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 .
Status of the Claims
Claims 1-3, 5-11, 13, and 21-22 are pending. Claims 1 and 9 are amended. Claims 1-3, 5-11, 13, and 21-22 are examined herein.
Priority
The present application, filed 02/26/2026 is an RCE of U.S. Patent Application 17/730,337 filed, 04/27/2022, which claims benefit of U.S. Provisional Patent Application 63/180,327, filed 04/27/2021. The benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 04/27/2021.
Maintained Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-8 and 22 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In particular, claims 5-8 and 22 recite limitations directed solely to the identity or type of the target protein to be detected, such as an antibody, viral protein, heart fatty acid binding (H-FABP), specific viral sources, viral variants, or antibody isotypes (IgG or IgM). These limitations do not impose any additional structural limitation on the biosensor itself, but instead merely define the nature of an analyte external to the claimed device. Since the recited target proteins are not structural components of the biosensor, the limitations of claims 5-8 and 22 do not further limit the claimed biosensor as required for dependent claim form. Accordingly. Claims 5-8 and 22 are rejected under 35 U.S.C. 112(d) as being of improper dependent form.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Maintained 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 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Jafari et al (An azithromycin electrochemical sensor based on an aniline MIP film electropolymerized on a gold nano urchins/graphene oxide modified glassy carbon electrode. Journal of Electroanalytical Chemistry, 829:27-34. 2018) in view of Radi et al (Molecularly Imprinted Poly-o-phenylenediamine Electrochemical Sensor for Entacapone. Electroanalysis. March 22, 2021, 33, 1578 – 1584.)
Regarding claim 1, Jafari teaches an electrochemical sensor based on an aniline MIP film electropolymerized on a gold nano urchins comprising the use of electropolymerized aniline to create molecularly imprinted polymers (MIP), polymerized on gold nano urchins (GNU) (nano islands with a gold core of nanorough protrusions) which transfers electric charge based on binding of the target protein, in the abstract. Jafari teaches that MIP-based electrochemical sensors may be of use in the quality control of pharmaceutical industries and/or detection of food fraud. Polyaniline (PANI) is a conductive polymer with suitable electrochemical properties which can be easily synthesized and functionalized. The PANI-based MIPs have been reported electrochemical detection methods previously in combination with other materials/nanostructures on pg. 28, left column, 1st paragraph. This meets limitations in claim 1 that nano/micro islands (NMI) core of gold spatially oriented with nanorough protrusions. Further, on pg. 28 left column, 6th paragraph, GNU (nano islands with a core of gold and nanorough protrusions) are deposited on the conductive glass, and in the 7th paragraph a layer (or film) of electropolymerized, molecularly imprinted polymers are deposited onto gold nano urchins. This meets the limitations in claim 1 that MIP are electropolymerized onto the NMI. The target, which created a built-in recognition site, was extracted from the polymer matrix to create molecular imprints at the surface, meant to recognize and bind the designated target. This meets the limitations in claim 1 of the conductive monomer of the MIP comprising a built-in recognition site of the target. On pg. 30, right column, third paragraph, it is taught that the charge transfer resistance (Rct) changes based on whether or not the target is bound to the MIP, meeting the limitations of claim 1 that there is a change in Rct of the MIP upon binding of the target. Jafari discloses MIP made a conductive polymer, polyaniline. See page 28, left column, 1st paragraph.
Jafari differs from the instant invention in failing to teach MIP consisting of a monomer that is o-phenylenediamine (o-PD).
Radi discloses MIP electrochemical sensor for entacapone based on an electropolymerized polyphenylenediamine (Po-PD) on a glassy carbon electrode surface. Radi discloses direct electropolymerisation of the o-phenylenediamine monomer (o-PD) was carried out with ETC as a template. See Abstract. Radi discloses their sensor is simple electrochemical approach to produce an MIP film of poly (o-PD) on a GCE surface by oxidative electropolymerization of o-PD in the presence of ETC as a template, and has been used as a recognition element for the determination of ETC. The process has a number of advantages, such that the MIP film could be directly manufactured on the sensing surface with an easy and precise controllable manner. The MIP sensor exhibits enhanced sensitivity, good repeatability, hard stability, fast response and could be regenerated. The MIP sensor showed good recognition capability and high selectivity for the target molecule in the coexistence of biologically relevant compounds. These advantages of the sensor make it a good candidate to detect ETC in real samples.
