DETAILED 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 .
Election/Restrictions
[Copied from Nonfinal 06August2025 → ] Applicant's election with traverse of Group I (claims 1-14) in the reply filed on 16June2025 is acknowledged. Applicant's election without traverse of species (A)(i) Candidatus Liberibacter asiaticus, (B)(i) SEQ I DNO: 7, (C)(i) citrus, and (D)(i) primer pair SEQ ID NOs: 1 and 2 in the reply filed on 16June2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the Species Election Requirement, the species election has been treated as an election without traverse (MPEP § 818.01(a)).
The traversal is on the ground(s) that all claims (i.e., Groups I and II) are united by a single Cas and single stranded nucleotide pairing and no separate search is required. This is not found persuasive because, as said in the Restriction Requirement dated 18April2025, the kit claims (Group II) do not require a sample be present and appear to be useful for a materially different process (e.g., modifying the genome of a bacterial plant pathogen). It follows that at least a separate search regarding gene editing kits would be required for Group II that is not relevant to Group I.
The requirement is still deemed proper and is therefore made FINAL.
Claim 4 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species (claim 4) or group (claims 15-25), there being no allowable generic or linking claim. Applicant timely traversed the Restriction Requirement (relevant to electing either Group I or II) in the reply filed on 16June2025.
Status of the Claims
The claims filed 08December2025 are acknowledged and have been fully considered. Claims 7, 12, 15-25 are canceled. Claims 1-6, 8-11, 13-14 are pending. Claim 4 remains withdrawn (claims 15-25, which were withdrawn in the Nonfinal action, are now canceled). Claims 1-3, 5-6, 8-11, 13-14 are examined on the merits herein.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [US provisional 63364081 filed 03May2022] is acknowledged. Claims 1-3, 5-6, 8-11, 13-14 maintain an effective filing date of 03May2022.
Withdrawn Objections and/or Rejections
Objections and/or rejections made of record in the nonfinal office action dated 06August2025 that are not otherwise discussed herein are withdrawn. In particular:
RE ¶ 6: The Written Description rejection is withdrawn in view of the amendments to the claims (e.g., adding a requirement of amplification using isothermal amplification) and Applicant’s Remarks at the top of page 5 which states the following
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Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries 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.
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 as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention 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.
Claims 1-3, 5-6, 8-11, 13-14 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over CHEN et al. (“CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity” 2018 Science 360:436-439, of record IDS 10May2024); DOUDNA et al. (US Pat. No. 10253365, of record IDS 10May2024); VEROSLOFF et al. (“PLANT-Dx: A Molecular Diagnostic for Point-of-Use Detection of Plant Pathogens” 2019 ACS Synth. Biol. 8:902-905); and ZHENG et al. (“Unusual Five Copies and Dual Forms of nrdB in “Candidatus Liberibacter asiaticus”: Biological Implications and PCR Detection Application” 2016 Scientific Reports 6:39020 (9 total pages, DOI:10.1038/srep39020).
[Copied from Nonfinal 06August2025 ↓ Please see the Response to Remarks Section for New Content]
These claims read on Cas12-based nucleic acid detection/diagnostic methods such as that called “DETECTR” (for “DNA endonuclease-targeted CRISPR trans reporter”) taught by CHEN et al. (a summary of which is shown at Fig. 4 of CHEN et al. on page 3). In particular, these claims are directed toward the use of DETECTR, for example, to detect a bacterial plant pathogen within a sample (where the sample may be, amongst other things, soil or plant lysate [see claims 1, 9]). In particular claims, the method detects the presence of Candidatus Liberibacter asiaticus infection [see claims 1, 2] by using its nrdB gene as the target DNA [see claims 1, 3] and in certain claims it is specified that the sample is Citrus cell lysate [see claims 1, 10].
To be clear, the DETECTR methodology taught by CHEN et al. (demonstrated in the context of detecting human papillomavirus in human patient samples) delivers a Cas12a protein [see claims 1, 6] with a guide RNA (optionally being a precursor guide RNA (see claim 8)), and a single-stranded DNA reporter oligonucleotide (ssDNA) that, when cleaved, emits a fluorescent signal [see claims 1, 11] to signal that the target pathogen DNA is present (thus, signaling the presence of pathogen within the sample and indicating the patient may be infected with the pathogen). The DETECTR methodology taught by CHEN et al. includes isothermal amplification by recombinase polymerase amplification (RPA) [see claims 1,12-13]. The DETECTR methodology identifies targets “with attomolar sensitivity” (CHEN et al. at page 3, middle column) [see claims 1, 7] and is not believed to be limited to a particular pathogen type or a particular sample type (note that CHEN et al. say “[t]hese results demonstrate a new platform for CRISPR-based diagnostics … and suggest that DETECTR could, in principle, detect any DNA sequence with high sensitivity and specificity” (page 3, top of the right column)).
CHEN et al. do not specifically suggest the use of DETECTR for detecting the presence of bacterial pathogens or, in particular, bacterial plant pathogens (e.g., wherein the sample is a plant-originating sample or soil sample) [relevant to claim 1, and therefore, all claims].
