DETAILED ACTION
Applicant’s arguments, filed on 12/22/2025, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Applicants have amended their claims, filed on 12/22/2025, and therefore rejections newly made in the instant office action have been necessitated by amendment.
Claims 1-11 and 15 are the current claims hereby under examination.
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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-11 and 15 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 8, the claim recites the limitation “the substance present in the exhaled breath of the subject” in lines 8-9. It is unclear if this limitation is meant to refer to the substances present in the exhaled breath in claim 1, lines 3-4, or a different substance, as claim 1 claims a plurality of substances, yet claim 8 only refers to a single substance. It is unclear if the substance from claim 1 is included in the plurality of substances from claim 1, or is a different, singular substance. If it is meant to refer to the substances from claim 1, it needs to indicate it is part of the substances from claim 1. If it is a different substance, it needs to be distinguished from the substances from claim 1. For purposes of examination, it is being interpreted as being included in the substances from claim 1. Claims 9-11 and 15 are also rejected due to their dependence on claim 8.
Further regarding claim 8, the claim recites the limitation “metabolites whose concentration is modulated by administration of the drug” in line 14. It is unclear if this limitation is meant to refer to the metabolites whose concentration is modulated by administration of the drug from claim 1, line 11, or different metabolites. If it is referring to the metabolites from claim 1, it needs to refer back to it. If it is referring to a different metabolite, it needs to be distinguished from the metabolites from claim 1. For purposes of examination, it is being interpreted as referring to the metabolites from claim 1. Claims 9-11 and 15 are also rejected due to their dependence on claim 8.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 3-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Melker (US 20120016252).
Regarding independent claim 1, Melker teaches a method for therapeutic drug monitoring ([0002]: “The present invention relates to non-invasive monitoring of substance/compound concentrations in blood; and more particularly, to a system and method for the determination of drug concentrations and endogenous compounds in blood utilizing a breath detection system.”), the method comprising:
(a) providing a sample of breath exhaled by a subject to a mass spectrometer ([0130]: “a patient's breath sample can be captured in a container (vessel) for later analysis using a sensor of the subject invention (i.e., mass spectrometer)”; [0236]: “the marker detection method of the present invention is intended to cover detection not only through the exhalation by a patient with a device utilizing electronic nose technology, but also other suitable technologies, such as … mass spectrometers”);
(b) collecting mass spectra of substances present in the exhaled breath in positive and/or negative mode ([0174]: “Upon delivery of the therapeutic drug to a patient, a sensor of the invention analyzes a patient's expired gases to detect at least one target marker of the therapeutic drug. Upon detection of the target marker, the concentration of the therapeutic drug in blood can be determined for use in deriving the appropriate dosage amount of the therapeutic drug to next be delivered to the patient. In one embodiment, a system controller utilizes the derived appropriate dosage based on exhaled breath analysis to dispense an appropriate dosage from the supply means to the patient.”; [0205]: “After separation, the chemical components need to be detected. Mass spectrometry is one such detection method, which bombards the separated sample component molecules with an electron beam as they elute from the column. This causes the molecules to lose an electron and form ions with a positive charge. Some of the bonds holding the molecule together are broken in the process, and the resulting fragments may rearrange or break up further to form more stable fragments. A given compound will ionize, fragment, and rearrange reproducibly under a given set of conditions. This makes identification of the molecules possible. A mass spectrum is a plot showing the mass/charge ratio versus abundance data for ions from the sample molecule and its fragments. This ratio is normally equal to the mass for that fragment. The largest peak in the spectrum is the base peak. The GC/MS is accurate, selective and sensitive.”);
(c) analysing the mass spectra using a previously trained mathematical model ([0037]: “The systems and methods of the present invention utilize sensors that can analyze a patient's exhaled breath components to detect, quantify, and/or trend concentrations of endogenous compound markers in exhaled breath, which correlate to the endogenous compound concentration in the patient's body, in particular in blood”; [0091]: “this instrument communicates with computers to provide enhanced pattern analysis and report generation. In a preferred embodiment, this instrument includes neural networks for "training" purposes, i.e., to remember chemical vapor signature patterns for fast, "on-the-fly" analysis”); and
