Minimally invasive apparatus and method to electroporate drugs and genes into tissue

• US 6,181,964 B1
• Filed: 11/09/1998
• Issued: 01/30/2001
• Est. Priority Date: 08/01/1997
• Status: Expired due to Term

• Current Assignee: Oncosec Medical Incorporated (China Grand Pharmaceutical & Healthcare Holdings Ltd.)
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Dimmer, Steven C., Nanda, Gurvinder S., Levatter, Jeffrey I., Hofmann, Gunter A., Dev, Sukhendu B.
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US09/189,360
• Time in Patent Office: 813 Days
• Field of Search: 604/890.1, 604/19-22, 604/500, 604/501, 128/898, 607/2, 607/100, 607/115, 607/154, 607/3, 607/92, 607/116, 607/190, 607/120, 607/122, 607/130, 435/173.5, 435/173.6
• US Class Current: 604/21
• CPC Class Codes: A61N 1/0502 Skin piercing electrodes
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A method and apparatus for in vivo electroporation therapy. Using electroporation therapy (EPT) as described in the invention, tumors treated by a combination of electroporation using the apparatus of the invention and a chemotherapeutic agent caused regression of tumors in vivo. In one embodiment, the invention provides a method of EPT utilizing low voltage and long pulse length for inducing cell death. One embodiment of the invention includes a system for clinical electroporation that includes a needle array electrode having a “keying” element that determines the set point of the therapy voltage pulse and/or selectable array switching patterns. A number of electrode applicator designs permit access to and treatment of a variety of tissue sites. Another embodiment provides a laparoscopic needle applicator that is preferably combined with an endoscope for minimally invasive EPT.

Claims

1. A laparoscopic needle applicator for electroporation therapy, comprising:

a. a support rod;

b. a sheath surrounding the support rod, and configured to move relative to the support rod between an extended position covering the distal end of the support rod and a retracted position exposing the distal end of the support rod;

c. at least two electrode needles adapted for electroporation therapy and positioned between the support rod and the sheath;

d. a compressible mechanism, attached to at least one electrode needle, for moving each attached electrode needle from a sheathed configuration when the sheath is in the extended position, to a deployed configuration when the sheath is in the retracted position, wherein the electrode needles have greater separation with respect to each other in the deployed configuration than in the sheathed configuration.

3. The laparoscopic needle applicator of claim 1, wherein the compressible mechanism comprises a plurality of support arms, each support arm pivotally attached at one end to a slidable base, and attached at the other end to one of a plurality of primary extension arms, and wherein each primary extension arm is attached at one end to a first fixed base that is attached to the support rod, and attached at the other end to one of the electrode needles.

4. The laparoscopic needle applicator of claim 3, wherein the slidable base surrounds, and is free to move along the support rod.

5. The laparoscopic needle applicator of claim 3, further comprising a plurality of secondary extension arms, each secondary extension arm being attached at one end to a second fixed base, and being attached at the other end to one of the electrode needles.

6. The laparoscopic needle applicator of claim 3, further comprising a coiled spring interposed about the support arm and between the slidable base and the fixed base(s) and biasing the slidable base away from the fixed base(s).

7. The laparoscopic needle applicator of claims 5 and 6, wherein upon retraction of the retractable sleeve, the coiled spring biases the slidable base away from the fixed base(s) causing the plurality of support arms to exert a retractive force on the primary extension arm resulting in an angling-out of the extension arms and a spreading of the electrode needles.

8. The laparoscopic needle applicator of claim 1, wherein the compressible mechanism is constructed of a dielectric material.

9. The laparoscopic needle applicator of claim 8, wherein the compressible mechanism serves to electrically insolate each electrode needle from each other.

10. The laparoscopic needle applicator of claim 1, wherein the compressible mechanism comprises a cone of compressible, elastomeric material interposed around the support rod, wherein the cone has a wide and a narrow end, such that the wide end is at the distal end of the support rod.

11. The laparoscopic needle applicator of claim 1, wherein the compressible mechanism moves only one electrode needle.

12. The laparoscopic needle applicator of claim 1, wherein the compressible mechanism moves a plurality of electrode needles.

2. The laparoscopic needle applicator of claim 2, wherein the support rod comprises an endoscope.