IP Library › Granted Patent US 11,229,713
Granted Patent B2
US 11,229,713 · App. 15/526,584 · Granted Jan 25, 2022

Methods and compositions for 18F-radiolabeling of biologics

Inventor: David Donnelly (Doylestown, PA)
Assignee: BRISTOL-MYERS SQUIBB COMPANY
A61K51/0455A61K51/088C07B59/002C07B59/008G01T1/2985
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Quick Facts
Patent No.
US 11,229,713
App. No.
15/526,584
Granted
Jan 25, 2022
Kind
B2
Abstract

The invention relates to water soluble 18 F-prosthetic groups and the synthesis and use of 18 F-labeled biological molecules containing the 18 F-prosthetic groups for imaging various processes within the body, for detecting the location of molecules associated with disease pathology, and for monitoring disease progression are disclosed.

Claims (42)

1. An 18 F-radiolabeled protein-based probe comprising 18 F-radiolabeled prosthetic group, a bifunctional conjugating (BFC) moiety and a protein with the following structure,

wherein the 18 F is ortho to the N atom, x is an integer from 1 to 8, and the BFC comprises a cyclooctyne moiety and a reactive group that forms a covalent bond with an amine, carboxyl, carbonyl or thiol functional group on the protein, or pharmaceutically acceptable salt thereof.

2. The 18 F-radiolabeled protein-based probe of claim 1 , wherein x is 4.

3. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the BFC further comprises a polyethylene glycol (PEG) y spacer arm, wherein y is an integer from 1 to 8.

4. The 18 F-radiolabeled protein-based probe of claim 3 , wherein the BFC is DBCO-PEG4-NHS-Ester, DBCO-PEG4-Acid, DBCO-PEG4-Amine or DBCO-PEG4-Maleimide.

5. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the protein portion of the probe comprises a fibronectin type III (Fn3) domain.

6. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the protein portion of the probe comprises an antibody or antibody fragment.

7. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the [O(CH 2 ) 2 ] x moiety is present in the 1-3 configuration relative to the nitrogen on the pyridine ring.

8. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the [O(CH 2 ) 2 ] x moiety is present in the 1-2 configuration relative to the nitrogen on the pyridine ring.

9. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the [O(CH 2 ) 2 ] x moiety is present in the 1-4 configuration relative to the nitrogen on the pyridine ring.

10. The 18 F-radiolabeled protein-based probe of claim 1 , wherein the BFC is covalently linked to a thiol group on a cysteine residue of the protein.

11. The 18 F-radiolabeled protein-based probe of claim 10 , wherein the cysteine residue is at the C-terminus of the protein.

12. The 18 F-radiolabeled protein-based probe of claim 1 , having the structure

13. The 18 F-radiolabeled protein-based probe of claim 12 , wherein the BFC further comprises a polyethylene glycol (PEG) y spacer arm, wherein y is an integer from 1 to 8.

14. The 18 F-radiolabeled protein-based probe of claim 13 , wherein the BFC is DBCO-PEG4-NHS-Ester, DBCO-PEG4-Acid, DBCO-PEG4-Amine or DBCO-PEG4-Maleimide.

15. The 18 F-radiolabeled protein-based probe of claim 14 , wherein the BFC is DBCO-PEG4-Maleimide.

16. The 18 F-radiolabeled protein-based probe of claim 12 , wherein the protein portion of the probe comprises a fibronectin type III (Fn3) domain.

17. The 18 F-radiolabeled protein-based probe of claim 12 , wherein the BFC is covalently linked to a thiol group on a cysteine residue of the protein.

18. The 18 F-radiolabeled protein-based probe of claim 17 , wherein the cysteine residue is at the C-terminus of the protein.

19. The 18 F-radiolabeled protein-based probe of claim 12 , wherein the protein portion of the probe comprises an antibody or antibody fragment.

20. The 18 F-radiolabeled protein-based probe of claim 1 , having the following structure,

wherein the maleimide group of the BFC is covalently linked to a thiol group on a cysteine residue of the protein.

21. The 18 F-radiolabeled protein-based probe of claim 20 , wherein the cysteine residue is at the C-terminus of the protein.

22. The 18 F-radiolabeled protein-based probe of claim 20 , wherein the protein portion of the probe comprises a fibronectin type III (Fn3) domain.

23. The 18 F-radiolabeled protein-based probe of claim 20 , wherein the protein portion of the probe comprises an antibody or antibody fragment.

24. The 18 F-radiolabeled protein-based probe of claim 1 , having the following structure,

25. The 18 F-radiolabeled protein-based probe of claim 24 , wherein the protein portion of the probe comprises a fibronectin type III (Fn3) domain, an antibody or an antibody fragment.

26. The 18 F-radiolabeled protein-based probe of claim 24 , wherein the BFC is covalently linked to a thiol group on a cysteine residue of the protein.

27. The 18 F-radiolabeled protein-based probe of claim 26 , wherein the cysteine residue is at the C-terminus of the protein.

28. The 18 F-radiolabeled protein-based probe of claim 24 , wherein the BFC further comprises a polyethylene glycol (PEG) y spacer arm, wherein y is an integer from 1 to 8.

29. The 18 F-radiolabeled protein-based probe of claim 28 , wherein the BFC is DBCO-PEG4-NHS-Ester, DBCO-PEG4-Acid, DBCO-PEG4-Amine or DBCO-PEG4-Maleimide.

30. The 18 F-radiolabeled protein-based probe of claim 1 , having the following structure,

31. The 18 F-radiolabeled protein-based probe of claim 30 , wherein the protein portion of the probe comprises a fibronectin type III (Fn3) domain, an antibody or an antibody fragment.

32. The 18 F-radiolabeled protein-based probe of claim 30 , wherein the BFC is covalently linked to a thiol group on a cysteine residue of the protein.

33. The 18 F-radiolabeled protein-based probe of claim 32 , wherein the cysteine residue is at the C-terminus of the protein.

34. The 18 F-radiolabeled protein-based probe of claim 30 , wherein the BFC further comprises a polyethylene glycol (PEG) y spacer arm, wherein y is an integer from 1 to 8.

35. The 18 F-radiolabeled protein-based probe of claim 34 , wherein the BFC is DBCO-PEG4-NHS-Ester, DBCO-PEG4-Acid, DBCO-PEG4-Amine or DBCO-PEG4-Maleimide.

36. A pharmaceutical composition comprising the 18 F-radiolabeled protein-based probe of claim 1 , and a pharmaceutically acceptable carrier.

37. A pharmaceutical composition comprising the 18 F-radiolabeled protein-based probe of claim 12 , and a pharmaceutically acceptable carrier.

38. A pharmaceutical composition comprising the 18 F-radiolabeled protein-based probe of claim 20 , and a pharmaceutically acceptable carrier.

39. A pharmaceutical composition comprising the 18 F-radiolabeled protein-based probe of claim 24 , and a pharmaceutically acceptable carrier.

40. A pharmaceutical composition comprising the 18 F-radiolabeled protein-based probe of claim 30 , and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 15, 2017
From: DONNELLY, DAVID
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 044136/0049 →
Continuity (2)
Provisional Application 62084366 · Nov 25, 2014
Related Publication 20180326098A1 · Nov 15, 2018
Cited By (1)
US 12,194,110