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 .
ELECTION/RESTRICTIONS & STATUS OF CLAIMS
2. This action is responsive to the “AMENDMENT AND RESPONSE TO RESTRICTION REQUIREMENT” filed 08/10/2026 (“08/10/26 Amendment”).
3. Applicant’s election without traverse of Group I (claims 1-14) in the 08/10/26 Amendment is acknowledged. Claims 15 & 22 were amended to fall within Group I, and non-elected claims 16-21 were cancelled (claims 23-38 were previously cancelled). Claims 39-44 were newly added.
4. Claims 1-15, 22, & 39-44 are now pending, and have been examined on the merits.
CLAIM REJECTIONS - 35 USC § 102
5. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
6. Claims 1, 10-13, 15, & 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. 2017/02664389 to Sano et al. (“Sano”).
7. Regarding claim 1, Sano discloses an apparatus for specifically ablating a target tissue, the apparatus comprising:
a pulse generator [pulse generator (10) - ¶[0141]; FIG. 6];
an applicator [probe (22) - ¶’s [0141]-[0143]; FIG. 6] configured to apply electrical energy from the pulse generator [(10)] to two or more electrodes [bipolar electrodes - ¶[0143]]; and
a controller [treatment control computer (40) - ¶’s [0143], [0147]] comprising one or more processors [processor (CPU) (46) - ¶[0147]] and a memory [memory storage (44), program storage (48), data storage (50) - ¶[0147]] storing computer-program instructions [¶[0147]], that, when executed by the one or more processors, perform a computer-implemented method [¶’s [0144]-[0147]] comprising:
setting a packet size of a packet [a train of electrical pulses – e.g., ¶[0003]] of sub-microsecond [nanosecond] pulsed electrical energy [e.g., ¶’s [0026], [0027], [0162]] having a frequency of greater than 0.5 MHz [e.g., ¶’s [0132], [0170], [0187]] based on an identified membrane charging time constant for the target tissue or cells [NOTE: as broadly as currently claimed, Sano discloses that a membrane charging time constant is factored into the selection of pulse parameters – see, e.g., ¶’s [0006], [0013], [0023], [0123], [0175]; as such, it is already “identified,” or known (compare with claim 2 of the instant application --addressed below-- below which affirmatively requires that the claimed method itself actively identify the membrane charging time constant)]; and
applying, from the pulse generator [(10)], the packet of sub-microsecond pulsed electrical energy between the two or more electrodes [¶[0170]], when triggered by a user input [e.g., ¶’s [0144] (“The present invention includes computer software (treatment planning module 54) which assists a user to plan for, execute, and review the results of a medical treatment procedure”), [0148], [0149]], to selectively and specifically kill the target tissue [e.g., Abstract; ¶’s [0008]-[0011], [0123]].
8. Regarding claim 10, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano further discloses wherein the two or more electrodes comprise an array of needle electrodes [e.g., ¶’s [0096], [0152], [0161], [0172], [0205], [0276], [0296], [0320]; FIG. 6].
9. Regarding claim 11, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano further discloses wherein the computer-implemented method is configured to set the packet size of the packet of sub-microsecond pulsed electrical energy so that the sub-microsecond pulsed electrical energy comprises sub-microsecond pulses having a pulse duration of between about 1 ns to about 1000 ns [e.g., ¶’s [0026], [0027], [0030], [0162]].
10. Regarding claim 12, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano further discloses wherein the computer-implemented method is configured to set the packet size of the packet of sub-microsecond pulsed electrical energy comprises sub-microsecond pulses having a pulse amplitude of between about 1 kV/cm to about 12 kV/cm [e.g., ¶[0168]].
11. Regarding claim 13, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano further discloses wherein the computer-implemented method is configured to set the packet size of the packet of sub-microsecond pulsed electrical energy so that the packet size comprises between about 30 and 300 pulses [e.g., ¶’s [0161], [0166]].
