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 .
Response to Amendment
This Office Action is responsive to the amendment filed on 10 Sep 2026. As directed by the amendment: claims 1, 3, 5-6, 8, 10, 14, and 16-19 have been amended, claim 22 has been canceled, and no claims have been added. Thus, claims 1-21 are presently pending in this application.
Response to Arguments
Objection to Claims
Applicant’s arguments, see Remarks, filed 10 Sep 2026, with respect to the objections to the claims have been fully considered and are persuasive in light of the claim amendments. The objections to the claims have been withdrawn.
However, new objections are made below as necessitated by the claim amendments.
Rejections Under Post-AIA 35 U.S.C. § 112 - Second Paragraph
Applicant’s arguments, see Remarks, filed 10 Sep 2026, with respect to the rejections under 35 U.S.C. 112 have been fully considered and are persuasive in light of the claim amendments. The rejections under 35 U.S.C. 112 have been withdrawn.
Rejections Under Post-AIA 35 U.S.C. § 102
Applicant’s arguments, see Remarks, filed 10 Sep 2026, with respect to the rejection(s) of claim 19 under 35 U.S.C. 102 have been fully considered and are persuasive in light of the claim amendments. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Zhao et al. (US 20100010556 A1), hereinafter Zhao, and Pikov et al. (US 20200360696 A1), hereinafter Pikov, as explained in further detail below..
Rejections Under Post-AIA 35 U.S.C. § 103
Applicant’s arguments, see Remarks, filed 10 Sep 2026, with respect to the rejection(s) of claims 1 and 10 under 35 U.S.C. 103 have been fully considered and are persuasive in light of the claim amendments. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Zhao et al. (US 20100010556 A1), hereinafter Zhao, and Pikov et al. (US 20200360696 A1), hereinafter Pikov, as explained in further detail below.
Claim Objections
Claim 14 is objected to because of the following informalities:
Claim 14: “stimulation parameters” in line 4 should read “the one or more parameters of the electrical stimulation” for consistency with the term established in claim 10.
Appropriate correction is required.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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, 3, 5, 7, 9-15, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 20100010556 A1), hereinafter Zhao, in view of Pikov et al. (US 20200360696 A1), hereinafter Pikov.
Regarding claim 1, Zhao discloses a method for regulating inflammation in a patient using baroreflex activation therapy (paragraph [0030], vagal stimulation therapy), comprising:
delivering electrical stimulation to one or more baroreceptors to reduce sympathetic nervous system overactivity (paragraph [0035], "Examples of such responses that are beneficial for HF at the lower VST intensities include anti-inflammation, anti-sympathetic, and anti-apoptosis responses, and an increased NO") and enhance parasympathetic activity (paragraph [0070], "delivering parasympathetic stimulation and/or sympathetic inhibition");
monitoring, during the delivering of the electrical stimulation, real-time physiological signals (paragraph [0043], "The illustrated monitor 603 monitors the parameter during a time with stimulation to provide a first feedback signal 607 indicative of a parameter value corresponding to a time with stimulation") comprising:
(i) at least one inflammatory biomarker selected from TNF-alpha, IL-1, IL-6, (paragraph [0041], "Examples of anti-inflammatory cytokines include serum TNF-alpha, IL-1, IL6, etc."); and
(ii) at least one autonomic parameter comprising heart rate variability (HRV) (paragraph [0041], "Examples of autonomic balance markers include...heart rate variability (HRV)"), or blood pressure (paragraph [0042], "Physiological parameter(s) that quickly respond to VST can be used in closed loop systems or during the implantation process. Examples of such parameters include...blood pressure");
determining, from the real-time physiological signals, a change in the at least one inflammatory biomarker and a change in the at least one autonomic parameter indicative of autonomic balance (paragraph [0043], "The illustrated monitor 603 monitors the parameter during a time with stimulation to provide a first feedback signal 607 indicative of a parameter value corresponding to a time with stimulation and during a time without stimulation to provide a second feedback signal 608 indicative of a parameter value corresponding to a time without stimulation. ... A comparator 609 receives the first and second feedback signals 607 and 608 and determines a detected change in the parameter value based on these signals"); and
in a closed-loop feedback process, dynamically modifying one or more parameters of the electrical stimulation delivered to the one or more baroreceptors in response to the change in the at least one inflammatory biomarker or the change in the at least one autonomic parameter to suppress systemic inflammation and restore autonomic balance (paragraph [0041], "The therapeutic efficacy of the VST can be assessed acutely (e.g. within seconds or minutes) such as may be beneficial for a closed loop system"; paragraph [0042], "Physiological parameter(s) that quickly respond to VST can be used in closed loop systems"; paragraph [0049], "Various closed loop system embodiments monitor at least one parameter that has a quick and predictable response to VST, and uses the monitored parameter to appropriately change the neural stimulation signal to result in a desired stimulation of the parasympathetic nervous system").
