DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
2. Applicant’s Amendment filed August 29, 2025 (hereinafter “08/29/25 Amendment") has been entered, and fully considered. In the 08/29/25 Amendment, claims 1, 4, 6-20, & 22 were amended, claims 2, 3, 5, & 21 were cancelled, and claims 23-26 were newly added. Therefore, claims 1, 4, 6-20, & 22-26 are now pending in the application.
3. The 08/29/25 Amendment has overcome the claim objections, and the rejections under §§ 112(b), 102, & 103 previously set forth in the Non-Final Office Action mailed 04/29/25 (“04/29/25 Action”).
4. A new claim objection, and new rejections under §§ 112(b) & 103 are set forth herein, necessitated by Applicant’s Amendment.
5. Additionally, a new interpretation/rejection of dependent claim 12 is set forth herein that were not previously set forth in the 08/29/25 Action. As such, this action constitutes a second Non-Final Action.
Claim Objections
6. Claim 26 is objected to because of the following informalities:
In claim 26, line 4, the recitation of “initiating an apoptotic-like effect which causes permanent cell death at a later time” should instead recite --initiating apoptosis which causes permanent cell death at a later time--.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
7. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
8. Claims 23 & 24 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
9. Claim 23 recites the limitation “wherein evaluating comprises determining if the portion of the neural tissue that is stunned is appropriate for the non-thermal treatment” in lines 1-2. The term “appropriate” is a relative term which renders the claim indefinite. The term “appropriate” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Clarification is required.
10. Claim 24 recites the limitation “wherein evaluating comprises determining if the effect on the body is safe for the patient” in lines 1-2. The term “safe” is a relative term which renders the claim indefinite. The term “safe” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Clarification is required.
Claim Rejections - 35 USC § 103
11. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
12. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
13. Claims 1, 4, 6-11, 13-15, 17, 19, 20, & 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication No. 2016/0338758 to Davalos et al. (“Davalos ”) in view of U.S. Patent Application Publication No. 2016/0166310 to Stewart et al. ("Stewart").
14. Regarding claim 1, Davalos teaches a method of treating a portion of a neural tissue [brain tissue] of a body of a patient [see ¶[0056] (“a human subject or patient”)] [see also Abstract, & ¶[0002] (“Generally, the present invention provides for a combination of an electroporation-based therapy such as ECT, EGT, and IRE with the administration of therapeutic and diagnostic agents to cause the uptake of these agents into brain tissue”)] comprising:
positioning a delivery electrode near the neural tissue [¶[0101] (“The schematics in FIG. 1 show two basic hollow needle designs that may be implemented to enhance solution delivery prior to, during, or after IRE treatment. They both have multiple conducting surfaces 920 that may act as charged electrodes, grounded electrodes, or electric resistors, depending on the treatment protocol. Panel A shows a hollow tip 910 for injection of agents at its end while Panel B has distributed pores 961 throughout for a more generalized agent distribution. As shown in Panel B, the pores are disposed in the non-conducting regions 930 of the device”); ¶[0105]; & FIG. 1; see also ¶’s [0057], [0058]]; [and]
***
delivering a… pulsed electric field energy through the delivery electrode to the portion of the neural tissue [e.g., ¶’s [0010], [0012], [0016], [0057], & [0064] (“In general, methods of treating with IRE comprise temporarily implanting or disposing one or more electrodes, which may be present on the same or different devices, into or immediately adjacent a tumor, and applying an electrical field to the tumor in multiple pulses or bursts over a prescribed or predetermined period of time to cause irreversible cell death to some or all of the tumor cells”)] … to create a lesion [as broadly as claimed, the resulting region of tissue/ablation damage in the “killing zone” or ablation zone – e.g., ¶’s [0012], [0036], [0051], [0065] (“the location, shape, and size of electrodes can be selected to produce three-dimensional killing zones of numerous shapes and sizes, allowing for non-thermal treatment of tumors of varying shapes and sizes”); FIGS. 10A-10C], wherein the… pulsed electric field energy non-thermally treats cells of the lesion while maintaining non-cellular elements within the lesion [see ¶[0007] (“IRE primarily affects the cell membrane of target cells, sparing important tissue components such as major blood vessels and extracellular matrix”)].
