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 .
This Office Action is responsive to the Reply to Office Action filed December 29, 2025. The Examiner acknowledges the amendments to claims 15, 36, 39 and 48. Claims 15-23, 30-37, 39-43 and 48 are currently pending, with claims 39-43 being withdrawn from consideration.
Response to Arguments
Claims 15, 36, 39, and 48 have been amended to include language directed to “applying, by a pressure applying unit, a predetermined pressure on the tissue when the probe is pressed against the tissue during the impedance measurement session, wherein said pressure is constant during the impedance measurement session and wherein the predetermined pressure is within a range of 3 - 10 N.”
It is noted that claims 30-36 have not been amended to include the subject matter with respect to “applying a pressure by a pressure applying unit”.
Applicant’s arguments, see Remarks, filed 2/27/26, with respect to the rejection of claims 15-23, 30-37 & 48 under 35 USC 101 have been fully considered and are persuasive. The rejection of claims 15-23, 30-37 & 48 under 35 USC 101 has been withdrawn.
Applicant’s arguments, see Remarks, filed 2/27/26, with respect to the rejection of claim 48 under 35 USC 112 have been fully considered and are persuasive. The rejection of claim 48 under 35 USC 112 has been withdrawn.
Applicant’s arguments, see Remarks, filed 2/27/26, with respect to the rejection of claims 15-23, 30-37 & 48 under 35 USC 103 have been fully considered and not persuasive. It is noted that claims 30-36 have not been amended to include the subject matter with respect to “applying a pressure by a pressure applying unit”. The previously applied Davies reference does appear to teach applying pressure to improve the impedance measurements. Note the abstract and paragraph [0116 ] in Davies and as set forth in the rejection below.
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(s) 15, 19-23 & 30-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application Publication 20090306535 --as previously cited--, hereinafter referenced as "Davies" in view of US Patent Application Publication 20140086977, hereinafter referenced as "O'neill".
With respect to claim 15, Davies teaches a method for assessing and monitoring epithelial barrier function of a subject in vivo using only electrical impedance measurements (i.e., measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, abstract, par 0056) comprising:
initiating an impedance measurement session including passing an electrical current through skin of the subject to obtain data of electrical impedance of a target tissue region using a plurality of electrodes adapted to be placed in contact with the target tissue region (see Davies, par 0091, 0096, 0120, 0128, fig. 1 & 3), wherein each electrode is provided with spikes, thereby forming a spiked surface (i.e., the electrode is inserted into a tissue or an intradermal electrode is used) (see Davies, par 0091, 0095), said data comprising at least one impedance value measured in the target tissue region at different tissue layers (i.e., different depths) (see Davies, par 0037, 0090, 0094, 0099-0100);
selectively activating electrode pairs to gradually scan tissue of the subject so as to obtain a sequence of electrical impedance values from selected tissue depths (see Davies, par 0012, 0037, 0056, 0090-0091, 0122);
applying an evaluation procedure (i.e., evaluating the electrophysiological properties such as impedance, transepithelial potential, or changes in spontaneous oscillations in transepithelial potential or impedance) (see Davies, par 0102-0104) for analyzing the epithelial barrier function in the target tissue region based only on the measured data of impedance values for the target tissue region at different tissue layers (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0102-0104),
wherein the evaluation procedure of the measured electrical impedance values provides an outcome indicating a status of the epithelial barrier function of the subject (i.e., determine the condition of the investigated tissue based upon its measured electrophysiological properties), wherein the outcome indicating the status of the epithelial barrier function is based only on the measured electrical impedance values (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0102-0104, 0122-0123),
wherein the status of the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (i.e., electrical impedance measurements, when compared to healthy tissue, provide information about the functional state of the epithelium and can detect early changes that may become malignant) (see Davies, par 0090).
