Prosecution Insights
Last updated: April 19, 2026
Application No. 18/370,111

SENSOR FOR THE DETECTION OF HYDROXYL FREE RADICALS

Final Rejection §103
Filed
Sep 19, 2023
Examiner
QIAN, SHIZHI
Art Unit
1795
Tech Center
1700 — Chemical & Materials Engineering
Assignee
The University of Toledo
OA Round
2 (Final)
61%
Grant Probability
Moderate
3-4
OA Rounds
3y 3m
To Grant
99%
With Interview

Examiner Intelligence

Grants 61% of resolved cases
61%
Career Allow Rate
161 granted / 265 resolved
-4.2% vs TC avg
Strong +48% interview lift
Without
With
+48.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 3m
Avg Prosecution
60 currently pending
Career history
325
Total Applications
across all art units

Statute-Specific Performance

§101
1.2%
-38.8% vs TC avg
§103
49.4%
+9.4% vs TC avg
§102
16.8%
-23.2% vs TC avg
§112
28.0%
-12.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 265 resolved cases

Office Action

§103
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 . Status of the Claims The Amendment filed January 15, 2026 has been entered. Claims 7 and 15(w) have been amended; and claims 13-21 have been withdrawn. Claims 1-12 are currently examined herein. Status of the Rejection Applicant’s amendments to the Claims have overcome each objection previously set forth in the Non-Final Office Action mailed October 22, 2025. All 35 U.S.C. § 103 rejections from the previous office action are essentially maintained and modified only in response to the amendment. 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. Claims 1-2, 4-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Rubio et al. (US20210255132A1), and in view of Anandkumar et al. (Influence of age on the free-radical scavenging ability of CeO2 and Au/CeO2 nanoparticles, Journal of Materials Science, 2015, 50, 2522-2531) and Cheung et al. (US20130123100A1). Regarding claim 1, Rubio teaches a sensing composition (a composition [claim 1; para. 0011]) comprising: a conductive support (a carbon-based substrate wherein the carbon-based substrate comprises a conductive, amorphous carbon [claim 1; para. 0011]); and a sensing matrix on the conductive support (cerium oxide nanoparticles on the carbon-based substrate [claim 1; [para. 0011]), wherein the sensing matrix comprises cerium oxide nanoparticles (cerium oxide nanoparticles on the carbon-based substrate [claim 1; [para. 0011]). Rubio is silent to wherein the cerium oxide nanoparticles are arranged on, or intermingled with, metal nanoparticles. Rubio further teaches the sensing composition for detecting free radicals (claim 15). Anandkumar teaches Au nanoparticles were impregnated by deposition precipitation method on the surface of CeO2 nanoparticles in order to enhance the free-radical scavenging properties of Au-supported CeO2 nanoparticles. CeO2 and Au/CeO2 nanoparticles exhibited efficient scavenging of hydroxyl and superoxide radicals. Au/CeO2 showed better radical scavenging activity at lower concentrations than that of CeO2 (abstract). Cheung teaches cerium oxide having high catalytic performance (title). The catalyst includes cerium oxide. The catalyst can include small particles decorated near the surface of the fluorite structured cerium oxide lattice, in which the surface region of the cerium oxide lattice structure has a higher concentration of the small particles than an inner region of the cerium oxide lattice structure, the small particles having a diameter equal to or less than 1 nm. The small particles can include gold particles, and the concentration of the gold particles on the cerium oxide can range from 0.001 to 5.0 atomic percent compared to cerium [para. 0004-0005]. In some implementations, the cerium oxide is decorated with nanoparticles, such as gold nanoparticles, to enhance the catalytic ability of the cerium oxide. In some examples, the concentration of gold can range from about 0.001 to 5.0 atomic percent compared to cerium [para. 0024]. Given the teachings of Rubio regarding the use of the sensing composition for detecting free radicals; the teachings of Anandkumar regarding Au/CeO2 showed better radical scavenging activity at lower concentrations than that of CeO2 nanoparticles; and the teachings of Cheung regarding cerium oxide decorated with gold nanoparticles to enhance the catalytic ability of the cerium oxide, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the sensing matrix in Rubio by adding gold nanoparticles such that the cerium oxide nanoparticles are on or intermingled with gold nanoparticles, as taught by Anandkumar and Cheung, since it would enhance the catalytic ability of the cerium oxide ([para. 0024 in Cheung]) and Au/CeO2 would provide better radical scavenging activity than that of CeO2 (abstract in Anandkumar). Furthermore, one skilled in the art could have applied the same technique (cerium oxide