DETAILED ACTION
This office action is responsive to original claims filed on 02/01/2025. Presently, Claims 1 - 20 remain 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 .
Claim Objections
Claim 8 is objected to because of the following informalities:
Claim 8, Line 8, recites “7H.5z”, which should be changed to “7.5 Hz”.
Appropriate correction is required.
Applicant is advised that should Claim 2 be found allowable, Claim 9 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof, that should Claim 5 be found allowable, Claims 12 and 18 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof, and that should Claim 7 be found allowable, Claims 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 15-17 recite “… method of claim 13”, which misses antecedent basis for the limitation of “method” in Claim 13 or Claim 1. For present purposes of examination, the recited phrase is interpreted as “… method of claim 14”.
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.
Claims 1-7 and 9-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mishelevich et al (US 20170246481 A1; hereafter Mishelevich), in view of Lerman et al (US 20190030334 A1; hereafter Lerman).
With regard to Claim 1, Mishelevich discloses a transcranial focused ultrasound neurostimulation device (Mishelevich, Abstract; “… methods and systems for non-invasive neuromodulation using ultrasound for evaluating the feasibility of neuromodulation treatment using non-ultrasound/ultrasound modalities …”; Page 6; “Part II: Neuromodulation of Deep-Brain Targets Using Focused Ultrasound”), comprising:
at least one ultrasound transducer (Mishelevich, Para 0068; “Ultrasound transducers are positioned by spinning them around the head …”); and
a controller (Mishelevich, Para 0068; “… under control of direction of the energy emission, control of intensity for up-regulation or down-regulation, and control of frequency and phase for focusing on neural targets.” Para 0094; “an ultrasound controller generating varying the phase/intensity relationships to steer and shape the ultrasound beam …”) that directs the ultrasound transducer to deliver low intensity focused ultrasound (LIFU) (Mishelevich, Para 0272; “The present invention further includes control of focus, direction, intensity … of the ultrasound energy …”; Para 0496; “The power applied will determine whether the ultrasound is high intensity or low intensity (or medium intensity) and because the sound transducers are custom, any mechanical or electrical changes can be made, if and as required.” These disclosures show that the reference can choose and use low-intensity ultrasound) at a target brain region (Mishelevich, Para 0036; “… the method comprising modulating the activity of one target brain region …”) in order to treat a neurological condition (Mishelevich, Para 0037; “… the disorder treated is selected from the group consisting of: … depression …”), where the LIFU has:
a fundamental frequency between 250-750 KHz (Mishelevich, Para 0073; “In some variations, the acoustic ultrasound frequency is in the range of 0.3 MHz to 0.8 MHz.” In this disclosure, 0.3-0.8 MHz corresponds to 300-800 KHz);
a spatial peak, temporal average intensity between 0.5 and 5 W/cm2 (Mishelevich, Para 0074; “In some variations, the power applied is selected from group consisting of … greater than 180 mW/cm2 but less than that causing tissue damage.”); and
a pulse repetition frequency between 2.5Hz and 7.5Hz (Mishelevich, Para 0279; “a pulse duration from approximately 0.1 ms to 20 ms and a repetition frequency of approximately 2 Hz or higher to up regulate the target region”); and
where the LIFU is delivered in a theta burst pattern (Mishelevich, Para 0159; “Theta-burst neuromodulation is one form of applicable burst-mode pattern.”) over at least one session lasting between 1 minutes and 30 minutes (Mishelevich, Para 0597; “… the session length could be longer or shorter than 50 minutes.”; Para 0621; “Examples of session types include periodic sessions, such as a single session of length in the range from 15 to 60 minutes …”), during which a plurality of neurostimulation trains are delivered (Mishelevich, Para 0570; “In FIG. 35A, Pulse trains 3500 are composed of one or a plurality of sets of pulses (e.g., singletons, pairs, triplets, etc.) … with the trains separated by inter-pulse-train intervals 3515.”), each neurostimulation train separated by an interval of no neurostimulation lasting between 0 and 480 seconds (Mishelevich, Para 0584; “As an example, the bursts could be six second long and repeated every nine seconds”. Here in the disclosed example, between two adjacent bursts, there is an interval of 3 seconds), where each train comprises LIFU bursts lasting between 10 and 30 milliseconds which are repeated every 100 to 300 milliseconds (Mishelevich, Para 0164; “… if the duty cycle were 10% the duration of the pulses would be 10 ms.”).
Mishelevich does not clearly and explicitly disclose each train of bursts lasting for a total of 40 to 120 seconds, and where a duty cycle for each train is between 5% and 15%.
