IP Library › Granted Patent US 12,427,210
Granted Patent B2
US 12,427,210 · App. 17/625,139 · Granted Sep 30, 2025

Compounds comprising a fibroblast activation protein ligand and use thereof

Inventors: Frank Osterkamp (Berlin, DE); Dirk Zboralski (Berlin, DE); Eberhard Schneider (Brandenburg, DE); Christian Haase (Berlin, DE); Matthias Paschke (Berlin, DE); Aileen Höhne (Berlin, DE); Jan Ungewiss (Berlin, DE); Christiane Smerling (Berlin, DE); Ulrich Reineke (Berlin, DE); Anne Bredenbeck (Berlin, DE)
Assignee: 3B PHARMACEUTICALS GMBH
A61K51/088C07K7/08A61K38/00
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Quick Facts
Patent No.
US 12,427,210
App. No.
17/625,139
Granted
Sep 30, 2025
Kind
B2
Abstract

The present invention is related to a compound comprising a cyclic peptide and a chelator, and its use.

Claims (69)

1. A compound, which is:

or a pharmaceutically acceptable salt thereof, or a solvate thereof; or

or a pharmaceutically acceptable salt thereof, or a solvate thereof.

2. The compound of claim 1 , wherein the compound is:

or the pharmaceutically acceptable salt thereof, or the solvate thereof.

3. The compound of claim 1 , wherein the compound is:

or the pharmaceutically acceptable salt thereof, or the solvate thereof.

4. A compound, which is:

or a pharmaceutically acceptable salt thereof, or a solvate thereof,

wherein the compound comprises a diagnostically active radionuclide or a therapeutically active radionuclide.

5. A composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

6. The compound of claim 4 , wherein the compound comprises the diagnostically active radionuclide.

7. The compound of claim 6 , wherein the diagnostically active radionuclide is selected from the group consisting of 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 201 Tl, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, and 125 I.

8. The compound of claim 6 , wherein the diagnostically active radionuclide is selected from the group consisting of 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, and 125 I.

9. The compound of claim 6 , wherein the diagnostically active radionuclide is selected from the group consisting of 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F, 123 I, and 124 I.

10. The compound of claim 4 , wherein the compound comprises the therapeutically active radionuclide.

11. The compound of claim 10 , wherein the therapeutically active radionuclide is selected from the group consisting of 47 Sc, 67 Cu, 89 Sr, 90 Y, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, and 211 At.

12. The compound of claim 10 , wherein the therapeutically active radionuclide is selected from the group consisting of 47 Sc, 67 Cu, 90 Y, 177 Lu, 188 Re, 212 Pb, 213 Bi, 225 Ac, 227 Th, 131 I, and 211 At.

13. The compound of claim 10 , wherein the therapeutically active radionuclide is selected from the group consisting of 90 Y, 177 Lu, 225 Ac, 227 Th, 131 I, and 211 At.

14. A compound, which is:

or a pharmaceutically acceptable salt thereof, or a solvate thereof,

wherein the compound comprises a diagnostically active radionuclide or a therapeutically active radionuclide.

15. The compound of claim 14 , wherein the compound comprises the diagnostically active radionuclide, which is selected from the group consisting of 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 201 Tl, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, and 125 I.

16. The compound of claim 14 , wherein the compound comprises the therapeutically active radionuclide, which is selected from the group consisting of 47 Sc, 67 Cu, 89 Sr, 90 Y, 153 Sm, 149 Th, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, and 211 At.

17. A composition comprising the compound of claim 2 and a pharmaceutically acceptable excipient.

18. A composition comprising the compound of claim 4 and a pharmaceutically acceptable excipient.

19. The compound of claim 1 , wherein the solvate is a hydrate.

20. The compound of claim 4 , wherein the compound is:

21. The compound of claim 20 , wherein the compound comprises the therapeutically active radionuclide.

22. The compound of claim 14 , wherein the compound is:

23. The compound of claim 10 , wherein the therapeutically active radionuclide is a particle-emitting isotope having a decay energy of 0.039 to 10 MeV.

