DETAILED ACTION
This Office Action is in response to Applicant’s Amendment filed on 06/02/2026.
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 Rejections - 35 USC § 112(b)
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.
Claims 1-8,11-18,22-27 and 29-35 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 in lines 11-12 recites “an oxidant-antioxidant balance” which renders this claim unclear. More specifically, in light of instant application specification as-filed, it is unclear as to what is meant by oxidant-antioxidant balance and how it is even detected or determined objectively or what biomarkers are actually being used to determine the oxidant-antioxidant balance.
Claim 15 recites “a redox potential” which renders this claim unclear. More specifically, it is unclear as to whether claim 15 “a redox potential” is the same as, different than or in addition to claim 1 line 12 “a redox potential” .
Dependent claims 2-8,11-18, 22-27 and 29-35 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 112(b) because the additional recited limitations fail to cure the 35 U.S.C. 112 (b) issue in their respective base claims. Consequently, dependent claims 2-8,11-18,22-27 and 29-35 are also rejected under 35 U.S.C. 112(b) based in their direct/indirect dependency on their respective base claims.
Claim Interpretation
Claims terms where relevant are being interpreted in light of definitions enumerated in instant application specification as-filed [0009], [0104], [0208], [0049], [0053-0056], [0136].
Please note that USPTO personnel are to give claims their broadest reasonable interpretation in light of the supporting disclosure. In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997). Limitations appearing in the specification but not recited in the claim should not be read into the claim. E-Pass Techs., Inc. v. 3Com Corp., 343 F.3d 1364, 1369, 67 USPQ2d 1947, 1950 (Fed. Cir. 2003) (claims must be interpreted "in view of the specification" without importing limitations from the specification into the claims unnecessarily). In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-551 (CCPA 1969). See also In re Zletz, 893 F.2d 319, 321-22, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) ("During patent examination the pending claims must be interpreted as broadly as their terms reasonably allow.... The reason is simply that during patent prosecution when claims can be amended, ambiguities should be recognized, scope and breadth of language explored, and clarification imposed.... An essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.").
Claim Rejections - 35 USC § 103
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 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.
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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6, 8, 11-18, 22-27 and 29-31, 33, 35 are rejected under 35 U.S.C. 103 as being unpatentable over Hershey et al. (Pub. No.: US 20170143972 A1, hereinafter referred to as "Hershey") in view of Maurer (Pat. No.: US 4556051 A, hereinafter referred to as “Maurer”).
As per independent Claim 1, Hershey discloses a method (Hershey in at least abstract, fig. 1-5, fig. 9, [0002], [0005-0030], [0045-0051], [0056-0058], [0061-0063], [0067], [0069-0070], [0083-0089] for example discloses relevant subject-matter. More specifically, Hershey in fig. 9, [0002], [0020], [0045], [0083] for example disclose a method. See at least Hershey [0002] “methods for delivering neuromodulation to treat neuroinflammation and controlling the delivery of the neuromodulation using sensed biomarkers”), comprising:
delivering a therapy by delivering energy to tissue (Here, the term “tissue” is being interpreted in light of instant application specification as-filed para. [0009] [0104], [0208]. Hershey in at least [0018], [0047], [0058] for example discloses delivering a therapy by delivering energy to tissue. See at least Hershey [0058] “neuromodulation energy can be delivered in the form of electrical stimulation, magnetic stimulation… or a combination of two or more of such stimulations. Stimulation delivery device 314 can include one or more of lead and/or electrodes such as lead system 214 to deliver electrical stimuli such as electrical pulses, one or more electromagnets to deliver magnetic stimuli”), wherein delivering energy to the tissue includes:
providing a magnetic field in a first direction to the tissue using a magnetic field system including a magnetic field source to produce the magnetic field, wherein the magnetic field produced by the magnetic field source includes a magnetic field produced by at least one of a permanent magnet, a temporary magnet or electric current flow through a conductor (Hershey in at least [0018], [0047], [0058] for example discloses providing a magnetic field in a first direction to the tissue using a magnetic field system including a magnetic field source to produce the magnetic field, wherein the magnetic field produced by the magnetic field source includes a magnetic field produced by at least one of a permanent magnet, a temporary magnet or electric current flow through a conductor. See at least Hershey [0058] “neuromodulation energy can be delivered in the form of electrical stimulation, magnetic stimulation… or a combination of two or more of such stimulations. Stimulation delivery device 314 can include one or more of lead and/or electrodes such as lead system 214 to deliver electrical stimuli such as electrical pulses, one or more electromagnets to deliver magnetic stimuli”);
providing an electric field in a second direction to the tissue using an electric field system including an electric field source to produce the electric field (Hershey in at least [0018], [0047], [0058] for example discloses providing an electric field in a second direction to the tissue using an electric field system including an electric field source to produce the electric field. See at least Hershey [0058] “neuromodulation energy can be delivered in the form of electrical stimulation, magnetic stimulation… or a combination of two or more of such stimulations. Stimulation delivery device 314 can include one or more of lead and/or electrodes such as lead system 214 to deliver electrical stimuli such as electrical pulses, one or more electromagnets to deliver magnetic stimuli” ); and
detecting one or more biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state and performing a comparison of the one or more detected biomarkers to a reference value to perform at least one of: monitoring efficacy of the therapy based on the comparison; or calibrating or adjusting at least one parameter of the therapy based on the comparison ( Here, the “or” encompassing limitations is being broadly yet reasonably interpreted as requiring one of the elements in the enumerated list. Hershey in at least fig. 9, [0005], [0020], [0045], [0051], [0061-0062], [0086-0088] for example discloses detecting one or more biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state and performing a comparison of the one or more detected biomarkers to a reference value to perform at least one of: monitoring efficacy of the therapy based on the comparison; or calibrating or adjusting at least one parameter of the therapy based on the comparison as seen in fig. 9. See at least Hershey [0045] “system delivers neuromodulation for modulating neural activities at the tissue site of the patient. The system can deliver the neuromodulation and sense the biomarker in the surrounding environment for indicating the patient's response to the delivery of the neuromodulation. The system can store patient data, such as a biomarker parameter associated with the tissue site, and can compare the biomarker parameter to a reference value. Based on the comparison, the system can adjust a parameter set controlling the delivery of the neuromodulation. As used in this document, a “biomarker parameter” can include a measure of the biomarker and/or a measure of a derivative of the biomarker. In various examples, one or more biomarker parameters each being a measure of the biomarker or a measure of a derivative of the biomarker can be sensed.”; [0061] “the biomarker can be a metabolic biomarker…biomarker parameter can be a measure of metabolism of the patient at a particular tissue site through quantification of ATP or a derivative (e.g., ADP, oxygen consumption, lactate, or pyruvate) … cellular metabolic demand can increase relative to metabolic demand of a non-affected sites. The neuromodulation device can use the measure of the metabolism as the biomarker parameter… using the biomarker parameter to optimize neuromodulation targeting” [0062] “using the biomarker parameter to inform a treatment for the patient, such as an intervention that alleviates oxidative stress conditions”; [0086-0088] “one or more biomarker parameters associated with the tissue site are sensed using one or more biomarker sensors … biomarker parameters each indicate a neural or other physiological response to the delivery of the neuromodulation. The one or more biomarkers are each a measure of the biomarker or a measure of a derivative of the biomarker… one or more biomarker parameters are each compared to a reference value… reference value or value range can be a stored value in the memory 210…reference value or value range can be a previously sensed value of the corresponding biomarker parameter… neuromodulation parameter set are adjusted using an outcome of the comparison. In one example, the reference value or value range represents a threshold indicative of a need for treating …and the outcome of the comparison indicates such a need”).
Hershey does not explicitly disclose the electric field second direction is non-parallel to the magnetic field first direction.
