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 1-4, 6-8, and 10 are pending. Claims 5, 9, and 11-15 have been canceled. Claims 1-4, 6-8, and 10 have been amended. Claims 1-4, 6-8, and 10 are examined herein.
Priority
The present application, filed 10/27/2023, is a 371 of PCT/US2022/027031, filed 04/29/2022, which claims benefit of U.S. Provisional Patent Application 63/181,876, filed 04/29/2021. The benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 04/29/2021.
Specification
The disclosure is objected to because of the following informalities: Reference numeral 335 is used inconsistently to identify different elements. Applicant amended paragraph [0021] to identify reference numeral 335 as the condition control circuit. However, reference numeral 335 remains used elsewhere in the specification to identify the electrical sensor [0022], and Figure 3 continues to identify reference numeral 335 as the electrical sensor. Accordingly, the amendment does not resolve the inconsistency because the same reference numeral continues to identify different structural elements. Appropriate correction is required. Also, the specification is further objected to because Figure 3 includes reference numeral 355, but reference numeral 355 is not identified or described in the specification. Appropriate correction is required.
Maintained 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.
The rejection under 35 U.S.C. 112(b) is maintained in updated form in view of Applicant’s amendments.
Claim 6 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites “surface acoustic waves propagating through the sensing area at a surface of the piezoelectric substrate on which the sensing layer is formed.” However, claim 1, from which claim 6 ultimately depends, expressly recites “a pad formed on the piezoelectric substrate, having a roughened surface of the pad; a sensing layer formed on the roughened surface of the pad.” Accordingly, it is unclear whether the phrase “on which the sensing layer is formed” in claim 6 indicates that the sensing layer is formed on the surface of the piezoelectric substrate, or whether the sensing layer remains formed on the roughened surface of the pad as expressly required by claim 1. Thus, the structural relationship between the piezoelectric substrate, the pad, and the sensing layer is unclear, and the scope of claim 6 cannot be determined with reasonable certainty. For purposes of compact prosecution, claim 6 will be interpreted as retaining the structural relationship expressly recited in claim 1, such that the pad is formed on the piezoelectric substrate and the sensing layer is formed on the roughened surface of the pad. Appropriate correction is required.
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.
The rejection under 35 U.S.C. 103 is maintained in updated form in view of Applicant’s amendments. The amendments materially revised the structure and operation of the claimed sensing system, including the pad and roughened-surface arrangement, M13 phage fiber-bundle sensing layer, electrode configuration, and condition-control limitations. Accordingly, the prior-art combination and supporting rationale have been updated to address the amended claim language.
Claims 1-3, 6-8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Shachar et al. (WO2018057201A1) in view of Taylor et al. (A Prototype Antibody-Based Biosensor for Measurement of Salivary MMP-8 in Periodontitis Using Surface Acoustic Wave Technology. Scientific Reports. Vol. 9, No. 1, July 2019), Lee et al. (US20160312262A1), Viespe et al. (Love Wave Surface Acoustic Wave Sensor with Laser-Deposited Nanoporous Gold Sensitive Layer. Sensors. Vol. 19, No. 20. October 2019), and Wen et al. (Study on Fabrication of ZnO Waveguide Layer for Love Wave Humidity Sensor Based on Magnetron Sputtering. Sensors. Vol. 18, No. 10, October 2018).
Regarding claim 1, for a sensing system comprising a sensor chip that includes: a piezoelectric substrate, Shachar teaches a surface acoustic wave biosensor apparatus for biological detection. Shachar further teaches the use of miniature monolithic SAW sensor arrays allows on-chip signal processing, and allows the chips to be fully integrated into a larger system and easily packaged ([0045], p. 9). Shachar further teaches a piezoelectric substrate that has a guiding layer formed thereon in which there is an input interdigitated transducer (IDT) and output interdigitated transducer (IDT) ([0191], p. 32, Fig. 1A). Regarding a pad formed on the piezoelectric substrate, having a roughened surface, Shachar teaches the underlying localized sensing-region architecture, including that between the input and output IDTs is a sensitive layer, which may be a functionalized gold layer ([0191], p. 32, Fig. 1A).
Regarding a sensing layer formed on the roughened surface of the pad in a sensing area defined by the pad, Shachar teaches that conventional SAW biosensing employs a chemically functionalized area that immobilizes a targeted species with a selective surface coating and explains that attachment of the targeted species perturbs the propagating surface acoustic wave ([0045], p. 9). Shachar further teaches that the sensitive layer between the input and output IDTs may be a functionalized gold layer loaded by the detected analyte ([0191], p. 32, Fig. 1A). Regarding the M13 phages having analyte-binding sites configured to interact with a target analyte, Shachar teaches the use of engineered DNA encoded libraries as the probe while employing a phage display procedure to enhance specificity, capture statistics for the detection, screening, and analysis of the analyte in vitro ([0003], p. 1). Thus, Shachar expressly identifies phage-display recognition as an approach for enhancing the target-recognition function of the disclosed biosensor.
Regarding a first pair of interdigitated electrodes formed on the piezoelectric substrate on a first side of the pad, fingers of the first pair of interdigitated electrodes extending toward the pad; a second pair of interdigitated electrodes formed on the piezoelectric substrate on a second side of the pad opposite to the first side, fingers of the second pair of interdigitated electrodes extending toward the pad, Shachar teaches input interdigitated transducer (IDT) and output interdigitated transducer (IDT), and between these IDTs is a sensitive layer ([0191], p. 32, Fig. 1A). Shachar further teaches the interdigitated transducer is comprised of a series of interleaved electrodes made of a metal film deposited on a piezoelectric substrate ([0192], p. 32), with Fig. 1A depicting the input and output IDTs on opposite sides of the intervening sensing region.
