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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Nov. 4, 2022. Claims 1-23 are pending and currently examined.
Specification – Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) as follows:
The specification does not contain sequence identifiers (SEQ ID NO:) in all locations where sequences are disclosed, see at least FIGs 1, 7 and 8. To correct this, the sequences in figures can be referred to in either the figure or the Brief Description of Drawings. If the prior filed Sequence Listing does not contain updated sequences, Applicant is also required to submit a replacement Sequence Listing that includes all updated sequences.
Full compliance with the sequence rules is required in response to this Office Action. A complete response to this office action should include both compliance with the sequence rules and a response to the Office Action set forth below. Failure to fully comply with both these requirements in the time period set forth in this Office Action will be held non-responsive.
Claim Rejections - 35 USC § 112
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.
Claims 11, 14 and 23 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 11 and 14 recite “wherein the FIP primer has a sequence selected from SEQ ID Nos: 9, 10 or 11” and “wherein the BIP primer has a sequence selected from SEQ ID Nos: 12 and 13”, respectively. These limitations render the claims indefinite since it is not clear if the recited “FIP primer” and the “BIP primer” must comprise/consist the entire sequence set forth by one of the recited sequences or not. E.g., it is not clear if the FIP primer must comprise or consist the whole sequence of SEQ ID Nos: 9, 10 or 11, or any sequence region contained in the recited sequences may suffice. If the entirety of a recited sequence is required, applicant may consider such language as “wherein the FIP primer comprises (or consists) SEQ ID Nos: 9, 10 or 11”.
Claim 23 recites limitations modified by “preferably”. It is not clear if those limitations are required or not.
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 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 1-23 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Front. Microbiol., 2017, 7: 2166) and Park et al. (J Mol Diagn. 2020 Jun;22(6):729-735. Epub 2020 Apr 7), in view of GenBank: MN908947 (Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome. Dated March 18, 2020).
Claims 1-16 are directed to a primer set for detecting SARS-CoV-2 by reverse transcription loop-mediated isothermal amplification (RT-LAMP), comprising primers F3, B3, F2, B2, F1c and B1c comprising sequences at least 90% identical to SEQ ID NOs: 1, 2, 3, 4, 5(or 8) and 6, respectively. Claims 17-23 are directed to a method of using the RT-LAMP primers of claim 1.
Lee teaches that the authors developed an efficient and rapid method with high specificity for the Middle East Respiratory Syndrome coronavirus (MERS-CoV), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot RT-LAMP). A set of six LAMP primers [F3, B3, FIP, BIP, LF (Loop-F), and LB (Loop-B)] were designed using the sequence of nucleocapsid (N) gene with optimized RT-LAMP enzyme conditions: 100 U M-MLV RTase and 4 U Bst polymerase, implying that the reaction was able to detect four infectious viral genome copies of MERS-CoV within a 60 min reaction time period. See Abstract.
Table 1, shown below, provides detailed sequence information of the primers used in the study.
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356
1022
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Figure 2B shows the genome locations used in the RT-LAMP primer designs. See below.
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480
812
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Lee teaches that to design RT-LAMP primer sets for detection of MERS-CoV, the sequence of nucleocapsid protein (N protein) of MERS-CoV Korean isolate (KT029139, 2015) were compared with that of other MERS CoV isolated from South Korea (KT374050,2015; KU308549, 2015;KX034094,2015), Netherlands (JX869059, 2012), Saudi Arabia (KJ156944, 2013; KM027255, 2014; KT806054, 2015; KU851863, 2015), England (KM015348,2013), Egypt(KJ477102,2014),Qatar (KF961221,2014), and United States (KJ813439, 2014), and the conserved part was selected and used as the template of RT-LAMP. Lee teaches that to find out an efficient primer set, two sets of specific RT-LAMP primers were designed using Primer Explorer V4 software program based on the published sequence of N gene. See page 3.
Park teaches a study on development of RT-LAMP assays targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). RT-LAMP assays reported in the study can detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human coronaviruses was not observed. A colorimetric detection method was adapted for this RT-LAMP assay to enable higher throughput. See Abstract.
Park teaches that five SARS-CoV-2 sequences (MN908947, MN938384, MN988713, MN985325, and MN975262) and seven SARS-CoV sequences (NC_004718, AY613947, AY313906, AY559094, AY502924, AY278491, and AY502927) were aligned by MEGA software version for LAMP primer designs. Whole Nucleocapsid gene region is also included as Nucleocapsid is usual target of molecular diagnosis because of the abundance of its mRNA. Two to five basic LAMP primer sets are designed and selected with PrimerExplorer V5 for each target region. Loop primers are designed by PrimerExplorer V5 or manually selected. Sixteen LAMP primer sets, with loop forward primer and loop backward primer showing proper melting temperature, were selected and subjected to further screening. See page 731, right column, para 1. Figure 1 of Park shows the locations of the primer regions (F3, F2, F1, B3, B2, B1, LF and LB) on aligned sequences of SARS-CoV-2 and SARS-CoV.
Park teaches that isothermal incubation and fluorescence signal measurement were performed using LightCycler 96 instrument at 69oC with additional heat inactivation (5 minutes at 95oC) and melting curve analysis steps. Fluorescence signals were measured for every minute during 60 (screening and optimization) or 30 [limit of detection (LoD) and crossreactivity] minutes of incubation. Any changed conditions are specified for each experiment. See page 730, right column, para 3.
Accordingly, Lee and Park teach the RT-LAMP assays for the detection of three highly related coronavirus infectious agents for human, MERS, SARS-CoV and SARS-CoV-2. They teach the mechanisms of the RT-LAMP primer design. They teach that the nucleocapsid protein gene (N gene) of the viruses can be used as target for primer design and that the primers can be either manually selected or designed by primer design software (PrimerExplorer) based on known viral genome sequences. However, Lee and Park are silent on the specific primer sequences as claimed, which are designed to target the SARS-CoV-2 nucleocapsid (N) gene sequence.
GenBank: MN908947, cited in Park, discloses the complete genome of severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1. It contains an N gene sequence, nt 28274-29533, that comprises all of the primer sequences (SEQ ID NOs: 1-7) recited in the instant claims.
The instant claims specify primer sequences targeting a specific SARS-CoV-2 N gene sequence region. Since the genome sequence targeted by the claimed invention is known in the art at the time of invention, and the design of RT-LAMP primers are considered as routine in the art, the claimed primer sequences are considered as equivalent as those known in the art, which can be arrived through routine experimental optimization, unless there is evidence that the claimed sequences produce unexpected results.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Lee, Park and GenBank: MN908947 to arrive at the invention as claimed through routine experimental optimization.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JANET ANDRES, on (571) 272-0867, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/ Primary Examiner, Art Unit 1671