Device and method for single-needle in vivo electroporation

• US 20070287950A1
• Filed: 02/09/2007
• Published: 12/13/2007
• Est. Priority Date: 02/11/2006
• Status: Active Grant

• Current Assignee: Inovio Pharmaceuticals, Inc.
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Kjeken, Rune, Mathiesen, Iacob, McHugh, George, Tjelle, Elisabeth
• Granted Patent: US 10,369,359 B2
• Time in Patent Office: Days
• US Class Current: 604/21
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

Described is a device and method for administration of molecules to tissue in vivo for various medical applications, the device comprising a single hypodermic injection needle and at least two spaced elongate electrodes which provide for the ability, when the needle is inserted into tissue, such as skin or muscle, to pulse tissue with a non-uniform electric field sufficient to cause reversible poration of cells lying along or in close proximity to the track made by the needle upon its insertion into said tissue.

Claims

1. A device for electroporation of tissue in vivo for delivering therapeutic substances into cells of said tissue comprising:

a. An elongate delivery tube capable of penetrating a body tissue comprising at least two elongate electrodes exposed to an outer surface of said tube, said electrodes spaced and electrically isolated from one another and situated parallel with respect to one another; and

b. Electric conduits capable of connecting each of said electrodes to an electrical energy source;

c. Characterized in that said electrodes when said tube is inserted into a patient tissue and energized by said energy source are capable of generating an electric field to cells in a treatment zone surrounding said tube sufficient to cause cells along and near a track made by insertion of said tube into said tissue to become reversibly porated so as to allow said cells to take up said substances.

2. The device according to claim 1 further comprising an expandable or contractible reservoir.

3. The device according to claim 2 wherein said reservoir comprises a syringe.

4. The device according to claim 3 wherein said reservoir has a variable volume capacity selected from the group consisting of 0.0 to 0.5 ml, 0.0 to 1 ml, 0.0 to 3 ml, and 0.0 to 5 ml.

5. The device according to claim 1 wherein said electrical energy source is an electroporation pulse generator.

7. The device according to claim 5 wherein said generator is capable of generating electric pulses having a current of 1 mAmp to 400 mAmps.

11. The device according to claim 1 wherein said tube is a hypodermic needle sized to the gauge of an injection needle selected from the group consisting of 20 gauge, 21 gauge, 22 gauge, 23 gauge, 24 gauge, 25 gauge, 26 gauge, 27 gauge, 28 gauge and 29 gauge.

12. The device according to claim 1 wherein said tube is electrically insulated from each electrode.

13. The device according to claim 1 wherein said tissue comprises any body tissue type or organ selected from the group consisting of skin, subcutaneous tissue, intradermal tissue, subdermal tissue, skeletal muscle, striated muscle, smooth muscle, organs, heart, breast, lung, pancreas, liver, spleen and mucosa.

28. The device according to claim 1 wherein said electrical energy source is an electroporation pulse generator.

30. The method according to claim 13 wherein said generator is pulsed at a constant current selected from the group consisting of 1 to 400 mAmps.

31. The method according to claim 13 wherein said constant current range is selected from the group consisting of wherein said current is within a range selected from the group consisting of between 10 and 40, 25 and 100, 50 and 150, 125 and 200, 175 and 250, 225 and 300, 250 and 300, and 300 and 400.

33. The method according to claim 13 wherein said generator is pulsed for a time length between about 0.1 us to 1000 ms.

34. The method according to claim 13 wherein said tube is sized to a gauge of an injection needle selected from the group consisting of 20 gage, 21 gauge, 22 gauge, 23 gauge, 24 gauge, 25 gauge, 26 gauge, 27 gauge, 28 gauge and 29 gauge.

6. The device according to claim 6 wherein said generator is capable of generating electric pulses wherein the average voltage can range between 1 to 200 V.

9. The device according to claim 6 wherein said generator is capable of generating electric pulses having a frequency selected from the group consisting of 1 to 10,000 Hz.

10. The device according to claim 6 wherein said generator is capable of generating electric pulses having a time length selected from the group consisting of 0.1 us to 1000 ms.

8. The device according to claim 8 wherein said current is within a range selected from the group consisting of between 10 and 40, 25 and 100, 50 and 150, 125 and 200, 175 and 250, 225 and 300, 250 and 300, and 300 and 400.

14. A device for delivering a therapeutic substance into cells of a tissue comprising:

At least two parallel elongate electrodes capable of penetrating a body tissue wherein said electrodes each comprise an elongated shaft having a proximate end and a distal end wherein said electrodes are fixed in permanent relation to one another at said proximate end at a distance of no more that 1 mm and wherein said device has further components selected from the group consisting of an electrically inert material in contact with each electrode running the length of said electrodes, and no electrically inert material between said electrodes running the length of said electrodes.

15. A method of electroporating cells in vivo with a therapeutically useful composition comprising:

a. providing a tube for injection of said composition comprising at least two elongate electrodes positioned along at least a portion of said tube;

b. providing a reservoir containing said composition, said reservoir and composition being in fluid communication with a lumen running through said tube;

c. forming a channel in a preselected treatment site on a patient by inserting said tube into tissue in vivo in said patient;

d. injecting said composition from said reservoir through said lumen into said treatment site comprising said channel;

e. providing a source of electrical energy to each of said electrodes sufficient to cause reversible poration of cells in said treatment site; and

f. activating said source of electrical energy to provide an electric pulse thereby electroporating said cells for their uptake of said composition.

16. The method according to claim 16 wherein said composition comprises any of a drug, a nucleic acid, an antigen, a nucleic acid encoding an expressible antigen, a nucleic acid encoding an expressible immune modulating molecule.

19. The method according to claim 16 wherein said cells comprise cells of a live patient selected from the group consisting of subcutaneous cells, intradermal, subdermal cells, skeletal muscle cells, striated muscle cells, smooth muscle cells, organ cells, breast tissue cells, pancreas cells, spleen cells, heart cells, liver cells and mucosa cells.

20. The method according to claim 16 wherein said electrodes comprise gold and/or titainium.

21. The method according to claim 16 wherein said treatment site is located on a patient thigh, arm, or torso.

22. The method according to claim 16 wherein said composition is injected in a total volume selected from the group consisting of 0.01 ul, 50 ul, 100 ul, 150 ul, 200 ul, 250 ul, 300 ul, 400 ul, and 500 ul.

23. The method according to claim 16 wherein said composition is injected in a total active ingredient concentration selected from the group consisting of 2 ng/ml to 3 mg/ml.

24. The method according to claim 16 wherein said composition is injected either before or simultaneous with activating said energy source sufficient to reversibly porate said cells.

25. The method according to claim 24 wherein said composition after injection resides in and around said channel formed by said tube insertion into said tissue.

26. The method according to claim 16 wherein said composition is electroporated into said cells of said treatment site.

27. The method according to claim 22 wherein said treatment site comprises a zone of tissue/cells surrounding a track in said tissue made by said needle and extending radially out from said tract a distance selected from the group consisting of 1 mm, 2 mm, 3 mm, 4 mm and 5 mm.

29. The method according to claim 16 wherein said generator is pulsed such that the nominal voltage is between 1 to 200 V.

32. The method according to claim 16 wherein said generator is pulsed at a frequency selected from between the range 1 to 10,000 Hz.

17. The method according to claim 17 wherein said immune modulating molecule is a cytokine or a chemokine.

18. The method according to claim 18 wherein said immune modulating molecule is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, GM-CSF, M-CSF, G-CSF, LIF, LT, TGF-β

, IFN, TNF-α

, BCGF, CD2, or ICAM.