Delivery of First Pulsed Electric Field Energy for “Stunning” of Cells
Davalos does not, however, teach an initial step of delivering a pulsed electric field energy to “stun” cells within an area of neural tissue before delivering pulsed electric field energy to create a lesion. As such Davalos fails to teach the following emphasized claim imitations:
delivering a first pulsed electric field energy through the delivery electrode to an area of the neural tissue causing a stunning of cells within the area;
evaluating an effect on the body caused by the stunning; and
delivering a second pulsed electric field energy through the delivery electrode to the portion of the neural tissue based on the evaluating step to create a lesion, wherein the second pulsed electric field energy non-thermally treats cells of the lesion while maintaining non-cellular elements within the lesion.
However, the initial delivery of a pulsed electric field energy to a potential treatment site to “stun” the site to first test the effect of the stunning on the site, before permanently destroying it, was well known in the art, before the effective filing date of the claimed invention.
As one example, Stewart, in a similar field of endeavor, teaches that it was known to stun a suspected site before permanently destroying it [see ¶[0032] (“Deliveries of high amplitude in multiple pulses may be used for irreversible ablation while lower amplitudes may merely stun the tissue. Once a suspected focal site of origin of an arrhythmia is identified, it may be advantageous to test the effect of stunning this suspected site before permanently destroying it. If the desired resolution of the arrhythmia results from stunning, a higher amplitude pulse train may be delivered to irreversibly ablate this site”)]. While ¶[0032] describes “stunning” in the context of treating an arrhythmia, it is noted that Stewart is not so limited, and describes applicability in other areas of the body [see, e.g., ¶[0019]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Davalos to include delivering a first pulsed electric field energy through the delivery electrode to an area of the neural tissue causing a stunning of cells within the area, evaluating an effect on the body caused by the stunning, and delivering a second pulsed electric field energy through the delivery electrode to the portion of the neural tissue based on the evaluating step to create a lesion, since such a modification would provide the benefit/advantage of enabling a practitioner to “preview” the effectiveness of a planned treatment, and make adjustments as necessary (e.g., to electrode placement/positioning) to help achieve a better outcome for a patient. Still further, such a known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Stewart, and one of ordinary skill in the art would have been capable of applying this known technique to the known method of Davalos, and the results [determining whether a desired resolution is achievable at a site via stunning (prior to permanent ablation)] would have been entirely predictable to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
15. Regarding claim 4, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches delivering a fluid agent to the portion of neural tissue [e.g., ¶’s [0020]-[0022], [0079], [0080], [0100] (“Such a configuration allows for highly accurate distribution of injectable solutions, including those comprising bioactive agents”), & [0101]].
16. Regarding claim 6, the combination of Davalos and Stewart teaches all of the limitations of claim 4 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the fluid agent comprises a chemotherapeutic agent [e.g., ¶’s [0002] (“More specifically, embodiments of the invention provide electrical energy based therapies for disrupting the blood-brain barrier in a manner sufficient for delivering chemotherapeutic agents across the blood-brain barrier surrounding a zone of ablation”), [0013], [0100]].
17. Regarding claim 7, the combination of Davalos and Stewart teaches all of the limitations of claim 6 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein at least one cell within the portion of tissue undergoes cell death caused by uptake of the chemotherapeutic agent [e.g., ¶’s [0002], [0006], & [0060] (“the present invention provides for a combination of an electroporation-based therapy such as ECT, EGT, and IRE with the administration of therapeutic and diagnostic agents to cause the uptake of these agents into brain tissue. Embodiments of the present invention include therapeutic methods that employ IRE in combination with an exogenous agent to kill undesirable cells (e.g. infiltrating tumor cells) in the vicinity of treated tumors (e.g. tumor margins)”)].
18. Regarding claim 8, the combination of Davalos and Stewart teaches all of the limitations of claim 4 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the fluid agent comprises genetic material [e.g., ¶’s [0057], [0082] (“The exogenous agent may be a small molecule, a radioisotope, a natural protein, a synthetic protein, a natural peptide, synthetic peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody conjugate, a nucleic acid such as small interfering RNA (siRNA), antisense RNA, an aptamer, a ribozyme, or oligonucleotide, a viral vector comprising a nucleic acid sequence encoding a natural or synthetic bioactive protein peptide or serving as a vaccine to stimulate the immune system, or an engineered cell comprising such a viral vector”)].