Zhao does not explicitly disclose that the one or more parameters of the electrical stimulation are modified in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter.
However, Pikov teaches systems for delivering therapy to a nerve in a patient (Abstract) comprising in a closed-loop feedback process, dynamically modifying one or more parameters of the electrical stimulation delivered to the one or more baroreceptors in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter to suppress systemic inflammation and restore autonomic balance (paragraph [0086], "utilize both an autonomic nervous system sensor and a disease activity sensor to inform adjustment of one or more of the stimulation parameters", including inflammatory activity, Paragraph [0075], [0078], [0086]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teachings of Pikov so that the one or more parameters of the electrical stimulation are modified in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter, because doing so may allow for a more accurate determination of an autonomic nervous system state, physiological state, and/or disease state of a patient, which may result in a reduction of unwanted side effects and an improvement of therapy efficacy (Pikov, paragraph [0086]).
Regarding claim 3, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Zhao further discloses that dynamically modifying the one or more parameters of the electrical stimulation comprises adjusting stimulation amplitude, pulse width, frequency, or duty cycle (paragraph [0048], "Various modulator embodiments adjust VST intensity by changing an amplitude of a stimulation signal used to provide VST, by changing a frequency of a stimulation signal used to provide VST, by changing a burst frequency of a stimulation signal used to provide VST, by changing a pulse width of a stimulation signal used to provide VST, by changing a duty cycle of a stimulation signal used to provide VST, or various combinations of two or more of these stimulation signal characteristics").
Regarding claim 5, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Zhao further discloses that determining the change in the at least one inflammatory biomarker comprises analyzing a trend in the at least one inflammatory biomarker over time (paragraph [0041], "The therapeutic efficacy of the VST...can be assessed on a longer term basis (e.g. on the order of hours, days, weeks, and months)").
Regarding claim 7, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Zhao does not explicitly disclose that the inflammation is associated with a chronic inflammatory disease or an autoimmune disorder.
However, Pikov further teaches that the inflammation is associated with a chronic inflammatory disease or an autoimmune disorder (paragraphs [0030], [0039]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teachings of Pikov so that the inflammation is associated with a chronic inflammatory disease or an autoimmune disorder, because doing so may result in a reduction of unwanted side effects and an improvement of therapy efficacy (Pikov, paragraph [0086]).
Regarding claim 9, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Zhao does not explicitly disclose that the inflammation is associated with a chronic inflammatory pain condition.
However, Pikov further teaches that the inflammation is associated with a chronic inflammatory pain condition (paragraphs [0030], [0039]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teachings of Pikov so that the inflammation is associated with a chronic inflammatory pain condition, because doing so may result in a reduction of unwanted side effects and an improvement of therapy efficacy (Pikov, paragraph [0086]).
