Prosecution Insights
Last updated: April 18, 2026
Application No. 18/130,330

TREATMENT PLANNING FOR ELECTRICAL-ENERGY BASED THERAPIES BASED ON CELL CHARACTERISTICS

Non-Final OA §103
Filed
Apr 03, 2023
Examiner
HUPCZEY, JR, RONALD JAMES
Art Unit
3794
Tech Center
3700 — Mechanical Engineering & Manufacturing
Assignee
VIRGINIA TECH INTELLECTUAL PROPERTIES, INC.
OA Round
1 (Non-Final)
64%
Grant Probability
Moderate
1-2
OA Rounds
4y 0m
To Grant
87%
With Interview

Examiner Intelligence

Grants 64% of resolved cases
64%
Career Allow Rate
512 granted / 794 resolved
-5.5% vs TC avg
Strong +22% interview lift
Without
With
+22.1%
Interview Lift
resolved cases with interview
Typical timeline
4y 0m
Avg Prosecution
44 currently pending
Career history
838
Total Applications
across all art units

Statute-Specific Performance

§101
0.9%
-39.1% vs TC avg
§103
41.9%
+1.9% vs TC avg
§102
25.4%
-14.6% vs TC avg
§112
22.7%
-17.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 794 resolved cases

Office Action

§103
DETAILED ACTION Applicant’s preliminary amendment, filed June 20, 2023, is fully acknowledged by the Examiner. Currently, claims 20-45 are pending and newly added, with claims 1-19 cancelled. The following is a complete response to the June 20, 2023 communication. Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Rejections - 35 USC § 103 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. The factual inquiries 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 . This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim s 20-32, 34, 35, 38-40 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Neal et al. (“The Feasibility of Irreversible Electroporation for the Treatment of Breast Cancer and Other Heterogeneous Systems”) further in view of Zimmermann et al. (“Dielectric Breakdown of Cell Membranes”) . Regarding claim 20, Neal provides for a method for treating a target tissue, the method comprising administering a plurality of electrical pulses to the region of interest ( see pages 2633, left column, second paragraph providing for providing in vivo treatment via electrical pulses) and irreversibly electroporating one or more of the patient cells of the specific tissue type or specific tumor type while not irreversibly electroporating cells of one or more other type in the region of interest (See page 2622, right column, last paragraph to page 2623, right column, first column provide for the inducing of IRE in the targeted region with the peripheral tissue being not treated either via being less conductive that the tissue in the region of interest, or via the focusing of the targeted region to be between the electrodes) . While Neal contemplates basing the determination of the tissue/tumor type on specific properties of the tissue in the region of interest (see pages 2617, left column, last paragraph to page 2617, right column, up to the “ Numerical Model … ” heading providing for cell or tissue type based treatment parameters), Neal fails to specifically provide that such features are determined via a biopsy of a region of interest of a subject and for the identifying from the biopsy that the region of interest comprises patient cells of a specific tissue type or specific tumor type . Zimmermann provides direction regarding the determination of the effect of the application of electrical pulses on the tissue in a region of interest wherein the determination of electrical pulse parameters are based on parameters of the tissue taken from sample of various biological samples (see at least the abstract discussing the use of parameters being based on samples of red blood cells; see further page 886 discussing the determination of the shape factor of the red blood cells based on the cell size from the sample). Therefore, it is the Examiner’s position that it would have been an obvious consideration to one of ordinary skill in the art at the time of filing to have utilized a biopsy of tissue in the region of interest to determine the shape factor contemplated on page 2619 of Neal to provide for an accurate representation of the tissue to be treated by the IRE protocol described in Neal. Neal already contemplates utilizing known tissue parameters when determining the various parameters of the electrical pulses (see page 2618 with the table of tissue properties as well as page 2619 discussing the shape factor and cell diameter) with the teaching of Zimmermann exhibiting that such factors are known to be determined via tissue sample, especially when in the context of electroporation. Regarding claim 21, Neal provides that the patient cells of the specific tissue type or specific tumor type are cancer cells and the one or more other type of cells are non-cancerous (the disclosure throughout Neal provides for the focus on cancer cells as the target tissue and for the peripheral, non-target tissue to be tissue outside the tumor/cancel cells) . Regarding claim 22, Neal provides that the cancer cells are pancreatic, prostate, brain or breast cancer cells (Neal provides throughout