DETAILED CORRESPONDENCE
Summary
This is the initial Office Action based on the Davis, et al. application filed with the Office on 28 February 2024.
Claims 1-20 are currently pending and have been fully considered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is the US National Stage Application of an International Patent Application, PCT/GB2022/052282, files on 8 September 2022, which claims priority to a United Kingdom Patent Application, GB 2112927.5, filed on 10 September 2021. Therefore, 10 September 2021, is the effective filing date of the instant application.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted regarding the present application filed on 29 October 2024, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the Examiner.
Specification
The disclosure is objected to because of the following informalities: on page 8, at lines 22-23, the instant specification recites a number of abbreviations, “… TRIG; GPT; HSPA1 B; IGFBP2; LEP; ADIPOQ; CCL2; ENG; HP; IL2RA; SCp; SHBG; TIMP2 …”. However, these abbreviation are not, by themselves, proper identification for target protein molecules.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 9 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.
Instant claim 9 recites in part, “the target protein molecules are selected from the group … TRIG; GPT; HSPA1 B; IGFBP2; LEP; ADIPOQ; CCL2; ENG; HP; IL2RA; SCp; SHBG; … TIMP2.” These abbreviations are not, by themselves, proper identification for target protein molecules. Additionally, claim 9 recites some possible target protein molecules in parathesis. It is unclear if these limitation in parathesis are exemplary, and thus not clear if they are being positively recited as limitations. Therefore, claim 9 is indefinite for failing to particularly point out and distinctly claim the subject matter.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-8, 10, 11, 13, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by a published Chinese Patent Application, CN 111537584 A, to Wan et al. (hereinafter, “Wan”; references to English machine translation of application).
Regarding claim 1, Wan discloses an electrochemical method of sensing target protein molecules, which method comprises:
attaching redox active tagging moieties to protein molecules in a carrier medium that may contain said target protein molecules, wherein the redox active tagging moieties non-specifically bind to protein molecules ([0029]: “… antimicrobial peptide (Magainin I) and methylene blue (MB) to synthesize stable methylene blue-nanoflowers through a one-step reaction. Magainin I, an antimicrobial peptide, is a polypeptide that can recognize bacterial surface membrane proteins. This property can be used to successfully identify and isolate foodborne pathogens. Methylene blue (MB) can be used as an electrocatalytic signal tag to synthesize a nanopolymer that can recognize the characteristics of foodborne pathogens, thereby amplifying the signal.”; [0030]: “The methylene blue nanoflowers specifically bind to the target foodborne pathogens, forming a sandwich structure on the Au electrode, thereby functioning as a methylene blue signal tag.”);
contacting the carrier medium with an electrode that comprises receptors that specifically bind to target protein molecules that are bound to the redox active tagging moieties ([0030]: “… the target aptamer AP modified with thiol groups is fixed on the Au electrode through Au-S bonds. The aptamer can specifically grasp the target and stably cover the surface of the Au electrode.”); and
electrochemically determining whether target protein molecules are present in the carrier medium ([0030]: “Under the action of the electrolyte, a current signal is generated, which can be used for the quantitative detection of foodborne pathogens.”).
Regarding claim 2, Wan teaches The method of claim 1, wherein step (C) comprises determining the concentration of the target protein molecules in the carrier medium. ([0041]: “Figure 3B shows the linear analysis of the effect of Escherichia coli O157:H7 concentration (10<sup>2</sup>～10<sup>7</sup>cfu/mL) on hydrogen detector readings.”).
Regarding claims 3 and 4, Wan teaches The method of claim 1, wherein the carrier medium that may contain said target protein molecules is a biological sample & the carrier medium contains protein molecules that are different from the target protein molecules ([0069]: “After incubation, use differential pulse voltammetry (DPV) to quantitatively detect foodborne pathogens.”; food is known to contain a number of different proteins.)
Regarding claim 5, Wan teaches Magainin I as the recognition element for the redox active tagging moiety ([0029]). Magainin I inherently has broad spectrum activity against a number of bacteria, expressing a number of different membrane proteins.
