IP Library › Granted Patent US 12,514,843
Granted Patent B2
US 12,514,843 · App. 17/620,517 · Granted Jan 6, 2026

Biofilm disruption

Inventors: David William Thomas (Cardiff, GB); Paul Warren Reddell (Yungaburra, AU); Glen Mathew Boyle (Taringa, AU); Jason Kingsley Cullen (Thornside, AU); Victoria Anne Gordon (Yungaburra, AU); Katja Etel Hill (Cardiff, GB); Lydia Charlotte Powell (Neath, GB); Manon F. Pritchard (Whitchurch, GB); Peter G. Parsons (St. Lucia, AU)
Assignee: QBIOTICS PTY LTD
A61K31/336A61K45/06A61P31/04
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Quick Facts
Patent No.
US 12,514,843
App. No.
17/620,517
Granted
Jan 6, 2026
Kind
B2
Abstract

The present invention relates to methods of dispersing biofilms comprising Gram-negative bacteria, the methods comprising exposing the biofilm to an epoxytiglienone compound or a salt thereof. Methods of treating infections comprising the localised administration, for example, topically or by injection, of an epoxytiglienone compound into or onto an established biofilm comprising Gram-negative bacteria to disrupt the structure of that biofilm and methods of preventing biofilms comprising Gram-negative bacteria forming or dispersing biofilms comprising Gram-negative biofilms that have formed on medical devices are also described.

Claims (50)

1 . A method of treating a bacterial infection comprising a biofilm comprising Gram-negative bacteria, said method comprising locally administering to the bacterial infection an epoxytiglienone compound of formula (I):

wherein

R 1 is selected from hydrogen and C 1-6 alkyl;

R 2 is selected from —OC 1-8 alkyl, —OC 2-8 alkenyl, —OC 2-8 alkynyl, —OC(O)C 1-7 alkyl, —OC(O)C 2-7 alkenyl and —OC(O)C 2-7 alkynyl;

R 3 is selected from —OH, —OC 1-8 alkyl, —OC 2-8 alkenyl, —OC 2-8 alkynyl, —OC(O)C 1-7 alkyl, —OC(O)C 2-7 alkenyl and —OC(O)C 2-7 alkynyl;

R 4 and R 5 are independently selected from hydrogen and C 1-6 alkyl;

R 6 is selected from hydrogen, —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C(O)C 1-6 alkyl, —C(O)C 2-6 alkenyl, —C(O)C 2-6 alkynyl, —C(O)C 3-8 cycloalkyl, —C(O)C 1-6 alkylC 3-8 cycloalkyl, —C(O)C 2-6 alkenylC 3-8 cycloalkyl, —C(O)C 2-6 alkynylC 3-8 cycloalkyl, —C(O)aryl, —C(O)C 1-6 alkylaryl, —C(O)C 2-6 alkenylaryl and —OC(O)C 2-6 alkynylaryl;

R 7 is selected from hydroxy, —OC 1-6 alkyl, —OC 2-6 alkenyl, —OC 2-6 alkynyl, —OC(O)C 1-6 alkyl, —OC(O)C 2-6 alkenyl, —OC(O)C 2-6 alkynyl, —C(O)C 3-8 cycloalkyl, —C(O)C 1-6 alkylC 3-8 cycloalkyl, —C(O)C 2-6 alkenylC 3-8 cycloalkyl, —C(O)C 2-6 alkynylC 3-8 cycloalkyl, —OC(O)aryl, —OC(O)C 1-6 alkylaryl, —C(O)C 2-6 alkenylaryl and —C(O)C 2-6 alkynylaryl; and

R 8 is selected from hydrogen and C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

2 . The method according to claim 1 wherein the local administration is topical administration.

3 . The method according to claim 1 wherein the infection is a post-surgical infection or an infection at the site of insertion of a medical device or implantation of an implant.

4 . The method according to claim 1 wherein the bacterial infection is a chronic infection.

5 . The method according to claim 1 wherein the administration is in combination with an antibiotic to which the Gram-negative bacteria is susceptible when in planktonic state.

6 . The method according to claim 1 , wherein one or more of the following applies:

i) R 1 is C 1-3 alkyl;

ii) R 2 is selected from —OC(O)C 1-7 alkyl, —OC(O)C 2-7 alkenyl and —OC(O)C 2-7 alkynyl;

iii) R 3 is selected from —OC(O)C 1-7 alkyl, —OC(O)C 2-7 alkenyl and —OC(O)C 2-7 alkynyl;

iv) R 4 and R 5 are each methyl;

v) R 6 is selected from hydrogen, —C(O)C 1-6 alkyl, —C(O)C 2-6 alkenyl, —C(O)C 2-6 alkynyl and —C(O)aryl;

vi) R 7 is hydroxyl, —OC(O)C 1-6 alkyl, —OC(O)C 2-6 alkenyl or —OC(O)C 2-6 alkynyl; and

vii) R 8 is C 1-3 alkyl.

7 . The method according to claim 6 , wherein R 2 is selected from —OC(O)C 3-6 alkyl and —OC(O)C 3-6 alkenyl.

