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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/24/2025 has been entered.
Response to Amendment
Claims 33, 38, and 69 have been amended. Claims 33, 35, 38, and 64-74 remain pending.
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.
Claim(s) 33, 35, 38, and 64-74 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dev et al. (US 20040092860, henceforth Dev) in view of Palti (US 20060167499, henceforth Palti) and Orwar et al. (US 20040023394, henceforth Orwar).
Regarding claim 33, Dev discloses a method for reducing the viability of a cell ([0013], the method of electroporation can be used to kill, or reduce the viability of, a cancer cell), the method comprising: applying a first alternating electric field (the electroporation discussed in [0013] is an application of an electric field as in [0002], [0008], and [0109]; Examiner notes that an applied electric pulse must include application of an electric field as an electric field is how an electric pulse acts) at a first frequency to the cell (the pulse durations and delay between pulses as in [0109] denote a first frequency of application; these can be varied depending on the exact desired outcome and target area as disclosed in [0109]-[0113]) for a first period of time (the desired amount of time depends on the frequency of the alternating electric field to be applied and the number of pulses, which can be determined by one of ordinary skill in the art as desired as disclosed in [0113]), wherein application of the first alternating electric field at the first frequency to the cell for the first period of time increases permeability of the cell membranes of the cell (see [0002], [0013], [0113]); and introducing a vector to the cell (the vector can be a chemotherapy drug such as bleomycin, [0013], see also [0070]-[0082]), wherein the increased permeability of the cell membranes enables the vector to cross the cell membrane (“electroporation makes it possible to insert the bleomycin into the cells” [0013]). Additionally, Dev discloses that its method can be applied as a treatment for certain kinds of cancer ([0013]), and that it’s treatment method is not perfectly effective (see [0133], Dev discloses that “square wave form pulses provide increased efficiencies in transporting compounds into the cells in comparison to exponential decay wave form pulses”, which means that neither of the pulse types displays perfect efficacy, meaning some of the target cells would not be treated as desired; see also [0112] which denotes “reduced efficacy” depending on the treatment parameters, meaning it is not perfectly efficacious).
Dev does not disclose the method comprising applying a second alternating electric field at a second frequency to the cell for a second period of time, wherein the second frequency is different from the first frequency, and wherein the second alternating electric field at the second frequency reduces viability of the cell. Dev additionally does not disclose the specific types of cancer cells that its application could be applied to. Palti teaches a method for reducing the viability of a cell (“damages rapidly dividing cells like tumor cells”, see Abstract, where a damaging is a reduction in viability and the cell is a cell of a cancerous tumor), the method comprising: applying a second alternating electric field (AC electric field, see Abstract) at a second frequency (preferably 100 kHz-300 kHz as in [0079]) to the cell for a second period of time (see [0126], an example treatment time is given; additionally, since the treatment is given at a point in time, it is given for some second period of time during which the treatment lasts), and wherein the second alternating electric field at the second frequency reduces viability of the cell (see [0124], [0125], the administration of the electric field destroys the cancerous cells, which reduces their viability). Palti additionally teaches that its treatment modality can include the use of multiple frequencies and can effectively be applied to a broad variety of cancer types ([0017], [0018], [0125]), especially where the efficacy of electroporation known in the art is dependent on cell size and type ([0017]). However, Palti also teaches that, especially for a given set of treatment parameters, its treatment is not perfectly effective (see Palti [0121]-[0125]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the treatment method of Palti to the treatment method of Dev for the benefit of increasing treatment efficacy for cancers where electroporation is based on cancer cell sizes as those treatment methods are less effective in those instances (see Palti [0016]-[0018], Palti teaches that its treatment is less sensitive to cell type and size than known methods), and because using a second alternating electric field with at least a second frequency which is different from the first frequency is beneficial because it allows for a greater spectrum of cells to be affected by the treatment (see Palti [0123]-[0126]), and because neither of the treatment modalities are perfectly effective when administered on their own, and combining the therapies would have reasonably provided a benefit since they select their cells based on different methods (see at least Palti [0016] and [0017] and Dev [0063] and [0112]); additionally, a combination of the treatments could be useful in instances where multiple types of cancer are present as treatment modalities such as those used by Dev where electroporation is administered at one orientation are best utilized where the cancer cells are sized sufficiently from healthy cells, while Palti focuses additionally on target selection based on orientation of the cancer cells instead of size (see Palti [0016]-[0018]), and a combination of both methods would be able to more effectively target multiple types of cells if there is a combination of cancer types both with and without deviations in cancer cell sizes as compared to the healthy cells around them.
