IP Library Granted Patent US 8,137,540
Granted Patent B2
US 8,137,540 · App. 12/545,040 · Granted Mar 20, 2012

Methods and apparatus for continuous large-scale radiolabeling

Assignee: Peregrine Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 8,137,540
App. No.
12/545,040
Granted
Mar 20, 2012
Kind
B2
Abstract

Disclosed are improved methods and apparatus for radiolabeling, particularly methods and apparatus for large scale in-line radiolabeling of products, such as proteins and antibodies.

Claims (60)

1. A continuous mode apparatus for labeling a molecule with a radioactive label, said apparatus comprising:

a reaction chamber or tube comprising a first end and a second end;

a first reagent vessel fluidly connected to said first end of said reaction chamber or tube through a first reagent tubing, said first reagent tubing connected to at least a first pump that moves fluid through said apparatus to achieve substantially continuous flow of fluid through said apparatus;

a second reagent vessel fluidly connected to said first end of said reaction chamber or tube through a second reagent tubing, said second reagent tubing connected to a pump;

a third reagent vessel fluidly connected to said first end of said reaction chamber or tube through a third reagent tubing, said third reagent tubing connected to a pump; and

at least a first purification unit comprising an inlet and an outlet, said inlet of said purification unit fluidly connected to said second end of said reaction chamber or tube;

wherein said purification unit comprises a capture agent that captures an unattached or free radioactive label and an unattached or free molecule on the basis of size, charge or affinity, but allows a radiolabeled molecule to pass through.

2. The apparatus of claim 1 , wherein said apparatus comprises a reaction tube.

3. The apparatus of claim 1 , wherein said first reagent tubing and said second reagent tubing are each connected to said first pump.

4. The apparatus of claim 3 , wherein said first reagent tubing, said second reagent tubing and said third reagent tubing are each connected to said first pump.

5. The apparatus of claim 4 , Wherein said first pump is a multi-channel peristaltic pump.

6. The apparatus of claim 5 , wherein said multi-channel peristaltic pump is controllable by a computer.

7. The apparatus of claim 1 , wherein said apparatus further comprises a radioshield; and wherein at least one of said reagent vessels is comprised within said radioshield.

8. the apparatus of claim 1 , wherein said purification unit comprises at least a first substance that binds iodine, mixed halogen species, and oxidized iodide species.

9. The apparatus of claim 1 , wherein said purification unit comprises at least a first ion exchange column or size exclusion column.

10. The apparatus of claim 9 , wherein said ion exchange column is an anion exchange column.

11. The apparatus of claim 1 , wherein said purification unit comprises at least a first dialysis unit.

12. The apparatus of claim 1 , wherein said apparatus further comprises at least a first dispensing unit or collection vessel fluidly connected to said outlet of said purification unit.

13. The apparatus of claim 12 , wherein said apparatus further comprises a filter comprising an input end and an output end, said input end of said filter fluidly connected to said outlet of said purification unit; and said output end of said filter connected to said collection vessel.

14. A continuous mode apparatus for radiolabeling a molecule, said apparatus comprising:

a reaction chamber or tube comprising a first end and a second end;

a first reagent vessel fluidly connected to said first end of said reaction chamber or tube through a first reagent tubing, said first reagent tubing connected to a pump that moves fluid through said apparatus to achieve substantially continuous flow of fluid through said apparatus;

a second reagent vessel fluidly connected to said first end of said reaction chamber or tube through a second reagent tubing, said second reagent tubing connected to said pump;

a third reagent vessel fluidly connected to said first end of said reaction chamber or tube through a third reagent tubing, said reagent tubing connected to said pump; and

at least a first purification unit comprising an inlet and an outlet, said inlet of said purification unit fluidly connected to said second end of said reaction chamber or tube;

wherein said purification unit comprises a capture agent that captures an unattached or free radioactive label and an unattached or free molecule on the basis of size, charge or affinity, but allows a radiolabeled molecule to pass through.

15. The apparatus of claim 14 , wherein said apparatus further comprises a radioshield; and wherein at least one of said reagent vessels is comprised within said radioshield.

16. A continuous mode apparatus for radiolabeling a molecule, said apparatus comprising:

a reaction chamber or tube comprising a first end and a second end;

a first reagent vessel fluidly connected to said first end of said reaction chamber or tube through a first reagent tubing, said first reagent tubing connected to a first pump that moves fluid through said apparatus to achieve substantially continuous flow of fluid through said apparatus;

a second reagent vessel fluidly connected to said first end of said reaction chamber or tube through a second reagent tubing, said second reagent tubing connected to a second pump that moves fluid through said apparatus to achieve substantially continuous flow of fluid through said apparatus;

a third reagent vessel fluidly connected to said first end of said reaction chamber or tube through a third reagent tubing, said reagent tubing connected to a third pump that moves fluid through said apparatus to achieve substantially continuous flow of fluid through said apparatus;

at least a first purification unit comprising an inlet and an outlet, said inlet of said purification unit fluidly connected to said second end of said reaction chamber or tube;

wherein said purification unit comprises a capture agent that captures an unattached or free radioactive label and an unattached or free molecule on the basis of size, charge or affinity, but allows a radiolabeled molecule to pass through.

