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 10 December, 2025. Claims 1-8, 18, and 19 are pending in the instant application. Because Applicants did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (M.P.E.P. § 818.03(a)). Accordingly, claims 7, 8, and 18 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
35 U.S.C. § 119
Acknowledgment is hereby made of Applicant’s claim for foreign priority based on CN 2023/10107029.9 filed 06 February, 2023. It is noted, however, that Applicant has NOT filed a certified copy AND English translation of this application as required by 35 U.S.C. § 119(b)(3). Accordingly, the foreign priority claim has NOT been entered. For the purpose of applying prior art, the effective filing date of the claimed invention will be 16 May, 2023.
37 C.F.R. § 1.98
The information disclosure statement filed 05 December, 2025, has been placed in the application file and the information referred to therein has been considered.
37 C.F.R. § 1.84
The drawings filed 16 May, 2023, have been reviewed and are acceptable.
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.
Claims 1-6 and 19 are rejected under 35 U.S.C. § 103 as being unpatentable over Fozouni et al. (2021, Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy, Cell 184:323-33), in view of Wu et al. (2020, A new coronavirus associated with human respiratory disease in China, Nature 579:265-270; hereinafter referred to as Wu et al. (2020a)) and Wu et al. (2020, Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome, GenBank MN908947, pp. 1-12; hereinafter referred to as Wu et al. (2020b)). The claims are directed toward a CRISPR-Cas13 system for detecting SARS-CoV-2 comprising a Cas13a protein and crRNA, wherein the crRNA comprises first and second guide RNAs (gRNA), wherein the gRNAs are selected from one of SEQ ID NOS.: 1-33. Claim 2 simply references a crRNA designed for a SARS-CoV-2 target and claim 19 references a spike protein target. Claim 3 references a series of SARS-CoV-2 target sequences selected from one of SEQ ID NOS.: 34-65. Claim 4 references a series of probe sequences (SEQ ID NOS.: 66-97). Claim 5 stipulates that the first and second gRNAs comprise different sequences.
Fozouni et al. (2021) describe the development of an amplification-free CRISPR-Cas13a assay for direct detection of SARS-CoV-2 from nasal swab RNA. The assay used crRNAs to target SARS-CoV-2 RNA and was capable of detecting as few as ~100 copies/µL. In particular, Cas13a-crRNA RNP complex binds target RNA, resulting in activation of the HEPN nuclease domain. Upon target recognition and RNP activation, Cas13a indiscriminately cleaves a quenched-fluorophore RNA reporter, allowing for fluorescence detection as a proxy for Cas13a activation and target RNA (see Figure next page). This teaching did not disclose the precise crRNA guides, S target sequences, and S probe sequences.
Wu et al. (2020a) and (2020b) provide the complete nucleotide and amino acid sequence of a novel SARS-CoV-2 isolate obtained from an infected patient (see Fig. 1, next page). Deep meta-transcriptomic sequencing was performed and a novel coronavirus was identified and designated WH-Human 1 coronavirus (WHCV) (also referred to as ‘2019-nCoV’). The whole genomic sequence (29,903nt) was assigned assigned GenBank accession number MN908947. The WHCV viral genome was similar to other coronaviruses and comprises the following genomic organization (5′ to 3′): replicase ORF1ab, spike (S), envelope (E), membrane (M) and nucleocapsid (N). The predicted S, ORF3a, E, M and N genes of WHCV are 3,822, 828, 228, 669 and 1,260nt in length, respectively.
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 utilize the nucleotide sequences provided by Wu et al. (2020a) and (2020b), in combination with the teachings of Fozouni et al. (2021), to detect SARS-CoV-2 S sequences utilizing CRISPR-Cas13a reagents. Fozouni et al. (2021) provides all the necessary design parameters for generating suitable crRNAs, targets sequences, and probes (see crRNA design parameters, p. e4). Accordingly, absent evidence to the contrary, the skilled artisan would have been capable of producing and using the claimed gRNAs, identifying suitable SARS-CoV-2 target sequences, and generating suitable probe sequences.
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Figure 1. Quantitative direct detection of viral SARS-CoV-2 RNA with Cas13a. (A) Schematic of a Cas13a (beige)-crRNA (red) RNP complex binding target RNA (black), resulting in activation of the HEPN nuclease (denoted by scissors) domain. Upon target recognition and RNP activation, Cas13a indiscriminately cleaves a
quenched-fluorophore RNA reporter, allowing for fluorescence detection as a proxy for Cas13a activation and target RNA. Fozouni et al. (2021).
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Figure 1. Genome organization of SARS and SARS-like CoVs. The organization of genes for WHCV, bat SL-CoVZC45 and SARS-CoV Tor2. Wu et al. (2020a).
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 21 March, 2026
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