Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Group II, claims 14-20 in the reply filed on 30 July 2025 is acknowledged.
Nucleotide and/or Amino Acid Sequence Disclosures
3. 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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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 Objections
4. Claim 20 is objected to because of the following informalities: line 3 of claim 20 recites “…’5 nucleotide…” it is believed this is a typographical error that should read “…5' nucleotide…”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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.
6. Claims 14-20 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.
A. Claim 14 recites the phrase “a preserved binding domain nucleotide sequence of the aptamer,” but it is unclear what the binding domain nucleotide sequence is preserved compared to? There is no claimed comparator, and additionally claim 14 recites the phrase “a portion of a nucleotide sequence of an aptamer…” and “the portion of the nucleotide sequence forming the molecular beacon…” This language seems to imply that “the portion of a nucleotide sequence (of an aptamer)” comprises a binding domain sequence, a displacement domain sequence, and a first domain sequence. Does the aptamer already comprise all of these sequences? This language is circular and therefore the scope of this claim is unclear.
B. Claim 16 similarly recites a “preserved binding domain” with no claimed comparator. Additionally, claim 16 recites the term “apparent electron rate value,” and this term is not adequately defined in the claim language or in the applicant’s specification. There is no claimed structure that appears to facilitate an “apparent electron rate value,” therefore this claim is indefinite. Insofar as this claim relates to claim 20 and the claimed redox active center, it is noted here that claim 16 is not related to claim 20 by dependency or any other claim structure.
C. Claim 17 recites a ratio of k1/k2 or k2/k1 in the range of 2 to 1000, however this ratio is based on unclaimed factors such as the binding matrix (buffer vs. serum vs. whole blood, etc.) or the target concentration. Without additional context limiting this claim these ratios are relative values that don’t sufficiently describe or limit the claimed molecular beacon structure and the metes and bounds of this claim are unclear, therefore the claim is indefinite.
D. Claim 19 recites that “…the portion of the nucleotide sequence forming the molecular beacon is SEQ ID No. 1.” SEQ ID No. 1 appears to be a version of the cortisol aptamer, however it is unclear exactly how SEQ ID No. 1 limits claim 14. The limitation currently reads as though SEQ ID No. 1 already comprises the truncated or extended one or both of a first domain nucleotide sequence or a displacement domain nucleotide sequence, or is SEQ ID No. 1 supposed to be the aptamer prior to truncation/extension? These limitations are unclear and therefore the claim is indefinite.
E. Claims 15, 18, and 20 are additionally rejected as being dependent on a previously rejected claim.
Claim Rejections - 35 USC § 102
7. 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.
(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.
8. Claims 14-16, 18 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wilson et al (United States Patent Application No. US20210355496, published 18 November 2021).
Regarding claim 14, Wilson teaches a molecular beacon (FIG 1) comprising a portion of a nucleotide sequence that binds to ATP (i.e., a target analyte), a first domain nucleotide sequence, and an intramolecular displacement strand wherein the length is changed to modulate the effective binding affinity of the aptamer (i.e., a truncated or extended displacement domain; FIG 1 and [0013]). It is noted here that the phrase “wherein the truncation or extension is performed to develop the molecular beacon…” is simply stating the intended use of the claimed molecular beacon, and additionally the desired outcome of the truncation or extension steps. This phrase does not further limit the claimed structure of the molecular beacon. It is additionally noted that any “…nucleotide sequence of an aptamer…” inherently has a first Gibbs free energy value, and that the second Gibbs free energy value is not a required element of the claimed structure based on the existing claim language.
Regarding claim 15, Wilson teaches that a model system was used to mathematically test the anticipated effects of adjusting the length of the displacement strand (i.e., the length of the displacement strand was truncated or extended in silico; [0098]). Furthermore, performing the truncation or extension in silico is a process step that does not limit the claimed structure of the product.
Regarding claims 16 and 20, it is again noted that the phrase “apparent electron rate value” is not adequately described in the applicant’s specification or in the language of the claim, however, insofar as this language is related to the transfer of electrons between a redox active center of claim 20 and an unclaimed electron responsive surface (e.g., an electrode) these limitations are taught by Wilson for an embodiment where one label is an electrode and another label is a redox reporter (e.g., methylene blue; [0073]). Wilson teaches that these labels are present at the first and second termini of the aptamer (i.e., functionalizing either the 5' or 3' nucleotide of the aptamer; claim 1). Furthermore, regarding claim 16, “further performed to develop… wherein the difference between the first apparent election rate value and the second electron rate value is maximized” again describes a process step that does not additionally limit the structure of the claimed aptamer. The language “to develop” describes the goal of the developing process, not a specific limitation that is required or achieved.