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the first frequency be different from the second frequency as the first alternating electric field and the second alternating electric field are used to achieve different outcomes (see Dev [0013] and see Palti [0124]) which both contribute to the reduction of cell viability and cancer treatment and because both Dev and Palti teach that their specific frequencies used should be determined by one of ordinary skill in the art depending on the particular scenario surrounding the treatment protocol (see Dev [0113] and see Palti [0125]). Further, the use of multiple frequencies is taught as beneficial as it is more effective than using a single frequency (Palti [0124]).
Dev additionally discloses that the exact parameters of the alternating electrical field to be induced can be determined by one of ordinary skill in the art ([0113]) and that frequency is one of the parameters which can be changed.
Dev as modified does not disclose the method wherein the first frequency is between 50 kHz and 350 kHz. Orwar teaches a way in which one of ordinary skill in the art could reasonably determine a frequency at which to apply an alternating field for a given desired outcome depending on some of the factors mentioned in Dev (see Orwar [0005]-[0007]). Orwar additionally teaches that the alternating electric fields applied to achieve the outcome discussed in Dev can last only a few microseconds to a few milliseconds ([0006]), and that this was well known. {Examiner notes that a period of a few microseconds roughly translates to the top end of the claimed frequency range, as a period of 3 microseconds, or a few microseconds, is a frequency of about 330 kHz, and a higher period of a few milliseconds translates to 500 Hz; this encapsulates the frequency range as claimed.}
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have had the first frequency be a value in the claimed range since Orwar and Dev teach frequency to be readily determined by one of ordinary skill in the art depending on the particular circumstances and since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Regarding claim 35, Dev as modified discloses the method wherein the cell is a cancer or tumor cell (see Dev [0013] and see Palti [0007]).
Regarding claim 38, Dev as modified discloses the method wherein the second frequency is between 75 kHz and 300 kHz (Palti [0079], the second frequency is preferably 100 kHz-300 kHz).
Regarding claim 64, Dev as modified discloses the method wherein the vector comprises one or more nucleic acid sequences capable of encoding-one or more sequences of interest (see [0070]-[0075]).
Regarding claim 65, Dev as modified discloses the method wherein the sequence of interest is a selectable marker or a therapeutic agent (therapeutic agent as in [0071]-[0072] and [0075]).
Regarding claim 66, Dev as modified discloses the method wherein the therapeutic agent is a pro-apoptotic factor (cytokines as in [0075]).
Regarding claim 67, Dev as modified discloses the method wherein the pro-apoptotic factor is a cytokine, p53, a suicide gene, and/or an activator of known apoptosis genes (cytokine as in [0075]).
Regarding claim 68, Dev as modified discloses the method wherein the vector is a viral vector ([0080]).
Regarding claim 69, Dev as modified discloses the method wherein the viral vector is an adenovirus, an adeno- associated virus, a lentivirus or a herpes virus (adenovirus, [0080]).
Regarding claim 70, Dev as modified discloses the method wherein the vector is provided in a pharmaceutical composition (chemotherapeutic agent as in [0082]).
Regarding claim 71, Dev as modified discloses the method wherein the pharmaceutical composition further comprises a chemotherapeutic agent (see [0082]).
Regarding claim 72, Dev as modified discloses the method wherein the vector further comprises one or more targeting moieties (see [0075]-[0076]).
Regarding claim 73, Dev as modified discloses the method wherein the first alternating electric field has a field strength of at least 1 V/cm RMS (see [0113], nominal field strength of the electric field of Dev, which is the first alternating electric field, can be from about 10 V/cm to 20 V/cm, which corresponds to approximately 7 V/cm to 14 V/cm RMS, which is at least 1 V/cm RMS as claimed).
Regarding claim 74, Dev as modified discloses the method wherein the second alternating electric field has a field strength of at least 1 V/cm RMS (see Palti [0090], the electric field of Palti, which is the second alternating electric field, can be from about 0.1 V/cm to about 10 V/cm, this includes a strength of at least 1 V/cm with sufficient specificity, especially since Applicant has not drawn any criticality to the specific range of the desired field strength).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 33, 35, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 11,529,511 in view of Dev et al. (US 20040092860, henceforth Dev).