Davies also teaches Ambient and varying pressure measurements applied to epithelial tissue are also used for diagnosis. Improved diagnosis of tissue condition can be made based on the electrical properties and tissue electrophysiological response to altered ion transport and pressure. And in paragraph [0116] , A particularly improved device, will employ an automated suction pump connected to a manometer to suction rhythmically, analogous to a breast pump, then employ a holding suction pressure at a predetermined level and then change the holding pressure to another level so that the effect of altered suction on the impedance spectra can be used as a diagnostic test. It is the interpretation of the examiner that holding the pressure at a predetermined level is maintaining a constant pressure during the measurement.
Davies fails to teach the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function.
O’neill teaches that conditions with defective stratified epithelial barrier function include conditions such as dermatitis and eczema, and further that TEWL is used as a measurement of water loss via the skin wherein a greater water loss via the skin indicates a defective skin barrier (see O’neill par 0009, 0019, 0065-0066).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Davies such that the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function because it is known in the art that a greater water loss via the skin indicates a defective skin barrier (i.e., a defective epithelial barrier function) and Davies teaches that the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (see O’neill par 0009, 0019, 0065-0066, Davies par 0090).
Davies as modified by O’neill do not specifically teach where the predetermined pressure is within a range of 3 - 10 N.
As discussed above Davies does teach applying and holding a set pressure ( constant pressure) during impedance measurements. It is noted that there are a limited number of choices available to a person of ordinary skill in the art for applying pressure to the tissue for impedance measurements. Therefore, It would have been obvious to one of ordinary skill in the art at the time of the invention to include in the method of Davies as modified by O’neill where the pressure applied is within a range of 3 - 10 N with a reasonable expectation of successfully obtaining a more accurate impedance measurement. See KSR Int’l Co. v. Teleflex Inc., 127 S.Ct. 1727, 1742, 82 USPQ2d 1385, 1396 (2007). It is also noted that applicant’s specification does not set forth any particular criticality to the specific pressure applied.
With respect to claim 19, Davies as modified by O’neill further teaches that the step of evaluating comprises analyzing a magnitude of at least one measured impedance value and determining a reduction of the magnitude to indicate an impaired or decreased epithelial barrier function of the subject (see Davies, par 0035, 0138, 0155, 0160, 0173, fig. 11 & 14-15).
With respect to claim 20, Davies as modified by O’neill further teaches that reference data and/or clinical data is used in the evaluating (i.e., comparing epithelial impedance measurements in different lesion types (benign, proliferative, or malignant) using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B).
With respect to claim 21, Davies as modified by O’neill further teaches that the reference data and/or clinical data includes tissue data (i.e., comparing epithelial impedance measurements in different tissue lesion types (benign, proliferative, or malignant) using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B).
With respect to claim 22, Davies as modified by O’neill further teaches that the reference data and/or clinical data is based on earlier measurements of skin impedance of at least one patient (i.e., comparing epithelial impedance measurements in different lesion types (benign, proliferative, or malignant) from patients using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B).
With respect to claim 23, Davies as modified by O’neill further teaches that the method of claim 15 further comprises:
applying a trained evaluation procedure for analysis of the measured electrical impedance values, wherein said trained evaluation procedure performs (see Davies, par 0122-0123): extracting electrical impedance data from impedance spectra from obtained data sets of impedance values reflecting tissue characteristics of epithelial barrier function (i.e., extracting epithelial impedance measurements in different lesion types (benign, proliferative, or malignant) from patients using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B);
and evaluating the extracted electrical impedance data to provide the outcome indicating a status of the epithelial barrier function of the subject (see Davies, par 0122).