for the focus on breast cancer cells; Neal further provides for brain carcinomas on page 2617) . Regarding claim 23, Neal provides for identifying parameters including one or more of aggressiveness, rate of cell division, or stage of cancer of the cancer cells (see pages 2617, right column, top paragraph providing for the determination of the stage of cancer via the determination of “cell or tissue type”), and administering the plurality of electrical pulses using a combination of a specific pulse width range, voltage range, electrode spacing range, frequency range, range of number of pulses, and range of electrode diameters that will produce an electric field (see at least page 2623, right column, first paragraph discussing for the adjusting of electrode type, size, shape, placement and arrangement, as well as the changes in required voltage), (i) that is at or above a minimum electric field required to kill cells having the identified aggressiveness, rate of cell division, or stage of cancer (the focus of Neal is providing for the IRE treatment of the target tissue region based on the determined parameters), (ii) but that has a magnitude lower than required to kill the other type of cells which are less aggressive, a slower rate of or no cell division, or a lower stage of cancer (via the disclosure in Neal for the treatment to be lower to not treat peripheral tissue that is not in the target tissue region) . The Examiner is further of the position that the above identification of the parameters would be identified via biopsy in view of the combination with Zimmermann above that provides for the use of biopsy for tissue property determination. Regarding claim 24, the Examiner is of the position that the combination in the rejection of claim 20 above providing for the biopsy-based determination would then further provide for performing one or more measurements of the patient cells of the specific tissue type or specific tumor type and constructing from the measurement(s) a morphology of the patient cells . Such would be in view of the direction in Neal to provide for the determination of the various tissue properties and types as on page 2617. Neal then further provides for administering the plurality of electrical pulses to the region of interest and irreversibly electroporating only cells with the constructed cell morphology present in the region of interest and not killing the cells of the other type, which have a different cell morphology (See page 2622, right column, last paragraph to page 2623, right column, first column provide for the inducing of IRE in the targeted region with the peripheral tissue being not treated either via being less conductive that the tissue in the region of interest, or via the focusing of the targeted region to be between the electrodes) . Regarding claim 25, in view of the combination in the rejections of claims 20 and 24 above, the combined methodology provides that the cell morphology is based on one or more of cell diameter, cell radius, cell shape, cell volume, cell mass, or cell surface area (see page 2617 of Neal providing for “cell or tissue type” and “cell radius”) . Regarding claim 26, in view of the combination in the rejections of claims 20 and 24 above, the combined methodology further provides that the administering comprises using a combination of a specific pulse width range, voltage range, electrode spacing range, frequency range, range of number of pulses, and range of electrode diameters to achieve an applied electric field that will kill one or more of the cells having the constructed cell morphology but that is of a magnitude lower than needed to kill the other type of cells with the different cell morphology (see at least page 2623, right column, first paragraph discussing for the adjusting of electrode type, size, shape, placement and arrangement, as well as the changes in required voltage. The Examiner is further of the position that the balance of Neal provides for frequency, pulse width and number of pulses as a parameters for applying energy sufficient to cause the disclosed IRE) . Regarding claim s 27 and 28 , in view of the combination in the rejections of claims 20 and 24 above, the combined methodology further provides for measuring a size of the patient cells of the specific tissue type or specific tumor type wherein the cell size is the cell diameter or the cell radius (see page 2617 of Neal providing for “cell or tissue type” and “cell radius”), and administering the plurality of electrical pulses at or above the minimum electric field required to cause IRE of cells having the measured or estimated cell size but below the minimum electric field required to cause IRE of the other cells (see at least page 2623, right column, first paragraph discussing for the adjusting of electrode type, size, shape, placement and arrangement, as well as the changes in required voltage. The Examiner is further of the position that the balance of Neal provides for frequency, pulse width and number of pulses as a parameters for