DETAILED ACTION
Summary
Claims 15-37 are pending in the application. Claims 30, 33, and 35 rejected under 35 USC 112(b). Claim 15 is rejected under 35 USC 102(a)(1). Claims 16-27, 29-33, and 35-37 are rejected under 35 USC 103.
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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 15, 17, 18, 25, 31-33, and 37 objected to because of the following informalities:
Claim 15 recites “the brain” in line 6. It should recite “a brain”.
Claim 15 recites “the periaqueductal gray region, the locus coeruleus, the thalamus, the hypothalamus, the neocortex and the cerebellum” in lines 8-10. It should recite “a periaqueductal gray region, a locus coeruleus, a thalamus, a hypothalamus, a neocortex and a cerebellum”.
Claim 17 recites “to the ventrolateral periaqueductal gray (vlPAG)” in line 2. It should recite “to ventrolateral periaqueductal gray (vIPAG)”.
Claim 18 recites “to the hypothalamic arcuate nucleus (ARC) or the rostral ventrolateral medulla (rVLM)” in lines 2-3. It should recite “to hypothalamic arcuate nucleus (ARC) or rostral ventrolateral medulla (rVLM)”.
Claim 25 recites “the head of the subject” in line 4. It should recite “a head of the subject”.
Claim 31 recites “to the ventrolateral periaqueductal gray (vlPAG)” in lines 2-3. It should recite “to ventrolateral periaqueductal gray (vIPAG)”.
Claim 32 recites “the head of a subject” in line 3. It should recite “a head of a subject”.
Claim 33 recites “the positions and orientations of the ultrasound transducers” in lines 7-8. It should recites “positions and orientations of the ultrasound transducers”.
Claim 33 recites “the positions and orientations” in lines 10-11. It should recite “the positions and the orientations”.
Claim 37 recites “to the ventrolateral periaqueductal gray (vlPAG)” in lines 2-3. It should recite “to ventrolateral periaqueductal gray (vIPAG)”.
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.
Claims 30, 33, and 35 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 “closely spaced” in claim 30 is a relative term which renders the claim indefinite. The term “closely spaced” 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 examination, if the pressure nodes are both in the brain, they will be considered to be “closely spaced”.
Claim 33 recites “a specific subject” in line 3. It is not clear if this includes the “subject” set forth in claim 32, or if this is referring to a different subject. Clarification is required. For the purposes of examination, the former definition will be used.
The term “closely spaced” in claim 35 is a relative term which renders the claim indefinite. The term “closely spaced” 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 examination, if the pressure nodes are both in the brain, they will be considered to be “closely spaced”.
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.
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.
Claim 15 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lea-Banks et al. (Lea-Banks, Harriet, et al. "Localized anesthesia of a specific brain region using ultrasound-responsive barbiturate nanodroplets." Theranostics 10.6 (2020): 2849.).
Regarding Claim 15, Lea-Banks teaches a method of treating hypertension using focused transcranial ultrasound (Abstract) (as this reference discloses all the claimed steps, it is necessarily capable of treating hypertension), the method comprising:
after intravenous injection of nanodroplets to a subject (Pg. 2850, Col 2, ¶ 2) (Pg. 2851-2852, Col 2-1, ¶3-1), the nanodroplets comprising a perfluorocarbon core (Pg. 2850, Col 1, ¶2-3) and a lipid shell (Pg. 2850, Col 1-2, ¶4-1), the nanodroplets being loaded with a lipophilic anesthetic agent (Pg. 2849, Abstract)+(Pg. 2850, Col 2, ¶2):
transcranially delivering focused ultrasound to a region of the brain to vaporize the nanodroplets and release the lipophilic anesthetic agent (Pg. 2851-2852, Col 2-1,¶2-2), the region of the brain being selected from the group consisting of the neocortex (Pg. 2851, Col 2, ¶1, the motor cortex is a part of the neocortex).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li et al. (Li, Dapeng, et al. "Low-intensity focused ultrasound stimulation treatment decreases blood pressure in spontaneously hypertensive rats." IEEE Transactions on Biomedical Engineering 67.11 (2020): 3048-3056.).