Therefore, it would have been obvious to one of ordinary skill in the art at the time the application was filed to substitute the polyaniline taught by Jafari with the o-PD taught by Radi because o-PD is well known in the art and is commercially available as a conductive polymer for use in biosensor. A skilled artisan would have been motivated to make the substitution as suggested because Radi teaches MIP made with o-PD has a number of advantages such that the MIP film could be directly manufactured on the sensing surface with an easy and precise controllable manner. The MIP sensor exhibits enhanced sensitivity, good repeatability, hard stability, fast response and could be regenerated. The MIP sensor showed good recognition capability and high selectivity for the target molecule in the coexistence of biologically relevant compounds. These advantages of the sensor make it a good candidate to detect ETC in real samples.
Regarding claim 21, Radi discloses MIPs prepared by bulk polymerization have low integration between the recognition element and the transducer which limit binding kinetics. The electropolymerisation easily creates direct contact between the polymer and the sensor surface and allows fast and controlled deposition of polymer films with adjustable thickness and tight adhesion with the conductive electrodes. See page 1578, right column. Radi further teaches optimizing the sensor by controlling the thickness of the polymer film by the number of cycles in the electropolymerization process. The maximum sensitivity of MIP-GCE has been reached after 10 cycles of polymerisation of the MIP film. Page 1582, left column, section 3.5.
While Radi discloses optimizing the sensitivity of the sensor by controlling the thickness of the polymer film, Radi does not teach a MIP layer having a thickness from 5-10 nm. However, it would have been prima facie obvious to one having ordinary skill in the art at the time the application was filed to have modified the sensor of Jafari by substituting the polyaniline with the o-PD taught by Radi and to optimize the sensitivity of the sensor by varying the thickness of the polymer layer as a matter of routine optimization of experimental conditions, namely trying different thickness by varying the number of cycles in the electropolymerization process as taught by Radi in order to uncover the optimum workable thickness necessary to achieve sensitivity. Specifically, the thickness of the polymer layer is considered to be a result effective variable, i.e. a variable that achieves a recognized result, in the present case, the result is an appropriate thickness of the MIP layer to achieve assay sensitivity as disclosed by Radi. Radi specifically teaches optimizing the sensor by controlling the thickness of the polymer film by the number of cycles in the electropolymerization process. The maximum sensitivity of MIP-GCE has been reached after 10 cycles of polymerisation of the MIP film. Page 1582, left column, section 3.5.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Jafari in view of Radi et al as applied to claim 1 above, and further in view of Gholivand et al (Materials Science and Engineering, 2016) and Metrohm (Ag/AgCl Reference electrodes, 2018).
Regarding claim 2, Jafari in view of Radi are discussed as above. Radi teaches the use of electrochemical cell with a conventional three-electrode configuration. A bare or modified GCE, a platinum wire, and an Ag/AgCl/KCl was used as working, counter and reference electrode. See page 1579, section 2.1
However, Jafari and Radi fail to teach the use of an Ag/AgCl reference electrode and a platinum wire counter electrode.
Gholivand teaches the fabrication of an electrochemical sensor based on electropolymerization of nanocomposite gold nanoparticle-molecularly imprinted polymer for determination of valganciclovir (see title). Gholivand, on pg. 595, right column, 2nd paragraph teaches the use of an Ag/AgCl reference electrode and a platinum wire used as a counter electrode for an electro chemical sensor based on electro polymerization of nanocomposite gold nanoparticle electrodeposited on conductive glass in conjunction with molecularly imprinted polymers in order to create a biosensor with good reproducibility, good repeatability, and high selectivity and sensitivity (Abstract).
Metrohm teaches replacing calomel electrodes with silver based reference electrode. Silver/Silver chloride (Ag/AgCl) is the most widely used for potentiometric measure and can be applied for the same application as SCE. Metrohm discloses saturated calomel electrode (SCE) is based on the reaction between elemental mercury in mercury chloride and mercury is know to be a health hazard and harmful to the environment. See page 1. This meets the limitations of using a silver and composite for a reference electrode, platinum wire as a counter electrode, and conductive glass as a substrate for the NMI in the instant claim 2.
