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 .
Information Disclosure Statement
Information Disclosure Statement (IDS) submitted on 08/22/2023 has been entered and fully considered by the examiner.
Response to Amendment
The amendment of 04/13/2026 has been entered and fully considered by the examiner. Claims 1, 3, 4, 10, and 12-15 have been amended. Claims 16-21 are added. Claims 1-21 are currently pending in the application with claims 1 and 15 being independent.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1, 2, 4-6, 11, 14, and 15 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Myllyla et al. (“Assessment of the dynamics of human glymphatic system by near-infrared spectroscopy”, Bio Photonics, 2017) hereinafter “Myllyla”.
Regarding claim 1, Myllyla discloses an apparatus for measuring intracranial dynamics, [see abstract of Myllyla] comprising:
an optic measurement arrangement configured to direct optic radiation toward the brain through the cranium,[see page 3, left column, second paragraph and FIG. 3 disclosing the optical measurement of the brain through the cranium (behind the skin of the skull)] and receive the optic radiation reflected and/or scattered therefrom, [see FIG. 3]
a data processing arrangement [see FIG. 6, right column, first paragraph disclsoing a laptop computer. It is inherent that a laptop computer has a processing unit] configured to receive electric signals from the optic measurement arrangement, [see page 5, right column, last paragraph continued in page 6, right and left column, first paragraph disclosing receiving and processing the optical data]
analyze the electric signals reflecting cardiorespiratory brain pulsations, movement of the brain caused by head movements, neurofluidic pulsations and their relationship and/or vasomotion,[the signals are received from the brain includes all information regarding the movement of brain, neurofluidic pulsation, etc]
based on the electric signals, determine data on at least one of the following neurohydrodynamics including blood and water in and within the cranium [see FIGs. 9, 13, and 14 disclosing change in water concentration in the cranium] brain tissue and electrolyte movements.
Generate output of at least one piece of the data on the dynamics through a user interface [see FIG. 7, 9, 13, and 14 of Myllyla shows the concentration of the water dynamic changes in the cranium
Regarding claim 2, Myllyla, further discloses wherein the optic measurement arrangement is configured to measure the brain tissue at least one optic wavelength band [one band in 980nm and one band in 660 or 740nm], which is dominantly attenuated by the water within the cranium, [see page 3, left column, first paragraph disclosing that wavelength of 980 was used for sensitivity to water] and at least one optic wavelength band, which is dominantly attenuated by the blood within the cranium [see page 3, left column, first paragraph disclosing that wavelength of 660 or 740 was used for sensitivity to hemoglobin in the blood] in order to separately measure the dynamics of the water within the cranium and the cerebral blood where dynamical changes between the blood and water within the cranium reflect glymphatic activity and brain tissue pulsations. [see abstract and page 5, right column, second and third paragraphs disclosing studying the dynamics of water and hemoglobin changes in the skull]
Regarding claim 4, Myllyla further discloses that the data processing unit is configured to form data on glymphatic activity as a difference between the dynamics of water and the blood within the cranium [see page 5, second paragraph, last 5 lines disclosing subtracting water from HbT and FIGs. 7-14]
Regarding claim 5, Myllyla further discloses that the data processing unit is configured to determine the glymphatic activity based on correlation of the data on the water within the cranium and the cerebral arterial blood. [see page 7, section under 4. Results and Discussion and FIGs. 12-14 show the free water and BH concentration changes; page 8, section under conclusion discloses that changes in free water concentration is correlated with dynamics of glymphatic circulation]
Regarding claim 6, Myllyla further discloses wherein the data processing unit is configured to determine the glymphatic activity based on an envelope of a signal of the data on water within the cranium. [see FIG. 13 and its caption disclosing that the envelope of the free water signal is calculated and used in the calculations; page 8, section under conclusion discloses that changes in free water concentration is correlated with dynamics of glymphatic circulation]
Regarding claim 11, Myllyla further discloses that the data processing unit is configured to determine data on the glymphatic activity based on the data on the hydrodynamics of water within the cranium [see page 7, section under 4. Results and Discussion and FIGs. 12-14 show the free water changes in the cranium; page 8, section under conclusion discloses that changes in free water concentration is correlated with dynamics of glymphatic circulation] and the physiological model. [see page3, right column, continued in page 4 discloses simulation of the photon scattering and absorption in the brain tissue using Monte Carlo model; combining the results of the simulation for various wavelengths in then used to estimate the water variation which correlates with glymphatic activity (see abstract)]
Regarding claim 14, Myllyla further discloses wherein the data processing unit comprises one or more processors, one or more memories [see FIG. 6, right column, first paragraph disclosing a laptop computer. It is inherent that a laptop computer has a processing unit and a memory] including computer program code [Monte Cardo simulation code; see page 3, right column, section under 2.2 measurement volume of the NIRS optode] wherein the one or more memories and the computer program code are configured to with the one or more processors, cause the data processing unit to perform the receiving [see page 3, left column, second paragraph and FIG. 3 disclosing the optical measurement of the brain through the cranium (behind the skin of the skull by receiving optical signal] determining, and generating, [see FIGs. 9, 13, and 14 disclosing the dynamic change in water concentration in the cranium].
