Method and apparatus for delivery of therapeutic agents

• US 9,526,836 B2
• Filed: 04/18/2012
• Issued: 12/27/2016
• Est. Priority Date: 04/05/2002
• Status: Active Grant

• Current Assignee: Ichor Medical Systems, Inc.
• Original Assignee: Ichor Medical Systems, Inc.
• Inventors: Bernard, Robert M., Hannaman, Andrew W., Bernard, Brady M.
• Primary Examiner(s): STIGELL, THEODORE J
• Application Number:
  US13/450,320
• Publication Number:
  US 20120277661A1
• Time in Patent Office: 1,714 Days
• Field of Search: 604 20- 22, 604/134, 604/140, 604/500, 604/501
• US Class Current: 1/1
• CPC Class Codes: A61M 2005/206 With automatic needle insertion
• CPC Class Codes: A61M 5/20 Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically A61M5/142 , A61M5/46 take precedence; hypodermic projectiles F42B12/54
• CPC Class Codes: A61M 5/2033 Spring-loaded one-shot injectors with or without automatic needle insertion multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287
• CPC Class Codes: A61M 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/30 Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
• CPC Class Codes: A61M 5/326 Fully automatic sleeve extension, i.e. in which triggering of the sleeve does not require a deliberate action by the user
• CPC Class Codes: A61M 5/46 having means for controlling depth of insertion
• 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 1/306 Arrangements where at least part of the apparatus is introduced into the body

Abstract

Methods and apparatus for the reproducible, consistent and efficacious delivery of a therapeutic agent to a patient. The invention comprises means for the controlled administration of the therapeutic agent through an orifice to the patient, a plurality of penetrating electrodes arranged with a predetermined spatial relationship relative to the orifice, and means for generating an electrical signal operatively connected to the electrodes.

Claims

1. An apparatus for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising:

a sub-assembly comprising a plurality of penetrating electrodes, wherein a first penetration depth of the plurality of penetrating electrodes is such that said plurality of penetrating electrodes are located within the tissue of the patient to encompass said predetermined tissue site;

a main unit comprising an injection needle comprising an injection orifice, wherein a second penetration depth of the injection orifice is such that said injection orifice is located within the tissue region bounded by said plurality of penetrating electrodes, and wherein the second penetration depth is controllable by a depth controller and controllable independently from and relative to the first penetration depth of the plurality of penetrating electrodes; and

an electrical field generator operatively connected to said plurality of penetrating electrodes which provides an electric signal to facilitate the intracellular delivery of said therapeutic agent, and increases the intracellular uptake of said therapeutic agent,

wherein the sub-assembly is removably attached to the main unit.

2. The apparatus of claim 1, comprising a template useful to control the spatial relationship between said injection orifice and said plurality of penetrating electrodes in the tissue of said patient.

3. The apparatus of claim 1, wherein said therapeutic agent is a nucleic acid.

4. The apparatus of claim 3 wherein the nucleic acid is DNA.

5. The apparatus of claim 1, wherein said predetermined tissue site is located in a skeletal muscle of said patient, wherein the predetermined tissue site comprises healthy cells.

6. The apparatus of claim 1, wherein said electrical signal comprises at least one monopolar direct current pulse.

7. The apparatus of claim 6 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

8. The apparatus of claim 6 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said plurality of penetrating electrodes.

9. An apparatus for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising:

a sub-assembly comprising a plurality of penetrating electrodes;

a main unit comprising an injection needle comprising an injection orifice, wherein the tip of said injection needle is proximal to the tip of said plurality of penetrating electrodes,

wherein a penetration depth of the orifice is such that said injection orifice is located within the tissue region bounded by said plurality of penetrating electrodes; and

an electrical field generator operatively connected to said plurality of penetrating electrodes which provides an electric signal to facilitate the intracellular delivery of said therapeutic agent, and increases the intracellular uptake of said therapeutic agent,

wherein the sub-assembly is attachable to the main unit.

10. The apparatus of claim 9 wherein a template is used to control the spatial relationship between said injection orifice and said plurality of penetrating electrodes in the tissue of said patient.

