DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on January 16, 2026. Claims 1-3 and 18-32 are pending in the application.
Status of Objections and Rejections
All objections from the previous office action are withdrawn in view of Applicant’s amendment.
All rejections under 35 U.S.C. §112 from the previous office action are withdrawn in view of Applicant’s amendment. Other rejections under 35 U.S.C. §103 are maintained.
New grounds of rejection are necessitated by the amendments.
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.
Claim(s) 32 is/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 pre-AIA the applicant regards as the invention.
Claim 32 recites “an rGO biosensor” in line 3. It is suggested to be “the rGO biosensor.”
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) 1-2, 18, 21-22, 24-28, and 30-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo (G. Seo, Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor, AVS Nano 2020(14), pp. 5135-42) in view of Zhang (L. Zhang, Recent Advances in Emerging 2D Material-Based Gas Sensors: Potential in Disease Diagnosis, Advanced Materials Interfaces, 2019(6), 1901329, pp. 1-27), supported by Cotten (M. Cotten, Evolution of increased positive charge on the SARS-CoV-2 spike protein may be adaptation to human transmission, iSicence, 2023(26), 106230, pp. 1-14).
Regarding claim 1, Seo teaches a method comprising:
applying an analyte to a biosensor configured to bind to the analyte (Fig. 1: COVID-19 FET sensor; SARS-CoV-2 virus is applied to the FET sensor);
applying a DC voltage to the biosensor (p. 5141, col. 1, para. 2: a drain-source bias voltage of ~10 mV was maintained during measurement) while monitoring an electrical signal from the biosensor (p. 5141, col. 1, para. 2: the detected electrical response); and
detecting a response to the analyte based on a change in the monitored electrical signal (e.g. Fig. 6B: the monitored electrical signal, i.e., the normalized current, shows a response to the analyte based on a change between the normal sample and patient sample, a change in the current).
Seo does not teach the biosensor is a rGO biosensor.
However, Zhang teaches 2D material-based gas sensors and potential in disease diagnosis (title), including graphene and its derivative (p. 4: Section 2.3.1). Graphene oxide is a derivative of graphene, which generate abundant functional group on GO surface that would accelerate the charge transfer (p. 4, col. 1, para. 2). Reduced graphene oxide (rGO) is another graphene derivative prepared by further reduction of GO, which provide some new vacancies and defects as active locations for gas adsorption (p. 4, col. 1, para. 2). The conductivity of rGO is higher than GO, affording the sensor with admirable sensitivity to target gases at lower power consumption (p. 4, col. 1, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo by substituting the graphene sheet with rGO of the biosensor as taught by Zhang because rGO would provide some new vacancies and defects as active locations for gas adsorption and have higher conductivity to afford the sensor with admirable sensitivity to target gases at lower power consumption (p. 4, col. 1, para. 2).
Seo does not disclose wherein the DC voltage is: +0.0008V to +0.005V for a negatively charged analyte; or -0.005V to -0.0008 for a positively charged analyte.
However, Seo teaches a drain-source bias voltage of ~10 mV was maintained during measurement for the analyte (Fig. 3; p. 5141, col. 1, para. 2). As evidenced by Cotten, SARS-Covb-2 spike protein (title) is negatively charged (p. 7, para. 2: from a protein with a total charge of -8.28 in the original Lineage A and B virus to a protein with a total charge of -1.26 in the Omicon lineage viruses). Thus, Seo teaches a +10mV for a negatively charged analyte.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo by adjusting the DC voltage for monitoring current from the biosensor for the response to the analyte as suggested because in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Further, it would be obvious to one of ordinary skill in the art to switch the polarity of DC voltage for an analyte with opposite charge for not repelling the analyte away, i.e., the same voltage with opposite polarity for the opposite charged analyte.
Regarding claim 2, Seo teaches wherein the electrical signal is current (Fig. 4B; p. 5141, col. 1, para. 2), and monitoring the electrical signal comprises calculating a normalized current from the current and identifying a peak in the normalized current corresponding to a response to the analyte (Fig. 4C; p. 5141, col. 1, para. 2).
