DETAILED CORRESPONDENCE
Summary
This is the initial Office Action based on the Inal, et al. application filed with the Office on 20 May 2024.
Claims 56-75 are currently pending, and claims 56-61 and 65-75 have been fully considered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claim(s) 56-61 and 65-75, drawn to a biosensor.
Group II, claim(s) 62-64, drawn to a method of integrating a biorecognition layer on an electrode.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I & II lack unity of invention because the groups do not share the same or corresponding technical feature.
An interview with Yvonne Shyntum on 9 July 2026, resulted in a provisional election being made without traverse to prosecute the invention of Group I, claims 56-61 and 65-75. Affirmation of this election must be made by applicant in replying to this Office action. Claims 62-64 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Priority
The instant application is a US National Stage of an International Patent Application, PCT/IB2022/061164, filed on 18 November 2022. The International Patent Application claims the benefit of and priority to U.S. Provisional Application No. 63/280,887 filed November 18, 2021, U.S. Provisional Application No. 63/283,447 filed November 27, 2021, and U.S. Provisional Application No. 63/318,188 filed March 9, 2022. Thus, the earliest effective filing date of the present application is 18 November 2021.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted regarding the present application filed on 7 August 2024, 27 August 2024, 15 April 2025, 8 January 2026, and 23 February 2026, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the Examiner.
Specification
The following title is suggested:
DIRECTLY FUNCTIONALIZED ELECTROCHMICAL TRANSISTORS, AND CONVECTION DRIVEN ULTRA-RAPID DETECTION OF BIOMARKERS USING TRANSISTORS.
(the first instance of the word “transistor” is currently misspelled in the Application Data Sheet filed on 20 May 2024).
Claim Objections
Claim 56 is objected to because of the following informalities: a portion of the claim reads as follows: “… or the general formula or …” at the bridging of page number 2 and 3, as filed. Appropriate correction is required.
Claim 72 is objected to because of the following informalities: the claim ends in two periods (“. .”), rather than just one. Claims 73-75 are objected also as dependent from claim 72.
Claim Interpretation
The term “optionally” is used throughout the instant claim set. Limitations which follow this term are not considered to be positively recited, and the prior art need not teach such limitations to read upon the claim.
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 58 and 70 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.
Regarding claim 58, 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).
Regarding claim 70, 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 Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 56, 58-61, 65-69 and 71 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by a published and available medRxiv preprint of a paper submitted by K. Guo, et al. (“A nanobody-functionalized organic electrochemical transistor for the rapid detection of SARS-CoV-2 and MERS antigens at the physical limit”, retrieved from https://dio.org/10.1101/2020.11.12.20228874, posted on 13 November 2020; hereinafter, “Guo”).
Regarding claim 56, Guo discloses a biosensor comprising an organic electrochemical transistor (OECT) and a biorecognition layer (Abstract: “… a modular nanobody-organic electrochemical transistor architecture that enables the fast and specific detection and quantification of single-molecule to nanomolar protein antigen concentrations in complex bodily fluids. The sensor combines a new solution-processable organic semiconductor material in the transistor channel with the high-density and orientation-controlled bioconjugation of nanobody fusion proteins on disposable gate electrodes.”),
wherein the OECT comprises one or more source electrodes, one or more drain electrodes, one or more channels, and a gate or common gate electrode (Figure 1a & 1b),
wherein the source and drain electrodes are electronically connected via the one or more channel (Figure 1a & 1b), and
wherein the gate or common gate electrode is removable and is located apart from the source electrode, the drain electrode, and the channel (Figure 1a & 1b)
wherein the orientation of the biorecognition layer relative to the OECT surface can be represented by the general formula
N-L1-APi :AP2-L2-B Formula I' (Figure 2b)
wherein where N is an organic molecules capable of self-assembly to form a first SAM (Figure 1 caption: “1,6-hexanedithiol”), L1 is a first linker (last ¶, p. 6: “… alkane linkers that separate the chemically synthesized SpyTag sequence from the underlying HDT …”), AP1 is a first peptide binding partner (Figure 1 caption: “SpyTag peptide”); AP2 is a second peptide partner (Figure 1 caption: “SpyCatcher”); AP1 and AP2 are binding partners, L2 is a second linker (last ¶, p. 6: “A flexible 8-amino acid glycine-serine linker separates nanobody and SpyCatcher domains dynamically and sterically.”) and B is a biorecognition element (Figure 1 caption: “nanobody”), wherein N is chemically conjugated with AP1, resulting in a chemically self-assembled monolayer (Chem- SAM) (Figure 1c: Chem-SAM), and wherein binding of AP1 and AP2 results in a biologically self-assembled monolayer (Bio-SAM) (Figure 1c: Oriented Bio-SAM).
Regarding claim 58, Guo teaches a nanobody (Figure 1 caption: “nanobody”).
Regarding claim 59, Guo teaches upon functionalization with the HDT layer, the gold electrode displayed characteristic thiol-gold (S-Au) and free thiol (-SH) peaks in its high-resolution S 2p XPS spectrum31,32, indicating the upright orientation of HDT linked to gold through only one of the two -SH moieties (with the other terminal pointing away from the surface) (first ¶, p. 7).
