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 .
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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/12/2026 has been entered.
Priority
This is a U.S. application filed on 03/23/2022 which claims priority to U.S. Provisional Application No. 63/165,372 filed on 03/24/2021.
Claim Status
The Applicant amended claims 1 and 6 and noted that no new matter is added. The Applicant cancelled claims 2, 5, 7-9 and 14-19. Claims 3-4 and 10-12 are original. Claims 13 and 20-21 are previously presented.
Thus, claims 1, 3-4, 6, 10-13 and 20-21 are under examination.
Withdrawn Objections and Rejections
The previous rejection of claims 7-9 under 35 U.S.C. 102(a)(2), as being anticipated by Muthukumar et al. (US 2021/0325380 A1, Priority Date 04/20/2020), is withdrawn in lights of Applicant’s cancellation of the claims.
Maintained Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-4, 6, 10, 12-13 and 20-21 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Muthukumar et al. (US 2021/0325380 A1, Priority Date 04/20/2020).
Claim 1 recites:
“A system for detecting inflammation, comprising
at least one sensor comprising:
at least one port for receiving a biological sample,
a fluid distribution network in fluid communication with said at least one
port, the fluid distribution network comprising a plurality of channels,
a plurality of electrochemical cells, each cell being in fluid communication
with a respective one of the plurality of channels for receiving a
portion of said biological sample, each of said electrochemical cells comprising at
least two conductive electrodes, where at least one of said electrodes is
functionalized with at least one molecular recognition probe exhibiting specific
binding to at least one tissue damage biomarker, inflammation biomarker or genetic component associated with an inflammation biomarker,
circuitry for detecting any of a redox current flowing through said at least one
electrode and/or an electrical impedance across said electrodes in response to
interaction of said functionalized electrode with said sample and generating detection
signals in response to said detection,_
wherein the plurality of electrochemical cells comprises a first electrochemical cell
functionalized with a probe exhibiting specific binding to said inflammation biomarker and a
second electrochemical cell functionalized with a probe exhibiting specific binding to said
genetic component associated with the inflammation biomarker”.
Regarding claim 1, Muthukumar teaches a system for detecting inflammation (Abstract; [0194]). Muthukumar further teaches at least one sensor (Abstract; [0006-0007]; [0012]). Muthukumar also teaches at least one port for receiving a biological sample ([0047]; [0150]; page 35, claim 15). And Muthukumar teaches a fluid distribution network in fluid communication with at least one port [0011], “In some cases, the base module may comprise at least one receiving portion on the substrate for coupling to a discrete sensor. Additionally, the base module may comprise a plurality of receiving portions on the substrate for coupling to a plurality of discrete sensors”. Muthukumar further teaches the fluid distribution network comprising a plurality of channels ([0011], “plurality of receiving portions on the substrate for coupling to a plurality of discrete sensors”. And Muthukumar teaches a plurality of electrochemical cells, each cell being in fluid communication with a respective one of the plurality of channels for receiving portion of said biological sample ([0011]; [0035], [0130]; [0197]). Muthukumar further teaches an electrochemical cell comprising at least two conductive electrodes ([0130]; [0197]). Muthukumar also teaches that at least one of the electrodes is functionalized with at least one molecular recognition probe such as an antibody exhibiting specific binding to at least one tissue damage biomarker, inflammation biomarker or genetic component associated with an inflammation biomarker ([0017]; [0119]; [0194]; [0201]; [0268]; [0317]). Muthukumar further teaches a circuitry for detecting electron changes through at least one electrode or an electrical impedance across electrodes in response to interaction of functionalized electrode with a sample and generating detection signals in response to such detection ([0006-0007]; [0012] and [0017]). Muthukumar also teaches a first sensing device functionalized with a probe exhibiting specific binding to said inflammation biomarker such as IL-6 ([0197-0200]; [0318]). And Muthukumar teaches a second sensing device functionalized with a probe exhibiting specific binding to said genetic component associated with the inflammation biomarker ( [0171], “The sensing device 100 may be an electrochemical sensing device configured for both catalytic and affinity based detection of one or more target analytes in a sample.”; [0197-0200]; [0303], “Biomarkers exist in a variety of different forms, including antibodies, enzymes, microbes, DNA, RNA, lipids, metabolites, and proteins”; [0304]). Muthukumar teaches that a genetic component could be part of the molecular signature for a certain malady or disease [303].
