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 .
Response to Amendment/Disposition of Claims
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22 December 2025 has been entered.
Applicant’s Amendment filed on 22 December 2025 has been received and entered. Claims 18, 21, 24-25, and 27-40 were pending with Claims 21, 24-25, and 27-40 being examined on their merits. Claim 18 is pending but remains withdrawn from consideration per Applicant’s response to the Restriction Requirement filed on 01 February 2024. Claims 21, 25, 34, 37-38, and 40 have been amended. Claims 1-17, 19-20, 22-23, 26, 36, and 39 have been cancelled. New Claim 41 has been added.
Accordingly, Claims 21, 24-25, 27-35, 37-38, and 40-41 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2022/0042117 A1, Published 10 February 2022. Applicant’s amended Specifications as presented on 15 July 2024, 12 June 2024, and 22 October 2021 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Response to Arguments
Applicant's arguments filed 22 December 2025 regarding the previous Office action dated 24 September 2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Drawings
(New Objection) – The drawings are objected to because several of the drawings are blurry and difficult to read. Specifically, Figures 1-4 have details which are hard to discern due to the blurriness of the figures. These include the axes labels in Figure 4 and the sequences in Figure 2. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
(Objection withdrawn) – The objection to Claims 21, 25, and 34 for containing minor informalities is withdrawn in light of the amendments to the claims.
(Objection withdrawn) – The objection to Claims 21 and 37 for containing minor informalities is withdrawn in light of the amendments to the claims.
(New Objection) – Claims 21, 29, 37 are objected to because of the following informalities: It is suggested that all instances of “comprising/comprises an oligonucleotide sequence” should be replaced with “comprising/comprises the oligonucleotide sequence”.
Appropriate correction is required.
(New Objection – necessitated by amendment) – Claim 41 is objected to because of the following informalities: It is suggested that it say “is labeled” instead of “are labeled”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
(Rejection withdrawn) – The rejection of Claim 38, and dependent claim 39 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to one of the claims and the cancellation of the other.
(Rejection withdrawn) – The rejection of Claim 40 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claim.
(New Rejection) – Claims 28 and 33 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 28 and 33 contain the trademarks/trade names Cy2, Cy3, Cy5, Cy5.5, and Cy7. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe fluorescent moieties and, accordingly, the identification/description is indefinite.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 28 and 33 are rejected on the grounds of being indefinite.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim Rejections - 35 USC § 112(a); First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(Rejection withdrawn) – The rejection of Claims 37-39 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of the amendments to the claims and the cancellation of one of the claims.
Claim Rejections - 35 USC § 112(d); Fourth Paragraph
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
(Rejection withdrawn) – The rejection of Claim 36 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 is withdrawn in light of the cancellation of the claim.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
(New Rejection) – Claims 21, 24-25, 27-35, 37-38, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Lassaunière et al. (Lassaunière R, Kresfelder T, Venter M. A novel multiplex real-time RT-PCR assay with FRET hybridization probes for the detection and quantitation of 13 respiratory viruses. J Virol Methods. 2010 May;165(2):254-60.), Young (US 2004/0229261 A1, Published 18 November 2004), Kornegay et al. (U.S. Patent No. 7,482,142 B1, Issued 27 January 2009) (cited in a previous Office Action), Mehta (US 2017/0356058 A1, Published 14 December 2017) (cited in a previous Office Action), Li et al. (US 2021/0292856 A1, earliest Priority Date 18 February 2020), An et al. (US 2003/0050470 A1, Published 13 March 2003) (cited in a previous Office Action), Gardner et al. (US 2013/0267429 A1, Published 10 October 2013) (cited in a previous Office Action), Kirschner et al. (US 2023/0265484 A1, earliest Priority Date 24 March 2020), Juang and Juang et al. (US 2005/0233314 A1, Published 20 October 2005), Hang et al. (CN 111440896 A, earliest Priority Date 25 February 2020), Metsky et al. (US 2018/0340215 A1, Published 29 November 2018), King et al. (King DP, Reid SM, Hutchings GH, Grierson SS, Wilkinson PJ, Dixon LK, Bastos AD, Drew TW. Development of a TaqMan PCR assay with internal amplification control for the detection of African swine fever virus. J Virol Methods. 2003 Jan;107(1):53-61.), Buck et al. (Buck GA, Fox JW, Gunthorpe M, Hager KM, Naeve CW, Pon RT, Adams PS, Rush J. Design strategies and performance of custom DNA sequencing primers. Biotechniques. 1999 Sep;27(3):528-36.), and Rychlik and Rhoads (Rychlik W, Rhoads RE. A computer program for choosing optimal oligonucleotides for filter hybridization, sequencing and in vitro amplification of DNA. Nucleic Acids Res. 1989 Nov 11;17(21):8543-51.).
