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 Apr. 10, 2026. Claims 20-22 are pending and currently examined.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Apr. 10, 2026 has been entered.
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.
(Previous Rejection - Withdrawn) Claims 20-22 were rejected under 35 U.S.C. 102 as being anticipated by Kim et al. (Anal. Chem. 2014, 86, 5858−5864).
This rejection is withdrawn in view of Applicant’s arguments filed on April 10, 2026.
Applicant argues that Kim does not disclose inserting a genetic construct comprising both an indicator gene and a promoter controlling transcription of an indicator gene.
Based on Applicant’s arguments, the structure in Kim responsible for the expression of the indicator luxCDABE, which comprises the phage endogenous promoter Pcps to drive the transcription of the indicator genes, does not read on the “genetic construct” as claimed.
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, 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.
(New Rejection) Claims 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson (US 2015/0218616, published on Aug. 6, 2015; submitted in IDS filed on Sep. 6, 2024) and Kim et al. (Anal. Chem. 2014, 86, 5858−5864). Both references are of record in previous Office actions.
Anderson teaches an invention relating to a recombinant bacteriophage which comprises a non-native indicator gene in the late gene region. The indicator product is not a fusion protein. The specificity of infectious agents allows a specific microorganism to be targeted, and an indicator signal may be amplified to optimize assay sensitivity. See Abstract. Anderson teaches that embodiments of the invention comprise compositions, methods, systems and kits for the detection of microorganisms. See [0007].
Anderson teaches that bacterial cells detectable by the invention include, but are not limited to, bacterial cells that are food or water borne pathogens, including, but are not limited to, all species of Salmonella, all strains of Escherichia coli, including, but not limited to E. coli O157:H7, all species of Listeria, including, but not limited to L. monocytogenes, and all species of Campylobacter. See [0058].
FIG. 1 depicts a schematic representation of the genomic structure of a recombinant bacteriophage of the invention, Indicator Phage T7SELECT®415-Luc. For the embodiment depicted in FIG. 1, the detection moiety is encoded by a Firefly luciferase gene inserted within the late (class III) gene region, which is expressed late in the viral life cycle. Late genes are generally expressed at higher levels than other phage genes, as they code for structural proteins. Thus, in the embodiment of the recombinant phage depicted by FIG. 1, the indicator gene (i.e., Firefly luciferase) is inserted into the late gene region, just after gene 1 OB (major capsid protein), and is a construct comprising the Firefly luciferase gene. The construct depicted in FIG. 1 was designed to include stop codons in all 3 reading frames to ensure luciferase is not incorporated into the gene 1 OB product. Also as depicted by FIG. 1, the construct may comprise the consensus T7 late promoter to drive transcription and expression of the luciferase gene. The construct may also comprise a composite untranslated region synthesized from several T7 UTRs. This construct ensures soluble Firefly luciferase is produced such that expression is not limited to the number of capsid proteins inherent in the phage display system. See [0081]. Fig. 1 of Anderson is shown below:
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Accordingly, Anderson teaches a recombinant bacteriophage, e.g., Indicator Phage T7SELECT®415-Luc, shown in Fig. 1 above, comprising a heterologous genetic construct inserted into a late gene region of the bacteriophage genome, the genetic construct comprising an indicator gene and a late promoter (T7 late promoter).
However, Anderson is silent on if the disclosed recombinant bacteriophages are derived from a Salmonella-specific bacteriophage, even though teachings of Anderson indicate that recombinant phages of the invention may be used to detect Salmonella.
