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 . Claims 1-21 filed October 03, 2025 are currently pending.
Status of Claims
As indicated in the Office Action of 05/28/2024, claims 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/27/2024.
Response to Amendment
Applicant’s amendments filed 10/03/2025 are acknowledged. Support for the phrase “an electronically accessible signal from altered distribution of electrons induced by said at least one VOC” is found in page 10 of the specification (FETs).
Applicants arguments pertaining to the 35 U.S.C 112 paragraph B rejection of record is acknowledged. In view of Applicant’s discussion that the phrase “a nucleic acid functionalizing compound added to a single wall nanotube structure” should be interpreted as a single-walled nanotube that is further functionalized with a distinct nucleic acid, said rejection is withdrawn.
Applicant's arguments, filed 10/03/2025 have been fully considered. Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and objections presently being applied to the instant application.
NEW REJECTION(S) NECESSITATED BY AMENDMENT
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 3-4 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Shokry (Journal of Proteomics Vol. 159 pages 92-101 published online 03/09/2017), Haick (US2011/0098591 published 04/28/2011), Wang (Nanomaterials Vol. 70 pages 1-16 published March 07, 2020), Makaram (US2016/0356741 published 12/08/2016), Someya (Nanoletters Vol. 3 pages 877-881 published 2003) and Sitharaman (WO2015/168411 published 11/05/2015).
Claim 1 is directed to a method for assessing for a disease or condition, said method comprising: i) collecting a sample from the otic canal; ii) analyzing content of at least one VOC in said sample, said analyzing comprising selectively, capturing an electronically accessible signal from altered distribution of electrons induced by said at least one VOC molecule in proximity to a nucleic acid functionalyzing compound added to a single wall nanotube structure; iii) forming a signature indicative of said analyzed content; iv) comparing said signature to a library of signatures associated with a disease or condition; v) acknowledging similarities between said signature formed in iii) and one or a plurality of library signatures; and vi) producing a report indicating said similarities.
The examiner has interpreted that the limitation of “an electronically accessible signal from altered distribution of electrons induced by said at least one VOC” reads on a field effect transistor as found in page 10 of the instant specification.
Shokry (Journal of Proteomics Vol. 159 pages 92-101 published online 03/09/2017) teaches the method of analyzing volatile organic compounds (VOC) in earwax of a subject for detection and monitoring of biomarkers for type 1 and type 2 diabetes mellitus. Shokry teaches that this method is simple, non-invasive accurate and highly accepted by patients (abstract, page 93 left col.).
Regarding step (i) Shokry teaches collecting earwax from the otic canal of 33 healthy subjects and collecting earwax of 26 patients with diabetes mellitus (abstract, Table 2). Said earwax was isolated and subjected to HS-GC/MS analysis wherein the samples were thermally excited over a range from 30°C to up to 250°C (page 93-94 left col.). Regarding steps (ii)-(iv) Shokry teaches analysis of VOC concentrations in the earwax of healthy and diabetes patients. The concentration of VOC methoxyacetone, acetone, ethanol and hydroxyurea were identified as signature biomarkers for patients with diabetes mellitus compared to healthy patients (abstract, page 96, page 97 left col. to right col. and Figure 4). The VOC methoxyacetone was identified as a pivotal biomarker signature diabetic patients capable of discriminating between type 1 and type 2 diabetes in the subject (abstract). Regarding step (v), Shokry teaches acknowledging the similarities of elevated concentrations of methoxyacetone, acetone, ethanol, acetic acid, isobutyraldehyde and hydroxyurea in diabetic patients compared to healthy patients (page 98-99, Figures 4-5, 7). Regarding step (vi) and producing a report indicating said similarities, the peer-reviewed journal article of Shokry disclosing the similarities of VOCs in the earwax of diabetic patients compared to healthy patients reads on the limitation of a report. Regarding claims 3-4, 10-12, said sample of earwax from the otic canal was removed via a solid support (plastic curette) and transferred to an Eppendorf tube and stored at -20°C. (page 93, right col.).
