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 with traverse of Group 1, claims 1-7, 10, and 11, in the reply filed on October 29, 2025 was acknowledged but not considered persuasive. Accordingly, the election of Group 1 (claims 1-7, 10, and 11), and the species of DNA polymerase (claims 5-6) was made final in the office action dated December 1, 2025.
Claims 1-3, 5-7, 9-19, and 21-23 are pending. Claim 1 has been amended to recite new limitations of “when a temperature of the nucleic acid is at a certain temperature…enzyme activity of the nucleic acid polymerase is completely blocked without residual enzyme activity” and that the certain temperature is 50°C.
Claim 2 has been newly canceled. Claims 4, 8, and 20 were previously canceled. Claims 7, 9, 12-19, and 21-23 were previously withdrawn.
Claims 1, 3, 5-6, and 10-11 are examined on the merits.
Applicant’s submission filed on February 27, 2026 has been entered and considered. Rejections and/or objections not reiterated from the previous action mailed December 1, 2025 are hereby withdrawn. 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. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
The instant application is a 35 U.S.C 371 national stage filing of the International Application No. PCT/CN2021/101244 filed on June 21, 2021. The instant application claims foreign priority under 35 U.S.C 119(a)-(d) to Chinese Patent Applications CN202010576818.3 filed on June 22, 2020. Receipt is acknowledged of a certified copy of the foreign patent application in the original language as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on December 19, 2022; March 29, 2023; June 20, 2025; and December 18, 2025 are in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Withdrawn Objections to the Specification
The examiner concedes that the Abstract dated December 19, 2022 was with in the 150 word limit. In light of Applicant’s submission of an amended abstract dated February 27, 2026 which has less than 150 words the objection to the specification has been withdrawn.
Withdrawn Claim Rejections - 35 USC § 112
In light of Applicant’s amendment to claim 1 to recite “a temperature” in line 7 the antecedent basis rejection of claims 1-3, 5-6, and 10-11 has been withdrawn.
Withdrawn Claim Rejections - 35 USC § 102
The prior art rejection of claims 1-3, 5-6, and 10-11 under 35 U.S.C 102 as being anticipated by Dong et al. (WO 2007041201 A2) is withdrawn in light of Applicant’s amendment to claim 1 to recite a nucleic acid ligand which forms a stable structure with a nucleic acid polymerase when the temperature of the nucleic acid ligand is at a certain temperature and enzyme activity of the nucleic acid polymerase is completely blocked without residual enzyme activity and, when the temperature is higher than said certain temperature, the nucleic acid polymerase detaches from the nucleic acid ligand to exert activity, and wherein the certain temperature is 50°C. Additionally, applicant has canceled claim 2, rendering the previous rejection of claim 2 under 35 U.S.C. 102 moot.
Claim Rejections - 35 USC § 102
This is a new rejection necessitated by Applicant’s amendment. However, this rejection shares substantial similarity to the rejection as previously set forth in the office action dated December 1, 2025. Any aspect of Applicant’s traversal that pertains to the rejection as newly set forth will be provided following the new statement of rejection.
Claims 1, 3, 5-6, and 10-11 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Dong et al. (WO 2007041201 A2, found in IDS dated 06/20/2025, hereafter “Dong”).
With regard to claim 1, Dong discloses an enzyme inhibitor comprising a nucleic acid sequence designed to inhibit the activity of an enzyme and that the enzyme inhibitor can comprise an aptamer, which is considered to reasonably read on a nucleic acid ligand, capable of forming a double stranded segment (Para. [0007], lines 1-6) at a first temperature but is single stranded when heated to a second temperature (Para. [0007], lines 11-12). Dong discloses wherein the nucleic acid based enzyme inhibitor can form a stem-loop conformation (Para. [0010], lines 5-6, see also Figs. 1A-D), which is considered to reasonably read on forming intramolecular complimentary pairing, or can be two oligonucleotides which are annealed to form a duplex (Para. [0010], lines 8-9, see also Figs. 2A-E), which is considered to reasonably read on forming intermolecular complementary pairing. Dong discloses wherein the nucleic acid based enzyme inhibitor is not extendable by a polymerase due to the presence of a blocking group or non-extendable nucleotide at the 3’ end (Para. [0008], lines 5-8) and wherein the non-extendable nucleotides may be dideoxynucleotides (Para. [0051]). Additionally, Dong discloses wherein the nucleic acid based enzyme inhibitor can form a complex with an enzyme, which may be a polymerase (Paras. [0007], [00122]), to inhibit enzymatic activity at a first temperature (Paras. [00122], [00123]) and, when the nucleic acid based enzyme inhibitor-enzyme complex is heated to a second temperature, the complex dissociates and releases the enzyme allowing for enzyme activity (Paras. [0009], [00123]). Further, Dong defines inhibition of enzyme activity by the inhibitor as a decrease of enzymatic activity encompassing a greater than 99% reduction in activity (Para. [0042]), which is considered to reasonably read on complete blockage of activity. Dong further discloses that inhibition of DNA polymerase by an inhibitor can be indicated by the synthesis of secondary amplicons which can also be inhibited to an extent greater than 99% (Para. [00159], also see Fig 10B).