Regarding Claim 16, Lea-Banks teaches the invention as claimed. Lea-Banks fails to explicitly teach wherein the focused ultrasound is delivered to the periaqueductal gray region.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
Regarding Claim 17, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein the focused ultrasound is delivered to the ventrolateral periaqueductal gray (vIPAG).
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the ventrolateral periaqueductal gray (vIPAG) (Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
Regarding Claim 19, the combination of references teaches the invention substantially as claimed. Lea-Banks further teaches the lipophilic anesthetic agent is a barbiturate (Pg. 2849, Abstract, pentobarbital is a barbiturate).
Regarding Claim 20, the combination of references teaches the invention substantially as claimed. Lea-Banks further teaches the barbiturate is selected from the group consisting of amobarbital, alphenal, butabarbital, butalbital, butethal, pentobarbital, phenobarbital, secobarbital, and thiopental (Pg. 2849, Abstract, pentobarbital).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Shapiro et al. (U.S PGPub 2019/0175763 A1).
Regarding Claim 18, Lea-Banks teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach the focused ultrasound is delivered to the hypothalamic arcuate nucleus (ARC) or the rostral ventrolateral medulla (rVLM).
Shapiro teaches a system for stimulating brain tissue (Abstract). This system uses focused ultrasound to stimulate the tissue [0030]. This system stimulates the hypothalamic arcuate nucleus [0210].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system to stimulate the ARC, as taught by Shapiro, because this allows the user to treat eating disorders, thereby improving the health of the patient, as recognized by Shapiro [0210].
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li as applied to claim 16 above, and further in view of Lea-Banks et al. (Lea-Banks, Harriet, et al. "Ultrasound-sensitive nanodroplets achieve targeted neuromodulation." Journal of Controlled Release 332 (2021): 30-39.) (Lea-Banks’2021).
Regarding Claim 21, the combination of references teaches the invention substantially as claimed. Lea-Banks is silent regarding the lipophilic anesthetic agent is a GABA_A receptor agonist.
Lea-Banks’2021 teaches using nanodroplets for neuromodulation (Abstract). This system uses pentobarbital in the nanodroplet, and recognizes that it is a GABA_A receptor agonist (Pg. 31, Col 1, ¶ 2).
It would have been obvious to one of ordinary skill in the art to substitute the use of pentobarbital of Lea-Banks, with pentobarbital which is a GABA_A receptor agonist, as taught by Lea-Banks’2021 as the substitution for one known pentobarbital with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of pentobarbital being a GABA_A receptor agonist are reasonably predictable.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li as applied to claim 16 above, and further in view of Airan et al. (Airan, Raag D., et al. "Noninvasive targeted transcranial neuromodulation via focused ultrasound gated drug release from nanoemulsions." Nano letters 17.2 (2017): 652-659.).
Regarding Claim 22, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach the lipophilic anesthetic agent is selected from the group consisting of benzocaine, bupivacaine (Marcaine), ketamine, levobupivacaine, lidocaine, prilocaine, procaine, propofol, ropivacaine, and tetracaine.
Airan teaches a neuromodulation system that uses anesthetic agents (Abstract). This system uses neuromodulation of nanoparticles containing propofol (Abstract)+(pg. 653, Fig. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the anesthetic used by Lea-Banks to be propofol, as taught by Airan, as the substitution for one known anesthetic with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using propofol are reasonably predictable.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li as applied to claim 16 above, and further in view of National Center (National Center for Biotechnology Information. PubChem Compound Database; CID=4737, https://web.archive.org/web/20150920202037/https://pubchem.ncbi.nlm.nih.gov/compound/4737 (accessed Sept. 20, 2015).).
Regarding Claim 23, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein the lipophilic anesthetic agent has a molecular weight less than 400 Da and a partition coefficient logP of approximately 2.
National center teaches that pentobarbital has a molecular weight less than 400 Da and a partition coefficient log P or approximately 2 (Pg. 7, Computed Properties Table).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the anesthetic agent with pentobarbital with the claimed properties, as taught by National Center, as the substitution for one known pentobarbital with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using an anesthetic with the claimed parameters are reasonably predictable.
Claims 24-27, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li as applied to claim 16 above, and further in view of Hynynen et al. (U.S PGPub 2018/0177491 A1).
