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 .
Claim Status
The amendment of 04/06/2026 has been entered. Claims 1-29 are pending in this US patent application. Claims 15-20 and 25-27 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/20/2025.
Claims 1-14, 21-24, and 28-29 are currently under examination and were examined on their merits.
Withdrawn Rejections
The rejection of the claims under 35 U.S.C. 112(b) as being indefinite as set forth in the previous Office action is withdrawn in light of the amendment of 04/06/2026, which removed the indefinite language from the claims.
All rejections of the claims under 35 U.S.C. 102(a)(1) and 103 as set forth in the previous Office action are withdrawn in light of the amendment of 04/06/2026, which added a limitation to claim 1. Applicant’s argument in the remarks of 04/06/2026 that the previously cited art does not teach the newly-added limitation to claim 1 has been found persuasive.
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 1-7 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qiao et al., IEEE Transactions on Biomedical Engineering 59(8): 2321-2329 (2012; cited on the IDS filed 12/08/2022).
Qiao teaches the measurement of the impedance of cell suspensions (see entire document, including page 2322, left column, paragraph 2). The three cell lines investigated were invasive human breast cancer cell line MDA-MB-231, early-stage human breast cancer cell line MCF-7, and human breast tissue cell line MCF-10A (page 2322, left column, paragraph 3; reads on claims 3-5 and 21). The impedance measurements for each cell line were conducted five times (page 2323, left column, paragraph 1; reads on claim 2). The averaged impedance measured for each cell line was plotted (page 2324, right column, Figure 6), as were the conductivities for each cell line (page 2325, left column, Figure 7), allowing for the determination of key electrical parameters that can identify the three types of breast cell lines (page 2325, right column, paragraph 2; page 2326, Tables III and IV; reads on claims 1-2; the Examiner notes that the extensive graphing and calculation of the results, some of which apply to malignant neoplastic cells, can be interpreted as “comparing” the electrical activities and “subsequently assigning a score for the metastatic and/or invasive potential of the malignant neoplasm by ranking the recorded electrical activity of the one or more reference sample” as recited in claim 1, given that the types of comparing and ranking or of the assigned “score” are not limited in the instant claims; the Examiner further notes that the measurement of impedance as shown in Figure 6 involves the measurement of resistance, as plotted on the X axis of Figure 6, and is equivalent to voltage over current, and so the plot shown in Figure 6 incorporates the limitations of claims 6-7).
Therefore, claims 1-7 and 21 are anticipated by Qiao and are rejected under 35 U.S.C. 102(a)(1).
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 1-7, 21, and 28 are newly rejected as necessitated by amendment under 35 U.S.C. 103 as being unpatentable over Yang et al., Frontiers in Physiology 4: 185 (July 2013).
Yang teaches that the membrane potential of a cell, Vm, has been implicated in cancer development (see entire document, including page 2, left column, paragraph 1). Cell migration, an important step in metastasis, is tightly controlled by the movement of ions and water, and Vm is a factor that can affect cell migration (page 5, left column, paragraph 3). Given that the fluctuation of Vm can functionally regulate tumorigenesis, differentiation, and promote cancer progression, it may serve as a potential marker for tumor detection and treatment, with prognostic value (page 6, right column, paragraph 1). Figure 1 shows a plot of a plurality of measured Vm values of multiple types of human proliferating and non-proliferating cells, both tumor cells and non-tumor cells, including MDA-MB-231 cells and MCF-7 cells (page 2, Figure 1; cf. claims 1-7, 21, and 28; the extensive plotting of the results, some of which apply to malignant neoplastic cells, can be interpreted as “comparing” the membrane potentials of the cells, some of which derive from malignant neoplasms, and “subsequently assigning a score for the metastatic and/or invasive potential of the malignant neoplasm by ranking the recorded electrical activity of the one or more reference sample” as recited in claim 1, given that the types of comparing and ranking or of the assigned “score” are not limited in the instant claims; the Examiner further notes that the membrane potential plot as shown in Figure 1 involves the measurement of membrane potential, and so the plot shown in Figure 1 incorporates the limitations of claims 6-7; the Examiner further notes that the instant specification describes MDA-MB-231 cells as strongly metastatic and MCF-7 cells as weakly/non-metastatic [see specification as filed, page 3; cf. claim 28]).
However, Yang does not explicitly teach measuring the fluctuation of Vm as a marker for tumor progression.
