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 .
Information Disclosure Statement
The information disclosure statement (IDS) filed 20 August 2024 is considered, initialed, and attached hereto.
Claim Status
Claims 1-12 are pending and under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c), there are 7 such sequences in Table 1 on pages 16 and 17 of the specification filed 20 May 2024.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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 4 and 11 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 4 recites the limitation "the solution" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim. This recitation could refer to either the physiological solution recited in line 3 of claim 4 or the aqueous solution recited in line 10 of claim 1 upon which claim 4 depends.
Claim 11 recites the limitation "the reference solution" in line 7 and lines 7-8. There is insufficient antecedent basis for this limitation in the claim. This recitation could refer to either of the two reference solutions recited in line 3 of claim 11.
Claim 11 recites the limitation "the working electrode" in line 13. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the reference electrical intensity" in lines 12-13. There is insufficient antecedent basis for this limitation in the claim. This recitation could refer to the reference electrical intensity recited in lines 11-12 of claim 11 or either of the reference electrical intensities recited as being measured from each reference solution in line 5 of claim 11.
Claim 11 recites the limitation "the reference target nucleic acid concentration" in line 14. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the electrical in" in line 18. There is insufficient antecedent basis for this limitation in the claim. This recitation could refer to the reference electrical intensity recited in lines 11-12 of claim 11, either of the reference electrical intensities recited as being measured from each reference solution in line 5 of claim 11, or the electrical intensity recited in line 11 of claim 10 upon which claim 11 depends.
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.
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.
Claims 1,3, 5-7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Horny et al. (US Patent Document Cite No 1 in IDS filed 20 August 2024)(US 2020/0263241, published 20 August 2020, effectively filed 5 October 2017), herein Horny 1, in view of Lee et al. (“Electrically Addressable Biomolecular Functionalization of Carbon Nanotube and Carbon Nanofiber Electrodes” Nano Lett 4(9), pages 1713-1716 (2004)), herein Lee, Baker et al. (“Covalently Bonded Adducts of Deoxyribonucleic Acid (DNA) Oligonucleotides with Single-Wall Carbon Nanotubes: Synthesis and Hybridization” Nano Lett 2(12), pages 1413-1417 (2002)), herein Baker, and Kandory et al. (“Gold modification by reduction of a diazonium salt prepared from an aliphatic diamine: a new useful means to remove hazardous substances” Environ Sci Pollut Res Int 29(1), pages 1239-1245 (2022), published online 4 August 2021), herein Kandory.
Regarding claim 1, Horny 1 teaches a nucleic acid probe molecule attached to a gold, platinum, or carbon electrode for the purpose of detecting single stranded target molecules (“to detect the single-stranded target molecule dispersed in the flow by electrochemistry; the assembly comprises single-stranded nucleic acid probe molecules attached to a surface of one of the electrodes […] one of the electrodes comprises at least one thin layer chosen from among a thin gold layer, a thin platinum layer and a thin carbon layer” [0036-0038]). However, Horny 1 does not teach the specific method of attaching the nucleic acid to a platinum electrode claimed in claim 1. This deficiency is made up for in the teachings of Lee, Baker, and Kandory.
Regarding claim 1, Lee teaches attaching a thiol-modified DNA oligonucleotide to a carbon nanotube electrode using sulfo SMCC (referred to as SSMCC) as a crosslinker by reacting sulfo SMCC with a primary amine on the carbon nanotube electrode and with the thiol group of the thiol-modified DNA oligonucleotide (“To achieve selective modification of individual nanotube/nanofiber electrodes […] the primary amine (−NH2) groups […] are a ubiquitous starting point for covalently linking biomolecules such as DNA, peptides, and antibodies to surfaces (17,18) and nanostructures. (2) Here, we use a heterobifunctional cross-linker SSMCC to covalently link the amino-modified nanotubes to thio-modified DNA oligonucleotides” page 1714 left column paragraph 4 through end of page; Figure 1, note SSMCC reacting with the SH modified oligonucleotide and the NH2 attached to the carbon nanotube). Furthermore, Lee teaches this attachment occurring in an aqueous solution of 0.1 M triethanolamine buffer (same paragraph continuing on page 1715). However, the combination of Horny 1 and Lee does not teach reacting sulfo SMCC with an amine of ethylenediamine specifically or attaching an ethylenediamine molecule to a platinum electrode by electro-oxidation by cyclic voltammetry. This deficiency is made up for in the teachings of Baker and Kandory.
