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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on April 06, 2026. Claims 9-21 are pending. Claims 16-21 are withdrawn. Claims 9-15 are currently examined.
Specification Objection
(Previous objection-maintained) The specification is objected for the error code (CRFD) in the SLIC-sequence listing access such as the sequence listing in computer readable format is defective, where the SEQ ID NOs: 723-838 are not found in the sequence listing. See MPEP 2417 Helpful Hints for Sequence Rules Compliance under WIPO Standard ST.26. ─ An amended "Sequence Listing XML," including one submitted to address a defective sequence listing (validated as CRFD), must be accompanied by a statement: • indicating that no new matter has been introduced; • identifying the locations of additions, deletions or replacements of sequence information relative to the replaced listing; AND • identifying the support for the additions, deletions or replacements of sequence information within the application as filed.
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.
Claim 10 is 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.
(previous rejection-withdrawn) Claim 10 recites a phrase “…the FIP sequence further comprises a linking sequence from the sequences with SEQ ID NO: 723 to SEQ ID NO: 838 joining…” that renders the claim indefinite. It is unclear if the linking sequence comprises or consist of the SEQ ID NOs: 723 and 838.
This rejection is withdrawn in view of the amendments filed on April 06, 2026.
(New rejection) The amended claim 10 is rejected because they contain an improper Markush grouping of alternatives at ‘to” in the “…sequence selected from the sequences with SEQ ID NO: 723 to SEQ ID NO: 838”. See MPEP § 2117. A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim.
The amended claim 10 also recites “…the sequences with SEQ ID NO: 723 to SEQ ID NO: 838”, where the “with” renders the claim indefinite. It is not clear if the sequences “consist of “or “comprise” the SEQ ID NO: 723 to SEQ ID NO: 838. For purposes of compact prosecution and applying prior art, claim 10 was interpreted herein that the linking sequence comprises the SEQ ID NO: 723 to SEQ ID NO: 838.
The amended claim 10 also recites “incorporates” that render the claim indefinite. It is unclear how the FIP sequence incorporates a linking sequence and join other SEQ ID NOs. Applicant has not defined the criteria and methods for the “incorporates”. For example, it is not clear if the linking sequence is incorporated between SEQ ID NOS: 1-2, and SEQ ID NOs: 3 and 4, respectively, or among the SEQ ID NOS 1-4, and then how the linking sequence is incorporated. The specification does not define “incorporates” such that one of ordinary skill in the art would know what the “incorporates” is and how to properly make the “incorporates” for linking other sequences as claimed. Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claims. For purposes of compact prosecution and applying prior art, claim 10 was interpreted herein to encompass a linking sequence that joins SEQ ID NOs: 1-2 and SEQ ID NOs: 3-4, respectively.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action
Given the struggle to interpret the claim 10, a proposed amendment is drafted for consideration as follows:
10. (Currently Amended) The primer set of claim 9, wherein the FIP sequence further comprises a linking sequence selected from the sequences consisting of wherein the linking sequence joins [[:]] SEQ ID NO: 1 and SEQ ID NO: 2 [[;]] or SEQ ID NO: 3 and SEQ ID NO: 4, respectively.
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.
(Previous rejection-maintained) Claims 9 and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Christen (US20240376492A1- effective filing date 05-20-2020) in view of Montrasio (dissertation 2016- see attached form 892), and Schermer et al (PLoS One 2020- included on IDS).
The base claim 9 is directed to a primer set for reverse transcription loop-mediated isothermal amplification (RT-LAMP) analysis, comprising a forward inner primer (FIP) sequence that is at least 90% identical to a combination of SEQ ID NO: 1 and SEQ ID NO: 2; a backward inner primer (BIP) sequence that is at least 90% identical to a combination of SEQ ID NO: 3 and SEQ ID NO: 4; a forward outer primer (F3) sequence that is at least 90% identical to SEQ ID NO: 5; a backward outer primer (B3) sequence that is at least 90% identical to SEQ ID NO: 6; a forward loop primer (LF) sequence that is at least 90% identical to SEQ ID NO: 7; and a backward loop primer (LB) sequence that is at least 90% identical to SEQ ID NO: 8.
The claim 15 is directed to a primer set wherein: the FIP sequence is from 90% to 100% identical to a combination of SEQ ID NO: 1 and SEQ ID NO: 2; the BIP sequence is from 90% to 100% identical to a combination of SQ ID NO: 3 and SEQ ID NO: 4; the F3 sequence is from 90% to 100% identical to SEQ ID NO: 5; the B3 sequence is from 90% to 100% identical to SEQ ID NO: 6; the LF sequence is from 90% to 100% identical to SEQ ID NO: 7; and the LB sequence is from 90% to 100% identical to SEQ ID NO: 8.
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Christen et al. teaches a synthetic nucleic acid for using in coronavirus vaccines (See [0001]). Specifically, Christen teaches that the nucleic acid according to claim 1, characterized in that sequence parts A to C correspond to the sequence according to SEQ ID NO: 19 or the corresponding ribonucleic acid sequence (See page 21, claim 5), where the SEQ ID NO: 19 comprises the claimed SEQ ID NOs: 1-8 at 100% identity (See Table A and B below, where “/c” indicates identity to the complementary strand of SEQ ID NO: 19).
