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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 20January2026 has been entered. This is the second RCE of this application (the first having been filed 19March2025).
The amendment filed after-final 22December2025 was already entered and substantively considered (see the Advisory Action dated 08January2026). Because there are no new amendments or remarks filed with Applicant’s RCE (please note that the 20January2026 RCE, document code “RCEX”, references the 22December2025 filing as the requisite “submission”), this action is Final. MPEP § 706.07(b). For the sake of a clear record, the content of the Advisory Action dated 08January2026 is restated here if relevant (e.g., restating that certain objections or rejections are withdrawn via the filing 22December2025).
Status of the Claims
The claims filed 22December2025 were entered and fully considered with the Advisory Action dated 08January2026. No claims are filed with the RCE 20January2026, so the claims filed 22December2025 are the latest of record.
Claims 1-19 and 21 were previously canceled. Claims 20, 22-29 are pending and are examined on the merits herein. Claims 20, 22-24, 27-29 were previously presented. Claims 20, 25-26 are currently amended.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [11 US provisionals including 63059963, 63059813, and 63059860 filed 31July2020] and 35 U.S.C. 120 [Continuation of PCT/US2021/043919 filed 30July2021; Continuation of 18057867 filed 22November2023, now US Pat. No. 11814630] is acknowledged. Claims 20, 22-29 are supported by at least US provisional applications 63059963, 63059813, and 63059860; therefore, claims 20, 22-29 MAINTAIN an effective filing date of 31July2020.
Claim Interpretations
following claim interpretations have been made by the Examiner and relied upon for examination:
[Copied from the Final Action 19November2024 & Nonfinal Action 20June2024 →] The “DAS81419-2” soybean plants and the “DAS81419-2” transgenic loci (see claims 20, 25, 26) are well-known in the field. In particular, while the specification describes “DAS81419-2” with respect to issued patents and representative deposited seed (see screenshot below, from page 7 ¶27 of the specification); please note that “DAS81419-2” soybean plants are known commercially under the trade name CONKESTATM and publicly available by the DOW AGROSCIENCES family of companies.1
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Regarding the subject matter of claims 27-29, and for the sake of a clear record: the Office considers such DNA molecules, processed transgenic maize plant product(s), and biological sample(s) to have a well-recognized specific and substantial utility in the context of identifying whether or not a particular plant product, whole plant, or plant part comprises or originated from a transgenic maize plant cell as set forth in claims 20, 22-24. A real-world example being Applicant or a third party obtaining a commercialized maize plant (or plant product) then assaying a biological sample therefrom for the presence of the DNA molecule as set forth in claim 27 (which, if present, suggests that the commercialized maize plant/product comprises or originated from the subject matter of this application’s claims 20, 22, 23, or 24. Such uses are encompassed by the description of “detection/detecting” throughout ¶9 on page 3 of the specification; ¶60 on page 14 of the specification; and ¶62 on page 16 of the specification (see also embodiment #12 at ¶107 on page 50 of the specification). For at least this reason, there is no rejection herein or of-record for a lack of utility under 35 USC §§101,112(a).
Withdrawn Objections and/or Rejections
As stated in the Advisory Action dated 08January2026, the following objection(s) and/or rejection(s) were withdrawn in view of Applicant’s after-final claim amendments and/or remarks filed 22December2025 (paragraph references are those of the Final action dated 20October2025):
RE ¶ 5: The objection to claim 25 is withdrawn in view of the amendment to the claim (adding “soybean” as requested by the Office);
and
RE ¶ 6: The rejection of claims 25-26 as indefinite is withdrawn in view of the amendments to the claims (removing “is introduced using a guide RNA” language).
