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 Arguments
Applicant’s argument on Page 6 regarding the objection to the specification has been fully considered. The objection to the specification is withdrawn in view of the argument.
Applicant does not explicitly address the objections to Claims 4, 13, 16-18, 26, and 29-31, however, the objections to Claims 4, 13, 16-18, 26, and 29-31 are withdrawn in view of the amendments.
Applicant does not explicitly address the interpretation of Claim 8, however, the interpretation of Claim 8 is withdrawn in view of the amendments.
Applicant does not explicitly address the rejection of Claim 8 under 35 U.S.C. 112(a) and (b), however, the rejection of Claim 8 under 35 U.S.C. 112(a) and (b) is withdrawn in view of the amendments.
Applicant’s argument on Pages 6-7 regarding the rejection of Claims 1 and 19 under 35 U.S.C. 102(a)(1) as being anticipated by Silberg has been fully considered but is not persuasive under new grounds of rejection as below.
Regarding the rejection of all remaining corresponding claims, applicant’s argument submitted on Pages 6-7 relies on the supposed deficiencies with respect to the rejection of parent Claims 1 and 19. Applicant’s argument is moot for the same reasons detailed above.
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.
Claims 1-3, 6-16, 18-29, and 31-32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O’Reilly et al. (“Blood-Brain Barrier: Real-time […]”).
Regarding Claim 1, O’Reilly teaches a system for temporarily altering a tissue characteristic at a target region, (Abstract, Materials and Methods “Transcranial focused ultrasound (551.5 kHz, 10-msec bursts, 2-Hz pulse repetition frequency, 2 minute sonication) in conjunction with circulating microbubbles was applied in 86 locations in 27 rats to disrupt the BBB.”), the system comprising:
1) an ultrasound transducer (Materials and Methods “The ultrasound was generated by using a spherically focused transducer con structed in house (focal number = 0.8, external diameter = 75 mm, internal diameter = 20 mm), matched to 551.5 kHz by using an external matching circuit. The transducer had a focal depth of 60 mm and a −6-dB focal zone width of approximately 3 mm and a length of approximately 20 mm.”); and
2) a controller configured to:
(a) cause the transducer to transmit acoustic energy to the target region at a transmission frequency (Abstract, Materials and Methods “Transcranial focused ultrasound (551.5 kHz, 10-msec bursts, 2-Hz pulse repetition frequency, 2 minute sonication) in conjunction with circulating microbubbles was applied in 86 locations in 27 rats to disrupt the BBB.”);
(b) acquire a cumulative harmonic response from at least the target region, wherein the cumulative harmonic response is a sum or integral of signal components of acoustic responses of the transmitted acoustic energy (Abstract, Materials and Methods “Pressures were increased incrementally after each burst until ultraharmonic emissions were detected,” where the buildup to ultraharmonic are understood to be a type of cumulative harmonic response.); and
(c) operate the transducer based at least in part on the acquired cumulative harmonic response (Fig. 1b, Abstract, Materials and Methods “Pressures were increased incrementally after each burst until ultraharmonic emissions were detected, at which point the pressure was reduced to a percentage of the pressure required to induce the ultraharmonics and was maintained for the remainder of the sonication,” Introduction “We propose that ultraharmonic emissions may be used as the basis for a feedback control algorithm to safely modulate pressures during treatment,” and Benchtop Experiments, Ultrasound control algorithm development “A control algorithm was implemented to adjust the driving voltage for an ultrasound transducer driven in burst mode after each ultrasound burst.”).
Regarding Claim 2, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein the cumulative harmonic response is acquired at one or more positive integer multiples of the transmission frequency (Discussion “Changes in the harmonic emissions, as suggested by McDannold et al (16) and Tung et al (17), were observed during this study.”).
Regarding Claim 3, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein the cumulative harmonic response is acquired at one or more positive off-integer multiples of the transmission frequency (Discussion “In the current study, we demonstrated that acoustic emissions from micro bubbles could be controlled in real time to optimize treatment pressures used for disrupting the BBB. In our animal model, we were able to drive microbubbles to ultraharmonic oscillations without causing damage in the brain. […] Furthermore, driving microbubbles until they exhibit ultraharmonic behavior may be a sufficient end point if moderate disruption levels are desired.”).