With respect to claim 30, Davies teaches a method for screening epithelial barrier function of subjects in vivo using only electrical impedance measurements (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, abstract, par 0056, 0212, 0219) comprising:
performing impedance measurement sessions of subjects including passing an electrical current through skin of each subject to obtain data of electrical impedance of a target tissue region using a plurality of electrodes adapted to be placed in contact with the target tissue region (see Davies, par 0091, 0096, 0120, 0128, 0212, 0219, fig. 1 & 3), wherein each electrode is provided with spikes, thereby forming a spiked surface (i.e., the electrode is inserted into a tissue or an intradermal electrode is used) (see Davies, par 0091, 0095, 0212, 0219), said data comprising at least one impedance value measured in the target tissue region at different tissue layers for each subject (i.e., different depths) (see Davies, par 0037, 0090, 0094, 0099-0100, 0212, 0219);
selectively activating electrode pairs to gradually scan tissue of the subject so as to obtain a sequence of electrical impedance values from selected tissue depths (see Davies, par 0012, 0037, 0056, 0090-0091, 0122, 0212, 0219);
applying an evaluation procedure (i.e., evaluating the electrophysiological properties such as impedance, transepithelial potential, or changes in spontaneous oscillations in transepithelial potential or impedance) (see Davies, par 0102-0104, 0212, 0219) for analyzing epithelial barrier function in the target tissue region based on only of the measured data of impedance values for the target tissue region at different tissue layers for each subject (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0102-0104, 0212, 0219),
wherein the evaluation procedure of the measured data of electrical impedance values provides an outcome indicating a status of the epithelial barrier function of each subject (i.e., determine the condition of the investigated tissue based upon its measured electrophysiological properties), wherein the outcome indicating status of epithelial barrier function is based only on the measured data of electrical impedance values (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0102-0104, 0122-0123, 0212, 0219),
wherein the status of the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (i.e., electrical impedance measurements, when compared to healthy tissue, provide information about the functional state of the epithelium and can detect early changes that may become malignant) (see Davies, par 0090).
Davies fails to teach the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function.
O’neill teaches that conditions with defective stratified epithelial barrier function include conditions such as dermatitis and eczema, and further that TEWL is used as a measurement of water loss via the skin wherein a greater water loss via the skin indicates a defective skin barrier (see O’neill par 0009, 0019, 0065-0066).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Davies such that the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function because it is known in the art that a greater water loss via the skin indicates a defective skin barrier (i.e., a defective epithelial barrier function) and Davies teaches that the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (see O’neill par 0009, 0019, 0065-0066, Davies par 0090).
With respect to claim 31, Davies as modified by O’neill further teaches applying the evaluation procedure comprises analyzing a magnitude of at least one measured impedance value and determining a reduction of the magnitude to determine an impaired or decreased epithelial barrier function of a first subject of the subjects (i.e., of a subject) (see Davies, par 0035, 0138, 0155, 0160, 0173, fig. 11 & 14-15).
With respect to claim 32, Davies as modified by O’neill teaches providing preventative treatment to at least one of the subjects based on the predicted disorders of the subjects (i.e., assessing drug response in a patient to determine conditions/diseases of a patient, monitoring the progress of a patient’s disease and treatment based upon the drug response, and monitoring the process of cancer development before a malignancy develops) (see Davies, par 0101-0104, 0122, 0162, 0173, 0192, 0197-0198).
With respect to claim 33, Davies as modified by O’neill teaches the applying the evaluation procedure comprises using reference data and/or clinical data including tissue data (i.e., comparing epithelial impedance measurements in different tissue lesion types (benign, proliferative, or malignant) using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B).
With respect to claim 34, Davies as modified by O’neill teaches the reference data and/or clinical data is based on earlier measurements of skin impedance of at least one patient (i.e., comparing epithelial impedance measurements in different lesion types (benign, proliferative, or malignant) from patients using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B).
With respect to claim 35, Davies as modified by O’neill teaches that the method of claim 30 further comprises: applying a trained evaluation procedure (see Davies, par 0122-0123) for analysis of the measured data of electrical impedance values, wherein said trained evaluation procedure performs:
extracting impedance data from impedance spectra from obtained data sets of impedance values reflecting tissue characteristics of epithelial barrier function (i.e., extracting epithelial impedance measurements in different lesion types (benign, proliferative, or malignant) from patients using epithelial impedance spectroscopy) (see Davies, par 0088, fig. 22-1A – fig. 22-3B);
and evaluating extracted impedance data to provide the outcome indicating the status of the epithelial barrier function of each subject (see Davies, par 0122).
