DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The amendment filed 09/12/2025 has been entered. Amendments to claims 1 and 3-15, addition of new claim 16, and cancellation of claim 2 is acknowledged. Claims 1 and 3-15 remain pending in the application. Applicant’s amendments to the Specification, Drawings, and Claims have overcome each and every objection and 112(b) rejection previously set forth in the Non-Final Office Action mailed 03/14/2025.
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 1-16 are rejected under 35 U.S.C. 101 because the claimed invention, considering all claim elements both individually and in combination as a whole, do not amount to significantly more than a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea).
Claim 1 is a claim to a process, machine, manufacture, or composition of matter and therefore meets one of the categorical limitations of 35 U.S.C. 101. However, claim 1 meets the first prong of the step 2A analysis because it is directed to an abstract idea, as evidenced by the claim language of “b) measuring detecting by gas chromatography-ion mobility spectrometry (GC-IMS), in an exhaled sample from a subject, a concentration of one or both VOCs a VOC selected from a group consisting of 2-propanol hexanal, heptanal, and 2-propanol;”, “comparing the concentration measured in a) with a reference concentration;”, and “d) diagnosing the subject with MCI when the concentration of one or both VOCs detected in b) is more than about 5% higher than the reference concentration”. This claim language, under the broadest, reasonable interpretation, encompasses subject matter that may be performed by a human using mental steps or with pen and paper that can involve basic critical thinking, which are types of activities that have been found by the courts to represents abstract ideas (i.e., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). The claim language also meets prong 2 of the step 2A analysis because the above-recited claim language does not integrate the abstract idea into a practical application. The disclosed technologies do not improve a technical field (see MPEP 2106.05(a)), affect a particular treatment for a disease or medical condition (see MPEP 2106.04(d)(2)), effect a transformation or reduction of a particular article to a different state or thing (see MPEP 2106.04(d)(2)), apply the judicial exception with, or by use of, a particular machine (see MPEP 2106.05(b)), or apply the judicial exception in some meaningful way beyond generally linking the use of the abstract idea to a particular technological environment (MPEP 2106.04(d)(2) and 2106.05(e)). As a result, step 2A is satisfied and the second step, step 2B, must be considered.
With regard to the second step, the claim does not appear to recite additional elements that amount to significantly more. The additional elements are “a) obtaining an exhaled breath sample from a subject” and “detecting by gas chromatography-ion mobility spectrometry (GC-IMS)”. However, this element is well-known, routine, and/or conventional as evidenced by Grafman et al. (US20170254817A1) para [0003]: “Breath detection is currently performed through the analysis of mouth breath,”, and Zhang et al. (US 20170176299 A1) para [0008]: “, conventional IMS and GC technologies.”. Therefore, the claim as a whole does not amount to significantly more than a judicial exception.
Additionally, the ordered combination of elements do not add anything significantly more to the claimed subject matter. Specifically, the ordered combination of elements do not have any function that is not already supplied by each element individually. That is, the whole is not greater than the sum of its parts.
In view of the above, independent claim 1 fails to recite patent-eligible subject matter under 35 U.S.C. 101. Dependent claims 2-5 fail to cure the deficiencies of independent claim 1 by merely reciting additional abstract ideas, further limitations on abstract ideas already recited, and/or additional elements that are not significantly more. Thus, claim(s) 1-5 are rejected under 35 U.S.C. 101.
Claim 6 is a claim to a process, machine, manufacture, or composition of matter and therefore meets one of the categorical limitations of 35 U.S.C. 101. However, claim 6 meets the first prong of the step 2A analysis because it is directed to an abstract idea, as evidenced by the claim language of “b) detecting in an exhaled sample from a subject, a concentration of one or both VOCs a VOC selected from a group consisting of acetone and 2- butanone by gas chromatography-ion mobility spectrometry (GC-IMS);”, “comparing the concentration measured in a) with a reference concentration;”, and “d) diagnosing the subject with AD when the concentration of one or both VOCs detected in b) is more than about 5% higher than the reference concentration”. This claim language, under the broadest, reasonable interpretation, encompasses subject matter that may be performed by a human using mental steps or with pen and paper that can involve basic critical thinking, which are types of activities that have been found by the courts to represents abstract ideas (i.e., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). The claim language also meets prong 2 of the step 2A analysis because the above-recited claim language does not integrate the abstract idea into a practical application. The disclosed technologies do not improve a technical field (see MPEP 2106.05(a)), affect a particular treatment for a disease or medical condition (see MPEP 2106.04(d)(2)), effect a transformation or reduction of a particular article to a different state or thing (see MPEP 2106.04(d)(2)), apply the judicial exception with, or by use of, a particular machine (see MPEP 2106.05(b)), or apply the judicial exception in some meaningful way beyond generally linking the use of the abstract idea to a particular technological environment (MPEP 2106.04(d)(2) and 2106.05(e)). As a result, step 2A is satisfied and the second step, step 2B, must be considered.
