DETAILED ACTION
This office action is in response to the communication received on March 2, 2026 concerning application No. 17/794,098 filed on July 20, 2022.
Claims 1, 4, 6-9, 12-19 and 37 are currently pending.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 2, 2026 has been entered.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1 and 37 regarding the newly filed claim amendments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 4, 6-8, 12-19, and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable by Puleo et al. (US 20200094079, hereinafter Puleo) in view of Tikhomirova et al. (RU 2651116C1, hereinafter Tikhomirova) and Puleo et al. (US 20200054228, hereinafter Puleo 2).
Regarding claim 1, Puleo teaches a method for ultrasound stimulation of a subject (Abstract discloses applying a protocol having one or more treatment parameters to a target, where the treatment protocol includes ultrasound energy treatments), comprising:
applying responsive ultrasound stimulation to a subject to treat an inflammatory condition of the subject ([0098] “in step 84, neuromodulation treatment based on the determined treatment parameters (e.g., the treatment period, the frequency, and/or the rest period) in step 82 is applied to the subject to achieve a desired physiological outcome”, the part of the subject the protocol is applied is considered the target. As discussed above the abstract discloses applying the protocol includes applying ultrasound energy treatments, which are considered the ultrasound stimulation. Also see [0068]. [0112] discloses the treatment is used for reducing inflammation) by:
applying ultrasound stimulation to a spleen of the subject based on initial ultrasound stimulation parameters ([0098] “in step 84, neuromodulation treatment based on the determined treatment parameters (e.g., the treatment period, the frequency, and/or the rest period) in step 82 is applied to the subject to achieve a desired physiological outcome”, [0086] and fig. 3 disclose the stimulation is being applied to the spleen. As discussed above the abstract discloses applying the protocol includes applying ultrasound energy treatments, which are considered the ultrasound stimulation. Also see [0068]);
assessing the ultrasound stimulation by receiving feedback data between 3.5 days up to an including 14 days after the stimulation has been applied ([0098] discloses after the neuromodulation treatment is complete, “the effect of the neuromodulation treatments on the expression level of particular genes in the subject may be assessed in step 86”, the received effect is considered the received feedback. [0097] further discloses the treatment period of a subject is one week (7 days), therefore by receiving the effect of neuromodulation after the treatment period is over, feedback is being received at 7 days after the first stimulation has been applied. Additionally, [0095] discloses the assessing of the effects of neuromodulation is used as feedback),
wherein the feedback data are indicative of biomarkers being modulated over between 3.5 days up to and including 14 days by the applied ultrasound stimulation ([0100] discloses “one or more assessments of a change in concentration in one or more molecules of interest (e.g., glucose, neurotransmitters, neuropeptides, cholinesterases, or cytokines) may be performed in step 86”, in order to assess the change in concentration the feedback must include information about whether the molecules of interest (biomarkers) have been modulated (changed) over the period of treatment (7 days). Therefore the feedback data is indicative of biomarkers being modulated over 7 days by the applied ultrasound stimulation);
wherein the feedback data includes at least one of interleukin (IL) IL-6, IL-10, interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a ([0113] discloses the concentration of the cytokines includes the concentration of interleukin 6).
adjusting the initial ultrasound stimulation parameters based upon the received feedback data received between 3.5 days up to and including 14 days after the stimulation to create adjusted ultrasound stimulation parameters ([0101]-[0102] disclose in step 88 a determination of whether the effect of the neuromodulation treatment on the level of expression of particular genes of interest is desired is performed. Based on the determination “the method 80 may proceed to step 92, and the treatment parameters of the neuromodulation treatment may be modified based on the assessed effect on the expression level of the genes in the subject”); and
applying ultrasound stimulation to the spleen of the subject based on the adjusted ultrasound stimulation parameters, wherein the ultrasound stimulation of the spleen is configured to treat the inflammatory condition of the subject ([0106] “in step 94, neuromodulation treatment based on the modified treatment parameters…in step 92 is applied to the subject to achieve the desired physiological outcome and desired level of gene expression in the subject”. [0062] “neuromodulation may be used for the treatment…and the control of systemic inflammation”. [0086] and fig. 3 disclose the stimulation is being applied to the spleen).