With respect to claim 36, Davies teaches a medical device 100 for assessing and monitoring epithelial barrier function of a subject in vivo using only electrical impedance measurements (see Davies, abstract, par 0056, fig. 1) (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used), said medical device comprising:
an impedance measuring unit 105 configured to pass an electrical current through skin of the subject to obtain values of electrical impedance of a target tissue region, said impedance measuring unit comprising a plurality of electrodes adapted to be placed in contact with the target tissue region (see Davies, par 0091, 0096, 0120, 0128, fig. 1 & 3), wherein each electrode is provided with spikes, thereby forming a spiked surface (i.e., the electrode is inserted into a tissue or an intradermal electrode is used) (see Davies, par 0091, 0095), said values comprising at least one impedance value measured in the target tissue region at different tissue layers (i.e., different depths) (see Davies, par 0037, 0090, 0094, 0099-0100);
a switching circuit 120 adapted to activate adjacent electrodes of the plurality of electrodes in a successive manner to gradually scan tissue of the subject at different tissue depths so as to obtain a sequence of electrical impedance values from the different tissue depths (see Davies, par 0122, fig. 1);
and an evaluation unit 180 configured to apply an evaluation procedure for analyzing the epithelial barrier function in the target tissue region based only on the measured electrical impedance values for the target tissue region at different tissue layers, wherein the evaluation procedure of the measured electrical impedance values provides an outcome 185 indicating a status of the epithelial barrier function of the subject, wherein the outcome indicating status of the epithelial barrier function is based only on the measured electrical impedance values (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0122-0123, fig. 1);
wherein the evaluation unit is further configured to determine a response of the subject to an epithelial barrier treatment based on the outcome indicating the status of epithelial barrier function and clinical data including treatment prescriptions (i.e., evaluating/assessing a patient’s response to drugs by performing electrical measurements of epithelial barriers to determine altered structure and function in response to the drugs, wherein clinical data is used to define patient responses including typical responses to a particular drug) (see Davies, par 0122, 0162, 0173, 0197-0198), wherein the status of the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (i.e., electrical impedance measurements, when compared to healthy tissue, provide information about the functional state of the epithelium and can detect early changes that may become malignant) (see Davies, par 0090), and wherein the response is used to predict disorders of the subject (see Davies, par 0122, 0162, 0173, 0197-0198).
Davies fails to teach the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function.
O’neill teaches that conditions with defective stratified epithelial barrier function include conditions such as dermatitis and eczema, and further that TEWL is used as a measurement of water loss via the skin wherein a greater water loss via the skin indicates a defective skin barrier (see O’neill par 0009, 0019, 0065-0066).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Davies such that the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function because it is known in the art that a greater water loss via the skin indicates a defective skin barrier (i.e., a defective epithelial barrier function) and Davies teaches that the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (see O’neill par 0009, 0019, 0065-0066, Davies par 0090).
Claim(s) 16, 18, 37 & 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davies as modified by O'neill, as applied to claims 15 and 36, in view of US Patent Application Publication 20070238941 --as previously cited--, hereinafter referenced as "Nikolovski".
With respect to claim 16, Davies teaches determining cancer in a patient based upon evaluated measured data that indicates a decrease of impedance over time and indicates an impaired or decreased epithelial barrier function of a subject (see Davies, par 0035, 0138, 0155, 0160, 0173, fig. 11 & 14-15).
Davies as modified by O’neill does not teach that the method further comprises determining atopic dermatitis (AD) of a subject using the evaluated measured electrical impedance values, wherein a decrease of impedance over time indicates AD.
