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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/14/2023 and 05/21/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The Third-Party Submission Under 37 CFR 1.290 submitted on 03/19/2026 is being considered by the examiner.
Status of Claims
This office action is in response to an Amendment filed on June 15, 2026.
Claims 1-2, 4-7, 9-12, 14-17, 19-21, 23, 26-33 and 35-36 were previously pending. Applicant amended claims 1-2 and 7; cancelled claim 35.
Claims 1-2, 4-7, 9-12, 14-17, 19-21, 23, 26-33 and 36 are currently pending, with claims 6 and 29-32 withdrawn.
Claims 1-2, 4-5, 7, 9-12, 14-17, 19-21, 23, 26-28, 33 and 36 are under consideration. This is the first action on the merits.
Election/Restrictions
Applicant’s election without traverse of the following species in the reply filed on June 15, 2026 is acknowledged:
Species of method detecting target nucleic acids using duplex compositions: Figure 12 (combination 5);
Species of signal-changing temperature range: A) the signal-changing temperature ranges (SChTR) do not overlap between compositions for detecting different target nucleic acids (claim 5; see Figure 4 (a))1;
Species of signal detection: C) the detection of signals is carried out at at least two of the plurality of cycles (claim 27)2 .
Claims 6 and 29-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Examination on the merits commences on claims 1-2, 4-5, 7, 9-12, 14-17, 19-21, 23, 26-28, 33 and 36.
Priority
The effective filling date of the instant claims 1-2, 4-5, 7, 9-12, 14-17, 19-21, 23, 26-28, 33 and 36 is 06/17/2022, the filling date of the PCT application PCT/KR2022/008659.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Specifically, Applicant's claim to foreign priority to REPUBLIC OF KOREA Application 10-2021-0078463 is acknowledged. However, the submitted foreign priority document is NOT in English, and NO English translation has been submitted.
The foreign priority date may be the effective filing date of the claimed invention if:
• the foreign application supports the claimed invention under 35 U.S.C. 112(a), AND
• the applicant has perfected the right of priority by providing a certified copy of the priority application, and a translation of the certified copy (if not in English) along with a statement that the translation of the certified copy is accurate.
See MPEP 213.04 and 216; See also MPEP 2304.01(c)
In this instant case, the priority document submitted is not in English and without a translation; without an English translation, the examiner is unable to verify whether the earlier applications provide written description support for the claimed invention under 35 U.S.C. 112(a). Thus, since an English translation of the foreign priority document has not been filed, the effective filing date (EFD) of the claimed invention is the filing date of the PCT application.
However, if applicant perfects the right of priority by providing an certified English translation of the priority application that supports the claimed invention under 35 U.S.C. 112(a), the effective filing date will be the filing date of the foreign application.
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
For the purpose of applying prior art, claim 20 recites terms "single-typed duplex" and "plural-typed duplexes," which are not expressly defined in the application's disclosure.
Relevant descriptions in the specification are as follows:
"In one embodiment, when the duplex providing the signal change is a single-typed duplex, the amount of the single-typed duplex changes depending on the presence of a target nucleic acid, thereby changing the signal.
…
In one embodiment, when the duplex is plural-typed duplexes, the amount ratio between the plural-typed duplexes changes depending on the presence of a target nucleic acid, thereby changing the signal. " (page 42-43)
Accordingly, under BRI and in light of the specification, the term "single-typed duplex" is interpreted to encompass oligonucleotide duplexes that are capable of changing their amounts based on the presence of a target nucleic acid, including a PTOCE (probing and tagging oligonucleotide cleavage and extension) duplex.
The term "plural-typed duplex" is interpreted to encompass oligonucleotide duplexes that are capable of changing the ratio of amount of duplexes in a reaction, based on the presence of a target nucleic acid.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 19 is an improper dependent claim because it refers back to "claim 1718," which is not a claim previously set forth in the application.
A dependent claim must refer back to and further limit a preceding claim, see MPEP§608.01(n). In this instant case, because claim 1718 is not in the listing of the claims, claim 19 does not properly depend from an existing claim and therefore is incomplete.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
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 –
(a)(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 1-2, 4-5, 7, 9-12, 14-17, 19-21, 23, 26-28, 33 and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KO (WO2019203623A1- Method and apparatus for detecting a plurality of target nucleic acid sequences in sample ; Published on: 2019-10-24).