Claim Rejections - 35 USC § 112 - Indefiniteness
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 20 (and, therefore, claims 22-29 which refer thereto without correcting the issue) REMAIN rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
↓ Copied from the Advisory Action dated 08January2025, But-for correction of typographical errors ↓
Please note that the amendments to claim 20 introduce new indefiniteness issues. In particular, the claim now states that the claimed plant cell may both comprise SEQ ID NO: 2 and comprise a deletion OF ALL of the 3' junction sequence SEQ ID NO: 21. Based on sequence alignment; the sequence SEQ ID NO: 2 only has a PARTIAL deletion of the sequence SEQ ID NO: 27. To that end, it does not appear to be possible for a plant cell to both comprise SEQ ID NO: 2 and comprise a deletion of all of SEQ ID NO: 27. The following amendment would remedy this issue: "... comprises a deletion of part [[or all]] of the 3' junction polynucleotide sequence ... and wherein the deletion [[of the 3' junction polynucleotide sequence]] is introduced using ...."
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.
I.) Claims 20, 22-29 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over DANILO et al. (“The DFR locus: A smart landing pad for targeted transgene insertion in tomato” 2018 PLOS ONE 13(12):e0208395 (14 total pages) of record IDS 29November2023); RUDGERS & SASTRY-DENT (“EXZACTTM Precition Technology: Scientific and Regulatory Advancements in Plant-Genome Editing with ZFNs” in the 2014 NABC REPORT 26 titled “New DNA-Editing Approaches: Methods, Applications & Policy for Agriculture” Eaglesham & Hardy Eds. (12 total pages) of record IDS 29November2023); BARD et al. (US Pat. No. 8680363 issued 25March2014 to DOW AGROSCIENCES LLC); and DE FRAMOND et al. (WO2010/077816 published 08July2010 to SYNGENTA PARTICIPATIONS AG).
With the amendment filed 21August2025, claims 25-26 were amended to refer to a particular guide RNA (SEQ ID NO: 4), the use of which is understood to result in the modified DNA molecule set forth in SEQ ID NO: 2 (recited in claim 20). Because it is unclear if one must use the recited guide RNA sequence SEQ ID NO: 4 to perform the methods of claims 25-26 and because, in any event, use thereof would direct the nuclease to the target site needed for generating the modified sequence SEQ ID NO: 2; and because the sequence SEQ ID NO: 2 would have been obvious to a person with ordinary skill in the art at the time this application was filed (a “POSA”) for the reasons stated of record, there is no change to the obviousness rejection(s) as set forth in the nonfinal Action dated 21April2025 and as set forth in the Final Action dated 20October2025.
To be clear, in the nonfinal action dated 21April2025 and then again via a Request for Information (under 37 CFR § 1.105) with the Final action dated 20October2025, the Office asked Applicant to please identify any functional effect that the 7-nucleotide deletion of SEQ ID NO: 2 has (as compared to the known DAS81419-2 loci sequence SEQ ID NO: 1) (see the nonfinal 21April2025 at the top of page 13)—Applicant has not done so in their reply filed 21August2025 or After-Final reply filed 22December2025 nor otherwise explained how the claimed structures would have been unexpected. Such information remains material to overcoming this rejection because, without it, the sequence SEQ ID NO: 2 represents an obvious minor/de minimus structural change (a 7-nucleotide deletion) without a corresponding new or unexpected functional effect as compared to the known DAS81419-2 loci and it remains the Office’s belief that this 7-nucleotide deletion is simply the result of having a CRISPR/Cas approach to the DAS81419-2 loci such as an InDel caused by non-homologous end joining (i.e., the 7-nucleotide deletion was an unintentional consequence by Applicant and simply an artifact of CRISPR/Cas). This would be disproven by more information from Applicant about the nature of the 7-nucleotide deletion. To that end, it is highly recommended that Applicant provide some statement regarding any function that the 7-nucleotide deletion has and/or any function that a transgenic soybean plant cell comprising a modified DAS81419-2 transgenic loci comprising SEQ ID NO: 2 has that a soybean plant cell comprising a DAS81419-2 loci (i.e., comprising SEQ ID NO: 1) does not have. Asked another way, how can the plants/plant cells of these claims be used in a manner that the known plant/plant part comprising a DAS81419-2 loci cannot?