Lassaunière et al. teach a multiplex real-time RT-PCR assay with FRET hybridization probes for the detection and quantitation of 13 respiratory viruses (see Abstract), wherein the assay is used to detect and distinguish between viruses such as Influenza A, Influenza B, and human coronavirus (see Table 1). Lassaunière et al. do not teach a multiplex real-time RT-PCR assay for detecting SARS-CoV-2 or such an assay for distinguishing between Influenza A, Influenza B, and SARS-CoV-2. This deficiency is remedied by the use of Li et al. below.
Young teaches a method of detecting and distinguishing between different flaviviruses and different variants of the same virus using multiplex amplification reactions comprising primers and FRET probes with different detectable labels (see Abstract; Paragraphs 0093-0096, 0160-0164, 0180-0182), wherein the donor fluorescent moiety can be Cy5, a fluorescein dye, a rhodamine dye, a cyanine dye, or a coumarin dye and wherein the acceptor/quencher moiety can be Cy5, a fluorescein dye, a rhodamine dye, a cyanine dye, or a coumarin dye (see Paragraphs 0009, 0010, 0027, 0058, 0162, 0167-0168). Young does not teach a method of detecting and distinguishing between respiratory viruses such as Influenza and coronavirus. This deficiency is remedied by the use of Lassaunière et al. above and Li et al. below.
Li et al. teach a method of detecting and distinguishing between SARS-CoV-2, Influenza A, and Influenza B in samples using multiple pairs of primers and multiple probes (see Abstract; Column 7, Lines 7-67) as well as teach SEQ ID NO: 365, which comprises a sequence that is 100% identical to instant SEQ ID NO: 17 and thus this reference teaches using instant SEQ ID NO: 17 for detecting SARS-CoV-2 (see Sequence Listing). Li et al. also teach detection of SARS-CoV-2 using multiple genes of the genome, including the ORF1ab region, N gene, and S gene (see Paragraphs 0014, 0016, 0018; Figures 2A, 2C, and 2E). Thus, Li et al. teach using the ORF1ab region and N gene to detect infection with SARS-CoV-2. Li et al. does not teach a multiplex method for detecting these viruses or any of the other specific primer and probe sequences recited by the instant claims. These deficiencies are remedied by the use of Lassaunière et al. and Young above and several of the references below, respectively.
An et al. teach that various primers and probes can be designed around known or disclosed nucleotide sequences as well as an algorithm for defining and designing any and all primers, given a specific nucleotide sequence (see Paragraphs 0065-0067). Therefore, An et al. not only taught designing primers of any length based on a known sequence, but also taught an algorithm for defining all possible primers of a given length based on a known sequence. In this respect, An et al. taught all possible subsequences of a known sequence could be considered as a primer for that sequence. While An et al. was discussing in particular sequences having to do with prostate, bladder, and breast cancer (see Abstract), one of ordinary skill in the art would have recognized that the principles of designing primers and probes based on a disclosed nucleotide sequence would have applied to any nucleotide sequence under study.
Kornegay et al. teach oligonucleotides with modified nucleotides (see Column 5, Lines 8-18; Claim 4) as well as the use of probes which can hybridize to and distinguish between different target nucleic acids even when there are single nucleotides differences between the sequences (see Column 14, Lines 34-60).
