IP Library › Granted Patent US 12,419,977
Granted Patent B2
US 12,419,977 · App. 18/947,606 · Granted Sep 23, 2025

Radiopharmaceuticals

Inventors: Simon Puttick (Sydney, AU); William Tieu (Sydney, AU); Kevin Kuan (Sydney, AU)
Assignee: AdvanCell Isotopes Pty Limited
A61K51/0482C07B59/002A61K2121/00C07B2200/05
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Quick Facts
Patent No.
US 12,419,977
App. No.
18/947,606
Granted
Sep 23, 2025
Kind
B2
Abstract

This application relates generally to prostate specific membrane antigen (PSMA) targeting compounds which may be complexed to a radioisotope. Pharmaceutical compositions including such compounds also disclosed. Such compounds or pharmaceutical compositions may be used in nuclear medicine for the in-vivo imaging of various tissues, and the treatment and/or prevention of various PSMA-expressing cancers, especially prostate cancer.

Claims (87)

1. A compound of Formula (II) having the following structure:

wherein the compound of Formula (II) is also referred to as (3S,7S,26R,29R,32R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6, 12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate, thereof;

where the compound of Formula (II) is complexed to 212 Pb.

2. A compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof,

wherein the compound of Formula (III) is complexed to 212 Pb.

3. The compound of claim 2 , comprising a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

wherein the compound of Formula (III) is complexed to 212 Pb.

4. A comprising a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7, 10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof,

wherein the compound of Formula (IV) is complexed to 212 Pb.

5. The compound of claim 4 , comprising a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

wherein the compound of Formula (IV) is complexed to 212 Pb.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (II) having the following structure:

wherein the compound of Formula (II) is also referred to as (3S,7S,26R,29R,32R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof,

where the compound of Formula (II) is complexed to 2

a pharmaceutically acceptable excipient.

7. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

8. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid.

9. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

10. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid.

11. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) comprises a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof, and

a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

12. A method of treating a PSMA-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of Formula (II) having the following structure:

wherein the compound of Formula (II) is also referred to as (3S,7S,26R,29R,32R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5, 13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate, thereof,

wherein the compound of Formula (II) is complexed to 212 Pb, thereby treating the PSMA-expressing cancer in the patient.

13. The method of claim 12 , wherein the PSMA-expressing cancer is prostate cancer.

14. The method of claim 12 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

15. The method of claim 12 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid.

16. The method of claim 12 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

17. The method of claim 12 , wherein the compound of Formula (II) comprises at least 50% of a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid.

18. The method of claim 12 , wherein the compound of Formula (II) comprises a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7, 10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof, and

a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

19. The method of claim 18 , comprising administering to the patient a therapeutically effective amound of the compound of Formula (III) and the compound of Formula (IV) in substantially equal amounts.

20. The compound of claim 1 , comprising at least 50% of a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

21. The compound of claim 1 , comprising at least 50% of a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

22. The compound of claim 1 , wherein the compound is a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

23. The compound of claim 1 , wherein the compound is a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

24. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) is a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

25. The pharmaceutical composition of claim 6 , wherein the compound of Formula (II) is a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

26. The pharmaceutical composition of claim 11 , wherein the compound of Formula (II) comprises about 50% of the compound of Formula (III) and about 50% of the compound of Formula (IV).

27. The method of claim 12 , wherein the compound of Formula (II) is a compound of Formula (III) having the following structure:

wherein the compound of Formula (III) is also referred to as (3S,7S,26R,29R,32R,37S)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

28. The method of claim 12 , wherein the compound of Formula (II) is a compound of Formula (IV) having the following structure:

wherein the compound of Formula (IV) is also referred to as (3S,7S,26R,29R,32R,37R)-29-benzyl-32-(4-hydroxy-3-iodobenzyl)-5,13,20,28,31,34-hexaoxo-37-(4,7,10-tris (2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)-4,6,12,21,27,30,33-heptaazaheptatriacontane-1,3,7,26,37-pentacarboxylic acid,

or a pharmaceutically acceptable salt or solvate thereof.

29. The method of claim 18 , wherein the compound of Formula (II) comprises about 50% of the compound of Formula (III) and about 50% of the compound of Formula (IV).

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2026
From: ADVANCELL PTY LTD
To: ADVANCELL IPCO US NO. 1 PTY LTD
Reel/Frame 074728/0860 →
CHANGE OF NAME Recorded Jan 30, 2026
From: ADVANCELL ISOTOPES PTY LIMITED
To: ADVANCELL PTY LIMITED
Reel/Frame 074603/0151 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2025
From: PUTTICK, SIMON; TIEU, WILLIAM; KUAN, KEVIN
To: ADVANCELL ISOTOPES PTY LIMITED
Reel/Frame 070209/0812 →
Priority Claims (2)
AU 2022902273 · Aug 11, 2022 · national
AU 2022902274 · Aug 11, 2022 · national
Continuity (2)
Continuation PCTAU2023050763 · Aug 11, 2023
Related Publication 20250064994A1 · Feb 27, 2025
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