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 4/24/2024 has been considered by the examiner.
Election/Restrictions
Applicant's election of Group I, Claims 1-2, 4-6, 9-10, 12-13 and 15, without traverse in the reply filed on 01/29/2026 is acknowledged.
Specification
35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are: the specification disclose: an average Mw ranging from 1,000 to 100,000 [para. 0080] in PG-Pub; The polyaniline can have an average Mw ranging from 1,000 to 100,000, such as 5,000 to 75,000, or 5,000 to 65,000, or 5,000 to 50,000, or 5,000 to 20,000 [para. 0049] in Pg-Pub. But the values of the average Mw do not have units.
Claim Objection
Claims 1-2, 6, 10, and 12-13 are objected to because of the following informalities:
Claim 1: please amend “the functionalized nanotubes” to -- the plurality of functionalized nanotubes--.
Claim 2: please amend “wherein metal oxide-based nanotubes” to -- wherein the metal oxide-based nanotubes--.
Claim 6: please amend “Mw ranging from 1,000 to 100,000” to – molecular weight (Mw) ranging from 1,000 to 100,000 Da--.
Claim 10: please amend “biomolecule ” to – the biomolecule --.
Claim 12: please amend “the functionalized nanotubes” to -- the plurality of functionalized nanotubes--.
Claim 13: please amend “the functionalized nanotubes” to -- the plurality of functionalized nanotubes--.
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.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 13, claim 13 recites “wherein the electrode further comprises a blocking agent that covers regions of the functionalized nanotubes and/or surface binding agent that do not further comprise a biomolecule”. It is unclear if both “the functionalized nanotubes and/or surface binding agent” limit the regions or only “the functionalized nanotubes” limits the regions and/or the electrode further comprises surface binding agent. Furthermore, it unclear if “surface binding agent” is the same as or different than the surface binding agent of claim 1. Thus, the scope of claim 13 is indefinite.
Claim Rejections - 35 USC § 102
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 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 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.
(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, 4-6, 9, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gao et al. (Signal-amplified platform for electrochemical immunosensor based on TiO2 nanotube arrays using a HRP tagged antibody-Au nanoparticles as probe, Biosensors and Bioelectronics, 2013, 41, 771-775).
Regarding claim 1, Gao teaches an electrode (Ti foil having TiO2 nanotube arrays as the working electrode [sections 2.3 and 2.5; Scheme 1]) , comprising a plurality of functionalized nanotubes on a support (TiO2 nanotube arrays on a Ti foil [section 2.3; scheme 1]; the TiO2 nanotubes were functionalized by APTES, EDC/NHS and Ab1 [section 2.5 and Scheme 1]), wherein the plurality of functionalized nanotubes comprise metal oxide-based nanotubes (TiO2 nanotubes [section 2.3 and scheme 1]) that are associated with a coating comprising a surface binding agent (APTES [section 2.5 and scheme 1]) and biomolecule (anti-rabbit IgG in scheme 1; Ab1 [section 2.5]).
Regarding claim 4, Gao teaches the electrode of claim 1, wherein the metal oxide-based nanotubes are TiO2 nanotubes that exist in amorphous form (TiO2 nanotube arrays [section 2.3 and scheme 1]; the as-formed TiNT is amorphous [section 3.1]).
Regarding claim 5, Gao teaches the electrode of claim 1, wherein the surface binding agent is an amino-containing compound (APTES [section 2.5 and scheme 1], and APTES is an amino-containing compound).
Regarding claim 6, Gao teaches the electrode of claim 5, wherein the amine-containing compound is an amino-silane compound selected from aminopropyl triethoxysilane (APTES [section 2.5 and scheme 1]).
Regarding claim 9, Gao teaches the electrode of claim 1, wherein the biomolecule is capable of specifically binding an antigen (anti-rabbit IgG is capable of specifically binding rabbit IgG [scheme 1; section 2.5]).
Regarding claim 13, Gao teaches the electrode of claim 1, wherein the electrode further comprises a blocking agent that covers regions of the functionalized nanotubes (a blocking treatment with BSA for 2h [section 2.5]; BSA is deemed as the blocking agent) and/or wherein the support is a metal support (Ti foil [section 2.3], which is a metal support).
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 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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Gao, as applied to claim 1 above, and in view of Mavric et al. (Electrochemical biosensor based on TiO2 nanomaterials for cancer diagnostics, Advances in Biomembranes and Lipid Self-Assembly, Vol. 27, ISSN 2451-9634, 2018, 63-105).
Regarding claim 2, Gao teaches the electrode of claim 1, wherein metal oxide-based nanotubes comprise a titanium oxide (TiO2 nanotube arrays [section 2.3 and scheme 1]).
Gao further teaches 0.4 µm, 0.8 µm, and 1.4 µm long tube layers are grown by anodization for 1h, 2h, and 4h, respectively [section 3.1]. Thus, Gao is silent to wherein the metal oxide-based nanotubes of the plurality of functionalized nanotubes have an average length greater than 3 µm.
Mavric teaches TiO2 biosensors for human cancer detection (section 5.1), and Fig.10 shows TiO2 nanotubes on an electrode base such as Ti foil, and antibody is immobilized on the TiO2 nanotubes followed by blocking the nonspecific sites with BSA (section 5.1 from pages 86 to 88). The length, diameter, nanopore/nanotube formation, and open top morphology of TiO2 nanotubes can be controlled by varying synthesis parameters, e.g., anodization time, applied voltage, and electrolyte composition as shown in Fig.6. Fig.6b shows length of the TiO2 nanotubes is 61.54 µm (section 4.1 on pages 78-79). TiO2 nanotubes with higher length have a higher total surface area, and therefore protein adhesion is higher (section 4.2.1 on page 80).