These claims are now limited to making a particular deletion in the 3’ junction polynucleotide of the DAS81419-2 transgenic locus (specifically, that shown in SEQ ID NO: 2 which, as clarified by Applicant in the Remarks dated 20September2024 (pages 4-5), comprises a seven nucleotide deletion in the 3’ junction sequence of the DAS81419-2 transgenic locus as compared to the original DAS81419-2 locus sequence SEQ ID NO: 1:
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[↓ Copied from Nonfinal 20June2024 EXCEPT THAT, in view of Applicant’s Remarks and Amendments 20September2024, (1) “DAS81419” is updated to “DAS81419-2”, (2) BARD et al. is assumed to teach SEQ ID NO: 1 rather than SEQ ID NO: 2 and (3) “5’ junction” is updated to “3’ junction” as appropriate ↓]
For clarity, simply deleting a part of the “DAS81419-2 transgenic locus” would be relevant to two sub-fields of the art ((1) efforts to delete markers of transgenic loci to generate marker-free transgenic plants and (2) efforts to delete any other portion of a transgenic loci so that the loci can be re-used as a “landing pad”/”safe harbor” for other, desired transgenes; the latter of which is not necessarily concerned with marker sequences or even maintaining the original transgene(s) but rather re-use of the loci location itself). This application appears to be about the latter ((2) “landing pads”/”safe harbors”) at least because the claims specify that the deletion is in the “3’ junction polynucleotide” which (as shown in FIG. 2 of BARD et al.) is far downstream of the phosphinothricin acetyltransferase (PAT) selective marker sequence that is within the “DAS81419-2 transgenic loci”.2 To that end, this rejection will focus on “landing pads”/”safe harbors” and not (1) the precise excision of selectable marker sequences for the purpose of making marker-free transgenic plants. This context is significant when thinking about motivation, for example, but also important for understanding why certain prior art references have been identified by the Office as being more relevant to the claimed subject matter than others. Also for clarity, discussions of “landing pads”/”safe harbors” within the field can be generalized into two types of contexts: (a) swapping out transgenes (coding sequences or regulatory sequences) at a particular loci (such as deletion of polynucleotides, perhaps coding or regulatory sequences, followed by insertion of a different transgene’s expression construct there using, for example, gene editing like CRISPR/Cas), or (b) “gene stacking” meaning the insertion of a different transgene coding sequence within the “landing pad”/”safe harbor” loci but not necessarily with a prior deletion/excision step3. Because these claims focus on deletion and do not specify later insertion (for example, of one or more transgenes), this rejection will focus on (a) swapping out transgenes (coding or regulatory sequences) at a particular loci and (b) starting materials for “gene stacking” (i.e., “gene stacking” is only relevant to the extent that a deletion would first be made in the “landing pad”/”safe harbor” loci before new transgene insertion (such as to make room at the loci for the new transgene). Said another way, while it is understood that the claimed starting materials could be used for (b) gene “stacking” (where a prior deletion step as in these claims would make room in the “DAS81419-2 transgenic loci” for a later insertion of at least one new transgene whilst maintaining the original genes encoded by the “DAS81419-2 transgenic locus”); just inserting genes into a “landing pad”/”safe harbor” (i.e., “stacking” them) without a prior deletion step will not be a focus here (of this rejection or the rejection that follows this one). Like that above, this context is important for thinking about motivation, for example, and for understanding why certain prior art references have been identified by the Office as being more relevant to the claimed subject matter than others. The Office considers prior art references that are specifically about (1) generating marker-free plants or (b) gene “stacking” at a “landing pad”/”safe harbor” (without, first, deleting polynucleotides within the loci) to be less than the references cited here (such as DANILO et al.). Please note that within the obviousness rejection below, “gene stacking” with a prior deletion step is the focus (which is consistent with what has been said here—that rejection below doesn’t just focus on gene insertion for “gene stacking,” but rather gene insertion that is preceded by a deletion step).