Significantly, Shachar itself provides an express reason for incorporating phage-based recognition into its disclosed SAW architecture because Shachar teaches use of phage display procedure to enhance specificity and capture statistics. Thus, Shachar itself directs one of ordinary skill toward phage-display recognition for improving the specificity and capture performance of the SAW biosensor.
However, Shachar does not expressly teach that the sensing region is implemented as the particular claimed pad formed on the piezoelectric substrate, having a roughened surface, that the sensing layer comprises fiber bundles formed from a plurality of M13 phages, that the roughened surface affects anchoring of the fiber bundles, or a condition control circuit configured to monitor and control, during measurement, conditions in the sensing area, wherein the conditions include temperature and humidity. Shachar also does not expressly identify its localized sensing region as the particular claimed pad structure.
Taylor teaches the particular sensor-chip/pad implementation of Shachar’s SAW architecture. Taylor teaches the prototype sensor comprises a disposable SAW biochip functionalised with specific antibodies and further teaches the biochip comprises interdigitating input and output gold electrodes linked by a gold film coated sensing area built on a plane piezoelectric quartz crystal (Materials and Methods, p. 6). Taylor further teaches that this structure facilitates excitation of a shear horizontal SAW of defined wavelength and frequency (p. 6). Thus, Taylor’s gold-film-coated sensing area provides the claimed pad/sensing area formed on the piezoelectric substrate and positioned between the opposed interdigitated input and output electrodes. Taylor further teaches capture antibodies on the surface of the gold film and this biochip thereby become sensitive to reactions (e.g. antigen binding) by means of a SAW velocity and /or amplitude changes due to surface condition changes and that the resulting perturbation is detected by the difference in wave phases between the input and output electrodes (p. 6). Accordingly, Taylor provides a working biological SAW biochip having a discrete gold sensing area built on the piezoelectric quartz crystal and disposed between the input and output interdigitated electrodes.
Lee teaches the claimed M13-phage fiber-bundle sensing layer. Regarding wherein the sensing layer comprises fiber bundles formed from a plurality of M13 phages, Lee expressly teaches an exemplary sensor is described herein by reference to the use of a plurality of M13 phage bundles immobilized on a substrate ([0092], p. 55) and teaches a phage-bundle structure that comprises a plurality of the recombinant M13 bacteriophages ([0094], p. 55). Lee further teaches that genetically engineered phages self-assemble into colored matrices composed of quasi ordered bundled structures ([0096], p. 55), and expressly identifies self-assembled fiber bundles comprising filamentous M13 phage ([0101], p. 55). Regarding the M13 phages having analyte-binding sites configured to interact with a target analyte, Lee teaches through phage display and genetic engineering, any kind of recognition motif can be imparted on the phage of the detection layer, incorporating the specific function of detection of the analyte of interest ([0095], p. 55), and phages genetically engineered to recognize an analyte of interest ([0096], p. 55). Lee further expressly teaches the genetically engineered bacteriophage is a recombinant M13 bacteriophage comprising one or more recombinant phage coat protein comprising an amino acid sequence capable of binding the analyte of interest ([0122], p. 57), and the M13 phage display various peptides that bind an analyte of interest ([0124], p. 57).
Regarding anchoring of the fiber bundles on the sensing surface, Lee teaches that the M13 bundles are immobilized on a substrate and that phage-bundle structures may be made or deposited on any suitable substrate that does not interfere in the assembly of the phage bundle structure and the ability of the bacteriophage to bind to the analyte of interest ([0092]-[0094], p. 55). Lee further teaches that the M13 phage possesses a large surface area and an ability to present ligands or analyte of interest in high densities ([0127], p. 57). Lastly, Lee expressly teaches that the fiber bundles swell or contract as the humidity in the ambient environment increases or decreases, respectively ([0102], p. 55). Lee therefore supplies the particular sensing-layer architecture toward which Shachar’s phage-display teaching directs the artisan: analyte-binding M13 phages organized into surface-supported fiber bundles.
Viespe teaches the claimed roughened surface affecting anchoring of the fiber bundles by expressly establishing the effect of gold-surface roughness/morphology upon immobilization of biological material in a SAW sensor. Viespe teaches gold layers having measured roughnesses of 0.7 nm, 6 nm, and 30 nm, with the latter surfaces exhibiting porous and irregular morphology (p. 5, Fig. 2). Most importantly, Viespe experimentally teaches a larger quantity of enzyme is loaded onto the porous surfaces (S2 and S3) than onto the dense one (S1) and identifies S1 as having a dense and relatively smooth Au layer (p. 6). The relatively smooth surface produced a 9-kHz shift after enzyme immobilization, whereas the porous surfaces produced 24- and 26-kHz shifts (p. 6). Viespe further explains that the increased sensor response results because a larger mass of enzyme was immobilized onto nanoporous gold layers than onto the dense one (p. 6). Viespe further teaches that sensing properties depend not merely upon the amount of immobilized biological material but also upon its morphology and roughness (p. 7). Accordingly, Viespe establishes that roughening/nanostructuring the gold biological immobilization surface affects biological immobilization thereon. When applied to Lee’s surface-supported M13 phage bundles, the combined teachings provide the claimed roughened pad surface affecting anchoring of the fiber bundles.
