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 .
Status of the Claims
Claims 19-21, 24-37, and 41-42 were pending. Claims 36-37 were withdrawn.
Claims 27-29 and 32 are amended.
Claims 19-21, 24-35, and 41-42 are examined herein.
Withdrawn Rejections
The rejection of claims 27-29 and 32 under 35 U.S.C. 112(b) is withdrawn in view of claims amendments.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 19, 21, 24, 26-35, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (KR 10-1460066, English translation) in view of Schoeniger et al. (US 2003/0211637) and Cha et al. (Journal of Nanoscience and Nanotechnology, 2013, pgs. 5245-5249), for reasons of record which are reiterated herein below.
Regarding claim 19, Park teaches an electrochemical biosensor device for sensing presence of a molecule in solution (analysis by electrochemical impedance analysis (pg. 14, first 2 paragraphs), the device comprising:
A substrate layer (p-type silicon substrate, pg. 11, Embodiment 1, second paragraph);
A plurality of electrodes in parallel (Fig. on pg. 2; pg. 6, Metal layer deposition step), the electrodes further comprising:
A buffer layer laid on the substrate layer (silicon oxide film formed on the substrate, Oxidation formation step, pg. 6);
An electrode layer laid on the buffer layer (electrode pattern is formed on the silicon oxide film, pg. 11, embodiment 1, first paragraph), the electrode layer configured to provide binding sites for analytes (immobilizer that immobilizes the detecting probe is immobilized on the electrode which configures the electrode to provide binding sites for analytes, pg. 13, Experimental example 4); and
An insulator layer comprising Si3N4 (silicon nitride, pg. 8, par. 4) having a plurality of bores (insulating layer having nanowell bores formed therein, pg. 8, paragraphs 4-5), the insulator layer laid on the electrode layer (insulator layer formed on the electrode layer, pg. 11, Embodiment 1, 2nd paragraph) and the insulator having a plurality of bores configured to form a plurality of nanowells having side walls that are defined by the insulator layer and having bottom floors that are defined by a top surface of the electrode layer that is not covered by the insulator layer (representative drawing, pg. 2, specifies that the base of the nanowell is gold and the side walls are formed by the insulation layer; insulating layer defines the well height and therefore forms the walls, pg. 8, 4th paragraph; paragraph spanning pgs. 11-12), wherein the nanowells are of uniform size and pattern (in the representative drawing, pg. 2, the nanowells are illustrated as uniform size and pattern; uniform size and arrangement of nanowell array, pg. 7, 3rd paragraph),
wherein the insulator layer is configured to substantially confine binding of the analyte to the top surface of the electrode layer that define the bottom floors of the plurality of nanowells (insulator layer is patterned to have nanowells wherein an immobilizer that immobilizes a probe that is specific for the target analyte to the top surface of the electrode, therefore binding of the analyte occurs within the nanowell that is formed by the insulator layer and the insulator layer confines the binding of the analyte to the top surface of the electrode, pg.13, Experimental example 4),
wherein the insulator layer comprises silicon dioxide or silicon nitride (representative drawing, pg. 2; Silicon oxide or silicon nitride film, pg. 8, 4th paragraph), and
wherein the nanowell is configured to have at least one analyte that binds to the electrode without binding to the insulator (antigen analyte binds to the probe that is immobilized within the nanowell, the probe is immobilized to the electrode via an immobilizer that is applied only to the electrode, not the insulator, therefore the target binds only to the electrode without binding to the insulator, pg.13, Experimental example 4).
Park does not specifically teach the plurality of electrodes having different analyte probes on the bottom floor of the nanowells, each configured to bind to an analyte and a buffer layer comprising a titanium alloy or a chromium alloy configured to provide bonding of the plurality of electrodes to the substrate layer.
Regarding claims 19, Schoeniger teaches a biosensor device comprising:
A substrate layer (substrate is interpreted as combination of 11 and 12, Fig. 2; par. 39) and a plurality of electrodes in parallel (plurality of electrodes, 13, Fig. 2; electrodes arranged in parallel, Fig. 7 A; par. 44 and 56), the electrodes comprising: an electrode layer and binding of molecules directly coupled to the bottom floor of the nanowells (electrode, 13, on substrate, 11 /12, and having bioaffinity coating that provides binding sites, 17, Fig. 2; bioaffinity coating may be immobilized to the electrode itself (par. 38) and an insulator layer having a plurality of bores that form nanowells having bottom floors that are defined by a top surface of the electrode (insulator layer, 14, has plurality of wells, 15, wherein the insulator forms the sidewalls and the electrode, 13, forms the bottom floor of the well, Fig. 2; par. 39), in order to provide an device circuitry for an array of electrodes that provide detection of a target (par. 35).