DANILO et al. teach that the “targeted integration of a gene of interest of pyramiding of several genes4 in elite genotypes without the undesirable effects associated with random transgene insertion in the genome” is desirable within the art.5 DANILO et al. demonstrate this principle in tomato plants using the location of the anthocyanin biosynthesis gene dihydroflavonol 4-reductase (DFR) as the “landing pad”/”safe harbor” for transgene insertion.6 In particular, DANILO et al. demonstrate successful 1013 bp deletion within the DFR loci (including DFR coding sequence and specifically including the 3’ end of the DFR gene7) and subsequent insertion (and expression) of a transgene via gene editing technology (therein using CRISPR/Cas technology):8
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DANILO et al. do not specify that the deletion is in a “5’ junction polynucleotide” of the “landing pad”/”safe harbor” loci. While DANILO et al. say that their technique “can potentially be applied to other crops”,9 DANILO et al. do not specifically teach this technique within a soybean plant or plant part (and, therefore, do not teach the soybean plants being “DAS81419-2 soybean” plants and, therefore, also do not teach the “landing pad”/”safe harbor” being the “DAS81419-2 transgenic locus”).
RUDGERS & SASTRY-DENT is cited because they explain what “landing pads”/”safe harbors” are and explain that known transgenic “event” plants (such as commercialized plants) may be used to identify the locations of such “landing pads”/”safe harbors”.10 In particular, RUDGERS & SASTRY-DENT say that “[i]n a plant genome, not all locations are suitable for targeted gene insertion. Safe-harbor locations are genomic regions where transgenes can be added with minimal unintended side effects and for consistent, reproducible transgene performance.”11 RUDGERS & SASTRY-DENT exemplify selecting the corn-rootworm-resistant/herbicide-tolerant gene stack of a commercial maize “event” transgenic plant (“Event-32” by DOW AGROSCIENCES) as a potential “landing pad”/”safe harbor” because the plant “performed well in the field as demonstrated by stable trait expression and efficacy, and exhibited neutral agronomics and good breeding characteristics”.12 RUDGERS & SASTRY-DENT then explain how that gene stack (loci) had been successfully targeted using zinc finger nucleases (“ZFN” therein) to add a gene of interest (“GOI” therein), i.e., modified using zinc finger nucleases for targeted gene insertion/”gene stacking” (notably, without a prior deletion step).13
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BARD et al. identify the “event DAS81419-2 insertion site”, as well as that “in the vicinity of” the event, as a “landing pad”/”safe harbor” (there, referred to as a “target site”) into which one or more genes of interest (or regulatory elements) may be inserted; including, for example, first deleting polynucleotides within or near the event loci then inserting a new sequence at that location.14 A specific example given by BARD et al. is to replace a transgene (e.g., cry1F and/or cry1Ac) or selectable marker gene (there, for example, the PAT sequence) such as by performing a deletion step (of the marker sequence) and then an insertion step (to introduce a different polynucleotide sequence at the location where the marker sequence formerly was).15 BARD et al. evidence that “DAS81419-2” soybean plants may be used to produce inbred plants (e.g., using backcrossing) and/or hybrid plants and that sequences for the “DAS81419-2” loci can be used to confirm that the loci is maintained in downstream progeny16 [relevant to claims 25-26]. And while BARD et al. do suggest that modifications (deletions or insertions) may be made within the 5’ junction/flanking sequences of the “DAS81419-2” event loci;17 because that teaching is only inferred, BARD et al. is (conservatively) interpreted as not explicitly teaching or suggesting a deletion within the 5’ junction/flanking sequence of the “DAS81419-2” event loci (a deficiency which is compensated by the teachings of DE FRAMOND et al., discussed below). As said in the above anticipation rejection, BARD et al. also teach soybean plants and plant parts (including seeds) comprising the transgenic “soybean event 9582.814.19.1” (representative seed for which was deposited with ATCC as PTA-12006) as well as the loci for the event itself (including sequences thereof such as 5’ and 3’ junction/flanking sequences) [relevant to claims 20, 22-24].18 Absent evidence to the contrary, BARD et al.’s event “9582.814.19.1” language is interpreted as being synonymous with the “DAS81419-2 transgenic locus” language of these claims and, it follows that, BARD et al. is assumed to teach the sequences SEQ ID NOs: 19 and 1 of these claims [relevant to claims 20 and 27]. BARD et al. obtained the sequence for “the event DAS81419-2 insert”/” DAS81419-2 transgenic locus” by isolating the DNA from “soybean tissue” (per the headers of Example 2, where “tissue” is believed to be leaf tissue based on the header at Example 6). Because “soybean tissue” (including soybean leaf tissue) is within the description of what constitutes a “biological sample”19 and “processed transgenic soybean plant product”20 of these claims; BARD et al. also teach the subject matter of claims 28 and 29.
