Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 24 June, 2026. Claims 1, 5, 7, 8, and 13-19 are pending in the instant application. Claims 17-20 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 C.F.R. § 1.144). See M.P.E.P. § 821.01.
37 C.F.R. § 1.98
The information disclosure statement filed 06 March, 2026, has have been placed in the application file and the information referred to therein h
Joint Inventors, Common Ownership Presumed
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. § 102(b)(2)(C) for any potential 35 U.S.C. § 102(a)(2) prior art against the later invention.
35 U.S.C. § 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 of this title, 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.
Graham v. Deere
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied 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.
Claims 1, 5, 7, 8, 13, and 14 stand rejected under 35 U.S.C. § 103 as being unpatentable over Chu et al. (U.S. Pub. No. 2022/0017979, published 20 January, 2022; hereinafter referred to as “Chu et al. (2022)”), in view of Srivastava et al. (U.S. Pat. No. 11,634,762 B2, issued 25 April, 2023, and claiming priority to Appl. No. 16/874,647, filed 14 May, 2020; hereinafter referred to as “Srivastava et al. (2023)”), Marlowe et al. (U.S. Pat. No. 8,124,335 B2, issued 28 February, 2012; hereinafter referred to as “Marlowe et al. (2012)”), Chen et al. (U.S. Pat. No. 8,354,230 B2, issued 15 January, 2013; hereinafter referred to as “Chen et al. (2013)”), and Rota et al. (U.S. Pat. No. 7,220,852, issued 22 May, 2007; hereinafter referred to as “Rota et al. (2007)”).
The amended claims are directed toward a method to determine whether a sample from a subject contains an infections respiratory virus comprising: 1) obtaining the sample from a subject; 2) isolating RNA from the sample; 3) performing a multiplex reverse transcriptase polymerase chain reaction (RT-PCR) amplification using primers and probes specific for the following infectious respiratory viruses: SARS-CoV-2, influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV); and 4) determining the amount and/or presence of at least one of the at least two distinct respiratory viruses in the sample using a series of primers and probes corresponding to SEQ ID NOS.: 1-14. Claims 5 and 7 are directed toward a sample obtained from a nasal or nasopharyngeal (NP) swab, preferably by the subject. Claims 8, 13, and 14 recite further limitations with respect to the assay (e.g., multiplex RT-PCR; real-time RT-PCR (claim 8) and primers and probes corresponding to SEQ ID NOS.: 15-17 (claim 13)). Claim 14 further requires the utilization of a control gene to assess the amplification reaction.
As previously set forth, Chu et al. (2022) discloses a multiplex PCR method for the detection of SARS-CoV-2, IAV, IBV, and/or RSV in a subject sample. The method discloses isolating a sample from the subject, performing RT-PCR on the sample to assess the presence or absence of multiple respiratory viruses. Various assay formats are contemplated including PCR, LCR, LDR, MLPA, SDA, MDA, and NASB A (see p. 22). Samples (e.g., nasopharyngeal swab, see ¶ [0435]) may be subjected to direct amplification or additional processing (e.g., RNA purification) prior to the reaction. The inclusion of suitable controls to monitor amplification is also discussed (see ¶s [0457-0461]). Target RNA can be prepared in any one of a number of standard ways (see ¶s [0467-0471]). Various target genes were identified including IAV/IBV MP, NS, PB2, and PA, as well as, SARS-CoV-2 E, N2, and RdRP. This teaching does not disclose a multiplex amplification reaction wherein the RNA was subjected to an isolation/purification step or the primers/probes set forth in SEQ ID NOS.: 1-17.
Srivastava et al. (2023) disclose an RT-qPCR multiplex reaction for the detection of SARS-CoV-2 (2019-nCoV). Various probes and primers were disclosed including those corresponding to SEQ ID NOS.: 1-4 and 11-14 (corresponding to SEQ ID NOS.: 28-31, 34, 35, and 40, respectively). This teaching does not disclose a multiplex amplification reaction wherein the RNA was subjected to an isolation/purification step or the primers/probes set forth in SEQ ID NOS.: 5-10 and 15-17.
