DETAILED ACTION
Notice of 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 arguments filed 01/10/2026 have been fully considered but they are not persuasive.
1) Page 8 of the Applicant Remarks states, “Yoo does not disclose or suggest selecting and modifying sonication parameters to elicit a known or desired change in neural activity”. The Examiner respectfully disagrees because the desired change in neural activity is the “stimulation or suppression” as discussed in the Abstract.
2) Page 8 of the Applicant Remarks states, “Etkins discloses, at a high-level of generality, methods for detecting changes in blood flow associated with changes in neural activity following presentation of a stimulus using non-invasive stimulation including focused ultrasound stimulation”. In response, the Examiner respectfully submits that the “desired change in neural activity” is also recited at a high-level of generality. Thus, the account of blood flow caused by focused ultrasound neuro-stimulation as taught by Etkins would have been found to be well in line with the ultrasound neuro-stimulation taught by Lee since it is known in the art that non-spontaneous blood flow follows presentation of a focused ultrasound stimulus at the focal site. It would have been obvious to one of ordinary skill in the art to apply the known effect of neuro-stimulation as taught by Etkins to the neuro-stimulation of Lee.
3) Page 10 of the Applicant Remarks argues against the propriety of Stubbeman. In response, the Examiner respectfully submits that Stubbeman appropriately combines with Lee, Yoo, and Etkins since they are in the same field of endeavor directed to ultrasound stimulation, and because Stubbeman teaches utilizing the well-known feedback mechanism to make adjustments to system parameters. The details directed to adjusting ultrasound parameters for the express purposes recited in the claimed invention are arrived at within the combination of citations.
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.
Claim(s) 14 is/are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Regarding claim 14, “the target objective” lacks proper antecedent basis in the claim since it has been struck out in claim 1.
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.
Claim(s) 1-3, 16, 21, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Transcranial focused ultrasound stimulation of human primary visual cortex” by W. Lee et al. Scientific Reports. pp. 1-12, 2016 (hereinafter as Lee, of record) in view of “Focused ultrasound modulates region-specific brain activity” by S. Yoo et al. NeuroImage. 56, pp.1267-1275, 2011 (hereinafter as Yoo, of record) in view of Etkin (US 2018/0236225, of record) in view of Stubbeman (US 2016/0008620, of record).
Regarding claims 1 and 16, Lee discloses a system and method for stimulating neural activity in at least one target region (Title: “stimulation of human primary visual cortex”) associated with at least one brain disease or disorder using focused ultrasound (p.8: “results suggest…may lead to many applications, for example, assessment of the regional brain functions and their functional connectivity to different parts of the brain”…FUS may also be able to provide a new mode of neurotherapeutics”), the system comprising: an ultrasound transducer comprising a plurality of transducer elements (p.2: “FUS transducer”; Fig. 1 shows that the transducer is connected to a coupling hydrogel and housing, which are considered “transducer elements”); and a controller configured to: (a) transmit a first sequence of ultrasound pulses to the target region (p.2: “pulsing scheme”); (b) cause measurements of a changes corresponding to a change in the neural activity at the target region resulting from the ultrasound pulses (p.2: “event-related fMRI was simultaneously conducted…to capture the neural activity associated with (1) FUS”). Lee does not explicitly disclose (c) based at least in part on the measurements, adjust a frequency, a phase, an amplitude, or an activation duration associated with at least one of the transducer elements to cause a change corresponding to a desired change in the neural activity at the target region. However, Yoo teaches that a range of sonication parameters are considered to assess potential modulatory effects and adjusting for effective sonication parameters, to at least, minimize the potential effects of tissue damage (p.1269: “Test of FUS parameters for modulatory effects”; “modified using different tone burst durations, pulse repetition frequencies, acoustic intensities”). Also, Yoo teaches that only a limited number of sonication parameters resulted in observable activity (pp.1270-1271), which suggests that parameters are adjusted in response to monitoring. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the adjustment of parameters as performed by Yoo to the sonication of Lee, as to attain optimal parameters. Neither Lee nor Yoo explicitly disclose that the recited change is one of blood-flow. However, Etkins teaches transcranial focused ultrasound stimulation that induces a blood flow change and that these changes are associated with neural activity in the brain ([0036]). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the blood flow modulation of Etkin to the system of Lee and Yoo, as to provide a manner of manipulating neural activity. While neither Lee, Yoo, nor Etkins explicitly disclose real-time measurements and a controller configured to compare the measured changes in blood flow against the desired change in the neural activity at the target region and repeat steps (a)-(c) until the desired change in neural activity is satisfied, Stubbeman teaches real-time measurement that are used in a feedback mechanism for the adjustment and optimization of stimulation parameters which may include ultrasound stimulation ([0094], [0095]). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the feedback mechanism of Stubbeman to the system of Lee, Yoo, and Etkins, as to provide a conventional optimization loop.
Regarding claims 2 and 3, Lee discloses a monitoring system for measuring the changes in blood flow at the target region wherein the system uses fMRI (p.2: “event-related fMRI was simultaneously conducted”).
Regarding claims 21 and 22, Lee does not explicitly disclose that the monitoring system is utilized in conjunction with a blood oxygen level-dependent (BOLD) contrast agent for detecting changes in the blood flow at the target region in real time. And that measured changes in blood flow in the target region result in a BOLD signal change detected by the monitoring system. However, Yoo teaches measuring a BOLD signal to indicate presence of cortical excitation (p.1269). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the BOLD detection of Yoo, as to provide a robust manner of detecting an MR signal.
