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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on Dec. 02, 2025.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Dec. 02, 2025. Claims 9-21 are pending. Claims 16-21 are withdrawn. Claims 9-15 are currently examined.
Specification Objection
(Previous objection- withdrawn) The disclosure is objected to because the
specification contains sequences not identified by SEQ ID NOs on pages 89-105 of the clean specification submitted 08-19-2025.
This objection is withdrawn in view of the amendment filed on Dec. 02, 2025.
(New objection) 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. 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.
(Previous rejection- withdrawn) Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and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.
This rejection is withdrawn in view of the amendment filed on Dec. 02, 2025.
(New rejection) 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.
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.
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.
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.
(New Rejection-necessitated by amendment) 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.1 (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.
(New Rejection-necessitated by amendment) 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 comprises a linking sequence from the sequences with SEQ ID NO: 723 to SEQ ID NO: 838 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 can not 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 Dec. 02, 2025 has been received and fully considered.
The drawing is accepted as the petition to accept color drawings was granted on 12/09/2025.
2). The specification objection on sequence listing is withdrawn based on the amendment filed on Dec. 02, 2025.
3). The rejection under 35 U.S.C. § 112(b) is withdrawn based on the amendment filed on Dec. 02, 2025.
4). Applicant’s arguments on rejection under 35 U.S.C. § 103 is not found persuasive as follows:
i). Primer design is a routine technique in the art. Christen teaches that the primer target sequence is known. 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 the claimed primer sets for RT-LAMP through routine experimentation, especially the base claim 9 allows up to 10% variation for the claimed primer sequences.
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ii). Huang et al., the newly cited prior art, teaches using a nest type RPA method to detect SARS CoV-2 virus nucleic acid (See Abstract) and discloses several primers that are identical to the claimed SEQ ID NOs: 1-8, 723 and 838. For example, the claimed SEQ ID NO: 3 is identical to Huang’s outer primers F5-10 (SEQ ID NO: 30) (See page 8; Table F below). Here it further demonstrates that Christen’s sequences can be a target sequence of the RT-LAMP primer sets as claimed.
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.
Accordingly, applicant’s arguments, for example as “the Office has merely shown that flour, butter, eggs, and sugar exist and that there's a textbook out there that says it is possible to bake a cake. General "principles" of primer design do not a guarantee of success make nor do they designate what specific sequences for any given vector are necessary” (See instant remarks, page 7), are not persuasive.
Conclusion
No claims are allowed.
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-4:30 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