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 .
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.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claims 1-2, 5, 7, and 13 are objected to because of the following informalities: typographical and grammatical errors.
Regarding Claim 1, the limitation "ouput" recited in the last line of the claim should recite "output".
Regarding Claim 2, the limitation "removal step of is performed" recited in the fourth line of the claim is not proper grammar. This limitation should recite something similar to "removal step is performed".
Regarding Claim 5, the limitation term "but" recited in the fourth line of the claim is not proper. This limitation should recite something similar to "wherein extracting a pure water fraction by removing the oxidized hemoglobin fraction and reduced hemoglobin fraction from the water fraction is calculated using Linear Minimum Mean Square Error (LMMSE)".
Regarding Claim 7, the term "the" in the limitation "the glymphatic system activity" recited in the last line of the claim is not needed. This limitation should recite something similar to "measured glymphatic system activity" without the extra "the".
Regarding Claim 13, the limitation “constructing database comprising” recited in the fourth line of the claim is not proper grammar. This limitation should recite something similar to “constructing a database comprising”.
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 2-5, 8-12, 15, and 17-18 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 Claim 2, the limitation “the signal” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the signals”.
Regarding Claim 3, the limitation “the signal” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the signals”.
Regarding Claim 4, the limitation “the oxidized hemoglobin fraction” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the calculated oxidized hemoglobin”.
Regarding Claim 5, the limitation “the oxidized hemoglobin fraction” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the calculated oxidized hemoglobin”. Additionally, “the reduced hemoglobin fraction” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the calculated reduced hemoglobin”.
Regarding Claim 8, the limitation “the selected group” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “a selected group”.
Regarding Claim 9, the limitation “the difference” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the significant difference”.
Regarding Claim 10, the limitation “the selected group” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “a selected group”. Additionally, the limitation “the sleep state” lacks proper antecedent basis. This limitation is being interpreted to mean “a sleep state”.
Regarding Claim 11, the limitation “the difference” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the significant difference”.
Regarding Claim 15, the limitation “the difference” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “the significant difference”.
Regarding Claim 17, the limitation “the initial” recited in the claim lacks proper antecedent basis. This limitation is being interpreted to mean “an initial”.
Regarding Claim 18, the limitation "the cerebral pressure regulator" recited in line 3 of the claims lacks proper antecedent basis. This limitation is being interpreted to mean "cerebral pressure regulator". Additionally, the limitation "the cerebral pressure information" recited in line 4 of the claim lacks proper antecedent basis. This limitation is being interpreted to mean "the cerebral pressure measured in the information provision step".
Claims not explicitly rejected above are rejected due to their dependence on the above claims.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than an abstract idea. A streamlined analysis of Claim 1 follows.
STEP 1
Regarding Claim 1, the claim recites a series of steps or acts, including monitoring brain water, calculating oxidized hemoglobin, calculating reduced hemoglobin, calculating water fraction, extracting a pure water fraction, and outputting the water fraction. Thus, the claim is directed to a process, which is one of the statutory categories of invention.
STEP 2A, PRONG ONE
The claim is then analyzed to determine whether it is directed to any judicial exception. The steps of calculating oxidized hemoglobin, reduced hemoglobin, and water fraction as well as extracting a pure water fraction set forth a judicial exception. These steps recite mathematical concepts or merely limitations that are based on or involve a mathematical concept. Thus, the claim is drawn to a Mathematical Concept, which is an Abstract Idea.
STEP 2A, PRONG TWO
Next, the claim as a whole is analyzed to determine whether the claim recites additional elements that integrate the judicial exception into a practical application. The claim fails to recite an additional element or a combination of additional elements to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception. Claim 1 recites outputting the water fraction extracted in the extraction step, which is merely adding insignificant extra-solution activity to the judicial exception (MPEP 2106.05(g)). The outputting of the water fraction does not provide an improvement to the technological field, the method does not effect a particular treatment or effect a particular change based on the extracted water fraction, nor does the method use a particular machine to perform the Abstract Idea.
