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 .
Amendments
In the reply filed 4/29/2023, Applicant has amended Claims 1, 2, 7, 13, 15, 16.
Claims 10, 20, 22, 24, 28, and 29 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-2, 5, 7, 11, 13, 15-16, 18-19 are under consideration.
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 8/21/2025 has been acknowledged.
Group I, claims 1-2, 5, 7, 10-11, 13, 15-16, 18-19, drawn to a method for providing improved transection efficiency and/or intracellular delivery in eukaryotic cells.
Applicant’s election of the following species has been acknowledged.
Applicant elected pharmaceutical agents as the naked agent.
Claim 10 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Withdrawn Claim Objections
The objection to Claim 2 has been withdrawn due to applicant’s amendment.
Withdrawn 35 USC § 112(b)
The prior rejection of Claims 1-2, 5, 7, 11, 13, 15-16, 18-19 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 pre-AIA the applicant regards as the invention. is withdrawn in light of Applicant’s amendments of Claim 1 to describe the transduction and/or intracellular delivery step, Claim 13 to describe the electronic device, and Claim 15 to describe the distance to the transmission device.
Withdrawn 35 USC § 112(d)
The prior rejection of Claim 2 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in light of Applicant’s amendments of Claim 2 to limit the naked agent.
Withdrawn 35 USC § 102
The prior rejection of Claims 1-2, 5, 7, 11, 13, 15-16, 18-19 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Ostrow et al. (US2002/0147424, filed 12/26/2001, published 10/10/2002) is withdrawn in light of Applicant’s amendment of Claim 1 to limit the electromagnetic signal frequency to 2.2-2.6 GHz, which is a limitation Ostrow does not anticipate.
New 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 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.
Claims 1-2, 5, 7, 11, 13, 15-16, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Schoenbach et al., (US Patent 10,143,519, filed 4/29/2010, patented 12/04/2018), in view of Wu et al., (Oncology Letters, 2017, 14:7250-7256).
Schoenbach teaches methods of directing pulses of electromagnetic radiation to induce a hyperthermic response in a target cancer cell (Abstract, Background, 1st para., Detailed Description, col 4, last three para. to col 6, last para., Figs. 1-3, and 6). In regard to the frequency of the electromagnetic signal, Schoenbach teaches a pre-determined frequency of 2.45 GHz, which was shown to improve intra-cellular uptake of the reporter molecule trypan blue in cancer cells upon electromagnetic radiation exposure of a mixture of the naked agent with cancer cells (col 6, last three para., see Fig. 6).
However, although Schoenbach teaches the radiation induced hyperthermal treatment make the cells more sensitive to collateral modes of treatment, and the treatment can be in combination with other agents, e.g., pharmaceutical cancer treatments (Background, 1st para.), they do not provided a preferred embodiment of introducing a pharmaceutical cancer agent to the cancer cells in combination with the pulses of electromagnetic radiation.
With respect to claim 1, steps a)-c), Wu teaches a method for improving the intra-cellular delivery of a pharmaceutical cancer agent into eukaryotic cancer cells comprising a) providing ta naked anti-cancer agent such as docetaxel, b) introducing the anti-cancer agent to the cancer cells to form a mixture, c) allowing the mixture to undergo intra-cellular delivery to form treated cancer cells, wherein the method includes the step of directing radiofrequency hyperthermia (RFH) at the mixture of anti-cancer agent and cancer cells (Abstract, p. 7251, Materials and methods). Specifically, Wu teaches the mechanism underlying RFH-enhanced chemotherapy is increased permeability of the cancer cell’s membrane (p. 7255, Discussion, 5th para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to methods of directing pulses of electromagnetic radiation to induce a hyperthermic response in a target cancer cell combined with a pharmaceutical cancer agent as suggested by Schoenbach, and combine the steps of providing the pharmaceutical cancer agent, introducing the naked agent to cancer cells to form a mixture, which is exposed to electromagnetic radiation (i.e., RFH), and allowing uptake of the naked agent by the treated cancer cells as taught by Wu with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, as stated supra, Schoenbach teaches the radiation induced hyperthermal treatment make the cells more sensitive to collateral modes of treatment such as pharmaceutical cancer treatments, and demonstrates that directing a 2.45 GHz electromagnetic signal to a mixture of cancer cells and naked agent (albeit trypan blue) improved intracellular delivery. Furthermore, Wu teaches that combining RF hyperthermia technology with chemotherapy increased the efficacy of a variety of anti-cancer agents (Abstract, p. 7251, Introduction, last para., p. 7255, Discussion, last five para.).
In regard to claim 2, as stated supra, Schoenbach teaches a pharmaceutical cancer agent, and Wu specifically teaches docetaxel as an example of the taxen class of pharmaceutical cancer agents.
In regard to claim 5, as stated supra, Schoenbach teaches the cells are tumors or other cancers (Background, first three para., col 4, lines 45-47, col 5, 3rd para., col 6, last three para), which would have been obviously derived from the tissue of a human or animal subject.
In regard to claim 7, as stated supra, Schoenbach teaches a pharmaceutical cancer agent, and Wu specifically teaches docetaxel, and while they do not explicitly teach mixing the pharmaceutical cancer agent with a carrier, most pharmaceutical agents arrive from the manufacturer in a carrier (e.g., docetaxel from Hopira), and/or it would have been obvious to mix them with a carrier to achieved the effective dose for chemotherapy. Thus, it would have been obvious to one having ordinary skill in the art at the time the invention was made to mix the pharmaceutic agent with a carrier, since it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice. In re Leshin, 125 USPQ 416.
In regard to claim 11, Schoenbach teaches the step of directing the electromagnetic radiation takes place for a pre-determined time period (col 7, 2nd para.).
In regard to claim 13, Schoenbach teaches the pulsed electromagnetic radiation is generated by an electronic device comprising a single transmission means (see “antenna” in Figs. 1-3).
In regard to claim 15, as stated supra, Schoenbach teaches the pulsed electromagnetic radiation is generated by an electronic device comprising a single transmission means (see Figs. 1-3). In regard to the transmission means being about 25 cm (i.e., 10 inches) from the target cancer cell, Schoenbach explains the tumor tissue can be in or on the patient and is positioned at an appropriate location with respect to the system (col 4, lines 45-47, col 5, 3rd para.), wherein the system is placed on the skin to treat cancers such as melanoma, or is inserted directly into a tumor (col 1, last para.). Thus, Shoenbach reasonably suggests the transmitter for the electromagnetic radiation is about 25 cm or less from the cancer cells, and it would have been obvious to position the cells at a distance equal to or less than this distance 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.
In regard to claim 16, as stated supra, Schoenbach teaches the pulsed electromagnetic radiation is approximately 2.45 GHz.
In regard to claims 18 and 19, Schoenbach teaches the electronic device further comprises a “reflector” for controlling signal strength of the electromagnetic radiation by directing it at focal point comprising the target cells (col 4, 3rd and 4th para., see Figs. 1-3).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 4/29/2026 are acknowledged.
Applicant argues that the cited prior art of Ostrow does not teach an electromagnetic pulse at a frequency of 2.2-2.6 GHz.
Applicant's arguments have been fully considered and they are found persuasive.
However, as necessitated by Applicant’s amendment, the Examiner has put forth the prior art of Schoenbach in view of Wu, who make obvious a method of improving intra-cellular delivery of a naked pharmaceutical agent to cancer cells by directing an electromagnetic signal at a frequency of 2.45 GHz.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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