Lerman in the same field of endeavor discloses each train of bursts lasting for a total of 40 to 120 seconds (Lerman, Para 0154; “For example, an ultrasonic treatment may include at least one activation period in the range of 2 seconds to 5 minutes. The ultrasonic treatment may, for example, include a plurality of activation periods, each of the plurality of activation periods followed by a deactivation period.” Here the disclosed “activation period” corresponds to a train of LIFU bursts of Application), and where a duty cycle for each train is between 5% and 15% (Lerman, Para 0154; “In an example, the duty cycle of the ultrasonic pulses may, for example, be adjustable from 10% to 90%”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Mishelevich, as suggested by Lerman, in order to limit duration of a train of ultrasonic stimulation to less than few minutes and duty cycle of each train to 10%. One of ordinary skill in the art would have been motivated to make the modification for the benefit of limiting the overall energy applied to tissue to a low and thus safe level so that potential tissue damage can be avoided.
With regard to Claim 2, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the neurological condition is major depressive disorder (Mishelevich, Para 0037; “… the disorder treated is selected from the group consisting of: … depression …”).
With regard to Claim 3, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is the left dorsolateral prefrontal cortex (Mishelevich, Para 0036; “… the target brain regions are selected from the group consisting of … any of the subregions of the Pre-Frontal Cortex”).
With regard to Claim 4, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is the striatum (Mishelevich, Para 0036; “… the target brain regions are selected from the group consisting of … Nucleus Accumbens …”. Nucleus Accumbens is a part of the striatum).
With regard to Claim 5, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is deeper than 4cm into the brain (Mishelevich, Para 0036 list multiple target brain regions that are typically deeper than 4 cm in the brain, such as cerebellum and brainstem).
With regard to Claim 6, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein each session is separated by an interval of between 25 and 120 minutes of no neurostimulation (Mishelevich, Para 0176; “Other inter-session times such as 15 minutes to three hours … are applicable”).
With regard to Claim 7, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein:
the fundamental frequency is 500 kHz (Mishelevich, Para 0073; “In some variations, the acoustic ultrasound frequency is in the range of 0.3 MHz to 0.8 MHz.” In this disclosure, 0.3-0.8 MHz corresponds to 300-800 KHz)
the spatial peak, temporal average intensity is 1 W/cm2 (Mishelevich, Para 0074; “In some variations, the power applied is selected from group consisting of … greater than 180 mW/cm2 but less than that causing tissue damage.”);
the pulse repetition frequency is 5Hz (Mishelevich, Para 0279; “a pulse duration from approximately 0.1 ms to 20 ms and a repetition frequency of approximately 2 Hz or higher to up regulate the target region”);
the at least one session lasts 20 minutes (Mishelevich, Para 0597; “… the session length could be longer or shorter than 50 minutes.”; Para 0621; “Examples of session types include periodic sessions, such as a single session of length in the range from 15 to 60 minutes …”); and
each neurostimulation train is separated by an interval of no neurostimulation lasting 0-320 seconds (Mishelevich, Para 0584; “As an example, the bursts could be six second long and repeated every nine seconds”. Here in the disclosed example, between two adjacent bursts, there is an interval of 3 seconds), where each train comprises LIFU bursts 20 milliseconds which are repeated every 200 milliseconds (Mishelevich, Para 0164; “… if the duty cycle were 10% the duration of the pulses would be 10 ms.”).
Mishelevich and Lerman as discussed above do not disclose each train of bursts lasting for a total of 80 seconds, and the duty cycle for each train being 10%.
Lerman further discloses each train of bursts lasting for a total of 80 seconds (Lerman, Para 0154; “For example, an ultrasonic treatment may include at least one activation period in the range of 2 seconds to 5 minutes. The ultrasonic treatment may, for example, include a plurality of activation periods, each of the plurality of activation periods followed by a deactivation period.” Here the disclosed “activation period” corresponds to a train of LIFU bursts of Application) and the duty cycle for each train being 10% (Lerman, Para 0154; “In an example, the duty cycle of the ultrasonic pulses may, for example, be adjustable from 10% to 90%”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Mishelevich and Lerman, as further suggested by Lerman, in order to limit duration of a train of ultrasonic stimulation to less than few minutes and duty cycle of each train to 10%. One of ordinary skill in the art would have been motivated to make the modification for the benefit of limiting the overall energy applied to tissue to a low and thus safe level so that potential tissue damage can be avoided.
With regard to Claim 9, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the neurological condition is major depressive disorder (Mishelevich, Para 0037; “… the disorder treated is selected from the group consisting of: … depression …”).