STEP 2B
Next, the claim as a whole is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Besides the Abstract Idea, Claim 1 recites additional steps of outputting the water fraction extracted in the extraction step. The outputting step is recited at a high level of generality such that it amounts to insignificant extra-solution activity to the judicial exception. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional step that distinguishes it from well-understood, routine, and conventional extra-solution activity engaged in by medical professionals prior to Applicant's invention. Additionally, it is well established that the mere physical or tangible nature of additional elements such as the outputting step do not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int'l, 134 S.Ct. 2347, 2358-59 (2014)). Furthermore, the recited “processor” is a generic computer device with a generic computer program that is configured to perform outputting the water fraction extracted in the extraction step. The generic computer and its program are configured to perform the above as well as the Abstract Idea. According to section 2106.05(f) of the MPEP, merely using a computer as a tool to perform an abstract idea does not integrate the Abstract Idea into a practical application.
Consideration of the additional elements as a combination also adds no other meaningful limitations to the exception not already present when the elements are considered separately. Unlike the eligible claim in Diehr in which the elements limiting the exception are individually conventional, but taken together act in concert to improve a technical field, the claim here does not provide an improvement to the technical field. Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claim as a whole does not amount to significantly more than the exception itself. The claim is therefore drawn to non-statutory subject matter.
Dependent Claims 2-18 fail to add something more to the abstract independent claims as they generally recite steps pertaining to data gathering and processing.
The calculating, extracting, and outputting steps recited in the independent Claim 1, maintain a high level of generality even when considered in combination with the dependent claims.
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.
Claims 1-2, 4, 6-9, 13, and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Izzetoglu et. al.'054 (U.S. Patent Publication 20160310054 - cited by applicant).
Regarding Claim 1, Izzetoglu et. al.'054 discloses a method for monitoring brain water based on near- infrared spectroscopy (Paragraph [0084] - One embodiment of a method of use of the NIR system or device described herein is for a method of assessing cerebral autoregulation; Paragraph [0084] - obtaining multiple measurements from the subject over time of oxygenated (oxyHb), deoxygenated hemoglobin (deoxyHb) and water using near infrared spectroscopy (NIR)), performed by a processor (Paragraph [0062] - The system 10 may also include a control box 16 for data acquisition, a power supply for the control box (not shown), and a computer or electronic processing device 18 having or providing access to data analysis software), which is characterized by:
a calculation step of calculating oxidized hemoglobin, reduced hemoglobin, and water fraction based on signals measured by near-infrared spectroscopy (Paragraph [0084] - obtaining multiple measurements from the subject over time of oxygenated (oxyHb), deoxygenated hemoglobin (deoxyHb) and water using near infrared spectroscopy (NIR));
an extraction step of extracting a pure water fraction from the water fraction calculated in the calculation step (Paragraph [0073] - With the use of these three wavelengths together, spectroscopic measurements for the extraction of the primary chromophores of interest in the tissue such as water, oxyHb and deoxyHb can be performed; Paragraph [0078] - the signal processing component of the device will have the capability to automatically adjust the signal separation algorithm embedded in the system and use the temperature information to adjust the extinction coefficients in the MBLL accordingly for more reliable separation in Hb, HbO.sub.2, and water content; Paragraph [0079] – Using the oxygen saturation measurements that can be obtained by the device, adjustments to DPF values can be established in the system for more reliable separation of water content from the remainer of the chromophores; Paragraph [0101] - This pre-clinical prototype is capable of measuring changes in water and blood content of the tissue within the head beneath the sensor collecting data; Paragraph [0113] - The tests justified the use of MBLL in resolving Hb, HbO.sub.2 and water concentrations and the selection of 960 nm wavelength light source to focus the measurements to the water content of the brain; Paragraph [0118] - The device and the analysis methods based on MBLL are tested in the separation of blood and water content under different blood oxygenation conditions; Paragraph [0130] - For the same subject and conditions, the change in oxygenated (HbO.sub.2) and deoxygenated hemoglobin (Hb) and water content extracted using MBLL is presented in FIG. 27); and
an output step of outputting the water fraction extracted in the extraction step (Paragraph [0062] - As shown in FIG. 3, the computer 18 may have a display for displaying and presenting measurements taken by the device; Paragraph [0113] - The tests justified the use of MBLL in resolving Hb, HbO.sub.2 and water concentrations and the selection of 960 nm wavelength light source to focus the measurements to the water content of the brain).