(d) determining a risk estimate of side effects of a drug and/or probability estimate of drug response in the subject based on the analysis of the mass spectra of the exhaled breath ([0111]: “A data analyzer can compare a pattern of response to previously measured and characterized responses from known substances. The matching of those patterns can be performed using a number of techniques, including neural networks. By comparing the analog output from each of the 32 polymers to a "blank" or control, for example, a neural network can establish a pattern that is unique to that substance and subsequently learns to recognize that substance. The particular resistor geometries are selected to optimize the desired response to the particular substance being sensed”; [0146]: “The computing/processor device runs under control of a program stored in the memory of the computing/processor device and determines a desired therapeutic drug and/or dosage of a therapeutic drug in response to the results provided by the sensor. Preferably, the computing/processor device comprises a data monitor/analyzer that can compare a pattern of results communicated from the sensor device to previously measured and characterized results, where the results are indicative of patient condition. The computing/processor device preferably utilizes a trainable neural network to determine the therapeutic drug and/or therapeutic drug dosage to be administered to the patient based on the patient's condition and generates a response signal. In one embodiment, responsive to the response signal of the computing/processor device, the system controller directs the controlled supply means to dispense a dosage or adjust a dosage for a therapeutic drug.”. The response signal generated from the patient’s condition and dosage of the therapeutic drug is the probability estimate.);
wherein the previously trained mathematical model relies on a signal intensity or area under a curve of selected m/z peaks in the mass spectra as predictors ([0205]: “A mass spectrum is a plot showing the mass/charge ratio versus abundance data for ions from the sample molecule and its fragments. This ratio is normally equal to the mass for that fragment. The largest peak in the spectrum is the base peak. The GC/MS is accurate, selective and sensitive.”. The base peak is the peak with the highest signal intensity and shows the most abundant ion detected, which is used for marker detection ([0236]: “the marker detection method of the present invention is intended to cover detection not only through the exhalation by a patient with a device utilizing electronic nose technology, but also other suitable technologies, such as gas chromatography, transcutaneous/transdermal detection, semiconductive gas sensors, mass spectrometers”).) which are due to metabolites whose concentration is modulated by administration of the drug ([0039]: “the subject invention contemplates administering to a patient a therapeutic drug, wherein the therapeutic drug contains a therapeutic drug marker that is detectable in exhaled breath by a sensor of the subject invention. In certain embodiments of the invention, the therapeutic drug marker is the therapeutic drug itself or a metabolite of the drug, which is detectable in exhaled breath. As contemplated herein, the blood concentration of the therapeutic drug and the exhaled concentration of the therapeutic drug marker are substantially proportional. By using a sensor of the subject invention for analyzing the concentration of a therapeutic drug marker in exhaled breath, which substantially corresponds to the blood concentration of a therapeutic drug, the present invention enables non-invasive, continuous monitoring of therapeutic drug blood concentration.”; [0236]: “the marker detection method of the present invention is intended to cover detection not only through the exhalation by a patient with a device utilizing electronic nose technology, but also other suitable technologies, such as gas chromatography, transcutaneous/transdermal detection, semiconductive gas sensors, mass spectrometers”. Mass spectrometry is used for marker detection, the marker can be a metabolite of the drug, and the concentration of the metabolite of the drug is related to the blood concentration of the therapeutic drug, which is then used to estimate a response signal of the user to the drug ([0146]: “The computing/processor device preferably utilizes a trainable neural network to determine the therapeutic drug and/or therapeutic drug dosage to be administered to the patient based on the patient's condition and generates a response signal. In one embodiment, responsive to the response signal of the computing/processor device, the system controller directs the controlled supply means to dispense a dosage or adjust a dosage for a therapeutic drug.”), therefore acting as a predictor.).
Regarding claim 3, Melker teaches the method of claim 1, wherein the therapeutic drug is a substance used as an anti-epileptic medication ([0167]: “For example, the subject invention can effectively monitor concentrations of the following non-limiting list of therapeutic drugs in blood: … antiepilepsy medication”).
Regarding claim 4, Melker teaches the method of claim 3, wherein the antiepileptic medication is valproate ([0169]: “Additional therapeutic drugs whose blood concentration levels can be monitored in accordance with the subject invention include … Depakene (Valproic Acid); Depakote (Divalproex) (Measured as Valproic Acid)”).