However, in an analogous therapy delivering via combined electrical and magnetic energy to treat tissue field of endeavor, Maurer discloses a method (Maurer in abstract, fig. 1-10, col. 1 lines 61-col.10 line 26 for example discloses relevant subject-matter. More specifically, Maurer in abstract, fig. 1, fig. 13, col. 1 line 61- col. 2 line 10, col. 9 lines 60-68 for example discloses a method. See at least Maurer col. 1 line 61- col. 2 line 10 “method is a non-intrusive treatment utilizing electrode means attached to the skin of the patient adjacent the fracture of a bone and coil means located adjacent the skin and the fracture. The electrode means and coil means are used to establish interacting electric and magnetic fields to enhance tissue healing. The coil means is angularly spaced from the electrode means. The electric generator means is electrically connected to the electrode means and the coil means to provide current pulses to the electrode means and coil means. The energized coil means establishes a pulsed magnetic field. The current pulses and the pulsed magnetic field are in a phase relationship with each other so as to produce a unidirectional net current along the length of the bone and through the region of the injured tissue.”), comprising:
delivering a therapy by delivering energy to tissue (Maurer in abstract, fig. 1, fig. 13, col. 1 line 61- col. 2 line 10, col. 9 lines 60-68 for example discloses delivering a therapy by delivering energy to tissue. See at least Maurer col. 1 line 61- col. 2 line 10 “method is a non-intrusive treatment utilizing electrode means attached to the skin of the patient adjacent the fracture of a bone and coil means located adjacent the skin and the fracture. The electrode means and coil means are used to establish interacting electric and magnetic fields to enhance tissue healing”), wherein delivering energy to the tissue includes:
providing a magnetic field in a first direction to the tissue using a magnetic field system including a magnetic field source to produce the magnetic field, wherein the magnetic field produced by the magnetic field source includes a magnetic field produced by at least one of a permanent magnet, a temporary magnet or electric current flow through a conductor (Maurer in at least fig. 1, fig. 13, fig. 10, abstract, col. 1 line 61- col. 2 line 10, col. 9 lines 60-68 for example discloses providing a magnetic field in a first direction to the tissue using a magnetic field system including a magnetic field source/coil means to produce the magnetic field, wherein the magnetic field produced by the magnetic field source includes a magnetic field produced by at least one of a permanent magnet, a temporary magnet or electric current flow through a conductor. See at least Maurer col. 1 line 61- col. 2 line 10 “method is a non-intrusive treatment utilizing … coil means located adjacent the skin and the fracture”);
providing an electric field in a second direction to the tissue using an electric field system including an electric field source to produce the electric field, wherein the second direction is non-parallel to the first direction (Maurer in at least abstract, fig. 1, fig. 13, fig. 10, col. 1 line 61- col. 2 line 16, col. 9 lines 60-68 for example discloses providing an electric field in a second direction to the tissue using an electric field system including an electric field source/electrodes to produce the electric field, wherein the second direction is non-parallel to the first direction. See at least Maurer abstract “apparatus and method for promoting healing of injured tissue, such as fractured bone, with interacting electric current and a magnetic flux field. Electrodes are adhesively attached to the skin adjacent the injured tissue. One or more coil assemblies normally spaced from the electrodes are located adjacent the tissue in alignment with the fractured bone. A current generator electrically connected to the electrodes operates to provide electric current pulses to the electrodes. A field generator electrically connected to the coil assemblies is operable to energize the coil assemblies to produce magnetic field pulses. The pulse generator and field generator are electrically coupled to maintain the electrode current pulses and magnetic field pulses in fixed phase relationship to produce a net current in the region of the fractured bone and generally perpendicular to the plane of the fracture.”; col. 1 line 61- col. 2 line 16 “method is a non-intrusive treatment utilizing electrode means attached to the skin of the patient adjacent the fracture of a bone … The electrode means and coil means are used to establish interacting electric and magnetic fields to enhance tissue healing. The coil means is angularly spaced from the electrode means. The electric generator means is electrically connected to the electrode means and the coil means to provide current pulses to the electrode means and coil means. The energized coil means establishes a pulsed magnetic field. The current pulses and the pulsed magnetic field are in a phase relationship with each other so as to produce a unidirectional net current along the length of the bone and through the region of the injured tissue. The unidirectional current flows generally perpendicular to the surface of the fracture and is of a magnitude and duration appropriate to the specific ion or cellular charge and mobility. ”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the directions of electric field and magnetic fields used in the method as taught by Hershey, such that the electric field direction is non-parallel to the magnetic field direction, as taught by Maurer. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of establishing interacting electric and magnetic fields in a manner as to enhance tissue healing (Maurer, abstract, col. 2 lines 1-15).
As per dependent Claim 2, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one of glutathione (GSH) or glutathione disulfide (GSSG) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “antioxidants such as the glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CysS)…which participate in neutralizing oxidants by supporting or directly donating reducing equivalents to reduce and neutralize oxidants (see Jones, D. P. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295, C849-C868 (2008); Jones, D. P. & Sies, H. The Redox Code. Antioxidants & redox signaling 23, 734-746 (2015); Harris, I. S., et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer cell 27, 211-222 (2015);”).
As per dependent Claim 3, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one cysteine (Cys) or cystine (CysS) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “antioxidants such as the glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CysS)…which participate in neutralizing oxidants by supporting or directly donating reducing equivalents to reduce and neutralize oxidants (see Jones, D. P. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295, C849-C868 (2008); Jones, D. P. & Sies, H. The Redox Code. Antioxidants & redox signaling 23, 734-746 (2015); Harris, I. S., et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer cell 27, 211-222 (2015);”).
As per dependent Claim 4, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include protein S-glutathionylation (PrSSG) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0238] “see Dalie-Donne, I., Rossi, R., Colombo, G., Giustarini, D. and Milzani, A., Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends in Biochemical Sciences 34, 86-96 (2008)”).
As per dependent Claim 6, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one of a redox potential of glutathione (GSH) or a redox potential of glutathione disulfide (GSSG) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “Schafer, F. Q. & Buettner, G. R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine 30, 1191-1212 (2001).”).
As per dependent Claim 8, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include F2-isoprostane (Applicant in at least instant application specification as-filed [0233] discloses and admits use of F2-isoprostane as an oxidative stress biomarker as well-known prior art. See instant specification as-filed [0233] “F2-isoprostanes … a product of free radical mediated oxidation of arachidonic acid (see Sampson, M. J., Gopaul, N., Davies, I. R., Hughes, D. A. & Carrier, M. J. Plasma. F2 Isoprostanes. Diabetes Care 25, 537 (2002); Milne, G. L., Sanchez, S. C., Musick, E. S. & Morrow, J. D. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nature protocols 2, 221-226 (2007); Il, et al. Urinary F2-Isoprostanes as a Biomarker of Reduced Risk of Type 2 Diabetes. Diabetes Care 35, 173 (2012)),”).
As per dependent Claim 11, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include a product of free radical mediated oxidation of arachidonic acid (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See Schmidlin instant specification as-filed [0233] “F2-isoprostanes … a product of free radical mediated oxidation of arachidonic acid (see Sampson, M. J., Gopaul, N., Davies, I. R., Hughes, D. A. & Carrier, M. J. Plasma. F2 Isoprostanes. Diabetes Care 25, 537 (2002); Milne, G. L., Sanchez, S. C., Musick, E. S. & Morrow, J. D. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nature protocols 2, 221-226 (2007); Il, et al. Urinary F2-Isoprostanes as a Biomarker of Reduced Risk of Type 2 Diabetes. Diabetes Care 35, 173 (2012)),”).