Regarding Claim 6, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein the controller is further configured to compute the cumulative harmonic response by integrating a received acoustic signal from at least the target region over a predetermined time period (Benchtop Experiments “The presence of the 1.5 and 2.5 f0 ultraharmonics were evaluated by integrating over the spectrum around those frequencies (6180 Hz) and by comparing the resulting values to their respective values at time t = 0 seconds, when no microbubbles would be in circulation.”).
Regarding Claim 7, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein the controller is further configured to cause generation of microbubbles in the target region (In Vivo Experiments “All sonications consisted of 10-msec bursts at a pulse repetition frequency of 2 Hz for 2 minutes. The microbubble contrast agent (0.02 mL/kg, Definity; Lantheus Medical Imaging, North Billerica, Mass) was diluted 1:50 in normal saline and injected through a tail vein catheter by using an automated syringe pump (Chemyx NanoJetXF MR Imaging Compatible Syringe Pump; Chemyx, Stafford, Tex). Microbubbles were infused over 1 minute starting simultaneously with the start of sonication.”).
Regarding Claim 8, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein the controller is further configured to cause microbubbles to be introduced into at least one of the target region or its surrounding regions (In Vivo Experiments “All sonications consisted of 10-msec bursts at a pulse repetition frequency of 2 Hz for 2 minutes. The microbubble contrast agent (0.02 mL/kg, Definity; Lantheus Medical Imaging, North Billerica, Mass) was diluted 1:50 in normal saline and injected through a tail vein catheter by using an automated syringe pump (Chemyx NanoJetXF MR Imaging Compatible Syringe Pump; Chemyx, Stafford, Tex). Microbubbles were infused over 1 minute starting simultaneously with the start of sonication.”).
Regarding Claim 9, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein temporarily altering a tissue characteristic comprises disrupting target tissue (Assessment “Sonication locations were selected from T2 weighted images obtained with a 1.5-T MR imaging system (Signa 1.5 T; GE Healthcare, Milwaukee, Wis). T1 weighted images enhanced with 0.2 mL/kg contrast material (gadodiamide, Omniscan; GE Healthcare) were used to confirm BBB disruption.”).
Regarding Claim 10, O’Reilly teaches all limitations of Claim 9, as discussed above. Furthermore, O’Reilly teaches wherein the target tissue is the blood-brain barrier (BBB) and the disruption alters a permeability of the BBB (Introduction “Focused ultrasound disruption of the blood-brain barrier (BBB) by using circulating microbubbles offers potential to improve the treatment of brain and central nervous system disorders. The BBB prevents passage of molecules greater than approximately 500 Da from the vasculature into the brain tissue, greatly reducing the effectiveness of many types of therapeutic agents. Focused ultrasound disruption of the BBB has been successfully used to deliver amyloid b antibodies, large-molecule immunotherapy agents for cancer, and other large molecules.”).
Regarding Claim 11, O’Reilly teaches all limitations of Claim 1, as discussed above. Furthermore, O’Reilly teaches wherein the controller is configured to control a parameter of the transmitted acoustic energy based at least in part on spectral components of the cumulative harmonic response (Abstract, Materials and Methods “Pressures were increased incrementally after each burst until ultraharmonic emissions were detected, at which point the pressure was reduced to a percentage of the pressure required to induce the ultraharmonics and was maintained for the remainder of the sonication,” Introduction “We propose that ultraharmonic emissions may be used as the basis for a feedback control algorithm to safely modulate pressures during treatment,” and Benchtop Experiments, Ultrasound control algorithm development “A control algorithm was implemented to adjust the driving voltage for an ultrasound transducer driven in burst mode after each ultrasound burst.”).
Regarding Claim 12, O’Reilly teaches all limitations of Claim 11, as discussed above. Furthermore, O’Reilly teaches wherein the parameter is at least one of power, frequency, pulse duration or pulse repetition frequency (Benchtop Experiments, Ultrasound control algorithm development “A control algorithm was implemented to adjust the driving voltage for an ultrasound transducer driven in burst mode after each ultrasound burst.” Where voltage is directly related to power.).
