Surgery – Means for introducing or removing material from body for... – Infrared – visible light – ultraviolet – x-ray or electrical...
Reexamination Certificate
1998-10-22
2001-06-05
Kennedy, Sharon (Department: 3763)
Surgery
Means for introducing or removing material from body for...
Infrared, visible light, ultraviolet, x-ray or electrical...
C607S116000
Reexamination Certificate
active
06241701
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates generally to the use of electric pulses to increase the permeability of cell, and more specifically to a method and apparatus for the application of controlled electric fields for in vivo delivery of pharmaceutical compounds and genes into cells by electroporation therapy (EPT), also known as cell poration therapy (CPT) and electrochemotherapy (ECT).
In the 1970's it was discovered that electric fields could be used to create pores in cells without causing permanent damage. This discovery made possible the insertion of large molecules into cell cytoplasm. It is known that genes and other molecules such as pharmacological compounds can be incorporated into live cells through a process known as electroporation. The genes or other molecules are mixed with the live cells in a buffer medium and short pulses of high electric fields are applied. The cell membranes are transiently made porous and the genes or molecules enter the cells, where they can modify the genome of the cell.
Electroporation in vivo is generally limited to tissue or cells that are close to the skin of the organism where the electrodes can be placed. Therefore, tissue which would otherwise be treatable by systemic drug delivery or chemotherapy, such as a tumor, is generally inaccessible to electrodes used for electroporation. In the treatment of certain types of cancer with chemotherapy, it is necessary to use a high enough dose of a drug to kill the cancer cells without killing an unacceptable high number of normal cells. If the chemotherapy drug could be inserted directly inside the cancer cells, this objective could be achieved. Some of the anti-cancer drugs, for example, bleomycin, normally cannot penetrate the membranes of certain cancer cells effectively. However, electroporation makes it possible to insert bleomycin into cells.
Treatment typically is carried out by injecting an anticancer drug directly into the tumor and applying an electric field to the tumor between a pair of electrodes. The field strength must be adjusted reasonably accurately so that electroporation of the cells of the tumor occurs without damage, or at least minimal damage, to any normal or healthy cells. This can normally be easily carried out with external tumors by applying the electrodes to opposite sides of the tumor so that the electric field is between the electrodes. When the field is uniform, the distance between the electrodes can then be measured and a suitable voltage according to the formula E=V/d can then be applied to the electrodes (E=electric field strength in V/cm; V=voltage in volts; and d=distance in cm). When large or internal tumors are to be treated, it is not easy to properly locate electrodes and measure the distance between them. The aforementioned parent application discloses a system of electrodes for in vivo electroporation wherein the electrodes may be inserted into the tumor. In related U.S. Pat. No. 5,273,525, a syringe for injecting molecules and macromolecules for electroporation utilizes needles for injection which also function as electrodes. This construction enables subsurface placement of electrodes.
Treatment of a subject using cell poration therapy provides a means for avoiding the deleterious effects typically associated with administration of anticancer or cytotoxic agents. Such treatment would allow introduction of these agents to selectively damage or kill undesirable cells while avoiding surrounding healthy cells or tissue.
SUMMARY
It is a primary object of the invention to provide an improved apparatus that can be conveniently and effectively positioned to generate predetermined electric fields in preselected tissue.
In accordance with a primary aspect of the invention, an electrode apparatus for the application of electroporation to a portion of the body of a patient comprises a support member, a needle electrode array formed of a plurality of needle electrodes and mounted on said support member for insertion into tissue at selected positions and distances from one another, and means including a signal generator responsive to said distance signal for applying an electric signal to the electrodes proportionate to the distance between said electrodes for generating an electric field of a predetermined strength.
The invention includes needles that function for injection of therapeutic substances into tissue and function as electrodes for generating electric fields for portion of cells of the tissue.
One embodiment of the invention includes a system for clinical electroporation therapy that includes a needle array electrode having a “keying” element, such as a resistor or active circuit, that determines the set point of the therapy voltage pulse, as well as selectable array switching patterns (the apparatus having this system has been termed MedPulser™). A number of electrode applicator designs permit access to and treatment of a variety of tissue sites.