Regarding Claim 24, the combination of references teaches the invention substantially as claimed. Lea-Banks further teaches the focused ultrasound is transcranially delivered by controlling ultrasound transducers to deliver focused ultrasound energy (Pg. 2851, Col 2, ¶ 1).
Lea-Banks fails to explicitly teach wherein the focused ultrasound is delivered to the periaqueductal gray region.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
The combination fails to explicitly teach a transcranial headset.
Hynynen teaches a system for performing transcranial procedures (Abstract). This system uses a transcranial headset (Fig. 1A, 100) to apply focused ultrasound [0055]-[0056].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to apply the ultrasound using a transcranial headset, as taught by Hynynen, because this allows for high levels of beam steering, thereby allowing for more accurate treatment, as recognized by Hynynen [0054].
Regarding Claim 25, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein the transcranial headset comprises a support structure supporting the ultrasound transducers, and wherein the support structure conforms to an anatomical contour of at least a portion of the head of the subject.
Hynynen further teaches teach wherein the transcranial headset comprises a support structure supporting the ultrasound transducers [0055], and wherein the support structure conforms to an anatomical contour of at least a portion of the head of the subject [0063]+[0067].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to apply the ultrasound using a transcranial headset, as taught by Hynynen, because this allows for high levels of beam steering, thereby allowing for more accurate treatment, as recognized by Hynynen [0054].
Regarding Claim 26, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach delivering the focused ultrasound energy to the periaqueductal gray region.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
Li fails to explicitly teach wherein known positions and orientations of the ultrasound transducers relative to volumetric image data associated with the subject are employed to control the ultrasound transducers for delivering the focused ultrasound energy to the subject when the transcranial headset is worn by the subject.
Hynynen further teaches known positions and orientations of the ultrasound transducers relative to volumetric image data associated with the subject (Fig. 2, 260) [0074] are employed to control the ultrasound transducers for delivering the focused ultrasound energy to the subject when the transcranial headset is worn by the subject [0074]+[0089].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to apply the ultrasound using a transcranial headset based on known positions of the transducers, as taught by Hynynen, because this allows for high levels of beam steering, thereby allowing for more accurate treatment, as recognized by Hynynen [0054].
Regarding Claim 27, the combination of references teaches the invention substantially as claimed. Lea-Banks further teaches processing signals received from the ultrasound transducers to detect acoustic emissions generated by vaporization of the nanodroplets in response to the focused ultrasound energy (Pg. 2852, Col 1, ¶ 3); and employing the detected acoustic emissions as feedback to control delivery of the focused ultrasound energy according to an association between nanodroplet vaporization and delivery of an effective dose of the lipophilic anesthetic agent (Pg. 2852, Col 1, ¶ 3) (the measured harmonics are used to control the focused ultrasound based on whether a sufficient amount of nanodroplets are vaporizing (which indicates an effective dose of the agent is being applied as the agent is being released from the droplets)).
Lea-Banks fails to explicitly teach within the periaqueductal gray region
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
Regarding Claim 31, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein the ultrasound transducers are controlled to focus the focused ultrasound energy to the ventrolateral periaqueductal gray (vIPAG).
Li further teaches wherein the ultrasound transducers are controlled to focus the focused ultrasound energy to the ventrolateral periaqueductal gray (vIPAG) (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the vIPAG, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li and Hynynen as applied to claim 27 above, and further in view of Lea-Banks’2021.
Regarding Claim 29, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein the signals received from the ultrasound transducers are employed to detect one or more of subharmonic acoustic emissions and harmonic acoustic emissions.
Lea-Banks’2021 further teaches detecting subharmonic acoustic emissions using the ultrasound transducers (Pg. 311, Col 2, ¶ 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the detected emission to detect subharmonic emissions, as taught by Lea-Banks’2021 as the substitution for one known emission with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of detecting subharmonic emissions are reasonably predictable.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li and Hynynen as applied to claim 24 above, and further in view of Shoham et al. (U.S PGPub 2013/0079621 A1).
Regarding Claim 30, the combination of references teaches the invention substantially as claimed. Lea-Banks further teaches wherein the ultrasound transducers are controlled to generate mechanical stress on tissue by forming two or more closely spaced ultrasound pressure nodes (Pg. 2852, Fig. 1B) (Pg. 2851, Col 1, ¶ 2).
