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 Amendment
Applicant’s amendment filed 1/20/2026 is acknowledged.
Claims 1, 2, 5-7, and 11-22 remain pending in the current application.
Claim Objections
Claim 19 objected to because of the following informalities: the limitation ‘a frequency of 0.4 MHz (MHz) does not require the repetition of MHz in parenthesis. Appropriate correction is required.
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.
Claim 1 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.
The term “about” in claim 1 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For the purposes of this office action any pulse width will be deemed analogous to the claimed pulse width.
Dependent claims are also rejected by virtue of their dependency.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The limitation of a focused ultrasound is already presented in independent claim 1. Furthermore, in light of the applicant’s amendments, the limitation the ‘neuromodulation treatment’ in claim 2 now lacks antecedent basis. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
(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.
Claim(s) 1, 2, 5, 6, and 11-22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Etkin (US 20180236255 A1).
Regarding claim 1, Etkin teaches a method of improving a cognitive disorder in a patient suffering therefrom comprising:
diagnosing the patient with the cognitive disorder; applying a focused ultrasound to a pulvinar nucleus of the patient ([0004] In a first aspect, there is provided a method of treating a brain dysfunction in a subject in need thereof. The method includes administering a first plurality of non-invasive stimulations to a first plurality of different brain regions of the subject, measuring a first plurality of responses to the first plurality of non-invasive stimulations, determining a dysfunctional brain network circuit in the subject based on the measuring of the first plurality of responses, and administering a second plurality of non-invasive stimulations, based on the determining of the dysfunctional brain network circuit, to a second plurality of different brain regions of the subject, thereby treating the brain dysfunction in the subject; [0022] The term “brain region(s)” is used according to its plain and ordinary meaning and refers to a brain anatomical region following standard neuroanatomy hierarchies (e.g. a functional, connective or developmental region). Exemplary brain regions include, but are not limited to…pulvinar; [0029] transcranial focused ultrasound stimulation, as used herein refers to a non-invasive form of brain stimulation involving the delivery of acoustic pressure waves to specific, highly localize, and potentially deep areas of the brain, to influence (e.g., stimulate) neural activity in the targeted brain tissue. fUS may be used to target regions of neural tissue on the order of a few millimeters in size)
the focused ultrasound signal having a power of less than 150 watts (W) ([0067] magnitude of the response is measured in microvolts; [0069] magnitude that falls within a range of about 10 to about 1000 pA/m)
a pulse width of between about 10 milliseconds (ms) and 200 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
a frequency of 0.2 megahertz (MHz) to 0.3 MHz ([0025] “high frequency” protocol, involving stimulation at >5 Hz (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300 Hz or higher))
and a repetition time of 5 seconds on and 10 seconds off ([0126] Paired pulse TMS can be administered at a time offset of about … 300 msecs, or more)
and improving the cognitive disorder in the patient ([0004] treating the brain dysfunction in the subject)
Regarding claim 2, Etkin teaches focused ultrasound ([0029] transcranial focused ultrasound stimulation, as used herein refers to a non-invasive form of brain stimulation involving the delivery of acoustic pressure waves to specific, highly localize, and potentially deep areas of the brain, to influence (e.g., stimulate) neural activity in the targeted brain tissue. fUS may be used to target regions of neural tissue on the order of a few millimeters in size).
Regarding claim 5, Etkin teaches wherein improving the cognitive disorder comprises improving a visual attention function, a visio-spatial orientation, or both of the patient ([0021] The terms “brain dysfunction”, “brain abnormality” or “brain disorder” may refer to any type or degree of impairment in brain function that can affect, for example, perception)
Regarding claim 6, Etkin teaches applying a neuromodulation treatment to a nucleus basalis of maynert, a ventral capsule/ventral striatum, a nucleus accumbens, a hippocampus, a thalamic intralaminar nucleus, a subthalamic nucleus, a sub genual cingulate, a fornix, a medial or inferior temporal lobe, a temporal pole, an angular gyrus, a superior or medial frontal lobe, a superior parietal lobe, a precuneus, a supramarginal gyrus, a calcarine sulcus, or combinations thereof ([0022] The term “brain region(s)” is used according to its plain and ordinary meaning and refers to a brain anatomical region following standard neuroanatomy hierarchies (e.g. a functional, connective or developmental region). Exemplary brain regions include, but are not limited to…subthalamic nucleus…hippocampus…frontal lobe…parietal lobe…ventral striatum…precuneus…nucleus accumbens…temporal lobe)
Regarding claim 11, Etkin teaches acquiring a clinical parameter associated with the patient after diagnosing the patient with the cognitive disorder and applying or adjusting the focused ultrasound signal to the pulvinar nucleus of the patient based on the clinical parameter ([0116] Optimization of parameters such as coil angle, pulse width, pulse height, pulse shape etc. based on their evocation of a brain response that is being targeted for remediation).