Regarding Claim 13, O’Reilly teaches all limitations of Claim 11, as discussed above. Furthermore, O’Reilly teaches wherein the controller is configured to control the parameter of the transmitted acoustic energy based at least in part on cumulative harmonic response data from within a defined interval (Benchtop Experiments “The control algorithm allowed the applied pressure during each burst to increase, starting from an estimated in situ pressure of 0.09 MPa. The in situ pressure was incremented in steps of 3 kPa. […] When ultraharmonic emissions were detected, the program would respond by reducing the applied pressure to a predetermined target level (either 75%, 50%, 25%, or 0% of the pressure at which ultraharmonics were detected).”).
Regarding Claim 14, O’Reilly teaches all limitations of Claim 13, as discussed above. Furthermore, O’Reilly teaches wherein the defined interval is within a current sonication (Fig. 1b and Abstract, Purpose “real-time modulation of treatment pressures on the basis of acoustic emissions from the exposed microbubbles.”).
Regarding Claim 15, O’Reilly teaches all limitations of Claim 13, as discussed above. Furthermore, O’Reilly teaches wherein the defined interval includes data from at least one previous sonication (Fig. 1b, “FLAG = Boolean flag to indicate if ultraharmonics have been previously detected” (emphasis added)).
Regarding Claim 16, O’Reilly teaches all limitations of Claim 11, as discussed above. Furthermore, O’Reilly teaches wherein the controller is configured to control the parameter to select for a harmonic frequency band while maintaining at least one of cumulative broadband emission or cumulative ultra-harmonics below corresponding safety thresholds (Discussion “we were able to drive microbubbles to ultraharmonic oscillations without causing damage in the brain. Results with a 75% emissions target level suggest that repeated exposures at such pressure levels may be damaging to brain tissue, causing tissue vacuolation in the sonicated region. Furthermore, driving microbubbles until they exhibit ultraharmonic behavior may be a sufficient end point if moderate disruption levels are desired. Disruption at levels of 50% and lower were safely performed, with few cases of edema as indicated by T2-weighted MR images. Target levels above 50% should be avoided, as they may result in damage.”).
Regarding Claim 18, O’Reilly teaches all limitations of Claim 11, as discussed above. Furthermore, O’Reilly teaches wherein the controller in configured to control the parameter to increase a ratio between (i) at least one of cumulative harmonics or cumulative ultra-harmonics and (ii) cumulative broadband emission (Benchtop Experiments “When ultraharmonic emissions were detected, the program would respond by reducing the applied pressure to a predetermined target level (either 75%, 50%, 25%, or 0% of the pressure at which ultraharmonics were detected). The optimal target level for consistent and safe BBB disruption was investigated in vivo after benchtop testing of the algorithm. The remainder of the sonication would be performed at the target level. If ultraharmonics were detected again during the remainder of the sonication, another drop in applied pressure would occur.”).
Regarding Claim 19, O’Reilly teaches a method of applying ultrasound sonication from a transducer to temporarily alter a tissue characteristic at a target region, (Abstract, Materials and Methods “Transcranial focused ultrasound (551.5 kHz, 10-msec bursts, 2-Hz pulse repetition frequency, 2 minute sonication) in conjunction with circulating microbubbles was applied in 86 locations in 27 rats to disrupt the BBB.”), the method comprising:
(a) causing an ultrasound transducer to transmit acoustic energy to the target region at a transmission frequency (Abstract, Materials and Methods “Transcranial focused ultrasound (551.5 kHz, 10-msec bursts, 2-Hz pulse repetition frequency, 2 minute sonication) in conjunction with circulating microbubbles was applied in 86 locations in 27 rats to disrupt the BBB.”);
(b) acquiring a cumulative harmonic response from at least the target region, wherein the cumulative harmonic response is a sum or integral of signal components of acoustic responses of the transmitted acoustic energy (Abstract, Materials and Methods “Pressures were increased incrementally after each burst until ultraharmonic emissions were detected,” where the buildup to ultraharmonics are understood to be a type of cumulative harmonic response.); and
(c) operating the transducer based at least in part on the acquired cumulative harmonic response (Fig. 1b, Abstract, Materials and Methods “Pressures were increased incrementally after each burst until ultraharmonic emissions were detected, at which point the pressure was reduced to a percentage of the pressure required to induce the ultraharmonics and was maintained for the remainder of the sonication,” Introduction “We propose that ultraharmonic emissions may be used as the basis for a feedback control algorithm to safely modulate pressures during treatment,” and Benchtop Experiments, Ultrasound control algorithm development “A control algorithm was implemented to adjust the driving voltage for an ultrasound transducer driven in burst mode after each ultrasound burst.”).