Lea-Banks fails to explicitly teach within the periaqueductal gray region.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
The combination fails to explicitly teach wherein neighboring nodes are in different acoustic phase to create a force between the ultrasound pressure nodes that stimulates or inhibits neuronal activity.
Shoham teaches a method of applying multi-focused ultrasound energy (Abstract). This system applies ultrasound to different nodes (focuses) which are in different acoustic phases to create a desired force between the pressure nodes(Fig. 5A+5B) [0094]-[0096]. This system is used to stimulate of inhibit neuronal activity [0074]+[0076].
It would have been obvious to one of ordinary skill in the art to generate the different pressure nodes with different acoustic phases, as taught by Shoham, because this allows the user to optimize the energy applied to the target, thereby improving the effectiveness of the treatment, as recognized by Shoham [0059]
Claims 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li and Hynynen.
Regarding Claim 32, Lea-Banks teaches a system for treatment using focused transcranial ultrasound (Abstract), the system comprising:
controlling the ultrasound transducers to deliver focused ultrasound energy to a brain (Pg. 2851-2852, Col 2-1,¶2-2), the focused ultrasound energy being configured to cause vaporization of intravenously administered nanodroplets (Pg. 2852, Col 1,¶2-3 loaded with a lipophilic anesthetic agent (Pg. 2849, Abstract)+(Pg. 2850, Col 2, ¶2) to release the lipophilic anesthetic agent (Pg. 2852, Col 1, ¶ 3);
processing signals received from the ultrasound transducers to detect acoustic emissions generated by vaporization of the nanodroplets in response to the focused ultrasound energy (Pg. 2852, Col 1, ¶ 3); and
employing the detected acoustic emissions as feedback to control delivery of the focused ultrasound energy according to an association between nanodroplet vaporization and delivery of an effective dose of the lipophilic anesthetic agent (Pg. 2852, Col 1, ¶ 3) (the measured harmonics are used to control the focused ultrasound based on whether a sufficient amount of nanodroplets are vaporizing (which indicates an effective dose of the agent is being applied as the agent is being released from the droplets)).
Lea-Banks fails to explicitly teach wherein the focused ultrasound is delivered to the periaqueductal gray region for treating hypertension.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region for treating hypertension (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
The combination fails to explicitly teach a transcranial headset configured to be worn on the head of a subject, the transcranial headset comprising a support structure and a plurality of ultrasound transducers supported by the support structure; and control and processing circuitry configured to perform operations.
Hynynen teaches a system for performing transcranial procedures (Abstract). This system uses a transcranial headset (Fig. 1A, 100) to apply focused ultrasound [0055]-[0056]. The transcranial headset comprises a support structure and a plurality of ultrasound transducers [0055], and wherein the support structure is worn on the head of the subject (Fig. 3, 100) [0055]+[0063]. The system is controlled by control and processing circuitry [0085].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to apply the ultrasound using a transcranial headset, as taught by Hynynen, because this allows for high levels of beam steering, thereby allowing for more accurate treatment, as recognized by Hynynen [0054].
Regarding Claim 33, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein delivering the focused ultrasound energy to the periaqueductal gray region.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
The combination fails to explicitly teach wherein the support structure of the transcranial headset conforms to an anatomical contour of at least a portion of the head of a specific subject; and wherein the system further comprises a storage medium, the storage medium comprising: volumetric image data associated with the specific subject; and transducer registration data enabling registration of the positions and orientations of the ultrasound transducers relative to the volumetric image data; and wherein the control and processing circuitry is configured to employ the positions and orientations of the ultrasound transducers relative to the volumetric image data to control the ultrasound transducers for delivering the focused ultrasound energy to the specific subject when the transcranial headset is worn by the specific subject.