With regard to the second step, the claim does not appear to recite additional elements that amount to significantly more. The additional elements are “a) obtaining an exhaled breath sample from a subject” and “detecting by gas chromatography-ion mobility spectrometry (GC-IMS)”. However, this element is well-known, routine, and/or conventional as evidenced by Grafman et al. (US20170254817A1) para [0003]: “Breath detection is currently performed through the analysis of mouth breath,”, and Zhang et al. (US 20170176299 A1) para [0008]: “, conventional IMS and GC technologies.”. Therefore, the claim as a whole does not amount to significantly more than a judicial exception. Additionally, the ordered combination of elements do not add anything significantly more to the claimed subject matter. Specifically, the ordered combination of elements do not have any function that is not already supplied by each element individually. That is, the whole is not greater than the sum of its parts.
In view of the above, independent claim 6 fails to recite patent-eligible subject matter under 35 U.S.C. 101. Dependent claims 7-11 fail to cure the deficiencies of independent claim 6 by merely reciting additional abstract ideas, further limitations on abstract ideas already recited, and/or additional elements that are not significantly more. Thus, claim(s) 6-11 are rejected under 35 U.S.C. 101.
Claim 12 is a claim to a process, machine, manufacture, or composition of matter and therefore meets one of the categorical limitations of 35 U.S.C. 101. However, claim 12 meets the first prong of the step 2A analysis because it is directed to an abstract idea, as evidenced by the claim language of “b) detecting, in an exhaled sample of a subject, the a concentration of a VOC, 1-butanol by gas chromatography-ion mobility spectrometry (GC-IMS)”, “comparing the concentration measured in a) with a reference concentration;”, “c) comparing the concentration measured detected in b) with a reference concentration;” and, “d)diagnosing the subject with MCI when determining that if the concentration measured detected in b) is about 5% to about 60% higher than the reference concentration, or diagnosing the subject with AD when the concentration measured in b) is more than about 60% higher than the reference concentration”. This claim language, under the broadest, reasonable interpretation, encompasses subject matter that may be performed by a human using mental steps or with pen and paper that can involve basic critical thinking, which are types of activities that have been found by the courts to represents abstract ideas (i.e., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). The claim language also meets prong 2 of the step 2A analysis because the above-recited claim language does not integrate the abstract idea into a practical application. The disclosed technologies do not improve a technical field (see MPEP 2106.05(a)), affect a particular treatment for a disease or medical condition (see MPEP 2106.04(d)(2)), effect a transformation or reduction of a particular article to a different state or thing (see MPEP 2106.04(d)(2)), apply the judicial exception with, or by use of, a particular machine (see MPEP 2106.05(b)), or apply the judicial exception in some meaningful way beyond generally linking the use of the abstract idea to a particular technological environment (MPEP 2106.04(d)(2) and 2106.05(e)). As a result, step 2A is satisfied and the second step, step 2B, must be considered.
With regard to the second step, the claim does not appear to recite additional elements that amount to significantly more. The additional elements are “a) obtaining an exhaled breath sample from a subject” and “detecting by gas chromatography-ion mobility spectrometry (GC-IMS)”. However, this element is well-known, routine, and/or conventional as evidenced by Grafman et al. (US20170254817A1) para [0003]: “Breath detection is currently performed through the analysis of mouth breath,”, and Zhang et al. (US 20170176299 A1) para [0008]: “, conventional IMS and GC technologies.”. Therefore, the claim as a whole does not amount to significantly more than a judicial exception.
Additionally, the ordered combination of elements do not add anything significantly more to the claimed subject matter. Specifically, the ordered combination of elements do not have any function that is not already supplied by each element individually. That is, the whole is not greater than the sum of its parts.
In view of the above, independent claim 12 fails to recite patent-eligible subject matter under 35 U.S.C. 101. Dependent claims 13-15 fail to cure the deficiencies of independent claim 12 by merely reciting additional abstract ideas, further limitations on abstract ideas already recited, and/or additional elements that are not significantly more. Thus, claim(s) 12-15 are rejected under 35 U.S.C. 101.
