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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 21, 2026 has been entered.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 45 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 45 is unclear with the scope of the claim, particularly in that it appears to contradict claim 21, from which claim 45 depends. Claim 21 requires the step of administering an exogenous agent that comprises a monoclonal antibody or a monoclonal antibody conjugate. Claim 45 recites that the administering step “comprises or further comprises” administering one or more exogenous agents which comprises an exhaustive list that does not include the monoclonal antibody or monoclonal antibody conjugate required by claim 21. Hence, it appears claim 45 should recite “further comprises administering on or more additional exogenous agents” or similar language.
It is again noted that the exhaustive list of agents is deemed to be a list of obvious various different exogenous agents since there is no criticality associated with any particular agent.
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.
Claim 21-33 and 35-43 and 45 are rejected under 35 U.S.C. 103(a) as being unpatentable over Davalos et al (2010/0030211) in view of the teaching of Har-Noy (2011/0142887).
Regarding claim 21, Davalos et al provide a method for treating tissue comprising placing a probe in tissue, the probe having a first electrode (Figure 8b, for example). A plurality of electrical pulses are applied to tissue, the pulses having pulse parameters as claimed (see paragraphs [0104-0110], for example). The pulses are intended to generate a uniform electric field (para. [0044], for example) to cause cell death, and the treatment is also known to stimulate an immune response within the body (para. [0009], for example). Davalos et al also disclose that one or more exogenous or endogenous agents may be administered into tissue during treatment (Figure 9 and para. [0063], for example). Davalos et al also specifically teach a multi-modal treatment including the use of one or more monoclonal antibody or monoclonal antibody conjugate. See, for example, paragraph [0053]. In as much as newly added claim 45 indicates that administering chemotherapeutic agents will stimulate or otherwise modulate an immune system response within the body, the use of the same agents as disclosed by Davalos et al would obviously have the same effect. Additionally, Har-Noy disclose a method comprising the steps of ablating tissue with, for example, irreversible electroporation energy (para. [0036], for example) and then providing an agent to stimulate or otherwise modulate the immune response. In particular, Har-Noy disclose numerous different agents, including monoclonal antibodies and monoclonal antibody conjugates (para. [0026], for example).
To have provided the Davalos et al method with the step of administering an agent specifically to stimulate or modulate the immune response within the body would have been an obvious consideration for one of ordinary skill in the art at the time of the invention, particularly since Davalos et al disclose the steps of administering chemotherapeutic agents in a multi-modality treatment and further since Har-Noy expressly teach it is known to administer agents such as monoclonal antibodies and monoclonal antibody conjugates to modulate the immune response of the body after irreversible electroporation.
Regarding claim 22, there is necessarily a delay between pulses, and Davalos et al disclose a pulse length that may be less than 10 microseconds (para. [0105], for example). Regarding claim 23, Davalos et al disclose a frequency of pulse application of 0.001-100 Hz which would necessarily include a delay between pulses much longer than the pulse length (e.g. if using the smaller end of the pulse application frequency. Regarding claim 24, see paragraph [0110]. Regarding claim 25, the pulses are applied in bursts having a frequency of approximately 1Hz. See, also, paragraph [0039]. Regarding claim 26, IRE is well-known to alter the transmembrane potential of cells (para. [0009], for example) and Har-Noy discuss the use of exogenous agents taken up by cells that have been ablated.
Regarding claim 27, Davalos et al provide a method for treating tissue comprising applying a plurality of biphasic pulses with a frequency, voltage and pulse length within the claimed range (para. [0104-0110]). There is inherently a delay between pulses, and the pulses cause irreversible disruption of a cellular membrane (e.g. IRE) in a first zone of tissue and also promotes an immune response (para. [0009]). Again, Davalos et al disclose using chemotherapeutic agents during the treatment, which agent is identified as being capable of stimulating or otherwise modulating the immune response within the body in applicant’s claim 45. Additionally, Har-Noy disclose a method comprising the steps of ablating tissue with, for example, irreversible electroporation energy and then providing a non-chemotherapeutic agents (e.g. monoclonal antibodies) to stimulate or otherwise modulate the immune response. See discussion of claim 21 above.
