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 7/31/23, 10/19/23, 1/2/24, 8/27/24, 4/15/25, and 1/30/26 is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of 1-6, 8, and 11-14 in the reply filed on 1/16/26 is acknowledged.
Claims 15, 16, 19, 21, 22, 23, 24, 25, and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (a method of integrating a biorecognition layer on an electrode and a method of detecting), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/16/26.
Claim Status
Claims 1-6, 8, and 11-14 are pending and examined. Claims 15, 16, 19, 21, 22, 23, 24, 25, and 27 are withdrawn and are not examined.
Claim Objections
Claim 4 is objected to because of the following informalities: “chem-SAM” should be “Chem-SAM”. Note the capitalization for consistency because the term is used again in claim 4. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: “MoonCatcher.” should be “MoonCatcher,”. Note the punctuation. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: “SAR-CoV-2” should be “SARS-CoV-2”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “dithols” should be “dithiols”. 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 3 and 5 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.
Claims 3 and 5 recite the limitation "the biorecognition element". There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites “a biorecognition layer”. Did the applicant intend to state “biorecognition layer” in claims 3 and 5? Please clarify.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 5, 6, 13, and 14 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wustoni (US Pub 2022/0283116).
The applied reference has a common applicant and joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding Claim 1, Wustoni teaches a biosensor comprising an organic electrochemical transistor (OECT) ([0009] The devices include a bio-functional, nanostructured, isoporous membrane (BNIM)-integrated organic electrochemical transistor (OECT), herein BNIM-OECT, for the rapid and sensitive detection of the presence of an analyte of interest, in a sample),
and optionally an array of two or more OECTs (the examiner notes that the terms following “optionally” are not required structures), and
a biorecognition layer [0009] This concept can be used for sensing any analyte/biomarker in a sample, as long as the membrane has the right biorecognition units that recognize the analyte/biomarker. Accordingly, the isoporous membrane is preferably functionalized to include a binding partner for the analyte being detected.),
wherein the OECT or each of the OECTs in the array comprises a source electrode, a drain electrode, a channel, and a gate electrode ([0009] The OECT include a source electrode, a drain electrode, a channel, and a gate electrode.).
Regarding Claim 2, Wustoni teaches the biosensor of claim 1, wherein the biorecognition layer is integrated on the gate electrode of the OECT ([0084] Gate electrodes 202c and 202d are functionalized with antibody Aβ-42 (see, for example FIG. 9D). Gate electrodes 202e and 202f are functionalized with antibody Aβ-40 (see, for example FIG. 9E).
Regarding Claim 5, Wustoni teaches the biosensor of any one of claim 1, wherein the biorecognition element is an antibody, or a two-domain or a single-domain antibody fragment, such as a nanobody ([0084] Gate electrodes 202c and 202d are functionalized with antibody Aβ-42 (see, for example FIG. 9D). Gate electrodes 202e and 202f are functionalized with antibody Aβ-40 (see, for example FIG. 9E).
Regarding Claim 6, Wustoni teaches the biosensor of claim 5, wherein the nanobody recognizes SAR-CoV-2 receptor binding domain (the nanobody is capable of recognizing the SARS-CoV-2 receptor binding domain. The examiner notes that in claim 5 above the term “nanobody” was stated after the claim language “or”. Therefore, the nanobody is not required.)
Regarding Claim 13, Wustoni teaches the biosensor of claim 1, wherein the channel is formed from a conducting polymer selected from the group consisting of PEDOT:PSS, PEDOT-S, PEDOT:TOS, PEDOTOH:C104, PEDOT-co-PEDOTOH:C104, P3HT, PTHS, BBL, p(g2T-TT), PTHS-TMA+-co-P3HT, p(gNDI-g2T), p(gOT2-g6T2), and P-90 ([0106] Exemplary transfer curves of OECSs containing PEDOT:PSS channels, OECTs containing p(g0T2-g6T2) channels, and OECTs containing P-90 channels for the detection of Aβ aggregates are shown in FIG. 4B, FIG. 11A, and FIG. 11B, respectively. Exemplary transfer curves of OECT containing a PEDOT:PSS channel integrated with microfluidics for the detection of Aβ aggregates are shown in FIG. 10.).
Regarding Claim 14, Wustoni teaches the biosensor of claim 1, wherein the OECT or each of the OECTs in the array ([0080] In some embodiments, a plurality of independently addressable source and drain electrodes and corresponding channels are patterned on the supporting substrate to form an array. An exemplary configuration for the array (100) is shown in FIGS. 8A-8B.).
Claim Rejections - 35 USC § 103
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.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Wustoni (US Pub 2022/0283116), in view of Howarth (WO 2016/193746).
Regarding Claims 3 and 4, Wustoni teaches the biosensor of claims 1 and 3.