12. Regarding claim 15, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano further discloses wherein the packet size of the packet of sub-microsecond pulsed electrical energy has a frequency of between 0.5 MHz and 5 MHz based on the identified membrane charging time constant [e.g., ¶’s [0132], [0161], [0170]].
13. Regarding claim 43, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano further discloses wherein the applicator [probe (22)] comprises a removable or disposable tip [as broadly as claimed, the entirety of probe (22), including its tip, is capable of being discarded or disposed of (thrown away) at any time, including, e.g., after use in a procedure].
CLAIM REJECTIONS - 35 USC § 103
14. 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.
15. 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.
16. Claims 2-4, 6-9, 14, 22, 39, & 40 are rejected under 35 U.S.C. 103 as being unpatentable over Sano in view of U.S. 2019/0117964 to Bahrami et al. ("Bahrami").
17. Regarding claim 2, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
As established in the rejection of claim 1 (above), Sano discloses setting a packet size based on an identified membrane charging time constant for the target tissue or cells. Sano does not, however, explicitly disclose that the computer-implemented method itself include the active step of identifying (or determining) the membrane charging time constant, and therefore fails to disclose:
wherein the computer-implemented method further comprises identifying the membrane charging time constant for the target tissue or cells.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶[0211] (“As described above, capacitance and resistance measurements are an indicator of how healthy the cells are, and may be used to determine how long an electric pulse to apply in order to disrupt the cell membrane and provide conditions sufficient for electroporation. Once the average impedance of the cells has been determined, it is possible to determine several characteristics of the measured cells including, but not limited to Initial condition of cells or tissue—for example, whether the cells are diseased (demonstrated by lower than average capacitance), whether the cells are healthy, positioning of electrodes—whether the electrodes are properly positioned surrounding area around tissue/cells of interest/and whether they are in right location for effective electroporation, and the time constant, as briefly discussed above (to be described further below) for the cells”); see also ¶[0217] (“Impedance may be measured based on charge redistribution in the cells in response to low frequency electric field excitations of the low voltage interrogation circuit. Impedance may be measured before, between and after electroporation electric fields are applied to determine cell conditions, including, but not limited to cell health, placement of electrodes relative to cells for optimum electroporation, and most importantly a time constant which can be used to determine pulse width of electric fields to be applied to the cells in the electric field zone”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the controller be further configured to identify the membrane charging time constant for the target tissue or cells (using a bioimpedance measurement from the two or more electrodes) since such a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Bahrami, and one of ordinary skill in the art would have been capable of applying this known technique to the known device of Sano, and the results [determining a time constant that can then be used to determine pulse parameters] 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).
18. Regarding claims 3 & 4, the combination of Sano and Bahrami teaches all of the limitations of claim 2 for the reasons set forth in detail (above) in the Office Action.
Bahrami further teaches: [claim 3] wherein the computer-implemented method includes receiving a description of the target tissue or cells and wherein identifying the membrane charging time constant comprises identifying the membrane charging time constant for the target tissue or cells based on the description; & [claim 4] wherein receiving the description comprises receiving one or more of: a tissue type of the target tissue or cells, a cell size of the target tissue or cells, a cell shape of the target tissue or cells, a fat content of the target tissue or cells, and a water content of the target tissue or cells [Bahrami further teaches that the acquired data may be used together with old data from previously conducted experiments, including on tissue samples with tumors having similar characteristics (“tumor type”), when determining optimal parameters/conditions [see, e.g., ¶’s [0199], [0370]].
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 Sano & Bahrami to include receiving a description of the target tissue or cells [e.g., tumor type from prior data] and wherein identifying the membrane charging time constant comprises identifying the membrane charging time constant for the target tissue or cells based on the description, and wherein receiving the description comprises receiving a tissue type (“tumor type”) of the target tissue or cells, since such a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Bahrami, and one of ordinary skill in the art would have been capable of applying this known technique to the known device of Sano, and the results [determining a time constant that can then be used to determine pulse parameters] 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).
