DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
Regarding limitations recited in claims 25-39 which are directed to a manner of operating the disclosed system, it is noted that neither the manner of operating a disclosed device nor material or article worked upon further limit an apparatus claim. Said limitations do not differentiate apparatus claims from prior art. See MPEP § 2114 and 2115.
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.
Claims 31 and 38 are 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 31 recites the limitation "the first sensing unit" in line 2. There is insufficient antecedent basis for this limitation in the claim. The Applicants are advised, amending the limitation to recite :”the first testing unit” is one way to resolve the indefiniteness issues.
Claim 31 recites the limitation "the second sensing unit" in line 3. There is insufficient antecedent basis for this limitation in the claim. The Applicants are advised, amending the limitation to recite :”the second testing unit” is one way to resolve the indefiniteness issues.
Claim 38 recites the limitation "the first sensing unit" in line 1. There is insufficient antecedent basis for this limitation in the claim. The Applicants are advised, amending the limitation to recite :”the first testing unit” is one way to resolve the indefiniteness issues.
Appropriate corrections are required.
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.
Claim(s) 25-29, 32-37, and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tuteja et al. (Graphene-gated biochip for the detection of cardiac marker Troponin I, cited in IDS filed 06/20/2024), in view of Elnathan et al. (Biorecognition Layer Engineering: Overcoming Screening Limitations of Nanowire-Based FET Devices, cited in IDS filed 06/20/2024) and Rasooly et al. (US 2011/0217763 A1, cited in IDS filed 06/20/2024).
Regarding claims 25, 26, and 32, Tuteja discloses a system for detecting a panel of biomarkers in a biological sample based on an applied alternating current, comprising: a sensor (Scheme 1; Fig. 5; pg. 154/3.3. Assay development on graphene gated biochip) comprising:
a first testing unit (Scheme 1) that includes:
a first functionalized graphene layer that includes a first graphene layer and first antibodies couple to the first graphene layer, wherein the first antibodies exhibit specific binding to troponin or an isoform of troponin (see: anti-cTnI antibody functionalized graphene), and
first electrical conductors electrically coupled to the first functionalized graphene layer, wherein the first electrical conductors are configured to measure a first electrical property of the first functionalized graphene layer (see: S and D electrodes),
a second testing unit (pg. 154/3.3. Assay development on graphene gated biochip) including:
a second functionalized graphene layer that includes a second graphene layer and second antibodies coupled to the second graphene layer, wherein the second antibodies exhibit specific binding to a different second biomarker (see: anti-myoglobin antibody functionalized graphene), and
second electrical conductors electrically coupled to the second functionalized graphene layer, wherein the second electrical conductors are configured to measure a second electrical property of the second functionalized graphene layer (see: S and D electrodes),
a fluidic delivery device that includes an inlet configured to receive the biological sample and an outlet configured to deliver a first portion of the biological sample to the first testing unit and a second portion of the biological sample to the second testing unit (Scheme 1, see: inlet and outlet), and
an analyzer coupled to the first testing unit and the second testing unit and configured to determine a presence of the first biomarker based on the first electrical property of the first functionalized graphene layer (pg. 150/2.5.cTnI quantification with graphene-gated biochip, see: Keithley semiconductor parameter analyzer; Fig. 6, see: calibration curves).
Tuteja does not explicitly disclose determining the presence of the second biomarker based on the second electrical property of the second functionalized graphene layer and the second biomarker including a second isoform of troponin.
Elnathan teaches an analogous nanostructure based FET device (Figure 2) comprising a SiNW-FET functionalized with anti-cTnT (Figure 8) and anti-cTnI (pg. 5253/col. 2/para. 2).
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to functionalize a second set of the plurality of sensors in the device disclosed by Tuteja, with anti-cTnT taught by Elnathan, since such a modification would have provided for a sensor capable of detecting both cTnI and cTnT, which Elnathan teaches would have been advantageous as both biomarkers are established as useful for the diagnosis of acute myocardial infarction. Additionally, it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice. In re Leshin, 125 USPQ 416.