Therefore, it would have been obvious, to a person of ordinary skill in the art,
before the effective filing date of the claimed invention, to modify the sensor taught by Jafari as modified by Radi by substituting the reference electrode made of saturated calomel electrode with the Ag/AgCl reference electrode taught by Jafari because Metrohm teaches Ag/AgCL electrodes are superior and is better for the environment. It also would have been obvious to substitute the counter electrode made of platinum flake with a counter electrode made of platinum wire as taught by Jafari because these materials are functionally equivalent and would be expected to produce the same results to obtain a biosensor which comprises gold GNU having MIP polymerized thereon. Ag/AgCl electrodes provides the advantage of a mercury-free and more environmentally friendly material while SCE contains mercury and is more susceptible to contamination. The person of ordinary skill in the art would have been motivated to use these materials as electrodes to achieve the same reliable results as Gholivand. The person of ordinary skill in the art would have had a reasonable expectation of success using these materials as electrodes for their biosensor because of the good reproducibility, good repeatability, and high selectivity and sensitivity achieved.
Therefore, the invention, as claimed, is obvious.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Jafari in view of Radi et al, Gholivand et al, and Metrohm as applied to claims 1 and 2 above, and further in view of and Aydin et al (Trends in Analytical Chemistry, 2017).
Regarding claim 3, Jafari, Radi, Gholivand and Metrohm teach as above, but do not teach the conductive glass as a tin oxide substrate.
Aydin teaches how Indium tin oxide (ITO) is a promising material in biosensing technology. In the introduction Aydin teaches that Indium tin oxide is one of the most widely utilized transparent conductive oxide thin film and is a promising material for biosensors due to its two main properties, good electrical conductivity and optical transparency. Aydin teaches ITO is an excellent material, which has been extensively utilized in biosensor studies owing to its unique properties such as good optic transparency, wide working window, high electrical conductivity, substrate adhesion, low capacitive current, and stable electrochemical and physical features. Owing to these unique features, it can be used in electrochemical researches (pg. 310, paragraph 2). Further, Aydin teaches ITO coated glass used in biosensors in areas such as clinical diagnosis, food analysis, and environmental monitoring on pg. 310 paragraph 3. Aydin also teaches ITO is a very useful material as an electrode due to its electrical and optical properties. Materials that are utilized as electrode have an important role in the biosensor technology, because the conductivity and robustness of the electrode effect the results. ITO based electrodes have a long shelf life due to high stability of ITO coated electrodes. The most important feature of ITO electrode is its low cost. Page 314, section 4.This meets the limitations of a conductive glass substrate made of a tin oxide compound in the instant claim 3.
Therefore, it would have been obvious, to a person of ordinary skill in the art,
before the effective filing date of the claimed invention, to use the ITO coated glass substrate taught by Aydin in the sensor of Jafari as modified by Radi, Gholivand and Metrohm because of its unique properties such as good optic transparency, wide working window, high electrical conductivity, substrate adhesion, low capacitive current, and stable electrochemical and physical features. The person of ordinary skill in the art would have been motivated to use an ITO substrate because it is a very useful material as an electrode due to its electrical and optical properties and because the conductivity and robustness of the electrode effect the results. The person of ordinary skill in the art would have had a reasonable expectation of success of using ITO as a substrate for gold nano particles, GNU, or gold nano/micro islands due to demonstrated excellent physical, electrical, and optical properties.
Claims 5-8 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Jafari and Radi as applied to claim 1 above, and further in view of Gluckman (WO 2021/195626).
Regarding claims 5 and 6, Jafari and Radi teaches as above, but does not teach the target protein is a viral antibody.