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Accordingly, Christen et al. teaches a sequence that comprises the required SEQ ID NOs: 1-8. However, Christen does not teach that these sequence fragments being used as primers for the RT-LAMP.
Schermer et al. teaches primer sets for detection of SARS-CoV-2 using RT-LAMP assays. Specifically, Schermer et al teaches "among these new primer sets, the oligos targeting Orf7a showed the highest sensitivity and specificity in several tests on diluted isolated RNA" (See page 4, paragraph 6; The examiner notes that the claimed RegX3.1 primer set (i.e. SEQ ID NOs 1-8) targets SARS-CoV-2 orf7ab (See the instant specification, [0099])). Schermer et al. also teaches using the primerexplorer V5 tool (http://primerexplorer.jp/e/) to design LAMP primer and the primers can be ordered from IDT, purified with standard desalting, as PAGE purification did not improve the performance of the assays (See page 3, paragraph 3).
Accordingly, Schermer et al. teaches using RT-LAMP assay for rapidly detecting SARS-COV-2 and discloses a LAMP primer design tool.
Montrasio teaches a principle for primer designing for LAMP. LAMP requires minimally four primers (F3, FIP, B3, and BIP) that recognize six distinct regions on the target gene (section 1.1 page 16 and Figure 1). In addition to these four primers, one can optionally include two additional "loop primers", LF and LB (section 1.2 page 20 and Figure 4). The examiner has interpreted based on the disclosed sequences and Table 10 of the specification that the claimed SEQ ID NOs correspond to the following primers required for LAMP (See Table C below):
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It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Christen, Schermer and Montrasio to arrive at LAMP primers that can be used to amplify the SARS-CoV-2 sequence disclosed by Christen. One would have been motivated to do so for the advantage of using the LAMP assay for SARS-CoV-2 detection, which is a cheaper and faster method than conventional PCR detection (Montrasio page 16 paragraph 1). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 11, based on the sequence analysis in Tables A and B above, Christen et al. teaches that the GC content of Christen SEQ ID NO: 19 is 40.2% ((874 guanines + 930 cytosines)/ 4486 total bases = 40.2%).
Regarding claims 12 and 14, Montrasio teaches the key factors for LAMP primer design (sections 2.2.1 and 2.2.2). Specifically, Montrasio teaches the stability at the end of each primer by stating that the 3’ends of F2/B2, F3/B3 and LF/LB and the 5’end of F1c/B1c (corresponding to the 3’end of F1/B1) are designed so that the change in free energy (ΔG value) is -4kcal/mol or less (See page 31, paragraph 1). Montrasio also teaches that it is important that primers, particularly the inner primers FIP and BIP, are designed to avoid the formation of secondary structures. A 3'end hairpin with a ΔG of -2 kcal/mol and an internal hairpin with a ΔG of -3 kcal/mol are generally tolerated (See bridging pages 31-32). Here Montrasio’s kcal/mol can teaches the range of the claimed “less than -2.5 kcal/mol” (claim 12) and/or “less than -3.0 kcal/mol” (claim 14). Because the claimed SEQ ID NOs: 1-8 are known sequence based on Christen’s teaching, it would be obvious for one of ordinary skill in the art to follow the primer design rules of Montrasio and design the primers as claimed.
Also, it is noted that the courts have stated where the claimed ranges "overlap or lie inside the ranges disclosed by the prior art" and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 13, Montrasio teaches the Melting Temperature (Tm) by stating that base on the Primer Explorer V4 manual (https://primerexplorer.jp/e/ v4_manual/), the Tm for each LAMP region is designed to be about 65°C (64 - 66°C) for F1c and B1c, about 60°C (59 - 61°C) for F2, B2,F3, and B3, and about 65°C (64 - 66°C) for the loop primers. Primers with higher melting temperatures (above 66°C) have a tendency for secondary annealing (See page 32), where the Tm is comparable to the ranges of the claimed melting temperature. Therefore, it would be obvious for one of ordinary skill in the art to use the primer melting temperature range of Montrasio to design a RT-LAMP primer set as claimed, and the result would be predictable by targeting the known sequence of Christen et al.
In addition, according to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”). Since Montrasio teaches a similar melting temperature range for designing the LAMP primers, one of ordinary skills would be able to test for an optimal condition for the claimed melting temperatures through routine experimentation. Therefore, the claimed melting temperature would have been obvious unless there is evidence showing that they produce unexpected results.
(Previous rejection-maintained) Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Christen et al. (US20240376492A1- effective filing date 05-20-2020) in view of Montrasio (dissertation 2016- see attached form 892), and Schermer et al (PLoS One 2020- included on IDS) as applied to claims 9 and 11-15 above, and further in view of Huang et al. (CN112739833A, the priority filing date: April 25, 2020).