8 . The method according to claim 6 , wherein R 3 is selected from —OC(O)C 3-6 alkyl, —OC(O)C 3-6 alkenyl and —OC(O)C 3-6 alkynyl.

9 . The method according to claim 6 , wherein R 6 is selected from hydrogen, —C(O)CH 3 , —C(O)CH 2 CH 3 , —C(O)CH(CH 3 ) 2 or —C(O)CH 2 CH 2 CH 3 .

10 . The method according to claim 1 , wherein the alkyl or alkenyl group of R 2 and/or R 3 are branched alkyl or alkenyl groups.

11 . The method according to claim 1 , wherein the alkyl or alkenyl group of R 2 and/or R 3 are linear alkyl or alkenyl groups.

12 . The method according to claim 1 , wherein the compound of formula (I) is selected from:

12-tigloyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 1);

12,13-di-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 2);

12-hexanoyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 3);

12,13-dihexanoyl-6,7-epoxy-4,5,9,12, 13,20-hexahydroxy-1-tiglien-3-one (Compound 4);

12-tigloyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12, 13-pentahydroxy-20-acetyloxy-1-tiglien-3-one (Compound 5);

12-propanoyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 6);

12,13-ditigloyl-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 7);

12-(2-methylbutanoyl)-13-tigloyl-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 8);

12-butanoyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 9);

12-(3,3-dimethylbut-2-enoyl)-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 10);

12-hex-2,4-dienoyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 11);

12-tigloyl-13-(2-methylpropanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 12);

12-but-2-enoyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 13);

12-tigloyl-13-butanoyl-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 14);

12, 13-dibutanoyl-6,7-epoxy-4,5,9,12, 13,20-hexahydroxy-1-tiglien-3-one (Compound 15);

12, 13-dipentanoyl-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 16);

12,13-di-(2E,4E)-hexa-2,4-dienoyl-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglien-3-one (Compound 17);

12-(2-methylprop-2-enoyl)-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tigliaen-3-one (Compound 19);

12,13-di-heptanoyl-6,7-epoxy-4,5,9,12, 13,20-hexahydroxy-1-tigliaen-3-one (Compound 20); and

12,13-di-(3-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tigliaen-3-one (Compound 21);

or a pharmaceutically acceptable salt thereof.

13 . The method according to claim 1 , wherein the biofilm comprising Gram-negative bacteria comprises at least one Gram-negative bacteria selected from Pseudomonas species, Acinetobacter species, Aeromonas species, Bacteroides species, Bordetella species, Borrelia species, Burkholderia species, Citrobacter species, Compylobacter species, Escherichia species, Enterobacter species, Flavobacterium species, Fusobacterium species, Klebsiella species, Leptospira species, Neisseria species, Helicobacter species, Hemophilus species, Legionella species, Moraxella species, Yersinia species, Oligella species, Pantoea Species, Porphyromonas species, Prevotella species, Proteus species, Raoultella species, Salmonella species, Serratia species, Shigella species, Sphingomonas species, Stenotophomonas species, Treponema species, Veillonella species and Vibrio species.

14 . The method according to claim 13 , wherein the Gram-negative bacteria is selected from Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, Hemophilus influenzae, Legionella pneumophila, Yersinia pestis, Yersinia enterocolitica, Salmonella enterica, Salmonella bongori, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens, Bacteroides fragilis, Fusobacterium necrophorum, Burkholderia cepacian and Prevotella intermedia.

Assignments (7)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 2, 2025
From: QBIOTICS GROUP LIMITED
To: QBIOTICS PTY LTD
Reel/Frame 073088/0912 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 24, 2024
From: CARDIFF UNIVERSITY
To: QBIOTICS GROUP LIMITED
Reel/Frame 069011/0481 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 24, 2024
From: QBIOTICS GROUP LIMITED
To: QBIOTICS PTY LTD
Reel/Frame 069011/0509 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 24, 2024
From: THOMAS, DAVID WILLIAM; HILL, KATJA ETEL; POWELL, LYDIA CHARLOTTE; PRITCHARD, MANON F.
To: CARDIFF UNIVERSITY
Reel/Frame 069011/0460 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 24, 2024
From: GORDON, VICTORIA ANNE; REDDELL, PAUL WARREN; PARSONS, PETER GORDON
To: QBIOTICS GROUP LIMITED
Reel/Frame 069270/0004 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 24, 2024
From: BOYLE, GLEN MATHEW; CULLEN, JASON KINGSLEY
To: THE COUNCIL OF THE QUEENSLAND INSTITUTE OF MEDICAL RESEARCH
Reel/Frame 069274/0323 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 24, 2024
From: THE COUNCIL OF THE QUEENSLAND INSTITUTE OF MEDICAL RESEARCH
To: QBIOTICS GROUP LIMITED
Reel/Frame 069267/0701 →
Priority Claims (1)
AU 2019902144 · Jun 19, 2019 · national
Continuity (1)
Related Publication 20220313648A1 · Oct 6, 2022
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