Regarding claim 1, Baker teaches that SMCC is able to be used to attach thiol-modified DNA oligonucleotides to carbon nanotubes by reacting with an amine group of a ethylenediamine molecule attached to the carbon nanotube (Figure 1). In the context of this reaction, SMCC and sulfo SMCC are functionally equivalent and substitutable because each contain the same group being attacked by the primary amine, the main difference being that the sulfo group of sulfo SMCC improves solubility in aqueous solution. However, the combination of Horney, Lee, and Baker does not teach attaching an ethylenediamine molecule to a platinum electrode by electro-oxidation by cyclic voltammetry. This deficiency is made up for in the teachings of Kandory.
Regarding claim 1, Kandory teaches the attachment of an ethylenediamine molecule to a gold electrode comprising an electro-oxidation by cyclic voltammetry of a primary amine comprised in the ethylenediamine molecule (“Figure 1a illustrates the cyclic voltammetry (CV) on gold under cathodic reduction of the aminoethane diazonium salt in an aqueous acidic solution […] According to the literature (Wang 2010), the most probable mechanisms which
lead to the formation of 2-aminoethane-1-diazonium and its grafting on the surface of the gold electrode are the following: (1) through the preparation of the fresh sodium nitrite solution, (2) 2-aminoethane-1-diazonium formation, and (3) its cathodic reduction on a smooth gold electrode (Fig. 2)” page 1240-1 Results and discussion first paragraph; Fig. 2 (2) and (3) show ethylenediamine undergoing the reaction to graft it onto the gold electrode, yielding the same attachment shown in Fig. 1 of the drawings of the instant application). This reaction taught by Kandory, as shown at the end of Fig. 2, provides an available primary amine of an ethylenediamine molecule like that taught by Baker, except that it is attached to a gold electrode instead of a carbon nanotube electrode. Though Kandory does not explicitly teach this reaction being done with a platinum electrode, based off Horny 1’s teaching that the electrode may be gold, platinum, or carbon, one of ordinary skill in the art could make the substitution of platinum for gold and would have a reasonable expectation of success in this substitution because platinum would be expected to be able to perform the same cathodic reduction as gold in this reaction.
Therefore, regarding claim 1, the combination of Horny 1, Lee, Baker, and Kandory teach the attachment of ethylenediamine to a platinum electrode in an aqueous solution through the teachings of Kandory combined with Horny 1, the attachment of sulfo SMCC to the ethylenediamine in an aqueous solution through the teachings of Lee combined with Baker, and the attachment of a thiol-modified nucleic acid to the sulfo SMCC in an aqueous solution through the teachings of Lee combined with Horny 1.
Regarding claim 3, the combination of Horny 1, Lee, Baker, and Kandory teach the method according to claim 1 (see 35 U.S.C. 103 rejection of claim 1 above), and Horny 1 further teaches a step of introducing the electrode at least partly in a microfluidic channel (“FIG. 24 illustrates a system in which electrodes 15 are arranged in the micro-channel 2” [0130]; FIG. 24), the electrode being a micro-electrode as defined in the instant specification on page 11 lines 11-12: “A micro-electrode is defined here as an electrode whose dimensions are at least less than or equal to 1000 µm” (“so as to form the wall of the micro-channel 2, for example of a width of 300 μm and, for example, of a height of 50 μm” [0116], since the electrodes are arranged in the micro-channel as described above, they are implicitly of dimensions less than these so that they are capable of fitting in the micro-channel and therefore are micro-electrodes).
Regarding claim 5, as discussed with regard to claim 1 above, the combination of Horny 1, Lee, Baker, and Kandory teach a primary electrode comprising a platinum electrode, an ethylenediamine molecule attached to the platinum electrode, a sulfo SMCC molecule attached to a primary amine of the ethylenediamine molecule, and a probe nucleic acid attached to the sulfo SMCC molecule, the probe nucleic acid comprising a thiol function (see 35 U.S.C. 103 rejection of claim 1 above). Horny 1, Lee, and Baker all further teach the probe nucleic acid being complementary to a target nucleic acid (“said single-stranded molecules being designed to be at least partially hybridized to single-stranded nucleic acid target molecule(s)” Horny 1 [0132]; Lee Figure 1; “DNA molecules covalently linked to SWNTs are accessible to hybridization and strongly favor hybridization with molecules having complementary sequences compared with noncomplementary sequences” Baker page 1413 left column paragraph 1).