Dong discloses an exemplary embodiment of DNA polymerase inhibitor B in Fig 10B (and Example 5) which appears to inhibit DNA polymerase activity at 50°C and allows amplification of a desired product when heated to temperatures above 50°C. Based on Fig 10B, no non-specific peaks are present at or around 50°C, which is considered to indicate complete blocking of the DNA polymerase by Dong’s DNA polymerase.
With regard to claim 3, Dong discloses wherein the melting temperature (i.e., the second temperature) of the nucleic acid based enzyme inhibitor can be increased or decreased by changing the length of the complementary sequences of the nucleic acid based enzyme inhibitor, specifically within the complementary sequences of the first and third regions (Para. [0139], lines 1-8) which anneal to form the double stranded portion of a stem loop enzyme inhibitor (Para. [0157], line 1-3). Dong further discloses an exemplary embodiment of a DNA polymerase inhibitor comprising a sequence wherein the complementary first and third regions comprise 20 base pairs (Para. [00144], lines 1-7).
With regard to claim 5, Dong discloses wherein the nucleic acid enzyme inhibitor can form a complex with a DNA polymerase (Paras. [0007], line 14, [00122], [00123]).
With regard to claim 6, Dong discloses wherein the DNA polymerase is Thermus thermophilus (Para. [0098], lines 11-12) which is considered to reasonably read on DNA polymerases of Family A as disclosed in the instant specification on Pg. 8, lines 23-25.
With regard to claim 10, Dong discloses a kit for amplifying target nucleic acids (Para. [0006], lines 1-2) comprising the nucleic acid based enzyme inhibitor (Para. [0016], lines 2-3).
With regard to claim 11, Dong discloses a method of nucleic acid amplification (Para. [0013], line 1) use of a “reaction composition” comprising a DNA polymerase, DNA polymerase inhibitor (i.e., the nucleic acid based enzyme inhibitor), an NTP, a target nucleic acid (i.e., a nucleic acid template), and a primer (Para. [0012], lines 3-5), which is considered to reasonably read on a nucleic acid extension mixture.
Response to Arguments
Applicant's traversal filed February 27, 2026 have been fully considered but they are not persuasive.
Applicant traverses the rejection under 35 U.S.C. 102 over Dong based on assertion that the prior art reference fails to disclose all limitations of the claims as newly amended (Pg. 10). Applicant explains on Pg. 11 that newly amended claim 1 recites that when a temperature of the instantly claimed nucleic acid ligand is maintained at a certain temperature, the enzyme activity of the nucleic acid polymerase is completely blocked without residual activity and when the temperature is higher than said certain temperature, the nucleic acid polymerase detaches from the ligand and is able to exert enzymatic activity and that the certain temperature is 50°C.
First, Applicant asserts that although Dong’s Figures 3-6 include 50°C, the prior art reference of Dong “nowhere emphasizes or highlights 50°C throughout the entire document” (Pg. 11, 3rd para.).