19. Regarding claim 9, the combination of Davalos and Stewart teaches all of the limitations of claim 8 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the second pulsed electric field energy causes transfection [those skilled in the art will appreciate that transfection is the process of artificially introducing nucleic acids (DNA or RNA) into cells] of the treated cells with the genetic material [e.g., ¶’s [0079], [0082]].
20. Regarding claim 10, the combination of Davalos and Stewart teaches all of the limitations of claim 9 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the transfection treats Alzheimer's disease [see ¶[0146]] or Parkinson's disease [see ¶[0146]].
21. Regarding claim 11, the combination of Davalos and Stewart teaches all of the limitations of claim 4 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the fluid agent comprises an immunostimulant [e.g., ¶’s [0020], [0083] (“Immunotherapy agents include monoclonal antibody therapies such as rituximab (RITUXAN) and alemtuzumab (CAMPATH), non-specific immunotherapies and adjuvants, such as BCG, interleukin-2 (IL-2), and interferon-alfa, immunomodulating drugs, for instance, thalidomide and lenalidomide (REVLIMID), and cancer vaccines such as PROVENGE. It is within the capabilities of a skilled artisan to chose an appropriate cancer therapeutic agent in the methods of the invention based on characteristics such as the type of tumor (e.g. primary brain tumor or metastatic), stage of the tumor, previous exposure to cancer therapeutic agents, and molecular characteristics”); & [0084]; NOTE: as one example, those skilled in the art will appreciate that interferon-alfa is a known immunostimulant].
22. Regarding claim 13, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the neural tissue comprises brain tissue and/or neuroglia [Davalos teaches that the neural tissue comprises brain tissue - e.g., Abstract, ¶’s [0002], [0010], [0017], [0055], [0058]].
23. Regarding claim 14, the combination of Davalos and Stewart teaches all of the limitations of claim 13 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the second pulsed electric field energy is configured to transiently disrupt a blood brain barrier [e.g., ¶’s [0010], [0012], [0033], [0057], [0060] (“the present inventors have found that delivery of pulsed electric fields through irreversible electroporation causes a transient disruption in the BBB”)].
24. Regarding claim 15, the combination of Davalos and Stewart teaches all of the limitations of claim 14 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches delivering a fluid agent [e.g., ¶’s [0020]-[0022], [0079], [0080], [0100] (“Such a configuration allows for highly accurate distribution of injectable solutions, including those comprising bioactive agents”), & [0101]] so as to pass through the disrupted blood brain barrier to the neural tissue [e.g., Abstract, ¶’s [0010]-[0012], [0023], [0036], [0057], [0060], [0093]].
25. Regarding claim 17, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the delivery electrode has a needle shape [FIG. 1] and wherein positioning the delivery electrode comprises penetrating the portion of the neural tissue with the delivery electrode [¶’s [0100], [0101], [0105]; FIGS. 1, 10A-10C].