Modified Tuteja does not explicitly disclose the first testing unit, the second testing unit, and the fluidic delivery device being integrated into a single sensor, wherein the fluidic delivery device comprises a plurality of channels in fluidic communication with the first testing unit and the second testing unit.
Rasooly teaches an analogous biosensor comprising a plurality of functionalized bioFETs arranged in parallel (Fig. 2).
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention to combine the elements of the device disclosed by modified Tuteja into a single device, as taught by Rasooly, since making elements integral is generally recognized as being within the level of ordinary skill in the art. In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965). Additionally, one of ordinary skill in the art, before the effective filing date of the claimed invention, would have been led by the applied references to forgo use of separate modules, along with their function and benefit, where doing so is technically feasible and would reduce cost. See In re Thompson, 545 F.2d 1290, 1229, 188 USPQ 365, 367 (CCPA 1976).
Regarding claim 27, modified Tuteja further discloses the first testing unit is configured to detect the first biomarker in anti coagulated whole blood (Tuteja: pg. 150/2.5. cTnI quantification with graphene-gated biochip, see: anti-cTnI antibody covalently immobilized on the surface of activated carboxylated graphene) and the second testing unit is configured to detect the second biomarker in anti coagulated whole blood (Elnathan: Figure 8, see: anti-cTnT).
Regarding claim 28, modified Tuteja further discloses the biological sample is blood plasma (Tuteja: pg. 154/4. Conclusion, see: blood samples).
Regarding claim 29, modified Tuteja further discloses the first antibodies includes a control antibody (Tuteja: pg. 154/3.3. Assay development on graphene gated biochip, see: developed control sensors which are incubated with non-specific antibodies).
Regarding claim 33, modified Tuteja further discloses the analyzer is configured to determine a quantity of the first or second biomarkers (Tuteja: pg. 150/2.5.cTnI quantification with graphene-gated biochip, see: Keithley semiconductor parameter analyzer; Fig. 6, see: calibration curves).
Regarding claim 34, modified Tuteja further discloses the first antibodies are coupled to a portion of the surface of the first graphene layer and the second antibodies are coupled to a portion of the surface of the second graphene layer (Tuteja: Scheme 1, see: anti-cTnI antibody functionalized graphene).
Regarding claims 35-37, modified Tuteja does not explicitly disclose the portion of the surface of the first and second graphene layer is 100 percent of the graphene layer. As the maximum detection limit is a variable that can be modified, among others, by adjusting said percent of the surface of the first and second graphene layer coupled with antibodies, with said maximum detection limit increasing as the percent of the first and second graphene layer coupled with antibodies is increased, the precise percent of the surface of the first and second graphene layer coupled with antibodies would have been considered a result effective variable by one having ordinary skill in the art, before the effective filing date of the claimed invention. As such, without showing unexpected results, the claimed percent of the first and second graphene layer coupled with antibodies cannot be considered critical. Accordingly, one of ordinary skill in the art, before the effective filing date of the claimed invention, would have optimized, by routine experimentation, the percent of the first and second graphene layer coupled with antibodies in the apparatus of modified Tuteja to obtain the desired maximum detection limit (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Regarding claim 39, modified Tuteja further discloses the analyzer is configured to modulate an electrical property of the first and second graphene layer (pg. 150/2.5. cTnI quantification with graphene-gated biochip, see: Keithley semiconductor parameter analyzer).
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tuteja et al. (Graphene-gated biochip for the detection of cardiac marker Troponin I, cited in IDS filed 06/20/2024), in view of Elnathan et al. (Biorecognition Layer Engineering: Overcoming Screening Limitations of Nanowire-Based FET Devices, cited in IDS filed 06/20/2024) and Rasooly et al. (US 2011/0217763 A1, cited in IDS filed 06/20/2024), as applied to claim 25 above, and further in view of Labroo et al. (Graphene nano-ink biosensor arrays on a microfluidic paper for multiplexed detection of metabolites, cited in IDS filed 06/20/2024).
Regarding claim 30, Tuteja further discloses the fluidic delivery device includes a central capillary channel having an input port for receiving the biological sample (Scheme 1, see: inlet, outlet, and channel which couples them).