Regarding claim 6, Wan teaches wherein the receptors: (i) specifically bind to target protein molecules that are bound to the redox active tagging moieties; and (ii) do not specifically bind to protein molecules that are different from the target protein molecules and that are bound to the redox active tagging moieties ([0030]: “Aptamers (APs) are single-stranded oligonucleotide sequences that exhibit high affinity and specificity for target molecules by forming unique secondary and tertiary structures.”).
Regarding claims 7 and 8, Wan teaches receptors are aptamers ([0030]: “Aptamers (APs) are single-stranded oligonucleotide sequences that exhibit high affinity and specificity for target molecules by forming unique secondary and tertiary structures.”).
Regarding claim 10, Wan teaches wherein the redox active tagging moieties comprise a redox active portion and a protein-binding portion ([0029]: “… this invention utilizes antimicrobial peptide (Magainin I) and methylene blue (MB) to synthesize stable methylene blue-nanoflowers …”).
Regarding claim 11, Wan teaches wherein the redox active tagging moieties comprise a redox active portion that is … methylene blue ([0029]: “… this invention utilizes antimicrobial peptide (Magainin I) and methylene blue (MB) to synthesize stable methylene blue-nanoflowers …”).
Regarding claim 13, Wan teaches wherein said electrochemically determining in step (C) comprises determining whether target protein molecules are present in the carrier medium by differential pulse voltammetry ([0018]: “ … use differential pulse voltammetry to quantitatively detect foodborne pathogens.”).
Regarding claim 16, Wan teaches a kit for use in the method of claim 1, which comprises:
redox active tagging moieties that non-specifically bind to protein molecules ([0029]: “… antimicrobial peptide (Magainin I) and methylene blue (MB) to synthesize stable methylene blue-nanoflowers through a one-step reaction. Magainin I, an antimicrobial peptide, is a polypeptide that can recognize bacterial surface membrane proteins. This property can be used to successfully identify and isolate foodborne pathogens. Methylene blue (MB) can be used as an electrocatalytic signal tag to synthesize a nanopolymer that can recognize the characteristics of foodborne pathogens, thereby amplifying the signal.”; [0030]: “The methylene blue nanoflowers specifically bind to the target foodborne pathogens, forming a sandwich structure on the Au electrode, thereby functioning as a methylene blue signal tag.”); and
an electrode that comprises receptors that specifically bind to target protein molecules that are bound to the redox active tagging moieties ([0030]: “… the target aptamer AP modified with thiol groups is fixed on the Au electrode through Au-S bonds. The aptamer can specifically grasp the target and stably cover the surface of the Au electrode.”)
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 9 is rejected under 35 U.S.C. 103 as being unpatentable over Wan in view of a published paper by Negahdary, et al. (“An aptamer-based biosensor for Troponin I detection in diagnosis of myocardial infarction”, Journal of Biomedical Physics & Engineering, 8(2): p. 167-178, June 2018; hereinafter, “Negahdary”).
Regarding claim 9, Wan teaches the limitations of claim 1, as outlined above.
Wan does not teach the claimed method has a target protein molecule that is among those listed in instant claim 9.
However, Negahdary discloses an electrochemical aptamer-based sensor utilizing an aptamer which binds cardiac troponin I (Abstract).
At the time of the filing of the instant application, it would have been obvious to one of ordinary skill in the art to have made the simple substitution of the taught aptamer in Wan with the cardiac troponin I-sensitive aptamer taught by Negahdary with predictable success.
Claims 14, 15, and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wan in view of a published paper by O. Sadik, et al. (“Status of biomolecular recognition using electrochemical techniques”, Biosensors & Bioelectronics, 24(9): p. 2749-2765, May 2009; hereinafter, “Sadik”).
Regarding claim 14, Wan teaches the limitations of claim 1, as outlined above.
Wan does not teach the claimed method is carried out in a microfluidic device.
