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 .
Claim Status
Claims 1, 2, 6, 7, 8, 9, 10, 11, and 12, are pending and are examined. Claims 13-17 are withdrawn and are not examined.
Affidavit
The affidavit filed 5/19/26 was reviewed. Applicant argues on page 11 the advantageous performance of the sensors. Regarding the thickness on pages 4 and 6, the average including the standard deviation (error bars) between each of the samples (treatments) does not appear to be significant. Applicant argues “The increased film thickness was accompanied by increased surface hydrophilicity, further supporting the presence of multiple attachment points per polymer chain and a dense interfacial nanoarchitecture.” The applicant may show how the thicknesses are statistically significant for supporting multiple attachment points.
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 1, 2, 4, 6, 8, 9, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith (“Digital Biosensing by Foundry-Fabricated Graphene Sensors.” Scientific Reports. 2019.”; previously cited), in view of Piccinini (“Enzyme-polyelectrolyte multilayer assemblies on reduced graphene oxide field-effect transistors for biosensing applications.” 92. 661-667. 2017; previously cited).
Regarding Claim 1, Goldsmith teaches a sensor comprising:
a field-effect transistor (These sensors can be described as a biologically specialized Ion Sensitive Field Effect Transistor (ISFET). See introduction.)
comprising semiconducting two-dimensional nanosheets, a gate electrode, a drain electrode, a source electrode and an interfacial nanoarchitecture ((See Fig. 1, Pt, SiN, SiO2 for the substrate, graphene, epoxy above the SiN, source and drain electrodes.),
the interfacial nanoarchitecture comprising:
a recognition element (anti-IL6, see methods),
a structural element (protein, IL-6), and
wherein the gate electrode of the transistor is coplanar with the drain electrode and the source electrode of the transistor (See Fig. 1, Pt, SiN, SiO2 for the substrate, graphene, epoxy above the SiN, source and drain electrodes. (a) Diagram of the sensor architecture. Circular sections on top of the graphene represents proteins embedded in a blocking layer, represented by curved lines. (b) A microscopy image showing an entire sensor surface. Red scalebar is 1 mm. There are fifteen graphene strips grouped into three groups of five, exposed through the silicon nitride protective layer.).
Goldsmith further teaches a polymeric antifouling coating (In the Background Theory section, the immobilized layer of proteins, peptides, surfactants, polyethylene glycol (PEG), or other soft molecules separate the graphene channel and double-layer from the bulk solution. In the Methods section, A blocking layer such as PEG is necessary to control non-specific surface chemistry. PEG would be a polymer antifouling coating).
wherein the structural element is attached to a semiconducting two-dimensional nanosheet surface of the transistor by a plurality of non-covalent bonds mediated by one or more of the following forces: hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, π-π interactions and electrostatic interactions (see method section for attachment of the structural element to the graphene. A blocking layer and embedded biomolecules such as proteins are immobilized onto 15 graphene sensors on the surface. See 2nd paragraph on page 2. Further, proteins bind to graphrene through pi-pi stacking, hydrophobic bonding, and electrostatic forces. The examiner also notes that “mediated by” does not affect the structural element. “Process-of-making” limitations generally do not receive patentable weight in product claims unless it is recognized to affect the structure.).
Goldsmith is silent to the source and drain electrodes of the transistor are interdigitated electrodes.
Piccinni teaches in the related art of biosensors. Interdigitated gold microelectrodes (ED-IDA1-Au). See 2. Materials and Methods.
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 interdigitated electrodes, as taught by Piccinni, for the source and drain electrodes in the device of Goldsmith, to allow for enhanced sensitivity and detection limits.
Goldsmith is silent to the recognition element is immobilized by the structural element at a distance of up to 100 nm from a semiconducting nanosheet surface of the transistor.
A particular parameter can be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, and the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation (see MPEP 2144.05.II.B.). There is no evidence indicating that the distance of the recognition element from the semiconducting nanosheet surface of the transistor is critical. Where 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).
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 positioned the recognition element to be immobilized by the structural elements at a distance of up to 100 nm from a semiconducting nanosheet surface of the transistor in the device of Goldsmith to allow for rapid detection of a signal.
Regarding Claim 2, Goldsmith teaches the sensor of claim 1, wherein the semiconducting two-dimensional nanosheets are made of a substance selected from graphene, reduced graphene oxide, few-layer graphene, twisted bilayer graphene, conducting polymers, transition metal dichalcogenides, black phosphorous, and hexagonal boron nitride (Fig. 1. (b) A microscopy image showing an entire sensor surface. Red scalebar is 1 mm. There are fifteen graphene strips grouped into three groups of five, exposed through the silicon nitride protective layer.).
Regarding Claim 4, Goldsmith teaches the sensor of claim 1, wherein the structural element is attached to a semiconducting nanosheet surface of the transistor by one or more supramolecular binding-points ((c) Diagram of the sensor regions near the graphene. See Fig. 1. The orange is in contact with the graphene layer).
Regarding Claim 6, Goldsmith teaches the sensor of claim 1, wherein the electrodes are made of a conductive material selected from gold, platinum, graphite, silver, conducting polymers and combinations thereof (Fig. 1. The platinum counter and reference electrodes built into the sensor surface control and monitor a voltage in the bulk liquid. See Introduction).
