Tolerable and minimally invasive skin electroporation device

Patent metadata

Field	Value
Publication number	US-11565107-B2
Application number	US-201113581702-A
Country	US
Kind code	B2
Filing date	Mar 1, 2011
Priority date	Mar 1, 2010
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

A novel electroporation device for the delivery of vaccines that is both effective in generating a protective immune response and tolerable delivery to a subject (or near painless); and also methods of using same device to vaccinate a subject against a variety of infectious diseases and types of cancer in a near painless.

First claim

What is claimed is:

1. An electroporation device capable of delivering to a subject a tolerable electrical potential to layers of epidermal tissue between stratum corneum and basal layers that results in electroporation of cells in said epidermal tissue, comprising:
a voltage generator; and
an array having a plurality of needle electrodes in electrical communication with the voltage generator;
wherein each one of the plurality of needle electrodes is spaced apart from each adjacent needle electrode at a spacing distance of about 0.5 mm to about 2.5 mm;
wherein the voltage generator delivers via the plurality of needle electrodes an electrical potential of about 0.1 volts to about 70 volts to the epidermal tissue; and
wherein each of the plurality of needle electrodes defines a central axis and a distal end, wherein the distal end defines a trocar tip having a sharp point and a plurality of planar surfaces that extend distally to the sharp point, wherein the plurality of planar surfaces are oriented, respectively, at generally blunt angles between 10 degrees from the central axis and substantially perpendicular to the central axis, and
wherein the generally blunt angles and the sharp point of the trocar tip of each needle electrode and the spacing distance collectively allow the plurality of needle electrodes to 1) penetrate the layers of the epidermal tissue between stratum corneum and basal layers at depths of 0.1 mm or less, and 2) deliver the electrical potential from the voltage generator to the layers of epidermal tissue between stratum corneum and basal layers such that at least a majority of the electroporation of cells occurs in cells of stratum granulosum.

2. The electroporation device of claim 1 , wherein the plurality of needle electrodes deliver a tolerable electrical potential to the cells of the epidermal tissue that is near painless as measured by a visual analog scale.

3. The electroporation device of claim 1 , wherein the plurality of needle electrodes are adapted to penetrate the epidermal tissue at depths of from about 0.01 mm to about 0.04 mm.

4. The electroporation device of claim 1 , wherein the spacing distance is about 1.5 mm.

5. The electroporation device of claim 1 , wherein the voltage generator delivers to the epidermal tissue an electrical potential of about 1 volt to about 15 volts.

6. The electroporation device of claim 1 , wherein the voltage generator delivers to the epidermal tissue an electrical potential at a current ranging from about 1 mA to about 50 mA.

7. The electroporation device of claim 1 , wherein the voltage generator delivers to the epidermal tissue an electrical potential for a duration ranging from about 5 msec to about 250 msec.

8. The electroporation device of claim 1 , wherein the plurality of needle electrodes deliver the electrical potential to the layers of the epidermal tissue between stratum corneum and basal layers in a manner that results in no visible tissue damage per a histopathology analysis of the tissue.

9. The electroporation device of claim 1 , wherein each of the plurality of needle electrodes comprises stainless steel and is gold-plated.

10. The electroporation device of claim 9 , wherein the plurality of planar surfaces consists of three planar surfaces.

11. A tolerable method of delivering a biomolecule to cells of epidermal tissue of a subject by electroporation-assisted delivery using the electroporation device of claim 1 , the method comprising:
administering the biomolecule to the cells;
contacting the plurality of needle electrodes to the epidermal tissue so that the sharp points of the plurality of needle electrodes penetrate through the stratum corneum and reside in layers above the basal layers; and
delivering a tolerable electrical potential from the voltage generator to the cells of the epidermal layer via the plurality of needle electrodes.

12. The method of claim 11 , wherein the contacting step comprises manipulating the plurality of needle electrodes to penetrate the epidermal tissue at depths of 0.1 mm or less.

13. The method of claim 11 , wherein the contacting step comprises manipulating the plurality of needle electrodes to penetrate the epidermal tissue at depths of from about 0.01 mm to about 0.04 mm.

14. The method of claim 11 , wherein the delivering step comprises delivering a tolerable electrical potential that generates a pain assessment by said subject that is near painless as measured by a visual analog scale.

15. The method of claim 11 , wherein the delivering step comprises delivering an electrical potential of about 0.1 volts to about 15 volts to the cells.

16. The method claim 11 , wherein the delivering step comprises delivering an electrical potential at a current ranging from about 1 mA to about 50 mA to the cells.

17. The method of claim 11 , wherein the delivering step comprises delivering an electrical potential for a duration ranging from about 5 msec to about 250 msec.

18. An electroporation device capable of delivering to a subject a tolerable electrical potential to layers of epidermal tissue between stratum corneum and basal layers that results in electroporation of cells in said tissue, comprising:
a portable housing configured for hand-held operation;
a voltage generator contained in the portable housing; an array housing carrying a plurality of needle electrodes; and
an electrode housing coupled to the array housing, wherein the electrode housing has a plurality of electrical sockets, the plurality of needle electrodes are received within the plurality of electrical sockets, the plurality of electrical sockets place the plurality of needle electrodes in electrical communication with the voltage generator, and the array housing is attachable to and detachable from the portable housing;
wherein each one of the plurality of needle electrodes is spaced apart from each adjacent needle electrode at a spacing distance of about 0.5 mm to about 2.5 mm;
wherein the voltage generator delivers via the plurality of needle electrodes an electrical potential of about 0.1 volts to about 70 volts to the epidermal tissue; and
wherein the plurality of needle electrodes extends distally from the array housing, and the plurality of needle electrodes each have a distal end that defines a trocar tip having a sharp point and a plurality of planar surfaces that extend distally to the sharp point, wherein the plurality of planar surfaces are oriented, respectively, at generally blunt angles, wherein the generally blunt angles and the sharp point of each needle electrode and the spacing distance collectively allow the plurality of needle electrodes to 1) penetrate the layers of the epidermal tissue between stratum corneum and basal layers at depths of 0.1 mm or less while avoiding penetration into the basal layers, and 2) deliver the electrical potential from the voltage generator to the layers of the epidermal tissue between stratum corneum and basal layers such that at least a majority of the electroporation of cells occurs in cells of stratum granulosum.

19. The electroporation device of claim 18 , wherein the voltage generator comprises at least one battery.

20. The electroporation device of claim 19 , wherein the portable housing further comprises:
a circuit board having an electric circuit that is in electrical communication with the at least one battery and is powered by the at least one battery; and
at least one capacitor in electrical communication with the electric circuit,
wherein the battery provides the ele

Assignees

• Broderick Kate
• Mccoy Jay
• Kemmerrer Stephen V
• Lin Feng
• Kjeken Rune
• Inovio Pharmaceuticals Inc

Inventors

• Broderick Kate
• Mccoy Jay
• Kemmerrer Stephen V
• Lin Feng
• Kjeken Rune

Classifications

• A61N1/327 Primary

  for enhancing the absorption properties of tissue, e.g. by electroporation · CPC title

• A61K39/145

  Orthomyxoviridae, e.g. influenza virus · CPC title

• A61N1/0502 Primary

  Skin piercing electrodes · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title