Gluckman teaches the use of molecularly imprinted polymers for the rapid detection of emerging viral outbreaks. Gluckman teaches in paragraph [0074] suitable binding monomers have functionality complimentary to the virus of a target viral genus thus, providing an active binding pocket in the final MIP. Various different physicochemical interactions between the binding monomer and the virus of a target viral genus can be exploited to prepare MIPs materials according to the disclosure. Gluckman teaches in paragraph [0075] suitable surrogates include all or part of a macromolecule associated with the target virus, such as a polysaccharide group of a glycoprotein macromolecule, or analog thereof. In some embodiments, suitable surrogates include micelles with expressed viral proteins, such as assembled proteins of viral capsid. In some embodiments, the surrogate is an antibody or portion of an antibody of the target virus. Further, Jafari does teach on pg. 28, left column, first paragraph that MIP based electrochemical sensors may be of use in the quality control of pharmaceutical industries and/or detection of food fraud. PANI is a conductive polymer with suitable electrochemical properties which can be easily synthesized and functionalized. The PANI-based MIPs have been reported electrochemical detection methods previously in combination with other materials/nanostructures allowing for a generic scaffold that can be designed for a variety of targets. This meets the limitations of the instant claims 5 and 6 of the target protein being a viral antibody.
Regarding claims 7 and 8, Jafari and Radi teaches as above, but does not teach the target as a viral antibody to SARS-CoV-2.
Gluckman teaches in paragraphs [0057-0058] MIPs against emerging target viruses including novel influenza virus or a novel coronavirus [0065]. In certain embodiments, the virus is a coronavirus such as SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS); and SARS- CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19). See paragraph [0066].This meets the limitations in the instant claims 7 and 8 of the target viral antibody being for SARS-CoV-2 and other coronaviruses. This meets limitations in the instant claims 7 and 8.
Regarding claim 22, Jafari and Radi teaches as above, but does not teach the target protein is an IgG or IgM antibody.
Gluckman teaches in paragraphs [0053] and [00208] that rapid diagnostic technologies for viral detection may be expanded to include detection of antibodies to the virus, including IgM and IgG antibodies, as recognized biomarkers of infection stage and immune responses. This meets the limitation in the instant claim 22 specifying that the antibody is an IgG or IgM.
Therefore, it would have been obvious, to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to use the biosensor taught by Jafari as modified by Radi to detect a variety of targets and use molecularly imprinted polymers for the rapid detection of emerging viral outbreaks as taught by Gluckman to include viral antibodies to coronaviruses, including SARS-CoV-2 and known subclasses thereof such as IgG and IgM, because the sensor of Jafari is generic to the analytes that it may be used to detect. The person of ordinary skill in the art would have been motivated to use customizable MIPs to identify one or more species of coronavirus viral antibodies because of the need for new MIP technologies that can be used to selectively bind, isolate and/or label the targets with high efficiency, high capacity, and are regenerable if necessary [0006]. The person of ordinary skill in the art would have had a reasonable expectation of success using the biosensor with MIP electropolymerized onto GNU where the charge transfer resistance changes on binding the target for the detection of corona viruses indirectly through viral antibodies towards several species as taught by Gluckman above.
Therefore, the invention, as claimed, is obvious.
Claims 9-11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Jafari and Radi et al as applied to claim 1 above, and further in view of Talukder et al (Biomed Microdevices, 2017) and espressif.com (2020).
Regarding claim 9, Jafari and Radi teach as above, but fails to teach a microfluidic readout apparatus.
Talukder teaches A portable battery powered microfluidic impedance device with a smartphone readout. Talukder teaches on pg. 5 of 15, 2nd paragraph of fabricating a biosensor with a glass substate and gold electrodes with integrated microfluidics channel which converts the electric signal from the biosensor to an analog output and converted to digital output (pg. 7 of 15 left column, 2nd paragraph) through the use of an Arduino Uno Rev3 microcomputer board which allows for analog signals, translation to digital signals for output, and interchangeable modules which allow for different functions such as wireless or visual output which would be applied to a biosensor comparable to the biosensor taught by Jafari. This meets limitations in the instant claim 9 of a biosensor combined with a microfluidic reader.
Regarding claim 10, Jafari in view of Radi teach as above, but fails to teach a multiplex device.
As a customizable microcomputer the device taught by Talukder is capable of supporting a wide variety of tests allowing for wide panels of biomarkers including proteins, nucleic acids, and various cell types or pieces (Abstract).