As per dependent Claim 12, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one antioxidant from thioredoxin (Trx), peroxiredoxin (Prdx), glutathione-S-transferase (GST), or glutathione peroxidase 3 (GPX3) (Applicant in at least instant application specification as-filed [0148], [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0148] “There is a growing body of evidence showing that the activation of hormesis can be therapeutic in a wide range of diseases or adverse conditions, including diabetes mellitus, obesity, cancer, neurodegenerative disease, inflammation and aging.sup.2-7. (Radak, Z., Chung, H. Y. & Coto, S. Exercise and hormesis: oxidative stress-related adaptation for successful aging. Biogerontology 6, 71-75 (2005); De Haes, W., et al. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proceedings of the National Academy of Sciences 111, E2501 (2014)”; [0233] “antioxidants such as the glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CysS), thioredoxin (Trx), peroxiredoxin (Prdx), glutathione-S-transferase (GST), glutathione peroxidase 3 (GPX3) which participate in neutralizing oxidants by supporting or directly donating reducing equivalents to reduce and neutralize oxidants (see Jones, D. P. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295, C849-C868 (2008); Jones, D. P. & Sies, H. The Redox Code. Antioxidants & redox signaling 23, 734-746 (2015); Harris, I. S., et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer cell 27, 211-222 (2015)”).
As per dependent Claim 13, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include an expression of genes that induce an antioxidant response, including NRF2 (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “NRF2, which translocates to the nucleus upon activation by oxidative stimuli where they induce expression of genes that mediate an antioxidant response (see Kansanen, E., Kuosmanen, S. M., Leinonen, H. & Levonen, A.-L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1, 45-49 (2013); Schmidlin, C. J., Dodson, M. B., Madhavan, L. & Zhang, D. D. Redox regulation by NRF2 in aging and disease. Free Radical Biology and Medicine 134, 702-707 (2019), expression of genes that are activated by NRF2 to mediate the antioxidant response: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM) (see Kansanen et al.)”).
As per dependent Claim 14, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include an expression of genes that are activated by NRF2 to mediate an antioxidant response, including at least one of: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), the redox couples, NADP+, NADPH, NAD+, NADH, redox post-translational modifications, long-chain fatty acids (LCFAs), poly unsaturated fatty acids (PUFAs), medium chain fatty acids (MCFAs), fatty acids dicarboxylate, amino fatty acids, acyl glycine and carnitines or beta-hydroxybutyrate (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “NRF2, which translocates to the nucleus upon activation by oxidative stimuli where they induce expression of genes that mediate an antioxidant response (see Kansanen, E., Kuosmanen, S. M., Leinonen, H. & Levonen, A.-L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1, 45-49 (2013); Schmidlin, C. J., Dodson, M. B., Madhavan, L. & Zhang, D. D. Redox regulation by NRF2 in aging and disease. Free Radical Biology and Medicine 134, 702-707 (2019), expression of genes that are activated by NRF2 to mediate the antioxidant response: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM) (see Kansanen et al.)”).
As per dependent Claim 15, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include a redox potential (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “Schafer, F. Q. & Buettner, G. R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine 30, 1191-1212 (2001).”).
As per dependent Claim 16, the combination of Hershey and Maurer as a whole further discloses method wherein detecting the one or more biomarkers includes detecting at least one biomarker in whole blood, plasma, serum, red blood cells, tears, urine, stool, cerebrospinal fluid, lymphatic fluid, breath or sweat (Hershey in at least [0044] for example discloses wherein detecting the one or more biomarkers includes detecting at least one biomarker in whole blood, plasma, serum, red blood cells, tears, urine, stool, cerebrospinal fluid, lymphatic fluid, breath or sweat. See at least Hershey [0044] “Cerebrospinal fluid (CSF) levels of TSPO can be detected using an implantable sensor system to determine a surrogate measure of pain intensity… TSPO levels at a tissue site can be detected using an implantable sensor system, and the detected level of TSPO at the tissue site can be used a surrogate for pain intensity of the patient.”).
As per dependent Claim 17, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one of glutathionylation or cysteinylation (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0238] “see Dalie-Donne, I., Rossi, R., Colombo, G., Giustarini, D. and Milzani, A., Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends in Biochemical Sciences 34, 86-96 (2008)”).
As per dependent Claim 18, the combination of Hershey and Maurer as a whole further discloses method, wherein the one or more biomarkers include NRF2 (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “NRF2, which translocates to the nucleus upon activation by oxidative stimuli where they induce expression of genes that mediate an antioxidant response (see Kansanen, E., Kuosmanen, S. M., Leinonen, H. & Levonen, A.-L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1, 45-49 (2013); Schmidlin, C. J., Dodson, M. B., Madhavan, L. & Zhang, D. D. Redox regulation by NRF2 in aging and disease. Free Radical Biology and Medicine 134, 702-707 (2019), expression of genes that are activated by NRF2 to mediate the antioxidant response: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM) (see Kansanen et al.)”).
As per dependent Claim 22, the combination of Hershey and Maurer as a whole further discloses method further comprising changing a dose for at least one of the electric field or the magnetic field based on the detected one or more biomarkers (Hershey in at least [0020], [0045-0046], [0087-0088] for example discloses changing a dose for at least one of the electric field or the magnetic field based on the detected one or more biomarkers. See at least Hershey
As per dependent Claim 23, the combination of Hershey and Maurer as a whole further discloses method wherein changing the dose includes changing a duty cycle or a duration of the therapy during a period of time (Hershey in at least [0045-0046], [0049] for example discloses wherein changing the dose includes changing a duty cycle or a duration of the therapy during a period of time. See at least Hershey [0049] “neuromodulation parameters (also referred to as “the parameters”) can define a neuromodulation pattern (or waveform of stimuli), such as a stochastic pattern, a burst pattern, a frequency modulated pattern, a pulse width modulated pattern, an amplitude modulated pattern, or a biomimetic pattern. In an example, a biomimetic pattern includes a combination of two or more patterns, such as a stochastic pattern and a rate modulated pattern. In one example, the neuromodulation pattern can be a dynamic pattern that can change over time, such as in response to changing results of measurement of a biomarker of the tissue site.”).
As per dependent Claim 24, the combination of Hershey and Maurer as a whole further discloses method wherein changing the dose includes changing a strength of at least one of the magnetic field or the electric field (Hershey in at least [0045-0046], [0049] for example discloses wherein changing the dose includes changing a strength of at least one of the magnetic field or the electric field. See at least Hershey [0049] “neuromodulation parameters (also referred to as “the parameters”) can define a neuromodulation pattern (or waveform of stimuli), such as a stochastic pattern, a burst pattern, a frequency modulated pattern, a pulse width modulated pattern, an amplitude modulated pattern, or a biomimetic pattern. In an example, a biomimetic pattern includes a combination of two or more patterns, such as a stochastic pattern and a rate modulated pattern. In one example, the neuromodulation pattern can be a dynamic pattern that can change over time, such as in response to changing results of measurement of a biomarker of the tissue site.”).
As per dependent Claim 25, the combination of Hershey and Maurer as a whole further discloses method wherein changing the dose includes changing timing for delivering at least one of the magnetic field or the electric field (Hershey in at least [0045-0046], [0049] for example discloses changing the dose includes changing timing for delivering at least one of the magnetic field or the electric field. See at least Hershey [0049] “neuromodulation parameters (also referred to as “the parameters”) can define a neuromodulation pattern (or waveform of stimuli), such as a stochastic pattern, a burst pattern, a frequency modulated pattern, a pulse width modulated pattern, an amplitude modulated pattern, or a biomimetic pattern. In an example, a biomimetic pattern includes a combination of two or more patterns, such as a stochastic pattern and a rate modulated pattern. In one example, the neuromodulation pattern can be a dynamic pattern that can change over time, such as in response to changing results of measurement of a biomarker of the tissue site.”).
As per dependent Claim 26, the combination of Hershey and Maurer as a whole further discloses method wherein the electric field is a static electric field, and the magnetic field is a static magnetic field (Maurer in at least col. 10 lines 5-15 for example discloses the electric field is a static electric field, and the magnetic field is a static magnetic field. See at least Maurer col.10 lines 5-13 “the patient requires uninterrupted currents and magnetic flux fields. The apparatus can be provided with a mode whereby a static magnetic flux field is created by constantly energizing the coil assemblies… a static magnetic flux field can be created with the use of one or more permanent magnets located adjacent the patient. Direct current is provided to the electrodes simultaneously with the energization of the coil assemblies.”).