Regarding claim 1, KO teaches a method for detecting n target nucleic acids in a sample (Fig. 2; p.37-39), comprising:
(a) detecting signals at n detection temperatures (Fig. 2),
while incubating with n compositions for detecting the target nucleic acids, a sample suspected of containing at least one of the n target nucleic acids in a reaction vessel (Fig. 2; page 38, lines 19-20, “FIG. 2 illustrates three detection temperature ranges for three target nucleic acid sequences”; page 39, lines 18-20; Fig. 1; page 3, lines 24-25 “methods for detecting a plurality of target nucleic acid sequences using a label having an identical signal property in a single reaction vessel.”);
wherein n is an integer of 3 or more (Fig. 2),
wherein the incubation comprises a plurality of cycles and the detection of signals is carried out at at least one of the plurality of cycles (Fig. 1),
wherein each of the n compositions for detecting the target nucleic acids provides a signal change at a corresponding detection temperature among the n detection temperatures in the presence of a corresponding target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27),
the signal change indicating the presence of a corresponding target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27),
wherein a composition for detecting an ith target nucleic acid among the n compositions for detecting the target nucleic acids provides a signal change at an ith detection temperature among the n detection temperatures and provides a constant signal at the other detection temperatures in the presence of the ith target nucleic acid, the signal change indicating the presence of the ith target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27), and
wherein i represents an integer from 1 to n, and the ith detection temperature is lower than the (i+1)th detection temperature (Fig. 2) ; and
(b) determining the presence of the n target nucleic acids from the signals detected in step (a), wherein the presence of the ith target nucleic acid is determined by the signal change detected at the ith detection temperature (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27).
Regarding claim 2, KO teaches wherein in the temperature range covering all of the n detection temperatures, the composition for detecting the ith target nucleic acid has a signal-changing temperature range (SChTR) in which the signal changes depending on the presence of the ith target nucleic acid, and one or two signal-constant temperature ranges (SCoTRs) in which the signal is constant even in the presence of the ith target nucleic acid (Fig. 2, the signal-changing temperature range for one target is the signal-constant temperature range for the others; p. 37, lines 15-27, duplex for detecting targets; p. 39, lines 20-22 “first detection temperature range is a temperature range in which the signal for the first target nucleic acid sequence is changed but the signals for the second and the third target nucleic acid sequences remain substantially unchanged; p. 38, lines 26-27 – p. 39 lines 1-6 “each of the detection temperature ranges is a temperature range in which the amount of duplexes for other target nucleic acid sequences remains unchanged”).
Regarding claim 4, KO teaches wherein the composition for detecting the ith target nucleic acid is an Under-Signal-Change (UnderSC) composition having a characteristic that the signal-changing temperature range is lower than the signal-constant temperature range (Fig. 2; 1st detection temperature range for 1st target).
Regarding claim 5, KO teaches wherein the ith detection temperature is selected within the signal-changing temperature range of the composition for detecting the ith target nucleic acid, wherein the ith detection temperature is not included in the signal-changing temperature ranges of the compositions for detecting the other target nucleic acids (Fig. 2, Fig 3).
Regarding claim 7, KO teaches the composition for detecting the first target nucleic acid is an UnderSC composition or an InterSC composition, the composition for detecting the nth target nucleic acid is an InterSC composition or an OverSC composition, and each of the compositions for detecting target nucleic acids other than the first target nucleic acid and the nth target nucleic acid is an InterSC composition (Fig. 2; 3).
Regarding claim 9, KO teaches wherein the composition for detecting the ith target nucleic acid comprises a label that provides a signal dependent on the presence of the ith target nucleic acid (p. 69 lines 16-24, “the signal-generating compositions comprise a composition which comprises a labeled oligonucleotide for generating a detectable signal by a cleavage reaction dependent on the presence of one of the plurality of target nucleic acid sequences”) .
Regarding claim 10, KO teaches the label is linked to an oligonucleotide (p. 70, lines 10-12 “a label linked to the oligonucleotide to generate a signal by cleavage”).
Regarding claim 11, KO teaches the composition for detecting the ith target nucleic acid provides a duplex providing a signal change; wherein the duplex providing the signal change comprises a label (p. 69, lines 19-22).