Mehta teaches a probe where the donor fluorescent moiety and the acceptor moiety are separated by 8-20 nucleotides, specifically 8 or 10 nucleotides (see Paragraph 0015). Mehta also teaches primers and/or probes comprising a modified nucleotide, such as t-butyl benzyl and C5-methyl-dC (see Paragraph 0035), as well as the use of multiple different hybridization probes comprising different fluorescent or donor moieties and the use of other types of fluorophores in conjunction with FRET probes (see Paragraphs 0066-0067), wherein the donor moiety can be a fluorescein dye, a cyanine dye, or a coumarin dye and the acceptor moiety can be a cyanine dye, a fluorescein dye, or a rhodamine dye (see Paragraph 0061).
Gardner et al. teach SEQ ID NOs: 84010, 80588, 52424, 89757, 91308, 90080, which comprise sequences that are 100% identical to instant SEQ ID NOs: 23, 24, 26, 28, 29, and 30, respectively, and thus this reference teaches the use of these instant primers and probes for detecting Influenza A and Influenza B (see Sequence Listing).
Kirschner et al. teach SEQ ID NO: 1010, which comprises a sequence that is 100% identical to instant SEQ ID NO: 22 (see Sequence Listing).
Juang and Juang teach SEQ ID NO: 5, which comprises a sequence that is 100% identical to instant SEQ ID NO: 12 and thus this reference teaches the use of instant SEQ ID NO: 12 for detecting SARS-CoV and SARS-CoV-2 as the target sequence is common to both viruses (see Sequence Listing).
None of the references above teaches use of instant SEQ ID NOs: 3, 4, and 18 for the detection of SARS-CoV-2 in an assay such as those supra.
This deficiency is remedied by the references below.
Metsky et al. teach SEQ ID NO: 317464, which comprises a sequence that is 100% identical to instant SEQ ID NO: 4 and thus this reference teaches the use of instant SEQ ID NO: 4 for detecting SARS-CoV-2 (see Sequence Listing).
Hang et al. teach SEQ ID NO: 240, which comprises a sequence that is 100% identical to both instant SEQ ID NOs: 3 and 18, and thus this reference teaches the use of instant SEQ ID NOs: 3 and 18 for detecting SARS-CoV-2 (see Sequence Listing).
King et al. teach a TaqMan PCR assay for the detection of a virus, namely African swine fever virus (ASFV).
Rychlik and Rhoads teach that it is routine and predictable to make primers for DNA amplification wherein primers are designed to a known oligonucleotide sequence. Rychlik and Rhoads teach criteria to design/choose suitable primers for DNA amplification (see whole document and Abstract).
Buck et al. expressly provide evidence of the equivalence of primers. Specifically, Buck et al. invited primer submissions from a number of labs (39) (Pg. 532, Column 3), with 69 different primers being submitted (Pg. 530, Column 1). Buck et al. also tested 95 primers spaced at 3 nucleotide intervals along the entire sequence at issue, thereby testing more than 1/3 of all possible 18 met primers on the 300-base pair sequence (Pg. 530, Column 1). When Buck et al. tested each of the primers selected by the methods of the different labs, Buck et al. found that every single primer worked (Pg. 533, Column 1). Further, every single control primer functioned as well (Pg. 533, Column 1). Buck et al. expressly states "The results of the empirical sequencing analysis were surprising in that nearly all of the primers yielded data of extremely high quality (Pg. 535, Column 2)." Therefore, Buck et al. provide direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria. This clearly shows that every primer would have a reasonable expectation of success and each is obvious including those in the instant claims and the prior art above for use in amplifying/binding the known target.
Thus, the primers of the instant claims were known in the prior art and would have been viewed as functional in the assay types above because the primer pairs disclosed by the prior art are close enough to each other that they can be viewed as functional pairs in the prior art assays.