Regarding claim 11, Jafari, Radi and Talukder teach as above, but fail to teach a WIFI adapter for transferring the read-out signals from the microfluidic reader to a platform.
Talukder taches a device that can be modified according to the ESP8266 datasheet which teaches the use of a WIFI adapter used for wireless communication that can be attached to the Arduino Uno Rev3 as taught by Talukder. This meets the limitations in the instant claim 11 of using a WIFI adapter to transfer data from the biosensor.
Regarding claim 12, Jafari in view of Radi teach as above, but fails to teach a BLE adapter in conjunction with their biosensor.
Talukder teaches on pg. 11 of 15 - right column, instead of USB, Bluetooth Low Energy (BLE) was used to eliminate any wires attaching the readout hardware to the mobile platform. BLE is a relatively new wireless communication standard that aims to reduce power usage, cost, bandwidth, and complexity that other technologies could not optimize. BLE is the perfect choice for a medical Internet-of-things device which allows for wireless transfer of data to both computers and smartphones and similar devices. This meets the limitations of using Bluetooth communication in the instant claim 12.
Regarding claim 13, Jafari teaches as above, but doesn’t teach the use of a computer or smartphone in conjunction with their biosensor.
Talukder teaches in Fig. 9 - a Mobile Data Interface. From left to right, the LIA output feeds into an Arduino Uno, which samples the data. The serial output of the UNO is coupled with the HM-10 BLE module, which sends the data to a phone. All of the communication is controlled with a mobile interface on the phone. This meets the limitations of using a computer of smartphone for obtaining results in the instant claim 13.
Therefore, it would have been obvious, to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to utilize the readout device, taught by Talukder, that can receive data from a biosensor, taught by Jafari as modified by Radi, allowing the microcomputer to read the analog electrical signals from the biosensor in place of the potentiostat/galvanostat used by Jafari (pg. 28, 5th paragraph) for the electrochemical measurements caused by the Rct of binding conformation changes of one or more targets of interest. For this same Arduino device to have the capability to add WIFI and Bluetooth adapters, it would have been obvious to do so to use a wireless protocol such as WIFI or Bluetooth, and to send the data to a smartphone of computer as taught by Talukder espressif.com. Talukdar teaches using these technologies, a combination of biosensor and mobile phone technologies, with no compromise to performance when compared to state-of-the-art benchtop analysis and data acquisition systems (Talukder, conclusion). The person of ordinary skill in the art would have been motivated to use a reader that can obtain data from a biosensor which is then communicated to a computer or smartphone, to expand availability, reduce power usage, cost, bandwidth and complexity. The person of ordinary skill in the art would have had a reasonable expectation of success when integrating the device of Talukder into a biosensor because of comparable performance when compared to more expensive technologies.
Therefore, the invention as claimed, is obvious.
For the reasons stated above, all claims are rejected.
Response to Arguments
Applicant’s arguments filed 06/15/2026 have been fully considered but they are not persuasive. The rejections under 35 U.S.C. §§ 112(d) and 103 are maintained for the reasons set forth below.
Claim Objections
Applicant states that the objections to claims 1 and 9 have been addressed because the claims have been amended as per the Examiner’s suggestions. Applicant’s amendments to claims 1 and 9 have been considered. The objections to claims 1 and 9 are withdrawn.
Claim Rejections — 35 U.S.C. § 112(d)
Applicant argues that claims 5-8 and 22 are proper dependent claims because § 112(d) only requires that a dependent claim reference a previous claim and specify a further limitation of the subject matter claimed. Applicant further argues that claim 5 narrows the genus of “target protein” to an antibody, viral protein, or H-FABP; claims 6-8 further narrow the target protein to viral antibody, viral source, or viral variant; and claim 22 narrows the antibody to IgG or IgM. Applicant also argues that the § 112(d) inquiry is distinct from whether a recitation is entitled to patentable weight. Applicant’s arguments are not persuasive.