It should be noted that Izzetoglu et. al.'054 refers to “deoxygenated hemoglobin” as “Hb” within their specification as recited in Paragraph [0118].
Regarding Claim 2, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the method is characterized by further comprising a removal step of removing motion artifacts from the signal measured using the near-infrared spectroscopy (Paragraph [0081] - Thus, in addition to the above referenced parameter adjustments in the signal analysis component of the proposed device, the system will also have algorithms to identify and remove artifacts due to head movement or patient laying position adjustment by using the measurements obtained from contralateral sides (expected to be in reverse direction for artifacts), the timing and amount of change in the signal values (larger amount changes in shorter time as compared to changes that can be expected when there is edema or hematoma development)), wherein
the removal step of is performed before or after the calculation step (Paragraph [0081] - This type of signal change may be identified and corrected from the measurements).
Regarding Claim 4, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the extraction step is characterized by extracting a pure water fraction by removing the oxidized hemoglobin fraction and the reduced hemoglobin fraction from the water fraction calculated in the calculation step (Paragraph [0113] - The tests justified the use of MBLL in resolving Hb, HbO.sub.2 and water concentrations and the selection of 960 nm wavelength light source to focus the measurements to the water content of the brain; Paragraph [0118] - The device and the analysis methods based on MBLL are tested in the separation of blood and water content under different blood oxygenation conditions).
Regarding Claim 6, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the method is characterized by further comprising an information provision step of providing information on glymphatic system activity based on the water fraction extracted in the extraction step (Paragraph [0054] - According to an embodiment, a system, device and method for quantitatively monitoring and evaluating changes in water and hemoglobin content in the brain in a non-invasive manner are provided. Such a system or device may be used for real-time detection and monitoring of brain edema and/or for an assessment of cerebral autoregulation).
Regarding Claim 7, Izzetoglu et. al.'054 discloses the method outlined in Claim 6 above as well as wherein the information provision step is characterized by measuring glymphatic system activity based on the water fraction in the extraction step and providing information on measured the glymphatic system activity (Paragraph [0074] - decrease in cerebral blood flow (CBF) or increased cerebral blood volume which are very common consequences of traumatic brain injury. Thus, the embodiment disclosed herein monitors both the hemoglobin and water contents in the brain; Paragraph [0132] - Further analysis was performed separately on the correlations of ICP and cerebral perfusion pressure (CPP) with HbO.sub.2, Hb and water content).
Regarding Claim 8, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the method is characterized by further comprising: a standard data construction step of constructing standard data of brain tissue water based on measurements taken in the selected group (Paragraph [0084] - The multiple measurements obtained from the subject are evaluated against a reference standard to identify any change in the measurements of oxyHb, deoxyHb and water characteristic of hypoxic injury or aberrent cerebral autoregulation); and
an information provision step of providing information comprising evaluating glymphatic system activity based on the water fraction extracted in the extraction step and the standard data of brain tissue water and providing evaluation information (Paragraph [0062] - The system 10 may also include a control box 16 for data acquisition, a power supply for the control box (not shown), and a computer or electronic processing device 18 having or providing access to data analysis software. As shown in FIG. 3, the computer 18 may have a display for displaying and presenting measurements taken by the device; Paragraph [0074] - decrease in cerebral blood flow (CBF) or increased cerebral blood volume which are very common consequences of traumatic brain injury. Thus, the embodiment disclosed herein monitors both the hemoglobin and water contents in the brain).
