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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/15/2024, 10/14/2024, and 03/06/2025 have been considered by the examiner.
Claim Objections
Claims 5, 9, 13, 18, and 20 are objected to because of the following informalities:
Claim 5, please amend “a saliva of a subject” to “[[a]] the saliva of [[a]] the subject”.
Claim 9, please amend “claim 1, being a carbon electrode” to “claim 1, the electrode being a carbon electrode”.
Claim 10: please amend “said viral biomarker” to “said [[viral]] biomarker”.
Claim 13, please amend “wherein a detectable change is an electrochemical parameter is generated” to “wherein [[a]] the detectable change is [[an]] the electrochemical parameter is generated”.
Claims 18: “for determining a presence and/or amount of a viral infection” to “for determining [[a]] the presence and/or amount of [[a]] the viral infection”.
Claim 20, please amend “for determining a presence and/or amount of a viral infection” to “for determining [[a]] the presence and/or amount of [[a]] the viral infection”; “biomarker is SARS-CoC-2” to “biomarker is SARS-Co[[C]]V-2”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding Claim 15, the limitation “said electroactive agent undergoes an electrochemically detectable (e.g., redox) reaction” is indefinite as this limitation uses the phrase “such as”. The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 16 is further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 15.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12 and 17-20 is rejected under 35 U.S.C. 103 as being unpatentable by Mahari (eCovSens-Ultrasensitive Novel In-House Built Printed Circuit Board Based Electrochemical Device for Rapid Detection of nCovid-19 antigen, a spike protein domain 1 of SARS-CoV-2 bioRxiv, 2020, pages 1-20, provided in IDS dated 07/14/2024) in view of O’Brien (Detecting SARS-CoV-2 3CLpro expression and activity using a polyclonal antiserum and a luciferase-based biosensor Virology, 2021; 556, 73-78, provided in IDS dated 07/14/2024).
Regarding Claim 1, Mahari teaches an electrode (FTO/AuNPs/nCovid-10 Ab modified electrode [Section 2.5 Fabrication of FTO electrode with AuNPs/nCovid 19- Ab, page 4]) having attached thereto an agent (nCovid-19 Ab is immobilized on different FTO/AuNPs [Section 2.5 Fabrication of FTO electrode with AuNPs/nCovid 19- Ab, page 4]) that specifically binds to a biomarker of a viral infection (nCovid-19 Ab binds with nCovid-19 Ag [first and second para., page 3]), wherein:
the biomarker is found in a saliva of a subject having said viral infection (spiked saliva samples [abstract]).
Mahari is silent on the biomarker is a proteolytic enzyme indicative of said viral infection.
O’Brien teaches detecting SARS-CoV-2 using 3C-like protease (abstract), and teaches the biomarker is a proteolytic enzyme indicative of said viral infection (SARS-CoV-2 3CLpro [first para. col. 2, page 73]).
Mahari and O’Brien are considered analogous art to the claimed invention because they are in the same field of SARS-CoV-2 biosensors. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to substitute the biomarker in the method of Mahari to be SARS-CoV-2 3CLpro, as taught by O’Brien, as using coronavirus 3C-like proteases can be used to develop strategies to identify inhibitors that block highly conserved viral proteins essential for virus replication (O’Brien, [first para. col. 1, page 74]).
Regarding Claim 2, modified Mahari teaches the electrode of claim 1, and teaches wherein said biomarker is said proteolytic enzyme (as outlined in the claim 1 rejection above, O’Brien teaches the biomarker is SARS-CoV-2 3CLpro [first para. col. 2, page 73].
Regarding Claim 3, modified Mahari teaches the electrode of claim 2.
Mahari teaches wherein said agent that specifically binds to said biomarker is an antibody specific to said proteolytic enzyme (nCovid-19 antibody specifically binds with its protein biomarker counterpart [first and second para., page 3]).
Regarding Claim 4, modified Mahari teaches the electrode of claim 1, and teaches wherein said biomarker is a SARS-CoV-2-specific proteolytic enzyme (as outlined in the claim 1 rejection above, O’Brien teaches the biomarker is SARS-CoV-2 3CLpro [first para. col. 2, page 73]).
Regarding Claim 5, modified Mahari teaches the electrode of claim 4.