DE FRAMOND et al. evidence that (albeit, in the context of maize plants) targeting the 5’ or 3’ junction/flanking sequence of a “landing pad”/”safe harbor” loci for, for example, “gene stacking” was known in the prior art.21
CONCLUSION: Based on what else was known in the prior art at the time this application was filed (discussed above), it is the Office’s position that a person with ordinary skill in the art (a “POSA”) would have found it obvious to modify the teachings of DANILO et al. using the “DAS81419-2 transgenic locus” information taught by BARD et al. to arrive at the presently claimed subject matter and with a reasonable expectation of success because doing so would have amounted to no more than:
“combining prior art elements (soybean “DAS81419-2” transgenic plants and its “DAS81419-2” loci via BARD et al.) according to known methods (those taught by DANILO et al.) to yield predictable results (the claimed subject matter being in alignment with what was achieved by DANILO et al.) (MPEP § 2143(I)(A));
the “simple substitution of one known element (DFR in tomato as taught by DANILO et al.) for another (the “DAS81419-2” loci in “DAS81419-2” soybean via BARD et al.) to obtain predictable results (the claimed subject matter being in alignment with what was achieved by DANILO et al.) (MPEP § 2143(I)(B));
the “use of known technique (that taught and demonstrated by DANILO et al.) to improve similar [products] (“DAS81419-2” soybean via BARD et al.) in the same way” (MPEP § 2143(I)(C));
and/or
“applying a known technique (that of DANILO et al.) to a known [product] ready for improvement (“DAS81419-2” soybean and its “DAS81419-2” transgenic loci via BARD et al.) to yield predictable results” (the claimed subject matter being in alignment with what was achieved by DANILO et al.) (MPEP § 2143(I)(D).
To be clear, and absent evidence to the contrary, DANILO et al., BARD et al., and DE FRAMOND et al. evidence that choosing to place a deletion “in the 3’ junction polynucleotide” comprising SEQ ID N: 19 of “the DAS81419-2 transgenic locus” comprising SEQ ID NO: 1 would have been “an obvious matter of design choice” (MPEP § 2144.04(VI)(C)).
The Office believes that a POSA would have been motivated to modify DANILO et al. for the purpose of arriving at the subject matter of claims 20, 22-24, 27-29 at least because BARD et al. identify the “DAS81419-2 transgenic loci” as a soybean “landing pad”/”safe harbor” (similar to the DFR loci in tomato) and a POSA would then reasonably expect (absent evidence to the contrary) that targeted manipulation at that loci (including the deletion of the entire “DAS81419-2 transgenic loci” with subsequent insertion of a transgene expression construct there—such as transgene swapping) would have the associated benefits from the loci being a “landing pad”/”safe harbor” (namely “minimal unintended side effects and [] consistent, reproducible transgene performance” as summarized by RUDGERS & SASTRY-DENT). And, in any event, a POSA would have been motivated to modify DANILO et al. for the purpose of arriving at the presently claimed subject matter because it would result in soybean starting materials (ready for transgene insertion by gene editing) that facilitate the benefits of more efficient, more durable, and cheaper generation of soybean transgenic “event” plants as compared to traditional (random insertion) transformation or biolistic methods.22 To be clear, and absent evidence to the contrary, BARD et al. evidence that it would have been obvious to a POSA to practice the methods of claims 25 and 26 for generating downstream inbred or hybrid plants at least because it is customary to do so for generating plant lines with stable genomes (inbreds) and/or for generating heartier plants with improved, combined genomes (hybrids). And, again, this would be understood as involving plant cells, plant parts (seeds), and plants that comprise the “landing pad”/”safe harbor” loci [relevant to claims 22-29].
