Claims for Patent: 11,369,590

Summary for Patent: 11,369,590

Title:	PSMA binding ligand-linker conjugates and methods for using
Abstract:	Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.
Inventor(s):	Low; Philip Stewart (West Lafayette, IN), Kularatne; Sumith A. (West Lafayette, IN)
Assignee:	Purdue Research Foundation (West Lafayette, IN)
Application Number:	17/359,277
Patent Claims:	1. A compound of the formula. B-L-D or a salt thereof, wherein B is a urea of two amino acids; L comprises (i) a divalent alkylenecarbonyl and (ii) at least one nitrogen atom, wherein the divalent alkylenecarbonyl is optionally substituted with one or more substituents X.sup.1 selected from the group consisting of alkyl, alkoxy, alkoxyalkyl, hydroxy, hydroxyalkyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, halo, haloalkyl, sulfhydrylalkyl, alkylthioalkyl, aryl, arylalkyl, heteroaryl, carboxy, carboxyalkyl, and alkyl carboxylate, and wherein L is about 7 to about 9 atoms in length; and D comprises a radioactive isotope of a metal coordinated to a chelating group. 2. The compound of claim 1, or a salt thereof, wherein B is of the formula ##STR00104## wherein R.sup.1 is hydrogen and R.sup.2 is a substituted carboxylic acid, and the substituted carboxylic acid is covalently bound to L. 3. The compound of claim 1, or a salt thereof, wherein L is covalently bound to B through an amide bond. 4. The compound of claim 1, or a salt thereof, wherein L is covalently bound to D through an amide bond. 5. The compound of claim 1, or a salt thereof, wherein the radioactive isotope of a metal is .sup.68Ga. 6. The compound of claim 3, or a salt thereof, wherein the radioactive isotope of a metal is .sup.68Ga. 7. The compound of claim 4, or a salt thereof, wherein the radioactive isotope of a metal is .sup.68Ga. 8. The compound of claim 2, or a salt thereof, wherein L is covalent boundd to B through an amide bond. 9. The compound of claim 2, or a salt thereof, wherein L is covalently bound to D through an amide bond. 10. The compound of claim 2, or a salt thereof, wherein the radioactive isotope of a metal is .sup.68Ga. 11. The compound of claim 8, or a salt thereof, wherein the radioactive isotope of a metal is .sup.68Ga. 12. The compound of claim 9, or a salt thereof, wherein the radioactive isotope of a metal is .sup.68Ga. 13. A pharmaceutical composition comprising a compound of the formula B-L-D or a salt thereof, wherein B is a urea of two amino acids; L comprises (i) a divalent alkylenecarbonyl and (ii) at least one nitrogen atom, wherein. the divalent alkylenecarbonyl is optionally substituted with one or more substituents X.sup.1 selected from the group consisting of alkyl, alkoxy, alkoxyalkyl, hydroxy, h.ydroxyalkyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, halo, haloalkyl, sulfhydrylalkyl, alkylthioalkyl, aryl, arylalkyl, heteroaryl, carboxy, carboxyalkyl, and alkyl carboxylate, and wherein L is about 7 to about 9 atoms in length; and D comprises a radioactive isotope of a metal coordinated to a chelating group; and one or more carriers, diluents or excipients. 14. The pharmaceutical composition of claim 13, wherein the carrier is an aqueous solution. 15. The pharmaceutical composition of claim 13, wherein B is of the formula ##STR00105## wherein R.sup.1 is hydrogen and R.sup.2 is a substituted carboxylic acid, and the substituted carboxylic acid is covalently bound to L. 16. The pharmaceutical composition of claim 15, wherein the carrier is an aqueous solution. 17. The pharmaceutical composition of claim 13, wherein the radioactive isotope of a metal is .sup.68Ga. 18. The pharmaceutical composition of claim 14, wherein the radioactive isotope of a metal is .sup.68Ga. 19. The pharmaceutical composition of claim 15, wherein the radioactive isotope of a metal is .sup.68Ga. 20. The pharmaceutical composition of claim 16, wherein the radioactive isotope of a metal is .sup.68Ga. 21. The pharmaceutical composition of claim 13, wherein L is covalently bound to B through an amide bond and the radioactive isotope of a metal is .sup.68Ga. 22. The pharmaceutical composition of claim 13, wherein L is covalently bound to D through an amide bond and the radioactive isotope of a metal is .sup.68Ga. 23. The pharmaceutical composition of claim 14, wherein L is covalently bound to B through an amide bond and the radioactive isotope of a metal is .sup.68Ga. 24. The pharmaceutical composition of claim 14, wherein L is covalently bound to D through an amide bond and the radioactive isotope of a metal is .sup.68Ga. 25. A method of imaging comprising administering to a subject a compound of claim 1, or a salt thereof, in an amount effective to image tissue or cells associated with pathogenic populations of cells expressing or over-expressing prostate-specific membrane antigen. 26. The method of claim 25, wherein the radioactive isotope of a metal is .sup.68Ga. 27. A method of imaging comprising administering to a subject a pharmaceutical composition of claim 13, or a salt thereof, in an amount effective to image tissue or cells associated with pathogenic populations of cells expressing or over-expressing prostate-specific membrane antigen. 28. The method of claim 27, wherein the radioactive isotope of a metal is .sup.68Ga. 29. The method of claim 27, wherein B is of the formula ##STR00106## wherein R.sup.1 is hydrogen and R.sup.2 is a substituted carboxylic acid, and the substituted carboxylic acid is covalently bound to L. 30. The method of claim 29, wherein the radioactive isotope of a metal is .sup.68Ga.