Regarding claim 6, the combination of Horny 1, Lee, Baker, and Kandory teach the primary electrode according to claim 5 (see 35 U.S.C. 103 rejection of claim 5 above), and Horny 1 further teaches a device for detecting a target nucleic acid comprising the primary electrode, a counter electrode, and an electrical measurement system electrically connected to the primary electrode and to the counter electrode (“detecting the single-stranded target molecule dispersed in the flow is implemented by electrochemistry by imposing an electrical potential difference between two electrodes, the electrodes being partly arranged in the micro-channel; at least one electrode couple comprising a working electrode and a counter-electrode” [0025-0026]; “The various electrodes 15 can be connected to one or more voltage generators, controlled by a control unit, so as to impose an electric potential difference between a working electrode 16 and a counter electrode 17 […] the impedance between a working electrode 16 and a counter electrode 17 depends on the state of hybridization of single-stranded nucleic acid probe molecules 18 attached on the surface of electrodes 15” [0133-0134]; Figure 24).
Regarding claim 7, the combination of Horny 1, Lee, Baker, and Kandory teach the device according to claim 6 (see 35 U.S.C. 103 rejection of claim 6 above), and Horny 1 further teaches the device comprising a micro-fluidic channel, the primary electrode being a micro-electrode, the primary electrode and the counter electrode being placed at least partly in the micro-fluidic channel (“at least one electrode couple comprising a working electrode and a counter-electrode, is arranged in the micro-channel” [0026]; also see the teachings discussed in the 35 U.S.C. 103 rejection of claim 3 covering similar limitations and the limiting definition of micro-electrode).
Regarding claim 10, as discussed with regard to claim 5 above, the combination of Horny 1, Lee, Baker, and Kandory teach a primary electrode according to claim 5, and Horny 1 further teaches a method for detecting a target nucleic acid in a solution comprising a step E1 of providing the primary electrode, a step E2 of providing a counter electrode, a step E3 of setting an electrical voltage between the primary and the counter electrode, a step E4 of bringing the primary and counter electrodes into contact with the solution (“FIG. 24 illustrates a system in which electrodes 15 are arranged in the micro-channel 2” [0130]; “The various electrodes 15 can be connected to one or more voltage generators, controlled by a control unit, so as to impose an electric potential difference between a working electrode 16 and a counter electrode 17” [0133]), a step E5 of measuring an electrical impedance (equivalent to measuring the intensity since, by Ohm’s law, impedance and intensity are inversely proportional and can be calculated from each other for a known voltage) between the primary electrode and the counter electrode, and a step E6 of determining the presence of a target nucleic acid in the solution based on the electrical intensity (entirety of [0134], teaching the step of detecting the nucleic acid target molecule and that the measurement of impedance changes before and after hybridization of the target with the probe).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of the method of attaching a nucleic acid to a carbon electrode by reacting a thiol group attached to the nucleic acid with a sulfo SMCC molecules and reacting the sulfo SMCC molecule with a primary amine attached to the carbon electrode as taught by Lee for the generally recited attachment of a nucleic acid to a carbon, gold, or platinum electrode taught by Horny 1 because this substitution is merely the substitution of a specific way to accomplish the attachment for a general recitation of the attachment (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because both references teach the attachment of a nucleic acid to an electrode. Therefore, the combination of Horny 1 and Lee would have been obvious.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of ethylenediamine as the primary amine-containing molecule attached to the electrode as taught by Baker for the primary-amine containing molecule attached to the electrode in the method taught by the combination of Horny 1 and Lee because both provide a primary amine for reacting with sulfo SMCC (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because both references teach the attachment of a nucleic acid to an electrode through the reaction of SMCC or sulfo SMCC with a primary amine. Therefore, the combination of Horny 1, Lee, and Baker would have been obvious.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to further perform the simple substitution of the gold electrode taught by Kandory for the carbon electrode in the method taught by the combination of Horny 1, Lee, and Baker because both carbon and gold are taught as options for electrode materials by Horny 1 and because Kandory teaches a method of attaching an ethylenediamine molecule to a gold electrode to obtain a similar attachment to that taught by Baker (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because the attachment of ethylenediamine to a gold electrode taught by Kandory provides an available primary amine for reaction with sulfo SMCC like that taught by the combination of Horny 1, Lee, and Baker. Therefore, the combination of Horny 1, Lee, Baker, and Kandory would have been obvious. Furthermore, as discussed in the paragraph regarding the teachings of Kandory relevant to claim 1, the substitution of platinum as the electrode material for gold would be obvious because both materials are taught by Horny 1 and there would be a reasonable expectation that the reaction taught by Kandory would be successful due to the similar relevant properties of platinum and gold.
Therefore, the invention as a whole of claims 1, 3, 5-7, and 10 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention in view of the combination of Horny 1, Lee, Baker, and Kandory.
