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 .
Election/Restrictions
Applicant’s election without traverse of RdRP in the reply filed on January 13, 2026 is acknowledged.
Status of Claims
Claims 1-8 are currently pending and under examination on the merits in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
1. The disclosure is objected to because page 23 of the substitute specification filed on March 22, 2023 is blank in its entirety. That is, the entire page is blank. As such, it is unclear whether a piece of disclosure is missing or whether page 23 is mistakenly added.
Appropriate correction and/or clarification is required.
2. The disclosure is objected to for containing sequence rule non-compliant subject matter. See Tables 1-2. Appropriate correction is required as instructed below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency - This application contains a “Sequence Listing as a PDF file (37 CFR 1.821(c)(2)) or as physical sheets of paper (37 CFR 1.821(c)(3)), but fails to comply with the requirements of 37 CFR 1.821 - 1.825 because a copy of the "Sequence Listing" in computer readable form (CRF) has not been submitted as required by 37 CFR 1.821(e)(1)(i) or 1.821(e)(2)(i) as indicated in item 2) above.
Required response - Applicant must provide:
A new CRF of the “Sequence Listing” in accordance with 37 CFR 1.821(e)(1)(i) or 1.821(e)(2)(i) and
A statement that the content of the CRF is identical of the “Sequence Listing” part of the disclosure, submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
Specific deficiency – Nucleotide sequences appearing in the specification, see Tables 1-2, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
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.
Drawings
The drawings in FIG. 18 are objected to because FIG. 18 contains irrelevant subject matter pertaining to “[Sequence List]” as reproduced below.
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Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 6 is objected to because of the following informalities: “A Biosensor” should be “A biosensor”. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: “A Kit” should be “A kit”. 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.
Claims 1-8 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 1 recites the limitation "the nucleic acid strand" in line 3. There is insufficient antecedent basis for this limitation in the claim. Note that line 2 recites “nucleic acid strands”. Now, should “the nucleic acid strand” be interpreted as the plurality of nucleic acid strands recited in line 2, it is unclear whether a single gold component is required to bind to the plurality of the nucleic acid strands or whether a single gold component is required to bind to each nucleic acid strand constituting the plurality of the nucleic acid strands such that there is a 1:1 ratio between the gold component and the nucleic acid strand. Since claims 2-7 depend from claim 1, claims 2-7 are deemed indefinite for the same reasons stated above.
Claim 5 recites “a structure consisting of RNA transferred on the surface” in line 2. There is insufficient antecedent basis for “the surface” limitation in the claim. In addition, it is unclear what is meant by “RNA” being “transferred” on the surface as the term “transfer” or “transferred” on a surface is not normally used in relation to an RNA. Further, there is no definition of the term “transfer” or the phrase “transferred” on a surface in the specification or in the claim. Hence, the metes and bounds pertaining to “a structure consisting of RNA transferred on the surface” cannot be clearly ascertained.
Claim 5 recites “RNA polymerase.” It is unclear whether the “RNA polymerase” recited in claim 5 is same as or different from the “RNA polymerase” recited in lines 4-5 of claim 1.
Claim 8 recites the limitation "the gold ion" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites “the nucleic acid membrane to which the gold ion binds.” It is unclear whether “the nucleic acid membrane” is referring to “a nucleic acid membrane in which the gold ion is bound” in lines 4-5 or is meant to refer to a different nucleic acid membrane because of the wording difference in “in which the gold ion is bound” in line 5 and “to which the gold ion binds” in line 6.
Claim Rejections - 35 USC § 102
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 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.
Claim 8 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (Journal of Colloid and Interface Science, 2021, 594:160-172, applicant’s citation).
Lee teaches a method of generating a gold nanoparticle (AuNP)-bound DNA template membrane, wherein the method comprises preparing a DNA template membrane comprising double-stranded DNA strands; providing Au3+ ions to the DNA template membrane, thereby generating Au3+-bound DNA template membrane; and reducing the Au3+-bound DNA membrane in a reaction “with NH2OH at room temperature for 12 h” for providing “reduction of Au3+ ions to metallic Au nanostructures”, thereby generating an AuNP-bound DNA membrane. See pages 163-164 and 166.
Since all method steps recited in claim 8 are fully satisfied by Lee’s method, it necessarily follows that Lee’s method inherently serves the intended purpose “for RNA polymerase-activated nucleic acid membrane manufacturing” recited in the preamble of claim 8, absent objective evidence to the contrary.
Accordingly, claim 8 is described by Lee et al.
Claims 1-4 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guo et al. (ACS Applied Bio Materials, 2018, 1:1647-1655).