To have provided the Davalos et al method with the step of administering a non-chemotherapeutic agent specifically to stimulate or modulate the immune response within the body would have been an obvious consideration for one of ordinary skill in the art at the time of the invention, particularly since Davalos et al disclose the steps of administering various different agents in a multi-modality treatment and further since Har-Noy expressly teach it is known to administer non-chemotherapeutic agents to modulate the immune response of the body after irreversible electroporation.
Regarding claim 28, Davalos et al discuss different effects including IRE (abstract) and ECT (para. [0082]). Regarding claim 29, Davalos et al disclose a single burst duration within the claimed range (based on the disclosed number of pulses and pulse lengths disclosed in paragraphs [0104-0109]). Regarding claim 30, again Davalos et al disclose the use of pulse bursts having a pulse burst frequency (e.g. up to 100 Hz), each pulse burst necessarily comprising a pulse train. Regarding claim 31, Davalos et al disclose multiple bursts of pulse trains, and there is necessarily a delay between bursts. Regarding claims 32, 33 and 35, see again discussion of claims 22 and 23 and the Davalos et al frequency of pulse application which would provide such a delay. Regarding claims 36-38, Davalos et al disclose promoting an immune response by the application of a chemotherapeutic agent as addressed previously, which immune response would necessarily occur in the same areas given the use of similar parameters. Har-Noy also disclose the use of non-chemotherapeutic agents that are administered in a large zone that may be considered to encompass multiple zones. Regarding claim 39, see paragraph [0107] of Davalos et al, for example.
Regarding claim 40, Davalos et al again disclose a method of treating tissue comprising generating a plurality of biphasic pulses in bursts to cause non-thermal ablation of cells. See paragraphs [0104-0112] which discloses the use of bursts having biphasic properties and parameters within the claimed ranges. See paragraph [0069] for the discussion of using a monopolar electrode. As addressed above, Davalos et al teach that IRE treatment is known to promote an immune response (para. [0009]) in treated tissue and further disclose the use of chemotherapeutic agents which are indicated to be an agent to promote an immune response as now recited in claim 45. Additionally, Har-Noy disclose a method comprising the steps of ablating tissue with, for example, irreversible electroporation energy and then providing an exogenous antibody to stimulate or otherwise modulate the immune response. See discussion of claim 21.
To have provided the Davalos et al method with the step of administering an exogenous antibody specifically to stimulate or modulate the immune response within the body would have been an obvious consideration for one of ordinary skill in the art at the time of the invention, particularly since Davalos et al disclose the steps of administering exogenous agents in a multi-modality treatment and further since Har-Noy expressly teach it is known to administer exogenous antibodies to modulate the immune response of the body after irreversible electroporation.
Regarding claim 41, see again discussion of claim 23 and the delays that would result from using the smaller end of the frequency range. Regarding claims 42-43, see again paragraphs [0104-0111] of Davalos et al. Regarding claim 45, see again paragraph [0053] of Davalos et al which discloses the use of chemotherapeutic agents. Also, Har-Noy disclose the use of several other agents that may be used to stimulate an immune response after irreversible electroporation. The exhaustive list of claim 45 is taken to mean that all the agents listed are obvious variants, particularly since there is no disclosure of criticality or unexpected results associated with any individual agent. Rather, applicant has merely provided a comprehensive list of known agents, and all agents are deemed to be within the purview of the skilled artisan.
Response to Arguments
Applicant’s arguments with respect to the pending claims have been considered but are moot because the new ground of rejection provides an additional reference to teach the newly claimed subject matter.
Regarding the exhaustive list of agents provided in claim 45, the examiner again maintains such a listing would indicate the various agents are all obvious alternatives that would be within the purview of the skilled artisan. Again, there is no express disclosure of criticality or unexpected results associated with any of the agents, and no indication that any of the agents would be unknown to those of ordinary skill in the art. Further, the support for some of the agents seem questionable, particularly where applicant relies on the background section (e.g. paragraphs [0005] and [0009]) which recite prior art references that are not clear if the disclosed agents are being used in the same procedure of applying electrical pulses within the scope of the independent claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL PEFFLEY whose telephone number is (571)272-4770. The examiner can normally be reached Mon-Fri 8 am-5 pm.
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/MICHAEL F PEFFLEY/Primary Examiner, Art Unit 3794
/M.F.P/July 14, 2026
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