Regarding claim 12, Etkin teaches applying another focused ultrasound signal to the pulvinar nucleus if the patient's clinical parameter has not improved ([0117] Selection of the best repetitive stimulation protocol that best alters brain function in the direction of normalization of the observed abnormality (including frequency, intensity and pattern of stimulation))
Regarding claim 13, Etkin teaches the clinical parameter is visual performance, visio-spatial performance, perceptual motor tasks, working memory, or combinations thereof ([0133] impaired verbal memory).
Regarding claim 14, Etkin teaches the cognitive disorder comprises Alzheimer's disease, autism, schizophrenia, mild cognitive impairment (MCI), Lewy body dementia, frontotemporal dementia, vascular dementia, Parkinson's dementia, chronic traumatic encephalopathy, Huntington's disease, multi system atrophy, corticobasal degeneration, striatonigral disease, multiple sclerosis, or combinations thereof ([0123] The systems and methods according to the disclosures herewith can generally be applicable to any condition affecting an individual's mental condition, in particular, the central nervous system that leads to changes in evoked brain responses through non-invasive neurostimulation. In embodiments, this can includes all psychiatric disorders, many neurological disorders (e.g. stroke, Parkinson's, Alzheimer's) and other conditions such as chronic pain)
Regarding claim 15, Etkin teaches the cognitive disorder is Parkinson's dementia and improving the patient's cognitive disorder comprises improving the patient's visual attention function, visio-spatial orientation, or both ([0123] The systems and methods according to the disclosures herewith can generally be applicable to any condition affecting an individual's mental condition, in particular, the central nervous system that leads to changes in evoked brain responses through non-invasive neurostimulation. In embodiments, this can includes all psychiatric disorders, many neurological disorders (e.g. stroke, Parkinson's, Alzheimer's) and other conditions such as chronic pain)
Regarding claim 16, Etkin teaches the pulse width is between 50 ms and 200 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
Regarding claim 17, Etkin teaches the pulse width is between 100 ms and 200 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
Regarding claim 18, Etkin teaches the pulse width is 100 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
Regarding claim 19, Etkin teaches a method of improving a cognitive disorder in a patient suffering therefrom comprising: diagnosing the patient with the cognitive disorder; applying a focused ultrasound to a pulvinar nucleus of the patient ([0004] In a first aspect, there is provided a method of treating a brain dysfunction in a subject in need thereof. The method includes administering a first plurality of non-invasive stimulations to a first plurality of different brain regions of the subject, measuring a first plurality of responses to the first plurality of non-invasive stimulations, determining a dysfunctional brain network circuit in the subject based on the measuring of the first plurality of responses, and administering a second plurality of non-invasive stimulations, based on the determining of the dysfunctional brain network circuit, to a second plurality of different brain regions of the subject, thereby treating the brain dysfunction in the subject; [0022] The term “brain region(s)” is used according to its plain and ordinary meaning and refers to a brain anatomical region following standard neuroanatomy hierarchies (e.g. a functional, connective or developmental region). Exemplary brain regions include, but are not limited to…pulvinar; [0029] transcranial focused ultrasound stimulation, as used herein refers to a non-invasive form of brain stimulation involving the delivery of acoustic pressure waves to specific, highly localize, and potentially deep areas of the brain, to influence (e.g., stimulate) neural activity in the targeted brain tissue. fUS may be used to target regions of neural tissue on the order of a few millimeters in size)
the focused ultrasound signal having a power of less than 150 watts (W) ([0067] magnitude of the response is measured in microvolts; [0069] magnitude that falls within a range of about 10 to about 1000 pA/m)
a pulse width of between 10 milliseconds (ms) and 200 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
a frequency of 0.4 MHz to 0.8 MHz ([0025] “high frequency” protocol, involving stimulation at >5 Hz (e.g… 300 Hz or higher))
and a repetition time of 5 seconds on and 10 seconds off ([0126] Paired pulse TMS can be administered at a time offset of about … 300 msecs, or more)
and improving the cognitive disorder in the patient ([0004] treating the brain dysfunction in the subject)
Regarding claim 20, Etkin teaches the frequency is between 0.4 MHz and 0.6 MHz ([0025] “high frequency” protocol, involving stimulation at >5 Hz (e.g… 300 Hz or higher))
Regarding claim 21, Etkin teaches the pulse width is between 50 ms and 200 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
Regarding claim 22, Etkin teaches the pulse width is 50 ms ([0026] single pulses that may be short (e.g. 1, 2, 3 up to 50 ms) or long (e.g. 50 ms or longer, up to 500 ms) in duration)
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 7 is rejected under 35 U.S.C. 103 as being unpatentable over Etkin as applied to claim 1 above, and further in view of Miskovik (US 20220062580 A1) and Poos (Non-Patent Literature).
Regarding claim 7, Etkin fails to teach allowing the patient to explore a virtual reality environment and identify a plurality of items within the virtual reality environment; instructing the patient to recount locations of the plurality of items in the virtual reality environment and the relationship of a location of each of the plurality of items relative to a starting point; and determining the patient's ability to recall a spatial relationship among the locations of the plurality of items; and adjusting application of the neuromodulation treatment based on the determination.