Hynynen further teaches wherein the support structure conforms to an anatomical contour of at least a portion of the head of the subject [0063]+[0067]. The system further comprises a storage medium [0085], the storage medium comprising: volumetric image data associated with the specific subject [0086]. The storage also contains transducer registration data enabling registration of the positions and orientations of the ultrasound transducers relative to the volumetric image data [0086]+[0089]. The control and processing circuitry [0085] is configured to employ the positions and orientations of the ultrasound transducers relative to the volumetric image data to control the ultrasound transducers for delivering the focused ultrasound energy to the specific subject when the transcranial headset is worn by the specific subject [0074]+[0089].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to apply the ultrasound using a transcranial headset based on known positions of the transducers, as taught by Hynynen, because this allows for high levels of beam steering, thereby allowing for more accurate treatment, as recognized by Hynynen [0054].
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li and Hynynen as applied to claim 32 above, and further in view of Shoham et al. (U.S PGPub 2013/0079621 A1).
Regarding Claim 35, the combination of references teaches the invention substantially as claimed. Lea-Banks further teaches wherein the ultrasound transducers are controlled to generate mechanical stress on tissue by forming two or more closely spaced ultrasound pressure nodes (Pg. 2852, Fig. 1B) (Pg. 2851, Col 1, ¶ 2).
Lea-Banks fails to explicitly teach within the periaqueductal gray region.
Li teaches method for transcranial ultrasound (Abstract). This system delivers focused ultrasound to the periaqueductal gray region (Abstract)+(Pg. 3053, Fig. 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the system of Lea-Banks to irradiate the periaqueductal gray region, as taught by Li, because this allows the physician to non-invasively treat hypertension, thereby providing an alternative, non-invasive, method for treating hypertension, as recognized by Li (Pg. 3055, Col 2, Conclusion).
The combination fails to explicitly teach wherein neighboring nodes are in different acoustic phase to create a force between the ultrasound pressure nodes that stimulates or inhibits neuronal activity.
Shoham teaches a method of applying multi-focused ultrasound energy (Abstract). This system applies ultrasound to different nodes (focuses) which are in different acoustic phases to create a desired force between the pressure nodes(Fig. 5A+5B) [0094]-[0096]. This system is used to stimulate of inhibit neuronal activity [0074]+[0076].
It would have been obvious to one of ordinary skill in the art to generate the different pressure nodes with different acoustic phases, as taught by Shoham, because this allows the user to optimize the energy applied to the target, thereby improving the effectiveness of the treatment, as recognized by Shoham [0059]
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Lea-Banks in view of Li and Hynynen as applied to claim 32 above, and further in view of Lea-Banks’2021.
Regarding Claim 29, the combination of references teaches the invention substantially as claimed. Lea-Banks fails to explicitly teach wherein the signals received from the ultrasound transducers are employed to detect one or more of subharmonic acoustic emissions and harmonic acoustic emissions.
Lea-Banks’2021 further teaches detecting subharmonic acoustic emissions using the ultrasound transducers (Pg. 311, Col 2, ¶ 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the detected emission to detect subharmonic emissions, as taught by Lea-Banks’2021 as the substitution for one known emission with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of detecting subharmonic emissions are reasonably predictable.
Allowable Subject Matter
Claims 28 and 34 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 28 recites “inferring a plasma noradrenaline content based on a correlation between plasma noradrenaline content and the detected acoustic emissions”. This limitation, in combination with the limitations of the base and intervening claims, is not taught by the prior art without the benefit of improper hindsight.
None of the cited references suggest “inferring a plasma noradrenaline content based on a correlation between plasma noradrenaline content and the detected acoustic emissions”. While Li teaches the irradiation of the periaqueductal gray region may reduce norepinephrine (noradrenaline) (Pg. 3052, Fig. 4), Li measures the norepinephrine levels from the blood plasma (Pg. 3050, Section E). Li does not infer the noradrenaline content based on acoustic emissions (which are generated by the vaporization of the nanodroplets). None of the other cited references suggest the claimed features. Therefore, claim 28 would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 34 contains similar limitations, and would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims for substantially the same reasons.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Creutzfeldt (Creutzfeldt, Otto D. "Generality of the functional structure of the neocortex." Naturwissenschaften 64.10 (1977): 507-517.) which teaches the motor cortex is a part of the neocortex.
Acker et al. (U.S Patent 6,508,774 B1) which teaches controlling ultrasound therapy using acoustic emissions.
Tyler (U.S PGPub 2012/0289869 A1), which teaches a transcranial ultrasonic headset.
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/SEAN D MATTSON/Primary Examiner, Art Unit 3798