Puleo does not specifically teach the feedback data includes a ratio of two or more biomarkers including interleukin (IL) IL-6, IL-10, interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a and adjusting the initial ultrasound stimulation parameters based upon the feedback data comprising the ratio of two or more biomarkers.
However,
Tikhomirova in a similar field of endeavor teaches feedback data includes a ratio of two or more biomarkers including interleukin (IL) IL-6, IL-10, interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a (pg. 2, paras. 4-5 and 8 disclose determining the concentration of IL-6 and IL-10 both before and after exercise and comparing their ratios) and adjusting the initial treatment parameters based upon the feedback data comprising the ratio of two or more biomarkers (pg. 2, paras. 4-5 and 8 discloses determining the effectiveness and recommending a daily exercise (treatment) based on the determined ratio in order to improve the users condition).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known technique of having the feedback data include a ratio of two or more biomarkers including interleukin (IL) IL-6, IL-10, interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a and adjusting the initial treatment parameters based upon the feedback data comprising the ratio of two or more biomarkers of Tikhomirova to the method of Puleo to allow for the predictable results of slowing down the inflammatory changes in the patient.
Puleo in view of Tikhomirova does not specifically teach the inflammatory condition of the subject being treated by applying ultrasound stimulation to the spleen is rheumatoid arthritis.
Puleo 2 teaches the inflammatory condition of the subject being treated by applying ultrasound stimulation to the spleen is rheumatoid arthritis ([0176] and claims 37, 50, and 51 disclose applying ultrasound stimulation to the spleen in order to treat rheumatoid arthritis).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known technique of applying ultrasound stimulation to the spleen in order to treat rheumatoid arthritis of Puleo 2 to the method of Puleo in view of Tikhomirova to allow for the predictable results of increase the number of disorders the process treats, thereby making the process more versatile and have a wider application.
Regarding claim 4, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches the feedback data is received between 3.5 days up to and including 7 days after the stimulation ([0098] discloses after the neuromodulation treatment is complete, “the effect of the neuromodulation treatments on the expression level of particular genes in the subject may be assessed in step 86”, the received effect is considered the received feedback. [0097] further discloses the treatment period of a subject is one week (7 days), therefore by receiving the effect of neuromodulation after the treatment period is over, feedback is being received at 7 days after the first stimulation has been applied. Additionally, [0095] discloses the assessing of the effects of neuromodulation is used as feedback).
Regarding claim 6, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Tikhomirova further teaches the ratio of biomarkers includes a ratio of at least one of IL-6 to IL-10, TNF-a to ESR, or IL-6 to TNF-a (pg. 2, paras. 4-5 and 8 disclose the ratio includes a ratio of IL-6 to IL-10).
Regarding claim 7, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches the feedback data is received by at least one of a sensor or a blood draw ([0081] discloses “the system 10 includes an assessment device 20, the assessment device 20 may provide feedback to the controller 16”, the assessment device 20 is considered a sensor).
Regarding claim 8, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 7, as set forth above. Puleo further teaches the sensor includes a cytokine sensor ([0070] discloses the assessment device 20 is configured to assess the changes in concentration of certain molecules. [0100] discloses the molecules being assessed include cytokines, meaning the device 20 is a cytokine sensor).
Regarding claim 12, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches the initial ultrasound stimulation parameters includes at least one of stimulation in the range of greater than or equal to 500 kHz to less than or equal to 1 MHz; pressures in a range of greater than or equal to 100kPa to less than or equal to 500 kPa; or duty cycles of greater than or equal to 16% to less than or equal to 50% ([0077] “the energy application device is an ultrasound transducer…peak positive pressure are in the range of…0.1MPa to 7MPa (peak pressure)” which encompasses 100kPa to 500kPa).
Regarding claim 13, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches the adjusted ultrasound stimulation parameters includes at least one of stimulation in the range of greater than or equal to 100 kHz to less than or equal to 7 MHz; pressures in a range of greater than or equal to 25kPa to less than or equal to l0MPa; stimulation on time of greater than or equal to 50 microseconds to less than or equal to 2 seconds; or stimulation off time of greater than or equal to 1 ms to less than or equal to 10 s ([0077] “the energy application device is an ultrasound transducer…peak positive pressure are in the range of…0.1MPa to 7MPa (peak pressure)”, meaning the adjusted pressure could not be less than 01.Mpa (100kPa) or greater than 7MPa. Therefore the adjusted pressure would be in the range of 25kPa to 10MPa).