applying energy sufficient to cause the disclosed IRE) . Regarding claim 29, Neal further provides that the minimum electric field is determined by: E IRE = (1V) /( ƒ s R cos Θ) wherein in: E IRE is the electrical field threshold for IRE , ƒ s is a shape factor reflecting the morphology and dielectric properties the cells and surrounding media , and R is the radius of the cells (see equation 1 on page 2617). Regarding claim 30, in view of the combination in the rejections of claims 20, 24 and 27 above, Zimmermann further provides that the size of the patient cells of the specific tissue type or specific tumor type is measured and expressed as an average or median size (see page 886 describing the determination of the average mean volume as well as table 1 on page 888 providing that the radius would be based on that average volume) . Regarding claim 31, Neal provides for a method for treating a target tissue, the method comprising: identifying a target region of a subject (via the selection throughout Neal of a location of treatment of the patient), i dentifying a specific cell type present in the target region (see pages 2617, left column, last paragraph to page 2617, right column, up to the “ Numerical Model … ” heading providing for cell or tissue type based treatment parameters), administering a plurality of electrical pulses to the target region with a pulse protocol sufficient to cause irreversible electroporation (IRE) of cells of the specific cell type and insufficient to cause IRE of a second cell type in the target region (See page 2622, right column, last paragraph to page 2623, right column, first column provide for the inducing of IRE in the targeted region with the peripheral tissue being not treated either via being less conductive that the tissue in the region of interest, or via the focusing of the targeted region to be between the electrodes) . While Neal contemplates basing the determination of the tissue/tumor type on specific properties of the tissue in the region of interest (see pages 2617, left column, last paragraph to page 2617, right column, up to the “ Numerical Model … ” heading providing for cell or tissue type based treatment parameters), Neal fails to specifically provide that such features are determined via the steps of performing a biopsy of a portion of the target region and identifying from the biopsy a specific cell type present in the target region. Zimmermann provides direction regarding the determination of the effect of the application of electrical pulses on the tissue in a region of interest wherein the determination of electrical pulse parameters are based on parameters of the tissue taken from sample of various biological samples (see at least the abstract discussing the use of parameters being based on samples of red blood cells; see further page 886 discussing the determination of the shape factor of the red blood cells based on the cell size from the sample). Therefore, it is the Examiner’s position that it would have been an obvious consideration to one of ordinary skill in the art at the time of filing to have utilized a biopsy of tissue in the region of interest to determine the shape factor contemplated on page 2619 of Neal to provide for an accurate representation of the tissue to be treated by the IRE protocol described in Neal. Neal already contemplates utilizing known tissue parameters when determining the various parameters of the electrical pulses (see page 2618 with the table of tissue properties as well as page 2619 discussing the shape factor and cell diameter) with the teaching of Zimmermann exhibiting that such factors are known to be determined via tissue sample, especially when in the context of electroporation. Regarding claim 32, Neal provides that administering the plurality of electrical pulses is in a manner to provide a voltage gradient in the target region that is lower than the minimum voltage gradient for causing IRE of the second type of cells (See page 2622, right column, last paragraph to page 2623, right column, first column provide for the inducing of IRE in the targeted region with the peripheral tissue being not treated either via being less conductive that the tissue in the region of interest, or via the focusing of the targeted region to be between the electrodes). Regarding claim 34, Neal provides for a method for treating a target tissue of a patient with irreversible electroporation (IRE), the method comprising: identifying a morphology of selected cells present within a spatial region of interest of a patient (see pages 2617, left column, last paragraph to page 2617, right column, up to the “ Numerical Model … ” heading providing for cell or tissue type based treatment parameters), selecting a magnitude of an applied electric field within the range of: a first magnitude equal to or above a magnitude of a first minimum electric field sufficient to kill by way of irreversible electroporation cells having the morphology of the selected cells and up to but below a second magnitude of a second