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 arguments filed 1/23/2026, with respect to the rejection(s) of claim(s) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made using Ludwig in view of Zhu and Lewis. Lewis is now replacing the Tendler reference from the previous rejection.
The examiner may go final as the applicant originally had the claim language “a sensing device measuring cerebral spinal fluid (CSF)/interstitial fluid (ISF) flow in the brain of the human patient or a representative measure of CSF/ISF flow”. By including the subject matter from claims 5 and 16, the applicant is electing the species of “a representative measure of CSF/ISF flow”. Thus, the changed the scope by choosing one of the two species in independent claims 1 and 13. A change in scope allows the examiner to make the action final.
Claim Objections
Claims 1, 10, 12, 13, 15, 18, and 19 are objected to because of the following informalities:
In claims 1, 12, 13, 15, 18, and 19, the term “CSF” and “CSF/ISF” flows should be preceded by “the” or “said” following the first occurrences of these terns in independent claims 1 and 13. Appropriate correction is required.
In claim 10, the limitation within the parentheses, “(e.g., auricular vagus nerve)” should be deleted.
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 1 and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1 and 13, the applicant has included the subject matter from claims 5 and 16. However, this subject matter being introduced now renders claims 1 and 13 unclear as they claim “a sensing device measuring cerebral spinal fluid (CSF)/interstitial fluid (ISF) flow in the brain of the human patient or a representative measure of CSF/ISF flow”. The use of the word “or” is problematic. The electrical activity is now being sensed (per the latest amendment), which is “a representative measure of CSF/ISF flow”. The applicant should either use the word “and” instead of “or” or remove the “measuring cerebral spinal fluid (CSF)/interstitial fluid (ISF) flow in the brain of the human patient” limitation. Either option changes the scope as stated above, allowing the examiner to make this action final.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-4, 6-8, 10-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ludwig et al. (Pub. No.: US 2021/0038884 A1); hereinafter referred to as “Ludwig”, in view of Zhu (Pub. No.: US 2015/0018634 A1) and Lewis et al. (WO 2020/210813 A1); hereinafter referred to as “Lewis”.
Regarding claims 1, 6, 13, and 19, Ludwig discloses an electrical stimulation device (e.g. see figure 2 element 58, [0058]) for modulating function of a glymphatic system or meningeal lymphatic system (e.g. see [0060]) of a human patient comprising: at least one electrode (e.g. see figure 1 element 50, [0055]-[0056]) configured to stimulate a cranial nerve (e.g. see [0008], [0010]) of the human patient; an electrical generator (e.g. see figure 2 element 60, [0058]-[0059]) configured to generate at least one carrier wave having a first carrier amplitude and a first carrier frequency (e.g. see [0059]); a modulator (e.g. see figure 2 element 64) receiving the at least one carrier wave and a modulation wave to modulate the at least one carrier wave (e.g. see [0060]) for application to the at least one electrode; an electrical modulation generator (e.g. see figure 2 element 70, [0060]) generating the modulation wave having a predetermined periodicity providing a first period of stimulation and a second period of a different or no stimulation (e.g. see [0060]), the predetermined periodicity selected to increase wall movement over continuous stimulation of the glymphatic system or meningeal system by the carrier frequency (e.g. see [0060]); a sensing device measuring cerebral spinal fluid (CSF)/interstitial fluid (ISF) flow in the brain of the human patient or a representative measure of CSF/ISF flow (e.g. see [0060]).
Ludwig discloses adjusting at least one of the at least one carrier wave and the modulation wave to increase CSF/ISF flow in response to a measurement of the sensing device (e.g. see [0060]) but Ludwig does not disclose using a controller to perform this function. Zhu teaches it is known to use a controller to perform electrical stimulation based on feedback from a CSF flow sensor as disclosed in [0070], figure 5, [0005]-[0007] to provide electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]). It would have been obvious to one having ordinary skill in the art at the time the invention was made to use a controller to perform electrical stimulation based on feedback from a CSF flow sensor as taught by Zhu in the system/method of Ludwig, since said modification would provide the predictable results of electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]).
Ludwig and Zhu disclose measuring CSF/ISF flow (e.g. see [0060] and [0070], figure 5, [0005]-[0007] respectively) but are silent as to the measurement of the sensing device is a measure of an electrical activity of the brain. Lewis teaches an imaging-based biomarker that indicates a neurological state of a subject is generated from magnetic resonance imaging data acquired from the subject while the subject was sleeping, or during both a sleep state and wake state (Abstract). These magnetic resonance imaging data are acquired in such a way so that they simultaneously enable measurement of cerebrospinal fluid ("CSF") flow and blood-oxygenation-level dependent ("BOLD") signals. The imaging-based biomarker can be generated based on a correlation between CSF signals and BOLD signals extracted from these magnetic resonance imaging data (Abstract). Using electroencephalography ("EEG") data, CSF flow dynamics can also be estimated based on a physiological model in which coherent neural activity is modeled as entraining oscillations in blood volume and CSF (Abstract).. It would have been obvious to one having ordinary skill in the art at the time the invention was filed to measure electrical activity of the brain in a CSF/ISF flow increasing device using EEG as taught by Lewis in the system/method of Ludwig and Zhu, since said modification would provide the predictable results of effective monitoring of CSF dynamics relate directly to the major changes in neural activity and important physiological states.