Regarding Claim 8, Goldsmith teaches the sensor of claim 1, wherein the recognition element is a substance selected from an enzyme, an antibody, an aptamer, clustered regularly interspaced short palindromic repeats (CRISPR) with a CRISPR associated protein (Cas), an ion-selective molecule, a high-affinity binding-protein, and combinations thereof (In this case, the immobilized layer of proteins, peptides, surfactants, polyethylene glycol (PEG), or other soft molecules separate the graphene channel and double-layer from the bulk solution.).
Regarding Claim 9, Goldsmith teaches the sensor of claim 8, wherein the substance is selected from urease, acetylcholinesterase, creatinine deiminase, streptavidin, avidin, valinomycin, tridodecylamine, an antibody or aptamer capable of binding an analyte selected from the group consisting of ferritin, Interleukin 6 (IL-6), SARS-CoV-2 spike protein, SARS- CoV-2 nucleocapsid (N) protein, follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), estradiol, Luteinizing hormone (LH), fragments thereof, and modified fragments thereof (To demonstrate measurement of a biological interaction, a monoclonal antibody against human interleukin-6 (anti-IL6) and recombinant human IL-6 (IL6) were used from a commercial ELISA kit. See Protein Measurements section).
Regarding Claim 12, Goldsmith teaches the sensor of claim 1, wherein the polymeric coating comprises a substance selected from polyethylene-glycol (PEG), a polyethylene-glycol derivatized polymer, a substance comprising polyethylene-glycol, a zwitterionic polymer, a fluoropolymer, a hydrogel and combinations thereof (In this case, the immobilized layer of proteins, peptides, surfactants, polyethylene glycol (PEG), or other soft molecules separate the graphene channel and double-layer from the bulk solution. See last paragraph of Background Theory section).
Claims 7, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith (“Digital Biosensing by Foundry-Fabricated Graphene Sensors.” Scientific Reports. 2019.”; previously cited), in view of Piccinini (“Enzyme-polyelectrolyte multilayer assemblies on reduced graphene oxide field-effect transistors for biosensing applications.” 92. 661-667. 2017.; previously cited), and further in view of Pourmand (US Pub 2012/0222958; previously cited).
Regarding Claim 7, Goldsmith teaches the sensor of claim 1 and the gate electrode is made of a conductive material selected from gold, platinum, graphite, silver, conducting polymers and combinations thereof (see platinum electrodes as listed in claim 1 above).
Goldsmith is silent to a coating of Ag/AgCl.
Pourmand teaches [0154] For measuring ionic current through a nanopipette, a two electrode setup was used. The nanopipette was backfilled with buffer solution and an Ag/AgCl electrode inserted.
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 added a coating of Ag/AgCl, as taught by Pourmand, to the gate electrode in the device of Goldsmith to allow for higher stability and less electrical noise when detecting a weaker (less detectable) signal.
Regarding Claim 10, Goldsmith teaches the sensor of anyone of claim 1.
Goldsmith is silent to the structural element comprises a substance selected from a polyelectrolyte, a polymer, a cross-linker, a heterofunctional nanoscaffold and combinations thereof.
Pourmand teaches in the related art of sensors. FIG. 1, where the bore is elongated and tapers to the opening); and a coating on an interior surface of the nanopore, comprising a polyelectrolyte bound directly to (i.e. contacting) said interior surface (typically quartz); and a binding molecule, linked to said polyelectrolyte, specific for binding an analyte selected from the group consisting of an ion or a small molecule.
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 selected a polyelectrolyte, as taught by Pourmand, for the substance of the structural element in the device of Goldsmith, to allow for specific for binding an analyte selected from the group consisting of an ion or a small molecule, as taught by Pourmand, in [0033].
Regarding Claim 11, Goldsmith teaches the sensor of claim 10.
Goldsmith is silent to the heterofunctional nanoscaffold comprises a substance selected from vinylsulfonated-polyamine (VS-PA), streptavidin, avidin and combinations thereof.
Pourmand teaches [0021] Electrostatic, biotin-streptavidin, and antibody-antigen interactions on the nanopipette tip surface were shown to affect ionic current flowing through a 50-nm pore.
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 added streptavidin, as taught by Pourmand, to the nanoscaffold in the device of Goldsmith, to allow for high affinity to biotin for increasing signal when detecting a biological molecule.
Response to Arguments
Applicant's arguments filed 5/19/26 have been fully considered but they are not persuasive.
Applicant argues on page 7 that the structural element is attached through plurality of binding points. This is distinct from the prior art. Further, on page 8, applicant argues the prior art fails to disclose an interfacial nanoarchitecture attached via the specific "plurality of non-covalent bonds" as claimed, which results in the distinct structural characteristics described above,
In response, the examiner notes that the specifics of the attachment (such as the binding points) are not specified in the claim beyond non-covalent bonds. Proteins (IL-6) attach to graphene primarily through non-covalent adsorption, driven by π-π stacking, hydrophobic interactions, and electrostatic forces. Noncovalent attachment (i.e. pyrene, See methods, 4th paragraph, page 8) see would use pi-pi stacking to attach flat onto the graphene sheet while the other side attaches to the antibody. Van der Waals forces and hydrophobic interaction also allow the physical adsorption of the protein. Therefore, the rejection is maintained.
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 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.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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