minimum electric field sufficient to kill by way of irreversible electroporation other cells that are present within the spatial region of interest and that have a morphology that is different from the morphology of the selected cells (See page 2622, right column, last paragraph to page 2623, right column, first column provide for the inducing of IRE in the targeted region with the peripheral tissue being not treated either via being less conductive that the tissue in the region of interest, or via the focusing of the targeted region to be between the electrodes), administering a plurality of electrical pulses to the spatial region of interest using selected pulse width, voltage, electrode spacing, frequency, number of pulses, and electrode diameter, together capable of producing the applied electric field at the selected magnitude (see pages 2633, left column, second paragraph providing for providing in vivo treatment via electrical pulses ; see further page 2623, right column, first paragraph discussing for the adjusting of electrode type, size, shape, placement and arrangement, as well as the changes in required voltage), thereby killing with irreversible electroporation cells having the morphology of the selected cells, while not killing with irreversible electroporation the other cells (See, again, page 2622, right column, last paragraph to page 2623, right column, first column provide for the inducing of IRE in the targeted region with the peripheral tissue being not treated either via being less conductive that the tissue in the region of interest, or via the focusing of the targeted region to be between the electrodes) . While Neal contemplates basing the determination of the tissue/tumor type on specific properties of the tissue in the region of interest (see pages 2617, left column, last paragraph to page 2617, right column, up to the “ Numerical Model … ” heading providing for cell or tissue type based treatment parameters), Neal fails to specifically provide that the morphology of selected cells present within a spatial region of interest of a patient via biopsy. Zimmermann provides direction regarding the determination of the effect of the application of electrical pulses on the tissue in a region of interest wherein the determination of electrical pulse parameters are based on parameters of the tissue taken from sample of various biological samples (see at least the abstract discussing the use of parameters being based on samples of red blood cells; see further page 886 discussing the determination of the shape factor of the red blood cells based on the cell size from the sample). Therefore, it is the Examiner’s position that it would have been an obvious consideration to one of ordinary skill in the art at the time of filing to have utilized a biopsy of tissue in the region of interest to determine the shape factor contemplated on page 2619 of Neal to provide for an accurate representation of the tissue to be treated by the IRE protocol described in Neal. Neal already contemplates utilizing known tissue parameters when determining the various parameters of the electrical pulses (see page 2618 with the table of tissue properties as well as page 2619 discussing the shape factor and cell diameter) with the teaching of Zimmermann exhibiting that such factors are known to be determined via tissue sample, especially when in the context of electroporation. Regarding claim 35, Neal provides that the cells having the morphology of the selected cells are pancreatic, prostate, brain or breast cancer cells and the other cells are non-cancerous (the disclosure throughout Neal provides for the focus on cancer cells as the target tissue and for the peripheral, non-target tissue to be tissue outside the tumor/cancel cells; Neal further provides throughout for the focus on breast cancer cells; Neal further provides for brain carcinomas on page 2617). Regarding claim 38, Neal provides that the cell morphology is based on one or more of cell diameter, cell radius, cell shape, cell volume, cell mass, or cell surface area (see page 2617 of Neal providing for “cell or tissue type” and “cell radius”) . Regarding claim 39, Neal provides that the selected cells are cancer cells (Neal provides throughout for the focus on breast cancer cells; Neal further provides for brain carcinomas on page 2617) . Regarding claim 40, Neal provides that the selected cells are dividing or are dividing more rapidly than the other cells that are present within the spatial region of interest (via the selected cells being cancer cells in comparison to the normal cells in the peripheral tissue being normal cells) . Regarding claim 42, Neal provides that the plurality of electrical pulses comprises monophasic electrical pulses. Neal provides that the plurality of electrical pulses comprises monophasic electrical pulses (via a first needle being charged and a second needle being grounded as in figure 1 and on page 2617, right column; this single direction in Neal would qualify as monophasic application). Claims 