Wustoni is silent to the orientation of the biorecognition element relative to the OECT surface can be represented by the general formula: N-L1-AP1-AP2-L2-B- Formula I where N is one or more organic molecules which self-assembly to form a fist SAM, L1 is an optional first linker, AP1 is a first peptide binding partner; AP2 is a second peptide partner; AP1 and AP2 are binding partners, L2 is a second linker and B is the biorecognition element, binding of AP1 and AP2 results in a biologically self-assembled monolayer (Bio-Sam, (a) the biorecognition layer comprises chem-SAM, wherein Chem-SAM comprises the first SAM formed by N, chemically modified with AP1; (b) the organic molecules in the first SAM comprise thiols; (c) wherein the Bio-Sam comprises AP1-AP2-L-B, and wherein the Bio-Sam is formed by interaction of AP1 with AP2; and/or (c) the AP1-AP2 are selected from the group consisting of SpyTag/Spy Catcherpeptide conjugate, snoopCatcher/snoopTag, MoonTag / MoonCatcher. SnoopTagJr/ SnoopCatcher or DogTag and SdyTag/SdyCatcher peptide conjugate.
Howarth teaches in the related art of assembly of linked proteins. Potential reactive functionalities include nucleophilic functional groups (amines, alcohols, thiols, hydrazides). Figure 1 shows two pairs of peptide linkers, termed SpyTag/SpyCatcher and SnoopTag/Snoop Catcher, wherein each pair, i.e. each "Tag" and "Catcher", react specifically and spontaneously to form an isopeptide bond thereby linking the "Tag" peptide to the "Catcher" peptide. In this respect, the pairs are orthogonal, meaning that they are mutually unreactive, i.e. SpyTag and SpyCatcher cannot react with either of SnoopCatcher or SnoopTag to form an isopeptide bond. As discussed below in more detail, in some embodiments, the "Tags" may be viewed as peptide tags and "Catcher" peptides may be viewed as binding partner proteins. The examiner notes that claim language following “or” and “and/or” is optional and are not required structures.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the biorecognition element in the device of modified Wustoni, with the general formula: N-L1-AP1-AP2-L2-B- Formula I where N is one or more organic molecules which self-assembly to form a fist SAM, L1 is an optional first linker, AP1 is a first peptide binding partner; AP2 is a second peptide partner; AP1 and AP2 are binding partners, L2 is a second linker and B is the biorecognition element, binding of AP1 and AP2 results in a biologically self-assembled monolayer (Bio-Sam, (a) the biorecognition layer comprises chem-SAM, wherein Chem-SAM comprises the first SAM formed by N, chemically modified with AP1; (b) the organic molecules in the first SAM comprise thiols; (c) wherein the Bio-Sam comprises AP1-AP2-L-B, and wherein the Bio-Sam is formed by interaction of AP1 with AP2; and/or (c) the AP1-AP2 are selected from the group consisting of SpyTag/Spy Catcherpeptide conjugate, snoopCatcher/snoopTag, MoonTag / MoonCatcher. SnoopTagJr/ SnoopCatcher or DogTag and SdyTag/SdyCatcher peptide conjugate, as taught by Howarth, to modify one or more residues in the peptide linker and/or protein to facilitate the conjugation of these molecules and/or to improve the stability of the peptide linker and/or protein, as taught by Howarth.
Claims 8, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Wustoni (US Pub 2022/0283116), in view of Howarth (WO 2016/193746), and further in view of Lakshmana (US Pub 2019/0271693).
Regarding Claims 8, 11, and 12, modified Wustoni teaches the biosensor of claim 4.
Modified Wustoni is silent to the thiols comprise dithols, preferably 1,6- hexanedithiols, comprising a blocking agent, and the blocking agent is bovine serum albumin (BSA).
Lakshmana teaches in the related art of detecting. [0203] Thiolated capture probe is prepared at a concentration of 0.05 μM in 300 μM 1,6-hexanedithiol (HDT), 10 mM Tris-HCl, pH 8.0, 0.3 M NaCl, 1 mM EDTA and is incubated in the dark at room temperature for 10 min. Incubation of the thiolated capture probe with HDT ensures that the thiol group on the capture probe is reduced, resulting in more consistent results. [0207] The bacterial lysate is neutralized by adding 50 μl of 1 M Phosphate Buffer, pH 7.2, containing 2.5% bovine serum albumin (BSA) and 0.25 mM of a fluorescein-modified detector probe. The neutralized lysate is incubated for 10 min at room temperature.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted 1,6-hexanedithiol (HDT), as taught by Lakshmana, with thiols, as taught by modified Wustoni, to ensure that the thiol group on the capture probe is reduced, resulting in more consistent results, as taught by Lakshmana, in [0203]. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used BSA as a blocking agent, as taught by Lakshmana, in the device of modified Wustoni, to allow for neutralizing in a physiological buffer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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, Charles Capozzi can be reached at 571-270-3638. 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.
/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798