Mahari teaches wherein said biomarker is found in a saliva of a subject having an active SARS-CoV-2 viral infection (spiked saliva samples used of SARS-CoV-2 [abstract]).
Regarding Claim 6, modified Mahari teaches the electrode of claim 4.
Mahari teaches wherein said agent that specifically binds to said proteolytic enzyme is an antibody specific to said SARS-CoV-2-specific proteolytic enzyme (immobilized nCovid-Ab is specific to target protein biomarker [abstract]).
Regarding Claim 7, modified Mahari teaches the electrode of claim 4, and teaches wherein said SARS-CoV-2-specific proteolytic enzyme is 3CLpro (SARS-CoV-2 3CLpro) (as outlined in the claim 1 rejection above, O’Brien teaches the biomarker is SARS-CoV-2 3CLpro [first para. col. 2, page 73]).
Regarding Claim 8, modified Mahari teaches the electrode of claim 7, and teaches wherein said 3CLpro comprises an amino acid sequence as set forth in SEQ ID NO:2 (as outlined in the claim 1 rejection above, O’Brien teaches the biomarker is SARS-CoV-2 3CLpro [first para. col. 2, page 73]; SARS-CoV-2 3CLpro has the sequence listed in SEQ ID NO:2 [see Fig. 3A of O’Brien, [page 76]).
Regarding Claim 9, modified Mahari teaches the electrode of claim 1.
Mahari is silent on the electrode being a carbon electrode, optionally a carbon fiber electrode.
However, in another embodiment, Mahari teaches the electrode being a carbon electrode (screen printed carbon electrode [abstract]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the electrode of modified Mahari to be a carbon electrode, as taught by Mahari, as electrodes made of carbon are suitable for immobilization of immobilizing Covid antibodies for sensing (Mahari, [abstract]).
Regarding Claim 10, modified Mahari teaches an electrochemical system comprising the electrode of claim 1 (see claim 1 rejection above);
the limitation “the electrochemical system being configured such that when said viral biomarker is contacted with said electrode, a detectable change in an electrochemical parameter is generated” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, cyclic voltammetry is used to measure the electrical current difference via the binding of nCovid-19 Ag [third para. page 6]. Thus, the electrochemical system of modified Mahari is capable of performing the claimed function above.
Regarding Claim 11, modified Mahari teaches the electrochemical system of claim 10. Mahari teaches wherein said electrode forms a part of an electrochemical cell (as illustrated in Scheme 1 (B), FTO working electrode is part of an electrochemical cell [page 7]) and the electrochemical cell is operable by electrically connecting said electrode to a power source (electrochemical cell is connected to a potentiostat as illustrated in Scheme 1 (B) [page 7]).
Regarding Claim 12, modified Mahari teaches the electrochemical system of claim 11.
Mahari teaches wherein the electrochemical cell is operable by contacting said electrode with an electrolyte (electrolyte is comprised of K3[Fe(CN)6]/K4[Fe(CN)6] (1:1) solution with 100 mM KCl [see Scheme 1 (B) page 7]).
Regarding Claim 17, modified Mahari teaches the electrode of claim 1.
Mahari teaches a method of determining a presence and/or amount of a viral biomarker in a sample (detect the presence of nCovid-19 spike Ag [first para. page 3]), the method comprising contacting the sample with the electrode of claim 1 (as outlined in the claim 1 rejection above, modified Mahari teaches the electrode recited in claim 1), and determining a change in an electrochemical parameter (variation in current as judged by cyclic voltammetry [first para. 10]; illustrated in cyclic voltammetry graphs on page 10) generated upon operating an electrochemical system comprising the electrode of claim 1 (Scheme 1 sensor is an electrochemical system that uses the FTO immunosensor outlined in claim 1 above [third para. page 6]; also illustrated in Scheme 1 (B), page 7), wherein said change is indicative of the presence and/or amount of the viral biomarker in the sample (as shown in Fig. 3A, current is varied based on concentration of nCovid-19 Ag [page 12]).
Regarding Claim 18, modified Mahari teaches the method of claim 17.
Mahari teaches wherein the sample is a biological sample drawn from a subject (saliva [first para. page 14]), the method being for determining a presence and/or amount of a viral infection in the subject (detection of nCovid-19 Ag [first para. page 14]).
Regarding Claim 19, modified Mahari teaches the method of claim 18.