Kim teaches that as an alternative to time-consuming and laborious conventional detection methods for pathogens of foodborne illnesses, a technique using recombinant reporter phages has been developed. The authors developed an advanced bioluminescent reporter phage SPC32H-CDABE by inserting a bacterial luxCDABE operon into the Salmonella temperate phage SPC32H genome. Whole SPC32H genome sequencing enabled the selection of nonessential genes, which can be replaced with approximately 6-kb luxCDABE operon, which provides both luciferase (LuxAB) and its substrate, fatty aldehyde, as generated by fatty acid reductase (LuxCDE). Thus, the SPC32H-CDABE detection assay is simpler and more efficient compared to the luxAB-based assay because the substrate addition step is excluded. At least 20 CFU/mL of pure S. Typhimurium culture was detectable using SPC32H-CDABE within 2 h, and the signals increased proportionally to the number of cells contaminated in lettuce, sliced pork, and milk. These results thereby demonstrate that this phage successfully detects live Salmonella without appreciable interference from food components. Furthermore, the presented data suggest that SPC32HCDABE represents a promising easy-to-use diagnostic tool for the detection of Salmonella contamination in food. See Abstract.
Figure 1 presents the construction of the bioluminescence reporter phage SPC32H-CDABE. Figure 1(A) shows that the indicator operon luxCDABE is driven by promoter Pcps which contain the cps promoter. See below:
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Kim teaches that the phage cps gene encodes a major capsid protein, implying that the cps promoter is a phage late gene promoter and the operon is inserted in a late gene region (phage capsid genes are considered late gene since they are transcribed later in the phage life cycle before packaging). See page 5861, left column, para 2, together with Figure 1(A).
Kim further teaches that SPC32H-CDABE and other luxCDABE-based reporter phages could be used to facilitate the development of an easy-to-use phage-based pathogen detection system, such as a portable laboratory diagnostic tool kit. See page 5863, right column, para 3.
Accordingly, Kim teaches a bioluminescence reporter phage, SPC32H-CDABE, derived from a Salmonella-specific phage, SPC32H, engineered to comprise a genetic construct inserted into a late gene region of the bacteriophage genome, the genetic construct comprising an indicator gene.
However, Kim teaches that the genetic construct inserted into the late gene region of the bacteriophage genome does not comprise a promoter. Instead, the indicator genes rely on the endogenous phage later promoter (Pcps) for transcription.
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 Anderson and Kim to arrive at the invention as claimed. One would have been motivated, e.g., to construct a Salmonella-specific recombinant bacteriophage by substituting bacteriophage of Anderson with the Salmonella-specific bacteriophage taught in Kim, or by modifying the study of Kim by changing the indicator gene expression strategy taught in Kim (i.e., insertion of a promoterless expression cassette in the late gene region of the bacteriophage genome) to the strategy taught in Anderson (i.e., insertion of a promoter-containing expression cassette). Based on the teachings of Anderson and Kim, both strategies are expected to be functional in the expression of indicator genes.
Regarding the limitation that the indicator gene is not contiguous with a gene encoding a structural bacteriophage protein and does not yield a fusion protein, and wherein expression of the indicator gene results in an indicator protein product detectable in progeny bacteriophage, there is no indication that the indicator genes in Anderson and Kim are contiguous with a phage structural gene and yield a fusion protein (which does not appear to be necessary in the studies of Anderson and Kim).
Regarding the limitation “wherein the recombinant bacteriophage detects Salmonella spp. in the powdered infant formula sample after a 30-120 minute incubation”, this limitation does not specify how the powdered infant formula sample is processed before the detection assay, how much Salmonella spp. bacteria are contained in the sample, and how the detection assay is performed. Since the recombinant bacteriophage suggested by the combined teachings of Anderson and Kim is indistinguishable from that as claimed, it is assumed to have the same property, including the ability of detecting Salmonella spp. in the powdered infant formula sample after a 30-120 minute incubation, as claimed.
Regarding claim 21, Anderson teaches that the indicator moiety may react with a substrate to emit a detectable signal or may emit an intrinsic signal (e.g., fluorescent protein). See [0109]. Kim also teaches that fatty aldehyde functions as the substrate of the luciferase (LuxAB). See Abstract. One of skill in the art would have found it obvious to include a substrate that react with the luciferase indicators of Anderson and Kim in a kit to act as a positive control or for calibration.
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
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