Regarding claim 60, Guo teaches originally engineered from a bacterial adhesion protein28, the SpyTag/SpyCatcher protein conjugation system has been used for several applications29, but has not yet been applied to FET or OECT biosensors. (first ¶, p. 6).
Regarding claim 61, Guo teaches the channel comprises PEDOT:PSS (Figure 1a).
Regarding claim 65, Guo discloses a method of detecting the absence, the presence, or the concentration of an analyte in a biological sample comprising contacting the biological sample with the biosensor of claim 56 (Abstract: “We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples.”), wherein the biosensor further comprises a reservoir (sample must inherently be contained by some means), the method comprising:
(v) incubating the gate electrode with the biological sample for a time period sufficient to allow binding between the analyte and the biorecognition element (Figure 1a1: 10 minute incubation);
(vi) rinsing the gate electrode with a rinsing buffer (Figure 1a2: Rinsed with PBS); and
(vii) measuring a signal ID (last ¶, p. 9: “We assessed the sensing signal by monitoring the drain current (ID) as a function of the VG at a fixed VD = -0.6 V.”),
wherein a difference between the signal ID and a background ID is indicative of the absence, the presence, or the concentration of the analyte in the biological sample (last ¶, p. 12: “The sensor responded to a GFP concentration as low as 4.7 aM (NR = 7%) (Fig. 3h) with a dynamic range spanning 10 orders of magnitude.”), and
wherein the biological sample is in a liquid form (Abstract: “We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples.”).
Regarding claim 66, Guo teaches incubating the gate electrode with a blank solution (Figure 4 caption: “The blank measurements were obtained by incubating the gate electrodes in PBS.”); placing the gate on top of the channel (Figure 1a3: Flipped over and placed above transistor base); applying a Vg and Vd (last ¶, p. 9: “… operated in PBS under ambient conditions by varying the gate voltage (VG) between -0.6 V and 0.6 V while the drain voltage (VD) was swept from 0 to -0.6 V.”); measuring background (calculation of LOD, top of p. 27).
Regarding claim 67, Guo teaches “We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples.” (Abstract).
Regarding claim 68, Guo teaches “We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples.” (Abstract). Guo further teaches the method was modified for saliva measurements to include cOmplete protease inhibitor cocktail with EDTA (Sigma) at 4 times the manufacturer recommended concentration (giving a two-fold concentration in the final 1:1 mixture with saliva (first ¶, p. 25). Guo teaches a 5 µL measurement volume (last ¶, p. 14). Finally, Guo also teaches the nanobody-OECT platform detects specific protein molecules from unprocessed samples in ambient conditions after only 10 minutes of incubation with the disposable biofunctionalized gate electrode (last ¶, p. 18).
Regarding claim 69, Guo teaches electrochemical impedance spectra were recorded at a DC voltage of 0 V versus open circuit potential (Voc) and an AC modulation of 10 mV over a frequency range of 0.1-100000 Hz. (first ¶, p. 23).
Regarding claim 71, Guo teaches the nanobody-OECT platform detects specific protein molecules from unprocessed samples in ambient conditions after only 10 minutes of incubation with the disposable biofunctionalized gate electrode (last ¶, p. 18).
Allowable Subject Matter
Claim 57 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the cited Guo reference is the closest prior art to the instant claims. However, Guo does not anticipate or render obvious the L1 linker comprises an N or C terminal cysteine residue.
Interview with the Examiner
If at any point during the prosecution it is believe an interview with the Examiner would further the prosecution of an application, please consider this option.
The Automated Interview Request form (AIR) is available to request an interview to be scheduled with the Examiner. First, an authorization for internet communications regarding the case should be filed prior or with an AIR online request.
The internet communication authorization form (SB/0439), which authorizes or withdraws authorization for internet-based communication (e.g., video conferencing, email, etc.) for the application must be signed by the applicant or the attorney/agent for applicant. The form can be found at:
https://www.uspto.gov/sites/default/files/documents/sb0439.pdf
The AIR form can be filled out online, and is automatically forwarded to the Examiner, who will call to confirm a requested time and date, or set up a mutually convenient time for the interview. The form can be found at:
https://www.uspto.gov/patent/uspto-automated-interview-request-air-form.html
The Examiner encourages, but does not require, interviews by the USPTO Microsoft Teams video conferencing. This system allows for file-sharing along audio conferencing. Microsoft Teams can be used as an internet browser add-on in Microsoft IE, Google Chrome, or Mozilla Foxfire, or as a temporary Java-based application on these browsers. Steps for joining an Examiner setup Microsoft Teams can be found at the USPTO website:
https://www.uspto.gov/patents/laws/interview-practice#step3
Additionally, a blank email to the Examiner at the time of a telephonic interview can be used for a reply to easily allow for Microsoft Teams communication. Please note, policy guidelines regarding Internet communications are detailed at MPEP §500-502.3, and office policy regarding interviews are detailed at MPEP §713.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN C BALL whose telephone number is (571)270-5119. The examiner can normally be reached M - F, 9 am - 5:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan Van can be reached at (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 published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J. Christopher Ball/ Primary Examiner, Art Unit 1795
Prosecution Insights