Regarding Claim 20, O’Reilly teaches all limitations of Claim 19, as discussed above. Furthermore, O’Reilly teaches wherein the cumulative harmonic response is acquired at one or more positive integer multiples of the transmission frequency (Discussion “Changes in the harmonic emissions, as suggested by McDannold et al (16) and Tung et al (17), were observed during this study.”).
Regarding Claim 21, O’Reilly teaches all limitations of Claim 19, as discussed above. Furthermore, O’Reilly teaches wherein the cumulative harmonic response is acquired at one or more positive off-integer multiples of the transmission frequency (Discussion “In the current study, we demonstrated that acoustic emissions from micro bubbles could be controlled in real time to optimize treatment pressures used for disrupting the BBB. In our animal model, we were able to drive microbubbles to ultraharmonic oscillations without causing damage in the brain. […] Furthermore, driving microbubbles until they exhibit ultraharmonic behavior may be a sufficient end point if moderate disruption levels are desired.”).
Regarding Claim 22, O’Reilly teaches all limitations of Claim 19, as discussed above. Furthermore, O’Reilly teaches wherein the cumulative harmonic response is acquired by integrating a received acoustic signal from at least the target region over a predetermined time period (Benchtop Experiments “The presence of the 1.5 and 2.5 f0 ultraharmonics were evaluated by integrating over the spectrum around those frequencies (6180 Hz) and by comparing the resulting values to their respective values at time t = 0 seconds, when no microbubbles would be in circulation.”).
Regarding Claim 23, O’Reilly teaches all limitations of Claim 19, as discussed above. Furthermore, O’Reilly teaches generating microbubbles in the target region (In Vivo Experiments “All sonications consisted of 10-msec bursts at a pulse repetition frequency of 2 Hz for 2 minutes. The microbubble contrast agent (0.02 mL/kg, Definity; Lantheus Medical Imaging, North Billerica, Mass) was diluted 1:50 in normal saline and injected through a tail vein catheter by using an automated syringe pump (Chemyx NanoJetXF MR Imaging Compatible Syringe Pump; Chemyx, Stafford, Tex). Microbubbles were infused over 1 minute starting simultaneously with the start of sonication.”).
Regarding Claim 24, O’Reilly teaches all limitations of Claim 19, as discussed above. Furthermore, O’Reilly teaches controlling a parameter of the transmitted acoustic energy based at least in part on spectral components of the cumulative harmonic response (Abstract, Materials and Methods “Pressures were increased incrementally after each burst until ultraharmonic emissions were detected, at which point the pressure was reduced to a percentage of the pressure required to induce the ultraharmonics and was maintained for the remainder of the sonication,” Introduction “We propose that ultraharmonic emissions may be used as the basis for a feedback control algorithm to safely modulate pressures during treatment,” and Benchtop Experiments, Ultrasound control algorithm development “A control algorithm was implemented to adjust the driving voltage for an ultrasound transducer driven in burst mode after each ultrasound burst.”).
Regarding Claim 25, O’Reilly teaches all limitations of Claim 24, as discussed above. Furthermore, O’Reilly teaches wherein the parameter is at least one of power, frequency, pulse duration or pulse repetition frequency (Benchtop Experiments, Ultrasound control algorithm development “A control algorithm was implemented to adjust the driving voltage for an ultrasound transducer driven in burst mode after each ultrasound burst.” Where voltage is directly related to power.).
Regarding Claim 26, O’Reilly teaches all limitations of Claim 24, as discussed above. Furthermore, O’Reilly teaches controlling the parameter of the transmitted acoustic energy based at least in part on cumulative harmonic response data from within a defined interval (Benchtop Experiments “The control algorithm allowed the applied pressure during each burst to increase, starting from an estimated in situ pressure of 0.09 MPa. The in situ pressure was incremented in steps of 3 kPa. […] When ultraharmonic emissions were detected, the program would respond by reducing the applied pressure to a predetermined target level (either 75%, 50%, 25%, or 0% of the pressure at which ultraharmonics were detected).”).
