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 .
The current application has a priority date of 05/16/2019 according to the priority chain on the record.
Claim Status
As per applicant’s response received on 06/05/2026, claims 35-62 are pending; claims 35-60 have been amended and claims 61-62 have been newly added.
Response to Amendment
The claim objection is withdrawn due to claim amendment.
The 35 USC 101 rejection is withdrawn in view of current claim amendments.
The 35 USC 112(b) and 112(d) rejections are also withdrawn in view of current claim amendments.
As for the 35 USC 102 rejection based on Levine et al. US 2017/0203103, the Applicant’s arguments have been fully considered but are moot in view of the new grounds of rejections below.
Claim 45 is allowable.
Claim Objections
Claim 42 is objected to because of the following informalities: “a disease activity sensor” should be amended to “the disease activity sensor” for proper antecedent basis referring to claim 1. Appropriate correction is required.
Claim Interpretations
Claim 48 recites “wherein the stimulation signal is configured to suppress the production of pro-inflammatory cytokines, increase the production of anti-inflammatory cytokines, and/or reduce the sympathetic tone in a patient that has a chronic gastrointestinal disorder, a chronic auto-immune disease, or a metabolic disorder.” The limitations following ‘configured to’ are treated as intended use/functional language of the “stimulation signal.”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 35, 38-40, 44, 46-48 and 52-62 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Thakur et al. US 2018/0085584 A1 (hereinafter “Thakur”).
Regarding claim 35, Thakur discloses a system (Figs. 2A-2B: pain management systems 200A or 200B) for delivering an electrical stimulus to a sacral nerve ([0056, 0076] delivering closed-loop electrostimulation to target tissue, e.g. sacral nerve stimulation) of a patient comprising:
an implantable pulse generator (210A, 210B) comprising:
a non-transitory computer readable memory (215) comprising instructions to:
calculate a heart rate parameter from cardiac data received from a cardiac sensor ([0051] sensor circuit 211 detects ECG and heart rate signals);
calculate a disease activity parameter from disease activity data received from a disease activity sensor ([0051] sensor circuit 211 senses biochemical signals, e.g. inflammatory (bio)markers etc., the described biochemical signals are taken to encompass “disease activity parameter” in this claim);
calculate a bodily activity parameter from bodily activity data received from a bodily activity sensor ([0051] sensor circuit 211 coupled with an accelerometer to detect body motion/activity);
determine an autonomic nervous system state (e.g. pain score, and calculated metrics associated with disease conditions; [0043: last sentence]) of the patient based on the heart rate parameter, a physiological state of the patient based on the bodily activity parameter, and/or a disease state of the patient based on the bodily activity parameter ([0062-0071] based on objective sensor data for calculating pain score and other metrics, including sympathetic nerve system activity, which can be used of sympathetic nerve modulation, see [0056: last sentence] and [0069]); and
adjust a sacral nerve stimulation parameter of a stimulation signal based on the determined autonomic nervous system state, the physiological state, and/or the disease state ([0060-0061] and [0072] “programmer circuit 235 may produce parameter values for operating the implantable neuromodulator 210A, including parameters for sensing physiological and functional signals and generating signal metrics, and parameters or electrode configurations for electrostimulation.”); and
a microcontroller configured to execute the instructions (214, see [0057-0059]); and
an implantable signal delivery device (213) configured to deliver the stimulation signal to the sacral nerve ([0056-0059] the generation and delivery of electrostimulation via electro-stimulator 213 is in a closed-loop fashion by adaptively adjusting one or more stimulation parameters or stimulation electrode configuration based on the detected signal metrics).
Regarding claim 38, Thakur discloses the system of claim 35, wherein the cardiac data is electrocardiographic or photoplethysmographic data. ([0051] ECG)
Regarding claim 39, Thakur discloses the system of claim 35, wherein the disease activity parameter comprises an inflammatory disease activity parameter or an oxidative stress activity parameter. ([0051: last sentence] inflammatory(bio)markers)
Regarding claim 40, Thakur discloses the system of claim 35, wherein the disease activity parameter comprises one or more of: an average of inflammatory disease activity data, a percentage of time with elevated inflammatory disease activity, an amplitude of oxidative stress activity, or a percentage of time with elevated oxidative stress activity. ([0069: last sentence] “signal metrics reflective of elevated sympathetic tone, such as heart sound, heart rate, or heart rate variability” and [0099] calculate statistical metrics of stress, pain and/or biomarkers)
Regarding claim 44, Thakur discloses the system of claim 35 including a motion sensor for detecting physical motion ([0052]), and a biochemical sensor for detecting disease activity parameter e.g. biomarkers ([0051]). Thakur further teaches wherein the disease activity parameter and the bodily activity parameter are calculated from disease activity data and bodily activity data received from the same sensor. Since the term “disease activity data” is non-specific disease, it can be taken to include any type of disease or disease activity. As taught in Thakur, motion related diseases include: “a posture, a gait, a balance indicator, a locomotion pattern, or a physical activity” ([0087: 3rd sentence]), and also “…patient posture, gait, balance, physical activity signals, or signals indicating sleep or awake state, among others… [these] functional signals may responsively co-variate with a pain episode. In an example, the functional signals may be sensed using accelerometer sensors.” ([0095], also see [0107]) Accordingly, Thakur teaches disease activity parameter (e.g. posture, gate, balance indicator, locomotion pattern, sleep or awake state etc.) and the bodily activity parameter (e.g. body motion) are calculated from disease activity data and bodily activity data received from the same sensor (e.g. accelerometer).