Claim 16 is a claim to a process, machine, manufacture, or composition of matter and therefore meets one of the categorical limitations of 35 U.S.C. 101. However, claim 16 meets the first prong of the step 2A analysis because it is directed to an abstract idea, as evidenced by the claim language of “b) detecting a concentration of one or both VOCs selected from a group consisting of hexanal and heptanal in the exhaled breath sample by gas chromatography-ion mobility spectrometry (GC-IMS)”. This claim language, under the broadest, reasonable interpretation, encompasses subject matter that may be performed by a human using mental steps or with pen and paper that can involve basic critical thinking, which are types of activities that have been found by the courts to represents abstract ideas (i.e., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). The claim language also meets prong 2 of the step 2A analysis because the above-recited claim language does not integrate the abstract idea into a practical application. The disclosed technologies do not improve a technical field (see MPEP 2106.05(a)), affect a particular treatment for a disease or medical condition (see MPEP 2106.04(d)(2)), effect a transformation or reduction of a particular article to a different state or thing (see MPEP 2106.04(d)(2)), apply the judicial exception with, or by use of, a particular machine (see MPEP 2106.05(b)), or apply the judicial exception in some meaningful way beyond generally linking the use of the abstract idea to a particular technological environment (MPEP 2106.04(d)(2) and 2106.05(e)). As a result, step 2A is satisfied and the second step, step 2B, must be considered.
With regard to the second step, the claim does not appear to recite additional elements that amount to significantly more. The additional elements are “obtaining an exhaled breath sample from a subject” and “gas chromatography-ion mobility spectrometry (GC-IMS)”. However, this element is well-known, routine, and/or conventional as evidenced by Grafman et al. (US20170254817A1) para [0003]: “Breath detection is currently performed through the analysis of mouth breath,”, and Zhang et al. (US 20170176299 A1) para [0008]: “, conventional IMS and GC technologies.”. Therefore, the claim as a whole does not amount to significantly more than a judicial exception.
Additionally, the ordered combination of elements do not add anything significantly more to the claimed subject matter. Specifically, the ordered combination of elements do not have any function that is not already supplied by each element individually. That is, the whole is not greater than the sum of its parts.
In view of the above, independent claim 16 fails to recite patent-eligible subject matter under 35 U.S.C. 101. Thus, claim(s) 16 are rejected under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 3 and 4 depend on cancelled claims 2. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 3-5 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.
Claim 1 recites the limitation “a group consisting of 2-propanol hexanal, heptanal, and 2-propanol”. It is unclear what “2-propanol hexanal” refers to.
Claims 3 - 5 are rejected due to dependency.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 3, 12-14, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grafman et al. (US 20170254817 A1) in view of Handa et al. (“Exhaled Breath Analysis for Lung Cancer Detection Using Ion Mobility Spectrometry”), hereinafter Handa.
Regarding claim 1, Grafman discloses a method of determining if a subject has a mild cognitive impairment (MCI) ([0006]: "assessing the condition of the person's brain."), the method comprising: a) obtaining an exhaled breath sample from a subject ([0004]: “collecting a sample of exhaled breath”), b) detecting in an exhaled sample from a subject, a concentration of a VOCs ( [0005]: "collecting a sample of exhaled breath from a person's nose and analyzing the sample to detect the presence of at least one biomarker. The method may further comprise measuring the concentration of the neural biomarker") selected from a group consisting of 2-propanol hexanal, heptanal, and 2-propanol ([0024]: "hexanal,"); c) comparing the concentration measured in a) with a reference concentration ([0062]: “Patients with certain conditions have differentiated levels of certain biomarkers and their related compounds. For example, patients with Alzheimer's disease, Frontotemporal Dementia, or traumatic brain injury (TBI) have differentiated levels of tau compared to individuals without these conditions”, [0074]: “tau concentration levels above 0.0100 pg/mL indicate more severe AD while tau concentration levels below 0.0100 pg/mL indicate less severe AD.”); and d) diagnosing the subject with MCI when the concentration of one or both VOCs detected in b) is more than 5% higher than the reference concentration, it is indicative that the subject has or will develop a MCI ([0062]: “Nasal breath samples may be analyzed for one or more biomarkers to indicate the likelihood that a patient has a medical condition.”, [0074]: “tau concentration from nasal breath of about 0.0090 pg/mL or lower… 0.0100 pg/mL… tau concentration levels above 0.0100 pg/mL indicate more severe AD while tau concentration levels below 0.0100 pg/mL indicate less severe AD.”, Fig 5A).