Regarding claim 33, claims 1 (which claim 4 depends on and thus requires) and 4 of the ‘511 patent discloses a method for reducing the viability of a cell (“reduces viability of the cancer cells.” Since the ‘511 patent is for cancer cells, cancer cells are species of cells, and since species anticipate genuses, this anticipates the claim limitation), the method comprising: applying a first alternating electric field at a first frequency to the cell for a first period of time, wherein application of the first alternating electric field at the first frequency to the cell for the first period of time increases permeability of the cell membrane of the cell (“the method comprising: applying a first alternating electric field at a first frequency to the cancer cells for a first period of time, wherein application of the first alternating electric field at the first frequency to the cancer cells for the first period of time increases permeability of cell membranes of the cancer cells”) wherein the first frequency is between 50 kHz and 350 kHz (“the first frequency is between 75 kHz and 175 kHz”, claim 4, this range is fully within the range of 50 kHz and 350 kHz and thus anticipates the claimed range); introducing a vector to the cell (“introducing a substance to the cancer cells”, see below), wherein the increased permeability of the cell membranes enables the vector to cross the cell membrane (“wherein the increased permeability of the cell membranes enables the substance to cross the cell membranes”); and applying a second alternating electric field at a second frequency to the cell for a second period of time, wherein the second frequency is different from the first frequency, and wherein the second alternating electric field at the second frequency reduces viability of the cell (“and applying a second alternating electric field at a second frequency to the cancer cells for a second period of time, wherein the second frequency is different from the first frequency, and wherein the second alternating electric field at the second frequency reduces viability of the cancer cells.”).
Claim 4 of the ‘511 patent does not disclose that the substance to be introduced into the cell was a vector. Dev teaches that a substance which can be introduced into a cell can be a vector ([0080]) and that it can be a vector for the benefit of incorporating a gene for a selectable marker into a cell so that affected cells can be identified ([0080]).
Regarding claim 35, claim 1 (which claim 4 depends on and thus requires) of the ‘511 patent as modified by Dev discloses that the cell is a cancer cell (“cancer cells”).
Regarding claim 38, claim 4 of the ‘511 patent with the modification from Dev as in claim 33 above discloses that the second frequency is between 75 kHz and 300 kHz (“the second frequency is between 100 kHz and 300 kHz”, this range is fully within the range of 75 kHz and 300 kHz and thus anticipates the claimed range).
Regarding claim 73, claim 6 of the ‘511 patent with the modification from Dev as in claim 33 above discloses that the first alternating electric field has a field strength of at least 1 V/cm RMS (“wherein the first alternating electric field has a field strength of at least 1 V/cm RMS.”).
Response to Arguments
Applicant's arguments filed 09/24/2025 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant has argued that Dev does not teach an alternating electric field as claimed. Examiner respectfully disagrees. While the alternating electric fields of Applicant’s disclosure may be different from the pulses of Dev, electric pulses work by movement of electric charges within a space at set frequencies and intervals; Merriam-Webster defines an electric field as “a region associated with a distribution of electric charge or a varying magnetic field in which forces due to that charge or field act upon other electric charges”, which encompasses electric pulses since they exist in a region where charge is distributed as a wave where the pulse then acts on other charges in the body. Additionally, Dev refers to its pulses as an electric field (see at least Dev’s Title, Abstract, [0002], [0016], [0019], [0020]). The electric pulses can be considered to be alternating where they alternate between being charged and not being charged between pulses.
Applicant additionally argues that Palti does not teach a first alternating field being applied to the cell at a first frequency for the first period of time and a second alternating field. This is not asserted in the rejection of record; Dev teaches the first alternating field as claimed, while Palti teaches the second alternating field as claimed. The combination of references as explained above thus teaches the claimed first and second alternating electric fields as claimed.
Applicant argues that Orwar also does not teach a first alternating electric field and a second alternating electric field as claimed. This is not asserted in the rejection of record. Orwar is relied upon for teaching the frequency of the first alternating electric field from Dev.
Thus, Applicants arguments are respectfully found unpersuasive and rejected as indicated above.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 SAMUEL J MARRISON whose telephone number is (703)756-1927. The examiner can normally be reached M-F 7:00a-3:30p ET.
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/SAMUEL J MARRISON/Examiner, Art Unit 3783 /EMILY L SCHMIDT/Primary Examiner, Art Unit 3783