Regarding claim 46, Thakur discloses the system of claim 35, wherein the bodily activity parameter comprises a respiratory activity parameter, a metabolic activity parameter, a gastrointestinal activity parameter, or a circadian rhythm parameter. ([0051] respiratory signal)
Regarding claim 47, Thakur discloses the system of claim 35, wherein the adjusted stimulation parameter comprises one or more of amplitude, frequency, pulse width, burst interval, or elapsed duration. ([0056, 0100] stimulation pulses are adjusted by pulse amplitude, pulse width, stimulation frequency, duration, on-off cycle, pulse shape or waveform, temporal pattern of the stimulation, among other stimulation parameters.)
Regarding claim 48, Thakur discloses the system of claim 35, wherein the stimulation signal is configured to suppress production of pro-inflammatory cytokines, increase production of anti-inflammatory cytokines, and/or reduce sympathetic tone in the patient ([0056] sympathetic nerve modulation; [0051] cytokine and inflammatory marker monitoring; [0069] sympathetic tone monitoring), wherein the patient has a chronic gastrointestinal disorder, a chronic auto- immune disease, or a metabolic disorder. (Intended use claim; see [0006, 0043: last sentence, 0073] chronic disease pain/symptom management)
Regarding claim 52, Thakur discloses the system of claim 35 further comprising: the cardiac sensor; the disease activity sensor; and the bodily activity sensor. (see [0050-0052])
Regarding claim 53, Thakur discloses the system of claim 52 further comprising a temporary signal delivery device (external/wearable electrodes) configured to deliver a screening stimulation signal to the sacral nerve. ([0047: 2ns to last sentence] self-diagnostic test; [0056] “the electrostimulator 213 may deliver transcutaneous electrical nerve stimulation (TENS) via detachable electrodes that are affixed to the skin”; detachable electrodes delivering a stimulation signal is taken to encompass “screening stimulation signal”)
Regarding claim 54, Thakur discloses the system of claim 53, wherein the stimulation signal is delivered using the implantable signal delivery device or the temporary signal delivery device. (See rejection to claim 53 above)
Regarding claim 55, Thakur discloses a system (Figs. 2A-2B: pain management systems 200A or 200B) for delivering an electrical stimulus to a sacral nerve([0056, 0076] delivering closed-loop electrostimulation to target tissue, e.g. sacral nerve stimulation) of a patient comprising:
a cardiac sensor ([0050-0051] sensor circuit 211 coupled to two or more sensors, e.g. detects ECG and heart rate signals);
an activity sensor ([0051] sensor circuit 211 coupled with an accelerometer to detect body motion/activity);
an implantable signal delivery device (213) configured to deliver a stimulation signal to the sacral nerve ([0056, 0076] delivering closed-loop electrostimulation to target tissue, e.g. sacral nerve stimulation); and
an implantable pulse generator (210A, 210B) comprising a microcontroller configured to:
receive cardiac data from the cardiac sensor and calculate a heart rate parameter from the cardiac data ([0051] heart rate data);
receive activity data from the activity sensor and calculate a disease activity parameter and a bodily activity parameter from the activity data ([0052] body motion parameter, and other motion related disease parameters, e.g. patient posture, gait, balance, or physical activity signals, taken to encompass “disease activity parameter” in this claim);
determine an autonomic nervous system state (e.g. pain score, and calculated metrics associated with disease conditions; [0043: last sentence]) of the patient based on the heart rate parameter, a physiological state of the patient based on the bodily activity parameter, and a disease state of the patient based on the disease activity parameter ([0062-0071] based on objective sensor data for calculating pain score and other metrics, including sympathetic nerve system activity, which can be used of sympathetic nerve modulation, see [0056: last sentence] and [0069]), and
adjust a sacral nerve stimulation parameter of a stimulation signal based on the determined autonomic nervous system state, physiological state, and/or disease state ([0060-0061] and [0072] “programmer circuit 235 may produce parameter values for operating the implantable neuromodulator 210A, including parameters for sensing physiological and functional signals and generating signal metrics, and parameters or electrode configurations for electrostimulation.”); and
instruct the implantable signal delivery device (213) to deliver an adjusted stimulation signal comprising the adjusted sacral nerve stimulation parameter ([0057-0059] the generation and delivery of electrostimulation via electro-stimulator 213 is in a closed-loop fashion by adaptively adjusting one or more stimulation parameters or stimulation electrode configuration based on the detected signal metrics).
