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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/23/2026 has been entered.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20210341480A1, Published 11/04/2021. Amendments to the specification presented on 01/31/2025 are acknowledged and entered.
Disposition of Claims
Claims 1-5, 7-8, 10-14, 22, and 25-28 were pending. Claims 6, 9, 15-24, and 29 are cancelled. Amendments to claim 1 are acknowledged and entered. Claims 1-5, 7-8, 10-14, and 25-28 will be examined on their merits.
Response to Arguments
Applicant's arguments filed 07/13/2026 regarding the previous Office action dated 04/23/2026 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 If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn.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arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/31/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claim 1 and dependent claims 2-5, 7-8, 10-14, 22, and 25-28 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
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 1 is drawn to a method of detecting a respiratory virus infection, the method comprising:
1) obtaining a saliva sample from an individual, wherein the sample is self-collected by the individual;
2) performing a first assay comprising nucleic acid amplification on a first portion of the saliva sample to determine a copy number of viral nucleic acid from the respiratory virus using one or more primers that bind to the viral nucleic acid; and
3) performing a second assay comprising an immunoassay on a second portion of the saliva sample to determine a quantitative level of IgA and IgG antibodies that bind to the respiratory virus, the Ig and IgG antibodies being produced by an immune response to the respiratory virus, and normalizing the quantitative levels of the IgA and IgG antibodies against total IgA and IgG antibodies in the saliva sample.
Further limitations on the method of claim 1 are wherein the sample was obtained within 3 days after onset of symptoms (claim 2); wherein the respiratory virus is a member selected from the group consisting of paramyxoviridae, picornaviradae, coronaviridae, parvoviridae, and enteroviridae (claim 3); wherein the respiratory virus is a virus causative of severe acute respiratory syndrome (SARS)(claim 4); wherein the virus c is severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2)(claim 5); wherein first assay is a polymerase chain reaction (PCR) (claim 7); wherein the first assay is PCR using primers that target one or more of the SARS CoV-2 nucleocapsid (N), open reading frame 1ab (ORF1ab), and envelope (E) genes (claim 8); wherein the first assay is quantitative PCR (qPCR) (claim 10), further comprising determining severity of the infection based on quantification of viral nucleic acid (claim 13); wherein the PCR is digital PCR (dPCR)(claim 11), wherein the dPCR is droplet digital PCR (ddPCR)(claim 12); further comprising comparing the respiratory viral nucleic acid quantities in a plurality of saliva samples obtained from the patient at successive time points and determining disease progression based on increases or decreases in the respiratory viral nucleic acid quantities over time (claim 14); wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA), bead-based assay, a luminescent assay, a metal-linked immunosorbent assay, or a point-of-care immunochromatographic assay (claim 25); wherein the saliva sample is collected in a sterile container (claim 26), further comprising sealing the sterile container and transferring the container to a laboratory (claim 27); and wherein the saliva sample is collected using an at-home kit and/or simple packaging (claim 28).
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 1, 3-5, 7-8, 10, 13-14, and 25-28 under 35 U.S.C. 102(a)(1) as being anticipated by Sullivan et. al. (Sullivan PS, et. al. JMIR Public Health Surveill. 2020 Apr 24;6(2):e19054.; hereafter “Sullivan”) is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 2 and 11-12 under 35 U.S.C. 103 as being unpatentable over Sullivan as applied to 1, 3-5, 7-8, 10, 13-14, and 25-28 above, and further in view of:
McDevitt et. al. (US20210311055A1, Priority 03/25/2020; CITED ART OF RECORD; hereafter “McDevitt”) as evidenced by Kojima et. al. (Kojima N, et. al. medRxiv 2020.04.11.20062372; 04/15/2020.; CITED ART OF RECORD; hereafter “Kojima”); and Wyatt et. al. (US20130217071A1, Pub. 08/22/2013; CITED ART OF RECORD; hereafter “Wyatt”) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 22 under 35 U.S.C. 103 as being unpatentable over Sullivan as applied to 1, 3-5, 7-8, 10, 13-14, and 25-28 above, and further in view of Lai et. al. (US20150284451A1, Pub. 10/08/2015; CITED ART OF RECORD; hereafter “Lai”) is withdrawn in light of the amendments to the claims.