The needle electrode array may be disposable to substantially eliminate possible contamination in reusing a needle array tip due to improper sterilization. In addition, each needle electrode may be partially insulated so that only a desired amount of the tip portion is exposed. Such a partially insulated needle array can be used to confine the electroporation in a targeted area with a tumor and significantly shield the skin and tissues above the target area from the electroporation process.
The invention provides a therapeutic method utilizing the needle array apparatus for the treatment of cells, particularly tumor cells.
REFERENCES:
patent: 4081340 (1978-03-01), Zimmermann et al.
patent: 4262672 (1981-04-01), Kief
patent: 4663292 (1987-05-01), Wong et al.
patent: 4907601 (1990-03-01), Frick
patent: 5019034 (1991-05-01), Weaver et al.
patent: 5058605 (1991-10-01), Slovak
patent: 5088977 (1992-02-01), Sibalis
patent: 5215088 (1993-06-01), Normann et al.
patent: 5273525 (1993-12-01), Hofmann
patent: 5304120 (1994-04-01), Crandell et al.
patent: 5328451 (1994-07-01), Davis et al.
patent: 5389069 (1995-02-01), Weaver
patent: 5425752 (1995-06-01), Vu'Nguyen
patent: 5439440 (1995-08-01), Hofmann
patent: 5468223 (1995-11-01), Mir
patent: 5498238 (1996-03-01), Shapland et al.
patent: 5507724 (1996-04-01), Hofmann et al.
patent: 5507802 (1996-04-01), Imran
patent: 5536267 (1996-07-01), Edwards et al.
patent: 5547467 (1996-08-01), Pliquett et al.
patent: 5554110 (1996-09-01), Edwards et al.
patent: 5634899 (1997-06-01), Shapland et al.
patent: 5667491 (1997-09-01), Pliquett et al.
patent: 5674267 (1997-10-01), Mir et al.
patent: 5702359 (1997-12-01), Hofmann et al.
patent: 5718702 (1998-02-01), Edwards
patent: 5720921 (1998-02-01), Meserol
patent: 5749847 (1998-05-01), Zewert et al.
patent: 5780052 (1998-07-01), Khaw et al.
patent: 5786454 (1998-07-01), Waksman et al.
patent: 5789213 (1998-08-01), Hui et al.
patent: 5800378 (1998-09-01), Edwards et al.
patent: 5807308 (1998-09-01), Edwards
patent: 5807309 (1998-09-01), Lundquist et al.
patent: 5810762 (1998-09-01), Hofmann
patent: 5814476 (1998-09-01), Kauffman et al.
patent: 5814599 (1998-09-01), Mitragotri et al.
patent: 5817483 (1998-10-01), Kauffman et al.
patent: 5823993 (1998-10-01), Lemelson
patent: 5845646 (1998-12-01), Lemelson
patent: 5868740 (1999-02-01), LeVeen et al.
patent: 5869326 (1999-02-01), Hofmann
patent: 5873849 (1999-02-01), Bernard
patent: 5874268 (1999-02-01), Meyer
patent: 5879891 (1999-03-01), Thompson
patent: 5908753 (1999-06-01), Kelly et al.
patent: 5911223 (1999-06-01), Weaver et al.
patent: 5944715 (1999-08-01), Goble et al.
patent: 5964726 (1999-10-01), Korenstein et al.
patent: 5968006 (1999-10-01), Hofmann
patent: 5980517 (1999-11-01), Gough
patent: 5983131 (1999-11-01), Weaver et al.
patent: 5993434 (1999-11-01), Dev et al.
patent: 5994127 (1999-11-01), Selden et al.
patent: 5995869 (1999-11-01), Cormier et al.
patent: 6001617 (1999-12-01), Raptis
patent: 6002961 (1999-12-01), Mitragotri et al.
patent: 6010613 (2000-01-01), Walters et al.
patent: 6040184 (2000-03-01), G
Genetronics Inc.
Gray Cary Ware & Freidenrich LLP
Haile Lisa A.
Kennedy Sharon
LandOfFree
Apparatus for electroporation mediated delivery of drugs and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Apparatus for electroporation mediated delivery of drugs and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Apparatus for electroporation mediated delivery of drugs and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2445932