Claim 1 already recites a biosensor for detecting a target protein, wherein the MIP comprises “a built-in recognition site of the target protein.” Thus, claim 1 already requires the MIP recognition site to correspond to the target protein being detected. Claims 5-8 and 22 identify categories or species of the target protein/analyte, such as an antibody, viral protein, H-FABP, viral antibody, viral source, SARS-CoV-2 variant, or IgG/IgM antibody. Claims 5-8 and 22 do not expressly recite any additional structural limitation of the biosensor, MIP layer, recognition site, binding cavity, binding chemistry, film thickness, template-removal condition, or biosensor configuration beyond the built-in recognition site already required by claim 1.
Applicant further argues that the Examiner’s premise is incorrect because the target protein is not purely external to the device. Applicant contends that, by the nature of molecular imprinting, the recognition site is a cavity structurally and chemically complementary to the template against which it is imprinted, and that specifying narrowing embodiments regarding the target protein therefore defines the geometry and binding chemistry of the imprinted cavity. Applicant’s arguments are not persuasive. The rejection does not dispute that an MIP may be formed using a template and may include a recognition site that corresponds to the template. Rather, the rejection is based on the actual scope and wording of the claims. Claim 1 already recites that the MIP has a built-in recognition site “of the target protein.” Therefore, the concept of a recognition site corresponding to the target protein is already present in claim 1. Claims 5-8 and 22 do not recite the alleged corresponding geometry, size, shape, chemical functionality, functional group arrangement, binding pocket dimensions, binding energy, or any other structural feature that Applicant now argues is implicitly associated with the recited target protein. The dependent claims name types or species of target protein.
Applicant’s explanation relies on unclaimed structural details allegedly inherent to the identity of the target protein. However, the dependent claims do not positively recite those structural details. In the absence of any recited additional structure of the biosensor or MIP recognition site, the dependent claims do not further limit the subject matter of claim 1 in the manner required by 35 U.S.C. § 112(d). Accordingly, the rejection of claims 5-8 and 22 under 35 U.S.C. § 112(d) is maintained.
Claim Rejections — 35 U.S.C. § 103
Applicant argues that claims 1 and 21 are patentable over Jafari et al. in view of Radi et al. Applicant argues that the Examiner has not established a prima facie case of obviousness because the alleged substitution of Jafari et al.’s polyaniline MIP with Radi et al.’s o-phenylenediamine (o-PD) MIP would not have been predictable. Applicant’s arguments are not persuasive. The rejection does not rely on Radi et al. for wholesale replacement of Jafari et al.’s sensing platform. Jafari et al. is relied upon as the primary reference for teaching an electrochemical molecularly imprinted polymer nanosensor having a gold nanostructured electrode architecture, specifically gold nanourchins/graphene oxide on a glassy carbon electrode, with an electropolymerized MIP film formed using a template molecule, template extraction, analyte rebinding, and electrochemical/electrochemical impedance characterization. Radi et al. is relied upon for teaching that o-phenylenediamine is a known electropolymerizable monomer for forming molecularly imprinted polymer films, that o-PD can be electropolymerized in the presence of a template, that the template can be removed to form recognition cavities, and that target rebinding produces measurable electrochemical impedance/charge-transfer-resistance changes.
Applicant argues that Jafari et al.’s device operates by electropolymerizing aniline into polyaniline, which Jafari et al. describes as a conductive polymer with suitable electrochemical properties, while Radi et al. forms its recognition layer by electropolymerizing o-PD into poly-o-phenylenediamine, which Radi et al. characterizes as an electrically insulating, compact, non-conductive film. Applicant argues that the two monomers are not interchangeable functional equivalents because one yields a conductive matrix and the other yields a non-conductive, self-limiting insulating film. Applicant’s arguments are not persuasive. Claim 1 expressly recites that the monomer is o-phenylenediamine (o-PD). Radi et al. teaches o-PD MIP chemistry for electrochemical/impedimetric sensing, which corresponds to the o-PD monomer limitation recited in claim 1. The fact that o-PD forms a compact or relatively insulating film does not teach away from the claimed invention because the claim itself requires o-PD and recites that charge transfer resistance and/or impedance magnitude change upon binding of the target protein. Radi et al. teaches that o-PD MIP films can be used in electrochemical sensing and that template removal and target rebinding alter electron transfer resistance/impedance. Thus, Applicant’s distinction between conductive PANI and insulating o-PD does not show inoperability or unpredictability; rather, it confirms that Radi et al. teaches the o-PD MIP material recited in the claim.