26. Regarding claim 19, Davalos teaches a method of treating a portion of tissue within a brain of a body of a patient [see ¶[0056] (“a human subject or patient”)] [see also Abstract, & ¶[0002] (“Generally, the present invention provides for a combination of an electroporation-based therapy such as ECT, EGT, and IRE with the administration of therapeutic and diagnostic agents to cause the uptake of these agents into brain tissue”)] comprising:
positioning a delivery electrode within the brain [e.g., Abstract (“placing first and second electrodes in a brain of the living mammal”)]; ¶[0101] (“The schematics in FIG. 1 show two basic hollow needle designs that may be implemented to enhance solution delivery prior to, during, or after IRE treatment. They both have multiple conducting surfaces 920 that may act as charged electrodes, grounded electrodes, or electric resistors, depending on the treatment protocol. Panel A shows a hollow tip 910 for injection of agents at its end while Panel B has distributed pores 961 throughout for a more generalized agent distribution. As shown in Panel B, the pores are disposed in the non-conducting regions 930 of the device”); ¶[0105]; & FIG. 1; see also ¶’s [0057], [0058]];
***
delivering a fluid agent [e.g., ¶’s [0020]-[0022], [0079], [0080], [0100] (“Such a configuration allows for highly accurate distribution of injectable solutions, including those comprising bioactive agents”), & [0101]] through a cerebrovascular system near the portion of the tissue [¶’s [0023], [0032] (“intravenous, intraarterial”), & [0080] (“The exogenous agent can be administered before, during, or after the EBT protocol (such as IRE) to provide an effective concentration of agent in the blood stream surrounding the volume of brain tissue during the period in which the BBB is disrupted”)]; and
delivering a… pulsed electric field energy through the delivery electrode [e.g., ¶’s [0010], [0012], [0016], [0057], & [0064] (“In general, methods of treating with IRE comprise temporarily implanting or disposing one or more electrodes, which may be present on the same or different devices, into or immediately adjacent a tumor, and applying an electrical field to the tumor in multiple pulses or bursts over a prescribed or predetermined period of time to cause irreversible cell death to some or all of the tumor cells”)]… to create a lesion [as broadly as claimed, the resulting region of tissue/ablation damage in the “killing zone” or ablation zone – e.g., ¶’s [0012], [0036], [0051], [0065] (“the location, shape, and size of electrodes can be selected to produce three-dimensional killing zones of numerous shapes and sizes, allowing for non-thermal treatment of tumors of varying shapes and sizes”); FIGS. 10A-10C] and so as to transiently disrupt a blood brain barrier near the portion of the tissue allowing the fluid agent to pass through the blood brain barrier to the portion of the tissue [e.g., ¶’s [0010], [0012], [0033], [0057], [0060] (“the present inventors have found that delivery of pulsed electric fields through irreversible electroporation causes a transient disruption in the BBB”)] allowing the fluid agent to pass through the blood brain barrier to the portion of tissue [e.g., Abstract, ¶’s [0010]-[0012], [0023] (“The agent can be administered at a selected dose, route of administration, and/or timing to provide a therapeutic concentration of the agent in blood during the interval of blood-brain barrier disruption”), [0036], [0057], [0093]].
Delivery of First Pulsed Electric Field Energy for “Stunning” of Cells
Davalos does not, however, teach an initial step of delivering a pulsed electric field energy to “stun” cells within an area of the brain before delivering pulsed electric field energy to create a lesion. As such Davalos fails to teach the following emphasized claim imitations:
delivering a first pulsed electric field energy through the delivery electrode to an area of the brain causing a stunning of cells within the area;
evaluating an effect on the body caused by the stunning;
delivering a second pulsed electric field energy through the delivery electrode based on the evaluating step to create a lesion and so as to transiently disrupt a blood brain barrier near the portion of the tissue allowing the fluid agent to pass through the blood brain barrier to the portion of the tissue.
However, the initial delivery of a pulsed electric field energy to a potential treatment site to “stun” the site to first test the effect of the stunning on the site, before permanently destroying it, was well known in the art, before the effective filing date of the claimed invention.
As one example, Stewart, in a similar field of endeavor, teaches that it was known to stun a suspected site before permanently destroying it [see ¶[0032] (“Deliveries of high amplitude in multiple pulses may be used for irreversible ablation while lower amplitudes may merely stun the tissue. Once a suspected focal site of origin of an arrhythmia is identified, it may be advantageous to test the effect of stunning this suspected site before permanently destroying it. If the desired resolution of the arrhythmia results from stunning, a higher amplitude pulse train may be delivered to irreversibly ablate this site”)]. While ¶[0032] describes “stunning” in the context of treating an arrhythmia, it is noted that Stewart is not so limited, and describes applicability in other areas of the body [see, e.g., ¶[0019]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Davalos to include delivering a first pulsed electric field energy through the delivery electrode to an area of the brain causing a stunning of cells within the area, evaluating an effect on the body caused by the stunning, delivering a second pulsed electric field energy through the delivery electrode based on the evaluating step to create a lesion and so as to transiently disrupt a blood brain barrier near the portion of the tissue allowing the fluid agent to pass through the blood brain barrier to the portion of the tissue, since such a modification would provide the benefit/advantage of enabling a practitioner to “preview” the effectiveness of a planned treatment, and make adjustments as necessary (e.g., to electrode placement/positioning) to help achieve a better outcome for a patient. Still further, such a known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Stewart, and one of ordinary skill in the art would have been capable of applying this known technique to the known method of Davalos, and the results [determining whether a desired resolution is achievable at a site via stunning (prior to permanent ablation)] would have been entirely predictable to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
27. Regarding claim 20, the combination of Davalos and Stewart teaches all of the limitations of claim 19 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the second pulsed electric field energy destroys cells within the lesion while maintaining non-cellular elements within the lesion [see ¶[0007] (“IRE primarily affects the cell membrane of target cells, sparing important tissue components such as major blood vessels and extracellular matrix”)].
