Method of treatment using electroporation mediated delivery of drugs and genes

• US 5,993,434 A
• Filed: 09/29/1995
• Issued: 11/30/1999
• Est. Priority Date: 04/01/1993
• Status: Expired due to Term

• Current Assignee: Oncosec Medical Incorporated (China Grand Pharmaceutical & Healthcare Holdings Ltd.), University of South Florida Research Foundation, Inc. (State University System of Florida)
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Hofmann, Gunter A., Dev, Sukhendu B.
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US08/537,265
• Time in Patent Office: 1,523 Days
• Field of Search: 604/20-21, 604/49, 604/51, 604/501, 607/115-116, 435/173.6
• US Class Current: 604/501
• 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: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion

Abstract

A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

Claims

1. A method for the therapeutic application of electroporation to a portion of the body of a patient for introducing molecules into tissues therein, comprising:

providing an array of multiple opposed pairs of electrodes connected to a generator, wherein at least two pairs of electrodes are activated simultaneously, at least one of said pairs of electrodes having a needle configuration for penetrating tissue;

inserting a first pair of said needle electrodes into selected tissue for introducing molecules into the tissue;

positioning a second pair of electrodes of said array of electrodes in conductive relation to said selected tissue so that said tissue is between said first and second opposed pairs of electrodes; and

separately applying pulses of high amplitude electric signals to at least two different pairs of electrodes, but not all electrodes simultaneously and proportionately to the distance between said pairs of electrodes causing in vivo electroporation of the tissue.

2. The method of claim 1 comprising the step of providing a switch assembly including a rotary switch selectively positionable for connecting alternate opposite pairs of electrodes to a pulse generator.

3. The method of claim 1 wherein the molecule is selected from the group consisting of a chemotherapeutic agent, a polynucleotide and a polypeptide.

4. The method of claim 3, wherein the chemotherapeutic agent is bleomycin.

5. The method of claim 1 wherein the molecule is introduced by a method selected fromthe group consisting of intratumorally, systemically and locally.

6. The method of claim 1, wherein the tissue is selected from the group consisting of pancreas, lung, heart, kidney, muscle, breast, colon, prostate, thymus, testis, and ovary.

7. A method for the in vivo electroporation-mediated therapy of a cell of a subject comprising:

administering a therapeutic composition to the subject such that the composition is delivered to the cell;

providing an array of multiple opposed pairs of electrodes connected to a generator, wherein at least two pairs of electrodes are activated simultaneously, at least one of said pairs of electrodes having a needle configuration for penetrating tissue;

inserting a first pair of said needle electrodes into selected tissue for introducing molecules into the cell;

positioning a second pair of electrodes of said array of electrodes in conductive relation to said selected tissue so that said cell is between said first and second opposed pairs of electrodes; and

separately applying electrical pulses of short duration to at least two different pairs of electrodes, but not all electrodes simultaneously and proportionately to the distance between said electrodes causing in vivo electroporation of a cell of the tissue.

8. The method of claim 7 comprising the step of providing a switch assembly including a rotary switch selectively positionable for connecting alternate opposite pairs of electrodes to a pulse generator.

9. The method of claim 7 wherein the therapeutic composition is selected from the group consisting of a chemotherapeutic agent, a polynucleotide and a polypeptide.

10. The method of claim 7 wherein the therapeutic composition is introduced by a method selected fromthe group consisting of intratumorally, systemically and locally.

11. The method of claim 9, wherein the chemotherapeutic agent is bleomycin.

12. The method of claim 7, wherein the tissue is selected from the group consisting of pancreas, lung, heart, kidney, muscle, breast, colon, prostate, thymus, testis, and ovary.