Applicant argues that importing Radi et al.’s process into Jafari et al. would render Jafari et al. unsatisfactory for its intended purpose and would change Jafari et al.’s principle of operation. Applicant asserts that Radi et al. requires mirror-polishing of the electrode surface before o-PD is applied, and that polishing would destroy Jafari et al.’s gold nanourchin/nanostructured surface. In response to applicant’s argument that importing Radi et al.’s polishing step into Jafari et al. would render Jafari et al. unsatisfactory for its intended purpose and change Jafari et al.’s principle of operation, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Applicant’s argument is not persuasive because it assumes bodily incorporation of Radi et al.’s entire electrode-preparation protocol into Jafari et al. The maintained rejection does not require polishing away Jafari et al.’s gold nanourchins or replacing Jafari et al.’s gold nanostructured architecture with Radi et al.’s flat polished glassy carbon electrode. Rather, Jafari et al. supplies the gold nanostructured electrochemical MIP sensor architecture, and Radi et al. supplies the known o-PD electropolymerized MIP chemistry. A person of ordinary skill in the art would have understood that Radi et al.’s mirror-polishing step is a substrate-preparation step for Radi et al.’s particular glassy carbon electrode experiment. It is not a teaching that o-PD MIP electropolymerization can only occur on a mirror-polished flat electrode and cannot be used with other electrochemical sensing architectures. Jafari et al. already teaches forming a MIP layer on a gold nanostructured electrochemical platform. Radi et al. teaches that o-PD can be used as a MIP-forming monomer and that the resulting MIP can function in electrochemical/impedimetric sensing. The proposed combination therefore preserves Jafari et al.’s nanostructured gold sensing surface while using Radi et al.’s known o-PD MIP chemistry as the recognition polymer.
Applicant further argues that Radi et al.’s polishing step is “mandatory” and that the Examiner’s position that the polishing step could be modified or omitted does not provide a reason why a person of ordinary skill would have made the combination. Applicant’s arguments are not persuasive. The reason to make the combination is not based on arbitrary omission of a “mandatory” step. The reason is based on the combined teachings of the references. Jafari et al. teaches an electrochemical MIP nanosensor using a nanostructured gold-containing electrode and template-created recognition sites. Radi et al. teaches o-PD as a known MIP monomer, electropolymerized in the presence of a template, followed by template removal and target rebinding, with impedance/charge-transfer-resistance changes used for sensing. These teachings would have suggested to a person of ordinary skill in the art that o-PD could be used as the MIP monomer/recognition layer in Jafari et al.’s electrochemical MIP sensing platform.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the motivation to combine is found in the shared teachings of Jafari et al. and Radi et al. regarding electrochemical MIP sensors, electropolymerized MIP films, template-based recognition sites, template removal, analyte rebinding, and electrochemical/impedimetric signal changes upon target binding. A person of ordinary skill in the art would have been motivated to use Radi et al.’s o-PD MIP chemistry in Jafari et al.’s MIP sensor to provide another known MIP-forming monomer capable of forming template-defined recognition sites and producing measurable impedance/charge-transfer-resistance changes upon target binding.
Applicant argues that there is no evidence that Radi et al.’s o-PD electropolymerization performs as taught on an unpolished, three-dimensional gold-nanourchin substrate. Applicant’s arguments are not persuasive. The rejection is not based on a requirement that Radi et al. expressly disclose o-PD electropolymerization on Jafari et al.’s exact gold nanourchin/graphene oxide substrate. Jafari et al. already teaches electropolymerization of a MIP layer on its gold nanourchin/graphene oxide modified electrode. Radi et al. teaches o-PD as a known MIP-forming monomer and teaches template removal/rebinding with impedimetric characterization. The combined teachings support the substitution/use of Radi et al.’s o-PD MIP chemistry in the MIP layer of Jafari et al.’s electrochemical nanosensor.