Wen teaches an acoustic Love-wave sensor measurement system in which the external environment affects acoustic propagation and provides a measurement system having active temperature and humidity control. Wen teaches that the sensor module, the temperature control module and the humidity control module are in the closed air chamber (p. 6, Fig. 3). Wen further teaches that the temperature control module is a semiconductor refrigerator and its control circuits and the humidity control module includes a humidification unit and a dehumidifying unit (p. 6). Wen further teaches that the display module is composed of the microprocessor and the DHT11 sensor which can measure the temperature and humidity simultaneously and expressly states they can simultaneously measure the temperature and humidity in the closed air chamber by the display module while the spectral characteristics of the sensor are measured by the network analyzer (p. 6, Figs. 3-4). Thus, Wen teaches monitoring both temperature and humidity and actively controlling both conditions in the same closed environment containing the acoustic sensing module during measurement.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Shachar’s SAW biosensor according to Taylor by implementing Shachar’s intervening functionalized sensing region as Taylor’s gold-film sensing area built on the piezoelectric sensor chip between the opposed input and output interdigitated electrodes. Taylor demonstrates that such a configuration is an operative SAW biochip in which biological target binding at the gold sensing surface produces measurable changes in the propagating SAW. Thus, the modification would have provided Shachar’s biosensor with a defined biological sensing region on a compact piezoelectric chip while preserving Shachar’s acoustic transduction mechanism. It would have been further obvious to modify the sensing layer according to Lee to comprise surface-supported fiber bundles formed from analyte-binding M13 phages because Shachar itself expressly directs one of ordinary skill toward phage-display recognition to enhance specificity, capture statistics, while Lee supplies a specific phage-display implementation in which M13 bacteriophages self-assemble into fiber bundles and carry analyte-binding recognition sites. Lee further teaches that the M13 phage possesses a large surface area and an ability to present ligands or analyte of interest in high densities, providing a specific technical advantage for using Lee’s M13 recognition material in Shachar’s functionalized sensing region. It would have been further obvious to modify Taylor’s gold sensing surface according to Viespe to provide a roughened/nanoporous morphology affecting anchoring of Lee’s biological sensing material because Viespe experimentally demonstrates that nanoporous/roughened gold immobilizes a greater quantity of biological material than a relatively smooth dense gold surface and provides improved SAW sensor response. The reason for the modification is therefore not merely that roughened surfaces were known, but that Viespe teaches the specific benefit relevant to the claimed sensing interface—greater biological immobilization on the SAW gold surface.
It would have been further obvious to provide the modified sensor with Wen’s temperature- and humidity-monitoring/control arrangement because environmental conditions affect acoustic sensing and because the proposed M13 fiber-bundle layer itself is responsive to humidity. Lee expressly teaches that the fiber bundles swell or contract as the humidity in the ambient environment increases or decreases, respectively. Wen provides the specific solution of simultaneously measuring temperature and humidity while actively controlling temperature by refrigeration/control circuitry and humidity by humidification/dehumidification. The modification would reduce environmental variation during measurement and thereby permit target-induced acoustic changes to be distinguished from changes attributable to uncontrolled temperature or humidity. One of ordinary skill would have had a reasonable expectation of success because Taylor demonstrates biological analyte detection using the proposed piezoelectric SAW biochip geometry; Lee demonstrates surface-supported, analyte-recognizing M13 phage bundles; Viespe experimentally demonstrates biological immobilization on roughened/nanoporous gold in a SAW sensor; and Wen demonstrates simultaneous temperature/humidity measurement and active environmental regulation in an operating Love-wave sensor system. The modifications employ the secondary teachings for the same functions for which the references teach them and do not require changing the basic acoustic sensing principle of Shachar. Additionally, the modification of Taylor’s gold sensing area according to Viespe constitutes application of a known SAW surface-engineering technique for its expressly taught biological-immobilization and sensitivity benefits.
Regarding claim 2, Shachar teaches an RF driver that creates the SAW waves in the guiding layer by means of the input IDT ([0191], p. 32, Fig. 1A).Shachar further teaches that the input IDT is excited electrically (applying an RF signal) and launches a mechanical acoustic wave into the piezoelectric material ([0262], p. 47, Figs. 32A-32B). Accordingly, Shachar directly teaches the driver circuit electrically coupled to the first/input interdigitated transducer and configured to apply a drive signal that creates acoustic vibrations in the piezoelectric substrate.
Regarding claim 3, Shachar teaches that the output IDT is excited by the modified SAW wave, and transduces it into an electrical signal, which is detected in data circuit and then communicated to output as the frequency, phase and/or amplitude of the modified SAW wave ([0191], p. 32, Fig. 1A). Shachar further teaches that the SAW waves are launched into sensitive layer, which will be loaded by the detected analyte, before the modified wave is received by output IDT ([0191], p. 32). Accordingly, Shachar directly teaches the sensing circuit associated with the second/output interdigitated electrodes and configured to measure target-induced changes in the acoustic vibrations.