Regarding Claim 9, Izzetoglu et. al.'054 discloses the method outlined in Claim 8 above as well as wherein the information provision step is characterized by comparing the water fraction extracted in the extraction step with the standard data of brain tissue water, and if a significant difference occurs with the standard data of brain tissue water, providing information by scoring it with a categorization result or standardized value corresponding to the difference (Paragraph [0062] - The system 10 may also include a control box 16 for data acquisition, a power supply for the control box (not shown), and a computer or electronic processing device 18 having or providing access to data analysis software. As shown in FIG. 3, the computer 18 may have a display for displaying and presenting measurements taken by the device; Paragraph [0084] - The multiple measurements obtained from the subject are evaluated against a reference standard to identify any change in the measurements of oxyHb, deoxyHb and water characteristic of hypoxic injury or aberrent cerebral autoregulation; Paragraph [0094] - To permit proper determination or identification of disease or injury based on the NIR measurements of oxyHb, deoxyHb and water, and optionally temperature, oxygen saturation or other data obtained from a subject, the subject's measurements are compared to reference; Paragraph [0109] - These percent levels of change in the NIR signals are comparable to signal level changes (20-to-40%) due to 1-3% change in the water content of the brain as measured by phantom tests for edema monitoring).
Regarding Claim 13, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the method is characterized by further comprising: a database (DB) construction step of constructing database comprising neurodegenerative brain disease indicators corresponding to glymphatic system activity (Paragraph [0094] - The terms “Reference”, “Reference Standard” or “Control” as used herein mean a level, standard or profile of reference NIR data e.g., OD or other signals detected by the NIR devices used in the methods described herein. To permit proper determination or identification of disease or injury based on the NIR measurements of oxyHb, deoxyHb and water, and optionally temperature, oxygen saturation or other data obtained from a subject, the subject's measurements are compared to reference); and
an information provision step of providing auxiliary information related to neurodegenerative brain disease based on the water fraction extracted in the extraction step and the database (Paragraph [0099] - Based on this evaluation and the relative changes in the subject's NIR data for oxyHb, deoxyHb and water compared to one or multiple reference standards, the physician can identify the occurrence of a hypoxic event or injury or disease in the subject by identifying a characteristic decrease in the NIR values occasioned by hypoxic injury. The same method is useful for monitoring and adjusting therapy for a subject recovering or under treatment for such a hypoxic injury).
Regarding Claim 15, Izzetoglu et. al.'054 discloses the method outlined in Claim 13 above as well as wherein the DB construction step constructs standard data of brain tissue water (Paragraph [0084] - The multiple measurements obtained from the subject are evaluated against a reference standard to identify any change in the measurements of oxyHb, deoxyHb and water characteristic of hypoxic injury or aberrent cerebral autoregulation), and
wherein the information provision step is characterized by comparing the water fraction extracted in the extraction step with the standard data of brain tissue water, and if a significant difference occurs with the standard data of brain tissue water, providing auxiliary information related to prediction, progression, diagnosis, and treatment of neurodegenerative brain disease by scoring it with a categorization result or standardized value corresponding to the difference (Paragraph [0094] - The selection of the reference standard is made by the physician to diagnose or identify the injury, its likely time or occurrence, and/or monitoring the subject's recovery from injury or response to treatment. The terms “Reference”, “Reference Standard” or “Control” as used herein mean a level, standard or profile of reference NIR data e.g., OD or other signals detected by the NIR devices used in the methods described herein. To permit proper determination or identification of disease or injury based on the NIR measurements of oxyHb, deoxyHb and water, and optionally temperature, oxygen saturation or other data obtained from a subject, the subject's measurements are compared to reference; Paragraph [0099] - Based on this evaluation and the relative changes in the subject's NIR data for oxyHb, deoxyHb and water compared to one or multiple reference standards, the physician can identify the occurrence of a hypoxic event or injury or disease in the subject by identifying a characteristic decrease in the NIR values occasioned by hypoxic injury. The same method is useful for monitoring and adjusting therapy for a subject recovering or under treatment for such a hypoxic injury).