(New rejection.) Claims 1, 3-5, 7-8, 10-14, and 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Sullivan et. al. (Sullivan PS, et. al. JMIR Public Health Surveill. 2020 Apr 24;6(2):e19054.; CITED ART OF RECORD; hereafter “Sullivan”) in view of Wyatt et. al. (US20130217071A1, Pub. 08/22/2013; CITED ART OF RECORD; hereafter “Wyatt”), and further in view of Simon et. al. (Simon JK, et. al. Clin Vaccine Immunol. 2011 Mar;18(3):355-61. Epub 2011 Jan 12.; hereafter “Simon”.)
The Prior Art
Sullivan teaches detection of SARS CoV-2 RNA and antibodies in diverse samples, such as home-collected blood, saliva, and oropharyngeal samples (entire document; see abstract.) Sullivan teaches that due to limitations in supplies during the SARS CoV-2 pandemic, alternate options for SARS CoV-2 screening were necessary, and included self-collection of specimens at home with kits and reagents while being observed through a telehealth portal by a healthcare provider (abstract, p. 5 “Saliva Self-Collection”). Sullivan teaches that the sample will them be subjected to isolation of viral RNA and reverse transcription of said RNA to DNA, with the resulting DNA subjected to quantitative polymerase chain reaction (qPCR)(p. 6, “Testing: RNA-PCR”). The sample will also be subjected to enzyme immunoassay serology tests with antibodies that bind to SARS CoV-2 antigens to analyze for IgG, IgM, and IgA antibodies (p. 7, “Serology Tests”; instant claims 3-5, 7, 10, 25, and 28.)
Sullivan notes these protocols and kits will allow for follow-up monitoring for viral shedding without the need for return office visits (p. 7, “Discussion”, ¶ bridging cols.; instant claim 14). Sullivan teaches that RNase P will be used as an internal amplification control and to quantify the nucleic acid content of the specimen (p. 6, “Specimen Sufficiency for RNA-PCR”). Sullivan teaches the reverse-transcribed DNA will undergo qPCR with primers and probes targeting N, S, and ORF1 of the SARS CoV-2 genome (p. 6, “Testing: RNA-PCR”; instant claim 8). Sullivan teaches the interpretation of the qPCR results will be made based on Ct values and positive identification of the nucleic acid, and these methods allow them to monitor the infection status of the patient while reducing burden on the medical supply chain and clinician’s office (p. 6, “Testing: RNA-PCR”; p. 7, “Discussion”; instant claim 13). Sullivan teaches the saliva will be tested for IgG, IgM, and IgA and would follow the manufacturer’s guidelines for reaction conditions, data interpretation, and internal controls (p. 7, “Serology Tests”.) Sullivan teaches that the saliva collection device was in a sealed container, which, absent evidence to the contrary, would be a sterile container used for collection of the saliva sample, which then after collection would be placed in a biohazard bag, sealed, and sent to a laboratory for testing (Fig. 3; instant claims 26-27).
While Sullivan teaches the interpretation of the qPCR results will be made based on Ct values and positive identification of the nucleic acid, Sullivan fails to explicitly teach determining a copy number of the viral nucleic acid. Sullivan is also silent as to the normalization of quantitative levels of virus-specific IgA and IgG against total IgA and IgG antibodies in the saliva sample. However, such determinations would be obvious optimizations to a skilled artisan, given the teachings of Wyatt and Simon.
Wyatt teaches fast, sensitive, and accurate nucleic acid-based detection methods, especially for the detection of pathogenic infections (entire document; see abstract, ¶[0196-0216]). Wyatt teaches methods to quantify specific and large numbers of mRNAs are known in the art, as well as the detection and quantification of patterns of expression of known and unknown genes (¶[0003]). Wyatt teaches the sample tested may be a clinical sample (¶[0116]), such as saliva (¶[0115]). Wyatt teaches the virus detected may be a SARS coronavirus (¶[0202]) or other respiratory viruses, such as other coronaviruses (¶[0202]), orthomyxoviruses (influenza A, B, and C viruses)(¶[0203], paramyxoviruses (¶[0201][0212]), picornaviruses (¶[0204-0205]), or enteroviruses (¶[0205]). Wyatt teaches the PCR detection method used to identify these viruses may be a digital PCR reaction, such as a droplet digital PCR reaction (¶[0010-0011]; instant claims 11-12), and are an excellent way of amplifying low-levels of RNAs (¶[0002]) as well as quantitating the amount of mRNA in the sample (¶[0024-0025][0058][0122][0140][0145]; Figs. 1-2). Wyatt teaches the methods provided permit determination of number of copies of an RNA molecule without a standard curve (¶[0148]). Wyatt teaches the subject may have signs or symptoms of a disease or infection (¶[0222]).