As per dependent Claim 27, the combination of Hershey and Maurer as a whole further discloses method wherein the delivering the therapy includes delivering the energy to one or more organs or tissues of a mammal to prevent, inhibit or treat one or more symptoms of a disease associated with aberrant reactive oxygen species levels in the mammal (Hershey in at least fig. 9, [0005], [0020], [0018], [0045-0047], [0058], [0061-0062], [0086-0088] for example discloses the delivering the therapy includes delivering the energy to one or more organs or tissues of a mammal to prevent, inhibit or treat one or more symptoms of a disease associated with aberrant reactive oxygen species levels in the mammal. See at least [0020] “a method for delivering neuromodulation to a patient … delivering the neuromodulation; controlling the delivery of the neuromodulation using a neuromodulation parameter set selected to modulate neural activity at a tissue site; sensing a biomarker parameter, and adjusting the neuromodulation parameter set using the biomarker parameter. The biomarker parameter may be a measure of a biomarker or a measure of a derivative of the biomarker. The biomarker may be indicative of neuroinflammation at the tissue site.”; [0061] “biomarker can be a metabolic biomarker… the biomarker parameter can be a measure of metabolism of the patient at a particular tissue site … using the biomarker parameter to optimize neuromodulation targeting.” [0062] “using the biomarker parameter to inform a treatment for the patient, such as an intervention that alleviates oxidative stress conditions … the treatment can be delivering neuromodulation to the inflamed tissue site”), and wherein
the monitoring the efficacy of the therapy includes monitoring efficacy of the magnetic and electric fields; or the calibrating or adjusting the therapy includes calibrating or adjusting at least one of the magnetic field or the electric field (Hershey in at least fig. 9, [0005], [0020], [0045-0046], [0086-0088] for example discloses detecting one or more biomarkers within at least one of a redox system and a metabolic system to perform at least one of: monitoring efficacy of the therapy; or calibrating or adjusting the therapy. See at least [0020] “a method for delivering neuromodulation to a patient … delivering the neuromodulation; controlling the delivery of the neuromodulation using a neuromodulation parameter set selected to modulate neural activity at a tissue site; sensing a biomarker parameter, and adjusting the neuromodulation parameter set using the biomarker parameter. The biomarker parameter may be a measure of a biomarker or a measure of a derivative of the biomarker. The biomarker may be indicative of neuroinflammation at the tissue site.”; [0046] “systems, devices, and methods for optimizing treatments for a patient. Metrics that quantify neuroinflammation can be used to determine optimal stimulation targets and parameters for the neuromodulation (e.g., temporal and spatial parameters in a parameter set), and to ensure therapy longevity. Examples of a biomarker can include a neuroinflammatory measure … cytokine concentration in the cerebrospinal fluid (CSF)…One application of the present subject matter can include determining patient-specific treatment approaches to meet a desired therapeutic goal.”).
As per dependent Claim 29, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one of glutathione (GSH) or glutathione disulfide (GSSG) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “antioxidants such as the glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CysS)…which participate in neutralizing oxidants by supporting or directly donating reducing equivalents to reduce and neutralize oxidants (see Jones, D. P. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295, C849-C868 (2008); Jones, D. P. & Sies, H. The Redox Code. Antioxidants & redox signaling 23, 734-746 (2015); Harris, I. S., et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer cell 27, 211-222 (2015);”).
As per dependent Claim 30, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one of cysteine (Cys) or cystine (CysS) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “antioxidants such as the glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CysS)…which participate in neutralizing oxidants by supporting or directly donating reducing equivalents to reduce and neutralize oxidants (see Jones, D. P. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295, C849-C868 (2008); Jones, D. P. & Sies, H. The Redox Code. Antioxidants & redox signaling 23, 734-746 (2015); Harris, I. S., et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer cell 27, 211-222 (2015);”).
As per dependent Claim 31, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include protein S-glutathionylation (PrSSG) (Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0238] “see Dalie-Donne, I., Rossi, R., Colombo, G., Giustarini, D. and Milzani, A., Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends in Biochemical Sciences 34, 86-96 (2008)”).
As per dependent Claim 33, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include at least one of a redox potential of glutathione (GSH) or a redox potential of glutathione disulfide (GSSG)( Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “Schafer, F. Q. & Buettner, G. R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine 30, 1191-1212 (2001).”).
As per dependent Claim 35, the combination of Hershey and Maurer as a whole further discloses method wherein the one or more biomarkers include F2-isoprostane(Applicant in at least instant application specification as-filed [0233] discloses and admits use of F2-isoprostane as an oxidative stress biomarker as well-known prior art. See instant specification as-filed [0233] “F2-isoprostanes … a product of free radical mediated oxidation of arachidonic acid (see Sampson, M. J., Gopaul, N., Davies, I. R., Hughes, D. A. & Carrier, M. J. Plasma. F2 Isoprostanes. Diabetes Care 25, 537 (2002); Milne, G. L., Sanchez, S. C., Musick, E. S. & Morrow, J. D. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nature protocols 2, 221-226 (2007); Il, et al. Urinary F2-Isoprostanes as a Biomarker of Reduced Risk of Type 2 Diabetes. Diabetes Care 35, 173 (2012)),”).
Claims 5 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Hershey in view of Maurer and further in view of Rossi et al. (Pub: Rossi R, Giustarini D, Milzani A, Dalle-Donne I. Cysteinylation and homocysteinylation of plasma protein thiols during ageing of healthy human beings. J Cell Mol Med. 2009 Sep;13(9B):3131-40, hereinafter referred to as “Rossi”).
As per dependent Claim 5, the combination of Hershey and Maurer as a whole discloses method of claim 1 (see claim 1 analysis above).
The combination of Hershey and Maurer as a whole does not explicitly disclose biomarkers that include protein S-cysteinylation.
However, in an analogous redox and/or metabolic biomarker use field of endeavor, Rossi discloses method wherein the one or more biomarkers include protein S-cysteinylation (PrCysS) (Rossi in at least abstract, page 3138 discloses wherein the one or more biomarkers include protein S-cysteinylation (PrCysS)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biomarkers used in the method of Hershey, as modified with Maurer, by further including biomarkers that include protein S-cysteinylation as disclosed in Rossi. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage that analyses of reduced protein sulphydryls, S-homocysteinylated and S-cysteinylated protein levels in human plasma can be used to assess efficacy of intervention strategies against oxidative stress prior to or early after onset of clinical symptoms in ageing and age-related diseases (Rossi in at least abstract, page 3138).
As per dependent Claim 32, the combination of Hershey and Maurer as a whole discloses method of claim 27 (see claim 27 analysis above).
The combination of Hershey and Maurer as a whole does not explicitly disclose biomarkers that include protein S-cysteinylation.
However, in an analogous redox and/or metabolic biomarker use field of endeavor, Rossi discloses method wherein the one or more biomarkers include protein S-cysteinylation (PrCysS) (Rossi in at least abstract, page 3138 discloses wherein the one or more biomarkers include protein S-cysteinylation (PrCysS)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biomarkers used in the method of Hershey, as modified with Maurer, by further including biomarkers that include protein S-cysteinylation as disclosed in Rossi. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage that analyses of reduced protein sulphydryls, S-homocysteinylated and S-cysteinylated protein levels in human plasma can be used to assess efficacy of intervention strategies against oxidative stress prior to or early after onset of clinical symptoms in ageing and age-related diseases (Rossi in at least abstract, page 3138).
Claims 7 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Hershey in view of Maurer and further in view of Grunwell et al. (Pub: Grunwell JR, Gillespie SE, Ward JM, Fitzpatrick AM, Brown LA, Gauthier TW and Hebbar KB (2015) Comparison of Glutathione, Cysteine, and Their Redox Potentials in the Plasma of Critically Ill and Healthy Children. Front. Pediatr. 3:46., hereinafter referred to as “Grunwell”).