nanoparticles intermingled/decorated with AuNPs to enhance the catalytic ability of the CeO2 NPs, as taught by Anandkumar and/or Cheung) in the same way to the cerium oxide nanoparticles in the sensing matrix of Rubio, yielding predictable results of enhancing the catalytic ability of the CeO2 NPs (MPEP 2143(I)(D)). Regarding claim 2, modified Rubio teaches the sensing composition of claim 1, wherein the metal nanoparticles comprise gold nanoparticles (as outlined in the rejection of claim 1 above, the metal nanoparticles comprise gold nanoparticles [gold nanoparticles in section of Gold-supported CeO2 nanoparticles on page 2523 in Anandkumar; gold nanoparticles in para. 0024 of Cheung]). Regarding claim 4, modified Rubio teaches the sensing composition of claim 1, and Rubio teaches wherein the conductive support comprises a conductive, amorphous carbon (wherein the carbon-based substrate comprises a conductive, amorphous carbon [claim 1]). Regarding claim 5, modified Rubio teaches the sensing composition of claim 1, and Rubio teaches wherein the conductive support comprises carbon black (the conductive, amorphous carbon comprises carbon black [para. 0013]). Regarding claim 6, modified Rubio teaches the sensing composition of claim 1, and Rubio teaches wherein the sensing composition is free of Prussian blue, graphene, and graphene oxide (wherein the composition does not include Prussian blue; and or/wherein the carbon-based substrate does not include graphene or graphene oxide [claim 5]; a conductive, amorphous carbon substrate [para. 0060]). Regarding claim 7, modified Rubio teaches a sensor (a sensor 10 [para. 0065 and claim 10 in Rubio]) comprising the sensing composition of claim 1 (claim 10 in Rubio; the sensing composition of Rubio is modified by Anandkumar and Cheung, as outlined in the rejection of claim 1 above) in electrical communication with an electrode (the carbon-based substrate on an electrode [claim 10 in Rubio]), wherein the electrode is configured to act as a transducer for the sensing composition (wherein the working electrode comprises a sensing composition configured to detect free radicals [para. 0024 in Rubio]; thus the electrode is configured to act as a transducer for the sensing composition), and the sensor is capable of detecting hydroxyl radicals generated by the Fenton reaction (wherein the working electrode comprises a sensing composition configured to detect free radicals [para. 0024 in Rubio]; Cyclic voltammetry was used to characterize the interaction of the composite sensor with ●OH radicals in the Fenton reaction [para. 0072 in Rubio]; thus the sensor is capable of detecting hydroxyl radicals generated by the Fenton reaction). Regarding claim 8, modified Rubio teaches the sensor of claim 7, and Rubio teaches wherein the electrode is a working electrode on a sensing area and the sensor further comprises a counter electrode on the sensing area (The sensor 10 includes a sensing composition on a working electrode 12, where the sensing composition comprises cerium oxide nanoparticles deposited on a carbon-based substrate. The sensor 10 may further include a counter electrode 14. The working electrode 12 and the counter electrode 14 are best seen in FIG. 8D. The sensor 10 directly interacts with the area where the source of free radical generation is. The sensor 10 may be utilized for real-time free radical detection [para. 0065]; Fig.8D shows the working electrode 12 and the counter electrode 14 are on sensing area 20 [para. 0067]). Regarding claim 9, modified Rubio teaches the sensor of claim 7, wherein the metal nanoparticles comprise gold nanoparticles (as outlined in the rejection of claim 1 above, the metal nanoparticles comprise gold nanoparticles [gold nanoparticles in section of Gold-supported CeO2 nanoparticles on page 2523 in Anandkumar; gold nanoparticles in para. 0024 of Cheung]). Regarding claim 10, modified Rubio teaches the sensor of claim 7, and Rubio teaches wherein the electrode is a screen-printed carbon electrode (Screen-printed carbon electrodes were used as the sensor base with 2 mm working electrodes [para. 0075]). Regarding claim 12, modified Rubio teaches the sensor of claim 7, and Rubio teaches wherein the sensor is in a hand-held sensor device (The sensor may be a handheld device capable of real-time, accurate, and consistent sensing of ROS such as, but not limited to, hydroxyl radicals [para. 0053]). Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Rubio, Anandkumar, and Cheung, as applied to claim 2 above, and further in view of Abdelrahim et al. (Study of the electrocatalytic activity of cerium oxide and glod-studden cerium oxide nanoparticles using a sonogel-carbon material as supporting electrode: electroanalytical study in apple juice for babies, Sensors, 2013, 13, 4979-5007). Regarding claim 3, modified Rubio teaches the sensing composition of claim 2, and Cheung further teaches the concentration of gold can range from about 0.001 to 5.0 atomic percent compared to cerium [para. 0024]. Anandkumar teaches the stoichiometry of Au to CeO2 was maintained in such a manner in order to obtain 3.5 weight percentage of Au over CeO2 (section of Gold-supported CeO2 nanoparticles on page 2523). Thus, modified Rubio is silent to wherein the sensing matrix includes an atomic ratio of Au:Ce of about 1:0.075. Abdelrahim teaches electrocatalytic activity of gold sononanoparticles (AuSNPs)/CeO2 nanocomposite, deposited on the surface of a Sonogel-carbon matrix used as supporting electrode, using different AuSNPs:CeO2 w/w ratios (abstract, section 2.6). Table 2 shows electrodes modified with higher proportion of AuSNPs seem to offer better sensitivity (consider that the higher percentage, the lower the CeO2 concentration) (the first paragraph on page 4995, Table 2). Thus, the AuSNPs:CeO2 w/w ratio affects the sensitivity of the sensing composition. Note that an atomic ratio of Au: Ce affects the AuSNPs:CeO2 w/w ratio, which further affects the sensitivity of the sensing composition. As the sensitivity of the sensing composition is a variable that can be modified, among others, by adjusting the weight ratio of AuNP: CeO2 through adjusting the atomic ratio of Au: Ce, with higher atomic ratio of Au: Ce resulting in the higher AuNP: CeO2 weight ratio which further leads to the better sensitivity, the precise atomic ratio of Au: Ce would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed atomic ratio of Au: Ce cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the atomic ratio of Au: Ce in modified Rubio to obtain the atomic ratio of Au: Ce being about 1:0.075 in order to provide the desired sensitivity, as taught by Abdelrahim. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Rubio, Anandkumar, and Cheung, as applied to claim 10 above, and further in view of Duanghathaipornsuk et al. (The effect of size and content of cerium oxide nanoparticles on a composite sensor for hydroxyl radicals detection, Sensors and actuators B: Chemical, 2020, 321, 128467). Regarding claim 11, modified Rubio teaches the sensor of claim 10, and Rubio teaches screen-printed carbon electrodes (Pine Instruments) were used as the sensor base with 2 mm working electrodes [para. 0075], and does not explicitly teach wherein the screen-printed carbon electrode comprises a carbon working electrode, a carbon auxiliary electrode, and an Ag/AgCl reference electrode. Duanghathaipornsuk teaches a sensor comprising a screen-printed carbon electrode for hydroxyl radicals detection (abstract), and further teaches screen-printed carbon electrodes (Pine Instruments) coated with a 2 mm carbon working electrode, Ag/AgCl reference electrode, and carbon counter electrode were used as the sensor base (section 2.1). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the screen-printed carbon electrode in modified Rubio to a screen-printed carbon electrode comprises a carbon working electrode, a carbon auxiliary electrode, and an Ag/AgCl reference electrode, as taught by Duanghathaipornsuk, since Duanghathaipornsuk teaches the suitable alternative screen-printed carbon electrode comprising a carbon working electrode, a carbon auxiliary electrode, and an Ag/AgCl reference electrode for a composite sensor comprising cerium oxide nanoparticles for hydroxyl radicals detection (abstract and section 2.1). Response to Arguments Applicant's arguments, see Remarks Pgs. 5-8, filed 1/15/2026, with respect to the 35 U.S.C. § 103 rejections have been fully considered, but are not persuasive. Applicant’s Argument #1: Regarding the 103 rejections for claims 1-2, 4-10 and 12, Applicant argues at pages 5-7 that there is no express or implicit motivation in Cheung or Anandkumar to add gold nanoparticles to Rubio's sensing matrix, particularly in the precise, low-temperature, electrochemical detection context Rubio teaches. The cited references address different problems (catalytic conversion at high temperature, in vitro antioxidant chemistry, etc.), use non-analogous matrices or loading, and demonstrate complex unpredictability in adding gold to ceria systems. Moreover, modifying Rubio to add gold nanoparticles would introduce variables such as agglomeration, gold-ceria interface chemistry, electrochemical compatibility, and non-thermal activation, that none of the cited references provide guidance for addressing. The technical modifications required to combine the teachings of Anandkumar/ Cheung with Rubio are not straightforward or predictable. The effects of gold on Ce³* site concentration, nanoparticle aggregation, electron transfer, and sensor efficiency are context-dependent, and both Anandkumar and Cheung indicate that such