11. The apparatus of claim 9 comprising a controlled source of energy that controls the rate of agent administration, wherein said controlled source of energy is a spring.

12. The apparatus of claim 9 comprising a controlled source of energy that controls the rate of agent administration, wherein said controlled source of energy is a compressed gas.

13. The apparatus of claim 9 wherein said therapeutic agent is a nucleic acid.

14. The apparatus of claim 13 wherein the nucleic acid is DNA.

15. The apparatus of claim 9 wherein said predetermined tissue site is located in a skeletal muscle of said patient, wherein the predetermined tissue site comprises healthy cells.

16. The apparatus of claim 9 wherein said electrical signal comprises at least one monopolar direct current pulse.

17. The apparatus of claim 16 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

18. The apparatus of claim 16 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said plurality of penetrating electrodes.

19. An apparatus for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising:

a main unit that comprises an injection needle comprising an injection orifice;

a sub-assembly that houses a plurality of penetrating electrodes in a retracted state such that the plurality of penetrating electrodes are not visible to the patient, and wherein upon deployment into the tissue of said patient, said plurality of penetrating electrodes encompass said predetermined tissue site; and

an electrical field generator operatively connected to said plurality of penetrating electrodes which provides an electric signal to facilitate the intracellular delivery of said therapeutic agent, and increases the intracellular uptake of said therapeutic agent,

wherein the sub-assembly is removably attached to the main unit.

20. The apparatus of claim 19, wherein said first device comprises a controlled source of energy that controls the rate of agent administration.

21. The apparatus of claim 20, wherein said controlled source of energy is a spring.

22. The apparatus of claim 20, wherein said controlled source of energy is a compressed gas.

23. The apparatus of claim 19 wherein said therapeutic agent is a nucleic acid.

24. The apparatus of claim 23 wherein the nucleic acid is DNA.

25. The apparatus of claim 19 wherein said predetermined tissue site is located in a skeletal muscle of said patient, wherein the predetermined tissue site comprises healthy cells.

26. The apparatus of claim 19 wherein said electrical signal comprises at least one monopolar direct current pulse.

27. The apparatus of claim 26 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

28. The apparatus of claim 26 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said plurality of penetrating electrodes.

29. An apparatus for the intracellular delivery of a therapeutic agent to a predetermined tissue site within a patient comprising:

a sub-assembly comprising a plurality of penetrating electrodes in a retracted state such that the plurality of penetrating electrodes are not visible to the patient, wherein upon deployment from the retracted state into the tissue of said patient said plurality of penetrating electrodes encompass said predetermined tissue site;

a main unit comprising an injection needle that comprises an injection orifice, wherein the tip of said injection needle is proximal to the tip of said plurality of penetrating electrodes, and wherein the depth of insertion of the orifice is such that said orifice is located within the tissue region bounded by said plurality of penetrating electrodes;

a controlled source of energy that controls the rate of agent administration; and

an electrical field generator operatively connected to said plurality of penetrating electrodes which provides an electric signal to facilitate the intracellular delivery of said therapeutic agent, and increases the intracellular uptake of said therapeutic agent,

wherein the sub-assembly is removably attached to the main unit.

30. The apparatus of claim 29 wherein said controlled source of energy is a spring.

31. The apparatus of claim 29 wherein said controlled source of energy is a compressed gas.

32. The apparatus of claim 29 wherein said therapeutic agent is a nucleic acid.

33. The apparatus of claim 32 wherein the nucleic acid is DNA.

34. The apparatus of claim 29 wherein said predetermined tissue site is located in a skeletal muscle of said patient, wherein the predetermined tissue site comprises healthy cells.

35. The apparatus of claim 29 wherein said electrical signal comprises at least one monopolar direct current pulse.

36. The apparatus of claim 35 wherein at least one of said monopolar direct current pulses has a duration of 0.1 milliseconds to 100 milliseconds.

37. The apparatus of claim 35 wherein at least one of said monopolar direct current pulses has an amplitude capable of inducing an electrical field of from approximately 50 to approximately 300 V/cm between at least two of said plurality of penetrating electrodes.