Nikolovski teaches that impedance measurements of the skin can be evaluated to determine the presence of atopic dermatitis (see Nikolovski, par 0015-0016, 0026).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Davies as modified by O’neill to include determining atopic dermatitis using the evaluated measured electrical impedance values, as Nikolovski teaches that impedance measurement values can be evaluated to determine atopic dermatitis. The modification to Davies as modified by O’neill would improve the method of Davies as modified by O’neill by providing another diagnostic measure by which to analyze the subject’s epithelial barrier function.
With respect to claim 18, Davies teaches determining cancer in a patient based upon evaluated measured data that indicates a decrease of impedance over time and indicates an impaired or decreased epithelial barrier function of a subject (see Davies, par 0035, 0138, 0155, 0160, 0173, fig. 11 & 14-15).
Davies as modified by O’neill does not teach that applying the evaluation procedure comprises using a differentiation in electrical impedance between non-lesional skin of an AD patient and healthy skin of a healthy patient to predict AD of the subject.
Nikolovski teaches that in subjects with skin conditions such as AD or eczema, the water content of the skin can be measured using impedance measurements to assess the skin barrier properties of the subject’s skin (see Nikolovski, par 0015-0016, 0026).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the modify the method of Davies as modified by O’neill to determine AD of a patient using evaluated measured electrical impedance values, wherein applying the evaluation procedure comprises using a differentiation in electrical impedance between non-lesional skin of an AD patient and healthy skin of a healthy subject is used to predict AD of the subject because it would merely be the application of a known technique (using impedance measurements to assess skin barrier properties in subjects with AD, as taught by Nikolovski) to a known device (the method of Davies as modified by O’neill that uses impedance measurements to assess cancer in tissue of a subject based upon decreased epithelial barrier function due to a decrease in impedance over time) to yield predictable results to one of ordinary skill in the art (the assessment of AD using impedance measurements that demonstrate decreased epithelial barrier function due to a decrease in impedance over time).
With respect to claim 37, Davies teaches an evaluation unit that with evaluated measured data determines cancer in a patient based upon a decrease of impedance over time which indicates an impaired or decreased epithelial barrier function of a subject (see Davies, par 0035, 0138, 0155, 0160, 0173, fig. 11 & 14-15).
Davies as modified by O’neill does not teach that the medical device further comprises determining atopic dermatitis (AD) of the subject using the measured electrical impedance values, wherein a decrease of impedance over time indicates AD.
Nikolovski teaches that impedance measurements of the skin can be evaluated to determine the presence of atopic dermatitis (see Nikolovski, par 0015-0016, 0026).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Davies as modified by O’neill to include determining atopic dermatitis using the measured electrical impedance values, as Nikolovski teaches that impedance measurement values can be evaluated to determine atopic dermatitis. The modification to Davies as modified by O’neill would improve the method of Davies as modified by O’neill by providing another diagnostic measure by which to analyze the subject’s epithelial barrier function.