Regarding claim 18, Wilson teaches that a model system was used to mathematically test the anticipated effects of adjusting the length of the displacement strand (i.e., the length of the displacement strand was truncated or extended in silico; [0098]). Furthermore, performing the truncation or extension in silico is a process step that does not limit the claimed structure of the product.
9. Claims 14 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stojanovic et al (United States Patent Application No. US20190136241, published 9 May 2019).
Regarding claims 14 and 19, Stojanovic teaches SEQ ID No. 1 used as an aptamer switch (i.e., a molecular beacon as defined in claim 1; FIG 14A and SEQ ID No. 5). Stojanovic teaches that this aptamer beacon binds to hydrocortisone (i.e., a portion of a nucleotide sequence of an aptamer that binds to a target analyte; [0170]). It is again noted that any nucleic acid sequence inherently has a first Gibbs free energy value. Stojanovic teaches a molecular beacon comprising a truncated or extended one or both of a first domain nucleotide sequence or a displacement domain nucleotide sequence (e.g., they hybridized beacon arms of SEQ ID No. 5) in the embodiment wherein the beacon arms are truncated or extended from any other longer or shorter nucleic acid sequence. It is again noted that the phrase “wherein the truncation or extension is performed to develop the molecular beacon…” is a process or development step describing a potential goal that is desired but not necessarily reached, and does not further limit the structure of claim 1.
10. 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.
11. 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.
12. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al (United States Patent Application No. US20210355496, published 18 November 2021) in view of Jimenez et al (Aptamer-based label-free impedimetric biosensor for detection of progesterone, Analytical Chemistry, 87, 1075-1082, published 8 December 2014).
Regarding claim 17, the method of claim 16 is discussed fully above and incorporated here.
Wilson teaches an aptamer switch comprising an electrode label at one terminus and a redox reporter label at the other, and that the aptamer switch undergoes a conformational change upon target binding that modulates the redox current and generates an electrochemical signal ([0073]).
Wilson does not specifically teach that the signal ratio of bound/unbound or unbound/bound aptamer switches (i.e., k2/k1 or k1/k2) is in the range of 2 to 1000.
However, Jimenez teaches a cortisol aptamer switch bound to a gold nanowire with an unbound/bound (i.e., k2/k1) signal ratio of 3-8.5 depending on target concentration (FIG S-4).
It would have been obvious to one having ordinary skill in the art to have identified electrochemical active aptamer switches as taught by Wilson having unbound/bound apparent electron rate value ratios (i.e., k2/k1) between 2 to 1000 as identified by Jimenez to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to identify aptamers having such a signaling ratio in order to develop aptamer switches having practically useful signal-to-noise ratios. In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably result in electrochemically active aptamer switches.
13. Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al (United States Patent Application No. US20210355496, published 18 November 2021) in view of Stojanovic et al (United States Patent Application No. US20190136241, published 9 May 2019).
Regarding claim 19, the method of claim 14 is discussed fully above and incorporated here.
Wilson does not teach that the nucleotide sequence forming the molecular beacon is SEQ ID No. 1 (i.e., the cortisol aptamer).
However, Stojanovic teaches SEQ ID No. 1 used as an aptamer switch (FIG 14A and SEQ ID No. 5).
It would have been obvious to one having ordinary skill in the art to have substituted the ATP aptamer taught by Wilson with the cortisol aptamer taught by Stojanovic to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to make this substitution because Wilson specifically teaches that virtually any aptamer could be used in their disclosed switch development framework ([0095]). In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably result in the formation of aptamer switches.
Conclusion
14. No claims are allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN ELLIS YOUNG whose telephone number is (703)756-5397. The examiner can normally be reached M-F 0730 - 1700.
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/BRIAN ELLIS YOUNG/Examiner, Art Unit 1684
/JULIET C SWITZER/Primary Examiner, Art Unit 1682