Regarding claim 12, KO teaches the composition for detecting the ith target nucleic acid provides a duplex providing a signal change, and the composition for detecting the ith target nucleic acid provides a signal from the label when the duplex providing the signal change is in an associated form or in a dissociated form (p. 69, lines 19-22).
Regarding claim 14, KO teaches the duplex providing the signal change has initially been included in the composition for detecting the ith target nucleic acid (p. 78 lines 6-10) .
Regarding claim 15, KO teaches the duplex providing the signal change is generated by hybridization between a label-linked oligonucleotide and an oligonucleotide hybridizable with the label-linked oligonucleotide (p. 20 lines 15-27).
Regarding claim 16, KO teaches the duplex providing the signal change is generated in incubating (p. 18, lines 15-27 – p.19 lines 1-26, PTOCE method which involves target-dependent duplex and signal formation driven by cleavage, thus a skilled artisan would readily understand that incubation is necessary for the reaction to take place ).
Regarding claim 17, KO teaches the duplex providing the signal change is generated by (i) hybridization between a label-linked oligonucleotide and the target nucleic acid or (ii) a cleavage reaction dependent on the presence of a target nucleic acid (p. 18, lines 15-27 – p.19 lines 1-26, PTOCE method).
Regarding claim 19, KO teaches the composition for detecting the target nucleic acid comprises a tagging oligonucleotide that hybridizes to the target nucleic acid, and the cleavage reaction dependent on the presence of the target nucleic acid involves cleavage of the tagging oligonucleotide (p. 18, lines 15-27 – p.19 lines 1-26, PTOCE method comprising a PTO (Probing and Tagging Oligonucleotide)).
Regarding claim 20, KO teaches the duplex providing the signal change is a single-typed duplex (p. 37, lines 26-27, a detection temperature range in which the amount of a duplex for each corresponding target nucleic acid sequence is changed; p. 2 lines 4-5; p.21 lines 11-12 “PTOCE-based methods commonly involve the formation of the extended
strand depending on the presence of a target nucleic acid sequence”).
Regarding claim 21, KO teaches when the duplex providing the signal change is the single-typed duplex, the amount of the single-typed duplex changes depending on the presence of the target nucleic acid, thereby changing the signal (p. 37, lines 26-27, a detection temperature range in which the amount of a duplex for each corresponding target nucleic acid sequence is changed; p. 2 lines 4-5; p.21 lines 11-12 “PTOCE-based methods commonly involve the formation of the extended strand depending on the presence of a target nucleic acid sequence”).
Regarding claim 23, it recites "wherein, when the duplex is the plural- typed duplexes, the Tm values of the duplexes are different from each other." This limitation is contingent language that is not essential to the operation of the claimed method, as it does not require an action upon every practice of the claim.
Here, KO anticipates claim 23 because it discloses the single-typed duplex in base claim 20, which recites "a single-typed duplex or plural-typed duplexes." Because KO satisfies the single-typed duplex alternative, the condition in claim 23 is not required to be met .
Regarding claim 26, KO teaches wherein the composition for detecting the ith target nucleic acid provides a duplex providing a signal change, and the signal-changing temperature range of the composition for detecting the ith target nucleic acid is determined depending on the length and/or sequence of the duplex (p. 19 lines 14-17; p.22 lines 6-10; p. 23 lines 9-19; p. 57 lines 2-10; p.82 lines 1-7) .
Regarding claim 27, KO teaches wherein the detection of signals is carried out at at least two of the plurality of cycles (fig. 1; p. 19 lines 25-26 signal generation by PTOCE method comprising “repeating all or some of the steps (a)-(e) with denaturation between repeating cycles” thus detection signal detection is carried out at at least two cycles) .
Regarding claim 28, KO teaches wherein the signal change is measured using the signals detected at the at least two of the plurality of cycles (Fig. 1; Fig. 2-3; p. 78 lines 10-20) .
Regarding claim 33, KO teaches nucleic acid amplification reaction (p. 33 lines 6-9).