Mahari teaches wherein said biological sample is a saliva sample of the subject (as outlined in the claim 18 rejection above, sample is saliva [first para. page 14]).
Regarding Claim 20, modified Mahari teaches the method of claim 17, and teaches wherein said biomarker is SARS-CoC-2 3CLpro (as outlined in the claim 1 rejection above, O’Brien teaches the biomarker is SARS-CoV-2 3CLpro [first para. col. 2, page 73]).
Mahari teaches the method being of determining a presence and/or amount of a viral infection caused by SARS-CoV-2 in the subject (as shown in Fig. 3A, current is varied based on concentration of nCovid-19 Ag [page 12]).
Claims 13-16 is rejected under 35 U.S.C. 103 as being unpatentable by Mahari and O’Brien, as applied to claim 12 above, and in view of Biloivan (Development of Enzyme Biosensor Basedd on ISFETs for Quantitative Analysis of Serine Proteinases. Electroanalysis 2004; 16(22), pages 1883-1889).
Regarding Claim 13, modified Mahari teaches the electrochemical system of claim 12.
Mahari is silent on wherein said electrolyte comprises a substance that is capable of interacting with said biomarker, wherein a detectable change is an electrochemical parameter is generated in response to an interaction between said biomarker and said substance.
Biloivan teaches a potentiometric biosensor for quantitative determination of proteinases (abstract), and teaches wherein said electrolyte comprises a substance (electrolyte includes substrate BAEE [second para. col. 2, page 1885]) that is capable of interacting with said biomarker wherein a detectable change is an electrochemical parameter is generated in response to an interaction between said biomarker and said substance (substrate BAEE interacts with immobilized trypsin-like proteinases to determine amount of proteinase via hydrolysis with water [fourth and fifth paras. col. 2, page 1885 and Scheme 1 page 1885] to create a pH dependent reaction [see Figure 4, page 1888]).
Modified Mahari and Biloivan are considered analogous art to the claimed invention because they are in the same field of biosensors using immobilized proteolytic enzymes. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to substitute said biomarker of modified Mahari to be a trypsin-like proteinase and modify the electrolyte to include BAEE so that said electrolyte comprises a substance that is capable of interacting with said biomarker wherein a detectable change is an electrochemical parameter is generated in response to an interaction between said biomarker and said substance, as taught by Biloivan, as BAEE interacts with trypsin to create hydrogen ions to measure the activity of trypsin (Bioloiva, [fourth and fifth paras. col. 2, page 1885; also Figures 1 and 4 pages 1885 and 1888, respectively).
Regarding Claim 14, modified Mahari teaches the electrochemical system of claim 13, and teaches wherein said electrolyte further comprises an electroactive agent that undergoes an electrochemically detectable reaction in response to said interaction to thereby generate said change in said electrochemical parameter (as outlined in the claim 13 reaction above, water is contained in the electrolyte and used in the hydrolysis of BAEE [fourth and fifth paras. col. 2, page 1885; illustrated in Figure 1 page 1885]).
Regarding Claim 15, modified Mahari teaches the electrochemical system of claim 14, and teaches wherein said biomarker, said substance, and said electroactive agent are selected such that said interaction between said biomarker and said substance generates a moiety or species (as outlined in the claim 13 reaction above, hydrolysis of BAEE generates and hydrogen ion [Figure 1 page 1885]), and said electroactive agent undergoes an electrochemically detectable reaction in response to a presence of said chemical moiety or species (as outlined in the claim 13 reaction above, generating a hydrogen ion allows for detection of change in pH [fourth and fith paras. col. 2, page 1885; illustrated in Figure 1 page 1885]).
Regarding Claim 16, modified Mahari teaches the electrochemical system of claim 15, and teaches wherein said interaction between said biomarker and said substance results in a pH change (as outlined in the claim 13 reaction above, water is contained in the electrolyte and used in the hydrolysis of BAEE [fourth and fifth paras. col. 2, page 1885; illustrated in Figure 1 page 1885]) and wherein said electroactive agent undergoes a pH-dependent electrochemically detectable reaction (as outlined in the claim 13 reaction above, water is used in the hydrolysis of BAEE [fourth and fith paras. col. 2, page 1885; illustrated in Figure 1 page 1885].
Conclusion
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/R.L.G./Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795