Saponin-based vaccine adjuvants

Patent metadata

Field	Value
Publication number	US-12497429-B2
Application number	US-201916981939-A
Country	US
Kind code	B2
Filing date	Mar 20, 2019
Priority date	Mar 20, 2018
Publication date	Dec 16, 2025
Grant date	Dec 16, 2025

Abstract

Provided are variants of saponins that are found in Quillaja saponaria (QS) Molina tree bark that are chemically modified to distinguish them from naturally occurring parent saponins. The modified saponins have increased adjunctive activity compared to the unmodified parent saponins. Defined structures allow for comparisons of the modifying groups with respect to their respective adjunct activity and permit characterized vaccine formulations that have one or more defined saponins.

First claim

What is claimed:

1 . A modified saponin having the formula:

wherein:
f3 and f4 are each independently OH, acetyl, or a cyclic ketal ring or cyclic carbonate ester formed by the C3 and C4 of the fucosyl unit, f3, and f4;
f5 is a methyl group, a carboxyl group, R 4 -NR 5 -C(O)—, or an alkoxy group having the structure R 4 —O—, wherein R 4 and R 5 are each independently a linear chain having the structure R 6 (CH 2 ) 0-20 —, and wherein R 6 is H, OH, COOH, COOMe, COOEt, COOiPr, COOtBu, or COOBn;
r3 is H, a monosaccharide, a disaccharide, or a trisaccharide;
x3 is H, a monosaccharide, or a disaccharide;
ga5 is a carboxyl group, R 4 —NR 5 —C(O)—, or an alkoxy group having the structure R 4 —O—, R 4 is a linear chain having the structure R 7 (CH 2 ) 0-20 —, and wherein R 7 is OH, COOH, COOMe, COOEt, COOiPr, COOtBu, COOBn, a monophosphoryl lipid A (MPL), or a dipalmitoyl-S-glyceryl cysteine (PamCys) unit, wherein R 5 is a linear chain having the structure R 8 (CH 2 ) 0-20 —, and wherein R 8 is H, OH, COOH, COOMe, COOEt, COOiPr, COOtBu, COOBn, a saccharide unit, a monophosphoryl lipid A (MPL), or a dipalmitoyl-S-glyceryl cysteine (PamCys) unit; and
when f3 and f4 are both OH and f5 is a methyl group, ga5 is not a carboxyl group or COOH(CH 2 ) 0-20 —NH—C(O)—.

2 . A modified saponin having the formula I:

wherein:
R 1 and R 2 are each independently OH, acetyl, or a cyclic ketal ring or cyclic carbonate ester formed by the C3 and C4 of the fucosyl unit, R 1 , and R 2 ;
R 3 is a carboxyl group, R 4 -NR 5 -C(O)—, or an alkoxy group having the structure R 4 —O—, wherein R 4 is a saccharide unit or a linear chain having the structure R 7 (CH 2 ) 0-20 -, and wherein R 7 is OH, COOH, COOMe, COOEt, COOiPr, COOtBu, COOBn, a monophosphoryl lipid A (MPL), or a dipalmitoyl-S-glyceryl cysteine (PamCys) unit, wherein R 5 is a linear chain having the structure R 8 (CH 2 ) 0-20 —, and wherein R 8 is H, OH, COOH, COOMe, COOEt, COOiPr, COOtBu, COOBn, a saccharide unit, a monophosphoryl lipid A (MPL), or a dipalmitoyl-S-glyceryl cysteine (PamCys) unit; and
when R 1 and R 2 are both OH, R 3 is not a carboxyl group or COOH(CH 2 ) 0-20 —NH—C(O)—.

3 . The modified saponin of claim 2 , wherein R 1 and R 2 are each OH.

4 . The modified saponin of claim 2 , wherein R 1 and R 2 are each acetyl.

5 . The modified saponin of claim 2 , wherein R 1 and R 2 form an acetonide group protecting the 3-OH and the 4-OH of the fucosyl unit.

6 . The modified saponin of claim 2 , wherein R 1 and R 2 form a carbonate ester group protecting the 3-OH and the 4-OH of the fucosyl unit.

7 . The modified saponin of claim 2 , wherein R 3 is a carboxyl group.

8 . The modified saponin of claim 2 , wherein R 4 is a long-chain fatty acid having the structure HOOC—(CH 2 ) 6-20 —.

9 . The modified saponin of claim 2 , wherein R 4 is a long-chain fatty acid having the structure HOOC—(CH 2 ) 11 .

10 . The modified saponin of claim 2 , wherein R 3 is an alkoxy group having the structure R 7 —(CH 2 ) 6-20 —O—.

11 . The modified saponin of claim 2 , wherein R 4 is a long-chain alcohol having the structure HO—(CH 2 ) 6-20 —.

12 . The modified saponin of claim 2 , wherein R 4 is R 7 —(CH 2 ) 6-20 —.

13 . The modified saponin of claim 2 , wherein the saccharide unit of R 4 is a monosaccharide, a disaccharide, or trisaccharide.

14 . The modified saponin of claim 2 , wherein R 4 is a MPL unit.

15 . The modified saponin of claim 2 , wherein R 4 is a Pam2Cys unit or Pam3Cys unit.

16 . A modified saponin having any of the formulas B-D:

Assignees

• Uab Res Found

Inventors

• Wang Pengfei

Classifications

• A61K2039/55577

  Saponins; Quil A; QS21; ISCOMS · CPC title

• A61K39/39

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

• C07J63/008 Primary

  Expansion of ring D by one atom, e.g. D homo steroids · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07H15/20 Primary

  Carbocyclic rings · CPC title