Regarding claim 56, Thakur discloses the system of claim 55, wherein the cardiac sensor is an implanted electrocardiographic electrode or external diagnostic device configured to measure values of the patient's heart rate. ([0050, 0056] sensor circuit 211 is coupled t to electrodes; see [0051] ECG, electrodes of implantable neuromodulator 210A and 210B are inherently also implanted)
Regarding claim 57, Thakur discloses the system of claim 55, wherein the activity sensor comprises one or more of: an implanted core body temperature sensor, an implanted electromyographic electrode, an implanted movement sensor, an implanted non-enzymatic electrochemical sensor, an implanted oxygenation sensor,or an external diagnostic device. ([0052: 2ns sentence] implantable accelerometer)
Regarding claim 58, Thakur discloses the system of claim 55, wherein the adjusted sacral nerve stimulation parameter comprises one or more of a stimulation amplitude, a pulse width, a frequency, a burst interval, or an elapsed stimulation duration. ([0056, 0100] stimulation pulses are adjusted by pulse amplitude, pulse width, stimulation frequency, duration, on-off cycle, pulse shape or waveform, temporal pattern of the stimulation, among other stimulation parameters.)
Regarding claim 59, Thakur discloses the system of claim 58 further comprising a temporary signal delivery device configured to deliver a screening stimulation signal to the sacral nerve. ([0047: 2ns to last sentence] self-diagnostic test; [0056] “the electrostimulator 213 may deliver transcutaneous electrical nerve stimulation (TENS) via detachable electrodes that are affixed to the skin”; detachable electrodes delivering a stimulation signal is taken to encompass “screening stimulation signal”)
Regarding claim 60, this claim is rejected by Thakur under the same rationale as discussed to claim 55 above.
Regarding claim 61, Thakur discloses the system of claim 35, wherein the non-transitory computer readable memory comprises instructions to determine the disease state of the patient, and wherein the disease state is further based on the bodily activity parameter. (See rejection to 35, see Thakur [0062-0071])
Regarding claim 62, Thakur discloses the system of claim 35, wherein the non-transitory computer readable memory comprises instructions to determine the physiological state of the patient, and wherein the physiological state is further based on the disease activity parameter. (see [0050-0051] physiological state and signals)
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 36-37, 41-43 and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Thakur as applied to claim 35 above, and further in view of Levine et al. US 2017/0203103 A1 (hereinafter “Levine”, previously cited).
Regarding claims 36 and 37, Thakur discloses the system of claim 35, wherein the heart rate parameter is a heart rate variability parameter, and in which metrics are calculated ([0069: last sentence] and [0079]), but does not explicitly discloses wherein the heart rate parameter is comprises a frequency-domain parameter, and wherein the frequency-domain parameter comprises a power of a low frequency (LF) band, a power of a high frequency (HF) band, or an LF/HF power ratio.
Levine, another prior art reference in the analogous art teaches an implantable system for delivering electrical stimulus to a nerve of a patient to treat inflammation (Abstract and [0010-0011]), comprising an implantable stimulator and electrodes for detecting heart rate signals, and wherein “HRV (heart rate variability) may be estimated by frequency domain (e.g., Fourier transform, including FFT) or time-domain methods (e.g., standard deviation of beat-to-beat intervals, root mean square of successive differences between adjacent beat-to-beat intervals, standard deviation of successive differences between adjacent beat-to-beat intervals, etc.” (see [0044]) It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Thakur to include the estimated heart rate using frequency-domain parameter analysis, that comprises a power of a low frequency (LF) band, a power of a high frequency (HF) band, or an LF/HF power ratio, in view of Levine, the motivation for doing so is to statistically analyze the ration of LF to HF power to determine a metric of sympathetic/parasympathetic balance (Levine: [0044]).