Regarding claim 6, for purposes of compact prosecution and consistent with the interpretation set forth under 35 U.S.C. 112(b), claim 6 is interpreted as retaining the structure required by claim 1, wherein the sensing layer is formed on the roughened surface of the pad formed on the piezoelectric substrate. Shachar teaches that the operation of the SAW device of Fig. 1 is based on acoustic wave propagation near the surface of piezoelectric solids ([0191], p. 32). Shachar further teaches that the device includes input IDT and output IDT and that between the IDTs is a sensitive layer, into which the SAW waves are launched and modified by detected analyte ([0191], p. 32, Fig. 1A). Shachar further teaches that SAW sensors include a transducing area and a sensing area ([0262], p. 46), and that the wave propagates through the sensing portion toward the output IDT, where it is transformed into a measurable electrical signal ([0262]-[0264], pp. 46-47). Accordingly, Shachar directly teaches measurement of changes in surface acoustic waves propagating through the sensing area at the piezoelectric-substrate surface. The sensing-layer/pad structural relationship is supplied by the claim 1 combination discussed above.
Regarding claim 7, Shachar teaches that the output IDT is excited by the modified SAW wave, and transduces it into an electrical signal, which is detected in data circuit ([0191], p. 32, Fig. 1A). Shachar further teaches that the interdigitated transducers provide conversion of electrical to mechanical signal, and vice versa ([0192], p. 32). Shachar additionally teaches that the propagated wave reaches output IDT, where it is transformed back into a measurable electrical signal ([0262]-[0264], pp. 46-47). Accordingly, Shachar directly teaches that the acoustic vibrations in the piezoelectric SAW structure excite the second/output interdigitated transducer, which converts those vibrations into an electrical signal measured by the associated sensing circuitry.
Regarding claim 8, Shachar teaches biosensing employing surface acoustic waves and further teaches that the use of miniature monolithic SAW sensor arrays allows on-chip signal processing, and allows the chips to be fully integrated into a larger system and easily packaged ([0045], p. 9). Accordingly, Shachar directly teaches a SAW sensing system implemented using chip-based SAW sensing structures.
Regarding claim 10, Shachar teaches that ST-cut quartz is the most stable and the easiest to operate among those tested and ST-cut quartz is also favorable for narrower bandwidth operation, and it does not need additional layers or gratings to concentrate the energy in the surface ([0267], p. 47). Shachar further expressly teaches that the substrates used in the illustrated embodiments are a 3-inch, single-side-polished, 500µm-thick ST-cut quartz wafers and that SH-SAWs are generated and sensed using a pair of interdigital transducers on the wafers ([0268], p. 48).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Shachar et al., Taylor et al., Lee et al., Viespe et al., and Wen et al., as applied to claims 1, 2, and 3 above, and further in view of Gaso et al. (Love Wave Immunosensor for the Detection of Carbaryl Pesticide. Sensors. Vol. 14, No. 9, September 2014).
With respect to the teachings of Shachar, Taylor, Lee, Viespe, and Wen, see the discussion above, which applies equally here. These references differ from the instant claim in not as expressly teaching or specifying the claimed control-circuit/calibration relationship.
Gaso teaches the additional functionality of claim 4. Regarding the sensing system of claim 3, further comprising a control circuit configured to: receive, from the sensing circuit, measurements of the changes in the acoustic vibrations, Gaso teaches that two parts can be distinguished in the circuit: the Sensor Circuit—which includes the sensor—and the Control and Communication System (Section 2.3, p. 16438, Fig. 3). Gaso further teaches that when a sensor perturbation occurs, a change in the phase velocity and energy of the acoustic wave is produced, generating a change in the electrical signal at the sensor’s output port and that the changes in the amplitude and phase of the sensor branch signal, relative to the unchanged reference signal, due to perturbations, are provided by the AD8302 Integrated Circuit (IC) (Section 2.3, p. 16439). Gaso then teaches that the Control and Communication System controls the test signal generation, and the signals, uA and uϕ, conversion and acquisition (Section 2.3, p. 16439). Regarding to use calibration data to generate a measurement signal indicating a concentration of the target analyte, Gaso teaches immunoassay protocol and standard calibration curves and that the increment in phase with respect to the one at the time of sample injection (baseline signal) was measured (Section 2.4.3, p. 16441). Gaso further teaches known standard analyte concentrations and expressly teaches that standard curves were obtained by plotting the voltage phase increment vs. the logarithm of analyte concentration (Section 2.4.3, p. 16442).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further configure the modified Shachar sensing system according to Gaso so that a control circuit receives the acoustic-response measurements and processes those measurements according to calibration data relating measured phase response to known analyte concentration. Gaso expressly teaches acquisition of the measured phase/amplitude response by its Control and Communication System and an experimentally generated calibration relationship between the acoustic-response signal and analyte concentration. The modification would advantageously permit the sensing system to provide a quantitative concentration-indicating measurement rather than merely a measured change in acoustic response. One of ordinary skill would have had a reasonable expectation of success because Gaso demonstrates this signal-acquisition and calibration approach in an operating Love-wave immunosensor using measured phase response and standard analyte concentrations. The modification merely processes the acoustic output already generated by the sensor and therefore does not alter the underlying acoustic sensing mechanism.
Response to Arguments
Applicant’s arguments filed 06/23/2026 have been fully considered. Claims 1–4, 6–8, and 10 remain pending. Claims 5, 9, and 11–15 have been canceled. Applicant amended independent claim 1. Applicant also amended claims 2–4, 6–8, and 10. The amendments materially alter the factual basis underlying the previous rejection under 35 U.S.C. 103. Accordingly, the prior rejection under 35 U.S.C. 103 is not maintained in its previous form. A new rejection is set forth herein based on the amended claim language. Specifically, claims 1–3, 6–8, and 10 are rejected over Shachar in view of Taylor, Lee, Viespe, and Wen, and claim 4 is rejected over that combination and further in view of Gaso. The new rejection expressly identifies the teachings relied upon for the newly recited pad geometry, M13-phage fiber-bundle sensing layer, roughened-surface/anchoring relationship, and temperature-and-humidity control limitations.
