Mixture of stereoisomers of a sulfated glycolipid

Patent metadata

Field	Value
Publication number	US-2025084116-A1
Application number	US-202218724432-A
Country	US
Kind code	A1
Filing date	Dec 21, 2022
Priority date	Jan 5, 2022
Publication date	Mar 13, 2025
Grant date	—

Abstract

A composition comprising a mixture of two or more stereoisomers of a synthetic charged isoprenoid glycolipid of Formula (I), or a pharmaceutically acceptable salt thereof, in which n is 0 or 1, R and R′ are independently hydrogen or hydroxyl, each Y is independently hydrogen or a sulfate group, and wherein at least one Y is a sulfate group, and less than 25% of the synthetic charged isoprenoid glycolipid molecules in the mixture comprise an archaeol moiety of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol. Further provided are archaeosomes and immunogenic compositions comprising the composition, use of the composition as an adjuvant or immunostimulant, and processes for synthesizing the composition.

First claim

What is claimed is:

1 . A composition comprising a mixture of two or more stereoisomers of a synthetic charged isoprenoid glycolipid comprising a sulfated saccharide group covalently linked to the free sn-1 hydroxyl group of the glycerol backbone of an archaeol moiety via a beta linkage, wherein the synthetic charged glycolipid is a compound of the formula:

or a pharmaceutically acceptable salt thereof,
wherein
n is 0 or 1;
R and R′ are independently hydrogen or hydroxyl;
each Y is independently hydrogen or a sulfate group, and wherein at least one Y is a sulfate group; and
less than 25% of the synthetic charged isoprenoid glycolipid molecules in the mixture comprise an archaeol moiety of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

2 . The composition of claim 1 , wherein only one Y is a sulfate group.

3 . The composition of claim 1 or 2 , wherein the sulfated saccharide group comprises monosaccharide moieties selected from the group consisting of mannose (Man), glucose (Glc), rhamnose (Rha), and galactose (Gal) moieties.

4 . The composition of claim 3 , wherein the compound comprises a sulfate group at the 6′ position of the terminal monosaccharide moiety.

5 . The composition of any one of claims 1 to 4 , wherein n is 0 and R is OH.

6 . The composition of any one of claims 1 to 5 , wherein the compound is 6′-sulfate-α-D-Man p -(1,6)-β-D-Gal p -(1,4)-β-D-Glc p -(1,1)-archaeol, or 6′-sulfate-β-D-Glc p -(1,6)-β-D-Gal p -(1,4)-β-D-Glc p -(1,1)-archaeol, or 6′-sulfate-β-D-Gal p -(1,4)-β-D-Glc p -(1,6)-β-D-Glc p -(1,1)-archaeol.

7 . The composition of any one of claims 1 to 6 , wherein the sulfated saccharide group is a sulfated lactosyl group.

8 . The composition of claim 7 , wherein the sulfated lactosyl group is a 6′-S-lactosyl group.

9 . The composition of claim 8 , wherein the 6′-S-lactosyl group is 6′-sulfate-β-D-Gal p -(1,4)-β-D-Glc p .

10 . The composition of any one of claims 1 to 9 wherein the synthetic charged glycolipid is a compound of the structure:

or a pharmaceutically acceptable salt thereof.

11 . The composition of any one of claims 1 to 10 , wherein less than 10% of the synthetic charged isoprenoid glycolipid molecules in the mixture comprise an archaeol moiety of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

12 . The composition of claim 11 , wherein about 5% to about 8% of the synthetic charged isoprenoid glycolipid molecules in the mixture comprise an archaeol moiety of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

13 . The composition of claim 12 , wherein about 6.5% of the synthetic charged isoprenoid glycolipid molecules in the mixture comprise an archaeol moiety of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

14 . An archaeosome comprising the composition of any one of claims 1 to 13 .

15 . An immunogenic composition comprising the composition of any one of claims 1 to 13 or the archaeosome of claim 14 , and an antigen.

16 . The immunogenic composition of claim 15 , wherein the antigen is a peptide, protein, or virus-like particle.

17 . The immunogenic composition of claim 15 or 16 , further comprising a pharmaceutically acceptable carrier.

18 . The immunogenic composition of any one of claims 15 to 17 , further comprising an adjuvant other than a synthetic charged isoprenoid glycolipid.

19 . The immunogenic composition of any one of claims 15 to 18 , wherein the immunogenic composition is a vaccine composition.

20 . A method of inducing an immune response in a subject, the method comprising administering the immunogenic composition of any one of claims 15 to 19 to a subject.

21 . A process for synthesizing a composition comprising a mixture of two or more stereoisomers of an archaeol, the process comprising treating (±)-3-benzyloxy-1,2-propanediol with a mesylated phytol derivative through a double nucleophilic substitution reaction, followed by a reductive debenzylation reaction,
wherein the archaeol is of the structure:

and wherein the mesylated phytol derivative is of the structure:

22 . The process of claim 21 , wherein the process comprises the following steps:

23 . A process for synthesizing a mixture of two or more stereoisomers of a synthetic charged isoprenoid glycolipid or a pharmaceutically acceptable salt thereof, the process comprising covalently linking a sulfated saccharide group of the formula:

to the free sn-1 hydroxyl group of the glycerol backbone of an archaeol,
wherein the archaeol comprises a mixture of two or more stereoisomers of the structure:

and wherein
n is 0 or 1;
R and R′ are independently hydrogen or hydroxyl;
each Y is independently hydrogen or a sulfate group, and wherein at least one Y is a sulfate group; and
less than 25% of the archaeol molecules in the mixture of two or more stereoisomers are of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

24 . The process of claim 23 , wherein the saccharide group is of the formula:

25 . The process of claim 23 or 24 , wherein less than 10% of the archaeol molecules in the mixture of two or more stereoisomers are of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

26 . The process of claim 23 or 24 , wherein about 5% to about 8% of the archaeol molecules in the mixture of two or more stereoisomers are of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

27 . The process of claim 23 or 24 , wherein about 6.5% of the archaeol molecules in the mixture of two or more stereoisomers are of the configuration (R)-2,3-bis(((3R,7R,11R)-3,7,11,15-tetramethylhexadecyl)oxy) propan-1-ol.

28 . The process of any one of claims 23 to 27 , wherein the archaeol is produced according to the process defined in claim 21 or 22 .

29 . Use of the composition of any one of claims 1 to 13 or the archaeosome of claim 14 for the manufacture of a vaccine or immunogenic composition.

30 . Use of the composition of any one of claims 1 to 13 or the archaeosome of claim 14 as an adjuvant in a vaccine or immunogenic composition.

31 . Use of the composition of any one of claims 1 to 13 or the archaeosome of claim 14 as an adjuvant to enhance or direct

Assignees

• Nat Res Council Canada

Inventors

• Hemraz Usha
• Régnier Sophie
• Lam Edmond
• Vasquez Vinicio
• Mccluskie Michael
• Stark Felicity
• Akache Bassel

Classifications

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07C41/09

  by dehydration of compounds containing hydroxy groups · CPC title

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• C07H15/08

  Polyoxyalkylene derivatives · CPC title