Regarding Claim 16, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the method is characterized by further comprising: an information provision step of providing information comprising measuring cerebral edema and cerebral pressure based on the water fraction extracted in the extraction step and providing information on the measured cerebral edema and cerebral pressure (Paragraph [0054] - Such a system or device may be used for real-time detection and monitoring of brain edema and/or for an assessment of cerebral autoregulation; Paragraph [0058] - Since hemoglobin content can change, for example, due to hematoma development together with changes in the water content due to edema, the device may be designed to monitor the changes in all of these absorbers simultaneously; Paragraph [0074] - Accordingly, changes in concentrations of water, oxyHb and deoxyHb due to edema can be reliably measured even in the presence of hemorrhage or hematoma which can occur simultaneously with edema or regardless of changes in the blood content due decrease in cerebral blood flow (CBF) or increased cerebral blood volume which are very common consequences of traumatic brain injury. Thus, the embodiment disclosed herein monitors both the hemoglobin and water contents in the brain; Paragraph [0077] - Hence, changes in blood content should be extracted and closely monitored together with the water content for the reliable and robust monitoring of edema; Paragraph [0101] - An overall edema monitoring system 110 according to an embodiment having a NIR sensor 112, data acquisition box 114, and presentation computer 116 is shown in FIG. 10 and was used during laboratory experimentation on a head mimicking phantom 118. This pre-clinical prototype is capable of measuring changes in water and blood content of the tissue within the head beneath the sensor collecting data on contra-lateral sides of the forehead at depth ˜2 cm with a sampling rate of 2 Hz; Paragraph [0131] - This change in intracranial pressure was also reflected in both the raw intensity measurements (FIG. 26) and also in blood and water level changes (FIG. 27); Paragraph [0132] - Further analysis was performed separately on the correlations of ICP and cerebral perfusion pressure (CPP) with HbO.sub.2, Hb and water content).
Regarding Claim 17, Izzetoglu et. al.'054 discloses the method outlined in Claim 16 above as well as wherein the information provision step is characterized by measuring water amount of brain tissue at regular intervals, comparing it with the initial value, and providing information on the cerebral edema and cerebral pressure by scoring the difference with a categorization result or standardized value corresponding to the difference (Paragraph [0094] - To permit proper determination or identification of disease or injury based on the NIR measurements of oxyHb, deoxyHb and water, and optionally temperature, oxygen saturation or other data obtained from a subject, the subject's measurements are compared to reference; Paragraph [0099] - Based on this evaluation and the relative changes in the subject's NIR data for oxyHb, deoxyHb and water compared to one or multiple reference standards; Paragraph [0110] - In real human subject testing, all the changes in the measurements can be obtained continuously, every hour or in 6 hour intervals will be calculated relative to the first measurement period).
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 3 is rejected under 35 U.S.C. 103 as being unpatentable over Izzetoglu et. al.'054 (U.S. Patent Publication 20160310054 - cited by applicant) as applied to Claim 2 above, and further in view of Rodriguez-Llorente et. al.'861 (U.S. Patent Publication 20140073861).