Regarding claim 363, KO teaches a method for detecting three target nucleic acids in a sample (Fig. 2), comprising:
(a) detecting signals at a first detection temperature, a second detection temperature, and a third detection temperature (Fig. 2),
while incubating the sample suspected of containing at least one of the three target nucleic acids with a composition for detecting a first target nucleic acid, a composition for detecting a second target nucleic acid, and a composition for detecting a third target nucleic acid in a reaction vessel (Fig. 2; page 38, lines 19-20, “FIG. 2 illustrates three detection temperature ranges for three target nucleic acid sequences”; page 39, lines 18-20; Fig. 1; page 3, lines 24-25 “methods for detecting a plurality of target nucleic acid sequences using a label having an identical signal property in a single reaction vessel.”);
wherein the incubation comprises a plurality of cycles, and the detection of signals is carried out at at least one of the plurality of cycles (Fig. 1),
wherein the composition for detecting the first target nucleic acid provides a signal change at the first detection temperature and provides a constant signal at the second detection temperature and the third detection temperature in the presence of the first target nucleic acid (Fig. 2; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27),
the signal change indicating the presence of the first target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27);
the composition for detecting the second target nucleic acid provides a signal change at the second detection temperature and provides a constant signal at the first detection temperature and the third detection temperature in the presence of the second target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27),
the signal change indicating the presence of the second target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27); and
the composition for detecting the third target nucleic acid provides a signal change at the third detection temperature and provides a constant signal at the first detection temperature and the second detection temperature in the presence of the third target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27),
the signal change indicating the presence of the third target nucleic acid (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27), and
wherein the first detection temperature is lower than the second detection temperature, and the second detection temperature is lower than the third detection temperature (Fig. 2) , and
(b) determining the presence of the three target nucleic acids from the signals detected in step (a),
wherein the presence of the first target nucleic acid is determined by the signal change detected at the first detection temperature, the presence of the second target nucleic acid is determined by the signal change detected at the second detection temperature, and the presence of the third target nucleic acid is determined by the signal change detected at the third detection temperature (Fig. 2; p. 37 lines 15-27; p. 38 lines 26-27 - p. 39 lines 1-6; p. 39 lines 18-27).
Double Patenting- Obvious Type
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4, 7, 9-12, 15-17, 19, 27-28, 33 and 36 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2, 4, 6, 9 of U.S. Patent No.12188082B2 in view of Agee (Sara Agee ; High-Multiplex Real-Time PCR Design; March 31, 2016; www .genengnews.com/insights/high-multiplex-real-time-pcr-design).
Instant claim 1 recites:
A method for detecting n target nucleic acids in a sample, comprising:
(a) detecting signals at n detection temperatures (‘082 Patent, claim 1, “obtaining at all or partial cycles of the reaction, signal values at at least two detection temperatures in each of a plurality of detection temperature ranges assigned to the plurality of target nucleic acid sequences”),
while incubating with n compositions for detecting the target nucleic acids, a sample suspected of containing at least one of the n target nucleic acids in a reaction vessel;
wherein n is an integer of 3 or more (‘082 Patent, claim 1, “a plurality of target nucleic acid” encompasses 3 or more target nucleic acids),
wherein the incubation comprises a plurality of cycles and the detection of signals is carried out at at least one of the plurality of cycles (‘082 Patent, claim 1 ),
wherein each of the n compositions for detecting the target nucleic acids provides a signal change at a corresponding detection temperature among the n detection temperatures in the presence of a corresponding target nucleic acid ( ‘082 Patent, claim 1, “obtaining a signal-change value of signal values between two reference temperatures selected from the at least two detection temperatures in each of the plurality of detection temperature ranges such that a data set of cycle/signal-change value for each of the plurality of target nucleic acid sequences is obtained”)
the signal change indicating the presence of a corresponding target nucleic acid (‘082 Patent, claim 1),
wherein a composition for detecting an ith target nucleic acid among the n compositions for detecting the target nucleic acids provides a signal change at an ith detection temperature among the n detection temperatures and provides a constant signal at the other detection temperatures in the presence of the ith target nucleic acid, the signal change indicating the presence of the ith target nucleic acid, and
wherein i represents an integer from 1 to n, and the ith detection temperature is lower than the (i+1)th detection temperature; and
(b) determining the presence of the n target nucleic acids from the signals detected in step (a), wherein the presence of the ith target nucleic acid is determined by the signal change detected at the ith detection temperature (‘082 Patent, claim 1).