Regarding claim 18, Seo teaches wherein the biosensor comprises substrate (Fig. 1: the substrate) and bioreceptors immobilized on the substrate (Fig. 1: SARS-CoV-2 spike antibody). As a result, the combined Seo and Zhang would necessarily result in the biosensor is rGO biosensor and the substrate is a rGO substrate.
Regarding claim 21, Seo teaches wherein the bioreceptors are antibodies are immobilized to the substrate by linker molecules (Fig. 1: via 1-pyrenebutyric acid N-hydroxysuccinimide ester). As a result, the combined Seo and Zhang would necessarily result in the biosensor is rGO biosensor and the substrate is a rGO substrate.
Regarding claim 22, Seo teaches wherein the linker molecules are PBASE molecules (p. 5137, col. 2, para. 1: 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE)).
Regarding claim 24, Seo teaches wherein the bioreceptors have a binding affinity to SARS-CoV-2 (Fig. 1; p. 5138, col. 2, para. 4).
Regarding claim 25, Seo teaches wherein the normalized current is calculated relative to an initial baseline current measured prior to application of the analyte (p. 5141, col. 1, para. 2: the detected electrical response signal was normalized as
∆
I
I
0
=
(
I
-
I
0
)
/
I
0
), where I is the detected real-time current and
I
0
is the initial current).
Regarding claim 26, Seo teaches wherein identifying the peak in the normalized current comprises identifying the peak during real-time monitoring of the current after application of the analyte (Fig. 6D: Real-time response of COVID-19 FET toward SARA-CoV-2 clinical sample; indicating peaks of the normalized current corresponding to the sample).
Regarding claim 27, Seo teaches, wherein the peak in the normalized current comprises a maximum in the normalized current relative to a baseline current (Fig. 6D: indicating a maximum in the normalized current, i.e., a peak, relative to the baseline).
Regarding claim 28, Seo teaches wherein the peak is transient (Fig. 6D: indicating after reaching the peak, the normalized current goes down to a baseline).
Regarding claim 30, Seo teaches wherein applying the analyte comprises: applying a liquid sample containing the analyte directly onto a surface of the biosensor (Fig. 1; further, the combined Seo and Zhang renders it obvious that the biosensor is a rGO biosensor).
Regarding claim 31, Seo teaches wherein applying the DC voltage comprises applying the DC voltage across electrical contacts coupled to the biosensor (Fig. 1: indicating the electrical leads have electrical contacts to the drain/source electrodes; p. 5140, col. 1, para. 2: a drain-source bias voltage of ~10 mV was maintained; col. 5139, col. 2, last para.: the linear I-V curves exhibited high stable ohmic contact; further, the combined Seo and Zhang renders it obvious that the biosensor is a rGO biosensor).
Regarding claim 32, Seo teaches a method of detecting an analyte using a biosensor (Fig. 1: COVID-19 FET sensor; graphene sheet) comprising:
applying an analyte to a biosensor functionalized with a bioreceptor configured to bind the analyte (Fig. 1: SARS-CoV-2 spike antibody for binding the SARS-CoV-2 virus);
applying a DC voltage to the biosensor (p. 5141, col. 1, para. 2: a drain-source bias voltage of ~10 mV was maintained during measurement);
measuring an electrical current through the biosensor over time while the DC voltage is applied (p. 5141, col. 1, para. 2: a drain-source bias voltage of ~10 mV was maintained during measurement);
determining an initial baseline current prior to binding of the analyte to the biosensor (e.g., Fig. 6(C): initial baseline before detecting patient sample #2);
calculating a normalized current signal based on the measured electrical current relative to the initial baseline current (Fig. 6(D); p. 5141, col. 1, para. 2: the detected electrical response signal was normalized as
∆
I
I
0
=
(
I
-
I
0
)
/
I
0
), where I is the detected real-time current and
I
0
is the initial current); and
detecting the analyte by identifying a peak in the normalized current signal indicative of binding of the analyte to the biosensor (Fig. 6(D): indicating peaks in the normalized current signal corresponding to the different amounts of the analyte; the current signal is based on the binding of the antibody and the virus as shown in Fig. 1)
Seo does not teach the biosensor is a rGO biosensor.