The difference between the presently claimed and that of Shokry is that Shokry does not specifically teach capturing said VOC molecules with a nucleic acid functionalizing compound added to a single wall nanotube structure. Nor does Shokry teach that the VOC is analyzed by capturing an electronically accessible signal from altered distribution of elections induced by said VOC molecule in proximity to a single-walled nanotube that is further functionalized with a distinct nucleic acid. The examiner has interpreted that the phrase “an electronically accessible signal from altered distribution of electrons induced by said at least one VOC” reads on a field effect transistor as found in page 10 of the instant specification.
Haick (US2011/0098591 published 04/28/2011) teaches preparation of single walled carbon nanotubes coated with functionalized molecules. Haick teaches the use of said single walled carbon nanotubes to detect volatile organic compounds in biopsied material and diagnose diseases in a subject in need. Diagnosis of diabetes with the measurement of volatile organic compounds by capturing said volatile compounds with single walled carbon nanotubes coated with functionalized molecules is embraced within the methodology of Haick (abstract, claims 25, 30-31, 34-37).
Wang (Nanomaterials Vol. 70 pages 1-16 published March 07, 2020) teaches the method of functionalizing a single strand DNA to a single-walled carbon nanotube via a pi-pi interaction between the carbon nanotube and the nucleotide in order to detect gaseous volatile organic compounds (abstract, page 2). Wang teaches that the incorporation of the nucleotide to the single-walled carbon nanotube enhances the performance of the sensor, increases the response to different odorants and provides novel material to develop biomimetic sensors for chemical compound detection (abstract, pages 2-3). As shown in Figures 14-15 and supplemental figures S3-S4, Wang teaches that said single strand DNA coordinated to a single-walled carbon nanotube is effective at capturing and measuring the changes of volatile organic compounds acetone and ethanol in a sample, the same volatile organic compounds recited by Shokry as signature biomarkers for patients with diabetes mellitus compared to healthy patients. Wang further teaches wherein said single stranded DNA single wall carbon nanotube shows a significant improvement in sensitivity to unmodified single walled carbon nanotubes with excellent recovery and respectability (page 11, Figures 14-15, supplemental figures S3-S4).
Makaram (US2016/0356741 published 12/08/2016) teaches functionalizing single walled carbon nanotubes as sensor devices (abstract, [0005]). Makaram teaches that the sensor device further includes a field effect transistor (FET) and the single walled carbon nanotube is electrically coupled to the FET ([0007], [0020]-[0024], claims 1, 18). Makaram teaches that the single walled carbon nanotube device is used to detect specific volatile organic compounds ([0019], [0022]).
Someya (Nanoletters Vol. 3 pages 877-881 published 2003) teaches preparation of a single walled carbon nanotube coupled with a field-electric transistor (FET) to measure the presence of volatile organic compounds such as ethanol and other alcohols (abstract, page 877 left col., Figures 1, 5). As shown in Figure 5, Someya teaches that when the surface of the carbon nanotube absorbs ethanol vapor and gets saturated, a detecting current is generated, which reads on “an electronically accessible signal from altered distribution of electrons induced by said at least one VOC” as found in page 10 of the instant specification.