Simon teaches performing the normalization of virus-specific IgG and IgA versus the total IgG and IgA in a sample (entire document; see abstract.) Simon teaches serum, oral fluid, and nasal wash samples were examined for measles virus-specific and total IgG and IgA on day 0 (prior to vaccination) and on days 14, 28, and 90 after vaccination. Simon performed the measles-virus specific IgG and IgA analysis by ELISA(p. 356, “Materials and Methods: Measles virus-specific IgG and IgA.”), and measured total IgG and IgA in the same sample by sandwich ELISA (p. 356, “Materials and Methods: Total IgG and IgA.”) Simon then calculated the ratios of virus-specific antibodies to total IgG and IgA (p. 358, rt. Col., ¶3). Simon provides express motivation for this normalization, namely to account for interspecimen variability of total antibody in nonhomogeneous fluids, such as oral fluid and nasal wash samples (p. 359, rt. Col., ¶4).
Accordingly, it would have been obvious to one of ordinary skill in the art to modify the method taught by Sullivan to determine viral RNA copy number using the quantitative nucleic acid amplification method taught by Wyatt and to normalize the quantitative levels of virus-specific IgA and IgG against total IgA and IgG as taught by Simon, thereby providing quantitative molecular and antibody measurements from the self-collected saliva sample. One would have been motivated to do so, given the use of quantitative molecular and serologic testing of saliva by Sullivan, the teaching by Wyatt that digital PCR permits determination of RNA copy number, and the teaching of Simon that normalization of virus-specific mucosal antibody measurements to total Ig accounts for interspecimen variability, especially given the variability known between oral fluid samples. Therefore, arriving at the limitations of instant claim 1 would have been obvious to a skilled artisan, given the teachings of Sullivan, Wyatt, and Simon.
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Sullivan in order to determine viral RNA copy number and to establish a normalized level of IgA and IgG antibodies in the saliva sample, thereby determining normalized levels of each parameter in the saliva sample. One would have been motivated to do so, given the suggestion by Wyatt that digital PCR permits determination of RNA copy number in the sample, and given the suggestion by Simon that antibody numbers should be normalized to account for known variations between saliva sampling. There would have been a reasonable expectation of success, given the knowledge that Sullivan teaches the dual detection of viral RNA and viral-specific antibodies for detection of infection from saliva, and also given the knowledge that specific methods for detection of different parameters were known, such as viral RNA copies and viral-specific antibodies, as taught by Sullivan, Wyatt, and Simon. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
(New rejection.) Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Sullivan, Wyatt, and Simon as applied to 1, 3-5, 7-8, 10-14, and 25-28 above, and further in view of To et. al. (To KK, et. al. Lancet Infect Dis. 2020 May;20(5):565-574. Epub 2020 Mar 23.; hereafter “To”.)
The Prior Art
The teachings of Sullivan, Wyatt, and Simon have been set forth supra. While Wyatt teaches the testing can be performed when the subject has a sign or symptom of disease or infection (¶[0222]), and Sullivan teaches that there are questions regarding when someone should be tested, as in, should they be tested when they have mild symptoms of COVID-19 disease, or should asymptomatic but potentially infected persons be screened (p. 2, left col., ¶2), neither Sullivan, Wyatt, nor Simon teach specific time frames of testing, especially after any symptomatic onset of infection. However, testing after onset of symptoms would be obvious to a skilled artisan, especially in light of the teachings of To.