Regarding Claim 27, O’Reilly teaches all limitations of Claim 26, as discussed above. Furthermore, O’Reilly teaches wherein the defined interval is within a current sonication (Fig. 1b and Abstract, Purpose “real-time modulation of treatment pressures on the basis of acoustic emissions from the exposed microbubbles.”).
Regarding Claim 28, O’Reilly teaches all limitations of Claim 27, as discussed above. Furthermore, O’Reilly teaches wherein the defined interval includes data from at least one previous sonication (Fig. 1b, “FLAG = Boolean flag to indicate if ultraharmonics have been previously detected” (emphasis added)).
Regarding Claim 29, O’Reilly teaches all limitations of Claim 24, as discussed above. Furthermore, O’Reilly teaches controlling the parameter to select for a harmonic frequency band while maintaining at least one of cumulative broadband emission or cumulative ultra-harmonics below corresponding safety thresholds (Discussion “we were able to drive microbubbles to ultraharmonic oscillations without causing damage in the brain. Results with a 75% emissions target level suggest that repeated exposures at such pressure levels may be damaging to brain tissue, causing tissue vacuolation in the sonicated region. Furthermore, driving microbubbles until they exhibit ultraharmonic behavior may be a sufficient end point if moderate disruption levels are desired. Disruption at levels of 50% and lower were safely performed, with few cases of edema as indicated by T2-weighted MR images. Target levels above 50% should be avoided, as they may result in damage.”).
Regarding Claim 31, O’Reilly teaches all limitations of Claim 24, as discussed above. Furthermore, O’Reilly teaches controlling the parameter to increase a ratio between (i) at least one of cumulative harmonics or cumulative ultra-harmonics and (ii) cumulative broadband emission (Benchtop Experiments “When ultraharmonic emissions were detected, the program would respond by reducing the applied pressure to a predetermined target level (either 75%, 50%, 25%, or 0% of the pressure at which ultraharmonics were detected). The optimal target level for consistent and safe BBB disruption was investigated in vivo after benchtop testing of the algorithm. The remainder of the sonication would be performed at the target level. If ultraharmonics were detected again during the remainder of the sonication, another drop in applied pressure would occur.”).
Regarding Claim 32, O’Reilly teaches all limitations of Claim 19, as discussed above. Furthermore, O’Reilly teaches introducing microbubbles into at least one of the target region or its surrounding regions (In Vivo Experiments “All sonications consisted of 10-msec bursts at a pulse repetition frequency of 2 Hz for 2 minutes. The microbubble contrast agent (0.02 mL/kg, Definity; Lantheus Medical Imaging, North Billerica, Mass) was diluted 1:50 in normal saline and injected through a tail vein catheter by using an automated syringe pump (Chemyx NanoJetXF MR Imaging Compatible Syringe Pump; Chemyx, Stafford, Tex). Microbubbles were infused over 1 minute starting simultaneously with the start of sonication.”).
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 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over O’Reilly et al. (“Blood-Brain Barrier: Real-time […]”) in view of Konofagou et al. (US 20140114216).
Regarding Claim 4, O’Reilly teaches all limitations of Claim 1, as discussed above. However, O’Reilly does not explicitly teach a filter for filtering acoustic signals measured from at least one of the target region or its surrounding regions to obtain the cumulative harmonic response.
In an analogous open a tissue barrier in primates field of endeavor, Konofagou teaches a system for temporarily altering a tissue characteristic at a target region, (Abstract “Systems and methods for cavitation-guided opening of a targeted region of tissue within a primate skull are provided.”), comprising a filter for filtering acoustic signals measured from at least one of the target region or its surrounding regions to obtain the cumulative harmonic response ([0078] “the harmonic, ultraharmonic, and the broadband signals in the spectra for each pulse can be separately filtered.”).
It would have been obvious to one of ordinary skill in the art at the time of applicant’s filing to modify the teachings of O’Reilly with the filter of Konofagou because the modification of including a filtering component results in clarity of the received signal and isolates the target components of the signal.