Wherein each individual electrode is coated with at least one specific analyte probe, and different analyte probes are immobilized to the bottom floors of the nanowells of the two distinct electrodes on the substrate layer, respectively, wherein the different analyte probes of each individual electrode is configured to bind to an analyte (Different affinity ligands can be used in different regions of the array, or even for each element, allowing many different targets to be detected, par. 34).
Park and Schoeniger do not specifically teach a buffer layer comprising a titanium alloy or a chromium alloy configured to provide bonding of the plurality of electrodes to the substrate layer.
Regarding claim 19, Cha teaches an electrochemical biosensor device for sensing a presence of a molecule in solution, the device comprising:
A substrate layer (silicon dioxide deposited on silicon substrate, pg. 5246, left column, last paragraph); and
A plurality of electrodes in an array (array of nanowells, pg. 5246, right column, section 2.3; each nanowell contains an electrode, pg. 5246, right column, first paragraph; individual nanowell illustrated with an electrode in Fig. 1; plurality of nanowells in an array illustrated in Fig. 2A and therefore indicate a plurality of electrodes, also a plurality of electrodes is discussed in section 2.3 pg. 5246), the electrodes further comprising:
A titanium buffer layer laid on the substrate layer configured to provide bonding of the plurality of electrodes to the substrate layer (titanium layer as an adhesion layer is laid on the substrate layer, pg. 5246, left column, last paragraph);
An electrode layer laid on the buffer layer, the electrode layer configured to provide binding sites for analytes (electrode on the titanium layer, pg. 5246 paragraph spanning left and right columns; electrode is functionalized with a SAM and immobilizer to provide binding sites for analytes, section 2.3, pg. 5246; Fig. 1).
The titanium buffer layer meets the limitation of claim 24 reciting the buffer layer comprising titanium.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Park by employing different affinity ligands attached to different electrodes as taught by Schoeniger in order to provide detection of multiple different targets, as an obvious matter of using of known technique (multiplexed detection of Schoeniger) to improve similar devices (Park) in the same way.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Park is generic with respect to a number of targets and Schoeniger teaches multiplexing in the biosensor similar to one taught by Park. Immobilization of different analyte probes to the wells is widely known in the art, so the results would have been predictable.
It would have further been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the biosensor of Park and Schoeniger by employing a titanium buffer layer between the substrate layer and electrode layer as taught by Cha, in order to provide improved adhesion between the substrate and electrode (Cha, pg. 5246, paragraph spanning left and right columns), as an obvious matter of using of known technique (improving adhesion) to improve similar devices (biosensor of Park and Schoeniger) in the same way.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Park and Cha teach very similar electrode-based biosensors comprising similar layers, technology, and materials.
Regarding claim 21, Park teaches the substrate layer comprising silicon (pg. 6, 4th paragraph).
Regarding claim 26, Park teaches the electrode layer comprising gold (pg. 6, 7th paragraph).
Regarding claims 27-32 and 42, Park teaches the nanowell is cylindrical in shape and has a circular nanowell opening with a diameter of between 100 nm and 1000 nm (reads on the overlapping diameters of an opening of the nanowell between 50 nm to 1000 nm and 100 nm to 1000 nm) (pg. 10, 2nd paragraph) and a diameter of the opening being 400 nm with the spacing between the nanowells being 400 nm, which results in a pitch ratio of 1:1 (pg. 12, 1st paragraph), but fail to teach the nanowell opening having a diameter of about 100 nm, 50 nm and a pitch ratio of 1:5 or 1:3. However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation" Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Since applicant has not disclosed that the specific limitations recited in instant claims 27-31 are for any particular purpose or solve any stated problem, and the prior art teaches that the nanowell opening and the pitch ratio may be varied depending on the desired target and the overall desired size of the array and desired number of nanowells in the array. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the nanowell array art.