Sitharaman (WO2015/168411 published 11/05/2015) teaches the method of preparing single-walled carbon nanotube structures. Sitharaman teaches that said single-walled carbon nanotube structures are safe and suitable be to inserted into the ear ([0054], claims 1-2, 10).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to analyze the at least one volatile organic compound in the earwax of 26 patients with diabetes mellitus taught by Shokry, wherein said volatile organic compound is sensed with a nucleic acid functionalizing compound added to a single wall nanotube structure in view of Haick and Wang.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art of Wang and Haick to detect diabetes in a subject by analyzing the concentration of volatile organic compounds in a subject, wherein said volatile organic compounds were captured by single walled carbon nanotubes coated with functionalized molecules. Considering that single strand DNA coordinated to a single-walled carbon nanotube is effective at capturing and measuring the changes of volatile organic compounds acetone and ethanol in a gaseous sample, the same volatile organic compounds recited by Shokry as signature biomarkers for patients with diabetes mellitus compared to healthy patients, coupled with the knowledge that single stranded DNA modified single walled carbon nanotubes yield a significant improvement in sensitivity to unmodified single walled carbon nanotubes with excellent recovery and respectability as taught by Wang above, said artisan would have readily applied the single stranded DNA modified single walled carbon nanotube technique of Wang and Haick to capture volatile organic compounds acetone and ethanol to the VOC analysis methodology of Shokry, arriving at presently claimed with a reasonable expectation of success.
Secondly, said skilled artisan would have found it prima facie obvious to apply the single walled carbon nanotubes coated with single strand DNA of Wang and Haick to the otic canal in order to capture said volatile organic compounds in the ear of the diabetic patient in view of Sitharaman. Considering single-walled carbon nanotube structures are safe and suitable be to inserted into the ear, said artisan would have readily applied single walled nanotube structure volatile organic compound sequestering technique of Haick, Wang and Shokry above to the otic canal of a subject in need, arriving at presently claimed with a reasonable expectation of success.
Thirdly, said skilled artisan would have found it prima facie obvious to analyze the presence of and content of said volatile organic compounds wherein a field-electric transistor (FET) is coupled to the single walled carbon nanotube in view of the combined teachings of Makaram and Someya above, arriving at the presently claimed. MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements, according to known methods to obtain predictable results;
In the present case, it was known in the art of Makaram and Someya to couple a field electric sensor to a single walled carbon nanotube in order to measure the presence of volatile organic compounds in samples, wherein the volatile organic compound is absorbed onto the surface of the carbon nanotube, resulting in a detecting current. Accordingly, said artisan would have applied the field electric sensor to the single walled carbon nanotube structure analytical methodology of Shokry, Wang and Haick in view of Makaram and Someya, arriving at presently claimed with a reasonable expectation of success.
Applicant traverses. Applicant argues that the teachings of Shokry do not qualify as prior art. Applicant further contends that the combination of Haick and Wang fail to cure the deficiencies of Shokry.
Response to Arguments
Applicant’s arguments, filed 10/03/2025 are acknowledged and have been carefully considered. Regarding Applicant’s contention that Shokry does not qualify as prior art, this argument is unavailing. As indicated in paragraphs 8-9 of the Office Action of 07/10/2025 , the disclosure of the prior-filed application, Application No. 15725872, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. This application does not repeat a substantial portion of prior Application No. 15725872, filed 10/05/2017. The instant specification adds disclosure not presented in the prior application. In the present case, neither in the specification nor claims of Application 15726872 includes a method for assessing for a disease or condition, said method comprising: i) collecting a sample from the otic canal; ii) analyzing content of at least one VOC in said sample; iii) forming a signature indicative of said analyzed content; iv) comparing said signature to a library of signatures associated with a disease or condition; and v) acknowledging similarities between said signature formed in (iii) and one or a plurality of library signatures, found within instant claims 1-18. The specification of Application No. 15725872, filed 10/05/2017 does not mention volatile organic compounds or (VOC), or otic canal, or signature library anywhere within the boundaries of the disclosure. As such, as said subject matter of the present claims was not adequately described in the aforementioned specifications or claims of the provisional applications. Therefore, as claims 1-18 comprise new matter not present in the prior application of 15725872, the priority of claims 1-18 in the instant application is awarded as of the effective filing date of 03/01/2021, wherein this is first time in the priority chain wherein the subject matter of claims 1-18 is disclosed.
As Shokry is published online on 03/09/2017 in the Journal of Proteomics Vol. 159 pages 92-101 prior to the effective filing date of claims 1-18 disclosed above, Shokry qualifies as prior art.