combinations can reduce rather than enhance critical sensor properties. Accordingly, the person of ordinary skill in the art would have no motivation, with a reasonable expectation of success, in modifying the sensing matrix of Rubio in the manner alleged. Examiner’s Response #1: Applicant’s arguments have been fully considered, but are not persuasive. Firstly, Anandkumar teaches Au nanoparticles were impregnated by deposition precipitation method on the surface of CeO2 nanoparticles in order to enhance the free-radical scavenging properties of Au-supported CeO2 nanoparticles. Au/CeO2 showed better radical scavenging activity at lower concentrations than that of CeO2 (abstract). The hydroxyl radical scavenging property of the nanoparticles was investigated at 37 oC (section of Hydroxyl radical scavenging assay on page 2524). Thus, even with the teachings of Anandkumar, one of ordinary skill in the art would be motivated to add gold nanoparticles to the cerium oxide nanoparticles since Au/CeO2 would provide better radical scavenging activity at lower concentrations than that of CeO2 (abstract in Anandkumar). Secondly, Rubio teaches the outstanding ability of CeNPs for scavenging ●OH radicals is due to their unique dual oxidation states, which can easily switch between Ce3+ and Ce4+ by reducing or oxidizing species in a medium. In the typical redox reaction with hydroxyl radicals, cerium (III) oxide is oxidized to cerium (IV) oxide with two moles of hydroxyl radicals (FIG. 1). The Ce3+ oxidation state of the CeNPs is believed to act as the active site for the redox reaction that scavenges ●OH radicals, as depicted in Fig.1 [para. 0054]. Thus, in the detection of free radicals, the cerium oxide works as a catalyst by switching between Ce3+ and Ce 4+ state. Thirdly, Cheung teaches cerium oxide is decorated with nanoparticles, such as gold nanoparticles, to enhance the catalytic ability of the cerium oxide [para. 0024], and the cerium oxide maintains catalytic ability at temperatures at least up to 450° C (abstract and claims 1 and 4). Since the decorated cerium oxide maintains catalytic ability at temperatures at least up to 450° C, it can be used for low-temperature applications. Since Rubio teaches the cerium oxide works as a catalyst for free radicals by switching between Ce3+ and Ce 4+ state, and Cheung teaches cerium oxide decorated with gold nanoparticles enhances the catalytic ability of the cerium oxide and the decorated cerium oxide maintains catalytic ability at temperatures at least up to 450° C, Rubio and Cheung are considered analogous art to the claimed invention because they are in the same field of cerium oxide catalyst. Thus, one of ordinary skill in the art would also add gold nanoparticles to the cerium oxide nanoparticles to enhance the catalytic ability of the cerium oxide. Accordingly, based on the teachings from both Anandkumar and Cheung, a person of ordinary skill in the art would be motivated, with a reasonable expectation of success, to modify the sensing matrix of Rubio by adding gold nanoparticles. Applicant’s Argument #2: Regarding claim 3, Applicant argues at page 7 that Abdelrahim fails to provide a person of ordinary skill in the art motivation, with a reasonable expectation of success, to modify the sensing matrix of Rubio in the manner alleged. Examiner’s Response #2: Based on the Examiner’s response #1 above, a person of ordinary skill in the art would be motivated, with a reasonable expectation of success, to modify the sensing matrix of Rubio by adding gold nanoparticles. Applicant’s Argument #3: Regarding claim 11, Applicant argues at page 8 that Duanghathaipornsuk fails to provide a person of ordinary skill in the art motivation, with a reasonable expectation of success, to modify the sensing matrix of Rubio in the manner alleged. Examiner’s Response #3: Based on the Examiner’s response #1 above, a person of ordinary skill in the art would be motivated, with a reasonable expectation of success, to modify the sensing matrix of Rubio by adding gold nanoparticles. 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 SHIZHI QIAN whose telephone number is (571)272-3487. The examiner can normally be reached Monday-Thursday 8:00 am-5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan V Van can be reached on 571-272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /SHIZHI QIAN/Examiner, Art Unit 1795
Read full office action

Prosecution Timeline

Sep 19, 2023
Application Filed
Oct 19, 2025
Non-Final Rejection — §103
Jan 15, 2026
Response Filed
Feb 08, 2026
Final Rejection — §103 (current)

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Prosecution Projections

3-4
Expected OA Rounds
61%
Grant Probability
99%
With Interview (+48.1%)
3y 3m
Median Time to Grant
Moderate
PTA Risk
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