Grafman discloses detecting by gas chromatography with mass spectrometry ([0063]: “Breath samples may be analyzed using Gas-Chromatographic techniques combined with Mass Spectrometry”). Grafman fails to disclose detection by gas chromatography-ion mobility spectrometry (GC-IMS).
Handa discloses a method of detecting by gas chromatography-ion mobility spectrometry (GC-IMS), in an exhaled sample from a subject (page 2 para 4: “Breath analysis using an ion mobility spectrometer (IMS) was randomly performed in healthy volunteers and patients with lung cancer”), a concentration of a VOC (page 5 para 1: “and their concentration related to the peak height”).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date to modify the GC-MS detection method disclosed by Grafman with the GC-IMS method disclosed by Handa in order to improve breath detection by reducing preparation time (page 1 para 2: “and is superior to GC/MS as it can be applied at the bed-site and direct sampling can be taken without preparation”).
Regarding claim 3, Grafman further discloses the subject is diagnosed with MCI when the concentration of hexanal detected in b) is more than 100% higher than the reference concentration of hexanal ([0074], Fig 5A, wherein points 100% higher than 0.01 would be indicative of an MCI).
Regarding claim 12, Grafman further discloses a method of determining if a subject has MCI or AD ([0006]), the method comprising a) obtaining an exhaled breath sample from a subject ([0004]: “collecting a sample of exhaled breath”), b) detecting, in an exhaled sample of a subject, the concentration of the VOC, 1-butanol ([0062]: "collecting a sample of exhaled breath from a person's nose and analyzing the sample to detect the presence of at least one biomarker. The method may further comprise measuring the concentration of the neural biomarker", [0024]: "butanol"; c) comparing the concentration detected in b) with a reference concentration ([0074]: “tau concentration levels above 0.0100 pg/mL indicate more severe AD while tau concentration levels below 0.0100 pg/mL indicate less severe AD.”); and d) diagnosing the subject with AD when the concentration measured in b) is more than about 60% higher than the reference concentration ([0062]: “Nasal breath samples may be analyzed for one or more biomarkers to indicate the likelihood that a patient has a medical condition.”, [0074]: “tau concentration from nasal breath of about 0.0090 pg/mL or lower… 0.0100 pg/mL… tau concentration levels above 0.0100 pg/mL indicate more severe AD while tau concentration levels below 0.0100 pg/mL indicate less severe AD.”, Fig 5A).
Grafman discloses detecting by gas chromatography with mass spectrometry ([0063]: “Breath samples may be analyzed using Gas-Chromatographic techniques combined with Mass Spectrometry”). Grafman fails to disclose detection by gas chromatography-ion mobility spectrometry (GC-IMS).
Handa discloses a method of detecting by gas chromatography-ion mobility spectrometry (GC-IMS), in an exhaled sample from a subject (page 2 para 4: “Breath analysis using an ion mobility spectrometer (IMS) was randomly performed in healthy volunteers and patients with lung cancer”), a concentration of a VOC (page 5 para 1: “and their concentration related to the peak height”).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date to modify the GC-MS detection method disclosed by Grafman with the GC-IMS method disclosed by Handa in order to improve breath detection by reducing preparation time (page 1 para 2: “and is superior to GC/MS as it can be applied at the bed-site and direct sampling can be taken without preparation”).
Regarding claim 13, Grafman discloses detecting, in an exhaled sample of a subject, the concentration of 1-butanol ([0024]: “butanol”) and one or both VOCs selected from the group consisting of hexanal and 2-propanol ([0024]: “hexanal”).
Regarding claim 14, Grafman discloses the subject is diagnosed with AD when the concentration of hexanal measured in a) is 5% to 100% higher than the reference concentration of hexanal ([0074], Fig 5A).
Regarding claim 16, Grafman discloses a method of detecting the concentration of one or both VOCs (0005]: "collecting a sample of exhaled breath from a person's nose and analyzing the sample to detect the presence of at least one biomarker. The method may further comprise measuring the concentration of the neural biomarker") selected from the group consisting of hexanal and heptanal ([0024]: "hexanal”), said method comprising: a) obtaining an exhaled breath sample from a subject ([0004]: “collecting a sample of exhaled breath”), b) detecting in an exhaled sample from a subject, a concentration of one or both VOCs ( [0005]: "collecting a sample of exhaled breath from a person's nose and analyzing the sample to detect the presence of at least one biomarker. The method may further comprise measuring the concentration of the neural biomarker") selected from a group consisting of hexanal and heptanal ([0024]: "hexanal”).