The ‘082 Patent claims a method for detecting a plurality of target nucleic acids in a sample. The method includes contacting the sample with signal-generating compositions comprising duplexes that provide signals indicating the presence or absence of corresponding target nucleic acids, wherein the duplex have Tm values different from each other (‘082 Patent, claim1). A signal change value between two reference temperatures is obtained for each target nucleic acid.
The method of the ‘082 Patent largely overlaps with the method recited in instant claim 1. The ‘082 Patent does not expressly recite that, in the presence of the ith target nucleic acid, the composition provides a signal change at a detection temperature for the ith target nucleic acid and a constant signal at the other detection temperatures for the other targets.
The ‘082 Patent does not expressly recite that the ith detection temperature is lower than the (i+1)th detection temperature. However, these features would have been obvious in view of Agee.
Similar to the method of the ‘082 Patent, Agee teaches detecting three target nucleic acids in a sample using duplexes having different Tm values (Figure 3).
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Agee teaches, for each target nucleic acid, detecting a signal change at a detection temperature and a constant signal at the other detection temperatures for the other targets (page 5, lines 5-7, “Figure 3 shows a representative example of Pitcher-Catcher designs to differentiate between three unique melt curves for three targets in a single channel”; Figure 3 shows each target detection is indicated by a signal peak (e.g., signal change) at a specific detection temperature, while there is no peak (e.g., constant signal) at the other two temperature).
Because signal generation depends on dissociation and hybridization of duplexes having different Tm values, the detection temperature for one target is lower than the detection temperature for another target, so that the targets can be detected in a multiplexed manner (see Agee., Figure 3, e.g., 65°C is lower than 70°C). Thus, Agee teaches the limitation that “the ith detection temperature is lower than the (i+1)th detection temperature.”
Given these teachings, it would have been prima facie obvious for one of ordinary skill in the art to use the signal detection scheme taught by Agee in the method of the ‘082 Patent, specifically to use the detection temperature for one target as the reference temperature for measuring a constant signal for another target. Both methods rely on different duplex Tm values for multiplex target detection. The ‘082 Patent already claims detecting signals at different temperatures to obtain signal change values for each target. Agee provides further detail that, in a multiplex assay using duplexes with different Tm values, a temperature that produces a signal for one target can also serve as a temperature at which provides a constant signal for another target.
This modification is a predictable and efficient use of the template-dependent signal behavior already used in the ‘082 Patent. For example, for three targets, the method does not need six separate measurements at six different temperatures; the same three detection temperatures can provide both signal-change and constant-signal information for distinct targets, as shown in Figure 3 of Agee. This modification represents a predictable use of prior art elements according to known methods to yield predictable results (see MPEP §2143).
Therefore, instant claims 1-2, 4, 7, 12, 27-28, 33 and 36 are obvious over claim 1 of the '082 patent, in view of Agee. Instant claims 9-11, 15, 16, 17, 19 are obvious over claims 2, 6, 4, 9 of the '082 patent, in view of Agee.
Prior Art
Other prior art also teach detecting target nucleic acids using composition comprising duplexes at different detection temperatures:
Lee et al. Single-channel multiplexing without melting curve analysis in real-time PCR. Sci Rep 4, 7439 (2014).; doi.org/10.1038/srep07439;
Fu (US20130267434A1 - Multiplex amplification and detection; Published 2013-10-10);
Li (US20200140931A1- Method for detecting target nucleic acid sequences; published 2020-05-07);
Nagano (US20180155764A1 - Kit for together detecting multiple target nucleic acids differing from each other and detection method using the same; published 2018-06-07);
Todd (WO2020206509A1 - Multiplex detection of nucleic acids using mixed reporters; Published 2020-10-15).
Conclusion
No claims are allowed.
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/TIAN NMN YU/Examiner , Art Unit 1681
1 Claim 6 is withdrawn as being drawn to non-elected species B.
2Claims 29-32 are withdrawn as being drawn to non-elected species D-E.
3 Claim 36 is analogous to claim 1, but narrower. The main difference is that claim 1 encompasses an n of 3 or more for the detection target, composition, and temperature ranges, while claim 36 specifies that n is 3.
Prosecution Insights