Claims 2, 4, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Horny et al. (US Patent Document Cite No 1 in IDS filed 20 August 2024)(US 2020/0263241, published 20 August 2020, effectively filed 5 October 2017), herein Horny 1, in view of Lee et al. (“Electrically Addressable Biomolecular Functionalization of Carbon Nanotube and Carbon Nanofiber Electrodes” Nano Lett 4(9), pages 1713-1716 (2004)), herein Lee, Baker et al. (“Covalently Bonded Adducts of Deoxyribonucleic Acid (DNA) Oligonucleotides with Single-Wall Carbon Nanotubes: Synthesis and Hybridization” Nano Lett 2(12), pages 1413-1417 (2002)), herein Baker, and Kandory et al. (“Gold modification by reduction of a diazonium salt prepared from an aliphatic diamine: a new useful means to remove hazardous substances” Environ Sci Pollut Res Int 29(1), pages 1239-1245 (2022), published online 4 August 2021), herein Kandory, as applied to claims 1, 3, 5-7, and 10 above, and further in view of Horny et al. (Non Patent Literature Document Cite No 4 in IDS filed 20 August 2024)(“Electrochemical DNA biosensors based on long-range electron transfer: investigating the efficiency of a fluidic channel microelectrode compared to an ultramicroelectrode in a two-electrode setup” Lab Chip 16(22), pages 4373-4381 (2016)), herein Horny 2.
Regarding claim 2, the combination of Horny 1, Lee, Baker, and Kandory teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above). However, none of these references alone or in combination teach that the aqueous solution is a physiological solution as defined by the instant specification stating: “A physiological solution is defined as an aqueous solution having a sodium chloride concentration greater than or equal to 0.4 mole/liter and less than or equal to 0.6 mole/liter” (page 7 lines 13-15).
Regarding claim 2, Horny 2 teaches immobilizing thiol-labeled DNA probes on electrodes in a physiological solution of 0.5 M NaCl (“The thiol-labeled DNA probe” page 4374 right column paragraph 2; “The DNA probe immobilization was performed by incubating the UME electrode for two hours in a 500 µL volume of 10 µg mL-1 DNA probe diluted in 0.5 M NaCl” page 4375 right column paragraph 2). One of ordinary skill in the art would have a reasonable expectation of success in performing the method of the combination of Horny 1, Lee, Baker, and Kandory since the reaction taught by Kandory occurs in the presence of NaCl (see Kandory Fig. 2 (1)) though with unclear molarity and Lee and Baker teach a similar reaction involving the thiol group of a thiol-modified DNA probe as that of Horny 2.
Regarding claim 4, the combination of Horny 1, Lee, Baker, and Kandory teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above). Horney 2 further teaches after probe immobilization, and therefore after claimed step S3, a step S4 of introducing the electrode in a physiological solution for a duration comprised between 20 minutes and 40 minutes, the physiological solution having a sodium chloride (NaCl) concentration comprised between 0.4 molar and 0.5 molar (“Between probe immobilization and target recognition, the UME is in contact for 30 minutes with 0.5 M NaCl to test the stability of the self-assembled monolayer (SAM)” page 4375 right column paragraph 2), which improves the combination of Horny 1, Lee, Baker, and Kandory by testing the stability of the attachment of the nucleic acid to the platinum electrode before using the electrode for target recognition.
Regarding claim 8, the combination of Horny 1, Lee, Baker, and Kandory teach the device according to claim 6 (see 35 U.S.C. 103 rejection of claim 6 above). Horny 2 further teaches a similar device for detecting a target nucleic acid comprising primary and counter electrodes and an electrical measurement system (Figure 1B and 1C and associated legend, section 2.5 titled Electrochemical detection), the system comprising a plurality of these devices and further comprising an inlet configured to receive a solution to be analyzed, the inlet being connected to each primary electrode of each device (Figure 1C identifying inlets connected to the electrodes of the devices, “Global picture of the microfluidic device comprising several pairs of two-microelectrode networks” Figure 1 legend page 4375).