Given the teachings of Gao regarding the biomolecule of anti-rabbit IgG is coated on the surface of the TiO2 nanotubes for capture rabbit IgG (see scheme 1), and the teachings of Mavric regarding TiO2 nanotubes with higher length having a higher total surface area, and therefore higher protein adhesion, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the length of the TiO2 nanotubes affects the total surface area, and accordingly the amount of antibody immobilized on the surface of the TiO2 nanotubes. Thus, the length of the TiO2 nanotubes is a result effective variable.
As the total surface area and amount of protein (antibody) are variables that can be modified, among others, by adjusting the length of the TiO2 nanotubes, the precise average length of the TiO2 nanotubes would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed average length of the TiO2 nanotubes greater than 3 µm cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the average length of the TiO2 nanotubes in Gao to obtain the average length of the TiO2 nanotubes being greater than 3 µm in order to obtain the desired total surface area and the desired amount of antibodies immobilized on the surface of the TiO2 nanotubes for the detection of the RIgG antigen. “[W]here 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). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Claim 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Gao, as applied to claim 1 above, and in view of Yakoh et al. (Paper-based electrochemical biosensor for diagnosing COVID-19: Detection of SARS-CoV-2 antibodies and antigen, Biosensors and Bioelectronics, 2021, 176, 112912).
Regarding claim 10, Gao teaches the electrode of claim 9, and is silent to wherein the biomolecule is an antibody that specifically binds a COVID-19 antigen.
Yakoh teaches an electrochemical biosensor for diagnosing COVID-19 (title) based on the immobilized antibody (SARS-CoV-2 IgM) specifically binds to the SARS-CoV-2 spike protein (section 3.6).
Gao and Yakoh are considered analogous art to the claimed invention because they are in the same field of electrochemical biosensor based on immobilized antibody specifically binding to the target antigen. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the immobilized anti-rabbit IgG antibody of Gao with SARS-CoV-2 IgM, as taught by Yakoh , since it would allow to diagnose COVID-19 , which plays a crucial role in making a proper decision of the isolation of infected patients and slowing the spread of this infectious disease (abstract, the first paragraph in section 1, and section 3.6 in Yakoh).
Regarding claim 12, modified Gao teaches the electrode of claim 10, and Gao teaches wherein the antibody is covalently bound to the surface binding agent (Ab1 binds to the APTES functionalized TiO2 nanotube arrays using EDC/NHS chemistry [section 2.5 and scheme 1], thus it forms a covalent bond between the antibody’s carboxylic acid groups and the amino groups on the APTES) and wherein the surface binding agent is coated on top of the functionalized nanotubes (TiNT chips were decorated a layer of APTES [section 2.5], Scheme 1 shows APTES is coated on top of the functionalized TiO2 nanotubes).
The limitation “such that antigen-binding regions of the antibody extend vertically upwards” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, Gao teaches wherein the antibody is covalently bound to the surface binding agent, as outlined in the rejection above. Scheme 1 of Gao also shows antigen-binding regions of the antibody extend vertically upwards.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Gao, as applied to claim 1 above, and in view of Song et al. (CN206960485U, English translation).
Regarding claim 15, Gao teaches the electrode of claim 1, and is silent to further comprising a substrate physically attached to the support of the electrode, wherein the substrate comprises a fiber-based material, a plastic material, a glass material, or a metal material.
Song teaches an immunosensor based on TiO2 nanotube array coupled to antibodies (title and abstract). The sensor comprises a base 2 that supports the substrate 1, as shown in Fig. 1. The substrate 1 is composed of a titanium sheet with TiO2 nanotubes 3 grown on its surface in an array. The TiO2 nanotubes 3 are coupled with nanoantibodies 4 [para. 0013]. The substrate 1 is mounted on the base 2 in a snap-on detachable manner [para. 0015]. The base can be made of PVC, glass or other materials [para. 0059]. The substrate 1 in Song corresponds to the plurality of TiO2 nanotube arrays on the Ti foil in Gao. Thus, Song teaches further comprising a substrate (base 2) physically attached to the support of the electrode (Ti foil/sheet), wherein the substrate comprises a plastic material or a glass material (the base can be made of PVC or glass).
Gao and Song are considered analogous art to the claimed invention because they are in the same field of electrochemical immunosensor comprising antibodies immobilized on TiO2 nanotube arrays. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the electrode in Gao by providing a substrate physically attached to the support of the electrode, wherein the substrate comprises a plastic material or a glass material, as taught by Song, since it would support the electrode [para. 0059 in Song]. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results [MPEP 2143 (I)(A)].
Conclusion
The prior arts made of record and not relied upon are considered pertinent to applicant's disclosure: Gao et al. (Signal Amplification Strategy Based on TiO2-Nanotube Layers and Nanobeads Carrying Quantum Dots for Electrochemiluminescent Immunosensors, ChemistryOpen, 2013, 2, 93-98) also teaches all limitations of claim 1. Nycz et al. (Fabrication of Electrochemical Biosensor Based on Titanium Dioxide Nanotubes and Silver Nanoparticles for Heat Shock Protein 70 Detection, Materials, 2021, 14, 3767) teaches all limitations of claim 1. Jin et al. (US20160158412A1) teaches TiO2 nanotubes on a support (see Fig.3).
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/SHIZHI QIAN/Examiner, Art Unit 1795