Regarding claim 14, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo 2 further teaches the initial ultrasound stimulation parameters or the adjusted ultrasound stimulation parameters includes stimulation of 1MHz ([0124] discloses the ultrasound stimulation is at 1.1 MHz. also see [0159]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the stimulation parameters of Puleo in view of Tikhomirova and Puleo 2 to include stimulation of 1MHz in order to achieve the target physiological response from the subject, thereby increasing the likelihood of a successful treatment.
Regarding claim 15, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches at least one of the initial ultrasound stimulation parameters or the adjusted ultrasound stimulation parameters includes a pressure of 350kPa ([0077] “the energy application device is an ultrasound transducer…peak positive pressure are in the range of…0.1MPa to 7MPa (peak pressure)” which includes 350kPa which is equivalent to 0.35Mpa).
Regarding claim 16, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches adjusting the initial ultrasound stimulation parameters includes stopping stimulation when the feedback data indicates at least one of the biomarkers has reached a plateau ([0082] discloses after a period of time the applications applied to the treatment protocol stop having an effect on the glucose concentrations, meaning the biomarker the treatment was affecting has plateaued and is no longer being affected by the treatments. When this occurs the recovery period (stopping stimulation) is implemented until the patient is once again responsive to the treatment protocol).
Regarding claim 17, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 16, as set forth above. Puleo further teaches the plateau occurs at greater than or equal to 3.5 days and less than or equal to 14 days after initial ultrasound stimulation ([0097] discloses the treatment period includes five, days, one week, one and a half weeks, two weeks).
Regarding claim 18, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 1, as set forth above. Puleo further teaches the adjusting the initial stimulation parameter includes adjusting at least one of a duty cycle, a duration, a number of bursts, a length of a burst, a frequency, a pressure, or a beamforming target of the ultrasound stimulation ([0106] “in step 94, neuromodulation treatment based on the modified treatment parameters (e.g., the treatment period, the treatment frequency, and/or the duration of the recovery period) in step 92 is applied to the subject”, the treatment period and treatment frequency correspond to at least a duration and a number of bursts. [0074] further discloses the treatment duration and application frequency will change).
Regarding claim 19, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 18, as set forth above. Puleo further teaches adjusting the duration of the ultrasound stimulation includes applying the ultrasound stimulation of up to and including 30 minutes ([0073] discloses delivering the treatment (stimulation) for thirty minutes).
Regarding claim 37, Puleo teaches a method for ultrasound stimulation of a subject (Abstract discloses applying a protocol having one or more treatment parameters to a target, where the treatment protocol includes ultrasound energy treatments), comprising:
applying responsive ultrasound stimulation to a subject to treat an inflammatory condition of the subject ([0098] “in step 84, neuromodulation treatment based on the determined treatment parameters (e.g., the treatment period, the frequency, and/or the rest period) in step 82 is applied to the subject to achieve a desired physiological outcome”, the part of the subject the protocol is applied is considered the target. As discussed above the abstract discloses applying the protocol includes applying ultrasound energy treatments, which are considered the ultrasound stimulation. Also see [0068]. [0112] discloses the treatment is used for reducing inflammation) by:
determining ultrasound stimulation parameters ([0097] “one or more neuromodulation treatment parameters in the treatment protocol may be selected or determined in step 82”); and
applying ultrasound stimulation to a spleen of the subject with the ultrasound stimulation parameters to treat the inflammatory condition of the subject ([0098] “in step 84, neuromodulation treatment based on the determined treatment parameters (e.g., the treatment period, the frequency, and/or the rest period) in step 82 is applied to the subject to achieve a desired physiological outcome”, [0086] and fig. 3 discloses the stimulation is applied to the spleen. As discussed above the abstract discloses applying the protocol includes applying ultrasound energy treatments, which are considered the ultrasound stimulation. [0062] “neuromodulation may be used for the treatment…and the control of systemic inflammation”), wherein at least two biomarkers are modulated in the treatment ([0096] discloses the assessment of whether the patient is responsive to the treatment includes expression for a group (two or more) of genes (biomarkers), meaning at least two biomarkers are modulated. Also see [0113]);
assessing the ultrasound stimulation by receiving feedback data after the stimulation has been applied ([0098] discloses after the neuromodulation treatment is complete, “the effect of the neuromodulation treatments on the expression level of particular genes in the subject may be assessed in step 86”, the received effect is considered the received feedback. [0095] discloses the assessing of the effects of neuromodulation is used as feedback),
wherein the feedback data is received between 3.5 days up to an including 14 days after the stimulation ([0097] discloses the treatment period of a subject is one week (7 days), therefore by receiving the effect of neuromodulation after the treatment period is over, feedback is being received at 7 days after the first stimulation has been applied),
adjusting the ultrasound stimulation parameters based upon the two biomarkers to create adjusted ultrasound stimulation parameters ([0102] “step 92, and the treatment parameters of the neuromodulation treatment may be modified based on the assessed effect on the expression level of the genes in the subject”); and
applying ultrasound stimulation to the spleen of the subject based on the adjusted ultrasound stimulation parameters to treat an inflammatory condition of the subject ([0106] “in step 94, neuromodulation treatment based on the modified treatment parameters…in step 92 is applied to the subject to achieve the desired physiological outcome and desired level of gene expression in the subject”. [0062] “neuromodulation may be used for the treatment…and the control of systemic inflammation”. [0086] and fig. 3 discloses the stimulation is applied to the spleen).