Regarding Applicant’s contention that neither Haick, nor Wang cure the deficiencies of Shokry, Applicant is reminded that “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references” In re Merck and Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). In the present case, it was known in the prior art of Wang and Haick to detect diabetes in a subject by analyzing the concentration of volatile organic compounds in a subject, wherein said volatile organic compounds were captured by single walled carbon nanotubes coated with functionalized molecules. Considering that single strand DNA coordinated to a single-walled carbon nanotube is effective at capturing and measuring the changes of volatile organic compounds acetone and ethanol in a gaseous sample, the same volatile organic compounds recited by Shokry as signature biomarkers for patients with diabetes mellitus compared to healthy patients, coupled with the knowledge that single stranded DNA modified single walled carbon nanotubes yield a significant improvement in sensitivity to unmodified single walled carbon nanotubes with excellent recovery and respectability as taught by Wang above, said artisan would have readily applied the single stranded DNA modified single walled carbon nanotube technique of Wang and Haick to capture volatile organic compounds acetone and ethanol to the VOC analysis methodology of Shokry, arriving at presently claimed with a reasonable expectation of success.
Claim(s) 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over the combination Shokry (Journal of Proteomics Vol. 159 pages 92-101 published online 03/09/2017), Haick (US2011/0098591 published 04/28/2011), Wang (Nanomaterials Vol. 70 pages 1-16 published March 07, 2020), Makaram (US2016/0356741 published 12/08/2016), Someya (Nanoletters Vol. 3 pages 877-881 published 2003) and Sitharaman (WO2015/168411 published 11/05/2015) as applied to claims 1, 3-4 and 10-12 in view of Cagle (US2004/0126436 published 07/01/2004).
As disclosed above, the combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman render obvious the collection and analysis of volatile organic compounds in the earwax of a subject in need, wherein the volatile organic compounds were captured via a sensor comprising a single stranded DNA complexed to a single wall nanotube structure, wherein a field electric sensor is coupled to the single walled carbon nanotube in order to measure the presence of volatile organic compounds in samples, wherein the volatile organic compound is absorbed onto the surface of the carbon nanotube, resulting in a detecting current. Said combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman further render obvious administering said single walled nanotube structure to the ear of the subject in need. The combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman additionally render obvious the comparison of a molecular signature afforded by the volatile organic compounds in the subject to a reference control and comparing the similarities in the molecular signature of the tested patients to the control.
However, the combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman does not explicitly teach wherein the earwax was extracted using a liquid solvent.
Cagle (US2004/0126436 published 07/01/2004) teaches the method of extracting earwax (cerumen) in a subject in need (abstract, [0010]). Extraction of said earwax comprising administering a liquid solvent comprising methyl trypsin, glycerin, bicarbonate, a sodium citrate/citric acid buffer and water ([0038], [0105], claims 1-12).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to collect the earwax sample from the otic canal in the methodology of Shokry, Haick, Wang, Makaram, Someya and Sitharaman above comprising extracting said earwax using a liquid solvent in view of Cagle.
MPEP 2143 provides rationale for a conclusion of obviousness including (D): Applying a known technique to a known method, ready for improvement to yield predictable results;
In the present case, it was known in the art of Cagle to extract earwax from a subject in need using a liquid bicarbonate and glycerin solvent. Consistent with this reasoning, it would have been obvious to have selected the liquid earwax extraction techniques from within the prior art of Cagle above and apply it to the methodology of Shokry, Haick, Wang, Makaram, Someya and Sitharaman above arriving at the claimed methodology “yielding no more than one would expect from such an arrangement”.
Secondly, said skilled artisan would have found it prima facie obvious to thermally excite said extracted earwax sample embraced within the methodology of Shokry, Haick, Wang, Makaram, Someya and Sitharaman and Cagle in order to convert said isolated otic canal sample to a gaseous phase and allow for the detection of the volatile organic compounds embraced within the collected sample by the single stranded DNA complexed to a single wall nanotube sensor.