A person having ordinary skill in the art would have been motivated to combine the teachings of Lassaunière et al., Young, Kornegay et al., Mehta, Li et al., An et al., Gardner et al., Kirschner et al., Juang and Juang, Hang et al., Metsky et al., King et al., Buck et al., and Rychlik et al. in order to develop a method for simultaneously detecting and distinguishing between SARS-CoV-2, Influenza A, and Influenza B. The multiplex assay to taught by Lassaunière et al. provides the basis for detecting and quantifying different respiratory viruses, including Influenza A, Influenza B, and human coronaviruses, specifically the common cold coronaviruses. As such, it would have been obvious to a person having ordinary skill in the art to adapt the assay using the method taught Li et al. to detect and distinguish between another coronavirus, such as SARS-CoV-2, Influenza A, and Influenza B. The assay disclosed by Lassaunière et al. would allow for the assessment of viral load at a given time point and detect possible co-infections in patients (see Page 254, Right Column, First Paragraph). The method disclosed by Li et al. would allow for the determination of the causative agent of a respiratory illness, as individuals infected with SARS-CoV-2 often experience symptoms similar to those infected with Influenza A or B and/or RSV, and a correct diagnosis is important so that appropriate safety measures can be taken (see Paragraph 0008). Using the ORF1ab region and N gene to detect the presence of SARS-CoV-2 is rendered obvious by the teachings of Li et al., as the genome of SARS-CoV-2 and it has been demonstrated that these genes/genomic regions are obvious to use for said detection of the virus. The combined teachings of Young, Kornegay et al., Mehta, and An et al. would allow for the use of multiple primer pairs and probes which can distinguish between the three target nucleic acids while allowing for the simultaneous and specific detection of any of the three target nucleic acids, even if they are all present in the same sample. Mehta teaches the principle behind selecting appropriate donor/acceptor pairs (see Paragraphs 0059-0061). As such, it would have rendered obvious the use of different donor/acceptor pairs for each target nucleic acid so that the signals are not confused. An et al. taught designing primers of any length based on a known sequence, but also taught an algorithm for defining all possible primers of a given length based on a known sequence. In this respect, An et al. taught all possible subsequences of a known sequence could be considered as a primer for that sequence, and thus renders all of the instant primers and probes obvious, particularly in light of the specific sequences taught by Li et al., Gardner et al., Kirschner et al., Juang and Juang, Metsky et al., and Hang et al. While the teachings of King et al. are in the context of a different virus, the same principles, including primer and probe design using a known genome/gene, would easily be transferrable to any other virus for a skilled artisan. The teachings of Buck et al. and Rychlik and Rhoads render all primers obvious and demonstrate that all properly designed primers would be expected to succeed. The combined teachings of the prior art illustrate that the instant primers are obvious because people have been close to selecting the same primers and demonstrate that anyone can identify functional primers for a known genome/gene sequence. Therefore, the combination of these teachings renders the invention encompassed by the instant claims obvious and thus render instant Claims 21, 24-25, 27-35, 37-38, and 40-41 obvious over the prior art.
Such modifications, combining prior art elements according to known methods in order to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, instant Claims 21, 24-25, 27-35, 37-38, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Response to Arguments
Applicant's arguments filed 22 December 2025 and 08 July 2025 have been fully considered. While the original rejections have been withdrawn in light of Applicant’s arguments, a new rejection was warranted that utilizes the teachings of An et al., and the arguments presented regarding these teachings will be addressed as applicable herein in the interest of compact prosecution.
In their Response on 08 July 2025, Applicant argued that that algorithm disclosed by the An et al. reference “is at least 20 years old” and claims it “is unlikely that one of ordinary skill in the art would consider An’s 20+ year old algorithm” for designing the instant primers and probes (see Page 8, Paragraph 3). Examiner, as presented in the previous Office Action, would like to state that the mere age of references is not persuasive of the unobviousness of the combination of their teachings, absent evidence that, notwithstanding knowledge of the references, the art tried and failed to solve the problem (see MPEP 2145(VIII)). Any alleged deficiencies of An et al. have been cured by the inclusion of the supporting references cited above.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Irshad et al. (2016)
Irshad et al. disclose the use of multiplex qPCR for the detection and subtyping of hepatitis viruses in body fluids. This reference has not been utilized, as rejection would have been redundant to those set forth above.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671