Guo teaches a “biosensor” or “detection system” comprising an RNA membrane that is formed by RNA strands which “are partially complementary” to each other, wherein the surface of the RNA membrane is functionalized/attached with luminol-gold nanoparticles (luau NPs), thereby providing “successful generation and attachment of luau NPs on the RNA membrane-based substrate” thus obtaining “luau NP/RNA membranes.” See pages 1648-1649 and 1651-1654. Guo teaches that RNA strands of the RNA membrane mixed with “T7 RNA polymerase” is capable of proving that “the RNA nanostructure product was fabricated”. See page 1651. As such, the RNA strands of the RNA nanostructure/membrane inherently have exposed ends that can react with the T7 RNA polymerase.
Accordingly, claims 1-4 and 6 are described by Guo et al.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (Biosensors and Bioelectronics, published online on December 10, 2021, 199:113880, applicant’s citation).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216. Hence, the effective filing date for claims 1-8 is the instant applicant’s filing date, which is December 12, 2022.
Kim discloses a biosensor/detection kit for detecting RNA virus, wherein the biosensor comprises a gold-functionalized RNA membrane template that is reduced, wherein the RNA membrane template comprises partially complementary RNAs whose 3’ ends are activated by RdRP, which amplifies viral RdRP transcripts, wherein the kit further comprises a TMB dye that has oxidation/reduction (redox) reaction with gold ion. See pages 5-9.
Kim teaches that the gold-functionalized RNA membrane is produced by using Au3+, wherein the “Au-NA membranes” are subjected to a “sequential reduction process” to generate AuNP-functionalized RNA membrane. See page 3.
Accordingly, claims 1-8 are described by Kim et al.
It is noted that applicant submitted a 37 CFR 1.130 declaration on March 14, 2023 declared by the three named co-inventors of the instant application, wherein the co-inventors state that the Kim reference was publicly disclosed by the joint inventors “who contributed to conceptualization of the subject matter” among the co-authors named in the Kim reference.
The declaration is insufficient to overcome the instant rejection because the effective filing date granted for claims 1-8 of the instant application is the instant application’s filing date, which is December 12, 2022 as noted above, whereas the publication date of the Kim reference is December 10, 2021. As such, the Kim reference was publicly available more than one year before the effective filing date granted for claims 1-8 thus the 1.130 declaration is inappropriate. Again, applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55.
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.
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 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (ACS Applied Bio Materials, 2018, 1:1647-1655) in view of Han et al. (Nano Letters, 2021, 21:462-468, applicant’s citation), Jang et al. (Analytical Chemistry, 2011, 83:1836-1842), and Lee et al. (Journal of Colloid and Interface Science, 2021, 594:160-172, applicant’s citation).
Guo teaches a “biosensor” or “detection system” comprising an RNA membrane that is formed by RNA strands which “are partially complementary” to each other, wherein the surface of the RNA membrane is functionalized/attached with luminol-gold nanoparticles (luau NPs), thereby providing “successful generation and attachment of luau NPs on the RNA membrane-based substrate” thus obtaining “luau NP/RNA membranes.” See pages 1648-1649 and 1651-1654.
Guo teaches that “luau NPs anchored on the RNA membrane play an important role, similar to that of the wires, to facilitate electron transfer” that involves “electrostatic adsorption of Au nanoparticles with a negative charge”, wherein the Au nanoparticles (Au NPs) “increased the interface area to capture more luminol molecules and promote electron transfer and the ECL production process”, wherein “the luminol is essential for the ECL production process” such that “the ECL came from the luminol”, and when the surface of the gold nanoparticle-functionalized RNA membrane is immobilized with captured target cells, the ECL (electrochemiluminescence) signal is decreased as the number of target cells bound to the RNA membrane surface increased because the captured cells “prevents the electron transfer from the interface.” See pages 1652-1653.
Guo teaches that the ECL signal intensity is measured by electrochemical impedance spectroscopy (ESI) or “electrochemiluminescence analysis system”. See pages 1648 and 1652.
Guo teaches that the Au NP-functionalized/attached “RNA membrane-based platform” “has a huge potential for many biological and biomedical applications, such as diagnosis”. See page 1654.
Guo does not teach that the Au NP-functionalized/attached RNA membrane is activated by RdRP. Guo also does not teach detecting virus using a dye that changes color.
Han teaches that SARS-CoV-2 virus in a sample can be detected comprising using RNA templates having “free 3’ ends” that are activated by RNA-dependent RNA polymerase (RdRP), which binds to the free 3’ ends of the RNA templates “for efficient initiation of RNA polymerization”, wherein the virus-infected sample contains RdRP, “which plays a key role in the replication of SARS-CoV-2”, wherein RdRP is able “to initiate de novo RNA synthesis from the 3’ ends of RNA templates without a primer”, wherein “RNA-directed RNA transcription specifically occurs with RdRP, which cannot naturally exist in human cells.” See pages 462-464 and 466; Figures 1A-1B.