With respect to claim 48, Davies teaches a method for assessing and monitoring epithelial barrier function of a subject in vivo using only electrical impedance measurements (i.e., measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, abstract, par 0056) comprising:
initiating an impedance measurement session including passing an electrical current through skin of the subject to obtain data of electrical impedance of a target tissue region using a plurality of electrodes adapted to be placed in contact with the target tissue region (see Davies, par 0091, 0096, 0120, 0128, fig. 1 & 3), wherein each electrode is provided with spikes, thereby forming a spiked surface (i.e., the electrode is inserted into a tissue or an intradermal electrode is used) (see Davies, par 0091, 0095), said data comprising at least one impedance value measured in the target tissue region at different tissue layers (i.e., different depths) (see Davies, par 0037, 0090, 0094, 0099-0100);
selectively activating electrode pairs to gradually scan tissue of the subject so as to obtain a sequence of electrical impedance values from selected tissue depths (see Davies, par 0012, 0037, 0056, 0090-0091, 0122);
applying an evaluation procedure (i.e., evaluating the electrophysiological properties such as impedance, transepithelial potential, or changes in spontaneous oscillations in transepithelial potential or impedance) (see Davies, par 0102-0104) for analyzing the epithelial barrier function in the target tissue region based only on the measured electrical impedance values for the target tissue region at different tissue layers (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0102-0104), wherein the evaluation procedure of the measured electrical impedance values provides an outcome indicating a status of the epithelial barrier function of the subject (i.e., determine the condition of the investigated tissue based upon its measured electrophysiological properties), wherein the outcome indicating the status of the epithelial barrier function is based only on the measured electrical impedance values (i.e., the measured impedance values are used to determine the epithelial barrier function and the measured impedance values are resultant from the different agents that may be used) (see Davies, par 0102-0104, 0122-0123);
determining a response of the subject to an epithelial barrier treatment based on the outcome indicating the status of epithelial barrier function and clinical data including treatment prescriptions (i.e., evaluating/assessing a patient’s response to drugs by performing electrical measurements of epithelial barriers to determine altered structure and function in response to the drugs, wherein clinical data is used to define patient responses including typical responses to a particular drug) (see par 0122, 0162, 0173, 0197-0198);
and using the response of the subject to predict disorders of the patient (i.e., assessing drug response to monitor a patient’s disease and treatment, and monitoring the process of cancer development before a malignancy develops) (see par 0122, 0162, 0173, 0197-0198);
wherein the status of the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (i.e., electrical impedance measurements, when compared to healthy tissue, provide information about the functional state of the epithelium and can detect early changes that may become malignant) (see Davies, par 0090).
Davies also teaches Ambient and varying pressure measurements applied to epithelial tissue are also used for diagnosis. Improved diagnosis of tissue condition can be made based on the electrical properties and tissue electrophysiological response to altered ion transport and pressure. And in paragraph [0116] , A particularly improved device, will employ an automated suction pump connected to a manometer to suction rhythmically, analogous to a breast pump, then employ a holding suction pressure at a predetermined level and then change the holding pressure to another level so that the effect of altered suction on the impedance spectra can be used as a diagnostic test. It is the interpretation of the examiner that holding the pressure at a predetermined level is maintaining a constant pressure during the measurement.
Davies fails to teach the status of the epithelial barrier function in the suspected lesional skin of the subject indicates atopic dermatitis (AD) if a decrease in the measured electrical impedance values compared to reference data is found, wherein the decrease in the measured electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with atopic dermatitis (AD).
O’neill teaches that conditions with defective stratified epithelial barrier function include conditions such as dermatitis and eczema, and further that TEWL is used as a measurement of water loss via the skin wherein a greater water loss via the skin indicates a defective skin barrier (see O’neill par 0009, 0019, 0065-0066).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Davies such that the change in electrical impedance values correlates with an increase in transepidermal water loss (TEWL) associated with an impaired epithelial barrier function because it is known in the art that a greater water loss via the skin indicates a defective skin barrier (i.e., a defective epithelial barrier function) and Davies teaches that the epithelial barrier function in the target tissue region of the subject indicates an impaired epithelial barrier function if a change in electrical impedance values compared to reference data is measured (see O’neill par 0009, 0019, 0065-0066, Davies par 0090).
Davies as modified by O’neill do not specifically teach where the predetermined pressure is within a range of 3 - 10 N.
As discussed above Davies does teach applying and holding a set pressure ( constant pressure) during impedance measurements. It is noted that there are a limited number of choices available to a person of ordinary skill in the art for applying pressure to the tissue for impedance measurements. Therefore, It would have been obvious to one of ordinary skill in the art at the time of the invention to include in the method of Davies as modified by O’neill where the pressure applied is within a range of 3 - 10 N with a reasonable expectation of successfully obtaining a more accurate impedance measurement. See KSR Int’l Co. v. Teleflex Inc., 127 S.Ct. 1727, 1742, 82 USPQ2d 1385, 1396 (2007). It is also noted that applicant’s specification does not set forth any particular criticality to the specific pressure applied.