Regarding claim 15, Myllyla discloses a method of measuring intracranial dynamics [see abstract of Myllyla], the method comprising :
directing optic radiation toward the brain through the cranium, [see page 3, left column, second paragraph and FIG. 3 disclosing the optical measurement of the brain through the cranium (behind the skin of the skull)] and receiving the optic radiation reflected and/or scattered therefrom with an optic measurement arrangement [see FIG. 3],
receiving by a data processing arrangement [see FIG. 6, right column, first paragraph disclsoing a laptop computer. It is inherent that a laptop computer has a processing unit] electric signals from the optic measurement arrangement, [see page 5, right column, last paragraph continued in page 6, right and left column, first paragraph disclosing receiving and processing the optical data]
analyzing the electric signals reflecting cardiorespiratory brain pulsations, movement of the brain caused by head movements, neurofluidic pulsations and their relationship and/or vasomotion,[the signals are received from the brain includes all information regarding the movement of brain, neurofluidic pulsation, etc]
determining, by a data processing arrangement, [see FIG. 6, right column, first paragraph disclosing a laptop computer. It is inherent that a laptop computer has a processing unit] based on electric signals from the at least one sensing device data [see page 5, right column, last paragraph continued in page 6, right and left column, first paragraph disclosing receiving and processing the optical data] on at least one of the following dynamics: neurohydrodynamics including blood and water in and within the cranium, [see FIGs. 9, 13, and 14 disclosing the dynamic change in water concentration in the cranium] brain tissue movements, water and/or electrolyte movements and intracranial pressure based on at least one electric signal from the at least one sensing device; [see FIG. 7, 9, 13, and 14 of Myllyla shows the concentration of the water dynamic changes in the cranium] and
outputting, through the interface, of at least one piece of the data [see FIG. 7, 9, 13, and 14 of Myllyla shows the concentration of the water dynamic changes in the cranium
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Myllyla et al.”, Bio Photonics, 2017) hereinafter “Myllyla” in view of Kiviniemi et al. (“Real-time monitoring of human blood-brain barrier disruption”, PLoS ONE 12(3), 2017) hereinafter “Kivineiemi” and Rovati et al. (“Near Infrared spectroscopy for non-invasive monitoring of drugs blood-brain barrier penetration”. IEEE, 2016) hereinafter “Rovati”.
Regarding claim 3, Myllyla discloses all the limitations of claim 1 [see rejection of claim 1]
Myllya does not disclose that the data processing unit is configured to detect an opening of a blood- brain-barrier based on concentration changes of the oxy-hemoglobin, deoxy-hemoglobin and water within the cranium.