24. The compound of claim 10 , wherein the therapeutically active radionuclide is a particle-emitting isotope having a decay energy of 0.4 to 6.5 MeV.

25. The compound of claim 10 , wherein the therapeutically active radionuclide is 177 Lu.

26. The compound of claim 10 , wherein the therapeutically active radionuclide is a radiometal complexed to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator of the compound.

27. The compound of claim 21 , wherein the therapeutically active radionuclide is a radiometal complexed to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator of the compound.

28. A compound:

wherein 177 Lu is complexed to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator of the compound.

29. A radionuclide chelate complex comprising:

the compound of claim 1 ; and

a radionuclide,

wherein the radionuclide is complexed to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator of the compound.

30. The complex of claim 29 , wherein the radionuclide is a therapeutically active radionuclide.

31. The complex of claim 29 , wherein the radionuclide is a diagnostically active radionuclide.

32. The complex of claim 30 , wherein the therapeutically active radionuclide is selected from the group consisting of 47 Sc, 67 Cu, 90 Y, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 212 Pb, 213 Bi, 225 Ac, 226 Th, and 227 Th.

33. The complex of claim 31 , wherein the diagnostically active radionuclide is selected from the group consisting of 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y, 111 In, 152 Tb, 155 Tb, 201 Tl, and 203 Pb.

34. A composition comprising the compound of claim 20 and a pharmaceutically acceptable excipient.

35. A composition comprising the compound of claim 25 and a pharmaceutically acceptable excipient.

36. A composition comprising the compound of claim 28 and a pharmaceutically acceptable excipient.

37. A method of treating a cancer in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound according to claim 10 .

38. The method of claim 37 , wherein the cancer involves cells expressing fibroblast activation protein (FAP).

39. A method of treating a tumor in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound according to claim 10 .

40. The method of claim 39 , wherein the tumor involves cells expressing fibroblast activation protein (FAP).

41. The method of claim 39 , wherein the tumor is a solid tumor.

42. The method of claim 39 , wherein the tumor is an epithelial tumor.

43. A method of treating a disease in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 10 , wherein the disease is selected from the group consisting of bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary carcinoma, sarcoma, squamous cell carcinoma, and thyroid cancer.

44. A method of treating a disease in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 10 , wherein the disease is breast cancer, non-small cell lung cancer, or pancreatic cancer.

45. A method of treating a cancer in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound according to claim 25 .

46. The method of claim 45 , wherein the cancer involves cells expressing fibroblast activation protein (FAP).

47. A method of treating a tumor in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 25 .

48. The method of claim 47 , wherein the tumor involves cells expressing fibroblast activation protein (FAP).

49. The method of claim 47 , wherein the tumor is a solid tumor.

50. The method of claim 47 , wherein the tumor is an epithelial tumor.

51. A method of treating a disease in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 25 , wherein the disease is selected from the group consisting of bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary carcinoma, sarcoma, squamous cell carcinoma, and thyroid cancer.

52. A method of treating a disease in a patient in need thereof, comprising administering to the patient in need thereof a therapeutically effective amount of a compound:

wherein 177 Lu is complexed to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator of the compound, and

wherein the disease is breast cancer, non-small cell lung cancer, or pancreatic cancer.

53. The method of claim 52 , wherein the disease is breast cancer.

54. The method of claim 52 , wherein the disease is non-small cell lung cancer.

55. The method of claim 52 , wherein the disease is pancreatic cancer.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 6, 2022
From: OSTERKAMP, FRANK; ZBORALSKI, DIRK; SCHNEIDER, EBERHARD; HAASE, CHRISTIAN; PASCHKE, MATTHIAS; HÖHNE, AILEEN; UNGEWISS, JAN; SMERLING, CHRISTIANE; REINEKE, ULRICH; BREDENBECK, ANNE
To: 3B PHARMACEUTICALS GMBH
Reel/Frame 058577/0471 →
Priority Claims (2)
EP 19000325 · Jul 8, 2019 · regional
EP 19198813 · Sep 20, 2019 · regional
Continuity (1)
Related Publication 20220273831A1 · Sep 1, 2022
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