As per dependent Claim 7, the combination of Hershey and Maurer as a whole discloses method of claim 1(see claim 1 analysis above)
The combination of Hershey and Maurer as a whole does not explicitly disclose the one or more biomarkers include at least one of a redox potential of cysteine (Cys) or a redox potential of cystine (CysS).
However, in an analogous redox and/or metabolic biomarker use field of endeavor, Grunwell discloses method wherein the one or more biomarkers include at least one of a redox potential of cysteine (Cys) or a redox potential of cystine (CysS) (Grunwell in at least abstract, page 5 col. 2 for example discloses use of biomarkers that include at least one of a redox potential of cysteine (Cys) or a redox potential of cystine (CysS). See Grunwell page col. “a decrease in the abundance of Total Cys, an increase in GSSG, and a more oxidized Eh GSH/GSSG may serve as potential markers of OS events in the plasma of critically ill children. Understanding changes that occur in redox metabolites, redox potentials, and redox signaling pathways in childhood diseases may lead to novel prognostic markers and therapeutic targets in pediatric critical illness. Future studies will work toward assessing the role of protein thiols, other markers of oxidative stress, and signal transduction pathways to elucidate the mechanism of oxidative stress in critically ill children. In addition to studying the biological mechanisms of how changes in Eh Cys/CySS and Eh GSH/GSSG correlate with other markers of OS and influence redox sensitive redox signaling pathways, we plan on evaluating whether the balance of Cys/CySS and GSH/GSSG can differentiate subpopulations of critically ill children with differing severity of critical illness”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biomarkers used in the method of Hershey, as modified with Maurer, by further including biomarkers that include protein S-cysteinylation Grunwell. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of understanding changes that occur in redox metabolites, redox potentials, and redox signaling pathways in diseases can serve as prognostic markers and therapeutic targets in critical ill patients (Grunwell, page 5 col. 2).
As per dependent Claim 34, the combination of Hershey and Maurer as a whole discloses method of claim 27 (see claim 27 analysis above)
The combination of Hershey and Maurer as a whole does not explicitly disclose the one or more biomarkers include at least one of a redox potential of cysteine (Cys) or a redox potential of cystine (CysS).
However, in an analogous redox and/or metabolic biomarker use field of endeavor, Grunwell discloses method wherein the one or more biomarkers include at least one of a redox potential of cysteine (Cys) or a redox potential of cystine (CysS) (Grunwell in at least abstract, page 5 col. 2 for example discloses use of biomarkers that include at least one of a redox potential of cysteine (Cys) or a redox potential of cystine (CysS). See Grunwell page col. “a decrease in the abundance of Total Cys, an increase in GSSG, and a more oxidized Eh GSH/GSSG may serve as potential markers of OS events in the plasma of critically ill children. Understanding changes that occur in redox metabolites, redox potentials, and redox signaling pathways in childhood diseases may lead to novel prognostic markers and therapeutic targets in pediatric critical illness. Future studies will work toward assessing the role of protein thiols, other markers of oxidative stress, and signal transduction pathways to elucidate the mechanism of oxidative stress in critically ill children. In addition to studying the biological mechanisms of how changes in Eh Cys/CySS and Eh GSH/GSSG correlate with other markers of OS and influence redox sensitive redox signaling pathways, we plan on evaluating whether the balance of Cys/CySS and GSH/GSSG can differentiate subpopulations of critically ill children with differing severity of critical illness”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biomarkers used in the method of Hershey, as modified with Maurer, by further including biomarkers that include protein S-cysteinylation Grunwell. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of understanding changes that occur in redox metabolites, redox potentials, and redox signaling pathways in diseases can serve as prognostic markers and therapeutic targets in critical ill patients (Grunwell, page 5 col. 2).
Response to Amendment
According to the Amendment filed 06/02/2026, the status of the claims is as follows:
Claims 1, 13, 14, 23, 27 are currently amended;
Claims 2-12, 15-18, 22-26, 30-35 are as originally filed; and
Claims 9-10,19-21,28 and 36-38 are withdrawn;
The Specification/Drawings has been amended in view of the Amendment, filed 06/02/2026 No new matter was introduced.
By the current amendment, as a result, claims 1-38 are now pending in this application while claims 1-8,11-18,22-27 and 29-35 are being examined on the merits as being drawn to elected invention/species.
Response to Arguments
Issues Raised and Arguments/Remarks to Rejections/Objections Not Based On Prior Art presented on Pages 12-13 of Applicant’s Amendment dated 06/02/2026
The Examiner agrees with the Applicant, and in light of the amendments/arguments, withdraws the following non prior art related objections/rejections raised in Office Action dated 03/02/2026: [1] The objection to Specification/Drawings is withdrawn in view of the amendment and arguments, filed 06/02/2026; [2] The objection to claims is withdrawn in view of the amendment and arguments, filed 06/02/2026; [3] The 35 U.S.C. 112(b), rejections to claims as raised in Office Action dated 03/02/2026are withdrawn in view of the amendment, filed 06/02/2026.
Issues Raised and Arguments/Remarks to Rejections Based On Prior Art presented on Pages 12-16 of Applicant’s Amendment dated 06/02/2026 where Applicant’s’ remarks inter alia that:
35 U.S.C. § 103 Rejection of the Amended Independent Claim 1[A] Claims 1-4, 6, 8, 11-18, 22-27, 29-31, 33, and 35 were rejected under 35 U.S.C. § 103 over Hershey (U.S. 2017/0143972) in view of Maurer (U.S. 4556051). Applicant respectfully traverses.
[B] Applicant is unable to find where Hershey and Maurer together teach or suggest using biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state, compared to a reference value, to monitor efficacy of or to calibrate or adjust a therapy that uses a magnetic field in a first direction and an electric field in a non-parallel second direction.
[C] Applicant acknowledges that Hershey at [0045] discusses comparing a biomarker parameter to a reference value and adjusting parameters based on the comparison. Applicant is unable to find in Hershey a teaching of biomarkers indicative of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state as recited in amended claim 1. Further, Hershey's neuromodulation is directed to neural tissue (spinal cord, dorsal column, dorsal horn), whereas the claimed therapy delivers a magnetic field and a non-parallel electric field to tissue with biomarker- based monitoring as recited. Applicant is unable to find in Hershey a disclosure of a biomarker that is a redox potential.
[D] Applicant is unable to find in Hershey a teaching of a magnetic field in a first direction and an electric field in a non-parallel second direction to tissue, as recited. Applicant is unable to find in Maurer a disclosure of detecting any biomarker, or of using a biomarker indicative of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state to monitor, calibrate, or adjust the applied fields
[E] A redox potential is a defined electrochemical quantity (see specification at [0233])
[F] Applicant respectfully submits that the record does not establish why a person of ordinary skill would have applied Maurer's field arrangement to Hershey's neuromodulation system, much less why such a person would have further configured the combination to use biomarkers indicative of an oxidant- antioxidant balance, a redox potential, or a cellular metabolic state, compared to a reference value, to monitor efficacy of or to calibrate or adjust the therapy as recited in claim 1. The proposed combination appears to rely on impermissible hindsight reasoning derived from the present application.
[G]. Hershey is directed to neuromodulation of neural tissue (e.g., spinal cord, dorsal column, dorsal horn, vagus nerve) for treatment of neuroinflammation. See Hershey [0002], [0067]-[0068]. Maurer is directed to a non- intrusive treatment for promoting healing of fractured bone.
[H]For at least these reasons, Applicant respectfully submits that the record does not establish that the cited combination discloses or suggests amended claim 1.