Regarding claim 41, Thakur discloses the system of claim 35 including monitoring disease activity monitor, e.g. inflammatory and other biomarkers ([0051]), but does not disclose wherein the disease activity parameter is calculated over a period of time of 1 hour to 12 hours. Levine, another prior art reference in the analogous art teaches an implantable system for delivering electrical stimulus to a nerve of a patient to treat inflammation at target tissue of a patient (Abstract and [0010-0011]). Levine discloses detecting a disease activity parameter (biomarker metric of inflammatory disease state) from disease activity data (e.g. temperature, cytokine level, and memory T cell level) received from a disease activity sensor ([0043, 0124, 0125, 0148] measured by the built-in analyte sensor at the microstimulator or thermometer, [0107] measured by a separate sensor, parameter received at microstimulator); and wherein the disease activity parameter is calculated over a period of time of 1 hour to 12 hours. ([0008] “metric(s) taken from the patient immediately or at one or more time intervals thereafter (e.g., within the first hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 12 hours”). It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Thakur to monitor the various inflammatory disease activity data within predetermined time periods, in view of Levine; the motivation for doing so is to monitor inflammation with respect to time in a patient and to determine dose (time) interval specific for that patient (Levine: [0104]).
Regarding claims 42 and 43, Thakur discloses the system of claim 35 including detecting various physiological parameters and inflammatory biomarkers ([0051]), but does not disclose wherein the disease activity parameter is calculated from disease activity data that is core body temperature data received from a disease activity sensor that is an implanted core body temperature sensor, and wherein the disease activity parameter comprises an average core body temperature or a percentage of time with elevated core body temperature.
Levine, another prior art reference in the analogous art teaches an implantable system for delivering electrical stimulus to a nerve of a patient to treat inflammation at target tissue of a patient (Abstract and [0010-0011]). Levine discloses detecting a disease activity parameter (biomarker metric of inflammatory disease state) from disease activity data (e.g. temperature, cytokine level, and memory T cell level) received from a disease activity sensor ([0043, 0124, 0125, 0148] measured by the built-in analyte sensor at the microstimulator or thermometer, [0107] measured by a separate sensor, parameter received at microstimulator); and the disease activity parameter is calculated from disease activity data that is a core body temperature data received the a disease activity sensor that is an implanted core body temperature sensor ([0107] microstimulator is an implanted device, and has a built-in temperature sensor for detecting temperature at the implanted site, this is taken to encompass “implanted core body temperature sensor/data” in this claim. Also see [0148:2nd sentence] “… core body temperature may be used to detect changes in body temperature indicative of disease states.”); and wherein the disease activity parameter comprises an average core body temperature or a percentage of time with elevated core body temperature (see [0148]). It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Thakur to include the core body temperature sensor in view of Levine; the motivation for doing so is because core temperature is an alternative parameter for monitoring inflammatory biomarker (Thakur: [0051] physiological parameter and biomarkers; also see Levine: [0148] core temperature and biomarkers).
Regarding claims 49-51, Thakur discloses the system of claim 35, wherein the disease activity data is inflammatory disease activity data ([0051]), but does not disclose wherein the disease activity parameter is a time-dependent disease activity parameter, the non-transitory computer readable memory comprises instructions to determine the disease state of the patient, and the disease state is an inflammatory disease state, and wherein the inflammatory disease state is early inflammatory response, flare of inflammatory disease activity, no flare in inflammatory disease activity, or late inflammatory response.
Levine, another prior art reference in the analogous art teaches an implantable system for delivering electrical stimulus to a nerve of a patient to treat inflammation at target tissue of a patient (Abstract and [0010-0011]). Levine discloses detecting calculate a heart rate parameter ([0010, 0039] physiological metric, e.g. heart rate, heart rate variability/HRV;) from cardiac data (ECG) received from a cardiac sensor ([0039] electrodes; also see [0107]); calculate a disease activity parameter (biomarker metric of inflammatory disease state) from disease activity data (e.g. temperature, cytokine level, and memory T cell level) received from a disease activity sensor ([0043, 0124, 0125, 0148] measured by the built-in analyte sensor at the microstimulator or thermometer, [0107] measured by a separate sensor, parameter received at microstimulator); calculate a bodily activity parameter (activity metric) from bodily activity data (body motion) received from a bodily activity sensor ([0147- 0151] motion sensor, accelerometer); and wherein the disease activity data is inflammatory disease activity data ([0043, 0124, 0125] (chronic) inflammatory disease), the disease activity parameter is a time-dependent disease activity parameter ([0104] time-dependent inflammatory disease), the implantable pulse generator is configured to determine a disease state of the patient, and the disease state is an inflammatory disease state. ([0093, 0151, 0158] determining patient disease state and modulate stimulation signal and dose). It would have been obvious to a person of ordinary skill in the art at the time of invention to modify Thakur to monitor the various inflammatory disease activity data based on time-dependent factors, in view of Levine; the motivation for doing so is to monitor inflammation with respect to time in a patient and to determine dose (time) interval specific for that patient (Levine: [0104]).
Allowable Subject Matter
Claim 45 is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHIRLEY X JIAN whose telephone number is (571)270-7374. The examiner can normally be reached M-F 8:00-4:00.
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/SHIRLEY X JIAN/ Primary Examiner, Art Unit 3792
September 3, 2026
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