; and
x is an integer from 6 to 20.
2 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are the same.
3 . The compound of claim 1 , wherein R 1 , R 3 , R 5 , and R 6 are the same.
4 . The compound of claim 1 , wherein R 2 and R 4 are the same.
5 . The compound of claim 1 , wherein R 1 , R 3 , R 5 , and R 6 are C x alkyl, and R 2 and R 4 are C x+1 alkyl.
6 . The compound of claim 1 , wherein R 1 , R 3 , R 5 , and R 6 are C x+1 alkyl, and R 2 and R 4 are C x alkyl.
7 . The compound of claim 1 , wherein x is 6, 7, 8, 9, 10, or 11.
8 . The compound of claim 1 , wherein x is 6.
9 . The compound of claim 1 , wherein x is 8.
10 . The compound of claim 1 , wherein x is 11.
11 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are C 6 alkyl.
12 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are n-hexyl.
13 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are C 8 alkyl.
14 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are n-octyl.
15 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are C n alkyl.
16 . The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are n-undecyl.
17 . A compound of formula:
wherein:
R 1′ , R 3′ , R 5′ , and R 6′ are C y alkyl;
R 2′ and R 4′ are independently C y alkyl, C y+1 alkyl, or C y+2 alkyl; and
y is 6 or 7.
18 . The compound of claim 17 , wherein R 2′ and R 4′ are C y alkyl.
19 . The compound of claim 18 , wherein y is 6.
20 . The compound of claim 17 , wherein R 2′ and R 4′ are C y+1 alkyl.
21 . The compound of claim 17 , wherein R 2′ and R 4′ are C y+2 alkyl.
22 . The compound of claim 21 , wherein y is 6.
23 . A composition comprising a compound of claim 1 and an antigen.
24 . The composition of claim 23 , wherein the antigen is a virus.
25 . The composition of claim 24 , wherein the virus is an attenuated virus.
26 . The composition of claim 24 , wherein the virus is an inactivated virus.
27 . The composition of claim 24 , wherein the virus is a whole virus.
28 . The composition of claim 24 , wherein the virus is a split virus.
29 . The composition of claim 24 , wherein the virus is hepatitis A.
30 . The composition of claim 24 , wherein the virus is influenza.
31 . The composition of claim 23 , wherein the antigen is selected from the group consisting of Bordetella pertussis, Vibrio cholerae and Salmonella typhi.
32 . The composition of claim 23 , wherein the antigen is a polypeptide.
33 . The composition of claim 32 , wherein the polypeptide is a recombinant polypeptide.
34 . The composition of claim 32 , wherein the polypeptide is a viral polypeptide.
35 . The composition of claim 34 , wherein the polypeptide is a hepatitis A polypeptide.
36 . The composition of claim 34 , wherein the polypeptide is a hepatitis B polypeptide.
37 . The composition of claim 36 , wherein the polypeptide is HBsAg.
38 . The composition of claim 34 , wherein the polypeptide is a hepatitis C polypeptide.
39 . The composition of claim 34 , wherein the polypeptide is an HIV polypeptide.
40 . The composition of claim 34 , wherein the polypeptide is an influenza polypeptide.
41 . The composition of claim 40 , wherein the polypeptide is hemagglutinin, neuraminidase, or a combination thereof.
42 . The composition of claim 23 , wherein the composition comprises a mixture of antigens.
43 . The composition of claim 42 , wherein the composition comprises a mixture of polypeptides.
44 . The composition of claim 43 , wherein the mixture of polypeptides comprises a mixture of polypeptides from the same virus.
45 . The composition of claim 23 , wherein the antigen is a polynucleotide.
46 . The composition of claim 23 , wherein the antigen is a polysaccharide.
47 . The composition of claim 23 , wherein the antigen is a virus-like particle.
48 . The composition of claim 23 , wherein the antigen is a peptide antigen.
49 . The composition of claim 48 , wherein the peptide antigen includes one or more fragments of an HIV polypeptide.
50 . The composition of claim 48 , wherein the peptide antigen includes one or more fragments of an influenza polypeptide.
51 . The composition of claim 23 , further comprising a vesicle which comprises a non-ionic surfactant.
52 . (canceled)
53 . (canceled)
54 . (canceled)
55 . (canceled)
56 . (canceled)
57 . (canceled)
58 . (canceled)
59 . (canceled)
60 . (canceled)
61 . (canceled)
62 . (canceled)
63 . (canceled)
64 . (canceled)
65 . (canceled)
66 . (canceled)
67 . The composition of claim 51 , wherein the vesicle comprises 1-monopalmitoyl glycerol, dicetylphospate and cholesterol.
68 . A method comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 51 .
69 . The method of claim 68 , wherein the composition is administered by intramuscular injection.