With regard to Claim 10, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is the subgenual anterior cingulate cortex (Mishelevich, Table 11, lists “anterior cingulate cortex” as one of primary targets for condition of depression).
With regard to Claim 11, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is the amygdala (Mishelevich, Table 11, lists “amygdala” as one of other targets for condition of depression).
With regard to Claim 12, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is deeper than 4cm into the brain (Mishelevich, Para 0036 list multiple target brain regions that are typically deeper than 4 cm in the brain, such as cerebellum and brainstem).
With regard to Claim 13, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein each session is separated by an interval of between 10 and 50 minutes of no neurostimulation (Mishelevich, Para 0176; “Other inter-session times such as 15 minutes to three hours … are applicable”).
With regard to Claim 14, Mishelevich discloses a method for transcranial focused ultrasound neurostimulation (Mishelevich, Abstract; “… methods and systems for non-invasive neuromodulation using ultrasound for evaluating the feasibility of neuromodulation treatment using non-ultrasound/ultrasound modalities …”; Page 6; “Part II: Neuromodulation of Deep-Brain Targets Using Focused Ultrasound”), comprising:
targeting a brain region (Mishelevich, Para 0036; “… the method comprising modulating the activity of one target brain region …”) for neurostimulation in order to treat a neurological condition (Mishelevich, Para 0037; “… the disorder treated is selected from the group consisting of: … depression …”);
positioning at least one ultrasound transducer (Mishelevich, Para 0068; “Ultrasound transducers are positioned by spinning them around the head …”) to be focused at the target brain region; and
directing low intensity focused ultrasound (LIFU) at the target brain region (Mishelevich, Para 0272; “The present invention further includes control of focus, direction, intensity … of the ultrasound energy …”; Para 0496; “The power applied will determine whether the ultrasound is high intensity or low intensity (or medium intensity) and because the sound transducers are custom, any mechanical or electrical changes can be made, if and as required.” These disclosures show that the reference can choose and use low-intensity ultrasound), where the LIFU has:
a fundamental frequency between 250-750 KHz (Mishelevich, Para 0073; “In some variations, the acoustic ultrasound frequency is in the range of 0.3 MHz to 0.8 MHz.” In this disclosure, 0.3-0.8 MHz corresponds to 300-800 KHz);
a spatial peak, temporal average intensity between 0.5 and 5 W/cm2 (Mishelevich, Para 0074; “In some variations, the power applied is selected from group consisting of … greater than 180 mW/cm2 but less than that causing tissue damage.”); and
a pulse repetition frequency between 2.5Hz and 7.5Hz (Mishelevich, Para 0279; “a pulse duration from approximately 0.1 ms to 20 ms and a repetition frequency of approximately 2 Hz or higher to up regulate the target region”);
where the LIFU is delivered in a theta burst pattern (Mishelevich, Para 0159; “Theta-burst neuromodulation is one form of applicable burst-mode pattern.”) over at least one session lasting between 1 minutes and 30 minutes (Mishelevich, Para 0597; “… the session length could be longer or shorter than 50 minutes.”; Para 0621; “Examples of session types include periodic sessions, such as a single session of length in the range from 15 to 60 minutes …”), during which a plurality of neurostimulation trains are delivered (Mishelevich, Para 0570; “In FIG. 35A, Pulse trains 3500 are composed of one or a plurality of sets of pulses (e.g., singletons, pairs, triplets, etc.) … with the trains separated by inter-pulse-train intervals 3515.”), each neurostimulation train separated by an interval of no neurostimulation lasting between 0 and 480 seconds (Mishelevich, Para 0584; “As an example, the bursts could be six second long and repeated every nine seconds”. Here in the disclosed example, between two adjacent bursts, there is an interval of 3 seconds), where each train comprises LIFU bursts lasting between 10 and 30 milliseconds which are repeated every 100 to 300 milliseconds (Mishelevich, Para 0164; “… if the duty cycle were 10% the duration of the pulses would be 10 ms.”).
Mishelevich does not clearly and explicitly disclose each train of bursts lasting for a total of 40 to 120 seconds, and where a duty cycle for each train is between 5% and 15%.