Regarding Claim 3, Izzetoglu et. al.'054 discloses the method outlined in Claim 2 above as well as removing motion artifacts by filtering signal measured using the near-infrared spectroscopy (Paragraph [0067] - The control box 16 may host analog filters and amplifies and may be connected to a data acquisition board (DAQ) 34 which is connected to the computer 18. The DAQ 34 may be designed to be responsible for switching the light sources 20 and photo detectors, 22 and 24, which collect the reflected light. Thus, operation of the light sources at the three wavelengths may be controlled by data acquisition software on the DAQ 34 and powered by driving current), but fails to explicitly disclose removing motion artifacts by low-pass filtering and spline interpolation. Rodriguez-Llorente et. al.'861 teaches using low pass filtering and spline interpolation to filter data (Paragraph [0228] -Signal conditioning may include applying a filter (e.g., a low pass, high pass, band pass, notch, or any other suitable analog or digital filter); Paragraph [0705] - In some such circumstances, the processing equipment may interpolate the data to generate additional data points in between the sampled data points. The interpolation may be linear, spline, or any other suitable interpolation technique. The interpolated data may include an increased number of data points, having a reduced spacing interval. Interpolation may, in some instances, aid implementation of one or more Qualification Techniques). It would have been obvious to one of ordinary skill in the art at the time the invention was effectively filed to have modified the method of Izzetoglu et. al.'054 to include low-pass filtering and spline interpolation in order to filter data using analog software as seen in Rodriguez-Llorente et. al.'861. Additionally, given that both Izzetoglu et. al.’054 and Rodriguez-Llorente et. al.'861 use analog digital filters, the simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Izzetoglu et. al.'054 (U.S. Patent Publication 20160310054 - cited by applicant) as applied to Claim 1 above, and further in view of Li et. al.'208 (U.S. Patent Publication 20020038208).
Regarding Claim 5, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the extraction step is characterized by removing the oxidized hemoglobin fraction and reduced hemoglobin fraction from the water fraction calculated in the calculation step (Paragraph [0079] - Hence, necessary adjustments are made to the DPF values when using it in MBLL for the reliable extraction of the chromophores by reducing crosstalk between measurements; Paragraph [0113] - The tests justified the use of MBLL in resolving Hb, HbO.sub.2 and water concentrations and the selection of 960 nm wavelength light source to focus the measurements to the water content of the brain; Paragraph [0118] - The device and the analysis methods based on MBLL are tested in the separation of blood and water content under different blood oxygenation conditions; Paragraph [0120] - The water, Hb and HbO.sub.2 concentration changes as measured by with 730, 850 and 940/960 nm wavelengths completely followed expected patterns in this experiment), but fails to disclose using Linear Minimum Mean Square Error (LMMSE). Li et. al.'208 teaches using Linear Minimum Mean Square Error to extract signals (Paragraph [0025] - According to an embodiment of the invention, a method employs a linear minimum mean-square error filter, know as the Kalman Filter, for extracting sinusoidal physiological signals, such as DPOAEs and ASSRs, from noise is described. The method includes signal modeling and fast signal processing algorithm. This method is also suitable for extracting any physiological signals of known frequency composition from background noise). It would have been obvious to one of ordinary skill in the art at the time the invention was effectively filed to have modified the method of Izzetoglu et. al.'054 to include a filtering technique such as LMMSE in order to extract physiological signals from other data, particularly being able to extract values from noise as seen in Li et. al.'208.
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Izzetoglu et. al.'054 (U.S. Patent Publication 20160310054 - cited by applicant) as applied to Claim 1 above, and further in view of Yokota et. al.’1989 (Overnight recordings of intracranial pressure and electroencephalography in neurosurgical patients. Part II: Changes in intracranial pressure during sleep).