Objection to the Specification
The specification is objected to because reference numeral 335 is used inconsistently to identify different elements. Applicant amended paragraph [0021] to identify reference numeral 335 as the condition control circuit. However, reference numeral 335 remains used elsewhere in the specification to identify the electrical sensor, and Figure 3 continues to identify reference numeral 335 as the electrical sensor. Accordingly, the amendment does not resolve the inconsistency because the same reference numeral continues to identify different structural elements. Applicant is required to amend the specification and/or drawings, as appropriate, so that reference numeral 335 consistently identifies the same element throughout the specification and drawings. The prior objection concerning reference numeral 335 is therefore maintained.
The specification is further objected to because Figure 3 includes reference numeral 355, but reference numeral 355 is not identified or described in the specification. Applicant is required to amend the specification as appropriate, to identify the element represented by reference numeral 355 and to ensure consistency between Figure 3 and the written description.
35 U.S.C. 112
Applicant first argues that the previous rejection of claim 5 under 35 U.S.C. 112(b) should be withdrawn because claim 5 has been canceled. Applicant further argues that amended claims 6 and 7 now expressly further limit claim 3 and therefore comply with 35 U.S.C. 112(d). Applicant’s arguments are persuasive to the extent explained below.
The previous rejection of claim 5 under 35 U.S.C. 112(b), based upon the lack of antecedent basis for the pad area, is withdrawn because claim 5 has been canceled. No rejection of canceled claim 5 is maintained.
The previous rejections of claims 6 and 7 under 35 U.S.C. 112(d) are also withdrawn. As amended, claim 6 now requires that the sensing circuit be configured to measure changes in surface acoustic waves propagating through the sensing area at a surface of the piezoelectric substrate on which the sensing layer is formed. Claim 7 now requires that the sensing circuit be configured to measure an electrical signal induced in the second pair of interdigitated electrodes by the acoustic vibrations in the piezoelectric substrate. These limitations further restrict the manner in which the sensing circuit recited in claim 3 operates. Thus, claims 6 and 7 now include limitations that further limit the subject matter of the claims from which they depend and the previous rejection under 35 U.S.C. 112(d) is no longer applicable. This withdrawal should not be understood as finding amended claim 6 definite under 35 U.S.C. 112(b), however. The amendment to claim 6 creates a separate ambiguity concerning the location of the sensing layer relative to the pad and piezoelectric substrate, as discussed above.
35 U.S.C. 103
Applicant’s arguments have been fully considered but they are not persuasive, for the reasons set forth below.
Applicant’s arguments principally contend that Shachar does not disclose the newly claimed roughened-pad/M13-phage-bundle interface or active temperature-and-humidity control; that Lee is directed to a colorimetric M13-phage matrix rather than an acoustic sensor; that Berg merely supplies conventional integrated-chip implementation; that Gaso does not cure the deficiencies asserted against claim 1; and that the prior combination lacked a technically supported motivation and allegedly depended upon Applicant’s disclosure as a roadmap. Applicant’s arguments do not overcome the rejection presently made because the rejection has been reformulated in view of the amended claims and does not rely upon Shachar, Lee, Berg, and Gaso in the manner addressed in Applicant’s remarks. The current rejection expressly acknowledges the limitations not taught by Shachar alone and relies upon Taylor, Lee, Viespe, and Wen for the particular limitations and technical functions for which those references are applied.
Applicant argues at length that Shachar does not itself disclose: (1) a pad formed on the piezoelectric substrate having a roughened surface; (2) an M13-phage fiber-bundle sensing layer formed on that roughened surface; (3) the roughened surface affecting anchoring of the M13 bundles; or (4) a condition-control circuit actively monitoring and controlling both temperature and humidity in the sensing area during measurement. These arguments have been considered but do not overcome the current rejection. The present rejection does not assert that Shachar alone expressly teaches those limitations. To the contrary, the rejection expressly states that Shachar does not expressly teach the particular claimed pad having a roughened surface, the M13-phage fiber-bundle sensing layer, the roughened-surface/anchoring relationship, or the claimed temperature/humidity condition-control arrangement. Shachar is relied upon for the underlying SAW-biosensor architecture and for teachings that provide a technical starting point for the proposed modifications. Shachar teaches a piezoelectric SAW biosensor having input and output interdigitated transducers with a sensitive layer between them, and teaches that the sensitive layer may comprise a functionalized gold region loaded by detected analyte. Shachar additionally teaches phage-display recognition as an approach for improving specificity and capture statistics. Thus, Applicant’s contention that Shachar lacks the complete amended arrangement does not rebut the rejection actually made. Obviousness does not require the primary reference to contain every limitation where the rejection properly relies on the combined teachings of multiple references.
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). Applicant’s arguments repeatedly identify what Shachar, Lee, or the formerly applied Berg reference does not individually disclose. Those observations do not establish nonobviousness of the claim as presently rejected because the claim is rejected based upon the combined teachings of Shachar, Taylor, Lee, Viespe, and Wen.