19. Regarding claim 6, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the controller is further configured to determine a bioimpedance measurement from the two or more electrodes and wherein the computer-program instructions further comprise identifying the membrane charging time constant for the target tissue or cells from the bioimpedance measurement.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶[0211] (“As described above, capacitance and resistance measurements are an indicator of how healthy the cells are, and may be used to determine how long an electric pulse to apply in order to disrupt the cell membrane and provide conditions sufficient for electroporation. Once the average impedance of the cells has been determined, it is possible to determine several characteristics of the measured cells including, but not limited to Initial condition of cells or tissue—for example, whether the cells are diseased (demonstrated by lower than average capacitance), whether the cells are healthy, positioning of electrodes—whether the electrodes are properly positioned surrounding area around tissue/cells of interest/and whether they are in right location for effective electroporation, and the time constant, as briefly discussed above (to be described further below) for the cells”); see also ¶[0217] (“Impedance may be measured based on charge redistribution in the cells in response to low frequency electric field excitations of the low voltage interrogation circuit. Impedance may be measured before, between and after electroporation electric fields are applied to determine cell conditions, including, but not limited to cell health, placement of electrodes relative to cells for optimum electroporation, and most importantly a time constant which can be used to determine pulse width of electric fields to be applied to the cells in the electric field zone”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the controller be further configured to determine a bioimpedance measurement from the two or more electrodes and wherein the computer-program instructions further comprise identifying the membrane charging time constant for the target tissue or cells from the bioimpedance measurement, since such a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Bahrami, and one of ordinary skill in the art would have been capable of applying this known technique to the known device of Sano, and the results [determining a time constant that can then be used to determine pulse parameters] 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).
20. Regarding claim 7, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the computer-implemented method further comprises identifying a membrane charging time constant for a non-target tissue or cells adjacent to the target tissue or cells.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶’s [0211], [0217]].
Bahrami additionally teaches identifying a membrane time constant for a number of cells in an area in order to identify healthy vs. diseased cells [see, e.g., ¶[0211] (“As described above, capacitance and resistance measurements are an indicator of how healthy the cells are, and may be used to determine how long an electric pulse to apply in order to disrupt the cell membrane and provide conditions sufficient for electroporation. Once the average impedance of the cells has been determined, it is possible to determine several characteristics of the measured cells including, but not limited to Initial condition of cells or tissue—for example, whether the cells are diseased (demonstrated by lower than average capacitance), whether the cells are healthy, positioning of electrodes—whether the electrodes are properly positioned surrounding area around tissue/cells of interest/and whether they are in right location for effective electroporation, and the time constant, as briefly discussed above (to be described further below) for the cells”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano to include identifying a membrane charging time constant for a non-target tissue or cells adjacent to the target tissue or cells, since such a modification would help better distinguish healthy cells from diseased cells, which in turn would help better define/outline a targeted treatment area/zone to ensure that only diseased (targeted) cells are treated while healthy cells are protected or spared, as taught by Bahrami.
21. Regarding claim 8, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the computer-implemented method is configured to limit a total number of pulses in the packet of sub-microsecond pulsed electrical energy to target tissue or cells having a sufficiently low time constant.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶’s [0211], [0217]].
Bahrami additionally teaches that it was known to adjust the number of pulses in real-time during a treatment --based on a time constant value that is continually updated during a procedure-- to obtain optimum electroporation [see, e.g., Abstract, ¶[0007], ¶[0215], ¶[0217] (“Impedance may be measured before, between and after electroporation electric fields are applied to determine cell conditions, including, but not limited to cell health, placement of electrodes relative to cells for optimum electroporation, and most importantly a time constant which can be used to determine pulse width of electric fields to be applied to the cells in the electric field zone”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the computer-implemented method be configured to adjust the number of pulses in the packet of sub-microsecond pulsed electrical energy to target tissue or cells during a procedure, as needed, based on updated time constant values, including, e.g., limiting a total number of pulses in the packet of sub-microsecond pulsed electrical energy to target tissue or cells having a sufficiently low time constant, since such a modification would provide the benefit/advantage of optimizing electroporation conditions (in real-time during a procedure) to ensure that targeted cells are being sufficiently treated while healthy cells outside of the electroporation location sustain minimal to no permanent damage, as explicitly taught by Bahrami.