Kiviniemi, directed towards monitoring of human BBB disruptions using optical methods [see abstract of Kiviniemi] further discloses that the data processing unit is configured to detect an opening of a blood- brain-barrier based on concentration changes of the oxy-hemoglobin, deoxy-hemoglobin within the cranium. [see FIGS. 1-2 and their caption showing detection of concentration of HbO and Hb in order to find any BBB openings]
Rovati, directed towards optical monitoring of BBB penetration [see abstract of Rovati] further discloses of the data processing unit is configured to detect an opening by monitoring water within the cranium. [see page 4, left column, section under A. Effects of exogenous oxygen showing detection of changes to the total blood volume which is an indication of water in the blood; see also FIG. 4b]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that the data processing unit is configured to detect an opening of a blood- brain-barrier based on concentration changes of the oxy-hemoglobin, deoxy-hemoglobin within the cranium according to the teachings of Kivineimi in order to detect and BBBD which inhibits the penetration of hydrophilic and polar drugs to the brain tissue and hinders the effective treatments to the brain [see page 2, section under Introduction, first paragraph]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that the data processing unit is configured to detect an opening by monitoring water within the cranium according to the teachings of Rovati in order to effectiveness of drug delivery to the brain tissue [see page 1, left column, section under I. introduction, second paragraph]
Claim 12, 16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Myllyla et al.”, Bio Photonics, 2017) hereinafter “Myllyla” in view of Kiviniemi et al. (“Real-time monitoring of human blood-brain barrier disruption”, PLoS ONE 12(3), 2017) hereinafter “Kivineiemi”.
Regarding claim 12, Myllyla discloses all the limitations of claim 1 [see rejection of claim 1]
Myllya does not disclose that the data processing unit is configured to detect an opening of a blood-brain-barrier based on electric signals from the electroencephalographic electrode arrangement of the at least one sensing device.
Kiviniemi, directed towards monitoring of human BBB disruptions using optical methods [see abstract of Kiviniemi] further discloses that the data processing unit is configured to detect an opening of a blood-brain-barrier based on electric signals from the electroencephalographic electrode arrangement of the at least one sensing device. [see page 3, section under DC-EEG and ECG data collection and analysis disclosing detection using electrodes; see the results showing a BBB disruption in FIG. 1a]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that the data processing unit is configured to detect an opening of a blood-brain-barrier based on electric signals from the electroencephalographic electrode arrangement of the at least one sensing device data processing unit is configured to detect an opening of a blood-brain-barrier based on electric signals from the electroencephalographic electrode arrangement of the at least one sensing device according to the teachings of Kivineimi in order to detect and BBBD which inhibits the penetration of hydrophilic and polar drugs to the brain tissue and hinders the effective treatments to the brain [see page 2, section under Introduction, first paragraph]
Regarding claim 16 and 19, Myllyla discloses all the limitations of claim 1 [see rejection of claims 1 and 15]
Kivineimi further discloses an electroencephalographic electrode arrangement [DC-EEG electrodes; see FIG. 1a] in electric contact with skin of the cranium configured to measure direct-current electroencephalographic signals from the brain. [see page 3, section under DC-EEG and ECG data collection and analysis disclosing detection using electrodes; see the results showing a BBB disruption in FIG. 1a]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that an electroencephalographic electrode arrangement in electric contact with skin of the cranium configured to measure direct-current electroencephalographic signals from the brain according to the teachings of Kivineimi in order to detect and BBBD which inhibits the penetration of hydrophilic and polar drugs to the brain tissue and hinders the effective treatments to the brain [see page 2, section under Introduction, first paragraph]
Claim 13, 17, 18, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Myllyla et al.”, Bio Photonics, 2017) hereinafter “Myllyla” in view of Jo et al. (“Real-time estimation of paracellular permeability of cerebral endothelial cells by capacitance sensor array, Scientific Reports, 2015) hereinafter “Jo”
Regarding claim 13, Myllyla discloses all the limitations of claim 1 [see rejection of claim 1]
Myllya does not disclose that the data processing unit is configured to determine an opening of a blood-brain-barrier based on signal of the capacitive sensor arrangement.
Jo, directed towards real time estimation of the permeability of brain cells using capacitance sensors [see abstract of Jo] further disclose that the data processing unit is configured to determine an opening of a blood-brain-barrier based on signal of the capacitive sensor arrangement.
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that the data processing unit is configured to determine an opening of a blood-brain-barrier based on signal of the capacitive sensor arrangement according to the teachings of Dong in order to
Regarding claims 17 and 18, Myllyla discloses all the limitations of claim 1 [see rejection of claims 1 and 16]
Jo further discloses a capacitive sensor arrangement in proximity to, but without electric contact with, skin of the cranium, configured to measure electric potential signals of the brain.[see page 2, second and third paragraph disclosing using a capacitive sensor array]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that it further includes a capacitive sensor arrangement in proximity to, but without electric contact with, skin of the cranium, configured to measure electric potential signals of the brain according to the teachings of Myllyla in order to obtain real-time electrical properties of the cytoplasm conductivity [see page 2, second paragraph of Jo]
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Myllyla et al. (“Assessment of the dynamics of human glymphatic system by near-infrared spectroscopy”, Bio Photonics, 2017) hereinafter “Myllyla” in view of Sutin et al. (U.S. Publication No. 2018/0103861) hereinafter “Sutin”.