17. The apparatus of claim 16 , wherein each of said first, second and third pump is a peristaltic pump.

18. The apparatus of claim 17 , wherein each of said first, second and third pump is controllable by a computer.

19. The apparatus of claim 16 , wherein said apparatus further comprises a radioshield; and wherein at least one of said reagent vessels is comprised within said radioshield.

20. A continuous mode apparatus for radiolabeling a molecule with an oxidizable radioactive label, comprising:

a reaction chamber or tube comprising a first end and a second end;

a first reagent vessel containing an oxidizing agent; wherein said first reagent vessel is fluidly connected to said first end of said reaction chamber or tube through a first reagent tubing, said first reagent tubing passing through at least a first pump;

a second reagent vessel containing said molecule; wherein said second reagent vessel is fluidly connected to said first end of said reaction chamber or tube through a second reagent tubing, said second reagent tubing passing through a pump;

a third reagent vessel containing said oxidizable radioactive label; wherein said third reagent vessel is fluidly connected to said first end of said reaction chamber or tube through a third reagent tubing, said third reagent tubing passing through a pump; and

at least a first purification unit comprising an inlet and an outlet, said inlet of said purification unit fluidly connected to said second end of said reaction chamber or tube;

wherein said purification unit comprises a capture agent that captures an unattached or free oxidizable radioactive label and an unattached or free molecule on the basis of size, charge or affinity, but allows a radiolabeled molecule to pass through;

wherein said molecule, said oxidizable radioactive label and said oxidizing agent substantially continuously flow through said reaction chamber or tube.

21. The apparatus of claim 20 , wherein said apparatus further comprises a radioshield; and wherein said third reagent vessel containing said oxidizable radioactive label is comprised within said radioshield.

22. A method of making a continuous mode apparatus for radiolabeling a molecule, said method comprising:

providing at least a first reagent vessel, a second reagent vessel and a third reagent vessel;

providing a reaction chamber or tube comprising a first end and a second end;

providing at least a first pump that moves fluid through said apparatus to achieve substantially continuous flow of fluid through said apparatus;

providing at least a first purification unit comprising an inlet, an outlet and a capture agent; wherein said capture agent is capable of capturing an unattached or free radioactive label and an unattached or free molecule on the basis of size, charge or affinity, but allows a radiolabeled molecule to pass through;

fluidly connecting said first reagent vessel to said first end of said reaction chamber or tube using a first reagent tubing, said first reagent tubing connected to said at least a first pump;

fluidly connecting said second reagent vessel to said first end of said reaction chamber or tube using a second reagent tubing, said second reagent tubing connected to a pump;

fluidly connecting said third reagent vessel to said first end of said reaction chamber or tube using a third reagent tubing, said third reagent tubing connected to a pump; and

fluidly connecting said second end of said reaction tube to said inlet of said purification unit.

23. The method of claim 22 , further comprising providing at least a first dispensing unit or collection vessel; and fluidly connecting said outlet of said purification unit to said at least a first dispensing unit or collection vessel.

24. The method of claim 22 , wherein said at least a first pump is a peristaltic pump having at least a first and second channel.

25. The method of claim 24 , wherein said first reagent tubing and said second reagent tubing are connected to said first and second channel of said peristaltic pump.

26. The method of claim 24 , wherein said peristaltic pump further includes a third channel.

27. The method of claim 26 , wherein said third reagent tubing is connected to said third channel of said peristaltic pump.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 3, 2014
From: PELLIKKA, RAIMO; KING, STEVEN W; BLAUENSTEIN, PETER; SCHUBIGER, PIUS A
To: PEREGRINE PHARMACEUTICALS, INC.
Reel/Frame 032116/0647 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2009
From: PELLIKKA, RAIMO; KING, STEVEN W; BLAUENSTEIN, PETER; SCHUBIGER, PIUS
To: PEREGRINE PHARMACEUTICALS
Reel/Frame 023126/0733 →
Continuity (5)
Division 10877959 · Jun 25, 2004
Provisional Application 60482387 · Jun 25, 2003
Provisional Application 60493121 · Aug 7, 2003
Provisional Application 60493689 · Aug 8, 2003
Related Publication 20090312523A1 · Dec 17, 2009