28. Regarding claim 22, the combination of Davalos and Stewart teaches all of the limitations of claim 19 for the reasons set forth in detail (above) in the Office Action.
Davalos further teaches wherein the second pulsed electric field energy causes cell death due to a combination of the second pulsed electric field energy and by uptake of the fluid agent [e.g., ¶’s [0002], [0060] (“the present invention provides for a combination of an electroporation-based therapy such as ECT, EGT, and IRE with the administration of therapeutic and diagnostic agents to cause the uptake of these agents into brain tissue. Embodiments of the present invention include therapeutic methods that employ IRE in combination with an exogenous agent to kill undesirable cells (e.g. infiltrating tumor cells) in the vicinity of treated tumors (e.g. tumor margins)”); & [0095]].
29. Regarding claim 23, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
As best understood [see the rejection under § 112(b) above], Davalos (as modified to include the stunning step of Stewart), further teaches wherein evaluating comprises determining if the portion of the neural tissue that is stunned is appropriate for the non-thermal treatment [effective, i.e., a desired result occurs - Stewart, ¶[0032]].
30. Regarding claim 24, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
As best understood [see the rejection under § 112(b) above], Davalos (as modified to include the stunning step of Stewart), further teaches wherein evaluating comprises determining if the effect on the body is safe for the patient [effective, i.e., a desired result occurs - Stewart, ¶[0032]].
31. Regarding claim 25, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Davalos (as modified above to include the stunning step of Stewart), further teaches
choosing the portion of neural tissue based on the evaluating step [as broadly as claimed, choosing to proceed to irreversibly ablate the site if a desired resolution is achieved at the site as a result of stunning - Stewart, ¶[0032]].
32. Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Davalos and Stewart, as evidenced by U.S. Patent Application Publication No. 2011/0105726 to Rosen et al. (“Rosen”).
33. Regarding claim 12, the combination of Davalos and Stewart teaches all of the limitations of claim 11 for the reasons set forth in detail (above) in the Office Action.
Claim 12 further recites the limitation “wherein the immunostimulant encourages expression of proteins that promote immune infiltration, activation or conversion.”
The immunostimulant interferon-alfa (cited in the rejection of claim 11 above) [Davalos, ¶’s [0083]-[0084]] is known to encourage expression of proteins that promote activation, as evidenced by Rosen [see Rosen, e.g., ¶[0009] (“Immunostimulants, which enhance the activity of immune cells and molecules, comprise another class of immunomodulatory agents with important clinical applications. Such applications include, for example, the treatment of immunodeficiency disorders (e.g. AIDS and severe combined immunodeficiency), chronic infectious diseases (e.g. viral hepatitis, papillomavirus, and herpesvirus), and cancer. An important class of endogenous immunostimulants is the cytokines. These soluble signaling molecules are produced by a number of cell types, and are critical to the regulation of the immune response Immunostimulatory mechanisms can include proliferation, differentiation and/or activation of immune cells or progenitors of immune cells. For example, interleukin-2 (IL-2) binds to IL-2 receptors on T lymphocytes and induces proliferation and differentiation. Another cytokine, interferon alpha, stimulates the immune system through a variety of mechanisms, including activation of macrophages, T lymphocytes, and natural killer cells. Interferon alpha also induces the expression of antiviral proteins (see Chapter 50, The Pharmacological Basis of Therapeutics, 9.sup.th Edition, Eds. Hardman, Limbird, Molinoff, Ruddon, and Gilman, McGraw Hill (1996))”)].
34. Claims 16 & 18 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Davalos and Stewart, and further in view of U.S. Patent Application Publication No. 2019/0223943 to Forsyth et al. (“Forsyth”).