Regarding Claim 5, the modified system of O’Reilly teaches all limitations of Claim 4, as discussed above. Furthermore, Konofagou teaches wherein the filter is configured to select at least one of a harmonic, an ultraharmonic or a sub-harmonic response to the transmitted acoustic energy ([0078] “The cavitation level-time derivative of the cavitation dose can be quantified, and as such the harmonic, ultraharmonic, and the broadband signals in the spectra for each pulse can be separately filtered. The stable cavitation level based on harmonics only (dSCD.sub.h) can be represented as the root-mean squared amplitude of the harmonic signals in a single pulse, with the harmonic signals represented as the maxima in the 20-kHz (-6-dB width) range around the harmonic frequency (0.5f*n) in the frequency spectrum. The stable cavitation level based on ultraharmonics only (dSCD.sub.u) can be represented as the root-mean squared amplitude of the ultraharmonic signals in a single pulse, with the ultraharmonic signals represented as the maxima in 20 kHz around the ultraharmonic frequency (0.5f*n+0.250 in the frequency spectrum. The inertial cavitation level (dICD) can be represented as the root-mean squared amplitude of the frequency spectrum after excluding the harmonics (360 kHz around the harmonic frequency) and ultraharmonics (100 kHz around the ultraharmonic frequency).”).
It would have been obvious to one of ordinary skill in the art at the time of applicant’s filing to modify the teachings of O’Reilly with the filter of Konofagou for the same reasons as Claim 4 above.
Claims 17 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over O’Reilly et al. (“Blood-Brain Barrier: Real-time […]”) in view of Geva et al. (WO 2016151595).
Regarding Claim 17, O’Reilly teaches all limitations of Claim 11, as discussed above. However, O’Reilly does not explicitly teach wherein the controller is configured to control the parameter to increase a ratio between cumulative harmonics and cumulative ultra-harmonics.
In an analogous ultrasonic drug delivery field of endeavor, Geva teaches a system for temporarily altering a tissue characteristic at a target region, ([0059] “The disclosed device, kit and method are based on the application of ultrasound to the bladder tissue and/or to a therapeutic agent adjacent to the bladder internal surface. Ultrasound may increase permeability through thermal and/or cavitation mechanisms.”), wherein the controller is configured to control the parameter to increase a ratio between cumulative harmonics and cumulative ultra-harmonics ([00165] “when sub-harmonics, high harmonics and ultraharmonics frequences are detected, control unit 997 computes a control signal to maintain the acoustic energy at constant level and continue treatment for a certain time duration. Alternatively, control unit 997 computes a control signal to continue to increase the acoustic energy until levels of the subharmonic or high harmonics, or their ratio, achieve predefined values.”).
It would have been obvious to one of ordinary skill in the art at the time of applicant’s filing to modify the teachings of O’Reilly with the controller functions of Geva because the combination improves signal to noise ratio while also ensuring optimal power consumption.
Regarding Claim 30, O’Reilly teaches all limitations of Claim 24, as discussed above. However, O’Reilly does not explicitly teach controlling the parameter to increase a ratio between cumulative harmonics and cumulative ultra-harmonics.
In an analogous ultrasonic drug delivery field of endeavor, Geva teaches a method of applying ultrasound sonication from a transducer to temporarily alter a tissue characteristic at a target region, ([0059] “The disclosed device, kit and method are based on the application of ultrasound to the bladder tissue and/or to a therapeutic agent adjacent to the bladder internal surface. Ultrasound may increase permeability through thermal and/or cavitation mechanisms.”), the method comprising controlling the parameter to increase a ratio between cumulative harmonics and cumulative ultra-harmonics ([00165] “when sub-harmonics, high harmonics and ultraharmonics frequences are detected, control unit 997 computes a control signal to maintain the acoustic energy at constant level and continue treatment for a certain time duration. Alternatively, control unit 997 computes a control signal to continue to increase the acoustic energy until levels of the subharmonic or high harmonics, or their ratio, achieve predefined values.”).
It would have been obvious to one of ordinary skill in the art at the time of applicant’s filing to modify the teachings of O’Reilly with the controller functions of Geva because the combination improves signal to noise ratio while also ensuring optimal power consumption.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA CHRISTINA TALTY whose telephone number is (571)272-8022. The examiner can normally be reached M-Th 8:30-5:30 EST.
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/MARIA CHRISTINA TALTY/Examiner, Art Unit 3797
/MICHAEL J CAREY/Supervisory Patent Examiner, Art Unit 3795
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