Applicants’ arguments [A-H] with respect to the above claim limitation in amended independent Claim 1 have been considered but are not persuasive for the following reasons:
With respect to Applicants’ arguments [C], Examiner notes that claim 1 recites “tissue” which when broadly yet reasonably interpreted in light of instant application specification as-filed para. [0009] (“Target tissues may include, but are not limited to, … nerve or brain. “) [0104] (“energy is delivered to … nerve … the brain … or any combination thereof of a mammal), [0208] (“delivering the therapy includes delivering energy to …nerve or brain”) would encompass neural tissue. It is unclear as to why claim 1 broad recitation of “tissue” would and/or should necessarily or narrowly exclude neural tissue in light of specification as-filed as argued by the Applicants. Additionally, with respect to Applicants’ assertions that “Applicant is unable to find in Hershey a disclosure of a biomarker that is a redox potential”, Examiner notes that claim 1 as now explicitly, positively and specifically recited “biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state” which due to use of “or” term does not necessarily require “a redox potential” clause when broadly yet reasonably interpreted.
With respect to Applicants’ arguments [D] above arguing against the references individually, Examiner notes that 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). In this case, claim 1 was rejected under 35 U.S.C 103 as a whole. More specifically, primary reference was brought in for disclosing all claim 1 limitations as now explicitly, positively and specifically recited by the Applicants except for electric field second direction being non-parallel to the magnetic field first direction. The secondary art was brought in for disclosing this feature i.e. providing an electric field in a second direction that is non-parallel to the first direction of the magnetic field feature. Thus, as also detailed above the combination of applied art as a whole discloses all claim 1 limitations as now explicitly, positively and specifically recited by the Applicants.
With respect to Applicants’ arguments [E] above, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “redox potential is a defined electrochemical quantity (see specification at [0233]“) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Additionally, With respect to Applicants’ arguments [E] above, para. [0233] of the instant specification as-filed (see below) lists numerous prior art and appears to be admit as prior art the “the redox potential” features as evidenced below:
[0233] The biological effects of MOEFs are mediated by interaction with redox and metabolic systems. Carter C. S., H. S. C., Searby C. C., Cassaidy B., Miller M. J., Grzesik W. J., Piorczynski T. B., Zhang Q., Bradberry K., Pak T. K., Walsh S. A., Dick D. W., Akurathi V., Acevedo M., Mapuskar K, A Milne G. L., Hinton A. O., Guo D. F., Falls-Hubert K. C., Wagner B. A., Carter W. A., Wang K., Norris A. W,, Rahtnouni K., Buettner G. R., Hansen J. M., Spitz D. R., Abel E. D. and Sheffield V. C. Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes. Cell Metabolism 32, 561-574 Oct. 6, 2020. Monitoring treatment efficacy is important to establish safe and effective dosing parameters. Fortunately, there are robust and chemically stable biomarkers within redox and metabolic systems that are useful as indicators of the biological and therapeutic efficacy of MOEFs . These include biomarkers of glucose metabolism, lipid peroxidation and oxidative stress which may be used individually or in combination to detect a positive therapeutic response of MOEFs: glucose, insulin, glucagon, HbA1c, glycogen, c-peptide, pyruvate, lactate, FGF21, GDF15, adiponectin, respiratory quotient (RQ) which is the volume of carbon dioxide produced divided by the amount of oxygen consumed, cortisol, F2-isoprostanes (e.g. 5-series, 12-series, 8-series and 15-series), a product of free radical mediated oxidation of arachidonic acid (see Sampson, M. J., Gopaul, N., Davies, I. R., Hughes, D. A. & Carrier, M. J. Plasma. F2 Isoprostanes. Diabetes Care 25, 537 (2002); Milne, G. L., Sanchez, S. C., Musick, E. S. & Morrow, J. D. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nature protocols 2, 221-226 (2007); Il, et al. Urinary F2-Isoprostanes as a Biomarker of Reduced Risk of Type 2 Diabetes. Diabetes Care 35, 173 (2012)), antioxidants such as the glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CysS), thioredoxin (Trx), peroxiredoxin (Prdx), glutathione-S-transferase (GST), glutathione peroxidase 3 (GPX3) which participate in neutralizing oxidants by supporting or directly donating reducing equivalents to reduce and neutralize oxidants (see Jones, D. P. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295, C849-C868 (2008); Jones, D. P. & Sies, H. The Redox Code. Antioxidants & redox signaling 23, 734-746 (2015); Harris, I. S., et al. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer cell 27, 211-222 (2015); Hauffe, R., et al. GPx3 dysregulation impacts adipose tissue insulin receptor expression and sensitivity. JCI Insight 5(2020), expression of genes that induce the antioxidant response: NRF2, which translocates to the nucleus upon activation by oxidative stimuli where they induce expression of genes that mediate an antioxidant response (see Kansanen, E., Kuosmanen, S. M., Leinonen, H. & Levonen, A.-L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1, 45-49 (2013); Schmidlin, C. J., Dodson, M. B., Madhavan, L. & Zhang, D. D. Redox regulation by NRF2 in aging and disease. Free Radical Biology and Medicine 134, 702-707 (2019), expression of genes that are activated by NRF2 to mediate the antioxidant response: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM) (see Kansanen et al.), the redox couples, NADP+, NADPH, NAD+, NADH, redox post-translational modifications such as glutathionylation, cysteinylation, nitrosylation, carbonylation etc.6, long-chain fatty acids (LCFAs) (e.g. myristate, myristoleate, pentadeconoate, palmitate, palmitoleate, margarate, 10-heptadecenoate, stearate, oleate, vaccinate, nonadecanoate, 10-nonadecenoate, arachidate, eicosenoate, erucate etc.), poly unsaturated fatty acids (PUFAs) (e.g. heneicosapentaenoate, tetradecadienoate, hexadecadienoate, hexadecatrienoate, stearidonate, eicosapentaenoate, docasapentaenoate, docosahexaenoate, docosatrienoate, nisinate, linoleate, linolenate, dihomo-linolenate, arachidonate, adrenate, docosapentaenoate, docosadienoate, dihomo-linoleate, mead acid, docosatrienoate), medium chain fatty acids (MCFAs) (e.g. heptanoate, cis-4-decenoate, 10-undecenoate, 5-dodecenoate etc.), fatty acids dicarboxylate (e.g. glutarate, 2-hydroxyglutarate, 2-hydroxyadipate, 3-hydroxyadipate, suberate, azelate, sebacate, dodecadienoate, dodecanedioate, tetradecanedioate, hexadecanedioate, octadecenedioate, tetradecadienedioate, 3-carbodyy-4-methyl-5-propyl-2-furanpropanoate, 3-carboxy-4-methyl-5-pentyl-2-furanpropionate etc.), amino fatty acids (e.g. 2-aminoheptanoate, 2-aminooctanoate, n-acetyl-2-aminooctanoate etc.), acyl glycine (e.g. isocaproylglycine, valerylglycine, hexanoylglycine, 4-methylhexanoylglycine, trans-2-hexenoylglycine, n-octanoylglycine, 2-butenoyiglycine, 3-hydroxybutyroyiglycine etc.) and carnitines (e.g. acetylcarnitine, (R)-3-hydroxybutyrylcarnitine, hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine, 5-dodecenoylcarnitine, cis-4-decenoylcarnitine, laurylcarnitine, myristoylcarnitine, palmitoylcarnitine palmitoleoylcarnitine, stearoylcarnitine, linoleoylcarnitine, linolenoylcarnitine, 3-hydroxyoleoylcarnitine, oleoylcarnitine, myristoleoylcarnitine, adipoylcarnitine, octadecenedioylcarnitine, arachidoylcarnitine, arachidonoylcarnitine, behenoylcarnitine, dihomo-linolenoylcarnitine, dihomo-linoleoylcarnitine, eicosenoylcarnitine, docosahexaenoyicarnitine, lignoceroylcarnitine, nervonovicarnitine, margaroylcarnitine, pentadecanoylcarnitine, 3-hydroxypaimitoylcarnitine, deoxycarnitine, carnitine etc.) and beta-hydroxybutyrate. The redox potential is a robust biomarker to assess the safety and efficacy of MOEF. The redox potential is calculated by the Nernst equation (Eo—RT/nF In [reduced]2/[oxidized]) to yield a half-cell reduction potential (Eh) for the couple, where Eo is the standard half-cell reduction potential for the redox couple, R is the gas constant, T is the absolute temperature, n is 2 for the number of electrons transferred, and F is Faraday's constant. Schafer, F. Q. & Buettner, G. R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine 30, 1191-1212 (2001).