To teaches determining SARS-CoV-2 viral load in posterior oropharyngeal saliva samples as a function of time after symptom onset and reports that salivary viral load was highest during the first week after symptom onset and subsequently declined with time (entire document; see Abstract: Findings.) To further teaches that serological assays can complement nucleic acid detection assays for diagnosis (Abstract: Interpretation). To teaches the median interval between symptom onset and hospitalization was 4 days (range of 0-13 days; “Results”, p. 567). To teaches the viral nucleic acid can be detected immediately after onset of symptoms (Fig. 2) but that antibody detection, namely IgG and IgM, can take 5 or more days after symptom onset to develop (Fig. 4).
Given the teachings of Sullivan, Wyatt, and Simon, one of skill in the art would be apprised as to the usefulness of testing for both antibody levels and viral levels after symptom onset in patients suspected of having SARS-CoV-2 infection. Given the teachings of To, the importance of testing both antibody and viral nucleic acid levels in a saliva sample was apparent, as after onset of symptoms, the viral nucleic acid could be detected in the saliva sample immediately, while the IgG and IgM antibodies took longer to develop. Therefore, if the sample was collected at a certain timepoint after onset of symptoms, one could determine, given the data from To, how long said person may have been infected with the virus, depending on what tests were positive and what tests were negative. Therefore, as To shows testing for anti-SARS-CoV-2 antibodies and viral RNA immediately after onset of symptoms, or within three days after onset of symptoms, it would be obvious to a skilled artisan to take the data from To and apply it to the method of Sullivan, Wyatt, and Simon in order to analyze the data obtained from testing both antibody levels and viral RNA levels in the saliva sample, making the limitations of instant claim 2 obvious to a skilled artisan.
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Sullivan, Wyatt, and Simon in order to collect saliva samples after onset of respiratory virus symptoms, thereby allowing diagnosis of the viral infection in a subject. One would have been motivated to do so, given the suggestion by To that teaches that in certain timeframes after symptom onset, the viral RNA would be detected, but not antibodies, allowing for proper follow-up and diagnosis of the potential infection and stage of infection. There would have been a reasonable expectation of success, given the knowledge that IgG antibodies do not start to show up immediately in saliva samples after the onset of symptoms, thus requiring a secondary test to ensure accuracy, as taught by To, and given that viral RNA is detectable immediately after onset of symptoms yet can still be present after resolution of symptoms, as taught by To and referenced by Sullivan. Therefore, for accuracy of determining infection from a respiratory virus through testing a saliva sample, it would be obvious to run both the serological and nucleic acid assays and determine the levels within each test to determine the potential stage of infection given the results. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant’s arguments, see “Remarks”, filed 07/13/2026, with respect to the rejections over Sulivan under 35 USC 102 have been considered in light of the amendments to the claims and are persuasive. Therefore, all prior art rejections under 35 USC 102 and 35 USC 103 have been withdrawn. However, upon further consideration, new grounds of rejection under 35 USC 103 are made utilizing the teachings of Sullivan, and further integrate the teachings of Wyatt, Simon, and To to show the obvious nature of the amended claims. Arguments regarding Sullivan and Wyatt will be addressed as applicable herein in the interest of compact prosecution.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
With respect to Sullivan, Applicant argues that Sullivan fails to anticipate the instant claims, namely that Sullivan failed to teach the determination of copy number of viral nucleic acid and the normalization of anti-viral IgG/IgA to overall IgG/IgA in the sample. This argument was persuasive, and the anticipation rejection was withdrawn. However, Sullivan, in further view of Wyatt and Simon, who both teach these limitations as detailed supra, still rendered obvious the instant claims, and thus was utilized in the new obviousness rejection.
Applicant argues that Wyatt fails to cure the deficiencies of Sullivan. While Wyatt does not cure all the deficiencies of Sullivan, it remains that Wyatt teaches dPCR and ddPCR, teaches that such an analysis may be performed on biological samples, such as saliva, and teaches that the number of copies of RNA in the sample may be reported. So while Wyatt may not cure every deficiency of Sullivan, Wyatt still renders obvious certain aspects of the method instantly claimed, such as the use of ddPCR on detection of RNA in a saliva sample. Applicant argues that the “lengthy list” of biological samples would not render the analysis of saliva obvious; however, there are only 24 biological samples listed (¶[0115]). This is clearly a finite, identified, and predictable set of options for analysis, especially given the express guidance from Sullivan and Simon to test saliva. With respect to “coronaviruses” also being within a “lengthy list”, again, the art is not viewed in a piecemeal analysis, but rather as a whole, and the art at the time of filing, as evidenced by the teachings of Sullivan, was focused on the home-setting analysis of samples to allow for accurate infection interpretation and to prevent exposure during the unprecedented pandemic. Wyatt notes that a “SARS coronavirus” can be analyzed with their methods from a list of other Nidovirales members (¶[0202]), a list that includes 15 other viruses. Again, this is not an unreasonable list for one to choose from, and this line of argument is not persuasive. The teachings of Wyatt remain relevant to aspects of the instantly claimed invention for these reasons and the reasons detailed supra.