Applicant argues that the rejection is based on hindsight because the Examiner selected o-PD from Radi et al. while simultaneously discarding Radi et al.’s polishing step. In response to applicant’s argument that the examiner’s conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Here, the rejection is based on teachings found in the references themselves, not on Applicant’s disclosure. Jafari et al. teaches the electrochemical MIP nanostructured sensor architecture. Radi et al. expressly teaches o-PD electropolymerized MIP chemistry, template removal, target rebinding, and impedance/charge-transfer-resistance changes. The selection of o-PD is therefore not hindsight; it is expressly supported by Radi et al. The rejection does not rely on Applicant’s disclosure as a template, nor does it require discarding a teaching that is essential to Radi et al.’s o-PD MIP chemistry. It merely applies Radi et al.’s o-PD MIP chemistry to the MIP layer of Jafari et al.’s known electrochemical MIP sensing platform.
Applicant argues that the Examiner improperly dismissed Applicant’s evidence that o-PD provides higher functional-group density, ultrathin film formation, and superior suitability for protein-scale imprinting. Applicant argues that this evidence is relevant to motivation and reasonable expectation of success, not merely secondary considerations. Applicant’s arguments are not persuasive. In response to applicant’s argument that o-PD provides higher functional-group density, ultrathin film formation, and superior suitability for protein-scale imprinting, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Radi et al. already teaches o-PD MIP chemistry for electrochemical sensing. To the extent o-PD provides higher functional-group density, ultrathin film formation, or suitability for protein-scale imprinting, those properties would have flowed naturally from using o-PD as taught by Radi et al. Applicant has not provided persuasive comparative evidence showing unexpected results commensurate in scope with the claims. Moreover, Applicant’s assertion that o-PD is superior for protein-scale imprinting does not negate the obviousness of using Radi et al.’s known o-PD MIP chemistry, especially where the claim expressly recites o-PD.
Applicant argues that claims 2 and 3 should be reconsidered and that withdrawal is requested because claim 1, on which claims 2 and 3 depend, is allegedly patentable over Jafari et al. in view of Radi et al. Applicant’s arguments are not persuasive. Applicant has not separately argued the additional limitations of claims 2 and 3 or identified any specific deficiency in the additional references relied upon for claims 2 and 3. Applicant’s arguments for claims 2 and 3 merely rely on the alleged patentability of claim 1. For the reasons discussed above, the rejection of claim 1 is maintained. Accordingly, the rejections of claims 2 and 3 under 35 U.S.C. § 103 are maintained.
Applicant argues that claims 5-8 and 22 should be reconsidered and that withdrawal is requested because claim 1, on which claims 5-8 and 22 depend, is allegedly patentable over Jafari et al. in view of Radi et al. Applicant’s arguments are not persuasive. Applicant has not separately argued the additional limitations of claims 5-8 and 22 or identified any specific deficiency in Gluckman as relied upon in the non-final rejection. Applicant’s arguments for claims 5-8 and 22 merely rely on the alleged patentability of claim 1. For the reasons discussed above, the rejection of claim 1 is maintained. Gluckman is relied upon for the target-protein, viral-protein, viral-source, viral-variant, and antibody limitations recited in claims 5-8 and 22. Accordingly, the rejection of claims 5-8 and 22 under 35 U.S.C. § 103 is maintained.
Applicant argues that claims 9-11 and 13 should be reconsidered and that withdrawal is requested because claim 1, on which claims 9-11 and 13 depend, is allegedly patentable over Jafari et al. in view of Radi et al. Applicant’s arguments are not persuasive. Applicant has not separately argued the additional limitations of claims 9-11 and 13 or identified any specific deficiency in Talukder as relied upon in the non-final rejection. Applicant’s arguments for claims 9-11 and 13 merely rely on the alleged patentability of claim 1. For the reasons discussed above, the rejection of claim 1 is maintained. Talukder is relied upon for the microfluidic read-out apparatus, microfluidic reader, wireless transfer/readout, and platform limitations recited in claims 9-11 and 13. Accordingly, the rejection of claims 9-11 and 13 under 35 U.S.C. § 103 is maintained.
In response to applicant’s arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Accordingly, the rejections of claims 1-3, 5-11, 13, 21, and 22 under 35 U.S.C. § 103 are maintained.
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 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.
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/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 25, 2026
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