Regarding claim 10, Zhao discloses a baroreflex activation therapy system for modulating inflammation (Fig. 6, paragraph [0042], vagal stimulation therapy system (VST) system 600), comprising:
a pulse generator configured to deliver electrical stimulation to one or more baroreceptors (Fig. 6, paragraph [0042, "pulse generator 601 to provide VST");
a lead configured for targeted baroreceptor activation (paragraph [0042], "The sensor(s) and electrode(s) can be integrated on a single lead or can use multiple leads"); and
a closed-loop feedback module (Fig. 6, paragraph [0042], VST response monitor 603) comprising:
(i) at least one inflammatory biomarker sensor configured to detect at least one inflammatory biomarker selected from TNF-alpha, IL-1, IL-6, (paragraph [0041], "Examples of anti-inflammatory cytokines include serum TNF-alpha, IL-1, IL6, etc."); and
(ii) at least one autonomic parameter comprising heart rate variability (HRV) (paragraph [0041], "Examples of autonomic balance markers include...heart rate variability (HRV)"), or blood pressure (paragraph [0042], "Physiological parameter(s) that quickly respond to VST can be used in closed loop systems or during the implantation process. Examples of such parameters include...blood pressure");
(iii) a controller operatively coupled to the pulse generator, the at least one inflammatory biomarker sensor, and the at least one autonomic sensor (Fig. 6, paragraph [0042], comparator 609), the controller configured to:
receive real-time physiological signals from the at least one inflammatory biomarker sensor and the at least one autonomic sensor (paragraph [0043], "comparator 609 receives the first and second feedback signals 607 and 608"),
determine, from the real-time physiological signals, a change in the at least one inflammatory biomarker or a change in at least one autonomic parameter indicative of autonomic balance (paragraph [0043], "determines a detected change in the parameter value based on these signals"); and,
in a closed-loop feedback process, dynamically modify one or more parameters of the electrical stimulation delivered by the pulse generator to the one or more baroreceptors in response to the change in the at least one inflammatory biomarker or the change in the at least one autonomic parameter (paragraph [0041], "The therapeutic efficacy of the VST can be assessed acutely (e.g. within seconds or minutes) such as may be beneficial for a closed loop system"; paragraph [0042], "Physiological parameter(s) that quickly respond to VST can be used in closed loop systems"; paragraph [0049], "Various closed loop system embodiments monitor at least one parameter that has a quick and predictable response to VST, and uses the monitored parameter to appropriately change the neural stimulation signal to result in a desired stimulation of the parasympathetic nervous system"),
the one or more parameters comprising stimulation amplitude, pulse width, frequency, or duty cycle (paragraph [0048], "Various modulator embodiments adjust VST intensity by changing an amplitude of a stimulation signal used to provide VST, by changing a frequency of a stimulation signal used to provide VST, by changing a burst frequency of a stimulation signal used to provide VST, by changing a pulse width of a stimulation signal used to provide VST, by changing a duty cycle of a stimulation signal used to provide VST, or various combinations of two or more of these stimulation signal characteristics").
Zhao does not explicitly disclose that the one or more parameters of the electrical stimulation are modified in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter.
However, Pikov teaches systems for delivering therapy to a nerve in a patient (Abstract) comprising in a closed-loop feedback process, dynamically modifying one or more parameters of the electrical stimulation delivered to the one or more baroreceptors in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter to suppress systemic inflammation and restore autonomic balance (paragraph [0086], "utilize both an autonomic nervous system sensor and a disease activity sensor to inform adjustment of one or more of the stimulation parameters"; including inflammatory activity, Paragraph [0075], [0078], [0086]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teachings of Pikov so that the one or more parameters of the electrical stimulation are modified in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter, because doing so may allow for a more accurate determination of an autonomic nervous system state, physiological state, and/or disease state of a patient, which may result in a reduction of unwanted side effects and an improvement of therapy efficacy (Pikov, paragraph [0086]).
Regarding claim 11, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses an implantable pulse generator (paragraph [0042], "An implantable device may provide the entire VST system").
Regarding claim 12, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses that the pulse generator comprises an external stimulation unit (paragraph [0079], Regarding claim 11, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses an implantable pulse generator (paragraph [0042], "An implantable device may provide the entire VST system").According to various embodiments, the external device includes a neural stimulator").
Regarding claim 13, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses an external programmer configured to adjust stimulation parameters (paragraph [0065], "The illustrated device further includes a transceiver 1036 and associated circuitry for use to communicate with a programmer or another external or internal device"; paragraph [0079]).