The obviousness rejection was updated in light of the prior art search and the amendments to the claims, and the teachings of Simon and To were employed in the newly presented rejections. For the reasons set forth supra, the claimed invention is still obvious in light of the teachings of prior art, and the teachings of Sullivan and Wyatt were still determined to render obvious aspects of the instant claims.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection withdrawn.) The rejection of Claims 1-5, 7-8, 10-14, 22, and 25-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Pat. No. 12,344,889 in view of Sullivan, McDevitt (as evidenced by Kojima), Wyatt (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 1-5, 7-8, 10-14, 22, and 25-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending application 19/250,489 (reference application) in view of Sullivan, McDevitt (as evidenced by Kojima), Wyatt (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 1-5, 7-8, 10-14, 22, and 25-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 19-21, and 30-31 of copending Application No. 17/864,160 (NB: Said application was recently allowed) in view in view of Sullivan, McDevitt (as evidenced by Kojima), Wyatt (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”) is withdrawn in light of the amendments to the claims.
(New rejection.) Claims 1-5, 7-8, 10-14, and 25-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Pat. No. 12,344,889 in view of Sullivan, Wyatt, Simon, To (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”). Both the instant claims and the ‘889 claims are drawn to methods of amplifying viral nucleic acid from SARS CoV-2. Both sets of claims are drawn to primers which amplify SARS CoV-2 N, ORF1ab, and E genes, both claim quantifying the target viral nucleic acid. Both claim the use of qPCR, both claim the steps of taking saliva at multiple timepoints to assess onset and/or severity of disease progression. Both claim predicting disease treatment or outcomes based on viral nucleic acid. While the instant claims provide for an additional step of analyzing the saliva sample for antibodies or antigens, such a difference would be obvious, given the teachings of Sullivan, Wyatt, Simon, and To (detailed supra). To summarize, Sullivan teaches testing saliva for the presence of viral nucleic acid and testing using antibodies for additional viral materials, with the saliva being self-collected. Wyatt teaches nucleic acid amplification technologies, such as ddPCR, were known in the art at the time of filing and could be used to detect coronaviruses in a saliva sample. Sullivan notes IgM, IgA, and IgG can be tested for from the saliva sample taken from a patient suspected of having a respiratory viral infection. Simon teaches the normalization of antiviral IgA and IgG in a saliva sample to overall IgA and IgG in the sample. To teaches the differences in SARS-CoV-2 viral RNA and antiviral immunoglobulins in a sample depending on when said sample was taken after symptom onset. The ‘889 claims also note that the saliva is mixed with respiratory samples and is tested using an “extraction-free method”; however, extraction-free polynucleotide isolation was known in the art at the time of filing for extraction of SARS CoV-2 nucleic acid, as evidenced by Zhang (entire document; see abstract; ¶[0008]). Zhang teaches the use of enzymatic inhibitors, such as proteinase K (¶). Further, “mixing” of saliva and sputum happens naturally at points along the nasopharynx, so saliva samples or sputum samples would likely inherently be a mixture of these two. Zhang teaches that extraction-free amplification can happen using saliva samples from the subject (Fig. 40; ¶[0056]). The use of reducing agents, such as BME or DTT, and protease inhibitors, such as proteinase K, are commonly used for sample prep prior to nucleic acid assays and would be obvious components to use for a skilled artisan. Therefore, the differences between the instant claims and the ‘889 claims would be obvious, given what was known in the art at the time of filing, and the claims are not patentably distinct.