Regarding claim 5, Melker teaches the method of claim 1, wherein the therapeutic drug is a substance used as an anti-cancer medication ([0170]: “Blood level concentrations of the following therapeutic drugs that can be monitored in accordance with the subject invention include, but are not limited to, … Methotrexate (Mexate)”).
Regarding claim 6, Melker teaches the method of claim 5, wherein the anti-cancer medication is methotrexate ([0170]: “Blood level concentrations of the following therapeutic drugs that can be monitored in accordance with the subject invention include, but are not limited to, … Methotrexate (Mexate)”).
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Melker as applied to claim 1 above, and further in view of Zhou (CN 108318590). Citations to CN 108318590 will refer to the English Machine Translation that accompanies this Office Action.
Regarding claim 2, Melker teaches the method for therapeutic drug monitoring according to claim 1.
However, Melker does not teach wherein the contribution of different metabolic routes in metabolizing the therapeutic drug is calculated based on the ratios of values of the predictors.
Zhou discloses a method and device to detect infection from exhaled gas using mass spectrometry. Specifically, Zhou teaches wherein a contribution of different metabolic routes in metabolizing the therapeutic drug is calculated based on ratios of values of the predictors (Page 3: “In the CC-MS method, VOCs are first ionized, and based on different mass /charge ratios, different VOCs gradually reach the end of the chromatographic column. This method can identify both individual VOCs related to metabolic processes and all substances in exhaled air. Its sample preparation and detection times and locations are relatively independent, and it has high sensitivity”. The different mass/charge ratios of each identified VOC related to metabolic processes will show the proportion of the sample that is related to the metabolic process, which will show its contribution.). Melker and Zhou are analogous arts as they are both related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the contribution of metabolic routes from Zhou into the method from Melker as it allows the method to account for the metabolic processes, which are important in the analysis of a therapeutic drug, which can provide a more accurate result to the user.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Melker as applied to claim 1 above, and further in view of Peterson (US 20200337566).
Regarding claim 7, Melker teaches the method of claim 1.
However, Melker is silent on the type of trained mathematical model that is used.
Peterson discloses a system for assessing health conditions of patients. Specifically, Peterson teaches wherein the previously trained mathematical model is Gaussian process regression ([0124]: “Regression algorithms can include both supervised (such as Gaussian process regression)”). Melker and Peterson are analogous arts as they are both related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the Gaussian process regression from Peterson into the method from Melker as the method from Melker is silent on the type of trained mathematical model used, and Peterson provides a suitable type of model in an analogous system.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Melker as applied to claim 1 above, and further in view of Verbeck (US 10813585) and Hazen (US 20220065829).
Regarding claim 8, Melker teaches an apparatus for use in the method of claim 1, the apparatus comprising
(a) a mouthpiece for collecting the sample of breath exhaled by the subject ([0129]: “a mouthpiece or nosepiece will be provided for interfacing a patient with the device to readily transmit the exhaled breath to the sensor”).
However, Melker does not disclose the mouthpiece being disposable.
Verbeck discloses a system for analyzing the breath of a user. Specifically, Verbeck teaches the mouthpiece being disposable (Column 6, lines 9-12: “a disposable mouthpiece (not shown in FIG. 1) may be removably coupled to a first end of the inlet 112 and a second end of the inlet 112 may be coupled to the sampling chamber 110”). Melker and Verbeck are analogous arts as they are both related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the mouthpiece being disposable from Verbeck into the apparatus from Melker as it allows the device to be used multiple times and still be sanitary for use between multiple people.
The Melker/Verbeck combination teaches (b) a connector for delivering the collected sample to an ionisation device (Melker, [0192]: “Inspired gases are monitored by connecting the sensor(s) of the present invention to the appropriate location(s) in the breathing circuit. Similarly, expired gases are monitored by connecting the sensor(s) of the present invention to the appropriate location(s) in the breathing circuit.”);
(c) a mass spectrometer (Melker, [0130]: “a patient's breath sample can be captured in a container (vessel) for later analysis using a sensor of the subject invention (i.e., mass spectrometer)”; [0002]: “The present invention relates to non-invasive monitoring of substance/compound concentrations in blood; and more particularly, to a system and method for the determination of drug concentrations and endogenous compounds in blood utilizing a breath detection system.”).