However, Miskovik teaches allowing the patient to explore a virtual reality environment and identify a plurality of items within the virtual reality environment ([0036] Immersive virtual reality system 130 provides subject 102 with a simulated experience. In some implementations, immersive virtual reality systems can be used to treat anxiety disorders. Immersive virtual reality system 130 generates realistic images, sounds and other sensations that simulate a user's physical presence in a virtual environment. Immersive virtual reality system 130 can include visual, audio, and tactile systems that provide stimulation to subject 102; [0037] When using immersive virtual reality system 130, subject 102 can interact with the artificial environment. For example, subject 102 can look around, move in, and otherwise interact with features or items within the environment. In some implementations, immersive virtual reality system 130 includes a camera that records subject 102's actual environment and displays the recorded footage to subject 102. For example, the camera can be a forward-facing external camera that records subject 102's actual environment and re-projects the actual environment to subject 102. The external facing camera and the display of immersive virtual reality system 130 provide augmented reality functionality that can modify the actual environment while it is being displayed to subject 102. Immersive virtual reality system 130 can include multiple cameras. For example, immersive virtual reality system 130 include a camera that faces subject 102's back and can project footage of subject 102's back to the subject 102. In some implementations, immersive virtual reality system 130 can induce an out of body experience by projecting, for example, footage of subject 102's environment that subject 102 is not usually able to see)
and adjusting application of the neuromodulation treatment based on a determination ([0132] In some implementations, dynamically adjusting, for each emitter and based on the measured response from the portion of the subject's brain, a set of stimulation parameters comprises using machine learning or artificial intelligence techniques to generate one or more adjusted stimulation parameters. For example, controller 110 can apply machine learning techniques to generate adjusted stimulation parameters for one or more of ultrasound stimulation system 120, immersive virtual reality system 130, and neurosensory stimulation system 140)
Etkin and Miskovik are considered analogous because both disclose ultrasound treatment to the brain. Therefore, it would have been obvious to one of ordinary skill in the art to use a patient’s response in a virtual reality environment to modulate treatment levels in order to provide a flexible platform for engineering brain states that is non-invasive, safe, and reversible (Miskovic [0004])
Etkin in view of Miskovic fails to teach instructing the patient to recount locations of the plurality of items in the virtual reality environment and the relationship of a location of each of the plurality of items relative to a starting point.
However, Poos teaches instructing the patient to recount locations of the plurality of items in the virtual reality environment and the relationship of a location of each of the plurality of items relative to a starting point ([Materials and Methods] Two 14.5 × 14.5 cm squares were shown on a touchscreen monitor, with ten randomly placed objects in the left square. Each participant was given the following instruction: “You will see two square frames, with the left containing ten objects. On the right there is an empty square with ten identical objects on top. You have to reconstruct the object array in the right frame, making sure the positions match those in the left frame”. For the memory trial, one 14.5 cm square was shown for 30 s with ten different objects. Participants were given the following instruction: “You will see a square containing objects for 30 s. You have to remember the locations of these objects as accurately as possible. After the object disappear, you will see an empty square, and you have to relocate the objects to the correct locations”)
Etkin as modified and Poos are considered analogous because both are related to treatment of a neurological disorder. Therefore, it would have been obvious to one of ordinary skill in the art to use a spatial memory test as disclosed in Poos in a virtual reality environment as disclosed in Miskovic in order to investigate the differential ability of a short digital test battery that is easy to administer and measures the most relevant aspects of spatial memory in a systematic and condensed, time-limited manner in patients with mild AD dementia and MCI (Poos [Introduction]).
Response to Arguments
Applicant's arguments filed 1/20/2026 have been fully considered but they are not persuasive. Applicant argues that the newly amended limitations regarding the particular operation parameters are not found in the Etkin reference. However, this is not true.
Regarding having a power less than 150 watts, while Etkin does not explicitly disclose a measurement in watts, Etkin does disclose a power magnitude measured in microvolts and picoamperes per meter, which when computed will assuredly come to be less than 150 Watts.
Regarding the pulse width, Etkin discloses a variety of pulse widths in paragraph [0026] which fall in the claimed range.
Regarding the frequency, Etkin discloses a number of frequency ranges in paragraph [0025] which fall within the claimed range.
Regarding the repetition time, Etkin discloses in paragraph [0126] a timed offset between pulses of more than 300 msecs, and the claimed values are both larger than 300 msecs.
Given these parameters and the fact that this ultrasound treatment is administered to a variety of neural target sites including a pulvinar nucleus as disclosed in paragraph [0022], the independent claim is considered to be anticipated by Etkin. Dependent claims are rejected at least by virtue of their dependency.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GABRIEL VICTOR POPESCU whose telephone number is (571)272-7065. The examiner can normally be reached M-F 8AM-5PM.
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/GABRIEL VICTOR POPESCU/Examiner, Art Unit 3797
/SERKAN AKAR/Primary Examiner, Art Unit 3797
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