Please note that while the claims previously recited a change to the 5’ junction and Applicant has clarified that SEQ ID NO: 2 comprises a change to the 3’ junction, this does not materially change the analysis of record at least because the cited references already teach targeting the 3’ junction (e.g., DANILO et al. at the last full paragraph on page 5 discussing targeting the 3’ end of the DFR gene for deletion of 1,013 base pairs there and De FRAMOND et al. at Example 8 at ¶141 on page 41 to ¶143 on page 42 and Example 9 at ¶145 on page 43 who teach targeting the 3’ junction sequence).
Response to Applicant’s Remarks:
As noted hereinabove, there are no new amendments or remarks filed with Applicant’s RCE (please note that the 20January2026 RCE, document code “RCEX”, references the 22December2025 filing as the requisite “submission”) and the amendment filed after-final 22December2025 was already entered and substantively considered (see the Advisory Action dated 08January2026). For the sake of a clear record, the content of the Advisory Action dated 08January2026 is restated here to the extent it is relevant to this rejection. For further clarity of the record, please note that the Final Action dated 20October2025 included a Request for Information (under 37 CFR § 1.105) which supplemented the of record requests by the Office for Applicant to please provide functional information about the claimed subject matter (see, e.g., one such request at the top of page 13 in the nonfinal action dated 21April2025).
↓ Copied from the Advisory Action dated 08January2025 ↓
The Office thanks Applicant for their response to the Request for Information (which was included within the Final action dated 20October2025, hereinafter "105 response"). Throughout the 105 response, Applicant states that information regarding a phenotype/functional impact imparted by the claimed modified locus (SEQ ID NO: 2) is either not known or not readily available. Further, the only disclosed utility by Applicant for the claimed modified locus (SEQ ID NO: 2) is that the claimed sequence(s) may be used as a marker to, for example, identify a plant/plant part comprising the claimed locus such as in marker-assisted breeding (see part V of the 105 response at page 6). In Applicant's comments regarding part xii (see page 8 of the 105 response), Applicant confirms the Office's belief that the location and length of the 7-nucleotide-deletion (which distinguishes the claimed SEQ ID NO: 2 from the prior art DAS81419-2 loci sequence SEQ ID NO: 1) is due to the inherent nature and function of an FnCpf1/Cas12a (i.e., it is an artifact of having applied FnCpf1/Cas12a to the DAS81419-2 loci). Therefore, while the 105 response and accompanying Remarks are informative, they are insufficient to overcome the obviousness rejection of record. To be clear, the information provided by Applicant in their response dated 22December2025 is consistent with the basis upon which the obviousness rejection was maintained (see the Final action at page 5, line 18 to page 6, line 4). For the sake of completeness, please note that the use of loci-specific sequences for detecting plants/plant parts such as in marker-assisted breeding is taught by BARD et al. (Column 1, line 54 to Column 2, line 14; Column 3, lines 11-67; Column 4, lines 42-58; Column 6, line 57 to Column 7, line 29; Column 8, lines 37-54; including 3' junction sequences discussed at Column 13, lines 14-39).
II.) Claims 20, 22-29 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over BARD et al. (US Pat. No. 8680363 issued 25March2014 to DOW AGROSCIENCES LLC) and DE FRAMOND et al. (WO2010/077816 published 08July2010 to SYNGENTA PARTICIPATIONS AG).
With the amendment filed 21August2025, claims 25-26 were amended to refer to a particular guide RNA (SEQ ID NO: 4), the use of which is understood to result in the modified DNA molecule set forth in SEQ ID NO: 2 (recited in claim 20). Because it is unclear if one must use the recited guide RNA sequence SEQ ID NO: 4 to perform the methods of claims 25-26 and because, in any event, use thereof would direct the nuclease to the target site needed for generating the modified sequence SEQ ID NO: 2; and because the sequence SEQ ID NO: 2 would have been obvious to a person with ordinary skill in the art at the time this application was filed (a “POSA”) for the reasons stated of record, there is no change to the obviousness rejection(s) as set forth in the nonfinal Action dated 21April2025 or as set forth in the Final action dated 20October2025.
