DETAILED ACTION
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.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Ronchetti (US 20140148876) in view of Gunther (US 20210330371) and Waldstreicher (US 20210236815).
With respect to claim 1, Ronchetti discloses an electroporation device adapted to supply to at least a pair of electrodes (Figure 1:5a, 5b) in a portion of tissue of the human body having a voltage V and a controllable total duration τ. Paragraph [0010] states that the electrodes 5a,b are “needle-shaped”, and therefore have an elongated rectilinear shape. An electronic unit (Figure 1:10) having a signal generator (Figure 1:3) and a power amplifier (Figure 1:4) is provided in order to supply voltage Vout to the electrodes. The electroporation device is configured to generate and supply a pulse to the pair of electrodes, and then to measure the current which flows between the pair of electrodes. A resistance (i.e., impedance) value may be calculated using Ohm’s Law. See paragraph [0019] (“The device 1 is provided with a plurality of sensors that monitor continuously the electrical quantities of the electroporation process in progress; in particular, sensors 12, 13, 14 are provided, designed to measure the instantaneous value of the current le supplied to each pair of electrodes 5a, 5b, the voltage value Ve applied to said pair of electrodes, and the impedance Z(ω) present between said pair of electrodes”). Paragraphs [0032]-[0036] state that the energy dose for electroporation is calculated as:
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where τ is the conductivity of the tissue (and therefore equal to the inverse of resistivity). Ronchetti indicates that t is the time duration of each pulse. E is known to be equal to (V/d). Ronchetti additionally considers the number of pulses supplied k. Ronchetti therefore describes considering time and voltage when determining an applied energy dose during electroporation. Ronchetti, however, does not expressly teach that duration and voltage values are selected so that the applied energy dose satisfies the inequality
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Gunther discloses an electroporation device adapted to supply to at least a pair of electrodes in a portion of tissue of the human body having a voltage V and a controllable total duration τ. Gunther recognizes that cell permeabilization is primarily dependent on the applied voltage and the duration of the applied pulses (“The effect on the cell membrane is a function of the electric field strength and pulse time duration”). Paragraphs [0036]-[0038] teach voltage and duration paired values that produce irreversible poration in a typical mammalian cell (i.e., values that produce an energy dose that is greater than an energy dose that realizes a reversible electroporation).
Before the effective filing date of the claimed invention, it would have been obvious to consider applying an energy dose greater than an energy dose known to realize reversible electroporation when operating the device of Ronchetti. Gunther indicates that energy dose is dependent on the applied voltage and duration of pulses, and that it is well within the ability of one of ordinary skill to calculate, select and store values of duration and voltage that are known to produce irreversible cell membrane poration. Gunther teaches that irreversible electroporation is often beneficial, such as when used for tissue ablation during the treatment of adverse medical condition (“Tissue ablation may be performed using the desired techniques (e.g. IRE, RE, E, IRE+E, or RE+E) by selecting a field strength and time associated with the domain of interest”).
As noted above, Ronchetti indicates that the conductivity of the tissue (τ) is considered when optimizing electroporation conditions. Ronchetti, however, does not appear to expressly teach that a resistance value RA,B is detected between the pair of electrodes by applying a test pulse at a known voltage Vtest and measuring the current Itest.
Waldstreicher discloses a system for applying a periodic voltage to the tissue of a human body using at least one pair of electrodes. Waldstreicher teaches in paragraphs [0326] and [0327] that variances in the resistance RA,B of a tissue are accounted for by initiating a series of test pulses at a known voltage Vtest and measuring the produced current Itest (“the monitoring and test pulse conditions may be used to determine the properties of the tissue in the electrical system and provide adjustments to the energy delivery algorithm… any change in output current due to impedance differences in the patient tissue system, will also result in compensatory changes in the delivered voltage”)
Before the effective filing date of the claimed invention, it would have been obvious to ensure that at least a first test pulse Vtest is performed when using the apparatus of Ronchetti. Waldstreicher teaches that it is important to determine the properties of the treated tissue and to provide necessary adjustments, including modifying voltage in response to detected impedance differences. Furthermore, Waldstreicher and Ronchetti each describe how voltage and treatment duration are modifiable variables that are optimized through routine experimentation. See for example paragraph [0044] of Ronchetti, which indicates that treatment time and the number of pulses per unit time may be adjusted in response to a reduction in voltage, as well as paragraph [0028] (“Block 130 computes (in a known way by applying Ohm's law once the impedance Z is known) the value of the voltage that can be applied to the electrodes necessary to obtain an increase of the current and bring the electroporation current to a target value”).
With respect to claim 2, Ronchetti, Gunther and Waldstreicher disclose the combination as described above. Solving an equation by fixing at random one of two parameters and then solving for the other according to an iterative process is considered to be well known in the art.
With respect to claims 3 and 4, Ronchetti, Gunther and Waldstreicher disclose the combination as described above. It is well known in the art that V=IR (again, Ohm’s Law), and so those of ordinary skill would understand how to solve for the maximum voltage deliverable given an established resistance value and a maximum current.
Response to Arguments
In response to Applicant’s amendment filed 21 July 2026, the previous rejections have been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the combination of Ronchetti with Gunther and Waldstreicher.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Tegg (US 20210267672) and Asconeguy (US 20220401146) references disclose the state of the art regarding electroporation devices that select voltage and duration values sufficient to produce an energy dose that is greater than an energy dose necessary for reversible electroporation (i.e., an energy dose that realizes irreversible electroporation).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at (571) 272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799
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