22. Regarding claim 9, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the computer-implemented method is configured to target a tumor tissue and spare a surrounding normal tissue by tuning the packet size.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known in the art to tune/adjust packet size to spare a surrounding normal tissue (a non-target tissue) [see, e.g., Abstract, ¶[0007] (“Accordingly, there is a need for implementing a control system using tissue-sensing based feedback to optimize the EP process with tumor-specific measurements acquired before and between each EP pulse”); ¶[0215], ¶[0217] (“Impedance may be measured before, between and after electroporation electric fields are applied to determine cell conditions, including, but not limited to cell health, placement of electrodes relative to cells for optimum electroporation, and most importantly a time constant which can be used to determine pulse width of electric fields to be applied to the cells in the electric field zone”); ¶[0284] (“Thus, the electroporation method of the present invention yields the advantage that healthy cells outside of the electroporation location but within the electric field zone 100 are subjected to electric pulses for only half of the duration of those in the electroporation location and insufficient for electroporation, these cells sustain minimal to no permanent damage”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the computer-implemented method be configured to target a tumor tissue and spare a surrounding normal tissue by tuning (adjusting) the packet size, since such a modification would provide the benefit/advantage of optimizing electroporation conditions (in real-time during a procedure) to ensure that targeted cells are being sufficiently treated while healthy cells outside of the electroporation location sustain minimal to no permanent damage, as explicitly taught by Bahrami.
23. Regarding claim 14, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the controller is configured to identify the membrane charging time constant by applying a low-energy test pulse and determining a time constant from a time course of a conductance from the test pulse.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶’s [0211], [0217]].
Bahrami additionally teaches measuring impedance --which is used to determine a time constant-- before electroporation electric fields are applied which, as broadly as claimed, can be considered a “test pulse” [see ¶[0217] (“Impedance may be measured based on charge redistribution in the cells in response to low frequency electric field excitations of the low voltage interrogation circuit. Impedance may be measured before, between and after electroporation electric fields are applied to determine cell conditions, including, but not limited to cell health, placement of electrodes relative to cells for optimum electroporation, and most importantly a time constant which can be used to determine pulse width of electric fields to be applied to the cells in the electric field zone”); note also the discussion of a “low voltage (interrogatory) signal” in ¶[0223]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano to include identifying the membrane charging time constant by applying a low-energy test pulse and determining a time constant from a time course of a conductance from the test pulse, since such a modification would provide the benefit/advantage of enabling a more accurate determination of electroporation pulse parameters based on data acquired in real-time immediately prior to the application of electroporation electric fields, as taught by Bahrami.
24. Regarding claim 22, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the computer-implemented method comprises estimating the membrane charging time constant from a biopsy of the target tissue.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶’s [0211], [0217]].
Bahrami further teaches that the acquired data may be used together with old data from previously conducted experiments, including on tissue samples with tumors having similar characteristics, when determining optimal parameters/conditions [see, e.g., ¶’s [0199], [0370]].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano to include estimating the membrane charging time constant from a biopsy of the target tissue, since such a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Bahrami, and one of ordinary skill in the art would have been capable of applying this known technique to the known device of Sano, and the results [determining a time constant that can then be used to determine pulse parameters] 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).
25. Regarding claim 39, the combination of Sano and Bahrami teaches all of the limitations of claim 14 for the reasons set forth in detail (above) in the Office Action.
Sano was modified above (in the rejection of claim 14) to apply a test pulse. Bahrami further teaches wherein the test pulse has a duration of 1 microsecond or longer [Bahrami, e.g., ¶[0223]].