Regarding claim 14, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses a patient interface configured to receive patient-reported symptoms, wherein the controller is further configured to integrate the patient-reported symptoms with the real-time physiological signals to optimize stimulation parameters (paragraph [0037], "Another VST testing example that may be performed during the implantation procedure verifies capture using another physiological response (e.g. laryngeal vibration sensed by sensors or by patient, detected nerve traffic, or other)").
Regarding claim 15, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses a wireless communication module enabling bidirectional data exchange between the pulse generator, the closed-loop feedback module, and an external programmer (paragraph [0072], "The external system and the IMD are capable of wirelessly communicating data and instructions").
Regarding claim 17, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses that the controller continuously analyzes the real-time physiological signals from the at least one inflammatory biomarker sensor and the at least one autonomic sensor during delivery of the electrical stimulation (paragraph [0049], continuous stimulation).
Regarding claim 18, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Zhao further discloses that the lead comprises multiple independently controllable stimulation channels configured to selectively activate distinct baroreceptor regions at independently adjustable stimulation intensities, frequencies, or duty cycles (paragraph [0070], "Neural stimulation channels, identified as channels D and E, are incorporated into the device for delivering parasympathetic stimulation and/or sympathetic inhibition ... the pulse generator for each channel outputs a train of neural stimulation pulses which may be varied by the controller as to amplitude, frequency, duty-cycle, and the like").
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 20100010556 A1), hereinafter Zhao, in view of Pikov et al. (US 20200360696 A1), hereinafter Pikov, and further in view of Mech et al. (US 20240189596 A1, previously cited), hereinafter Mech.
Regarding claim 2, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Neither Zhao nor Pikov explicitly discloses that delivering electrical stimulation comprises stimulating baroreceptors in a carotid sinus.
However, Mech teaches medical devices, medical systems including a medical device, and methods of providing stimulation treatment (paragraph [0024]) wherein delivering electrical stimulation comprises stimulating baroreceptors in a carotid sinus (paragraphs [0028], [0040]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao and Pikov with the teachings of Mech so that delivering electrical stimulation comprises stimulating baroreceptors in a carotid sinus, because doing so can treat both obesity and conditions comorbid with obesity (Mech, paragraphs [0028], [0092], [0104]) and increase insulin sensitivity and glucose tolerance (Mech, paragraph [0080]).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 20100010556 A1), hereinafter Zhao, in view of Pikov et al. (US 20200360696 A1), hereinafter Pikov, and further in view of Libbus et al. (US 20160045741 A1, previously cited), hereinafter Libbus 2016.
Regarding claim 4, the method of claim 3 is obvious over Zhao and Pikov, as explained above. Zhao does not explicitly disclose that the duty cycle varies between 20% and 60% of active stimulation.
However, Libbus 2016 teaches methods for delivering vagus nerve stimulation (Abstract) wherein the duty cycle varies between 20% and 60% of active stimulation (paragraphs [0049]-[0051]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao and Pikov with the teachings of Libbus 2016 so that the duty cycle varies between 20% and 60% of active stimulation, because doing so provides the highest targeted therapeutic efficacy with the lowest potential side effects (Libbus 2016, paragraph [0050]).
Claims 6, 16, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 20100010556 A1), hereinafter Zhao, in view of Pikov et al. (US 20200360696 A1), hereinafter Pikov, and further in view of Hamner et al. (US 20220233860 A1, previously cited), hereinafter Hamner.
Regarding claim 6, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Neither Zhao nor Pikov explicitly discloses dynamically modifying the one or more parameters of the electrical stimulation comprises executing an AI-driven algorithm or machine learning model configured to analyze historical patient response patterns and the real-time physiological signals.
However, Hamner teaches a system for stimulation of an autonomic nervous system (paragraph [0203]) wherein dynamically modifying the one or more parameters of the electrical stimulation comprises executing an AI-driven algorithm or machine learning model configured to analyze historical patient response patterns and the real-time physiological signals (paragraphs [0207], [0266]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao and Pikov with the teachings of Hamner so that dynamically modifying the one or more parameters of the electrical stimulation comprises executing an AI-driven algorithm or machine learning model configured to analyze historical patient response patterns and the real-time physiological signals, because doing so improves the prediction of the onset of symptoms associated with the treated disease by determining correlations between biological measures, tracked symptoms, and other recorded events (Hamner, paragraph [0207]).
