Prosecution Insights
Last updated: April 19, 2026
Application No. 18/116,138

CASCADED NUCLEIC ACID PROTOCOLS FOR ULTRA-SPECIFIC MOLECULAR DETECTION, TRANSDUCTION, AND AMPLIFICATION

Non-Final OA §102§112
Filed
Mar 01, 2023
Examiner
PRIEST, AARON A
Art Unit
1681
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Duke University
OA Round
1 (Non-Final)
61%
Grant Probability
Moderate
1-2
OA Rounds
3y 0m
To Grant
87%
With Interview

Examiner Intelligence

Grants 61% of resolved cases
61%
Career Allow Rate
486 granted / 794 resolved
+1.2% vs TC avg
Strong +26% interview lift
Without
With
+26.0%
Interview Lift
resolved cases with interview
Typical timeline
3y 0m
Avg Prosecution
30 currently pending
Career history
824
Total Applications
across all art units

Statute-Specific Performance

§101
7.0%
-33.0% vs TC avg
§103
31.8%
-8.2% vs TC avg
§102
21.7%
-18.3% vs TC avg
§112
22.4%
-17.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 794 resolved cases

Office Action

§102 §112
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 Status of the Claims Claims 1-20 are pending. Claims 1-7 are the subject of this NON-FINAL Office Action. This is the first action on the merits. Election/Restrictions Applicant’s election without traverse of Group I (claims 1-7) in the reply filed on 12/16/2025 is acknowledged. Claims 8-20 are withdrawn. Claim Rejections - 35 USC § 112- 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. Claims 2-5 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 pre-AIA the applicant regards as the invention. In claim 2, the phrase “nonstandard nucleic acid bases” is unclear. The specification fails to define this unconventional phrase, or compare to a “standard.” Thus, it is unclear in what way the bases are “nonstandard.” In claim 3, the phrase “full set of primers for an isothermal amplification reaction” is unclear. Specifically, the specification never defines what constitutes a “full set,” or how this is measured, much less what an “un-full” set would be. This it is not clear what is a “full” set of primers. In claim 4, the transduction reaction and “downstream amplification” are unclear. As to a “downstream amplification”: downstream of what? As to a “transduction reaction”: what is this unconventional phrase? At best, the specification states “[n]ucleic acid strand transduction is a reaction where one input nucleic acid strand is replaced with another output nucleic acid strand” (para. 0009). Does this encompass standard PCR in which a new strand replaces an old strand? Or does this “input strand” already exist in the solution without PCR (or other amplification)? This would mean that the “transduction reaction” before “amplification reaction” encompasses a single PCR. This would be an odd claim as it effectively claims PCR, rendering any distinction of “transduction reaction” meaningless. Simply put, the claim is so ambiguous that it is impossible to determine the metes and bounds. In claim 5, the phrases “LAMP-like” reaction and “incomplete set” of LAMP primers are unclear. As to a “LAMP-like” reaction, at best the specification states “the disclosed molecular mechanisms may be leveraged to improve the specificity of various isothermal amplification techniques other than the conventional LAMP and/or RT-LAMP methods, for example, including but not limited to variations of LAMP-like amplification techniques based on dual-priming, swarm priming, stem priming, hairpin primers, etcetera.20-25” (para. 0012). However, first, the citations are not incorporated-by-reference. Second, even if they were, essential subject matter cannot be incorporated via non-patent literature. See MPEP § 608.01(p)(I)(A)(2). Finally, mere mention of dual-priming, swarm priming, stem priming, hairpin primers fails to explain the common metes and bounds that render “LAMP-like” reactions reasonably clear. Thus, it is unclear the metes and bounds of “LAMP-like” reaction. As to “incomplete set” of LAMP primers, this is never defined. As explained above as a “complete” set, the opposite holds true as to an “incomplete” set: what are the metes and bounds? How are these two types of primer sets distinguished? No answer is provided. Claim Interpretations In claim 1, Applicants use intended use language of the claimed products at the potential point of novelty, which fail to distinguish over prior art products. Specifically, the following intended uses fail to distinguish the claimed double-stranded primers: “such that when the armor strand hybridizes to the first primer, the 3' section of the first primer becomes sequestered while the 5' section of the first primer is free to hybridize to a first target location of a target nucleic acid”; and “to enable, with the first primer, amplification of the target nucleic acid, wherein during the amplification, the 3' modification of the armor strand prevents polymerase extension of the armor strand.” Thus, the claims amount to the following composition: A first primer, with a strand of nucleic acid hybridized to any part of the 3’-half of the first primer and including a “modification” at 3’-end; and A second primer “associated” with the first primer. 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 – (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 1-3 and 6-7 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by PIEPENBURG (US 2005/0112631). As to claims 1-2, PIEPENBURG teaches the following double-stranded primer just like in instant Figure 1A: PNG media_image1.png 202 734 media_image1.png Greyscale PIEPENBURG, Fig. 34A PNG media_image2.png 190 596 media_image2.png Greyscale INSTANT Fig. 1A As is clear, PIEPENBURG teaches the exact same double-stranded primer structure with 3’-end block on the second strand hybridized to the 3’-portion of the first strand primer. The duplex primer of PIEPENBURG is designed for the same reason as here: to prevent spurious amplification in isothermal amplification reactions (c.f. Fig.34, as descriptions thereof with Spec., para. 0027). PIEPENBURG further teaches another primer associated with a second target location of the target nucleic acid (e.g. reverse primer, or second target primer, or nested primers; Figs. 2-4). As to claim 3, the amplification is an isothermal amplification with two or more primers (recombinase polymerase amplification, or RPA; e.g. Abstract and Fig. 2). As to claims 6-7, the RPA reaction can include DNA polymerase and reverse transcriptase (e.g. Abstract and Figs. 2-3; para. 0063 (“RNA can be turned into double stranded DNA by one of skill in the arts using known methods”)). Prior Art The following prior art also teaches double-stranded primers: US 2013/0274135; US20100279295. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm. 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, Gary Benzion can be reached at (571) 272-0782. 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. /AARON A PRIEST/Primary Examiner, Art Unit 1681
Read full office action

Prosecution Timeline

Mar 01, 2023
Application Filed
Jan 07, 2026
Non-Final Rejection — §102, §112 (current)

Precedent Cases

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
61%
Grant Probability
87%
With Interview (+26.0%)
3y 0m
Median Time to Grant
Low
PTA Risk
Based on 794 resolved cases by this examiner. Grant probability derived from career allow rate.

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