Puleo does not specifically teach the feedback data includes a ratio of the two biomarkers including interleukin (IL) IL-6, IL-10, IL-1B, interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a and adjusting the ultrasound stimulation parameters based upon the ratio of the two biomarkers to create adjusted ultrasound simulation parameters.
However,
Tikhomirova in a similar field of endeavor teaches feedback data includes a ratio of two or more biomarkers including interleukin (IL) IL-6, IL-10, IL-1B, interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a (pg. 2, paras. 4-5 and 8 disclose determining the concentration of IL-6 and IL-10 both before and after exercise and comparing their ratios) and adjusting the treatment parameters based upon the ratio of the two biomarkers to create adjusted treatment parameters (pg. 2, paras. 4-5 and 8 discloses determining the effectiveness and recommending a daily exercise (treatment) based on the determined ratio in order to improve the users condition).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known technique of having the feedback data include a ratio of two or more biomarkers including interleukin (IL) IL-6, IL-10, IL-1B interferon gamma (IFN-γ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or tumor necrosis factor (TNF) TNF-a and adjusting the treatment parameters based upon the ratio of the two biomarkers to create adjusted treatment parameters of Tikhomirova to the method of Puleo to allow for the predictable results of slowing down the inflammatory changes in the patient.
Puleo in view of Tikhomirova does not specifically teach the inflammatory condition of the subject being treated by applying ultrasound stimulation to the spleen is rheumatoid arthritis.
Puleo 2 teaches the inflammatory condition of the subject being treated by applying ultrasound stimulation to the spleen is rheumatoid arthritis ([0176] and claims 37, 50, and 51 disclose applying ultrasound stimulation to the spleen in order to treat rheumatoid arthritis).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known technique of applying ultrasound stimulation to the spleen in order to treat rheumatoid arthritis of Puleo 2 to the method of Puleo in view of Tikhomirova to allow for the predictable results of increase the number of disorders the process treats, thereby making the process more versatile and have a wider application.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Puleo in view of Tikhomirova and Puleo 2 as applied to claim 8 above, and further in view of Alford et al. (US 20170007853, as cited in applicant’s 11/28/2022 IDS, hereinafter Alford).
Regarding claim 9, Puleo in view of Tikhomirova and Puleo 2 teaches the method of claim 8, as set forth above. Puleo in view of Tikhomirova and Puleo 2 does not specifically teach the cytokine sensor is implanted in the subject.
However,
Alford in a similar field of endeavor teaches a cytokine sensor is implanted in the subject ([0038] discloses the sensors are used to detect one or more cytokines and [0036] discloses the sensors 18 are implanted in the patient 14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the cytokine sensor disclosed by Puleo in view of Tikhomirova and Puleo 2 to have the cytokine sensor be implanted in the subject in order to get continuous feedback from the sensor without having to draw the patient’s blood, thereby increasing the efficiency of the biomarker determination.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Carmena et al. (US 20190321640) discloses applying ultrasound stimulation to a spleen in order to treat rheumatoid arthritis.
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/ANDREW W BEGEMAN/Examiner, Art Unit 3798