Marlowe et al. (2012) disclose an RT-qPCR multiplex reaction for the detection of IAV and IBV. Various probes and primers were disclosed including those corresponding to SEQ ID NOS.: 5-8 (corresponding to SEQ ID NOS.: 70, 45, 41, and 73, respectively). This teaching does not disclose a multiplex amplification reaction wherein the RNA was subjected to an isolation/purification step or the primers/probes set forth in SEQ ID NOS.: 1-4 and 9-17.
Chen et al. (2013) disclose an RT-qPCR multiplex reaction for the detection of IAV, IBV, and RSV. Various probes and primers were disclosed including those corresponding to SEQ ID NOS.: 9-11 (corresponding to SEQ ID NOS.: 31, 37, and 10, respectively). This teaching does not disclose a multiplex amplification reaction wherein the RNA was subjected to an isolation/purification step or the primers/probes set forth in SEQ ID NOS.: 1-8 and 12-17.
Rota et al. (2007) discloses the identification and characterization of novel coronavirus (SARS-CoV-2). Various primers and probes (e.g., claimed SEQ ID NOS.: 15-17 which correspond to SEQ ID NOS.: 36-38, respectively) capable of detecting this virus were also disclosed.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform an RT-PCR multiplex assay as taught by Chu et al. (2022), to detect well-known respiratory viruses such as SARS-CoV-2, IAV, IBV, and RSV. One of ordinary skill in the art would have been motivated to include an RNA isolation step to facilitate detection. Moreover, one of ordinary skill in the art would have been motivated to use the various primer/probe sets taught by Srivastava et al. (2023), Marlowe et al. (2012), Chen et al. (2013), and Rota et al. (2007) in any given multiplex assay to facilitate detection of the aforementioned respiratory viruses.
Applicants traverse and submit none of the prior art relied upon discloses an RNA isolation or purification step. This argument is clearly not tenable in view of the teachings of Chu et al. (2022). This teaching clearly discloses various methods for isolating and preparing RNA prior to amplification (see ¶s [0467-0469]). In particular, the authors note that target RNA can be prepared by any appropriate method, including the utilization of RNA purification kits. Thus, one of ordinary skill in the art would have been motivated to isolate and purify the RNA sample prior to multiplex analysis.
It was further argued that one of ordinary skill in the art would not have had a reasonable expectation of success in combining the references to arrive at the claimed invention. It was noted that combining multiple primers and probes into a multiplex assay can impact the sensitivity and specificity of the assay. Applicant argues the claimed methods provided unexpectedly sensitive and specific assay results. These arguments are not persuasive. As previously set forth, Chu et al. (2022) disclosed a multiplex PCR method for the detection of SARS-CoV-2, IAV, IBV, and/or RSV in a subject sample. The method disclosed isolating a sample from the subject and performing multiplex RT-PCR on the sample to assess the presence or absence of multiple respiratory viruses. The remaining references provide specific and sensitive primers/probes capable of identifying the recited viruses. Thus, absent evidence to the contrary, one of ordinary skill in the art would have expected these viral-specific primers/probes to be effective at amplifying and detecting SARS-CoV-2, IAV, IBV, and RSV and a multiplex reaction.
Claims 15 and 16 stand rejected under 35 U.S.C. § 103 as being unpatentable over Chu et al. (2022), in view of Srivastava et al. (2023), Marlowe et al. (2012), Chen et al. (2013)”), and Rota et al. (2007), as applied supra to claim 1 and further in view of Yun et al. (2021). The claims further recite Ct values of >40 or <40 corresponding to negative and positive values, respectively (claim 15). Claim 16 references a limit of detection (LoD) value of < 10 copies/µL. Yun et al. (2021) evaluated three multiplex real-time RT-PCR assays for SARS-CoV-2, IAV, IBV, and RSV in nasopharyngeal swabs. The LoD values reported (see p. 4, Analytical performance: limit of detection (LoD) and cross-reactivity; Table 2, p. 6; lines 5-10, p. 6) meet the claimed limitations. Applicants’ traversal is noted and the rejection is maintained for the reasons clearly set forth in the preceding paragraphs.
Additional Prior Art
The following additional prior art, which was not relied upon, is also germane to the claimed invention:
- Huang, R., and J. Sun, U.S. Pat. Pub. No. 2022/0042117 A1, published 10 February, 2022, and claiming priority to Prov. Appl. No. 63/062,105, filed 06 August, 2020.
Action Is Final
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 C.F.R. § 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the Examiner are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 05 September, 2026
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