26. Regarding claim 40, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not, however, disclose:
wherein the packet size is set between about 3 or more times a membrane charging time constant for the target tissue or cells.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known in the art for a packet size to be set between about 3 or more times a membrane charging time constant for target tissue or cells [see, e.g., ¶[0217] (“the pulse width of the initial electroporation electric field pulse may be set to 5 times the time constant. This pulse width is insufficient to cause electroporation in the cells which are outside of the electroporation location 110, as described above, but sufficient to cause electroporation in the cells of the tissue in the electroporation location 110 which is subjected to the additive effects of the electric fields from all sets of EPEs being applied as one continuous electric field”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the packet size is set between about 3 or more times a membrane charging time constant for the target tissue or cells, since such a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Bahrami, and one of ordinary skill in the art would have been capable of applying this known technique to the known device of Sano, and the results [effectively treating target tissue or cells while avoiding/sparing non-target tissue or cells] 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. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Sano and Bahrami, and further in view of U.S. 2020/0289188 to Forsyth et al. ("Forsyth").
28. Regarding claim 5, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
As established in the rejection of claim 1 (above), Sano discloses setting a packet size based on an identified membrane charging time constant for the target tissue or cells. Sano does not, however, explicitly disclose that the computer-implemented method itself include the active step of identifying (or determining) the membrane charging time constant.
Bahrami, in a similar field of endeavor, relates generally to the use of control systems to improve an electroporation process [e.g., ¶[0002]], and teaches that it was known to determine a membrane charging time constant for tissue based on acquired impedance measurements, which is then used to determine pulse width of electric fields to be applied to the cells in the electric field zone [see, e.g., ¶[0211] (“As described above, capacitance and resistance measurements are an indicator of how healthy the cells are, and may be used to determine how long an electric pulse to apply in order to disrupt the cell membrane and provide conditions sufficient for electroporation. Once the average impedance of the cells has been determined, it is possible to determine several characteristics of the measured cells including, but not limited to Initial condition of cells or tissue—for example, whether the cells are diseased (demonstrated by lower than average capacitance), whether the cells are healthy, positioning of electrodes—whether the electrodes are properly positioned surrounding area around tissue/cells of interest/and whether they are in right location for effective electroporation, and the time constant, as briefly discussed above (to be described further below) for the cells”); see also ¶[0217] (“Impedance may be measured based on charge redistribution in the cells in response to low frequency electric field excitations of the low voltage interrogation circuit. Impedance may be measured before, between and after electroporation electric fields are applied to determine cell conditions, including, but not limited to cell health, placement of electrodes relative to cells for optimum electroporation, and most importantly a time constant which can be used to determine pulse width of electric fields to be applied to the cells in the electric field zone”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the controller be further configured to identify the membrane charging time constant for the target tissue or cells (using a bioimpedance measurement from the two or more electrodes) since such a particular known technique was recognized as part of the ordinary capabilities of one skilled in the art, as clearly demonstrated by Bahrami, and one of ordinary skill in the art would have been capable of applying this known technique to the known device of Sano, and the results [determining a time constant that can then be used to determine pulse parameters] 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).
Finally, the combination of Sano and Bahrami does not teach:
wherein the computer-implemented method is configured to identify the membrane charging time constant by determining a fat and/or water content of the target tissue or cells and estimating the membrane charging time constant from the fat and/or water content.
Forsyth, in a similar field of endeavor, teaches that it was known in the art for a time constant to be dependent upon, e.g., water content [e.g., ¶[0092]].
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 Sano and Bahrami such that a membrane charging time constant be correlated to factors known to impact the membrane charging time constant such as, e.g., water content, to ensure that the membrane charging time constant is as accurate as possible.
29. Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Sano and Bahrami, as applied to claim 40 above, and further in view of U.S. 2003/0199050 to Mangano et al. ("Mangano").
30. Regarding claim 41, the combination of Sano and Bahrami teaches all of the limitations of claim 40 for the reasons set forth in detail (above) in the Office Action.
The combination of Sano and Bahrami does not, however, teach:
wherein the packet size is set about 2 or less times a membrane charging time constant for a non-target tissue or cells.