Applicant argues that Shachar merely provides a functionalized region and does not disclose the claimed pad defining a localized sensing region between opposed interdigitated-electrode regions. The present rejection addresses this point through Taylor. Taylor teaches a working disposable SAW biochip comprising interdigitating input and output gold electrodes linked by a gold film coated sensing area built on a plane piezoelectric quartz crystal. The resulting discrete gold sensing area lies between the opposed input and output interdigitated electrodes and functions as the biological sensing region of the SAW chip. The rejection therefore relies on Taylor, rather than characterizing Shachar’s generic sensitive layer alone as necessarily constituting the entirety of the presently claimed pad structure. The modification is not based merely upon the fact that a gold sensing area was known. Taylor demonstrates that the particular implementation is a functioning biological SAW biochip in which binding at the gold sensing surface causes measurable changes in the propagating surface acoustic wave. Thus, Taylor supplies both the structural implementation and evidence that the configuration performs the same general acoustic biological-sensing function required by Shachar. The proposed modification therefore preserves Shachar’s basic acoustic transduction principle while providing a defined sensing region on a compact piezoelectric sensor chip. Applicant’s argument that the cited art lacks a pad-defined sensing region between the opposed transducer regions is therefore not persuasive against the current rejection.
Applicant next argues that Lee is fundamentally directed to a colorimetric sensing mechanism in which M13-phage bundles are organized to produce structural color, and that Lee does not itself teach a SAW sensor, the claimed roughened pad, opposed SAW transducers, or the claimed environmental-control arrangement. The Office agrees that Lee is not relied upon for those other portions of the claim. Lee is relied upon for the particular M13-phage fiber-bundle sensing architecture and analyte-recognition functionality. Lee expressly teaches a plurality of M13 phage bundles immobilized on a substrate, phage-bundle structures comprising recombinant M13 bacteriophages, genetically engineered phages that self-assemble into bundled structures, and self-assembled fiber bundles comprising filamentous M13 phage. Lee further teaches imparting recognition motifs by phage display/genetic engineering and recombinant M13 phages having amino-acid sequences capable of binding an analyte of interest. Lee also teaches immobilization or deposition of the bundles on suitable substrates and expressly reports that the fiber bundles swell or contract as ambient humidity changes. Applicant’s observation that Lee demonstrates those properties in a colorimetric implementation therefore does not negate the relied-upon teachings concerning the composition, self-assembly, analyte-recognition capability, substrate support, and environmental responsiveness of the M13 fiber bundles.
In response to applicant’s argument that Lee’s complete colorimetric M13-phage matrix, including its optical operating arrangement and deposition conditions, could not simply be bodily incorporated into Shachar’s SAW structure, 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). The rejection does not propose transplanting Lee’s entire optical sensor, its structural-color readout, or every fabrication condition into Shachar. Rather, Lee is relied upon for its specific teaching of surface-supported, self-assembled M13-phage fiber bundles carrying analyte-binding recognition sites. Shachar itself supplies the bridge to that recognition technology because Shachar expressly teaches the use of phage-display procedures to improve specificity and capture statistics in the disclosed SAW biosensor. The rejection therefore does not rely solely on the fact that Lee’s M13 bundles existed; it identifies why one of ordinary skill considering Shachar’s own phage-display teaching would have looked to a concrete M13 phage-display sensing implementation such as Lee. Applicant’s argument that Lee’s optical embodiment would require different design considerations does not demonstrate that the relied-upon M13 recognition material would have been unsuitable as biological recognition material in Shachar’s functionalized sensing region. The modification employs Lee’s M13 material for its disclosed recognition and surface-supported sensing functions, rather than requiring Lee’s optical transduction mechanism to replace Shachar’s acoustic transduction mechanism.
Applicant repeatedly emphasizes that neither Shachar nor Lee teaches a roughened surface affecting anchoring of the fiber bundles and argues that the feature is more than an arbitrary surface characteristic. That argument is specifically addressed by Viespe in the current rejection. Viespe is not relied upon merely for the proposition that rough surfaces existed. Viespe experimentally studies biological immobilization on gold SAW sensing surfaces having different morphologies and roughnesses. Viespe reports gold surfaces having roughness values of approximately 0.7 nm, 6 nm, and 30 nm and compares a relatively smooth dense gold surface against porous/rougher gold surfaces. Viespe reports substantially greater acoustic shifts after enzyme immobilization on the porous surfaces and explains that the increased response resulted from a larger mass of biological material being immobilized on the nanoporous gold. Viespe further states that sensing properties depend upon the amount of immobilized biological material as well as its morphology and roughness. Thus, Viespe provides precisely the technical relationship Applicant contends was absent from the former rejection: surface morphology/roughness affects biological immobilization at a SAW sensing surface.
When that teaching is applied to Lee’s surface-supported M13 bundles on Taylor’s gold sensing region, the modification has an articulated technical purpose—affecting and increasing biological immobilization at the sensing interface. The rationale does not depend upon the unsupported proposition that any rough surface would inherently be desirable. Viespe also provides a reasonable expectation of success because it experimentally demonstrates biological material immobilization on roughened/nanoporous gold in an operating SAW sensor. The present rejection therefore expressly states that the reason for using the roughened morphology is not merely that roughened surfaces were known, but Viespe’s taught biological-immobilization and SAW-sensitivity benefit. Applicant’s argument concerning lack of a technical reason for the claimed roughness/anchoring relationship is therefore not persuasive against the present rejection.