However, the Melker/Verbeck combination is silent on the structure of the mass spectrometer.
Hazen discloses methods for determining whether a subject is at risk of developing a disease. Specifically, Hazen teaches the mass spectrometer comprising an electrospray ionisation module and a detection module ([0086]: “Mass spectrometers include an ionizing source (e.g., electrospray ionization), an analyzer to separate the ions formed in the ionization source according to their mass-to-charge (m/z) ratios, and a detector for the charged ions”). Melker, Verbeck, and Hazen are analogous arts as they are all related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the structure of the mass spectrometer from Hazen into the apparatus from the Melker/Verbeck combination as the combination is silent on the structure of the mass spectrometer, and Hazen discloses a suitable structure in an analogous device.
The Melker/Verbeck/Hazen combination teaches (d) a computer interface for analysis and determination of a concentration of the substance present in the exhaled breath of the subject (Melker, [0045]: “sensor systems having computerized data analysis components can also be used in the subject invention”);
wherein the apparatus is configured for carrying out a previously trained mathematical model used in the determination of the concentration of the substance present in the exhaled breath of the subject (Melker, [0037]: “The systems and methods of the present invention utilize sensors that can analyze a patient's exhaled breath components to detect, quantify, and/or trend concentrations of endogenous compound markers in exhaled breath, which correlate to the endogenous compound concentration in the patient's body, in particular in blood”; [0091]: “this instrument communicates with computers to provide enhanced pattern analysis and report generation. In a preferred embodiment, this instrument includes neural networks for "training" purposes, i.e., to remember chemical vapor signature patterns for fast, "on-the-fly" analysis”), wherein the mathematical model relies on the signal intensity or area under the curve of selected m/z peaks in the mass spectra as predictors (Melker, [0205]: “A mass spectrum is a plot showing the mass/charge ratio versus abundance data for ions from the sample molecule and its fragments. This ratio is normally equal to the mass for that fragment. The largest peak in the spectrum is the base peak. The GC/MS is accurate, selective and sensitive.”) which are due to metabolites whose concentration is modulated by administration of the drug (Melker, [0039]: “the subject invention contemplates administering to a patient a therapeutic drug, wherein the therapeutic drug contains a therapeutic drug marker that is detectable in exhaled breath by a sensor of the subject invention. In certain embodiments of the invention, the therapeutic drug marker is the therapeutic drug itself or a metabolite of the drug, which is detectable in exhaled breath. As contemplated herein, the blood concentration of the therapeutic drug and the exhaled concentration of the therapeutic drug marker are substantially proportional. By using a sensor of the subject invention for analyzing the concentration of a therapeutic drug marker in exhaled breath, which substantially corresponds to the blood concentration of a therapeutic drug, the present invention enables non-invasive, continuous monitoring of therapeutic drug blood concentration.”), and wherein the mass spectrometer is calibrated for analyzing the breath samples (Melker, [0111]: “the sensor of the present invention is a self-calibrating polymer system suitable for liquid or gas phase biological solutions for detecting a variety of target markers simultaneously.”; [0130]: “a patient's breath sample can be captured in a container (vessel) for later analysis using a sensor of the subject invention (i.e., mass spectrometer).”).
Regarding claim 9, the Melker/Verbeck/Hazen combination teaches the apparatus of claim 8.
However, the Melker/Verbeck/Hazen combination is silent on the range of m/z that is optimal.
Hazen teaches wherein the connector is configured for optimal delivery of compounds that give rise to m/z in the range of 50-1000 ([0028]: “FIG. 1, panels A-C, provides graphs showing a peak area of extracted ion chromatograms in positive-ion MS1 mode at m/z ranging from 50 to 100”).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the range of the m/z from Hazen into the Melker/Verbeck/Hazen combination as the combination is silent on the optimal range, and Hazen provides a suitable range in an analogous device.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over the Melker/Verbeck/Hazen combination as applied to claim 8 above, and further in view of Jia (US 20220050109).
Regarding claim 10, the Melker/Verbeck/Hazen combination teaches the apparatus of claim 8.
However, the Melker/Verbeck/Hazen combination does not teach wherein the apparatus is configured to perform the analysis in real time.