Mangano, in a similar field of endeavor, teaches that, for poration, it was known in the art to supply a pulse at least three to four times the membrane charging time constant [see ¶[0131] (“In preferred embodiments, in order to achieve thorough membrane charging, the duration of the portion of the electric field pulse supplying an electric field strength greater than the critical field strength, Ec, to porate the cell, for example the flat-topped portion of a rectangular field pulse, should be at least three to four times the membrane charging time constant τm...”). As such, it is the Examiner’s position that a packet size which is set to be less than about 3 or 4 times the membrane charging time constant in Mangano (such as, e.g., 2 or less times) would be insufficient to porate the cell.
As such, 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 Sano and Bahrami such that the packet size is set about 2 or less times a membrane charging time constant for a non-target tissue or cells, in order to avoid electroporation of healthy cells.
Further, to the extent that it is noted that “les than about 3” does not necessarily equate to “2 or less,” it is noted that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).
31. Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Sano in view of U.S. 2022/0331601 to D’Agostino et al. ("D’Agostino").
32. Regarding claim 42, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
Sano does not explicitly disclose:
wherein the one or more processors comprises a series of processors configured to communicate with each other wirelessly, by wired connection, or both.
D’Agostino, in a similar field of endeavor, teaches devices, systems, and methods for applying pulsed electric fields to tissue [e.g., ¶[0002]], and teaches that it was known for a controller to include multiple processors in communication with one another [see, e.g., ¶[0282] (“The controller (5340) may comprise a processor... In some variations, the processor may be any suitable processing device configured to run and/or execute a set of instructions or code and may include one or more data processors, image processors, graphics processing units (GPU), physics processing units, digital signal processors (DSP), analog signal processors, mixed-signal processors, machine learning processors, deep learning processors, finite state machines (FSM), compression processors (e.g., data compression to reduce data rate and/or memory requirements), encryption processors (e.g., for secure wireless data and/or power transfer), and/or central processing units (CPU). The processor may be, for example, a general purpose processor, Field Programmable Gate Array (FPGA), an Application Specific Integrated Circuit (ASIC), a processor board, and/or the like. The processor may be configured to run and/or execute application processes and/or other modules, processes and/or functions associated with the system”)]. The communication therebetween would inherently be via either one of wired or wireless connection.
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the one or more processors comprises a series of processors configured to communicate with each other via either one of wired or wireless connection, since such a modification amounts merely to the simple substitution of one known processing configuration for another, yielding only predictable results to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
33. Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Sano in view of U.S. 2020/0297998 to Danitz et al. ("Danitz").
34. Regarding claim 44, Sano discloses all of the limitations of claim 1 for the reasons set forth in detail (above) in the Office Action.
While Sano further discloses a variety of electrode configurations [see, e.g., ¶’s [0142]-[0143]], Sano does not explicitly disclose:
wherein the two or more electrodes are non-penetrating electrodes.
Danitz, in a similar field of endeavor, teaches treatment of tissue by the application of pulsed electric fields, such as nanosecond electrical pulses [see ¶[0004]], and teaches the interchangeability of needle (penetrating) electrodes and surface (non-penetrating) electrodes [see ¶[0057] (“Any of these methods may include inserting a pair of electrodes into the patient's skin before applying the plurality of high-field strength, ultra-short electrical pulses... Alternatively or additionally, the high-field strength, ultra-short electrical pulses may be applied transdermally, without puncturing the skin. For example, any of these methods may include applying the set of electrodes on the surface of the patient's skin before applying the plurality of high-field strength, ultra-short electrical pulses”); and ¶[0075] (“The electrodes may be surface electrodes or penetrating electrodes...”)].
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to modify Sano such that the two or more electrodes are non-penetrating electrodes, since such a modification amounts merely to the simple substitution of one known electrode configuration for another, yielding only predictable results [application of pulsed electrical energy] to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
CONCLUSION
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/BRADFORD C. BLAISE/Primary Examiner, Art Unit 3794