Claim(s) 2, 5-9, 13 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Shokry (Journal of Proteomics Vol. 159 pages 92-101 published online 03/09/2017), Haick (US2011/0098591 published 04/28/2011), Wang (Nanomaterials Vol. 70 pages 1-16 published March 07, 2020), Makaram (US2016/0356741 published 12/08/2016), Somaeya (Nanoletters Vol. 3 pages 877-881 published 2003) and Sitharaman (WO2015/168411 published 11/05/2015) as applied to claims 1, 3-4 and 10-12 above, in view of Fink (WO2013/166127 published 11/07/2013).
As disclosed above, the combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman render obvious the collection and analysis of volatile organic compounds in the earwax of a subject in need, wherein the volatile organic compounds were captured via a sensor comprising a single stranded DNA complexed to a single wall nanotube structure, wherein a field electric sensor is coupled to the single walled carbon nanotube in order to measure the presence of volatile organic compounds in samples, wherein the volatile organic compound is absorbed onto the surface of the carbon nanotube, resulting in a detecting current. Said combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman further render obvious administering said single walled nanotube structure to the ear of the subject in need. The combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman additionally render obvious the comparison of a molecular signature afforded by the volatile organic compounds in the subject to a reference control and comparing the similarities in the molecular signature of the tested patients to the control.
However, the combination of Shokry, Haick, Wang, Makaram, Someya and Sitharaman does not specifically teach collecting a gaseous sample of a volatile organic compound from the otic canal of the subject. Nor does Shokry teach wherein said gaseous sample is collected by inserting a probe into the otic canal and contacting a sensing surface of the probe with otic canal gas.
Fink (WO2013/166127 published 11/07/2013) teaches measurement of gaseous volatile organic compounds in the ear comprising inserting a probe within the ear, wherein the probe comprises a gas-absorbing material encased in a capsule, which is integrated with a foam ear plug suitable for insertion into the ear cavity (claims 1-4). Said probe captures the gas emanating from the ear cavity, and said volatile organic compounds within the captured gas are measured with an electronic sensor such as a GC-MS, followed by analysis of volatile organic compounds present in the gas emanating from the ear cavity (page 3, lines 5-20, claims 1-6). Regarding claim 9, said gas-absorbent capsule or cartridge is embodied within an ear plug and is made out of inherently low VOC signature material, the ear plug is inserted into the ear to allow for the capture of the gas in the gas-absorbent cartridge. The ear-plug is removed and is sealed with a cap to store the gas-absorbing capsule for analysis of the absorbed gas signature at a later time. Regarding claims 6-8 and 18, the gas-absorbed capsule is then coupled to a GD-MS to characterizing the gas content of the ear (page 3 line 20 to page 4 line 15, Figures 1-8).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to collect the cerumen sample from the otic canal in the methodology Shokry, Haick, Wang, Makaram, Someya and Sitharaman above by using a probe that captures the gas emanating from the ear cavity and volatile organic compounds within the captured gas, followed by analyzing said volatile organic compounds present in the gas emanating from the ear cavity with an electronic sensor such as a GC-MS in view of Fink in order to arrive at the presently claimed methodology.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the art Fink to probe and measure the concentration of volatile organic compounds within the otic canal with gas-absorbent capsule or cartridge followed by coupling said gas-absorbed capsule a GC-MS to characterizing the gas content of the ear (page 3 line 20 to page 4 line 15, Figures 1-8). Consistent with this reasoning, it would have been obvious to have selected the measurement of gaseous volatile organic compounds within the ear using an gas-absorbing capsule of Fink above and apply it to the measurement of otic gaseous volatile organic compound methodology of Shokry, Haick, Wang, Makaram, Someya and Sitharaman above arriving at the claimed methodology “yielding no more than one would expect from such an arrangement”.
Conclusion
In view of the rejections set forth above, no claim is allowed.
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.
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/GEORGE W KOSTURKO/Examiner, Art Unit 1621