Regarding claim 16, the system of claim 10 is obvious over Zhao and Pikov, as explained above. Neither Zhao nor Pikov explicitly discloses that the controller executes an AI-driven algorithm or machine learning model configured to analyze trends in the at least one inflammatory biomarker and predict patient responses.
However, Hamner teaches a system for stimulation of an autonomic nervous system (paragraph [0203]) wherein dynamically modifying the one or more parameters of the electrical stimulation comprises executing an AI-driven algorithm or machine learning model configured to analyze historical patient response patterns and the real-time physiological signals (paragraphs [0207], [0266]).
However, Hamner teaches a system for stimulation of an autonomic nervous system (paragraph [0203]) wherein dynamically modifying the one or more parameters of the electrical stimulation comprises executing an AI-driven algorithm or machine learning model configured to analyze historical patient response patterns and the real-time physiological signals (paragraphs [0207], [0266]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao and Pikov with the teachings of Hamner so that the controller executes an AI-driven algorithm or machine learning model configured to analyze trends in the at least one inflammatory biomarker and predict patient responses, because doing so improves the prediction of the onset of symptoms associated with the treated disease by determining correlations between biological measures, tracked symptoms, and other recorded events (Hamner, paragraph [0207]).
Regarding claim 19, Zhao discloses a method for treating an arrhythmia associated with inflammation using baroreflex activation therapy (paragraph [0030], vagal stimulation therapy; claim 11), comprising:
delivering electrical stimulation to one or more baroreceptors (paragraph [0030], vagal stimulation therapy);
during the delivering of the electrical stimulation (paragraph [0043], "The illustrated monitor 603 monitors the parameter during a time with stimulation to provide a first feedback signal 607 indicative of a parameter value corresponding to a time with stimulation"), monitoring heart rate variability (HRV) (paragraph [0041], "Examples of autonomic balance markers include...heart rate variability (HRV)") and at least one inflammatory biomarker selected from TNF-alpha, IL-1, IL-6, (paragraph [0041], "Examples of anti-inflammatory cytokines include serum TNF-alpha, IL-1, IL6, etc.");
determining a change in HRV or a change in the at least one inflammatory biomarker (paragraph [0043], "The illustrated monitor 603 monitors the parameter during a time with stimulation to provide a first feedback signal 607 indicative of a parameter value corresponding to a time with stimulation and during a time without stimulation to provide a second feedback signal 608 indicative of a parameter value corresponding to a time without stimulation. ... A comparator 609 receives the first and second feedback signals 607 and 608 and determines a detected change in the parameter value based on these signals"); and
in a closed-loop feedback process, dynamically adjusting a frequency of the electrical stimulation (paragraph [0036]) delivered to the one or more baroreceptors in response to the change in HRV or the change in the at least one inflammatory biomarker (paragraph [0041], "The therapeutic efficacy of the VST can be assessed acutely (e.g. within seconds or minutes) such as may be beneficial for a closed loop system"; paragraph [0042], "Physiological parameter(s) that quickly respond to VST can be used in closed loop systems"; paragraph [0049], "Various closed loop system embodiments monitor at least one parameter that has a quick and predictable response to VST, and uses the monitored parameter to appropriately change the neural stimulation signal to result in a desired stimulation of the parasympathetic nervous system") to improve electrophysiological stability, and decrease arrhythmic risk (paragraph [0032], "various embodiments deliver therapeutically-effective doses of VST non-selectively to afferent and efferent axons at low levels to avoid or inhibit bradycardia responses induced by stimulation of the vagus nerve").
Zhao does not explicitly disclose that the one or more parameters of the electrical stimulation are modified in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter.
