DETAILED ACTION
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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Specification
The disclosure is objected to because of the following informalities: The specification uses the terms PDL1, PDL-1 and PD-L1 to refer, apparently, to the same element. Appropriate correction is required.
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 7 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.
Regarding claim 7, the term “minimize” is a relative term which renders the claim indefinite. The term “minimize” 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. It is unclear exactly how much cavitation must be reduced in order to have been “minimized.”
Claim Rejections - 35 USC § 102
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.
Claims 1-5, 8 and 11-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wasson (US 2021/0052882).
Regarding claims 1-5, 8 and 20, Wasson discloses an electroporation system including an instrument with two energy delivery bodies ([0120]) connected to a generator operated with an “algorithm” (i.e. whatever control processes produce the desired outcome) that results in outputting biphasic pulsed electric fields (fig. 1B) to create a plurality of zones in a bulls-eye arrangement, including at least a pulsed electric field zone and a thermal zone (e.g. fig. 13, [0137]), which will result in, among other things, an increase in an adaptive immune response ([0138]). Wasson further discloses that “inter-cycle delays” and “inter-packet” delays are used to control zone size ([0048], note that in this case “cycle” and “packet” are undefined).
Regarding claims 11-16, the various mechanisms of immune response are understood to be related in the presence of pulsed electric fields such that even a small amount of those responses are understood to be a necessary product of the type of pulsed electric field which results in the improved immune response disclosed by Wasson. This is the broadest reasonable interpretation of the claims that does not result in an indefiniteness rejection and potentially an enablement rejection. The specification does not describe what specific “algorithm” would produce these results independently, and it is not clear what specific values in the massive parameter ranges provided in the specification are necessary to produce these specific results. For example, the CD8+/CD4+ T-cell ratio appears in exactly one part of the specification ([00246]-[00249]) as a result of every treatment performed in a trial for which there appears to be no specific pulsed field parameters provided. If Applicant’s have invented a specific system that is capable of producing these results independently, and/or if there are specific parameters necessary to produce these specific results, the claims should reflect those details. It is also noted that the fact that these are apparatus claims and not method claims will complicate efforts to claim steps and not structure as apparatus claims are directed to what an invention is, not what it does (MPEP 2114). As long as the prior art is capable of producing the results (by, for example, disclosing certain operational parameters), it will read on the claimed structure that is merely capable of producing that result. In the interest of compact prosecution, a list of references which are relevant to the various immune responses have been provided in the conclusion below.
Regarding claims 17-19, the claims do not require the use of an immune checkpoint inhibitor, only that the system might produce some result if it so happened to be used with an immune checkpoint inhibitor. Being a functional limitation, the system of Wasson reads on the claims because there is some combination of parameters disclosed by Wasson that would produce the claimed result if used in some hypothetical combination with a hypothetical amount of an anti-PD1 therapy. However, in the interest of compact prosecution, it is noted that using pulsed electric fields to produce an abscopal effect in conjunction with anti-PDl1 is known in the art such as taught by Qiao ([0009], US 2020/0323583). Like claims 11-16, these claims must either be interpreted extremely broadly or as indefinite and potentially lacking enablement.
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.
Claims 6, 7, 9, 10 and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Wasson.
Regarding claims 6, 7 and 9, Wasson does not disclose the specific inter-cycle delays and inter-pulse delays, although it is noted these delays are not defined with respect to anything other than themselves. Wasson does teach that the inter-cycle and inter-pulse delays are used to control the size of the various zones ([0048]), where the delay between one of the pulses and the bursts are understood to be one of the “inter-cycle delay” and the “inter-pulse” delay since terms like cycle, burst, pulse, dose and train are used interchangeably to describe various elements of pulsed electric waveforms. For these delays, Wasson teaches a duration of a large range of values including specifically 10 microseconds and 3 seconds ([0063]). Therefore, before the application was filed, it would have bene obvious to one of ordinary skill in the art to modify the system of Wasson to use any commonly known inter-cycle delays and inter-pulse delays including on the order of microseconds and seconds as taught by Wasson that would produce the predictable result of controlling the size of the zones created by the procedure to produce the result desired by an operator. It is noted that the 10-microsecond delay will at least “minimize” cavitation relative to some unclaimed, undefined hypothetical alternative.
Regarding claims 10 and 21-25, Wasson does not specifically disclose that the treatment procedure involves, variously, a dose of 5-6 minutes, where a dose comprises 100 packets with 3 seconds between the packets, where a packet has 40 biphasic pulses with 100 microseconds between the pulses. However, these variables are all well within the parameters commonly used in the art for pulsed electric field treatment. Wasson discloses the three tiers of treatment: the dose being the total duration of treatment, the packet being the burst ([0059]) and the pulse being the pulse ([0062]). Wasson further discloses that the number of bursts and pulses within bursts can be from 1-5000 ([0062]). Wasson further discloses that the delay between the pulses and bursts can be between microseconds and seconds ([0063]). Finally, Wasson discloses that the pulses can be chosen to create cell death on the order of “minutes” ([0053]) which is understood to be a dose range that includes single digit minutes. Therefore, before the application was filed, it would have been obvious to modify the system of Wasson to use any of the values disclosed for the pulsed electric field by Wasson, including a dose of 5-6 minutes, 100 packets in a dose, 3 seconds between packets and 40 pulses a packet, 1000 microseconds between pulses, or any other ranges of those values disclosed by Wasson, that would produce the predictable result of ablating tissue while promoting an immune response as taught by Wasson. It is noted that claim 25 is extremely broad since neither “packets” nor “active time” are defined. The device of Wasson as modified discloses the breadth of those limitations even where “packets” may be defined differently than in claim 20.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Regarding all the subject matter in claims 11 and 13-15 see discussion of figure 16 of US 2019/0282294 to Davalos which also specifically teaches that promotion of the adaptive immune system is beneficial for tumor treatment ([0148]). Regarding the teaching that upregulation of PDL1 expression can be an inflammatory response, see paragraph [0273] of US 2021/0085777 to Steinmetz. Regarding the teaching that creating an immune response in tissue results in the formation of tertiary lymphoid structures, see paragraph [0022] of US 2006/0008808 to Yang. Regarding another pulsed electric field system that generates an immune response and discloses parameter ranges that overlap or encompass the claimed parameters, see table 2 on page 6 of US 2021/0315639 to Manucherhabadi.
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/DANIEL W FOWLER/Primary Examiner, Art Unit 3794