However, Sadik discloses the application of biomolecular recognition for electrochemical detection, wherein is taught the electrochemical microfluidic technology consisting of microfluidic mixer, valves, pumps, channels, chambers in a single chip device have been commercialized (5. Conclusions and future trends, p. 2763).
At the time of the filing of the present application, it would have been obvious to one of ordinary skill in the art that the method disclosed by Wan could have been performed within a microfluidic device, as this is state of the art in electrochemical system, as demonstrated by Sadik, wherein such utilization would have the advantages of dealing with smaller reagent quantities, which would provide economical value.
Regarding claim 15, Wan teaches the limitations of claim 1, as outlined above.
Wan does not teach the claimed method carried out in a format with at least two different electrodes to determine at least two different target protein molecules present in the carrier medium.
However, Sadik discloses the application of biomolecular recognition for electrochemical detection, wherein is taught the multianalyte detection in complex clinical and environmental samples (Abstract).
At the time of the filing of the present application, it would have been obvious to one of ordinary skill in the art that the method disclosed by Wan could have been performed for multianalyte detection by addition to the platform of a duplicate working electrode (MPEP 2144.04 (VI)(B)) with a different aptamer receptor, as suggested by the Sadik reference, as this would allow for monitoring of multiple proteins in a sample.
Regarding claim 17, Wan teaches the limitations of claims 1 and 16, as outlined above. Wan further teaches a working electrode ([0055]).
Wan does not teach the claimed method is carried out in a microfluidic device.
However, Sadik discloses the application of biomolecular recognition for electrochemical detection, wherein is taught the electrochemical microfluidic technology consisting of microfluidic mixer, valves, pumps, channels, chambers in a single chip device have been commercialized (5. Conclusions and future trends, p. 2763).
At the time of the filing of the present application, it would have been obvious to one of ordinary skill in the art that the method disclosed by Wan could have been performed within a microfluidic device, as this is state of the art in electrochemical system, as demonstrated by Sadik, wherein such utilization would have the advantages of dealing with smaller reagent quantities, which would provide economical value.
Regarding claim 18, Wan teaches an auxiliary (counter) electrode and a reference electrode ([0055]).
Regarding claim 19, Wan does not teach a microfluidic mixer.
However, Sadik discloses the application of biomolecular recognition for electrochemical detection, wherein is taught the electrochemical microfluidic technology consisting of microfluidic mixer, valves, pumps, channels, chambers in a single chip device have been commercialized (5. Conclusions and future trends, p. 2763).
At the time of the filing of the present application, it would have been obvious to one of ordinary skill in the art that the method disclosed by Wan could have been performed within a microfluidic device, including a microfluidic mixer, as this is state of the art in electrochemical system, as demonstrated by Sadik, wherein such utilization would have the advantages of dealing with smaller reagent quantities, which would provide economical value.
Regarding claim 20, Wan teaches the limitations of claims 1 and 16, as outlined above.
Wan does not teach the claimed method carried out in a format with at least two different electrodes to determine at least two different target protein molecules present in the carrier medium.
However, Sadik discloses the application of biomolecular recognition for electrochemical detection, wherein is taught the multianalyte detection in complex clinical and environmental samples (Abstract).
At the time of the filing of the present application, it would have been obvious to one of ordinary skill in the art that the method disclosed by Wan could have been performed for multianalyte detection by addition to the platform of a duplicate working electrode (MPEP 2144.04 (VI)(B)) with a different aptamer receptor, as suggested by the Sadik reference, as this would allow for monitoring of multiple proteins in a sample.
Allowable Subject Matter
Claim 12 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The Wan reference is considered the closet prior art to the instant claims. However, Wan does not anticipate nor render obvious the protein binding portion of the redox active tagging moieties as being any of an arenediazonium group, an azlactone group, a vinyl sulfone group, an NHS-ester group and/or an isothiocyanate, as required by instant claim 12.
Interview with the Examiner
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN C BALL whose telephone number is (571)270-5119. The examiner can normally be reached M - F, 9 am - 5:30 pm.
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/J. Christopher Ball/ Primary Examiner, Art Unit 1795