35. Regarding claim 16, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
While Davalos discloses that a probe may include a monopolar electrode [see ¶[0113]], Davalos does not explicitly teach:
positioning a remote return electrode so that the delivery electrode delivers the second pulsed electric field energy in a monopolar manner.
Forsyth, in a similar field of endeavor, teaches apparatuses for delivering one or more of thermal ablation and irreversible electroporation therapies to target tissue [Abstract]. More particularly, Forsyth teaches an instrument (700) including an energy delivery body [any of shaft electrode (702) or electrodes (706) comprises an energy delivery body - ¶[0077]; FIGS. 14A-14B] disposed near its distal end [(704)] [FIGS. 14A-14B] that is configured to deliver pulsed electric field energy [irreversible electroporation (“IRE”) pulses - ¶’s [0072], [0079], [0080]] toward a mass of undesired tissue [¶’s [0078], [0079]; FIGS. 14A-14B].
Forsyth further teaches positioning a return electrode on the patient [external return electrode (740) - ¶’s [0078], [0079]; FIGS. 14A-14B], and delivering the pulsed electric field energy [IRE] in a monopolar fashion so as to utilize the return electrode [(740)] [see ¶[0078] (“a first lesion field is generated at 770 by the use of a monopolar thermal or IRE therapy delivery using the needle electrodes 706 and an external return electrode 740”); note also ¶’s [0078], [0080]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to further modify the combination of Davalos and Stewart to include positioning a remote return electrode so that the delivery electrode delivers the second pulsed electric field energy in a monopolar manner, since use of a remote return electrode when delivering pulsed electric field energy in a monopolar fashion was recognized as part of the ordinary capabilities of one skilled in the art (as demonstrated by Forsyth), and one of ordinary skill in the art would have been capable of applying this known energy delivery technique to the known method of Davalos and Stewart, and the results [use of a single active electrode to deliver electrical energy to target tissue, with the current passing through the patient's body, and exiting via a dispersive electrode (return pad), completing the circuit] would have been entirely predictable to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
36. Regarding claim 18, the combination of Davalos and Stewart teaches all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
While Davalos contemplates the use of electrodes of different sizes and shapes, including plate-type and/or needle-type (whether blunt tip or sharp tip) electrodes [¶[0078], as well as electrode tips designed to have any number of geometrical shapes [¶[0105]], Davalos does not explicitly teach:
wherein positioning the delivery electrode comprises positioning the delivery electrode within a lumen near the portion of the neural tissue so that the second pulsed electric field energy passes through a wall of the lumen to the portion of the neural tissue.
Forsyth, in a similar field of endeavor, teaches apparatuses for delivering one or more of thermal ablation and irreversible electroporation therapies to target tissue [Abstract]. More particularly, Forsyth teaches an instrument (700) including an energy delivery body [any of shaft electrode (702) or electrodes (706) comprises an energy delivery body - ¶[0077]; FIGS. 14A-14B] disposed near its distal end [(704)] [FIGS. 14A-14B].
Forsyth further teaches positioning the delivery electrode within a lumen near the portion of tissue so that the pulsed electric field energy passes through a wall of the lumen to the portion of tissue [Forsyth teaches advancing a distal end (distal tip (704) - ¶[0076]; FIGS. 14A-14B) of an instrument (cannula (700) - ¶[0076]; FIGS. 14A-14B) into a luminal structure of a body of the patient {see ¶[0076] (“the distal tip 704 may be blunted to allow atraumatic passage through a body lumen such as a biliary duct, lymph vessel or duct, urethra, mammary duct, digestive passageway, blood vessel, or other body passageway, as the case may be”)}, and wherein the energy delivery body is configured to deliver pulsed electric field energy (irreversible electroporation (“IRE”) pulses - ¶’s [0072], [0079], [0080]) toward the mass of undesired tissue (¶’s [0078], [0079]; FIGS. 14A-14B)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to further modify the combination Davalos and Stewart such that wherein positioning the delivery electrode comprises positioning the delivery electrode within a lumen near the portion of the neural tissue so that the second pulsed electric field energy passes through a wall of the lumen to the portion of the neural tissue, since such an electrode introduction/positioning technique was recognized as part of the ordinary capabilities of one skilled in the art (as demonstrated by Forsyth), and one of ordinary skill in the art would have been capable of applying this known electrode introduction/positioning technique to the known method of Davalos and Stewart, and the results [positioning of a delivery electrode to enable the delivery of pulsed electric field energy] would have been entirely predictable to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
37. Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Davalos in view of U.S. Patent Application Publication No. 2017/0266438 to Sano et al. (“Sano”).