Claim(s) 5, 8, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Transcranial focused ultrasound stimulation of human primary visual cortex” by W. Lee et al. Scientific Reports. pp. 1-12, 2016 (hereinafter as Lee, of record) in view of “Focused ultrasound modulates region-specific brain activity” by S. Yoo et al. NeuroImage. 56, pp.1267-1275, 2011 (hereinafter as Yoo, of record) in view of Etkin (US 2018/0236225, of record) in view of Stubbeman (US 2016/0008620, of record), as applied to claims 1 and 16 above, in view of Levy (US 2015/0359603, of record).
Regarding claims 5 and 18, neither Lee, Yoo, Etkin, nor Stubbeman explicitly disclose that the controller is further configured to: cause the sequence of ultrasound pulses to create a focus at the target region; cause measurements of a temperature at the focus; and based at least in part on the measured temperature, adjust a parameter value associated with at least one of the transducer elements to avoid damage to the target region. However, Levy teaches MR temperature monitoring of a region undergoing focused ultrasound, wherein the acoustic intensity of the ultrasound beam may be increased or cut off depending on the measured temperature ([0007]). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the temperature monitoring and control of Levy to the ultrasound modulation of Lee, Yoo, Etkins, and Stubbeman as to provide appropriate safety measures when applying focused ultrasound radiation.
Regarding claim 8, neither Lee, Yoo, Etkin, nor Stubbeman explicitly disclose that the parameter value comprises an amplitude. However, Levy teaches MR temperature monitoring of a region undergoing focused ultrasound, wherein the acoustic intensity of the ultrasound beam may be increased or cut off depending on the measured temperature ([0007]). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the temperature monitoring and control of Levy to the ultrasound modulation of Lee, Yoo, Etkins, and Stubbeman, as to provide appropriate safety measures when applying focused ultrasound radiation.
Claim(s) 6 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Transcranial focused ultrasound stimulation of human primary visual cortex” by W. Lee et al. Scientific Reports. pp. 1-12, 2016 (hereinafter as Lee, of record) in view of “Focused ultrasound modulates region-specific brain activity” by S. Yoo et al. NeuroImage. 56, pp.1267-1275, 2011 (hereinafter as Yoo, of record) in view of Etkin (US 2018/0236225, of record) in view of Stubbeman (US 2016/0008620, of record) in view of Levy (US 2015/0359603, of record), as applied to claim 5 above, in view of Friedman (US 6613005, of record).
Regarding claim 6, neither Lee, Yoo, Etkins, Stubbeman, nor Levy explicitly disclose that the controller is further configured to cause steering of the focus at a plurality of sub-regions of the target region. However, Friedman teaches a focused ultrasound transducer system with a plurality of steerable array elements (1:66-67…2:1-27, “steering”). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the steering of Friedman to the transducer system of Lee, Yoo, Etkins, Stubbeman, and Levy, as to provide control over the placement of an ultrasound focal point.
Regarding claim 7, neither Lee, Yoo, Etkins, Stubbeman, nor Levy explicitly disclose that the controller is further configured to cause sequential steering of the focus at a plurality of target regions, each associated with a brain disease or disorder, different target regions associated with different brain diseases or disorders. However, Friedman teaches a focused ultrasound transducer system with a plurality of subarrays (fig. 1a, 4:39-52) and one having ordinary skill in the art would have found it obvious that the steerable sub-arrays of Friedman would be able to sequentially and or simultaneously irradiate multiple targets. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the sub-arrays of Friedman to the transducer system of Lee, Yoo, Etkins, Stubbeman, and Levy, as to provide individualized control and steering of elements in an ultrasound transducer.
Claim(s) 9-13, 19, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Transcranial focused ultrasound stimulation of human primary visual cortex” by W. Lee et al. Scientific Reports. pp. 1-12, 2016 (hereinafter as Lee, of record) in view of “Focused ultrasound modulates region-specific brain activity” by S. Yoo et al. NeuroImage. 56, pp.1267-1275, 2011 (hereinafter as Yoo, of record) in view of Etkin (US 2018/0236225, of record) in view of Stubbeman (US 2016/0008620, of record), as applied to claims 1 and 16 above, in view of Friedman (US 6613005, of record).
Regarding claim 9, neither Lee, Yoo, Etkins, nor Stubbeman, explicitly disclose a plurality of sub-arrays, each sub-array comprising a plurality of transducer elements. However, Friedman teaches a focused ultrasound transducer system with a plurality of subarrays (fig. 1a, 4:39-52). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the sub-arrays of Friedman to the transducer system of Lee, Yoo, Etkins, and Stubbeman as to provide individualized control and steering of elements in an ultrasound transducer.
Regarding claims 10-13, 19, and 20 neither Lee, Yoo, Etkins, nor Stubbeman, explicitly disclose the recited activation and order of transducer sub-arrays to irradiate between first and second target regions. However, Friedman teaches a focused ultrasound transducer system with a plurality of subarrays (fig. 1a, 4:39-52) and one having ordinary skill in the art would have found it obvious that the steerable sub-arrays of Friedman would be able to sequentially and or simultaneously irradiate multiple targets. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to apply the sub-arrays of Friedman to the transducer system of Lee, Yoo, Etkins, and Stubbeman, as to provide individualized control and steering of elements in an ultrasound transducer.
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 extension fee 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 date of this final action.
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/JASON M IP/Primary Examiner, Art Unit 3793