Davies as modified by O’neill fails to teach the medical device further comprises determining atopic dermatitis (AD) of the subject using the measured electrical impedance values, wherein a decrease of impedance over time indicates AD.
Nikolovski teaches that impedance measurements of the skin can be evaluated to determine the presence of atopic dermatitis (see Nikolovski, par 0015-0016, 0026).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Davies as modified by O’neill to include determining atopic dermatitis using the measured electrical impedance values, as Nikolovski teaches that impedance measurement values can be evaluated to determine atopic dermatitis. The modification to Davies as modified by O’neill would improve the method of Davies as modified by O’neill by providing another diagnostic measure by which to analyze the subject’s epithelial barrier function.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davies as modified by O'neill, as applied to claim 15, in view of US Patent Application Publication 20180015150 --as previously cited--, hereinafter referenced as "Park".
With respect to claim 17, Davies teaches determining cancer in a patient based upon evaluated measured data that indicates a decrease of impedance over time and indicates an impaired or decreased epithelial barrier function of a subject (see Davies, par 0035, 0138, 0155, 0160, 0173, fig. 11 & 14-15).
Davies as modified by O’neill does not teach that applying the evaluation procedure comprises determining a lesion at the target tissue region based on a decreased electrical impedance as compared to a non-lesional skin site of the subject.
Park teaches measuring transepidermal water loss (TEWL) in patients with AD at lesion sites (i.e., skin areas presenting AD) wherein there is an increased TEWL measured at a body site of an AD patient compared to predetermined TEWL values in healthy skin (i.e., non-lesion sites) (see Park, fig. 1, wherein in worsening conditions of AD vs stable conditions of AD, there is a greater TEWL). The increase of transepidermal water loss indicates a decrease of the electrical impedance. Park further teaches monitoring trends in TEWL (including increases in TEWL) in order to provide guidance for AD treatment (see Park, ABSTRACT).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to have modified the method of Davies as modified by O’neill to include applying the evaluation procedure to determine a lesion at the target tissue region based on a decreased electrical impedance as compared to a non-lesional skin site of the subject, as taught by Park, as it would provide a means by which to provide guidance on how to treat the subject. In the method of Davies as modified by O’neill in view of Park, a decrease in electrical impedance and an increase in TEWL would indicate a lesion at the body site.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Davies(US 20080009764) teaches methods and systems are provided for determining a condition of an organ, or epithelial or stromal tissue, for example in the human breast. The methods incorporate sonophoresis, the application of ultrasonic energy, in order to condition tissue for testing and enhance test measurements. A plurality of electrodes are used to measure surface and transepithelial electropotential and impedance of breast tissue at one or more locations and at several frequencies, particularly very low frequencies. Paragraphs [0174]- [0175], [0181]-[0202] set forth a particularly improved device will employ an automated suction pump connected to a manometer to suction rhythmically, analogous to a breast pump, then employ a holding suction pressure at a predetermined level and then change the holding pressure to another level so that the effect of altered suction on the impedance spectra can be used as a diagnostic test. [0175] Mechanical pressure can also be used to provide additional diagnostic information during DC and AC impedance measurement to characterize breast tissue. In this manner, positive pressure is applied to the skin surface and negative pressure, or vacuum is applied to the nipple. In this manner an additional approach can be used to obtain further diagnostic information that can be independently used or can be used in combination with the technique relating to nipple aspiration.
MORENO et al.( FR 3005844) teaches a portable autonomous device for measuring and analyzing (1) at least one parameter representing the fat of a cutaneous surface area comprising at least one probe (10) comprising at least two pairs of electrodes for contacting the skin surface area defining a first pair of injector electrodes (11, 12), and a second pair of injection response measuring electrodes.
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/BRIAN L CASLER/Primary Examiner, Art Unit 3791
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