With respect to Applicants’ arguments [F], in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, please note that it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
With respect to Applicants’ arguments [F], that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the directions of electric field and magnetic fields used in the method as taught by Hershey, such that the electric field direction is non-parallel to the magnetic field direction, as taught by Maurer. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of establishing interacting electric and magnetic fields in a manner as to enhance tissue healing (Maurer, abstract, col. 2 lines 1-15).
With respect to Applicants’ arguments [G] above, Applicant is arguing with respect to features absent in claims as now explicitly, positively and specifically recited by the Applicants. Claim 1 recites tissue which when interpreted in light of instant application specification as-filed would encompass tissue typed disclosed in applied art. Examiner suggest amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
With respect to Applicants’ arguments [B-C] above, Examiner notes that the combination of applied art, Hershey and Maurer, as a whole discloses the limitation “detecting one or more biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state and performing a comparison of the one or more detected biomarkers to a reference value to perform at least one of: monitoring efficacy of the therapy based on the comparison; or calibrating or adjusting at least one parameter of the therapy based on the comparison” as now explicitly, positively and specifically recited by the Applicants when limitations are interpreted in light of the instant application specification as-filed. More specifically, Hershey discloses detecting one or more biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state and performing a comparison of the one or more detected biomarkers to a reference value to perform at least one of: monitoring efficacy of the therapy based on the comparison; or calibrating or adjusting at least one parameter of the therapy based on the comparison, Still more specifically, first, here, the “or” encompassing limitations is being broadly yet reasonably interpreted as requiring one of the elements in the enumerated list. Further, Hershey in at least fig. 9, [0005], [0020], [0045], [0051], [0061-0062], [0086-0088] discloses detecting one or more biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state and performing a comparison of the one or more detected biomarkers to a reference value to perform at least one of: monitoring efficacy of the therapy based on the comparison; or calibrating or adjusting at least one parameter of the therapy based on the comparison as seen in fig. 9. See at least Hershey [0045] “system delivers neuromodulation for modulating neural activities at the tissue site of the patient. The system can deliver the neuromodulation and sense the biomarker in the surrounding environment for indicating the patient's response to the delivery of the neuromodulation. The system can store patient data, such as a biomarker parameter associated with the tissue site, and can compare the biomarker parameter to a reference value. Based on the comparison, the system can adjust a parameter set controlling the delivery of the neuromodulation. As used in this document, a “biomarker parameter” can include a measure of the biomarker and/or a measure of a derivative of the biomarker. In various examples, one or more biomarker parameters each being a measure of the biomarker or a measure of a derivative of the biomarker can be sensed.”; [0061] “the biomarker can be a metabolic biomarker…biomarker parameter can be a measure of metabolism of the patient at a particular tissue site through quantification of ATP or a derivative (e.g., ADP, oxygen consumption, lactate, or pyruvate) … cellular metabolic demand can increase relative to metabolic demand of a non-affected sites. The neuromodulation device can use the measure of the metabolism as the biomarker parameter… using the biomarker parameter to optimize neuromodulation targeting” [0062] “using the biomarker parameter to inform a treatment for the patient, such as an intervention that alleviates oxidative stress conditions”; [0086-0088] “one or more biomarker parameters associated with the tissue site are sensed using one or more biomarker sensors … biomarker parameters each indicate a neural or other physiological response to the delivery of the neuromodulation. The one or more biomarkers are each a measure of the biomarker or a measure of a derivative of the biomarker… one or more biomarker parameters are each compared to a reference value… reference value or value range can be a stored value in the memory 210…reference value or value range can be a previously sensed value of the corresponding biomarker parameter… neuromodulation parameter set are adjusted using an outcome of the comparison. In one example, the reference value or value range represents a threshold indicative of a need for treating …and the outcome of the comparison indicates such a need”).
Hershey does not explicitly disclose the electric field second direction is non-parallel to the magnetic field first direction. However, in an analogous therapy delivering via combined electrical and magnetic energy to treat tissue field of endeavor, Maurer discloses a method (Maurer in abstract, fig. 1-10, col. 1 lines 61-col.10 line 26 for example discloses relevant subject-matter. More specifically, Maurer in abstract, fig. 1, fig. 13, col. 1 line 61- col. 2 line 10, col. 9 lines 60-68 for example discloses a method. See at least Maurer col. 1 line 61- col. 2 line 10 “method is a non-intrusive treatment utilizing electrode means attached to the skin of the patient adjacent the fracture of a bone and coil means located adjacent the skin and the fracture. The electrode means and coil means are used to establish interacting electric and magnetic fields to enhance tissue healing. The coil means is angularly spaced from the electrode means. The electric generator means is electrically connected to the electrode means and the coil means to provide current pulses to the electrode means and coil means. The energized coil means establishes a pulsed magnetic field. The current pulses and the pulsed magnetic field are in a phase relationship with each other so as to produce a unidirectional net current along the length of the bone and through the region of the injured tissue.”), comprising: delivering a therapy by delivering energy to tissue (Maurer in abstract, fig. 1, fig. 13, col. 1 line 61- col. 2 line 10, col. 9 lines 60-68 for example discloses delivering a therapy by delivering energy to tissue. See at least Maurer col. 1 line 61- col. 2 line 10 “method is a non-intrusive treatment utilizing electrode means attached to the skin of the patient adjacent the fracture of a bone and coil means located adjacent the skin and the fracture. The electrode means and coil means are used to establish interacting electric and magnetic fields to enhance tissue healing”), wherein delivering energy to the tissue includes: providing a magnetic field in a first direction to the tissue using a magnetic field system including a magnetic field source to produce the magnetic field, wherein the magnetic field produced by the magnetic field source includes a magnetic field produced by at least one of a permanent magnet, a temporary magnet or electric current flow through a conductor (Maurer in at least fig. 1, fig. 13, fig. 10, abstract, col. 1 line 61- col. 2 line 10, col. 9 lines 60-68 for example discloses providing a magnetic field in a first direction to the tissue using a magnetic field system including a magnetic field source/coil means to produce the magnetic field, wherein the magnetic field produced by the magnetic field source includes a magnetic field produced by at least one of a permanent magnet, a temporary magnet or electric current flow through a conductor. See at least Maurer col. 1 line 61- col. 2 line 10 “method is a non-intrusive treatment utilizing … coil means located adjacent the skin and the fracture”); providing an electric field in a second direction to the tissue using an electric field system including an electric field source to produce the electric field, wherein the second direction is non-parallel to the first direction (Maurer in at least abstract, fig. 1, fig. 13, fig. 10, col. 1 line 61- col. 2 line 16, col. 9 lines 60-68 for example discloses providing an electric field in a second direction to the tissue using an electric field system including an electric field source/electrodes to produce the electric field, wherein the second direction is non-parallel to the first direction. See at least Maurer abstract “apparatus and method for promoting healing of injured tissue, such as fractured bone, with interacting electric current and a magnetic flux field. Electrodes are adhesively attached to the skin adjacent the injured tissue. One or more coil assemblies normally spaced from the electrodes are located adjacent the tissue in alignment with the fractured bone. A current generator electrically connected to the electrodes operates to provide electric current pulses to the electrodes. A field generator electrically connected to the coil assemblies is operable to energize the coil assemblies to produce magnetic field pulses. The pulse generator and field generator are electrically coupled to maintain the electrode current pulses and magnetic field pulses in fixed phase relationship to produce a net current in the region of the fractured bone and generally perpendicular to the plane of the fracture.”; col. 1 line 61- col. 2 line 16 “method is a non-intrusive treatment utilizing electrode means attached to the skin of the patient adjacent the fracture of a bone … The electrode means and coil means are used to establish interacting electric and magnetic fields to enhance tissue healing. The coil means is angularly spaced from the electrode means. The electric generator means is electrically connected to the electrode means and the coil means to provide current pulses to the electrode means and coil means. The energized coil means establishes a pulsed magnetic field. The current pulses and the pulsed magnetic field are in a phase relationship with each other so as to produce a unidirectional net current along the length of the bone and through the region of the injured tissue. The unidirectional current flows generally perpendicular to the surface of the fracture and is of a magnitude and duration appropriate to the specific ion or cellular charge and mobility. ”). Thus, in the manner, the combination of applied art, Hershey and Maurer, as a whole discloses the limitation “detecting one or more biomarkers indicative of at least one of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state and performing a comparison of the one or more detected biomarkers to a reference value to perform at least one of: monitoring efficacy of the therapy based on the comparison; or calibrating or adjusting at least one parameter of the therapy based on the comparison” as now explicitly, positively and specifically recited by the Applicants when limitations are interpreted in light of the instant application specification as-filed.