Regarding claim 3, Muthukumar teaches that a probe comprises an antibody specific to a target of interest ([0119]; [0144]).
Regarding claim 4, Muthukumar teaches an analyzer that is in communication with a circuitry for receiving signals and processing the received signals to identify an onset and/or an occurrence of a cytokine storm (Sheet 23 of 29, FIG. 23, “Pathogen Detection ”, “+”, “Immune Response”; [0041]; [0046]; [0213]; [0321]; page 34, claim 11).
Claim 6 recites:
“A system for detecting inflammation comprising:
at least one sensor comprising:
at least one port for receiving a biological sample,
a plurality of electrochemical cells in fluid communication with said at least
one port for receiving said biological sample, each of said electrochemical cells
comprising at least two conductive electrodes, where at least one of said electrodes is
functionalized with at least one molecular recognition probe exhibiting specific
binding to at least one tissue damage biomarker, or an inflammation biomarker,
a plurality of channels providing said fluid communication between a
respective electrochemical cell of the plurality of electrochemical cells and the at
least one port,
circuitry for detecting any of a redox current flowing through said at least one
electrode and/or an electrical impedance across said electrodes in response to
interaction of said functionalized electrode with said sample and generating detection
signals in response to said detection,
wherein the plurality of electrochemical cells comprises a first
electrochemical cell functionalized with a probe exhibiting specific binding to said
tissue damage biomarker and a second electrochemical cell functionalized with a
probe exhibiting specific binding to said inflammation biomarker, and
an analyzer configured to receive the detection signals generated by said first and
second electrochemical cells and process said detection signals to determine whether any of
the tissue damage biomarker and the inflammation biomarker is present in the biological
sample”.
Regarding claim 6, Muthukumar teaches a system for detecting inflammation (Abstract; [0194]). Muthukumar further teaches at least one sensor (Abstract; [0006-0007]; [0012]). Muthukumar also teaches at least one port for receiving a biological sample ([0047]; [0150]; page 35, claim 15). Muthukumar further teaches a plurality of electrochemical cells in fluid communication with at least one port for receiving said biological sample ([0011]; [0035], [0130]; [0197]). And Muthukumar teaches that each of said electrochemical cells comprising at least two conductive electrodes ([0130]; [0197]). Muthukumar also teaches that where at least one of said electrodes is functionalized with at least one molecular recognition probe exhibiting specific binding to at least one tissue damage biomarker, or an inflammation biomarker ([0017]; [0119]; [0194]; [0201]; [0268]; [0317]). Muthukumar further teaches a plurality of channels providing said fluid communication between a respective electrochemical cell of the plurality of electrochemical cells and the at least one port [0011], “plurality of receiving portions on the substrate for coupling to a plurality of discrete sensors”; [0035], [0130]; [0197]. And Muthukumar teaches circuitry for detecting any of a redox current flowing through said at least one electrode and/or an electrical impedance across said electrodes in response to interaction of said functionalized electrode with said sample and generating detection signals in response to said detection ([0006-0007]; [0012] and [0017]). Muthukumar further teaches wherein the plurality of electrochemical cells comprises a first electrochemical cell functionalized with a probe exhibiting specific binding to said tissue damage biomarker and a second electrochemical cell functionalized with a probe exhibiting specific binding to said inflammation biomarker ([0017]; [0119]; [0194]; [0201]; [0268]; [0317]). Muthukumar also teaches an analyzer configured to receive the detection signals generated by first and second electrochemical cells (Sheet 14 of 29, “1422”, “Analyzer”; [0009]; [0029] and [0033]; [0107]). And Muthukumar teaches processing the generated detection signals to determine if the tissue damage biomarker is present in the biological sample (Sheet 14 of 29, “1422”, “Analyzer”; [0009]; [0107]).