Jia discloses a method of detecting cancer. Specifically, Jia teaches wherein the apparatus is configured to perform the analysis in real time ([0177]: “The above online sampler and procedure is specially designed for proton-transfer-reaction mass spectrometry (PTR-MS) analysis. The online sampler is connected to the PTR-MS to transfer the breath sample to it in real time for analysis.”). Melker, Verbeck, Hazen, and Jia are analogous arts as they are all related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the real time analysis from Jia into the Melker/Verbeck/Hazen combination as it allows the device to provide up to date analysis of the user’s health, which can provide more information to the user.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over the Melker/Verbeck/Hazen combination as applied to claim 8 above, and further in view of Fuisz (US 9770192).
Regarding claim 11, the Melker/Verbeck/Hazen combination teaches the apparatus of claim 8.
However, the Melker/Verbeck/Hazen combination does not teach wherein the computer interface is configured to perform a quality control of the sample analysis based on the variability between repeated measurements and measurements with standardized gas composition, preferably containing compounds that give raise to m/z in the range of 100- 200.
Fuisz discloses a method and system to measure breathe analytes. Specifically, Fuisz teaches wherein the computer interface is configured to perform a quality control of the sample analysis based on a variability between repeated measurements and measurements with standardized gas composition (Claims 1 and 2: “A method of avoiding a contaminant which would skew an analyte result in a breath analysis method and of calibrating subject of the breath analysis comprising, immediately before a breath analysis method or collection of breath for a breath analysis method, administering to the subject a predetermined purified and standardized gas composition not comprising ambient air, the predetermined gas composition being free of a contaminant which would skew an analyte result in a breath analysis method., the method according to claim 1, wherein the step of administering to the subject the predetermined gas composition comprises having the subject inhale the predetermined gas mixture from a source of the predetermined gas mixture, and exhale outside the source of the predetermined gas mixture for a predetermined period of time, in order to calibrate the subject and eliminate through washout and non repeat inhalation the majority of ambient analyte contaminants, so that analytical results can be reasonably attributed to the individual subject.”). Melker, Verbeck, Hazen, and Fuisz are analogous arts as they are all related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the quality control from Fuisz into the apparatus from the Melker/Verbeck/Hazen combination as it allows the combination to determine that it is providing the correct results, making sure the system is as accurate as possible.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over the Melker/Verbeck/Hazen/Fuisz combination as applied to claim 11 above, and further in view of Singh (“Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry”).
Regarding claim 15, the Melker/Verbeck/Hazen/Fuisz combination teaches the apparatus of claim 11.
However, the Melker/Verbeck/Hazen/Fuisz combination does not teach wherein the standardized gas composition contains compounds that give rise to m/z in the range of 50-300.
Singh discloses standardization procedures for mass spectrometry. Specifically, Singh teaches wherein the standardized gas composition contains compounds that give rise to m/z in the range of 50-300 (Pages 4-7 disclose a multitude of standardized gas compositions with m/z values in the range of 50-300.). Melker, Verbeck, Hazen, Fuisz, and Singh are analogous arts as they are all related to systems that use exhaled breath for health parameter analysis of a user.
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to include the m/z range from Singh into the Melker/Verbeck/Hazen/Fuisz combination as the combination is silent on the m/z range produced from the standardized gas composition, and Singh discloses a suitable m/z range in an analogous art.
Response to Arguments
All of applicant’s argument regarding the rejections and objections previously set forth have been fully considered and are persuasive unless directly addressed subsequently.
Applicant has amended the claims to overcome the 112(b) rejections, however the amendments did not overcome the 112(b) rejection of claim 8 and has introduced a new 112(b) rejection.