Second, Applicant traverses that in the system comprising the nucleic acid polymerase inhibitor disclosed by Dong, the nuclease maintains activity at 50°C which “could be” corroborated by the description in Dong. Applicant asserts that the disclosure of Dong details a first temperature between 22-40°C where the DNA polymerase inhibitor binds to/complexes with the DNA polymerase and a second temperature between 42-72°C where the DNA polymerase inhibitor-DNA polymerase complex dissociates. Applicant traverses that, based on the disclosure of Dong, at a temperature of 50°C, the system of Dong would not block nuclease activity, blocking of nuclease activity in Dong’s system requires a lower temperature, and Dong’s system cannot completely block nuclease activity (Pgs. 11, 3rd para and 12, 1st para.). Further, Applicant traverses that nuclease activity in Dong’s system recovers at 40°C which differs from the instant invention where nuclease activity recovers at 50°C (Pg. 12, 2nd para.).
Finally, Applicant traverses that Dong neither teaches nor suggests the specific nucleic acid ligand as instantly claimed, specifically based on the instantly claimed dissociation temperature of 50°C and functional ability to completely block enzyme activity below 50°C (Pg. 12, 3rd para.) and therefore, the instantly claimed nucleic acid ligand is novel over the prior art reference of Dong.
Applicant’s traversal has been fully considered but is not found persuasive.
It is noted that although Applicant traverses that Dong does not disclose the limitations of the instant invention, Applicant does not cite the specific sections of Dong which are referenced to support the traversal.
With regard to Applicant’s traversal that the disclosure of Dong does not reference a temperature of 50°C throughout the document, Dong discloses in Para. [00124] exemplary “second temperatures”, i.e., the temperature at which Dong’s DNA polymerase inhibitor releases inhibition of the DNA polymerase and allows enzymatic activity and amplification which are higher than 50°C, which is consider to reasonably read on the instantly claimed temperature “higher than said certain temperature” of 50°C at which the nucleic acid polymerase detaches from the instantly claimed nucleic acid ligand and is able to exert enzymatic activity. Dong discloses an exemplary embodiment of DNA polymerase inhibitor B which appears to release inhibition of amplification at temperatures higher than 50°C (See Fig 10B and modified Fig 10B below). Further, Dong discloses that appropriate first and/or second temperatures for any given amplification reaction could be routinely determined, without undue experimentation, based on the enzyme and melting temperatures of the enzyme inhibitor and/or the primers/probes by methods known in the art and Dong’s teachings (Para. [00124]).
With regard to Applicant’s traversal that Dong’s system is unable to completely block enzymatic activity at 50°C as instantly claimed and nuclease activity recovers at 40°C, it is difficult to determine to which specific section of Dong’s disclosure Applicant is referencing as indicating nuclease activity at 40°C. Dong’s figures depict measurements of fluorescence as indicators of the ability of the enzyme inhibitor to complex with an enzyme and inhibit activity. Dong discloses that heating an amplification reaction to or above the melting temperature of Dong’s DNA polymerase inhibitor causes dissociation of the DNA polymerase inhibitor-DNA polymerase complex, releasing inhibition of the DNA polymerase (Paras. [00166], [00167]). Although Dong’s disclosure uses the term “inhibition” as it relates to the disclosed enzyme inhibitor’s effect on enzymatic activity, Dong defines inhibition as the decrease of enzymatic activity in the presence of Dong’s enzyme inhibitor which encompasses a greater than 99% reduction in enzyme activity (Para. [0042]), which is considered to reasonably read on complete blockage of activity, and further details that inhibition of DNA polymerase can be indicated by the synthesis of secondary amplicons which can also be inhibited to an extent greater than 99% (Para. [00159]). Dissociation peaks detailed in Example 1 and Figs 3-4 and 6 of Dong indicate that the melting temperature of Dong’s DNA polymerase inhibitors is above 50°C. Further, Fig 10B (Example 5) of Dong depicts amplification of a product in the presence of exemplary DNA polymerase inhibitor B and appears to show specific amplification of the desired amplicon with no non-specific peaks present at or around 50°C (see modified Fig 10B below), which indicates that DNA polymerase inhibitor B of Dong was able to block DNA polymerase activity at 50°C. Thus, Dong’s disclosed DNA polymerase inhibitors are considered to both complex with a DNA polymerase at temperatures of 50°C and completely block enzymatic activity.
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Therefore, a skilled artisan would have readily envisioned, based on Dong’s disclosure, a nucleic acid ligand which is able to bind to/complex with a nucleic acid polymerase and completely block activity of the nucleic acid polymerase at a certain temperature of 50°C and, at a temperature higher than 50°C, dissociate from the nucleic acid polymerase thereby allowing enzymatic activity.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631
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