Regarding claim 9, the combination of Horny 1, Lee, Baker, Kandory, and Horny 2 teach the detection system according to claim 8 (see 35 U.S.C. 103 rejection of claim 8 above), wherein two of the plurality of devices are configured to detect two different target nucleic acids (“several pairs of two-microelectrode networks for multi-detection possibility” Figure 1 legend page 4375; “Another advantage of the electrobiochip described here is the possibility of multi-detection for parallel analysis of numerous miRNAs” page 4381 left column paragraph 1).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine the teachings of Horny 2 with the combination of Horny 1, Lee, Baker, and Kandory because Horny 1 directly teaches the reference of Horny 2 as an example of electrochemical detection implemented by the detection step of the method of Horny 1 (“ the detection step may be implemented by electrochemical detection. Horny et al. (Horny, M. C., Lazerges, M., Siaugue, J. M., Pallandre, A., Rose, D., Bedioui, F., . . . & Gamby, J. (2016), Electrochemical DNA biosensors based on long-range electron transfer: investigating the efficiency of a fluidic channel microelectrode compared to an ultramicroelectrode in a two-electrode setup, Lab on a Chip, 16(22), 4373-4381) (MPEP §2143 I. G.). One of ordinary skill in the art would have a reasonable expectation of success in this combination because Horny 1 teaches that Horny 2 is a method of electrochemical detection used in the method of Horny 1, as further seen in the close similarities between the system of Figure 24 of Horny 1 and the system of Figure 1C of Horny 2. Therefore, the invention as a whole of claims 2, 4, and 8-9 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Horny et al. (US Patent Document Cite No 1 in IDS filed 20 August 2024)(US 2020/0263241, published 20 August 2020, effectively filed 5 October 2017), herein Horny 1, in view of Lee et al. (“Electrically Addressable Biomolecular Functionalization of Carbon Nanotube and Carbon Nanofiber Electrodes” Nano Lett 4(9), pages 1713-1716 (2004)), herein Lee, Baker et al. (“Covalently Bonded Adducts of Deoxyribonucleic Acid (DNA) Oligonucleotides with Single-Wall Carbon Nanotubes: Synthesis and Hybridization” Nano Lett 2(12), pages 1413-1417 (2002)), herein Baker, and Kandory et al. (“Gold modification by reduction of a diazonium salt prepared from an aliphatic diamine: a new useful means to remove hazardous substances” Environ Sci Pollut Res Int 29(1), pages 1239-1245 (2022), published online 4 August 2021), herein Kandory, as applied to claims 1, 3, 5-7, and 10 above, and further in view of Liu et al. (“Electrochemical detection of avian influenza virus H5N1 gene sequence using a DNA aptamer immobilized onto a hybrid nanomaterial-modified electrode” Electrochimica Acta 56(18), pages 6266-6270 (2011)), herein Liu.
Regarding claim 11, the combination of Horny 1, Lee, Baker, and Kandory teach the method according to claim 10 (see 35 U.S.C. 103 rejection of claim 10 above). However, they do not teach alone or in combination the determination of a target nucleic acid concentration in the solution based on a correspondence between the electrical intensity measured from using two reference solutions having different concentrations of the target nucleic acid. This deficiency is made up for in the teachings of Liu.
Regarding claim 11, Liu teaches a similar method of detecting target nucleic acid by using a nucleic acid probe attached to an electrode to detect complementary target DNA based on changes in electrical signal when the probe is bound to a complementary target DNA (section 3.3 page 6269; Figs. 1 and 4). Liu further teaches steps of supplying at least two solutions (note that the claim comprises the sub-step of supplying two reference solutions and therefore does not exclude numbers of reference solutions greater than 2) with different known concentrations of complementary target DNA concentration and measuring the changes in electrical signal to produce a regression equation that calculates the concentration of a target DNA in a solution based on the changes in electrical signal (section 3.4 pages 6269-6270; Fig. 5).
Regarding claim 12, the combination of Horny 1, Lee, Baker, and Kandory teach the method according to claim 10 (see 35 U.S.C. 103 rejection of claim 10 above). Liu also teaches a similar method, as discussed with regard to claim 11 above, wherein the target nucleic acid is a nucleic acid fragment of a pathogen (“The biosensor is based on the hybridization and preferred orientation of a DNA aptamer immobilized onto a modified electrode surface with its target (H5N1 specific sequence) present in solution” Abstract page 6266).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of the nucleic acid probe designed to detect a nucleic acid fragment of the H5N1 pathogenic virus as taught by Liu for general nucleic acid probe for detecting a target nucleic acid taught by each of Horny 1, Lee, and Baker in the combination of Horny 1, Lee, Baker, and Kandory (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because changing the specific sequence of the probe and the target is designed to would not be expected to prevent the method from functioning. Furthermore, the additional use of multiple solutions with different known concentrations to obtain a calibration curve for calculating the concentration of the target nucleic acid also taught by Liu would also not be expected to prevent the method from functioning. Therefore, the invention as a whole of claims 11-12 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Conclusion
Claim 1-12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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, Anne Gussow can be reached at (571)272-6047. 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.
/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
Prosecution Insights