33, 36, 37, 41 and 43-45 are rejected under 35 U.S.C. 103 as being unpatentable over Neal et al. (“The Feasibility of Irreversible Electroporation for the Treatment of Breast Cancer and Other Heterogeneous Systems”) in view of Zimmermann et al. (“Dielectric Breakdown of Cell Membranes”) as applied to claim s 31 and 34 respectively above, and further in view of Davalos et al. (US Pat. Pub. 2010/261994 A1) . Regarding claims 33, 37, 41 and 44-45, while Neal contemplates a plurality of IRE electrical pulses to be applied, Neal fails to contemplate that the pulses include the voltage range of 5 to 450 V , for an electrical field of 500 V/cm to 2500 V/cm for 10000 microseconds or less, or for an electrical field of up to 750 V/cm . Davalos provides for an exemplary manner of irreversible electroporation and specifically contemplates the use of pulses in a voltage range of 5 to 450 V (see [0069] providing for voltages up to 500V), for an electrical field of 500 V/cm to 2500 V/cm for 10000 microseconds or less (see at least [0025] and claim 14), or for an electrical field of up to 750 V/cm (see again, [0025] and claim 14). Therefore, it is the Examiner’s position that it would have been obvious to one of ordinary skill in the art at the time of filing to have utilized the various parameters set forth in Davalos to the protocol for irreversible electroporation as described in Neal to provide for an exemplary manner of generating irreversible electroporation in various tissue affected by cancer. Davalos readily provides that each of the listed ranges in each of claims 33, 37, 41 and 44-45 would be appreciated by one of ordinary skill in the art as capable of achieving IRE in a desired portion of tissue with a reasonable expectation of success while also providing the advantage, as disclosed throughout Davalos, as accomplishing such while also avoiding thermal-based effects on the target and peripheral tissue. Regarding claim 36, Neal provides that the pulse width is in the range of from 5 microseconds to 62,000 milliseconds (see page 2619, right column, last paragraph providing for 100µs), but fails to provide that each pulse of the plurality of electrical pulses produces an electric field below the transmembrane potential threshold for electroporating the cells having the morphology of the selected cells. Davalos contemplates for the use of a plurality of pulses that, when the overall affect is summed, “results in the generation of an electrical field” to induce IRE where the summation results in the transmembrane potential to be reached by the summation of those pulses (see [0025], [0058], [0068]). Therefore, it is the Examiner’s position that it would have been obvious to one of ordinary skill in the art at the time of filing to have utilized a pulse protocol as in Davalos to the protocol of Neal to provide for a summation of the effect of the applied pulses that result in the achieving of the TMP so as to thereby cause IRE in the target tissue. Davalos readily provides that such an alternative treatment protocol is suitable to achieve the IRE as contemplated in Neal and further provides for such to be accomplished while also avoiding thermal-based effects on the target and peripheral tissue. Regarding claim 43, while Neal provides that the plurality of electrical pulses to comprise monophasic electrical pulses (via a first needle being charged and a second needle being grounded as in figure 1 and on page 2617, right column), Neal fails to contemplate that such are biphasic pulses. Davalos contemplates that applied electrical pulses can either be monophasic or biphasic (see [0025]). Therefore, it is the Examiner’s position that it would have been obvious to one of ordinary skill in the art at the time of filing to have utilized biphasic pulses instead of monophasic pulses in view of the teaching of Davalos. Davalos readily contemplates that either manner of applying the pulses functions to generate IRE within a target tissue and would have been an obvious consideration to one of ordinary skill with a reasonable expectation of success when designing a protocol as set forth in Neal. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT RONALD HUPCZEY, JR whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-5534 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday; 8 am - 4 pm . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Joseph Stoklosa can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-1213 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Ronald Hupczey , Jr./ Primary Examiner, Art Unit 3794
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Prosecution Timeline

Apr 03, 2023
Application Filed
Feb 26, 2024
Response after Non-Final Action
Apr 02, 2026
Non-Final Rejection — §103 (current)

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Expected OA Rounds
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Grant Probability
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With Interview (+22.1%)
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