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 Feb. 14, 2023. Claims 1-21 and 23-37 are pending and currently examined.
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 9-18 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.
Claim 9 recites “The replicon system according to claim 8, comprising the following two expression vectors comprising: (i) a nucleic acid sequence encoding a novel coronavirus SARS-CoV-2 non-structural protein; and (ii) nucleic acid sequences of 5' UTR and 3' UTR of a novel coronavirus SARS-CoV-2, a transcription regulatory region on which the novel coronavirus SARS-CoV-2 non-structural protein can act, and a reporter gene.” Here, the limitation “the following two expression vectors” is not clear since neither claim 8 nor claim 1 from which claim 9 depends recite two expression vectors. Additionally, claim 9 does not recite anything that can be reasonably considered as two expression vectors, except for the two nucleic acid sequences (i) and (ii) which can be inserted in one or more expression vectors.
Claims 10, 11 and 14 depend from claim 9 and recite “expression vector (ii).” This limitation is not clear since (ii) refers to nucleic acid sequences, not “expression vector.” Similarly, claim 16 recites “wherein expression vector (i) comprises three expression vectors, in which nucleic acid sequences encoding one or more of novel coronavirus SARS-CoV-2 protein nsps 1-16 are respectively inserted.” Here, “expression vector (i)” is not clear since “(i)” in claim 9 refers to “a nucleic acid sequence encoding a novel coronavirus SARS-CoV-2 non-structural protein”, not an expression vector. Additionally, it is not clear how to interpret the limitation “expression vector (i) comprises three expression vectors.” It is not clear how an expression vector can comprise three expression vectors. Moreover, the phrase “in which nucleic acid sequences encoding one or more of novel coronavirus SARS-CoV-2 protein nsps 1-16 are respectively inserted” is not clear since it is not clear how the “one or more” SARS-CoV-2 nsps 1-16 should be “respectively inserted” into “three expression vectors”.
Claim 15 recites “wherein the encoded novel coronavirus SARS-CoV-2 non-structural protein is novel coronavirus SARS-CoV-2 protein nsps 1-16” which is not clear. This limitation appears to require a “non-structural protein”, however, the term “nsps 1-16” encompasses all non-structural proteins of SARS-CoV-2. Thus, it is not clear if all 16 of nsps are required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-8, 19-20, 23, 25-31 and 34-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hou et al. (Cell 182, 429–446; July 23, 2020).
These claims are directed to a SARS-CoV-2 replicon, comprising: (I) a nucleic acid sequence encoding a SARS-CoV-2 non-structural protein; and (II) nucleic acid sequences of 5' UTR and 3' UTR of the SARS-CoV-2, a transcription regulatory region on which the novel coronavirus SARS-CoV-2 non-structural protein can act, and a reporter gene.
Hou teaches a study using reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. See Abstract.
Hou teaches that a full-length infectious complementary DNA (cDNA) clone of a US SARS-CoV-2 clinical isolate WA1 was generated by cloning seven genomic fragments separately into vector plasmids (Figure 1A). Additionally, two reporter viruses were constructed by replacing a 276-bp region in ORF7 with a green fluorescent protein (GFP) or a GFP-fused nanoluciferase (nLuc) gene (Figure 1A). After assembly into full-length cDNA, full-length RNA was electroporated into Vero-E6 cells (Scobey et al., 2013; Yount et al., 2003). After recovering the wild-type (WT), icSARS-CoV-2-GFP, and icSARS-CoV-2-nLuc-GFP recombinant viruses, viral replication was confirmed by the presence of sub-genomic length leader-containing RNA transcripts 20 h after electroporation (Figure S1). All three recombinant viruses replicated (Figure S1), generated similar plaques in Vero E6 cells, and could be passaged serially in the cell culture without exogenous trypsin (Figure 1B). See page 430, right column, para 1. Figure 1A of Hou is shown below:
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Since the full-length viral genome sequence is included in the recombinant viral constructs (with only ORF7a replaced by GFP or GFP-nLuc genes in the reporter-gene-containing constructs) generating replicating viruses, the recombinant viral constructs (replicons) inherently comprise all of the coding and non-coding nucleic acid sequences required for viral replication and passaging in host cells, including viral non-structural proteins (e.g., nsp1-16 encoded by ORF1a and 1b), the 5’ UTR and 3’-UTR regions, and other transcription regulatory region(s) on the SARS-CoV-2 genome on which the viral non-structural protein can act.
Regarding claims 5 and 6, the icSARS-CoV-2-nLuc-GFP replicon comprises two reporter genes encoding GFP and nLuc respectively, and at least one of the genes (e.g., nLuc) is connected to a stop codon, and is located upstream of the transcriptional regulatory region of the N gene.
Regarding claim 20, Hou teaches infecting various human cells with icSARS-CoV-2-GFP reporter virus and observed production of progeny viruses. See page 436, left column, para 2 and 3.
Regarding claims 23, 30 and 31, which specify a method for screening an anti-SARS-CoV-2 drug, comprising adding a drug to be tested to an expression system comprising the replicon structure according to claim 1 (claim 23), an expression system comprising the replicon structure according to claim 8 (claim 30), or an expression system comprising the packaging cell according to claim 19 (claim 31), these claims do not specify the drug to be tested. Hou teaches neutralization assays using luciferase reporter coronaviruses on mAbs and COVID-19 sera. See e.g., Figure 3. Here, the mAbs and COVID-19 antisera can be considered as potential anti-SARS-CoV-2 drugs.
Regarding claims 25-28 and 34-37, these claims specify a system for drug screening or molecular epidemiological monitoring. The claims do not specify components of the system other than the replicon structure of claim 1 or 8 or packaging cells comprising the replicons (except for claim 26 which specifies a luciferase detection device). Referring a system by a different name does not change the structure and properties of the replicon system itself. As to claim 26, Hou teaches using luciferase activities in neutralizing assays (see e.g. Figure 3), implying that a luciferase assay device is used.
Accordingly, Hou anticipates claims 1-8, 19-20, 23, 25-31 and 34-37.
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 21, 24 and 32-33 are rejected under 35 U.S.C. 103 as being anticipated by Hou et al. (Cell 182, 429–446; July 23, 2020), as applied in the 102 rejection above.
Claim 21 specifies that the replicon structure or replicon system is codon-optimized. Claims 24 and 32-33 specify a kit for screening an anti-novel coronavirus SARS-CoV-2 drug.
Relevance of Hou is set forth above. However, it is silent on the additional limitations specified by claims 21, 24 and 32-33.
Regarding claim 21, Hou teaches the practice of codon optimization for expression of antibody genes in human cells. See page e8, last para. It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to make codon optimizations for genes involved in the SARS-CoV-2 replicons taught in Hou. One would have been motivated to do so to improve the expression of genes in host cells.
Regarding claims 24 and 32-33, it would have been obvious to those of ordinary skill in the art to produce a kit by combining the known ingredients with instructions for use as recited in the claims for the purpose of commercialization. The combination of the known elements would have predictable results to one of ordinary skill in the art since all the claimed elements would continue to operate in the same manner that is no more than the predictable use of prior-art elements according to their established functions. Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004). See MPEP 2112.01 III.
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