Regarding claim 10, Muthukumar teaches that an inflammation biomarker can be a cytokine and a chemokine ([0318]).
Regarding claim 12, Muthukumar teaches that a chemokine is induced by interferon-γ such as IP10 ([0318]).
Regarding claim 13, Muthukumar teaches that a biological sample can be a fluid sample ([0323] and [0325]; page 34, claim 9).
Regarding claim 20, Muthukumar teaches that the biological sample comprises any of: blood and urine ([0323] and [0325]; page 34, claim 9).
Regarding claim 21, Muthukumar teaches a third electrochemical cell functionalized with a probe exhibiting specific binding to a CRP biomarker (Page 34, [0326] and claim 2; [0185], [0194]).
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 (PHOSITA) 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.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Muthukumar et al. (US 2021/0325380 A1) as applied to claim 1 above, and further in view of Liu et al. (Anal. Chem. 2010, 82, 8131–8136).
Regarding claim 11, the teachings of Muthukumar are previously discussed.
Regarding claim 11, Muthukumar does not teach that the inflammation biomarker can be interferon-γ.
Regarding claim 11, Liu teaches that the inflammation biomarker is interferon-γ (Abstract).
It would have been obvious for a PHOSITA before the effective filing date of the application to modify the testing method of Muthukumar with Liu’s teachings to include interferon-γ because Liu suggested the important role of interferon-γ in immunology, cancer research and infectious disease monitoring (Abstract) and Muthukumar further noted the antagonism of interferon by SARS-CoV-2 in viral infections [0321]. Muthukumar warned against the use of interferons in later stages of a viral infection with SARS-CoV-2 due to the risk of a cytokine storm [0321]. A skilled artisan is motivated to test for interferon-γ to predict the possibility of a cytokine storm in a patient with SARS-CoV2 infection. A PHOSITA would have had a reasonable expectation of success in combining the methods of Liu and Muthukumar because both are methods directed to detecting biomarkers of inflammation by immunoassays.
It would have been obvious for a PHOSITA to test for the presence of interferon-γ in a patient to predict the response of the patient to treatment.
Response to Arguments
Applicant's arguments filed 06/12/2026 have been fully considered but they are not persuasive.
The Applicant still alleged that amended claim 1 has limitations that are not taught by Muthukumar. Specifically, the Applicant alleged that Muthukumar does not teach the claimed "fluid distribution network," and alleged that Muthukumar does not provide a disclosure of a manifold or distinct channels that actively partition and deliver portions of that sample to respective sensors.
This argument is not persuasive because Muthukumar teaches a fluid distribution network in fluid communication with at least one port [0011], “In some cases, the base module may comprise at least one receiving portion on the substrate for coupling to a discrete sensor. Additionally, the base module may comprise a plurality of receiving portions on the substrate for coupling to a plurality of discrete sensors”.
The Applicant alleged that Muthukumar fails to teach the claimed combination of a first electrochemical cell functionalized for an inflammation biomarker and a second electrochemical cell functionalized for a genetic component associated with that inflammation biomarker.
This argument is not persuasive because Muthukumar teaches a first sensing device functionalized with a probe exhibiting specific binding to an inflammation biomarker such as IL-6 ([0197-0200]; [0318]). And Muthukumar teaches a second sensing device functionalized with a probe exhibiting specific binding to said genetic component associated with the inflammation biomarker ([0171], “The sensing device 100 may be an electrochemical sensing device configured for both catalytic and affinity based detection of one or more target analytes in a sample”; [0197-0200]; [0303], “Biomarkers exist in a variety of different forms, including antibodies, enzymes, microbes, DNA, RNA, lipids, metabolites, and proteins”; [0304]). Last, Muthukumar teaches that a genetic component is part of the molecular signature for a certain malady or disease [303].
The Applicant alleged that the Office's argument of Muthukumar teaching a combination of biomarkers is based on an improper synthesis of separate, generic disclosures. The Applicant further alleged that while Muthukumar discloses a platform capable of detecting various analytes like proteins, DNA, and RNA (e.g., Muthukumar, [0171], [0303]), it does not teach or suggest the specific, functionally linked pairing of biomarkers that is recited in the claims. The Applicant alleged that Muthukumar does not describe a system for measuring, in a single sample, a specific inflammatory protein and the genetic material that codes for it.
