IP Library › Granted Patent US 12,497,429
Granted Patent B2
US 12,497,429 · App. 16/981,939 · Granted Dec 16, 2025

Saponin-based vaccine adjuvants

Inventor: Pengfei Wang (Hoover, AL)
Assignee: THE UAB RESEARCH FOUNDATION
C07J63/008A61K39/39A61K2039/55577
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Quick Facts
Patent No.
US 12,497,429
App. No.
16/981,939
Granted
Dec 16, 2025
Kind
B2
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.

Claims (27)

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:

Assignments (2)
CONFIRMATORY LICENSE Recorded Oct 17, 2023
From: UNIVERSITY OF ALABAMA AT BIRMINGHAM
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065256/0775 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2020
From: WANG, PENGFEI
To: THE UAB RESEARCH FOUNDATION
Reel/Frame 054269/0507 →
Continuity (2)
Provisional Application 62645497 · Mar 20, 2018
Related Publication 20210040143A1 · Feb 11, 2021
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