(New rejection.) Claims 1-5, 7-8, 10-14, and 25-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending application 19/250,489 (reference application) in view of Sullivan, Wyatt, Simon, To (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”). Both the instant claims and the ‘489 claims are drawn to methods of amplifying viral nucleic acid from SARS CoV-2. Both sets of claims are drawn to primers which amplify SARS CoV-2 N, ORF1ab, and E genes, both claim quantifying the target viral nucleic acid. Both claim the use of qPCR, both claim the steps of taking saliva at multiple timepoints to assess onset and/or severity of disease progression. Both claim predicting disease treatment or outcomes based on viral nucleic acid. While the instant claims provide for an additional step of analyzing the saliva sample for antibodies or antigens, such a difference would be obvious, given the teachings of Sullivan, Wyatt, Simon, and To (detailed supra). To summarize, Sullivan teaches testing saliva for the presence of viral nucleic acid and testing using antibodies for additional viral materials, with the saliva being self-collected. Wyatt teaches nucleic acid amplification technologies, such as ddPCR, were known in the art at the time of filing and could be used to detect coronaviruses in a saliva sample. Sullivan notes IgM, IgA, and IgG can be tested for from the saliva sample taken from a patient suspected of having a respiratory viral infection. Simon teaches the normalization of antiviral IgA and IgG in a saliva sample to overall IgA and IgG in the sample. To teaches the differences in SARS-CoV-2 viral RNA and antiviral immunoglobulins in a sample depending on when said sample was taken after symptom onset. The ‘489 claims also note that the saliva is mixed with respiratory samples and is tested using an “extraction-free method”; however, extraction-free polynucleotide isolation was known in the art at the time of filing for extraction of SARS CoV-2 nucleic acid, as evidenced by Zhang (entire document; see abstract; ¶[0008]). Zhang teaches the use of enzymatic inhibitors, such as proteinase K (¶). Further, “mixing” of saliva and sputum happens naturally at points along the nasopharynx, so saliva samples or sputum samples would likely inherently be a mixture of these two. Zhang teaches the extraction-free amplification can happen using saliva samples from the subject (Fig. 40; ¶[0056]). The use of reducing agents, such as BME or DTT, and protease inhibitors, such as proteinase K, are commonly used for sample prep prior to nucleic acid assays and would be obvious components to use for a skilled artisan. Therefore, the differences between the instant claims and the ‘489 claims would be obvious, given what was known in the art at the time of filing, and the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
(New rejection.) Claims 1-5, 7-8, 10-14, and 25-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of US Patent No. 12,680,130 in view in view of Sullivan, Wyatt, Simon, To (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”). Both the instant claims and the ‘130 claims are drawn to methods of amplifying viral nucleic acid from SARS CoV-2. Both sets of claims are drawn to primers which amplify SARS CoV-2 N, ORF1ab, and E genes, both claim quantifying the target viral nucleic acid. Both claim the use of qPCR, both claim the steps of taking saliva at multiple timepoints to assess onset and/or severity of disease progression. Both claim predicting disease treatment or outcomes based on viral nucleic acid. While the instant claims provide for an additional step of analyzing the saliva sample for antibodies or antigens, such a difference would be obvious, given the teachings of Sullivan, Wyatt, Simon, and To (detailed supra). To summarize, Sullivan teaches testing saliva for the presence of viral nucleic acid and testing using antibodies for additional viral materials, with the saliva being self-collected. Wyatt teaches nucleic acid amplification technologies, such as ddPCR, were known in the art at the time of filing and could be used to detect coronaviruses in a saliva sample. Sullivan notes IgM, IgA, and IgG can be tested for from the saliva sample taken from a patient suspected of having a respiratory viral infection. Simon teaches the normalization of antiviral IgA and IgG in a saliva sample to overall IgA and IgG in the sample. To teaches the differences in SARS-CoV-2 viral RNA and antiviral immunoglobulins in a sample depending on when said sample was taken after symptom onset. The ‘130 claims also note that the saliva is mixed with respiratory samples and is tested using an “extraction-free method”; however, extraction-free polynucleotide isolation was known in the art at the time of filing for extraction of SARS CoV-2 nucleic acid, as evidenced by Zhang (entire document; see abstract; ¶[0008]). Zhang teaches the use of enzymatic inhibitors, such as proteinase K (¶). Further, “mixing” of saliva and sputum happens naturally at points along the nasopharynx, so saliva samples or sputum samples would likely inherently be a mixture of these two. Zhang teaches the extraction-free amplification can happen using saliva samples from the subject (Fig. 40; ¶[0056]). The use of reducing agents, such as BME or DTT, and protease inhibitors, such as proteinase K, are commonly used for sample prep prior to nucleic acid assays and would be obvious components to use for a skilled artisan. Therefore, the differences between the instant claims and the ‘130 claims would be obvious, given what was known in the art at the time of filing, and the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
(New rejection). Claims 1-5, 7-8, 10-14, and 25-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 19-20, 27, and 30 of copending Application No. 19/733,145 in view of Sullivan, Wyatt, Simon, To (all supra), and Zhang et. al. (US20210292824A1, Priority 03/23/2020; CITED ART OF RECORD; hereafter “Zhang”).