This argument is not persuasive because the claims do not recite linked pairing and only recites the association of two measured biomarkers. And according to broadest reasonable interpretation (BRI), association entails measuring two biomarkers without either one coding for the other.
The Applicant alleged that Muthukumar fails to teach a "plurality of channels providing fluid communication between a respective one of the plurality of electrochemical cells and the at least one port".
This argument is not persuasive because Muthukumar teaches a plurality of channels providing fluid communication between a respective one of the plurality of electrochemical cells and the at least one port ([0011], “In some cases, the base module may comprise at least one receiving portion on the substrate for coupling to a discrete sensor. Additionally, the base module may comprise a plurality of receiving portions on the substrate for coupling to a plurality of discrete sensors”).
The Applicant alleged that the teaching of Muthukumar at [0273] and [0282] is a misreading of the reference regarding the plurality of channels providing fluid communication between a respective one of the plurality of electrochemical cells and the at least one port. The Applicant alleged that these sections are structurally and functionally distinct from the claimed integrated fluidic network.
This argument is not persuasive because Muthukumar clearly states coupling one or more discrete sensors to the base module electrically and mechanically [0282]. Muthukumar also states that the base module comprises at least one receiving portion as noted in [0011].
The Applicant alleged that although Muthukumar’s analyzer reports the presence or concentration of biomarkers, it does not disclose processing these signals to make the specific diagnostic determination of a “cytokine storm”. The Applicant further alleged that Muthukumar teaches a tool for measuring analytes and not a diagnostic system for identifying this specific, complex medical condition.
This argument is not persuasive because the term “cytokine storm” is drawn to the intended use of the system with its sensors. The measuring system is evaluated on its structural and functional components, in particular, the sensors that detect the analytes, and not on how the instrument is used.
Thus, the previous rejections of claims 1, 3-4, 6, 10, 12-13 and 20-21 under 35 U.S.C. 102(a)(2), as being anticipated by Muthukumar et al. (US 2021/0325380 A1, Priority Date 04/20/2020), is still maintained.
The previous rejection of claim 11 under 35 U.S.C. 103:
The Applicant alleged that the combination of Liu and Muthukumar does not arrive at the claimed subject matter as a whole. The Applicant alleged that claim 1, upon which claim 11 depends, requires a specific combination of sensors: a first for an inflammation biomarker (such as IFN-γ from Liu) and a second for a genetic component associated with that inflammation biomarker. The Applicant further alleged that Liu teaches only the detection of the IFN-γ protein, and that it does not teach nor suggest detecting the genetic component (e.g., mRNA) for IFN-γ. Last, the Applicant alleged that Muthukumar provides a generic platform but offers no reason or motivation to create this specific protein/gene pairing.
This argument is not persuasive because none of the claims of the instant application recite detecting the genetic component that encodes for IFN-γ. Also, the association of a genetic component with a biomarker does not entail that it encodes for that marker according to the broadest reasonable interpretation. Furthermore, Muthukumar teaches measuring the nucleic acid of a pathogen and the cytokine biomarkers that are associated with a cytokine response syndrome which is one type of cytokine storm ([0311]; [0312]; [0317]). And Muthukumar teaches that a genetic component is part of the molecular signature for a certain malady or disease [303].
The Applicant alleged that neither Muthukumar nor Liu teaches an analyzer in communication with the circuitry for receiving signals and processing the signals to identify an onset and/or an occurrence of a cytokine storm.
This argument is not persuasive because the term “cytokine storm” is drawn to the intended use of the system with its sensors as previously discussed.
Thus, the previous rejection of claim 11 under 35 U.S.C. 103 as being unpatentable over Muthukumar et al. (US 2021/0325380 A1) as applied to claim 1 above, and further in view of Liu et al. (Anal. Chem. 2010, 82, 8131–8136) is maintained.
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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