To be clear, in the nonfinal action dated 21April2025 and then again via a Request for Information (under 37 CFR § 1.105) with the Final action dated 20October2025, the Office asked Applicant to please identify any functional effect that the 7-nucleotide deletion of SEQ ID NO: 2 has (as compared to the known DAS81419-2 loci sequence SEQ ID NO: 1) (see the nonfinal 21April2025 at the top of page 13)—Applicant has not done so in their reply filed 21August2025 or After-final reply filed 22December2025 nor otherwise explained how the claimed structures would have been unexpected. Such information remains material to overcoming this rejection because, without it, the sequence SEQ ID NO: 2 represents an obvious minor/de minimus structural change (a 7-nucleotide deletion) without a corresponding new or unexpected functional effect as compared to the known DAS81419-2 loci and it remains the Office’s belief that this 7-nucleotide deletion is simply the result of having a CRISPR/Cas approach to the DAS81419-2 loci such as an InDel caused by non-homologous end joining (i.e., the 7-nucleotide deletion was an unintentional consequence by Applicant and simply an artifact of CRISPR/Cas). This would be disproven by more information from Applicant about the nature of the 7-nucleotide deletion. To that end, it is highly recommended that Applicant provide some statement regarding any function that the 7-nucleotide deletion has and/or any function that a transgenic soybean plant cell comprising a modified DAS81419-2 transgenic loci comprising SEQ ID NO: 2 has that a soybean plant cell comprising a DAS81419-2 loci (i.e., comprising SEQ ID NO: 1) does not have. Asked another way, how can the plants/plant cells of these claims be used in a manner that the known plant/plant part comprising a DAS81419-2 loci cannot?
These claims are now limited to making a particular deletion in the 3’ junction polynucleotide of the DAS81419-2 transgenic locus (specifically, that shown in SEQ ID NO: 2 which, as clarified by Applicant in the Remarks dated 20September2024 (pages 4-5), comprises a seven nucleotide deletion in the 3’ junction sequence of the DAS81419-2 transgenic locus as compared to the original DAS81419-2 locus sequence SEQ ID NO: 1:
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[↓ Copied from Nonfinal 20June2024 EXCEPT THAT, in view of Applicant’s Remarks and Amendments 20September2024, (1) “DAS81419” is updated to “DAS81419-2”, (2) BARD et al. is assumed to teach SEQ ID NO: 1 rather than SEQ ID NO: 2 and (3) “5’ junction” is updated to “3’ junction” as appropriate ↓]
For clarity, “gene stacking” with a prior deletion step is the focus of this rejection (which is consistent with what has been said above in the previous obviousness rejection—this rejection doesn’t just focus on gene insertion for “gene stacking,” but rather gene insertion that is preceded by a deletion step).