For the above reasons, the 35 U.S.C. § 103 rejection of claim 1 as now explicitly, positively and specifically recited by the Applicants still applies, is proper and is being maintained at this time. Please also cross-reference detailed claim 1 interpretation, claim limitation mapping to prior art disclosed features and method steps and detailed explanations above. Examiner suggest amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
Issues Raised and Arguments/Remarks to Rejections Based On Prior Art presented on Pages 12-16 of Applicant’s Amendment dated 06/02/2026 where Applicant’s’ remarks inter alia that:
35 U.S.C. § 103 Rejection of the Amended Dependent Claims 13-14, and claim 22
[i] claim 13 recites biomarkers including an expression of genes that induce an antioxidant response including NRF2;
[ii] claim 14 recites genes activated by NRF2;
[iii] claim 22 recites changing a dose based on the detected biomarkers.
[iv]Applicant is unable to find these features in the cited combination. Applicant respectfully requests withdrawal of the rejection.
Applicant’s arguments [i-iv] above, with respect to the above claim limitations in dependent claims 13-14 and 22 have been considered but are not persuasive for the following reasons:
In response to Applicants’ arguments [i] above, Examiner notes that the Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “NRF2, which translocates to the nucleus upon activation by oxidative stimuli where they induce expression of genes that mediate an antioxidant response (see Kansanen, E., Kuosmanen, S. M., Leinonen, H. & Levonen, A.-L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1, 45-49 (2013); Schmidlin, C. J., Dodson, M. B., Madhavan, L. & Zhang, D. D. Redox regulation by NRF2 in aging and disease. Free Radical Biology and Medicine 134, 702-707 (2019), expression of genes that are activated by NRF2 to mediate the antioxidant response: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM) (see Kansanen et al.)”
With respect to Applicants’ arguments [ii] above, Applicant in at least instant application specification as-filed [0233] discloses and admits use of the recited biomarkers as well-known prior art. See instant specification as-filed [0233] “NRF2, which translocates to the nucleus upon activation by oxidative stimuli where they induce expression of genes that mediate an antioxidant response (see Kansanen, E., Kuosmanen, S. M., Leinonen, H. & Levonen, A.-L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1, 45-49 (2013); Schmidlin, C. J., Dodson, M. B., Madhav an, L. & Zhang, D. D. Redox regulation by NRF2 in aging and disease. Free Radical Biology and Medicine 134, 702-707 (2019), expression of genes that are activated by NRF2 to mediate the antioxidant response: NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM) (see Kansanen et al.)”.
With respect to Applicants’ arguments [iii] above, Hershey in at least [0020], [0045-0046], [0087-0088] discloses changing a dose for at least one of the electric field or the magnetic field based on the detected one or more biomarkers as evidenced in Hershey [0020] “a method for delivering neuromodulation to a patient … delivering the neuromodulation; controlling the delivery of the neuromodulation using a neuromodulation parameter set selected to modulate neural activity at a tissue site; sensing a biomarker parameter, and adjusting the neuromodulation parameter set using the biomarker parameter. The biomarker parameter may be a measure of a biomarker or a measure of a derivative of the biomarker” (emphasis added) ; [0045] “system can store patient data, such as a biomarker parameter associated with the tissue site, and can compare the biomarker parameter to a reference value. Based on the comparison, the system can adjust a parameter set controlling the delivery of the neuromodulation. As used in this document, a “biomarker parameter” can include a measure of the biomarker and/or a measure of a derivative of the biomarker.”
For the above reasons, the 35 U.S.C. § 103 rejection of above dependent claims as now explicitly, positively and specifically recited by the Applicants still applies, is proper and is being maintained at this time. Please also cross-reference detailed claim 13-14 and 22 interpretation, claim limitation mapping to prior art disclosed features and method steps and detailed explanations above. Examiner also suggests amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
Issues Raised and Arguments/Remarks to Rejections Based On Prior Art presented on Pages 15-16 of Applicant’s Amendment dated 06/02/2026 where Applicant’s’ remarks inter alia that:
35 U.S.C. § 103 Rejection of Dependent Claims 2-8,11-12, 15-18,23-27 and 29-35.
[a] For at least these reasons, Applicant respectfully submits that the record does not establish that the cited combination discloses or suggests amended claim 1. The dependent claims are allowable for at least the reasons set forth above with respect to claim 1, and also recite additional features that further distinguish over the cited art.
[b] Claims 5 and 32 were rejected under 35 U.S.C. § 103 over Hershey (U.S. 2017/0143972) in view of Maurer (U.S. 4556051) and Rossi ("Cysteinylation and homocysteinylation of plasma protein thiols during ageing of healthy human beings"). Applicant respectfully traverses.
In addition, claims 5 and 32 are allowable for at least the same reasons as claim 1 set forth above. The cited combination of Hershey, Maurer, and Rossi does not disclose or suggest detecting one or more biomarkers indicative of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state, and performing …a magnetic field and a non-parallel electric field, as recited in amended claim 1 and inherited by claims 5 and 32. Applicant respectfully requests withdrawal of the rejection of claims 5 and 32.
[c] Claims 7 and 34 were rejected under 35 U.S.C. § 103 over Hershey (U.S. 2017/0143972) in view of Maurer (U.S. 4556051) and Grunwell ("Comparison of Glutathione, Cysteine, and Their Redox Potentials in the Plasma of Critically III and Healthy Children"). Applicant respectfully traverses. In addition, claims 7 and 34 are allowable for at least the same reasons as claim 1 set forth above. The cited combination of Hershey, Maurer, and Grunwell does not disclose or suggest detecting one or more biomarkers indicative of an oxidant-antioxidant balance, a redox potential, or a cellular metabolic state, and performing a … a magnetic field and a non-parallel electric field, as recited in amended claim 1 and inherited by claims 7 and 34. Applicant respectfully requests withdrawal of the rejection of claims 7 and 34.
Applicants’ arguments with respect to dependent claims 2-8,11-12, 15-18,23-27 and 29-35 have been considered but are not persuasive. Applicants’ arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the dependent claims 2-8,11-12, 15-18,23-27 and 29-35 define a patentable invention based on their dependency on base claims without specifically pointing out how the language of the dependent claims patentably distinguishes them from the references. Therefore, that argument above is not persuasive either.
For the above reasons, the 35 U.S.C. § 103 rejection of above dependent claims as now explicitly, positively and specifically recited by the Applicants still applies, is proper and is being maintained at this time. Please also cross-reference detailed claim 2-8,11-12, 15-18,23-27 and 29-35 interpretation, claim limitation mapping to prior art disclosed features and method steps and detailed explanations above.
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). Applicants are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUNITA REDDY whose telephone number is (571)270-5151. The examiner can normally be reached on M-Thu 10-4 EST.
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/SUNITA REDDY/Primary Examiner, Art Unit 3791
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