38. Regarding claim 26, Davalos teaches a method of treating a portion of neural tissue [brain tissue] [see ¶[0056] (“a human subject or patient”)] [see also Abstract, & ¶[0002] (“Generally, the present invention provides for a combination of an electroporation-based therapy such as ECT, EGT, and IRE with the administration of therapeutic and diagnostic agents to cause the uptake of these agents into brain tissue”)] comprising:
positioning a delivery electrode near the portion of the neural tissue [¶[0101] (“The schematics in FIG. 1 show two basic hollow needle designs that may be implemented to enhance solution delivery prior to, during, or after IRE treatment. They both have multiple conducting surfaces 920 that may act as charged electrodes, grounded electrodes, or electric resistors, depending on the treatment protocol. Panel A shows a hollow tip 910 for injection of agents at its end while Panel B has distributed pores 961 throughout for a more generalized agent distribution. As shown in Panel B, the pores are disposed in the non-conducting regions 930 of the device”); ¶[0105]; & FIG. 1; see also ¶’s [0057], [0058]]; and
delivering pulsed electric field energy through the delivery electrode to the portion of the neural tissue [e.g., ¶’s [0010], [0012], [0016], [0057], & [0064] (“In general, methods of treating with IRE comprise temporarily implanting or disposing one or more electrodes, which may be present on the same or different devices, into or immediately adjacent a tumor, and applying an electrical field to the tumor in multiple pulses or bursts over a prescribed or predetermined period of time to cause irreversible cell death to some or all of the tumor cells”)] so that that the energy non-thermally treats the portion of the neural tissue creating a lesion [as broadly as claimed, the resulting region of tissue/ablation damage in the “killing zone” or ablation zone – e.g., ¶’s [0012], [0036], [0051], [0065] (“the location, shape, and size of electrodes can be selected to produce three-dimensional killing zones of numerous shapes and sizes, allowing for non-thermal treatment of tumors of varying shapes and sizes”); FIGS. 10A-10C] while maintaining non-cellular elements within the lesion [see ¶[0007] (“IRE primarily affects the cell membrane of target cells, sparing important tissue components such as major blood vessels and extracellular matrix”)], and
Stunning & Apoptosis
Davalos does not, however, teach:
wherein at least a portion of the lesion comprises cells that are stunned by the pulsed electric field energy initiating an apoptotic-like effect which causes permanent cell death at a later time.
Sano, in a similar field of endeavor, teaches that it was known to treat cells in various zones, wherein a portion of cells (e.g., in a second treatment zone) are selectively inhibited, and later killed by apoptosis [e.g., ¶’s [0008], [0009], [0019], [0127], [0133]; NOTE: cells subject to a train of electrical pulses that are not immediately killed, but selectively killed later by apoptosis, can be broadly considered to be “stunned” by the train of pulses].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Davalos such that at least a portion of the lesion comprises cells that are stunned by the pulsed electric field energy initiating an apoptotic-like effect which causes permanent cell death at a later time, as taught by Sano, since such a method can allow infiltrating tumor cells disposed within a tumor margin to be effectively treated while sparing healthy tissue within the tumor margin [Sano, ¶[0003]].
Response to Arguments
39. As noted above, the 08/29/25 Amendment has overcome the claim objections, and the rejections under §§ 112(b), 102, & 103 previously set forth in the 04/29/25 Action.
40. A new claim objection, and new rejections under §§ 112(b) & 103 are set forth herein, necessitated by Applicant’s Amendment.
41. Further, as noted above, this action constitutes a second Non-Final Action since a new interpretation/rejection of dependent claim 12 is set forth herein that were not previously raised in the 08/29/25 Action.
Conclusion
42. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradford C. Blaise whose telephone number is (571)272-5617. The examiner can normally be reached on Monday - Friday 8 AM-5 PM.
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/Bradford C. Blaise/Examiner, Art Unit 3794