Lerman in the same field of endeavor discloses each train of bursts lasting for a total of 40 to 120 seconds (Lerman, Para 0154; “For example, an ultrasonic treatment may include at least one activation period in the range of 2 seconds to 5 minutes. The ultrasonic treatment may, for example, include a plurality of activation periods, each of the plurality of activation periods followed by a deactivation period.” Here the disclosed “activation period” corresponds to a train of LIFU bursts of Application), and where a duty cycle for each train is between 5% and 15% (Lerman, Para 0154; “In an example, the duty cycle of the ultrasonic pulses may, for example, be adjustable from 10% to 90%”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Mishelevich, as suggested by Lerman, in order to limit duration of a train of ultrasonic stimulation to less than few minutes and duty cycle of each train to 10%. One of ordinary skill in the art would have been motivated to make the modification for the benefit of limiting the overall energy applied to tissue to a low and thus safe level so that potential tissue damage can be avoided.
With regard to Claim 15, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation method of Claim 14. Mishelevich further discloses wherein the neurological condition is major depressive disorder (Mishelevich, Para 0037; “… the disorder treated is selected from the group consisting of: … depression …”).
With regard to Claim 16, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation method of Claim 14. Mishelevich further discloses wherein the target brain region is the left dorsolateral prefrontal cortex (Mishelevich, Para 0036; “… the target brain regions are selected from the group consisting of … any of the subregions of the Pre-Frontal Cortex”).
With regard to Claim 17, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation method of Claim 14. Mishelevich further discloses wherein the target brain region is the striatum (Mishelevich, Para 0036; “… the target brain regions are selected from the group consisting of … Nucleus Accumbens …”. Nucleus Accumbens is a part of the striatum).
With regard to Claim 18, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein the target brain region is deeper than 4cm into the brain (Mishelevich, Para 0036 list multiple target brain regions that are typically deeper than 4 cm in the brain, such as cerebellum and brainstem).
With regard to Claim 19, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein each session is separated by an interval of between 25 and 120 minutes of no neurostimulation (Mishelevich, Para 0176; “Other inter-session times such as 15 minutes to three hours … are applicable”).
With regard to Claim 20, Mishelevich and Lerman disclose the transcranial focused ultrasound neurostimulation device of Claim 1. Mishelevich further discloses wherein:
the fundamental frequency is 500 kHz (Mishelevich, Para 0073; “In some variations, the acoustic ultrasound frequency is in the range of 0.3 MHz to 0.8 MHz.” In this disclosure, 0.3-0.8 MHz corresponds to 300-800 KHz)
the spatial peak, temporal average intensity is 1 W/cm2 (Mishelevich, Para 0074; “In some variations, the power applied is selected from group consisting of … greater than 180 mW/cm2 but less than that causing tissue damage.”);
the pulse repetition frequency is 5Hz (Mishelevich, Para 0279; “a pulse duration from approximately 0.1 ms to 20 ms and a repetition frequency of approximately 2 Hz or higher to up regulate the target region”);
the at least one session lasts 20 minutes (Mishelevich, Para 0597; “… the session length could be longer or shorter than 50 minutes.”; Para 0621; “Examples of session types include periodic sessions, such as a single session of length in the range from 15 to 60 minutes …”); and
each neurostimulation train is separated by an interval of no neurostimulation lasting 0-320 seconds (Mishelevich, Para 0584; “As an example, the bursts could be six second long and repeated every nine seconds”. Here in the disclosed example, between two adjacent bursts, there is an interval of 3 seconds), where each train comprises LIFU bursts 20 milliseconds which are repeated every 200 milliseconds (Mishelevich, Para 0164; “… if the duty cycle were 10% the duration of the pulses would be 10 ms.”).
Mishelevich and Lerman as discussed above do not disclose each train of bursts lasting for a total of 80 seconds, and the duty cycle for each train being 10%.
Lerman further discloses each train of bursts lasting for a total of 80 seconds (Lerman, Para 0154; “For example, an ultrasonic treatment may include at least one activation period in the range of 2 seconds to 5 minutes. The ultrasonic treatment may, for example, include a plurality of activation periods, each of the plurality of activation periods followed by a deactivation period.” Here the disclosed “activation period” corresponds to a train of LIFU bursts of Application) and the duty cycle for each train being 10% (Lerman, Para 0154; “In an example, the duty cycle of the ultrasonic pulses may, for example, be adjustable from 10% to 90%”). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Mishelevich and Lerman, as further suggested by Lerman, in order to limit duration of a train of ultrasonic stimulation to less than few minutes and duty cycle of each train to 10%. One of ordinary skill in the art would have been motivated to make the modification for the benefit of limiting the overall energy applied to tissue to a low and thus safe level so that potential tissue damage can be avoided.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Mishelevich et al (US 20170246481 A1; hereafter Mishelevich), in view of Mishelevich et al (US 20140194726 A1; hereafter Mishelevich 2014).