Regarding Claims 10-12, Izzetoglu et. al.'054 discloses the method outlined in Claim 1 above as well as wherein the method is characterized by further comprising: a standard data construction step of constructing standard data of brain tissue water based on measurements taken in a selected group (Paragraph [0098] - the reference standard utilized is a standard or profile derived from averaged data from multiple reference subjects. The reference standard, in various embodiments, is a mean, an average, a numerical mean or range of numerical means, a numerical pattern, or a graphical pattern created from the NIRS data derived from a reference subject or reference population); providing information regarding to measurements taken from a subject in an unconscious or awake state (Paragraph [0062] - The system 10 may also include a control box 16 for data acquisition, a power supply for the control box (not shown), and a computer or electronic processing device 18 having or providing access to data analysis software. As shown in FIG. 3, the computer 18 may have a display for displaying and presenting measurements taken by the device; Paragraph [0080] - the system may be used may also primarily be critically ill patients who may be unconscious. Head movement and change in baseline measurements due to head movement, presents a problem for the NIR measurements. Even in patients that are awake; Paragraph [0132] - Further analysis was performed separately on the correlations of ICP and cerebral perfusion pressure (CPP) with HbO.sub.2, Hb and water content); and comparing measurements to a standard and identifying significant differences between an obtained measurement and differences (Paragraph [0062] - The system 10 may also include a control box 16 for data acquisition, a power supply for the control box (not shown), and a computer or electronic processing device 18 having or providing access to data analysis software. As shown in FIG. 3, the computer 18 may have a display for displaying and presenting measurements taken by the device; Paragraph [0084] - The multiple measurements obtained from the subject are evaluated against a reference standard to identify any change in the measurements of oxyHb, deoxyHb and water characteristic of hypoxic injury or aberrent cerebral autoregulation; Paragraph [0094] - To permit proper determination or identification of disease or injury based on the NIR measurements of oxyHb, deoxyHb and water, and optionally temperature, oxygen saturation or other data obtained from a subject, the subject's measurements are compared to reference; Paragraph [0109] - These percent levels of change in the NIR signals are comparable to signal level changes (20-to-40%) due to 1-3% change in the water content of the brain as measured by phantom tests for edema monitoring).
Izzetoglu et. al.'054 fails to disclose providing information on the sleep state according to glymphatic system activity in wakefulness-sleep or sleep stages based on the water fraction extracted in the extraction step and the standard data of brain tissue water. Yokota et. al.’1989 teaches identifying a sleep stage based on obtained intracranial pressure (ICP) (Abstract - The patients were conscious, and sleep stages including REM sleep were observed in all of them. During non-REM sleep, ICP significantly rose in Stage II on many occasions, and was always lower in Stage IV than in other sleep stages. A marked elevation of ICP was seen in REM sleep). It would have been obvious to one of ordinary skill in the art at the time the invention was effectively filed to have modified the method of Izzetoglu et. al.'054 to include identifying information pertaining to sleep stages of a subject based on measurements such as intracranial pressure (ICP) and water content in order to understand trends and changes occurring during a measurement process whenever a subject is in various stages of being unconscious and conscious as seen in Yokota et. al.’1989.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Izzetoglu et. al.'054 (U.S. Patent Publication 20160310054 - cited by applicant) as applied to Claim 13 above, and further in view of Dagum et. al.’184 (U.S. Patent 11478184).