But this deficiency is supplemented by the teachings of at least DOUDNA et al. (which appears to be a patent document corresponding to the content of the CHEN et al. publication (see DOUDNA et al. at Column 4, lines 28-30), please note J. A. Doudna is a named author of CHEN et al.) and VEROSLOFF et al.
DOUDNA et al. teach that the pathogen may be a bacterial pathogen (see, e.g., claim 5 of DOUDNA et al. at column 190) and that the sample may be a plant lysate (see, e.g., Column 16 at lines 10-11). VEROSLOFF et al. teach and suggest the use of CRISPR/Cas-based methods for point-of-use plant pathogen detection. In particular, VEROSLOFF et al. suggest the use of methods such as DETECTR (taught by CHEN et al., reference number “4” in VEROSLOFF et al.) for detecting plant pathogens because such technologies “have improved upon gold standard diagnostic methodologies by decreasing cost, increasing accuracy, and enhancing portability” (VEROSLOFF et al. at Abstract) and they “significantly improve upon the current laboratory-intensive PCR-based approaches” (VEROSLOFF et al. at page 902, top of the left column). This is material, because VEROSLOFF et al. is speaking to a known advantage of CRISPR/Cas detection methodologies (DETECTR in particular) over PCR-based approaches: the CRISPR/Cas-based methodologies increase at least accuracy over PCR-based approaches (note DETECTR methods provide attomolar sensitivity per CHEN et al. and DOUDNA et al.) and, per VEROSLOFF et al., CRISPR/Cas-based methodologies may also provide other benefits over PCR-based approaches such as decreasing cost and enhancing portability.
With respect to claims 2-3, 5, 10, and 14; PCR-based detection of Candidatus Liberibacter asiaticus within a citrus plant sample using (all five copies of) the nrdB gene was already known in the prior art (ZHENG et al., see Abstract).
Without more information from Applicant, the subject matter of these claims would have been obvious to a person with ordinary skill in the art at the time this application was filed (a “POSA”) because it would have been nothing more than the “use of a known technique (DETECTR per CHEN et al. and DOUDNA et al.) to improve similar methods (PCR-based detection per ZHENG et al.) in the same way” (MPEP § 2143(I)(C)); “applying a known technique (DETECTR per CHEN et al. and DOUDNA et al.) to a known method (PCR-based detection per ZHENG et al.) ready for improvement to yield predictable results” (MPEP § 2143(I)(D)); the “simple substitution of one known element (DETECTR protocol per CHEN et al. and DOUDNA et al.) for another (PCR-based detection per ZHENG et al.) to obtain predictable results” (MPEP § 2143(I)(B)); or, at the very least, “obvious to try” (MPEP § 2143(I)(E)). A POSA would have been motivated to at least try using the DETECTR methodology of CHEN et al. and DOUDNA et al. for detection of Candidatus Liberibacter asiaticus within a citrus plant sample using (all five copies of) the nrdB gene because, as emphasized by VEROSLOFF et al., CRISPR/Cas methodologies such as DETECTR are an improvement over previous PCR-based detection methods (providing, for example, increased accuracy of attomolar-level senstitivity of detection). Given the successful use of DETECTR and the suggestion to use it (per VEROSLOFF et al.), one such POSA would have a reasonable expectation of successfully detecting Candidatus Liberibacter asiaticus (e.g., within a citrus plant sample and using the nrdB gene) therewith. To be clear regarding the sequence particulars of claims 5 and 14, there is nothing in the current record to suggest that those structures are nonobvious in view of the prior art and, in any event, anything other than an obvious design choice by a POSA utilizing DETECTR detection (CHEN et al. and DOUDNA et al.) instead of PCR-based detection (ZHENG et al.) targeting the nrdB gene.
Response to Applicant’s Remarks dated 08December2025:
Applicant asserts that the claim amendments filed 08December2025 are sufficient to overcome this rejection, in particular, the requirement for “attomolar sensitivity of detection” of a phloem-limited bacterial plant pathogen (Remarks at page 8).
As an initial matter, please note that a “phloem-limited bacterial pathogen” may be Candidatus Liberibacter asiaticus within a citrus plant sample (using (all five copies of) the nrdB gene as target) (see claims 2-3). Because this content was already addressed via the rejection of record (see the discussions of ZHENG et al.), those claim amendments are not sufficient to overcome this rejection.
Regarding “attomolar sensitivity”, Applicant asserts that a POSA would not have had a reasonable expectation of successfully achieving “attomolar sensitivity” of detection of a phloem-limited bacterial pathogen at least because “phloem-limited bacterial plant pathogens [] exist at a very low titer and are notoriously difficult to reliably detect in plant tissues” (Remarks at page 8). This argument is not persuasive in view of at least ZHENG et al. who verified the sensitivity of the subject detection method in plant tissue. As said of record, the sensitivity of the subject detection method lends toward obviousness here (e.g., it would at least be a reason (motivation) to use the method in the context of low titer target DNA).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Rebecca STEPHENS whose telephone number is (571)272-0070. The examiner can normally be reached Monday through Friday 8:30-4:30.
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/REBECCA STEPHENS/Examiner, Art Unit 1663
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663