Applicant argues that Shachar merely compensates for temperature variation using a reference lane after environmental effects occur and does not actively monitor and control temperature and humidity in the sensing area during measurement. Applicant further argues that Lee merely demonstrates humidity-responsive physical behavior of the M13 matrix and does not actively control the environment. Again, the present rejection does not rely upon either Shachar or Lee alone for the claimed active temperature-and-humidity control. The current rejection relies on Wen. Wen teaches a Love-wave acoustic sensor measurement system having a closed air chamber containing the sensor module, temperature-control module, and humidity-control module. Wen teaches a semiconductor refrigerator and associated control circuits for temperature control, and a humidity-control module containing both a humidification unit and a dehumidifying unit. Wen further teaches a DHT11 sensor and microprocessor that simultaneously measure temperature and humidity while the spectral characteristics of the acoustic sensor are being measured. Accordingly, Wen provides both monitoring and active control of temperature and humidity in the environment containing the acoustic sensor during measurement.
Applicant’s distinction between Shachar’s differential/reference-lane compensation and the claimed active environmental control therefore does not defeat the rejection. The Office does not equate Shachar’s reference lane with the claimed condition-control circuit. Wen supplies the active environmental-control teaching. Shachar concerns acoustic sensing, for which environmental conditions can affect acoustic response, and Lee expressly teaches that the proposed M13 fiber bundles swell or contract as humidity changes. Thus, after the M13 bundles are employed as the recognition material, uncontrolled humidity provides a specific source of variation in the proposed sensing layer itself. Wen supplies the known acoustic-sensor solution of simultaneously monitoring and controlling temperature and humidity during measurement. The modification would reduce uncontrolled environmental variation and permit target-induced acoustic changes to be distinguished from changes attributable to temperature or humidity.
Applicant argues that even assuming each feature is separately known, the prior art fails to disclose the specific physical and functional relationship among the roughened pad, M13 fiber-bundle sensing layer, opposed IDTs, and controlled temperature/humidity environment. The argument is not persuasive because the obviousness rejection is based upon what the combined teachings would have suggested to one of ordinary skill, not whether one reference literally illustrates the final integrated device. Taylor teaches the functional SAW-chip geometry: a piezoelectric quartz chip, opposed input/output interdigitated electrodes, and a localized gold biological sensing region between them. Lee teaches surface-supported analyte-binding M13 fiber bundles. Viespe teaches that roughening/nanostructuring a gold SAW immobilization surface affects and increases biological material immobilization. Wen teaches temperature and humidity measurement and active regulation in an operating Love-wave acoustic-sensor environment. Shachar supplies the primary SAW architecture and, importantly, expressly identifies phage-display recognition as desirable for improving specificity and capture statistics.
The proposed combination therefore does not arbitrarily assemble unrelated features. Each modification addresses the same biological-acoustic sensing interface: Shachar supplies the acoustic biosensing framework and phage-display motivation; Taylor supplies a concrete, functioning gold sensing region on a piezoelectric SAW biochip; Lee supplies the particular analyte-binding M13 fiber-bundle recognition layer toward which Shachar’s phage-display teaching directs the artisan; Viespe supplies a known SAW gold-surface modification that affects biological immobilization; and Wen supplies control of environmental variables capable of affecting both acoustic propagation and Lee’s humidity-responsive M13 sensing material.
Applicant asserts that the previous combination did not identify a reason one of ordinary skill would have selected Lee’s M13 phage matrix, localized it in the SAW sensing region, roughened the pad to affect anchoring, and controlled temperature and humidity during measurement. The current rejection expressly provides such reasons. 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, Shachar expressly directs one of ordinary skill toward phage-display recognition to improve specificity and capture statistics; Taylor teaches a functioning gold-film biological SAW sensing region between opposed input and output IDTs on a piezoelectric quartz chip; Lee teaches surface-supported analyte-binding M13 phage fiber bundles and their high-density presentation of binding ligands; Viespe expressly teaches that increasing the roughness/porosity of a gold SAW biological immobilization surface increases biological immobilization and improves sensor response; and Wen teaches active temperature and humidity monitoring and control in an acoustic Love-wave measurement system. Lee additionally teaches that its M13 fiber bundles change with ambient humidity. These teachings supply specific reasons for each proposed modification and a reasonable expectation that the modifications would perform their known functions in the resulting SAW sensing system.
Applicant argues that the rejection allegedly recognizes separate problems only after reading amended claim 1 and then searches for separate references to reconstruct the claimed system. The argument is not persuasive. 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 motivation for the modifications is independently supplied by the prior art rather than Applicant’s disclosure.
First, Shachar itself teaches phage-display recognition to improve specificity and capture statistics, providing an express bridge from the primary SAW biosensor to phage-display sensing material. Second, Taylor independently demonstrates the proposed piezoelectric SAW biochip geometry with a defined gold biological sensing region between opposed input and output IDTs. Third, Lee independently teaches analyte-recognizing M13 phages self-assembled into surface-supported fiber bundles. Fourth, Viespe independently teaches that roughness/porosity of the gold biological immobilization surface in a SAW sensor affects the amount of biological material immobilized and sensor response. Fifth, Wen independently teaches active temperature and humidity control during acoustic sensor measurement, while Lee independently establishes that M13 fiber bundles physically respond to humidity. These are not technical problems or advantages supplied only by Applicant. They are expressly recognized by the prior art itself. The current rationale therefore does not merely use claim 1 as a checklist; rather, it explains why the references themselves would have led one of ordinary skill from Shachar’s SAW biosensor toward the proposed modifications. The Office also expressly addresses reasonable expectation of success. Taylor demonstrates the relevant biological SAW-chip geometry; Lee demonstrates analyte-recognizing M13 bundles on a substrate; Viespe demonstrates biological immobilization on roughened/nanoporous gold in a SAW sensor; and Wen demonstrates simultaneous temperature/humidity measurement and regulation in an operating Love-wave system. The respective modifications preserve the basic acoustic sensing mechanism and use the teachings for the functions for which the references themselves teach them. Accordingly, Applicant’s hindsight argument is not persuasive.