Regarding Claim 14, Izzetoglu et. al.'054 discloses the method outlined in Claim 13 above as well as a computer with an analysis software (Paragraph [0062] -The system 10 may also include a control box 16 for data acquisition, a power supply for the control box (not shown), and a computer or electronic processing device 18 having or providing access to data analysis software) providing information and indicators to a physician related to prediction, progression, diagnosis, and treatment of an illness (Paragraph [0094] - To permit proper determination or identification of disease or injury based on the NIR measurements of oxyHb, deoxyHb and water, and optionally temperature, oxygen saturation or other data obtained from a subject, the subject's measurements are compared to reference; Paragraph [0099] - Based on this evaluation and the relative changes in the subject's NIR data for oxyHb, deoxyHb and water compared to one or multiple reference standards, the physician can identify the occurrence of a hypoxic event or injury or disease in the subject by identifying a characteristic decrease in the NIR values occasioned by hypoxic injury. The same method is useful for monitoring and adjusting therapy for a subject recovering or under treatment for such a hypoxic injury). Izzetoglu et. al.'054 fails to explicitly disclose searching a neurodegenerative brain disease indicator corresponding to the measured the glymphatic system activity in the database, and then providing auxiliary information related to prediction, progression, diagnosis, and treatment of neurodegenerative brain disease based on the searched indicator. Dagum et. al.’184 teaches a software module comprising models and mapping of data to neurodengerative diseases (Column 10 Lines 11-20 - For example, the learning software module can comprise a machine learning algorithm or deep learning algorithm that determines a function mapping from the collected neurophysiological and neurovascular data to a target marker of glymphatic clearance or neurodegeneration. The prediction module can comprise a model based on the function mapping that is used to predict glymphatic clearance or neurodegeneration based on sensor data that is newly collected by the wearable computing device from a patient; Column 19 Lines 1-4 - The predictions can be continuous values of marker values used to monitor for disease progression or response to intervention, or categorical values to determine the presence or absence of a disease stage). It would have been obvious to one of ordinary skill in the art at the time the invention was effectively filed to have modified the method of Izzetoglu et. al.'054 to include in their analysis software a database correlating measurement indicators to neurodegenerative diseases in order to reduce the need of a physician to observe the data and allow a subject to intervene as early as possible for a chance to slow or stop progression of the disease/illness as seen in Dagum et. al.’184 (Column 4 Lines 42-48 - practitioners today use clinical assessment and cognitive evaluations to screen, diagnose and monitor neurodegenerative disorders such as Alzheimer's disease. The opportunity to intervene early in the 10-to-20-year pre-clinical period of these disorders is lost as is the ability to evaluate promising new treatments that could slow or stop disease progression).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Izzetoglu et. al.'054 (U.S. Patent Publication 20160310054 - cited by applicant) as applied to Claim 16 above, and further in view of Swoboda et. al.'998 (U.S. Patent Publication 20130109998).
Regarding Claim 18, Izzetoglu et. al.'054 discloses the method outlined in Claim 16 above as well as obtaining information pertaining to cerebral pressure (Paragraph [0127] - In addition to NIR measurements, patients' neurological status obtained through Glasgow coma scale (GCS) scores, intracranial pressure monitoring (ICP) and CT or magnetic resonance imaging (MRI) scans were also obtained serially for correlation analysis to validate the efficacy of NIR technology in edema monitoring; Paragraph [0138] - The data shows that the increase in NIRS-derived cerebral water signal correlated well with increases in both cerebral water content and intracranial pressure (see FIGS. 35, 36 and 37)), but fails to disclose a control step of controlling the cerebral pressure regulator based on the cerebral pressure information. Swoboda et. al.'998 teaches controlling a shunt (cerebral pressure regulator) in response to cerebral pressure measurements (Paragraph [0078] - The method of ICP assessment is claimed. Because the "opening pressure" of the adjustable shunt valve is a known parameter (e.g., 12 cmH.sub.2O), this method can be utilized if there is no natural CSF flow in the shunt. The operator takes following steps 1) continuously observes flow measured by the ShuntCheck device; and 2) simultaneously decreases opening pressure of the CSF shunt valve; the shunt valve opening pressure can be controlled by an operator using a remote control 802 (e.g., via magnetic coupling), as shown in FIG. 11). It would have been obvious to one of ordinary skill in the art at the time the invention was effectively filed to have modified the method of Izzetoglu et. al.'054 to include a controllable shunt in order to assist in flow is cerebral spinal fluid (CSF) and control pressure within the brain as seen in Swoboda et. al.'998 (Paragraph [0078] - the opening pressure of the adjustable shunt valve 800 coincides with first CSF flow detection and thus this identifies the ICP).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Nedergaard et. al.’867 (U.S. Patent Publication 20220031867) discloses a device correlating changes in intracranial pressure (ICP) as well as brain water content (BWC) to changes in glymphatic flow.
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/SARAH ANN WESTFALL/Examiner, Art Unit 3791
/ETSUB D BERHANU/Primary Examiner, Art Unit 3791
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