Regarding claim 2, Ludwig discloses adjusting the predetermined periodicity of the modulation wave in response to a measurement of the sensing device (e.g. see [0060], [0014], [0035]) but Ludwig does not disclose using a controller. Zhu teaches it is known to use a controller as disclosed in [0070], figure 5, [0005]-[0007] to provide electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]). It would have been obvious to one having ordinary skill in the art at the time the invention was made to use a controller as taught by Zhu in the system/method of Ludwig, since said modification would provide the predictable results of electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]).
Regarding claim 3, Ludwig discloses adjusting the first carrier frequency in response to a measurement of the sensing device (e.g. see [0035]-[0038], [0059]-[0061]) but Ludwig does not disclose using a controller. Zhu teaches it is known to use a controller as disclosed in [0070], figure 5, [0005]-[0007] to provide electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]). It would have been obvious to one having ordinary skill in the art at the time the invention was made to use a controller as taught by Zhu in the system/method of Ludwig, since said modification would provide the predictable results of electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]).
Regarding claim 4, Ludwig discloses adjusting the first carrier amplitude in response to a measurement of the sensing device (e.g. see [0059]-[0061]) but Ludwig does not disclose using a controller. Zhu teaches it is known to use a controller as disclosed in [0070], figure 5, [0005]-[0007] to provide electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]). It would have been obvious to one having ordinary skill in the art at the time the invention was made to use a controller as taught by Zhu in the system/method of Ludwig, since said modification would provide the predictable results of electrical stimulation systems having leads capable of detecting pulsation of cerebrospinal fluid within a patient (e.g. see [0002]).
Regarding claims 7 and 17, Ludwig discloses the measurement of the sensing device is a measure of blood perfusion in the brain (e.g. see [0011], [0067], [0060]).
Regarding claim 8, Ludwig discloses the sensing device is at least one of a computerized topography (CT) scanner, magnetic resonance imaging (MRI) scanner, functional magnetic resonance imaging (fMRI) scanner, positron emission tomography (PET) scanner, transcranial ultrasound, and single-photon emission computed tomography (SPECT) scanner (e.g. see [0060]).
Regarding claim 10, Ludwig discloses at least one electrode is adapted to stimulate at least one of a trigeminal nerve, buccal branch nerve, mental branch nerve, facial branch nerve, vagus branch nerve (e.g., auricular vagus nerve), cervical nerve, sympathetic trunk/sympathetic ganglia, and sympathetic efferent branches (e.g. see [0052]-[0056]).
Regarding claims 11 and 14, Ludwig discloses the at last one carrier wave comprises first and second carrier waves having first and second distinct frequencies and delivered simultaneously to the at least one electrode (e.g. see [0038], [0060]).
Regarding claim 12, Ludwig discloses sensors detecting salivary biomarkers indicating a change to CSF flow selected from at least one of amyloid beta peptide, tau protein, lactoferrin, alpha-synuclein, DJ-1 protein, chromogranin A, huntingtin protein, DNA methylation disruptions, and micro-RNA (e.g. see [0030], [0094]).
Regarding claim 15, Ludwig discloses adjusting the second carrier frequency to increase CSF/ISF flow in response to the measurement of the CSF/ISF flow in the brain of the patient (e.g. see [0038], [0060]).
Regarding claim 18, Ludwig discloses adjusting a position of the at least one electrode in response to the measurement of the CSF/ISF flow in the brain of the patient (e.g. see [0052]-[0056]).
Regarding claim 20, Ludwig discloses the at least one electrode is positioned over at least one of an inferior alveolar nerve and a mental branch nerve (e.g. see [0052]-[0056]).
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ludwig and Zhu and Lewis as applied to claim 1 above, and further in view of Nakatomi et al. (Pub. No.: US 2010/0241203 A1); hereinafter referred to as “Nakatomi”.
Regarding claim 9, Ludwig and Zhu and Lewis disclose the claimed invention except for the sensing device is at least one of a pupilometer measuring a dilation of the pupil, functional near-infrared spectroscopy (fNIRS) measuring changes in hemoglobin in cerebral blood, a device measuring blood perfusion in the skin of the face or head, and a device measuring an evoked neural signal in the facial or trigeminal nerves. Nakatomi teaches that it is known to use such a modification as set forth in [0093] to provide real-time stimulation feedback from the evoked neural signal in the facial nerve. It would have been obvious to one having ordinary skill in the art at the time the invention was made to use evoked signal sensing in the facial nerves as taught by Nakatomi in the system/method of Ludwig and Zhu and Lewis, since said modification would provide the predictable results of real-time stimulation feedback from the evoked neural signal in the facial nerve.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Ludwig et al. (US 20210038884 A1) teaches the following in [0076]:
The CSF/ISF flow may be monitored using known imaging modalities such as CT scan, MRI scan, and panoramic x-ray during electrical stimulation. It is understood that other physiological factors may also be monitored to determine the effectiveness of stimulation parameters, such as changes to heart rate, respiratory rate, or presence of certain biomarkers in the patient's blood or saliva as further described below. These physiological factors may be measured using, for example, neuroimaging techniques (e.g., panoramic x-ray, computerized topography (CT) scan, diffuse optical imaging (DOI), event-related optical signal (EROS), magnetic resonance imaging (MM), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and cranial ultrasound), cognitive function testing (e.g., learning tests and memory tests), motor function testing, sensory function testing, biopsy, CSF testing, blood testing and/or genetic testing.
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 PHILIP C EDWARDS whose telephone number is (571)270-1804. The examiner can normally be reached Mon-Fri, 9:00-5:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Unsu Jung can be reached at 571-272-8506. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/P.C.E/Examiner, Art Unit 3792
/UNSU JUNG/Supervisory Patent Examiner, Art Unit 3792
Prosecution Insights