However, Zhang teaches 2D material-based gas sensors and potential in disease diagnosis (title), including graphene and its derivative (p. 4: Section 2.3.1). Graphene oxide is a derivative of graphene, which generate abundant functional group on GO surface that would accelerate the charge transfer (p. 4, col. 1, para. 2). Reduced graphene oxide (rGO) is another graphene derivative prepared by further reduction of GO, which provide some new vacancies and defects as active locations for gas adsorption (p. 4, col. 1, para. 2). The conductivity of rGO is higher than GO, affording the sensor with admirable sensitivity to target gases at lower power consumption (p. 4, col. 1, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo by substituting graphene sheet with rGO as taught by Zhang because rGO would provide some new vacancies and defects as active locations for gas adsorption and have higher conductivity to afford the sensor with admirable sensitivity to target gases at lower power consumption (p. 4, col. 1, para. 2).
Seo does not disclose wherein the DC voltage is: +0.0008V to +0.005V for a negatively charged analyte; or -0.005V to -0.0008 for a positively charged analyte.
However, Seo teaches a drain-source bias voltage of ~10 mV was maintained during measurement for the analyte (Fig. 3; p. 5141, col. 1, para. 2). As evidenced by Cotten, SARS-Covb-2 spike protein (title) is negatively charged (p. 7, para. 2: from a protein with a total charge of -8.28 in the original Lineage A and B virus to a protein with a total charge of -1.26 in the Omicon lineage viruses). Thus, Seo teaches a +10mV for a negatively charged analyte.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo by adjusting the DC voltage for monitoring current from the biosensor for the response to the analyte as suggested because in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Further, it would be obvious to one of ordinary skill in the art to switch the polarity of DC voltage for an analyte with opposite charge for not repelling the analyte away, i.e., the same voltage with opposite polarity for the opposite charged analyte.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo in view of Zhang, and further in view of Zaretski (WO 2022/015814).
Regarding claim 3, Seo and Zhang disclose all limitations of claim 1. Seo further discloses the graphene is disposed on a substrate (Fig. 1). As described in claim 1, the combined Seo and Zhang would necessarily result in a rGO biosensor comprising a rGO layer being disposed on the substrate.
Seo and Zhang do not disclose the rGO layer having a thickness of 20 nm to 60 nm.
However, Zaretski teaches a patterned biosensor layer 115 disposed on the substrate 110 (Fig. 1). The layer maybe a reduced graphene-oxide layer, with a thickness of, e.g., 0.3 nm-100 nm (¶46), which overlaps the claimed range.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo and Zhang by adjusting the thickness of the rGO layer within the claimed range because they are suitable thickness of the biosensing layer, e.g., rGO, of a biosensor. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Claim(s) 19-20 and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo and Zhang, and further in view Singh (R. Singh, Label-free Detection of Influenza Viruses using a Reduced Graphene Oxide-based Electrochemical Immunosensor Integrated with a Microfluidic Platform., Scientific Reports, 2017(7), 42771, pp. 1-11).
Regarding claims 19 and 29, Seo and Zhang discloses all limitations of claim 18. Seo further teaches the substrate comprises a base (Fig. 1: the base below the graphene layer). Thus, the combined Seo and Zhang would necessarily have the rGO substrate comprising a base.
Seo and Zhang do not disclose wherein the substrate comprises five or more layers of reduced graphene oxide on the base (claim 19) or wherein the reduced graphene oxide substrate comprises seven layers of reduced graphene oxide (claim 29).
However, Singh teaches a RGO-based electrochemical immunosensor for label-free detection of an influenza virus ([Abstract]). The working electrode was functionalized using RGO ([Abstract]), and the prepared RGO has few layers (approximately 6-8 layers) (p. 3, para. 1), which overlaps the claimed range of the number of the reduced graphene oxide layers.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo and Zhang by adjusting the number of RGO layers within claimed range because in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Regarding claim 20, the designation “wherein the five or more layers were formed by a graphene oxide solution with a concentration of 2 mg/mL and reduction of the graphene oxide to form the graphene oxide substrate” does not further limit the method as recited in claim 19 because it does not positively recite a step to be performed in the method of claim 19 for monitoring an electrical signal for a response to the analyte using the rGO biosensor comprising a base and five or more layers of rGO on the base after applying the analyte and the voltage. Further, the method of manufacturing the rGO biosensor is a “product-by-process” limitation for the recited rGO biosensor. If Applicant intends to further limit the rGO biosensor used in the method of claim 19, Examiner suggests to amend the claim by reciting the structural limitations of the biosensor instead of reciting the manufacturing steps of the biosensor.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo and Zhang, and further in view Taniguchi (US 4,839,017).