While Yang does not explicitly teach measuring the fluctuation of Vm as a marker for tumor progression, it would have been obvious to one of ordinary skill in the art to do so because Yang teaches that, given that the fluctuation of Vm can functionally regulate tumorigenesis, differentiation, and promote cancer progression, it may serve as a potential marker for tumor detection and treatment, with prognostic value. Yang further teaches that cell migration, an important step in metastasis, is tightly controlled by the movement of ions and water, and Vm is a factor that can affect cell migration. One of ordinary skill in the art would have a reasonable expectation that measuring the fluctuations of Vm in a tumor cell sample and comparing the measured membrane potential to the plot of Figure 1 of Yang, which shows a clear progression in the polarization of Vm in rapidly proliferating cancer cells, would successfully result in obtaining useful information regarding the potential progression of the tumor from which the cells were isolated.
Therefore, claims 1-7, 21, and 28 are rendered obvious by Yang and are rejected under 35 U.S.C. 103.
Claims 1-12, 21-24, and 28 are newly rejected as necessitated by amendment under 35 U.S.C. 103 as being unpatentable over Yang et al., Frontiers in Physiology 4: 185 (July 2013), in view of Rocha et al., Sci. Rep. 6: 34843 (2016; cited on the IDS filed 12/08/2022).
As discussed above, claims 1-7, 21, and 28 are rendered obvious by Yang. However, this reference does not teach the particular measurement apparatus recited in instant claims 8-12 and 22-24.
Rocha teaches measuring the extracellular activity of electrogenic malignant cells using a microelectrode array (see entire document, including page 1, paragraph 2). Reducing the impedance of the electrode optimizes the signal-to-noise ratio, allowing for the measurement of current and voltage in cells that do not exhibit action potentials (page 2, paragraphs 3-4). The electrodes, which were coated in gold, had areas of 2 mm2, and the cells were allowed to adhere to the electrodes for two hours prior to measurement (page 2, paragraphs 5-9; cf. claims 8-12 and 23-24). Signals at low frequency, below 10 Hz, were measured (page 2, paragraph 8; cf. claim 22).
While Yang does not teach the use of the microelectrode array of Rocha in measuring the electrical activity of various cancer cell lines and non-cancerous cell lines, it would have been obvious to one of ordinary skill in the art to do so because Rocha teaches that their microelectrode array can measure electrical activity in malignant cells and that it optimizes the signal-to-noise ratio and allows for the detection of signals at low frequencies. One of ordinary skill in the art would have a reasonable expectation that using the measurement device of Rocha in the method of Yang would successfully result in the measurement of the electrical activities of the cells of Yang.
Therefore, claims 1-12, 21-24, and 28 are rendered obvious by Yang in view of Rocha and are rejected under 35 U.S.C. 103.
Claims 1-7, 13-14, 21, and 28-29 are newly rejected as necessitated by amendment under 35 U.S.C. 103 as being unpatentable over Yang et al., Frontiers in Physiology 4: 185 (July 2013), in view of Roger et al., Biochim. Biophys. Acta 1616: 107-111 (2003; cited on the IDS filed 12/08/2022).
As discussed above, claims 1-7, 21, and 28 are rendered obvious by Yang. In addition, Yang discusses the presence of functional voltage-gated sodium channels in a number of cancer types and that inhibition of these channels with pharmacological agents inhibits migration and invasion (page 5, right column, paragraph 2). However, Yang does not teach performing the measurements in the presence of a voltage gated sodium channel-inhibiting agent as recited in instant claims 13-14 and 29.
Roger examines the effect of sodium currents on the invasion capacity of breast cancer cell lines MDA-MB-231 and MCF-7 (see entire document, including page 107, left column, paragraph 2). The invasive cell line MDA-MB-231 exhibits a fast inward sodium current that is blocked by tetrodotoxin (page 109, Figures 1 and 2; cf. claims 13-14 and 29; the Examiner notes that all measurements taken in the presence of TTX must intrinsically have occurred after the addition of TTX as recited in instant claim 14), but this current was not observed in MCF-7 cells (page 109, left column, paragraph 1).
While Yang does not teach performing the measurements of the membrane potential of MCF-7 and MDA-MB-231 cells in the presence of a voltage gated sodium channel-inhibiting agent, it would have been obvious to one of ordinary skill in the art to do so because Yang teaches that pharmacological agents that inhibit VGSCs have been shown to affect cancer cell migration and invasion, and Roger teaches a particular electrical current from a sodium channel that is specific to MDA-MB-231, a cancer cell line whose membrane potential is included in Yang’s Figure 1, and blocked by tetrodotoxin, which is a voltage gated sodium channel-inhibiting agent. One of ordinary skill in the art would have a reasonable expectation that performing the measurements of Yang in the presence of the TTX of Roger would successfully provide more information regarding the electrical activity of the cell lines of Yang to allow for better differentiation between the cell lines and information regarding the role of particular ion channels in metastasis.
Therefore, claims 1-7, 13-14, 21, and 28-29 are rendered obvious by Yang in view of Roger and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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 Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 06/30/2026
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