Jang teaches that 3,3’,5,5’-tetramethylbenzidine dihydrochloride (TMB) is “an oxidizable color reagent”, which provides detection of “the blue charge-transfer complex of oxidized TMB” such that addition of the “TMB reagent to the Au(III) solution produced a color change from colorless to intense aqua blue in a time ranging from 5 s (high Au(III)) to 3 min (low Au(III)).” See Scheme 1; pages 1838-1839.
Lee teaches that a gold nanoparticle (AuNP)-bound nucleic acid template membrane can be synthesized by reacting Au3+ ion with the nucleic acid template membrane and reducing the Au3+ ion bound to the nucleic acid membrane, which can comprise “synthetic nucleic acids, such as RNA”, wherein the synthesis methodology is useful for providing controlled, uniform gold nanostructures having “better performance in sensitivity” with “strong” signal intensity. See pages 163-164, 166, and 171.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Guo’s “biosensor” or “detection system” comprising gold nanoparticle-attached RNA membrane by ensuring to provide “free 3’ ends” in the “partially complementary” RNA strands of Guo’s RNA membrane, wherein Guo’s “biosensor” or “detection system” is contacted with a biological sample comprising RdRP of the SARs-CoV-2 virus. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to make a biosensor for detecting/diagnosing SARS-CoV-2 infection via the presence of RdRP of the SARs-CoV-2 virus in a biological sample because it was an art-recognized detection methodology to detect SARS-CoV-2 virus in a sample containing RdRP that “plays a key role in the replication of SARS-CoV-2”, wherein SARS-CoV-2 virus’ RdRP mediates RNA synthesis from the “free 3’ ends” of RNA templates without a primer as taught by Han, and because one of ordinary skill in the art would have reasonably deemed Guo’s RNA membrane formed by “partially complementary” RNA strands would be suitable to serve as the RNA templates “to initiate de novo RNA synthesis from the 3’ ends” in the presence of SARS-CoV-2 virus’ RdRP, wherein the RNA strands synthesized de novo by SARS-CoV-2 virus’ RdRP would have been reasonably expected to interfere with the electron transfer activity of the gold nanoparticles attached to the surface of Guo’s RNA membrane, thereby preventing luminol-mediated ECL signal production process in view of the scientific mechanism of action of Guo’s luminol gold nanoparticle-attached RNA membrane. That is, Guo’s gold nanoparticle-attached RNA membrane was suggested to have a “huge potential” as a “diagnosis” tool in “biomedical applications” by utilizing the gold nanoparticle’s property to “facilitate electron transfer”, which is prevented when the RNA membrane is bound/covered with target cells such that there is a linear, inverse relationship between the target cell-bound RNA membrane and the detectable signal intensity as taught by Guo, who disclosed that the “ECL signal decreased by piecemeal as the number of Ramos cells increased.” (see page 1653). Hence, one of ordinary skill in the art would have reasonably deemed Guo’s gold nanoparticle-bound RNA membrane to be less likely to generate electron transfer and subsequent detectable ECL signal when new RNA strands are de novo synthesized from the 3’ ends of the RNA strands of Guo’s RNA membrane when contacted with SARS-CoV-2 virus’ RdRP because the newly synthesized RNA strands would have been reasonably expected to reduce free, available gold nanoparticle-containing surface area on the RNA membrane that is able “to capture more luminol molecules and promote electron transfer and the ECL production process”.
One of ordinary skill in the art would also have been motivated to replace Guo’s luminol with Jang’s TMB in order to simplify the detection of SARS-CoV-2 virus’ RdRP-mediated de novo synthesis of RNA strands without using additional detection analysis system, because Guo’s biosensor was known to require use of electrochemiluminescence analysis and detection system, whereas use of Jang’s TMB was taught to provide almost immediate (e.g., 5 seconds) detectable color change from colorless to intense aqua blue when reacted with gold ions as taught by Jang. It would also have been obvious to one of ordinary skill in the art to utilize Lee’s gold nanoparticle-bound nucleic acid membrane synthesis methodology when making the RNA membrane of Guo with a reasonable expectation of success, because Lee’s methodology comprising reacting Au3+ ion with a nucleic acid template membrane and reducing the Au3+ ion bound to the membrane was deemed useful for providing controlled, uniform gold nanostructures having “better performance” as detection agents as evidenced by Lee’s teachings.
Accordingly, claims 1-8 taken as a whole would have been prima facie obvious before the effective filing date.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635