Electroporetic gene and drug therapy

• US 6,132,419 A
• Filed: 10/25/1994
• Issued: 10/17/2000
• Est. Priority Date: 05/22/1992
• Status: Expired due to Fees

• Current Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Hofmann, Gunter A.
• Primary Examiner(s): Weiss, John G.
• Assistant Examiner(s): REICHLE, KARIN M
• Application Number:
  US08/328,895
• Time in Patent Office: 2,184 Days
• Field of Search: 600/1, 600/2, 600/12, 600/13, 600/14, 600/15, 604/890.1, 604/891.1, 604/892.1, 604/20, 604/21, 604/49, 604/52, 604/54, 435/172.2, 435/173.6, 435/287, 435/289, 204/180.1, 204/299 R, 938/52, 128/639, 128/642, 128/644, 607/1-3, 607/65, 607/72, 607/74, 607/98-101, 607/113, 607/115-117, 607/120-121, 607/144-145, 607/154-156
• US Class Current: 604/890.1
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• 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 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals

Abstract

A method and apparatus are provided for introducing molecules such as genes and pharmaceutical compounds into living blood cells of a patient for therapeutic purposes. A device is placed into contact with the body of the patient for generating an electric field at a preselected location within a selected blood vessel. Preselected molecules are infused into the selected blood vessel. Simultaneously an electric signal is applied to the applied device to repeatedly subject a quantity of blood flowing within the selected blood vessel past the preselected location to electric fields of a predetermined amplitude and duration. The parameters of the electric fields are precisely controlled in order to make the walls of preselected cells in the blood transiently permeable to permit the molecules to enter said preselected cells without killing said cells. The device can include either an induction coil that is placed into contact with the body over a blood vessel, or alternatively, an induction coil that surrounds the blood vessel. The electric signal is supplied by a power pack and the preselected molecules are infused with a supply pump.

Claims

1. A method of in vivo introduction of molecules into living blood cells of a patient for therapeutic purposes, comprising the steps of:

providing an inductance device including an induction coil, the induction coil comprising at least one conductor having opposite ends adapted for connection to an electrical power source and at least one turn forming a coil intermediate the ends;

positioning said inductance device external of and closely adjacent to a body of the patient directly over a selected blood vessel for inducing an electric field at a preselected location within the selected blood vessel;

infusing preselected ones of said molecules into the selected blood vessel upstream of the inductance device; and

applying time varying electric signals to the applied inductance device to generate time varying magnetic fields and repeatedly subject a quantity of blood flowing past the preselected location in the selected blood vessel to electric fields of a predetermined amplitude and duration, induced by the time varying magnetic fields, sufficient to make walls of preselected cells in said quantity of blood transiently permeable to permit the molecules to enter said preselected cells without killing said cells.

2. A method according to claim 1 wherein the molecules are selected from the group consisting of genes and pharmaceutical compounds.

3. A method according to claim 1 wherein the preselected cells are selected from the group consisting of red and white blood cells.

4. A method according to claim 1 wherein said induction coil surrounds a portion of the body containing the selected blood vessel.

5. A method according to claim 1 wherein the electric signals have a wave form comprising bipolar oscillating pulse train.

6. A method according to claim 5 wherein each pulse of the train has a duration of between approximately one microsecond and one hundred microseconds.

7. A method according to claim 5 wherein there are between approximately one pulse and one hundred pulses for a given unit of liquid volume as the unit passes through the selected blood vessel.

8. A method according to claim 1 wherein the electric fields have a strength of between approximately 0.2 kV/cm and 20.0 kV/cm.

9. A method according to claim 1 wherein the preselected cells are lymphocytes or red blood cells.

10. A method of in vivo introduction of molecules into living cells of a patient for therapeutic purposes, comprising the steps of:

providing an inductance device including an induction coil, the induction coil comprising at least one conductor having opposite ends adapted for connection to an electrical power source and at least one turn forming a coil intermediate the ends;

positioning said inductance device adjacent to an external portion of a body of the patient directly over a selected tissue for inducing an electric field at a preselected location within the selected tissue;

infusing preselected ones of said molecules into the selected tissue; and

applying a time varying electric signal to the applied inductance device to generate time varying magnetic fields and repeatedly subject tissue cells at the preselected location in the selected tissue to induce electric fields of a predetermined amplitude and duration sufficient to make the walls of preselected cells in the tissue transiently permeable to permit the molecules to enter said preselected cells without killing said cells.

11. A method according to claim 10 wherein the molecules are selected from the group consisting of genes and pharmaceutical compounds.

12. An apparatus for in vivo introduction of molecules into living blood cells of a patient, comprising:

induction means including an induction coil comprising at least one conductor having opposite ends adapted for connection to an electrical power source and at least one turn forming a coil intermediate the ends, the coil adapted for positioning adjacent to an external portion of a body over and inducing an electric field at a preselected location within a blood vessel of the patient;

means for injecting a predetermined quantity of a fluid medium carrying preselected ones of said molecules into the blood vessel up stream of the preselected location; and

means for applying time varying electric signals to said induction coil for causing it to repeatedly generate magnetic fields and induce electric fields of a predetermined amplitude and duration sufficient to make walls of preselected cells in blood flowing past the preselected location in the blood vessel to be transiently permeable to permit the molecules to enter said preselected cells without killing said cells.

13. An apparatus according to claim 12 wherein the means for injecting the quantity of fluid carrying the molecules includes a pump.

14. An apparatus according to claim 12 wherein the means for applying electric signals includes a signal generator for generating the electric signals.

15. An apparatus according to claim 14 wherein the induction coil is a pancake coil for placing in contact with the patient over the blood vessel.

16. An apparatus according to claim 14 wherein the induction coils a ring shaped coil for placing around a finger of the patient.

17. An apparatus according to claim 16 wherein the induction coil is a plurality of ring shaped coils for placing around a plurality of the fingers of the patient.

18. An apparatus according to claim 12 wherein the induction coil is a pancake coil for placing in contact with the patient over the blood vessel.

19. An apparatus according to claim 12 wherein the induction coil is a ring-shaped coil for placing around a finger of the patient.

20. An apparatus according to claim 12 wherein the induction coil is a plurality of ring shaped coils for placing around a plurality of the fingers of the patient.

21. An apparatus according to claim 20 wherein the means for applying electric signals includes a signal generator to generating the electric signals.