Grafman discloses detecting by gas chromatography with mass spectrometry ([0063]: “Breath samples may be analyzed using Gas-Chromatographic techniques combined with Mass Spectrometry”). Grafman fails to disclose detection by gas chromatography-ion mobility spectrometry (GC-IMS).
Handa discloses a method of detecting by gas chromatography-ion mobility spectrometry (GC-IMS), in an exhaled sample from a subject (page 2 para 4: “Breath analysis using an ion mobility spectrometer (IMS) was randomly performed in healthy volunteers and patients with lung cancer”), a concentration of a VOC (page 5 para 1: “and their concentration related to the peak height”).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date to modify the GC-MS detection method disclosed by Grafman with the GC-IMS method disclosed by Handa in order to improve breath detection by reducing preparation time (page 1 para 2: “and is superior to GC/MS as it can be applied at the bed-site and direct sampling can be taken without preparation”).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Grafman in view of Handa in further view of Campbell et al. (EP1682523B1), hereinafter Campbell.
Regarding claim 2, Grafman as modified by Handa discloses the method of claim 1 but fails to disclose measuring, in an exhaled sample of the subject, the concentration of 2-propanol. However, Grafman discloses that a variety of VOC biomarkers may be collected, including alcohols ([0025]: “butanol”)
Campbell discloses that 2-propanol (page 4 line 17: “isopropyl”) is associated with mild cognitive disorders (page 8 line 3: “mild cognitive disorders”).
Campbell and Grafman are considered analogous art as both pertain to cognitive disorders. As Grafman already discloses that the biomarkers detected by the disclosed method includes alcohol compounds and Campbell discloses that 2-propanol is associated with mild cognitive disorders, it would have been obvious to a person of ordinary skill in the art to expand the detected biomarkers to include 2-propanol in order to create a more robust data set for cognitive disorder detection. Furthermore, as there is a need to expand the measurements of compounds detected in the breath that are associated with neurological illness as opposed to respiratory illness (Grafman [0003]), it would have been obvious to try 2-propanol as a detection method as there are a finite number of biomarkers measurable in exhaled breath that may be an indication of the brain’s condition.
Regarding claim 4, Grafman as modified by Handa discloses the method of claim 1. Grafman further discloses the subject is diagnosed with MCI when the concentration of a VOC in b) is more than 10% higher than the reference concentration of a VOC is indicative that the subject has or will develop a MCI ([0062]: “Nasal breath samples may be analyzed for one or more biomarkers to indicate the likelihood that a patient has a medical condition.”, [0074]: “tau concentration from nasal breath of about 0.0090 pg/mL or lower… 0.0100 pg/mL… tau concentration levels above 0.0100 pg/mL indicate more severe AD while tau concentration levels below 0.0100 pg/mL indicate less severe AD.”, Fig 5A).
Grafman fails to disclose the VOC is 2-propanol.
Campbell discloses that 2-propanol (page 4 line 17: “isopropyl”) is associated with mild cognitive disorders (page 8 line 3: “mild cognitive disorders”).
Campbell and Grafman are considered analogous art as both pertain to cognitive disorders. As Grafman already discloses that the biomarkers detected by the disclosed method includes alcohol compounds and Campbell discloses that 2-propanol is associated with mild cognitive disorders, it would have been obvious to a person of ordinary skill in the art to expand the detected biomarkers to include 2-propanol in order to create a more robust data set for cognitive disorder detection. Furthermore, as there is a need to expand the measurements of compounds detected in the breath that are associated with neurological illness as opposed to respiratory illness (Grafman [0003]), it would have been obvious to try 2-propanol as a detection method as there are a finite number of biomarkers measurable in exhaled breath that may be an indication of the brain’s condition.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Grafman in view of Handa in further view of Yoo et al. (KR 20180077390 A), hereinafter Yoo.
Grafman as modified by Handa discloses the method of claim 1 and further discloses the subject is diagnosed with MCI when the concentration of an aldehyde ([0024]: “hexanal, octanal, nonanal, propanal”) in b) is more than about 10% higher than the reference concentration is indicative that the subject has or will develop a MCI (Fig 5A). However, Grafman fails to disclose that the detected aldehyde is heptanal.
Yoo discloses a method of diagnosing cognitive disorders (abstract) wherein detection of heptanal is indicative of a cognitive disorder (Background art para 10: "cognitive level for heptanal… is significantly reduced in the Alzheimer's animal model And completed the present invention.").