Modified Tuteja does not explicitly disclose a first capillary channel extending from the central capillary channel, and a second capillary channel extending from the central capillary channel, wherein the first capillary channel extends to the first testing unit and the second capillary channel extends to the second testing unit.
Labroo teaches an analogous graphene based biosensor array integrated into a multiplexed microfluidic device comprising a common inlet, and a plurality of channels extending perpendicularly from the common inlet, wherein the graphene sensors are arranged at terminal ends of the plurality of channels (Fig. 1; pg. 91/col. 1/para. 2). It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the biosensor array disclosed by modified Tuteja, into a multiplexed microfluidic device as taught by Labroo, in order to provide for the detection of multiple targets rapidly and simultaneously (Labroo: ABSTRACT).
Claim(s) 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tuteja et al. (Graphene-gated biochip for the detection of cardiac marker Troponin I, cited in IDS filed 06/20/2024), in view of Elnathan et al. (Biorecognition Layer Engineering: Overcoming Screening Limitations of Nanowire-Based FET Devices, cited in IDS filed 06/20/2024) and Rasooly et al. (US 2011/0217763 A1, cited in IDS filed 06/20/2024), as applied to claim 25 above, and further in view of Zheng et al. (Fabrication of Ultrasensitive Field-Effect Transistor DNA Biosensors by a Directional Transfer Technique Based on CVD-Grown Graphene, cited in IDS filed 06/20/2024).
Regarding claim 31, Tuteja further discloses a first calibration sensing element configured to calibrate the first sensing unit (pg. 150/2.3. Spectroscopic/morphological characterization of synthesized graphene, see: Ag/AgCl reference electrode).
Modified Tuteja does not explicitly disclose a second calibration sensing element configured to calibrate the second sensing unit.
Zheng teaches an analogous biosensor array comprising a plurality of functionalized graphene field-effect transistor (Figure 1), each comprising a silver wire reference electrode (pg. 16955/Electrical Measurements, see: silver wire reference electrode as a gate electrode). It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate additional sensors and respective reference electrodes in the device disclosed by modified Tuteja, as taught by Zheng, to provide for redundancies and parallel sensing functionality, as well as providing for a consistent reference potential from each sensor having a reference electrode spaced at a consistent distance from the sensing surface. Additionally, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. In re Harza, 124 USPQ 378, 380 (CCPA 1960). Further, it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. St. Regis Paper Co. v. Bemis Co., 193 USPQ 8.
Claim(s) 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tuteja et al. (Graphene-gated biochip for the detection of cardiac marker Troponin I, cited in IDS filed 06/20/2024), in view of Elnathan et al. (Biorecognition Layer Engineering: Overcoming Screening Limitations of Nanowire-Based FET Devices, cited in IDS filed 06/20/2024) and Rasooly et al. (US 2011/0217763 A1, cited in IDS filed 06/20/2024), as applied to claim 25 above, and further in view of Huang et al. (Graphene-based biosensors for detection of bacteria and their metabolic activities, cited in IDS filed 06/20/2024).
Regarding claim 38, modified Tuteja does not explicitly disclose the first sensing unit further includes a passivation layer configured to passivate a non-functionalized portion of the first functionalized graphene layer, wherein the non-functionalized portion of the first functionalized graphene layer includes a portion of the surface of the first graphene layer that is not coupled with the antibodies.
Huang teaches an analogous graphene field-effect transistor biosensor comprising a layer of Tween-20 to passivate the uncoated graphene areas (Fig. 2; pg. 12359/Functionalization of graphene device).
It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate a Tween-20 layer onto the non-functionalized portions of the graphene layers in the device disclosed by modified Tuteja, as taught by Huang, since such a modification would have improved sensor durability and increased sensor specificity by preventing non-specific binding to the non-functionalized graphene surface (Huang: pg. 12359-12361/Results and discussion).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J EOM whose telephone number is (571)270-7075. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM).
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/ROBERT J EOM/ Primary Examiner, Art Unit 1797
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