Applicant's arguments with regards to the 102 rejections of claims 1-14 have been fully considered but they are not persuasive. Applicant argues that Melker does not teach the determination of the risk estimate of side effects of a drug and/or probability estimate of drug response in the subject based on the analysis of the mass spectra of the exhaled breath. However, as stated in the 102 rejection above, the paragraphs [0111] and [0146] of Melker show determining the probability estimate of drug response in the subject ([0111]: “A data analyzer can compare a pattern of response to previously measured and characterized responses from known substances. The matching of those patterns can be performed using a number of techniques, including neural networks. By comparing the analog output from each of the 32 polymers to a "blank" or control, for example, a neural network can establish a pattern that is unique to that substance and subsequently learns to recognize that substance. The particular resistor geometries are selected to optimize the desired response to the particular substance being sensed”; [0146]: “The computing/processor device runs under control of a program stored in the memory of the computing/processor device and determines a desired therapeutic drug and/or dosage of a therapeutic drug in response to the results provided by the sensor. Preferably, the computing/processor device comprises a data monitor/analyzer that can compare a pattern of results communicated from the sensor device to previously measured and characterized results, where the results are indicative of patient condition. The computing/processor device preferably utilizes a trainable neural network to determine the therapeutic drug and/or therapeutic drug dosage to be administered to the patient based on the patient's condition and generates a response signal. In one embodiment, responsive to the response signal of the computing/processor device, the system controller directs the controlled supply means to dispense a dosage or adjust a dosage for a therapeutic drug.”. The response signal generated from the patient’s condition and dosage of the therapeutic drug is the probability estimate.), therefore teaches on this limitation.
Applicant also argues that Melker does not teach using mass spectrometry based breath analysis, however as stated in the 102 rejection above, Melker discloses using mass spectrometry ([0130]: “a patient's breath sample can be captured in a container (vessel) for later analysis using a sensor of the subject invention (i.e., mass spectrometer)”; [0236]: “the marker detection method of the present invention is intended to cover detection not only through the exhalation by a patient with a device utilizing electronic nose technology, but also other suitable technologies, such as … mass spectrometers”).
Applicant states that Melker uses an electronic nose, however as stated in Melker, this is only one example that can be used, and mass spectrometry can be used as well, therefore this argument is not persuasive.
Applicant also argues that Melker does not teach that the peaks in mass spectra are due to metabolites whose concentration is modulated by administration of the drug are used as predictors, however as stated in the 102 rejection above, the drug markers can be a metabolite of the drug ([0205]: “A mass spectrum is a plot showing the mass/charge ratio versus abundance data for ions from the sample molecule and its fragments. This ratio is normally equal to the mass for that fragment. The largest peak in the spectrum is the base peak. The GC/MS is accurate, selective and sensitive.”. The base peak is the peak with the highest signal intensity and shows the most abundant ion detected, which is used for marker detection ([0236]: “the marker detection method of the present invention is intended to cover detection not only through the exhalation by a patient with a device utilizing electronic nose technology, but also other suitable technologies, such as gas chromatography, transcutaneous/transdermal detection, semiconductive gas sensors, mass spectrometers”).; [0039]: “the subject invention contemplates administering to a patient a therapeutic drug, wherein the therapeutic drug contains a therapeutic drug marker that is detectable in exhaled breath by a sensor of the subject invention. In certain embodiments of the invention, the therapeutic drug marker is the therapeutic drug itself or a metabolite of the drug, which is detectable in exhaled breath. As contemplated herein, the blood concentration of the therapeutic drug and the exhaled concentration of the therapeutic drug marker are substantially proportional. By using a sensor of the subject invention for analyzing the concentration of a therapeutic drug marker in exhaled breath, which substantially corresponds to the blood concentration of a therapeutic drug, the present invention enables non-invasive, continuous monitoring of therapeutic drug blood concentration.”; [0236]: “the marker detection method of the present invention is intended to cover detection not only through the exhalation by a patient with a device utilizing electronic nose technology, but also other suitable technologies, such as gas chromatography, transcutaneous/transdermal detection, semiconductive gas sensors, mass spectrometers”. Mass spectrometry is used for marker detection, the marker can be a metabolite of the drug, and the concentration of the metabolite of the drug is related to the blood concentration of the therapeutic drug, which is then used to estimate a response signal of the user to the drug ([0146]: “The computing/processor device preferably utilizes a trainable neural network to determine the therapeutic drug and/or therapeutic drug dosage to be administered to the patient based on the patient's condition and generates a response signal. In one embodiment, responsive to the response signal of the computing/processor device, the system controller directs the controlled supply means to dispense a dosage or adjust a dosage for a therapeutic drug.”), therefore acting as a predictor.), therefore teaching on this limitation.
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 ERIN K MCCORMACK whose telephone number is (703)756-1886. The examiner can normally be reached Mon-Fri 7:30-5.
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/E.K.M./Examiner, Art Unit 3791
/MATTHEW KREMER/Primary Examiner, Art Unit 3791