Yoo and Grafman are considered analogous art as both pertain to cognitive disorders. As Grafman already discloses that the biomarkers detected by the disclosed method includes aldehydes and Campbell discloses that heptanal is associated with mild cognitive disorders, it would have been obvious to a person of ordinary skill in the art to expand the detected biomarkers to include heptanal in order to create a more robust data set for cognitive disorder detection. Furthermore, as there is a need to expand the measurements of compounds detected in the breath that are associated with neurological illness as opposed to respiratory illness (Grafman [0003]), it would have been obvious to try heptanal as a detection method as there are a finite number of biomarkers measurable in exhaled breath that may be an indication of the brain’s condition.
Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Stewart et al. (WO2019023239A1), hereinafter Stewart, in view of Handa.
Regarding claim 6, Stewart discloses a method of determining if a subject has AD (abstract) , the method comprising: :a) obtaining an exhaled breath sample from a subject (0007]: “obtaining a sample from the human patient”) b) measuring the concentration of one or both VOCs ([0007]: “obtaining a sample from the human patient, wherein the sample consists of one or more of the metabolites galactose, imidazole, acetone, creatinine”, wherein acetone is a VOC) selected from the group consisting of acetone and 2-butanone ([0045]: "acetone"); c) comparing the concentration detected in b) with a reference concentration ([0041]: "Based on the metabolite concentration data, the inventors were able to generate regression models that significantly differentiated both MCI and AD cases from controls"); and d) diagnosing the subject with AD when the concentration measured in b) is more than 5% higher or more than 5% lower than in the reference concentration, it is indicative that the subject has or will develop AD (Table 1, [0066]: “lx, at least 1.2x,”).
Stewart fails to disclose that VOCs are measured in an exhaled sample from a subject and further that the concentration is detected by gas chromatography-ion mobility spectrometry (GC-IMS).
Handa discloses a method of measuring, in an exhaled sample (page 4 para 4: “The exhaled breath of subjects was taken directly”) from a subject the concentration of one or both VOCs (page 5 para 1: “and their concentration related to the peak height”) by gas chromatography-ion mobility spectrometry (GC-IMS) (page 2 para 4: “Breath analysis using an ion mobility spectrometer (IMS) was randomly performed in healthy volunteers and patients with lung cancer”).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the method disclosed by Stewart to collect samples via exhaled breath as disclosed by Handa in order to improve patient comfort by using a noninvasive detection method and reducing preparation time (page 1 para 2: “it can be applied at the bed-site and direct sampling can be taken without preparation”).
Regarding claim 8, Stewart as modified by Handa discloses the method of claim 6. Stewart further discloses determining that the concentration of acetone measured in a) is higher than the reference concentration of acetone is indicative that the subject has or will develop AD ([0045]), and determining that the concentration of acetone measured in a) is more than about 5% higher than the reference concentration of acetone is indicative that the subject has or will develop AD (Table 1, [0066]: “lx, at least 1.2x,”).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Stewart in view of Handa in further view of Campbell.
Regarding claim 9, Stewart as modified by Handa discloses the method of claim 6 but fails to disclose measuring, in an exhaled sample of the subject, the concentration of 2-propanol.
Campbell discloses that 2-propanol (page 4 line 17: “isopropyl”) is associated with mild cognitive disorders (page 8 line 3: “mild cognitive disorders”).
As Campbell discloses that 2-propanol is associated with mild cognitive disorders, it would have been obvious to a person of ordinary skill in the art to expand the detected biomarkers to include 2-propanol in order to create a more robust data set for cognitive disorder detection. Furthermore, it would have been obvious to try 2-propanol as a detection method as there are a finite number of biomarkers measurable in exhaled breath that may be an indication of the brain’s condition.
Response to Arguments
Applicant's arguments filed 09/12/2025 respect to the rejection(s) of claim(s) 1-15 under 35 USC 102 1 have been fully considered but they are not persuasive. Applicant argues on pages 6-7 of applicant’s remarks that amended claim 1 is patent eligible under 35 USC 101. However, the amendments are not sufficient to overcome the rejection (see rejection above).
Applicant’s arguments with respect to the rejection(s) of claim(s) 1, 3, 12-14 under 35 USC 102(a)(2) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of 35 USC 103 (see rejection above).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/KAVYA SHOBANA BALAJI/Examiner, Art Unit 3791
/DANIEL L CERIONI/Primary Examiner, Art Unit 3791