Both the instant claims and the ‘145 claims are drawn to methods of amplifying viral nucleic acid from SARS CoV-2. Both sets of claims are drawn to primers which amplify SARS CoV-2 N, ORF1ab, and E genes, both claim quantifying the target viral nucleic acid. Both claim the steps of taking saliva at multiple timepoints to assess onset and/or severity of disease progression. Both claim predicting disease treatment or outcomes based on viral nucleic acid. While the instant claims provide for an additional step of analyzing the saliva sample for antibodies or antigens, such a difference would be obvious, given the teachings of Sullivan, Wyatt, Simon, and To (detailed supra). To summarize, Sullivan teaches testing saliva for the presence of viral nucleic acid and testing using antibodies for additional viral materials, with the saliva being self-collected. Wyatt teaches nucleic acid amplification technologies, such as ddPCR, were known in the art at the time of filing and could be used to detect coronaviruses in a saliva sample. Sullivan notes IgM, IgA, and IgG can be tested for from the saliva sample taken from a patient suspected of having a respiratory viral infection. Simon teaches the normalization of antiviral IgA and IgG in a saliva sample to overall IgA and IgG in the sample. To teaches the differences in SARS-CoV-2 viral RNA and antiviral immunoglobulins in a sample depending on when said sample was taken after symptom onset. The ‘145 claims also note that the saliva is mixed with respiratory samples and is tested using an “extraction-free method”; however, extraction-free polynucleotide isolation was known in the art at the time of filing for extraction of SARS CoV-2 nucleic acid, as evidenced by Zhang (entire document; see abstract; ¶[0008]). Zhang teaches the use of enzymatic inhibitors, such as proteinase K (¶). Further, “mixing” of saliva and sputum happens naturally at points along the nasopharynx, so saliva samples or sputum samples would likely inherently be a mixture of these two. Zhang teaches the extraction-free amplification can happen using saliva samples from the subject (Fig. 40; ¶[0056]). The use of reducing agents, such as BME or DTT, and protease inhibitors, such as proteinase K, are commonly used for sample prep prior to nucleic acid assays and would be obvious components to use for a skilled artisan. Therefore, the differences between the instant claims and the ‘145 claims would be obvious, given what was known in the art at the time of filing, and the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments, see “Remarks”, filed 07/13/2026, with respect to the NSDP rejections have been fully considered. In light of the amendments to the claims, the previous NSDP rejections have been withdrawn. However, upon further consideration, new grounds of rejection utilizing the combined teachings of Sullivan and Wyatt are made, supported by the teachings of Simon, To, and Zhang.
Applicant has requested that the non-statutory obviousness-type double patenting rejection be held in abeyance until allowable subject matter is indicated in the present application. However, said rejection must be maintained as a matter of record until the appropriate terminal disclaimers have been filed, or until the claims have been amended in such a way as to not claim patently identical subject matter.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Aita A, et. al. Clin Chim Acta. 2020 Nov;510:717-722. Epub 2020 Sep 16. Post-filing art that relates to the instant claims.
Okoturo E, et. al. Int J Infect Dis. 2022 Aug;121:166-171. Epub 2022 May 13. Post-filing review of RT-PCR testing of saliva samples for SARS-CoV-2.
Najjar D, et. al. Nat Biomed Eng. 2022 Aug;6(8):968-978. Epub 2022 Aug 8. Post-filing lab-on-a-chip system for detecting antibodies and viral RNA from saliva sample.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
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