However, Pikov teaches systems for delivering therapy to a nerve in a patient (Abstract) comprising in a closed-loop feedback process, dynamically modifying one or more parameters of the electrical stimulation delivered to the one or more baroreceptors in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter to suppress systemic inflammation and restore autonomic balance (paragraph [0086], "utilize both an autonomic nervous system sensor and a disease activity sensor to inform adjustment of one or more of the stimulation parameters"; including inflammatory activity, Paragraph [0075], [0078], [0086]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teachings of Pikov so that the one or more parameters of the electrical stimulation are modified in response to both the change in the at least one inflammatory biomarker and the change in the at least one autonomic parameter, because doing so may allow for a more accurate determination of an autonomic nervous system state, physiological state, and/or disease state of a patient, which may result in a reduction of unwanted side effects and an improvement of therapy efficacy (Pikov, paragraph [0086]).
Neither Zhao nor Pikov explicitly discloses that dynamically adjusting the frequency of the electrical stimulation increases HRV.
However, Hamner teaches a system for stimulation of an autonomic nervous system (paragraph [0203]) wherein dynamically adjusting stimulation frequency increases heart rate variability (paragraphs [0267], [0269]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao and Pikov with the teachings of Hamner so that dynamically adjusting stimulation frequency increases heart rate variability, because increased heart rate variability can signify increased parasympathetic response and/or decreased sympathetic response (Hamner, paragraph [0267]), and heart rate variability is an indicator of autonomic balance (Hamner, paragraph [0240]).
Regarding claim 20, the method of claim 19 is obvious over Zhao, Pikov, and Hamner, as explained above. Neither Zhao nor Pikov explicitly discloses that the arrhythmia comprises atrial fibrillation.
However, Hamner further teaches that the arrhythmia comprises atrial fibrillation (paragraphs [0203], [0303]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao, Pikov, and Hamner with the teachings of Hamner so that the arrhythmia comprises atrial fibrillation, because doing so can prevent or reduce the recurrence rate of fibrillation in people with persistent atrial fibrillation (AF) after pharmaco- or electro-cardioversion (Hamner, paragraph [0303]).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 20100010556 A1), hereinafter Zhao, in view of Pikov et al. (US 20200360696 A1), hereinafter Pikov, and further in view of Das et al. (Electrical Stimulation for Immune Modulation in Cancer Treatments, 2022, previously cited), hereinafter Das.
Regarding claim 8, the method of claim 1 is obvious over Zhao and Pikov, as explained above. Neither Zhao nor Pikov explicitly discloses that the inflammation is associated with cancer progression and stimulation is increased during a cancer treatment period.
However, Das teaches that electrical stimulation of the vagus nerve can slow tumorigenesis through its anti-inflammatory properties (page 11, first column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao and Pikov with the teachings of Das so that the inflammation is associated with cancer progression and stimulation is increased during a cancer treatment period, because doing so can promote innate and adaptive immune responses and direct antitumor activity (Das, page 12, first column).
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (US 20100010556 A1), hereinafter Zhao, in view of Pikov et al. (US 20200360696 A1), hereinafter Pikov, and further in view of Hamner et al. (US 20220233860 A1, previously cited), hereinafter Hamner, and Stavrakis et al. (Low-Level Vagus Nerve Stimulation Suppresses Post-Operative Atrial Fibrillation and Inflammation: A Randomized Study, 2017, previously cited), hereinafter Stavrakis.
Regarding claim 21, the method of claim 19 is obvious over Zhao, Pikov, and Hamner, as explained above. Neither Zhao nor Pikov explicitly discloses that the arrhythmia is associated with myocarditis or post-surgical inflammation-related atrial fibrillation.
However, Stavrakis teaches a method of post-operative low-level vagus nerve stimulation (page 930, second column) in order to suppress post-operative atrial fibrillation (POAF) and inflammatory cytokines (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao, Pikov, and Hamner with the teachings of Stavrakis so that the arrhythmia is associated with post-surgical inflammation-related atrial fibrillation, because doing so provides a safe and effective modality for the prevention of POAF and reduction of surgery-induced inflammation (Stavrakis, page 935).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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.
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/CHRISTINE SISON/Examiner, Art Unit 3796
/PAMELA M. BAYS/Primary Examiner, Art Unit 3796
