Surgery – Means for introducing or removing material from body for... – Infrared – visible light – ultraviolet – x-ray or electrical...
Reexamination Certificate
1999-01-08
2001-04-10
Kennedy, Sharon (Department: 3763)
Surgery
Means for introducing or removing material from body for...
Infrared, visible light, ultraviolet, x-ray or electrical...
C604S106000
Reexamination Certificate
active
06216034
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field 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).
2. Description of the Related Art
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 OF THE INVENTION
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 pre-selected 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 plurality of needle electrodes 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.
Another embodiment of the invention provides a laparoscopic needle applicator that is preferably combined with an endoscope for minimally invasive electroporation therapy.
The invention provides a therapeutic method utilizing the needle array apparatus for the treatment of cells, particularly tumor cells.
REFERENCES:
patent: 4262672 (1981-04-01), Kief
patent: 4907601 (1990-03-01), Frick
patent: 5019034 (1991-05-01), Weaver et al.
patent: 5058605 (1991-10-01), Slovak
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: 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: 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: 5814599 (1998-09-01), Mitragotri et al.
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: 6009347 (1999-12-01), Hofmann
patent: 6040184 (2000-03-01), Greener et al.
patent: 6041253 (2000-03-01), Kost et al.
patent: 863 111 (1953-01-01), None
patent: 40 00 893 A1 (1990-01-01), None
patent: 0 378 132 A3 (1990-01-01), None
patent: 0 378 132 A2 (1990-01-01), None
patent: WO97/07826 (1997-03-01), None
patent: WO99/44678 (1999-09-01), None
patent: WO99/52424 (1999-10-01), None
Dev Sukhendu B.
Dimmer Steven C.
Hofmann Gunter A.
Levatter Jeffrey I.
Nanda Gurvinder S.
Genetronics Inc.
Gray Cary Ware & Freidenrich LLP
Haile Lisa A.
Kennedy Sharon
LandOfFree
Method of programming an array of needle electrodes for... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of programming an array of needle electrodes for..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of programming an array of needle electrodes for... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2466347