Regarding claim 7, Myllyla discloses all the limitations of claim 1 [see rejection of claim 1]
Myllya does not disclose that the data processing unit is configured to determine the intracranial pressure and/or stiffness of the brain based on a waveform of a signal of the data on the hydrodynamics of at least one of the following: the water within the cranium and the cerebral blood, the waveform being caused by head movements, heartbeat and/or breathing.
Sutin, directed towards non-invasive intracranial monitoring [see abstract of Sutin] the data processing unit is configured to determine the intracranial pressure [see step 810 of FIG. 8 and [0081] of Sutin] and/or stiffness of the brain based on a waveform of a signal of the data on the hydrodynamics of at least one of the following: the water within the cranium and the cerebral blood, the waveform being caused by head movements, heartbeat and/or breathing. [see [0077]-[0081] disclosing using heart rate and respiration data, hemoglobin data and oximetry data to determine the intracranial pressure]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that the data processing unit is configured to determine the intracranial pressure and/or stiffness of the brain based on a waveform of a signal of the data on the hydrodynamics of at least one of the following: the water within the cranium and the cerebral blood, the waveform being caused by head movements, heartbeat and/or breathing according to the teachings of Sutin in order to monitor and determine any intracranial hemorrhage or traumatic brain injuries [see [0008] of Sutin]
Regarding claim 8, Myllyla as modified by Sutin discloses all the limitations of claim 7 [see rejection of claim 7]
Myllyla discloses that the data processing unit is configured to compare the waveform with a reference waveform, which is based on a physiological model of a brain, [see page 6, right column, section under 3.2. simultaneous NIRS and fMRI, first paragraph]
Myllyla does not disclose that the comparison is done for determining at least one of the following: brain stiffness, the intracranial pressure and deviation from the physiological model.
Sutin further discloses that the comparison is done for determining at least one of the following: brain stiffness, the intracranial pressure and deviation from the physiological model. [see [0084] of Sutin disclosing comparing the waveforms with reference to another signal or event at a different time]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that for determining at least one of the following: brain stiffness, the intracranial pressure and deviation from the physiological model.
Regarding claim 9, Myllyla as modified by Sutin discloses all the limitations of claim 7 [see rejection of claim 7]
Myllyla further discloses that the data processing unit is configured to decompose the waveform into decompositions, [see page 7, left column, discloses a linear decomposition of the waveform into independent components]
Myllyla does not disclose to determine at least one of the following: brain stiffness, the intracranial pressure and deviation from the physiological model.
Sutin further discloses to determine at least one of the following: brain stiffness, the intracranial pressure and deviation from the physiological model. [see step 810 of FIG. 8 and [0081] of Sutin]
It would have been obvious to a person of ordinary skill level in the art at the time of the filing of the invention to modify the teachings of Myllyla further such that it is configured to determine at least one of the following: brain stiffness, the intracranial pressure and deviation from the physiological model according to the teachings of Sutin in order to monitor and determine any intracranial hemorrhage or traumatic brain injuries [see [0008] of Sutin]
Regarding claim 10, wherein data processing unit is configured to form correlation relating to a phase difference and/or amplitude difference at specific frequencies of very low frequencies (0.001 Hz - 0.01 Hz), low frequency (0.01 Hz - 0.1 Hz), respiratory band and cardiac band between dynamics of blood and water within the cranium to determine data on glymphatic activity and/or BBB.
Response to Arguments
Applicant's arguments filed 04/13/2026 have been fully considered but they are not persuasive.
Allowable Subject Matter
Claims 20 and 21 are 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.
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 MARJAN - SABOKTAKIN whose telephone number is (303)297-4278. The examiner can normally be reached M-F 9 am-5pm CT.
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/MARJAN SABOKTAKIN/Examiner, Art Unit 3797
/MICHAEL J CAREY/Supervisory Patent Examiner, Art Unit 3795
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