The claim 10 requires that the FIP sequence further incorporates a linking sequence selected from the sequences with SEQ ID NO: 723 to SEQ ID NO: 838 and joining: SEQ ID NO: 1 and SEQ ID NO: 2; or SEQ ID NO: 3 and SEQ ID NO: 4.
Based on the specification objection above, SEQ ID NOs: 723 and 838 cannot be searched through ABSS because the computer readable format is defective. However, with a BLAST comparison, the SEQ ID NO: 19 of Christen et al. comprises an identical sequence matching to SEQ ID NO: 838 (See Table D below).
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For the claimed SEQ ID NO: 723, Huang et al. teaches primer pair, probe and kit for detecting SARS-CoV-2 by utilizing nested RPA technology and application thereof (See Abstract), where the outer primer SEQ ID NO: 36 of Huang teaches the SEQ ID NO: 723 (See e.g., page 3; Table E below). At the same time, Montrasio teaches that the important aspect of dumbbell visualization is linked to the possibility to display the loop primers on the dumbbell, allowing to more accurately evaluate their positioning on the loop regions, even by comparison with previous primer designs (See page 101).
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It would have been prima facie obvious to a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Christen, Montrasio, Schermer and Huang to arrive at a nucleotide sequence comprising a linking sequence joining SEQ ID NOs 1 and 2 or 3 and 4. One would have been motivated to do so for the advantage of having a linking sequence available for binding of loop primers, which increase the rate of DNA production and sensitivity of the LAMP method, as taught by Montrasio (page 21 ). Also, one of skill in the art would be motivated to use the known sequence that matches to the SEQ ID NOs: 723 and 838 (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Responses to Applicant’s Remarks
Applicant’s arguments filed on April 06, 2026 has been received and fully considered.
The rejection under 35 U.S.C. § 112(b) is withdrawn based on the amendment filed on April 06, 2026.
Applicant’s arguments regarding the rejection under 35 U.S.C. § 103 is not found persuasive as follows:
1). Applicant argued that in formulating the prima facie case, the Office relies on a combination of three (3) references with each reference providing its own unique contribution to an envisioned whole. Thus, in argument or in reference to a single reference, Applicant does so in view of the contribution to the whole and that failure of contribution, by necessity, leads to failure of combination (See Remarks, page 8), and the combination of references submitted by the Office provides no disclosure that is
enabling for the specific primers taught and claimed by Applicant in the configurations taught and claimed by Applicant (See Remarks, page 9).
The argument is not persuasive.
(i) Christen teaches the sequence that contain the identical SEQ ID NOs as claimed for the primer set. Schermer teaches that the RT-LAMP can be used for SARS-COV-2 detection, and Montrasio teaches the principles of primer design and the tools used for the primer design. Based on these descriptions, one of ordinary skills would be able to design a primer sets as claimed for RT-LAMP through routine experimentation, especially the base claim 9 allows up to 10% variation for the claimed primer sequences.
(iii) Additionally, such a combination, or a substitution of one element for another
known in the field to have the same function, is evidence that the claimed invention
may be found obvious. See e.g., KSR International v. Teleflex Inc., 82 U.S.P.Q.2d
1385, at 1395. Therefore, the instant invention as a whole was prima facie obvious to
one of ordinary skill in the art at the time the invention was made, as evidenced by the
references, especially in the absence of evidence to the contrary.
2). Applicant argued that although a process in and of itself may arguably seem "routine" (e.g., due to a ready supply of reagents, computer aid, usage of some
standardized techniques) it is the results of a process that matter. It is clear that applications of the same technique can bring forward exceptionally
different results (just as the same techniques can bring one a chocolate, vanilla, or carrot cake) (See Remarks, page 9).
The argument is not persuasive.
First, primer design and reaction conditions of RT-LAMP are routine technique in the art, one of ordinary skills would be able to test for an optimal primer set as claimed through routine experimentation. Therefore, the claimed primer set for RT-LAMP would have been obvious unless there is evidence showing that they produce unexpected results.
Second, for the “results” as argued, the instant claims are directed to a primer set and do not cite limitations regarding the results.
Also, although the primer set are not the same, one of the RT-LAMP primer set of Schemer is designed base on the ORF7a of SARS-COV-2 (See Table S1 below) that is a region of the ORF7ab disclosed in the instant specification (See e.g., instant specification, Example 8). Schemer teaches that they describe a newly designed multiplexed RT-LAMP assay targeting Orf3a and Orf7a of SARS-CoV-2 (See page 2, Introduction), and among those new primer sets, the oligos targeting Orf7a showed the highest sensitivity and specificity in several tests on diluted isolated RNA and was thus selected for further testing in primary material (See page 4, paragraph 6), which indicates that Christen in view of Schermer teaches a detection targeting region as disclosed in the instant application, and achieves a highest sensitivity and specificity detection by designing primer set to target the Orf7a region through RT-LAMP. It would be obvious that one of skilled in the art can focus on the Orf7a region to design the primer set as claimed through experimental optimization.
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Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am-5:00 pm, EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached on (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RUIXUE WANG/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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