Applicant devotes substantial argument to Berg and asserts that Berg merely demonstrates conventional integration of a SAW sensor into a chip and fails to provide the roughened-pad/M13-bundle interface or the claimed environmental-control arrangement. Those arguments do not overcome the present rejection because Berg is no longer relied upon in the current rejection. Taylor is instead applied for the particular compact SAW biochip/gold sensing-region geometry corresponding to the amended pad arrangement. Accordingly, Applicant’s arguments of the particular function previously assigned to Berg do not rebut the newly stated rejection.
Applicant argues that the number and nature of modifications demonstrate impermissible reconstruction rather than obviousness. The number of references does not itself establish nonobviousness. More importantly, the present rejection does not rely upon the number of references as evidence of obviousness; it provides a technical reason for each modification. In response to applicant’s argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991). Here, the references are not combined merely because each happens to contain a claim element. Their teachings are technically interrelated: Shachar, Taylor, Viespe, and Wen concern acoustic/SAW sensor technology; Taylor and Viespe concern biological sensing surfaces in SAW devices; Shachar expressly identifies phage-display recognition; Lee supplies the specific M13 phage-display fiber-bundle implementation; and Lee’s humidity responsiveness directly provides additional reason for the environmental control taught by Wen. Thus, the combination is supported by articulated technical relationships among the references rather than the bare accumulation of known elements.
Applicant argues that Gaso does not disclose or cure the alleged deficiencies concerning the roughened pad/M13-phage interface or condition-control circuit of claim 1. That argument is correct as to the limited proposition that Gaso is not relied upon for those claim 1 features, but it does not overcome the rejection. The present rejection relies upon Shachar, Taylor, Lee, Viespe, and Wen for the subject matter inherited by claim 4. Gaso is applied only for the additional claim 4 limitation concerning the control circuit receiving acoustic-response measurements and using calibration data to generate a measurement signal indicating analyte concentration. Gaso teaches a sensor circuit and a Control and Communication System; teaches acquisition of changes in phase and amplitude resulting from perturbations of the acoustic sensor; teaches standard solutions having known analyte concentrations; and teaches generating standard curves by plotting measured voltage-phase increments against the logarithm of analyte concentration. The rejection further explains why one of ordinary skill would have used that calibration approach: it converts the acoustic-response measurement already generated by the modified Shachar system into a quantitative concentration-indicating output without altering the underlying acoustic-sensing mechanism. Gaso experimentally demonstrates that approach in an operating Love-wave immunosensor, providing a reasonable expectation of success. Accordingly, Applicant’s argument that Gaso does not cure the independent-claim limitations is not persuasive because Gaso is not relied upon for those limitations.
Applicant generally argues that dependent claims 2–4, 6–8, and 10 are patentable at least by virtue of their dependency from amended claim 1 and their additional limitations. The argument has been considered but is not persuasive. The rejection above addresses the additional limitations of each dependent claim separately. Thus, Applicant’s general reliance on dependency from claim 1 and the presence of additional limitations does not overcome the specific teachings applied to those limitations.
Applicant notes that claims 5, 9, and 11–15 have been canceled. Accordingly, all previous rejections directed solely to those canceled claims are moot and are not maintained.
Conclusion
Applicant’s amendments and arguments have been fully considered. The prior objection concerning inconsistent use of reference numeral 335 is maintained because Applicant’s amendment to paragraph [0021] does not reconcile the remaining specification and drawing disclosures identifying numeral 335 as a different element. A further objection is made concerning numeral 355 because Figure 3 identifies that numeral without corresponding identification or description in the written specification.
The previous rejection of canceled claim 5 under 35 U.S.C. 112(b) is withdrawn. The previous rejections of claims 6 and 7 under 35 U.S.C. 112(d) are also withdrawn because amended claims 6 and 7 now further limit claim 3. A new/updated rejection of claim 6 under 35 U.S.C. 112(b) is made for the ambiguity created by the relationship between the recited substrate surface and the pad-supported sensing layer.
Applicant’s arguments concerning the previous §103 combination also do not overcome the rejection presently made. The current rejection expressly accounts for the amended limitations: Taylor provides the defined gold SAW sensing-region/pad implementation between opposed IDTs; Lee provides surface-supported, analyte-binding M13-phage fiber bundles; Viespe supplies the technical teaching that roughening/nanostructuring the biological immobilization surface affects biological immobilization and SAW response; and Wen supplies active temperature-and-humidity monitoring and control during acoustic measurement. Shachar remains the primary SAW reference and independently supplies an express reason to employ phage-display recognition. Accordingly, Applicant’s request for withdrawal of the prior-art rejections and allowance of claims 1–4, 6–8, and 10 is not persuasive, and the rejections set forth in this Final Office Action are maintained as stated herein.
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 ELIZABETH OGUNTADE whose telephone number is (571)272-6802. The examiner can normally be reached Monday-Friday 6:00 AM - 3 PM.
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, Bao-Thuy Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 September 15, 2026
Prosecution Insights