Regarding claims 33-35, Park teaches the device is capable of sending electronic signals to an electronic device from the nanowell electrodes (contact electrodes connected to the nanowell electrodes indicate capability of sending signals to an electronic device, representative drawing, pg. 2).
Specifically, Park teaches two electrodes (Fig. on pg. 2) and a gold electrode that serves as a reference electrode (pg. 13, 2nd paragraph). The limitation of detecting differences in electrochemical reaction parameters between an electrode containing a reference sample and an electrode containing a test sample to determine whether the analyte is present in the test sample is drawn to a functional limitation of the device and does not impart any structural limitations to the claimed device. When a functional limitation is claimed, the device of the prior art must only be capable performing the claimed functional limitation. The device of Park is capable of measuring and reporting electronic signals and is therefore considered capable of detecting a difference between signals at an electrode with a reference sample and an electrode with a test sample to determine the presence of analyte. Park teaches the device is capable of detecting electrochemical reaction parameters based on an electrochemical reaction variation (pg. 13, Experimental example 4). Although Park does not specifically teach the electrochemical reaction parameter comprising a variation in redox current, such a limitation is drawn to a functional limitation of the device and does not impart any structural limitation on the device itself. Because Park and Schoeniger teach the device structural limitations required by the claim, the device is considered capable of sending the same signals to an electronic device, including electrochemical reaction parameters comprising a variation in redox current as recited in claims 34 and 35.
Regarding claim 41, Park teaches an analyte binds only to the electrode via the analyte probe. Specifically, streptavidin is immobilized on the electrode in the nanowell and a biotinylated antibody is bound to the streptavidin (pg.13, Experimental example 4). Therefore, an analyte binds to the electrode via the analyte probe (biotinylated antibody).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Park in view of Schoeniger and Cha, as applied to claim 19, and further in view of Sierks et al. (US 2014/0011691), for reasons of record which are reiterated herein below.
The teachings of Park, Schoeniger, and Cha have been set forth above.
Park, Schoeniger, and Cha fail to teach the substrate layer comprising glass.
Regarding claim 20, Sierks teaches a biosensor analogous to Park’s biosensor (Abstract and Fig. on pg. 1). Sierks also teaches the substrate layer comprising glass. Specifically, the reference teaches the biosensor is comprising a substrate layer (base substrate, par. 62-63) comprising glass or silicon (par. 19) and a plurality of electrodes (microelectrode array, par. 14-16 and 51).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the silicon substrate taught by Park with a glass substrate as taught by Sierks, as an obvious matter of simple substitution of one known element (glass substrate) for another (silicon substrate). Sierks teaches glass and silicon as acceptable alternatives for the substrate; therefore, the results would have been predictable.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Park in view of Schoeniger and Cha, as applied to claim 19, and further in view of Wegner et al. (PGPub 2008/0003709), for reasons of record which are reiterated herein below.
The teachings of Park, Schoeniger, and Cha have been set forth above.
Park, Schoeniger, and Cha fail to teach the buffer layer comprising chromium.
Regarding claim 25, Wegner teaches a diagnostic test strip biosensor comprising layers of conductive and base material (Abstract). Wegner also teaches the buffer layer comprising chromium. Specifically, Wegner teaches “a bonding layer of titanium or chromium may be deposited on base layer 118 before depositing the conductive material on base layer 118” and “the bonding layer may be configured to enhance a bond strength between base layer 118 and the conductive material by providing stronger adhesion between the conductive material and the bonding layer” ([0066]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the titanium buffer layer of Park, Schoeniger, and Cha with a chromium buffer layer as taught by Wegner, as an obvious matter of simple substitution of one known element (chromium buffer layer of Wegner) for another (titanium buffer layer of Park). Wegner teaches chromium and titanium as acceptable alternatives for the bonding layer; therefore, the results would have been predictable.
Response to Arguments
Applicant’s arguments filed on November 5, 2025 have been fully considered.
Applicant respectfully submits that the cited references fail to render obvious the pending claims because they do not disclose the combination of all the recited elements. Accordingly, Applicant respectfully requests reconsideration and withdrawal of the above obviousness rejection. (pg. 6, last par.).
The argument is not persuasive because the cited references do render obvious the pending claims because they disclose the combination of all the recited elements. Since Applicant has not provided any specific arguments against the references, the claims remain unpatentable based on the teachings as described above.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677