Regarding claim 23, Seo and Zhang discloses all limitations of claim 22. Seo further discloses the antibody bound to the SARS-CoV-2 spike protein but not to bovine serum albumin (BSA) (p. 5138, col. 2, para. 4).
Seo and Zhang do not teach BAS are capped to prevent non-specific binding.
However, Taniguchi teaches immunosensors comprising an electrically-conductive film capable of binding an antigen or an antibody ([Abstract]). The immunosensor uses a receptor which can identify an antigen or an antibody to be determined on the surface by directly detecting an immuno reaction, i.e., an antigen-antibody reaction (col. 1, ll. 14-19, 21).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Seo and Zhang by utilizing BSA for blocking non-specific adsorption as taught by Taniguchi because all the claimed elements were known in the prior art and the combination of these elements by known methods would not have change in their respective functions, and thus the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Response to Arguments
Applicant’s arguments have been considered but are unpersuasive in light of new grounds for rejection.
Applicant argues Seo does not disclose the limitation “applying a DC voltage to the rGO biosensor while monitoring an electrical signal from the rGO biosensor, wherein the DC voltage is: +0.0008V to +0.005V for a negatively charged analyte; or -0.005V to -0.0008 for a positively charged analyte” in claim 1 (Response, p. 9). This argument is unpersuasive. Seo teaches the a drain-source bias voltage of ~10 mV (i.e., +0.001V) was maintained during measurement for the analyte (Fig. 3; p. 5141, col. 1, para. 2), for detecting SARS-Covb-2 spike protein which is negatively charged as evidenced by Cotton (p. 7, para. 2: from a protein with a total charge of -8.28 in the original Lineage A and B virus to a protein with a total charge of -1.26 in the Omicon lineage viruses). Thus, Seo teaches applying a DC voltage, +0.001V (i.e., +10mV), to a biosensor for detecting a negative charged analyte. It would be obvious to one of ordinary skill in the art to apply a DC voltage ranging from +0.0008V to +0.0005V for the negatively charged analyte, because a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Further, since +10mV is appropriate DC voltage for detecting negatively charged analyte, it would be obvious to one of ordinary skill in the art to using -10 mV for detecting positively charged analyte because switching the polarity of DC voltage for an analyte with opposite charge is well known in the art, so that the electrical field strength would be the same but the electrical direction is opposite for opposite charged analytes. Examiner notes that claim 1 does not recite a linear sweep from +0.0008V to +0.0005V, which is interpreted as a fixed bias voltage within the range of +0.0008V to +0.0005V.
Applicant argues there is no teaching or suggestion that the ~10 mV voltage would be a suitable voltage for the modified Seo device (p. 10, para. 2). This argument is unpersuasive because Applicant seems to attack the references individually and, therefore, do not address adequately the rejection the Examiner presents in the record. See In re Keller, 642 F.2d 413, 426 (CCPA 1981) (“[O]ne cannot show non-obviousness by attacking references individually where, as here, the rejections are based on combinations of references.”), 425 (“[T]he test [for obviousness] is what the combined teachings of the references would have suggested to those of ordinary skill in the art.”); see also In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986); and KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) (“[T]he [obviousness] analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.”).
Applicant argues the criticality for the applied DC voltage range (p. 10, para. 3), based on the comparison between 0.0008V and 0.005, 0.015, and 0.2V (e.g., Spec. Fig. 16). Applicant argues that Fig. 21 also shows the LOD of the biosensor was over 100 fold lower at the fixed voltage of 0.0008V than at a fixed voltage of 0.2 V (Response, p. 11). These arguments are not persuasive. Even if 0.0008V is better than 0.2V, it doesn’t negate the obviousness to use 0.0008V (8mV) from the teaching of using 10mV in the prior art.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795