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 .
DETAILED ACTION
Request for Continued Examination Under 37 CFR 1.1143
A request for continued examination (RCE) under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission mailed on January 21, 2025 has been entered.
New claims 21-32 are acknowledged. Claim 1 has been amended.
Claims 1-32 are pending in the instant application.
Claims 9-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicants made the election with traverse in the response filed on September 7, 2023.
Accordingly, claims 1-8 and 21-32 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Arguments
Applicant's Amendment and Response filed January 21, 2025 has been considered. Rejections and/or objections not reiterated from the previous Office Action mailed November 5, 2024 are hereby withdrawn. Any arguments addressing said rejections and/or objections are moot. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Information Disclosure Statement
It is noted that Applicants have not filed an information disclosure statement under § 1.97(c). Applicant is reminded of 37 CFR § 1.56, which details Applicants duty to disclose all information known to be material to patentability.
Claim Rejections - 35 USC § 102/103
In the previous Office Action mailed November 5, 2024, claims 1 and 3-7 were rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over WO 2010/059944 A1 to Columbia University. This rejection is withdrawn in view of Applicant’s Amendment to claim 1 filed January 21, 2025.
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In the previous Office Action mailed November 5, 2024, claims 1, 2 and 8 were rejected under 35 U.S.C. 103 as obvious over WO 2010/059944 A1 to Columbia University in view of U.S. Publication 2013/0029853 A1 to Flusberg et al. This rejection is withdrawn in view of Applicant’s Amendment to claim 1 filed January 21, 2025.
Applicant’s Amendment to the claims filed January 21, 2025 necessitated the new grounds of rejection as presented below:
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-8 and 21-32 are rejected under 35 U.S.C. 103 as obvious over Roembke et al. (Methods 64 (2013) 185-198) (hereinafter, “Roembke”) in view of U.S. Publication 2013/0029853 A1 to Flusberg et al. (hereinafter, “Flusberg”) (submitted and made of record in the Office Action filed April 4, 2024).
The claims are drawn a method of associating a tag to a nucleic acid, comprising: associating the tag to a split G-quadruplex, and binding the split G-quadruplex to the nucleic acid, wherein the tag is not a hemin bound to the G-quadruplex.
The Examiner would like to note that the present Specification discloses prior art known at the time the invention was filed. For example, the present Specification is explicit in disclosing:
“Methods of binding capture tags to capture targets, and binding capture targets to detectable molecules, are known in the art”;
“Methods of using capture tags to bind capture targets are known in the art, and are used to bind nucleic acids—associated with capture tags—to capture targets, including solid surfaces”;
“Tags are known in the art…and can be bound or incorporated into nucleic acids”; and
“Methods of template-directed nucleic acid synthesis are known in the art”
It is also important to note that, according to the present invention, capture tags are nucleic acids; and G-quadruplexes are considered to be DNA enzymes.
Roembke is relevant and relied upon in its entirety. Roembke is a review article that teaches nucleic acid detection using G-quadruplex amplification methodologies. In this review, Roembke focuses on strategies for the detection of nucleic acids, using G-quadruplexes as detection labels or as enzyme labels that amplify detection signals. See Abstract, for example.
Roembke highlight strategies in which a tag is associated to a split G-quadruplex and binding of the split G-quadruplex to the nucleic acid. See the teachings of Kolpashchikov, Willner, Wang and Sintim discussed in the Roembke review. Also, see Table 1 in its entirety. For example, Roembke summarize Kolpashchikov’s symmetric G-quadruplex probe, which could detect the tau protein encoding gene. Kolpashchikov’s group was able to detect the DNA target via colorimetric means, using DAB (3,3'-diaminobenzidine tetrahydrochloride) as the reductant (Fig. 2 and Table 1).
Roembke discuss Willner reported nucleic acid detection using a symmetric split G-quadruplex probe but instead of DAB, the Willner group used luminol as a reductant for a luminescent readout (Fig. 3 and Table 1). Roembke explain that Willner's approach uses a chemiluminescence turn-off probe to detect the target DNA
Roembke demonstrate that Wang describe a "split" molecular beacon G-quadruplex probe that can be used to detect DNA or thrombin (a dual probe, Fig. 12 and Table 1). This probe has two stem-loop structures, one of which is complimentary to the target DNA. The other stem loop contains an aptamer for thrombin. When there is no target DNA, and both molecular beacons are intact, the probe can form a complete G-quadruplex, resulting in an active DNAzyme peroxidase. However, in the presence of target DNA, the first stem-loop unfolds resulting in the unfolding of the G-quadruplex as well. In the presence of thrombin, the second stem-loop unfolds to bind to thrombin (which is also a G-quadruplex structure).
Roembke report that Zhou and co-workers have used an asymmetric split G-quadruplex, and ABTS as the peroxidase substrate to detect fragments of HIV genes (Fig. 5 and Table 1). Soon after Zhou's report, the Sintim group reported that appending a duplex overhang to the G-quadruplex region of an asymmetric split G-quadruplex probes facilitated G-quadruplex formation and improved the signal-to-noise ratio (S/N) of detection via split G quadruplexes (Fig. 6 and Table 1). Roembke go on to report that incorporation of a complementary region each probe (labeled A and B in Fig. 6) that formed a duplex, the S/N was increased by fivefold and the kinetics of the reaction was greatly enhanced, leading to sensitive detection of DNA.
Roembke also discuss an efficient way to improve sensitivity in DNA detection in which the nucleic acid is bound to a solid surface, the solid surface is washed to remove unbound molecules, and the bound detectable nucleic acid is observed. See Roembke at page 193, Section 3.2.
Roembke does not necessarily teach performing template-directed nucleic acid synthesis of the nucleic acid.
Flusberg teaches wherein the tag is associated to the G-quadruplex by template-directed nucleic acid synthesis (performing template-directed nucleic acid synthesis) for the purpose of attaching a primer comprising a complementary region at the reaction site that is capable of hybridizing with the template, thereby immobilizing it in a position suitable for monitoring.
The prior art is replete with examples showing that tagged G-quadruplexes can bind various analytes, including nucleic acids, giving rise to several different colorimetric, fluorescent and luminescent signals. This fact is substantiated and extensively detailed by the review article of Roembke. Before the effective filing date of the claimed invention, as the present Specification discusses, a method of associating a tag to a nucleic acid, comprising: associating the tag to a split G-quadruplex, and binding the split G-quadruplex to the nucleic acid was known in the art.
A person of ordinary skill in the art would have been motivated and expected reasonable success to devise the method of the claimed invention for the purpose of detecting target nucleic acids as taught and suggested by the prior art.
It would have been obvious to a person of ordinary skill in the art, at the time the invention was made, to have modified the teachings of Roembke to include wherein the tag is associated to the G-quadruplex by template-directed nucleic acid synthesis, as taught and suggested by Flusberg. The purpose would be to provide an improved method for associating the tag with the split G-quadruplex for further detecting and monitoring.
A person of ordinary skill in the art would have been motivated and expected reasonable success at incorporating the tag into one or two strands of the split G-quadruplex since Roembke teach such option is a matter of design choice made during the course of routine optimization and experimentation. See Roembke, Figures, for example.
For the reasons discussed above, claims 1-8 and 21-32 are obvious over Roembke in view of Flusberg.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635