With regard to Claim 8, Mishelevich discloses a transcranial focused ultrasound neurostimulation device (Mishelevich, Abstract; “… methods and systems for non-invasive neuromodulation using ultrasound for evaluating the feasibility of neuromodulation treatment using non-ultrasound/ultrasound modalities …”; Page 6; “Part II: Neuromodulation of Deep-Brain Targets Using Focused Ultrasound”), comprising:
at least one ultrasound transducer (Mishelevich, Para 0068; “Ultrasound transducers are positioned by spinning them around the head …”); and
a controller (Mishelevich, Para 0068; “… under control of direction of the energy emission, control of intensity for up-regulation or down-regulation, and control of frequency and phase for focusing on neural targets.” Para 0094; “an ultrasound controller generating varying the phase/intensity relationships to steer and shape the ultrasound beam …”) that directs the ultrasound transducer to deliver low intensity focused ultrasound (LIFU) (Mishelevich, Para 0272; “The present invention further includes control of focus, direction, intensity … of the ultrasound energy …”; Para 0496; “The power applied will determine whether the ultrasound is high intensity or low intensity (or medium intensity) and because the sound transducers are custom, any mechanical or electrical changes can be made, if and as required.” These disclosures show that the reference can choose and use low-intensity ultrasound) at a target brain region (Mishelevich, Para 0036; “… the method comprising modulating the activity of one target brain region …”) in order to treat a neurological condition (Mishelevich, Para 0037; “… the disorder treated is selected from the group consisting of: … depression …”), where the LIFU has:
a fundamental frequency between 325-925 KHz (Mishelevich, Para 0073; “In some variations, the acoustic ultrasound frequency is in the range of 0.3 MHz to 0.8 MHz.” In this disclosure, 0.3-0.8 MHz corresponds to 300-800 KHz);
a spatial peak, temporal average intensity between 0.5 and 5 W/cm2 (Mishelevich, Para 0074; “In some variations, the power applied is selected from group consisting of … greater than 180 mW/cm2 but less than that causing tissue damage.”); and
a pulse repetition frequency between 2.5Hz and 7.5Hz (Mishelevich, Para 0279; “a pulse duration from approximately 0.1 ms to 20 ms and a repetition frequency of approximately 2 Hz or higher to up regulate the target region”); and
where the LIFU is delivered in a continuous theta burst pattern (Mishelevich, Para 0570; “If the set of inter-pulse intervals 3530 is of length zero, then the train is continuous. … Sample patterns include … Theta-Burst Stimulation …”) over at least one session lasting between 2 minutes and 10 minutes (Mishelevich, Para 0597; “… the session length could be longer or shorter than 50 minutes.”; Para 0621; “Examples of session types include periodic sessions, such as a single session of length in the range from 15 to 60 minutes …”), during which a plurality of neurostimulation trains are delivered (Mishelevich, Para 0570; “In FIG. 35A, Pulse trains 3500 are composed of one or a plurality of sets of pulses (e.g., singletons, pairs, triplets, etc.) … with the trains separated by inter-pulse-train intervals 3515.”), each neurostimulation train separated by an interval of no neurostimulation lasting between 0 and 480 seconds (Mishelevich, Para 0584; “As an example, the bursts could be six second long and repeated every nine seconds”. Here in the disclosed example, between two adjacent bursts, there is an interval of 3 seconds), where each train comprises LIFU bursts lasting between 10 and 30 milliseconds which are repeated every 100 to 300 milliseconds (Mishelevich, Para 0164; “… if the duty cycle were 10% the duration of the pulses would be 10 ms.”).
Mishelevich does not clearly and explicitly disclose each train of bursts having a duty cycle between 1.25% and 3.75%.
Mishelevich 2014 in the same field of endeavor discloses each train of bursts having a duty cycle between 1.25% and 3.75% (Mishelevich 2014, Para 0054; “The duty cycle can be less than 50%, and can be within a range from about 0.1% to about 50%, for example within a range from about 1% to 25%.”It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Mishelevich, as suggested by Mishelevich 2014, in order to use a low duty cycle. One of ordinary skill in the art would have been motivated to make the modification for the benefit of reducing the overall energy applied to the brain tissue so as to avoid tissue injury due to heating (Mishelevich 2014, Para 0057; “one potential disadvantage of transcranial ultrasound neuromodulation protocols with CW pulses is that the temporal average intensity can be higher which may cause painful thermal stimuli on the scalp or skull and may also induce heating and thus damage in brain tissue.”).
Conclusion
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/L.Z./Examiner, Art Unit 3798
/PASCAL M BUI PHO/Supervisory Patent Examiner, Art Unit 3798