BARD et al. identify the “event DAS81419-2 insertion site”, as well as that “in the vicinity of” the event, as a “landing pad”/”safe harbor” (there, referred to as a “target site”) into which one or more genes of interest (or regulatory elements) may be inserted; including, for example, first deleting polynucleotides within or near the event loci then inserting a new sequence at that location.23 A specific example given by BARD et al. is to replace a transgene (e.g., cry1F and/or cry1Ac) or selectable marker gene (there, for example, the PAT sequence) such as by performing a deletion step (of the marker sequence) and then an insertion step (to introduce a different polynucleotide sequence at the location where the marker sequence formerly was).24 BARD et al. evidence that “DAS81419-2” soybean plants may be used to produce inbred plants (e.g., using backcrossing) and/or hybrid plants and that sequences for the “DAS81419-2” loci can be used to confirm that the loci is maintained in downstream progeny25 [relevant to claims 25-26]. And while BARD et al. do suggest that modifications (deletions or insertions) may be made within the 5’ junction/flanking sequences of the “DAS81419-2” event loci;26 because that teaching is only inferred, BARD et al. is (conservatively) interpreted as not explicitly teaching or suggesting a deletion within the 5’ junction/flanking sequence of the “DAS81419-2” event loci (a deficiency which is compensated by the teachings of DE FRAMOND et al., discussed below). BARD et al. also teach soybean plants and plant parts (including seeds) comprising the transgenic “soybean event 9582.814.19.1” (representative seed for which was deposited with ATCC as PTA-12006) as well as the loci for the event itself (including sequences thereof such as 5’ junction/flanking sequences and 3’ junction sequences) [relevant to claims 20, 22-24].27 Absent evidence to the contrary, BARD et al.’s event “9582.814.19.1” language is interpreted as being synonymous with the “DAS81419-2 transgenic locus” language of these claims and, it follows that, BARD et al. is assumed to teach the sequences SEQ ID NOs: 19 and 1 of these claims [relevant to claims 20 and 21, 27]. BARD et al. obtained the sequence for “the event DAS81419-2 insert”/” DAS81419-2 transgenic locus” by isolating the DNA from “soybean tissue” (per the headers of Example 2, where “tissue” is believed to be leaf tissue based on the header at Example 6). Because “soybean tissue” (including soybean leaf tissue) is within the description of what constitutes a “biological sample”28 and “processed transgenic soybean plant product”29 of these claims; BARD et al. also teach the subject matter of claims 28 and 29.
DE FRAMOND et al. evidence that (albeit, in the context of maize plants) targeting the 5’ or 3’ junction/flanking sequence of a “landing pad”/”safe harbor” loci for, for example, “gene stacking” was known in the prior art.30
CONCLUSION: Based on what else was known in the prior art at the time this application was filed (discussed above), it is the Office’s position that a person with ordinary skill in the art (a “POSA”) would have found it obvious in view of BARD et al. and DE FRAMOND et al. to delete one or more polynucleotides within the 5’ or 3’ junction/flanking sequence of the “DAS81419-2” transgenic loci before further modifying the loci (such as, for example, by inserting a new transgene therein) and, thereby, arriving at the presently claimed subject matter and with a reasonable expectation of success because doing so would have amounted to no more than:
the “use of known technique (that taught by DE FRAMOND et al. including modification at the 5’ or 3’ junction/flanking sequence of the “landing pad”/”safe harbor”) to improve similar [methods] (polynucleotide replacement in the “DAS81419-2” event/loci as taught by BARD et al.) in the same way” (MPEP § 2143(I)(C));
and/or
“applying a known technique (that taught by DE FRAMOND et al. including modification at the 5’ or 3’ junction/flanking sequence of the “landing pad”/”safe harbor”) to a known [method] ready for improvement (polynucleotide replacement in the “DAS81419-2” event/loci as taught by BARD et al.) to yield predictable results” (i.e., the claimed subject matter) (MPEP § 2143(I)(D).
To be clear, and absent evidence to the contrary, BARD et al. and DE FRAMOND et al. evidence that choosing to place a deletion “in the 5’ junction polynucleotide” comprising SEQ ID N: 19 or in the 3’ junction polynucleotide of “the DAS81419 transgenic locus” comprising SEQ ID NO: 1 would have been “an obvious matter of design choice” (MPEP § 2144.04(VI)(C)). To be clear, and absent evidence to the contrary, BARD et al. evidence that it would have been obvious to a POSA to practice the methods of claims 25 and 26 for generating downstream inbred or hybrid plants at least because it is customary to do so for generating plant lines with stable genomes (inbreds) and/or for generating heartier plants with improved, combined genomes (hybrids).
The Office believes that a POSA would have been motivated to target the 5’ or 3’ junction/flanking sequence of the DAS81419-2 loci (taught by BARD et al.) at least in the context of complete loci replacement or replacement of transgenes (Cry1F and/or Cry1Ac) which are located upstream in the DAS81419-2 event loci: if a POSA wanted to remove all of the expressed sequences within the original DAS81419-2 loci (a design choice), it would make sense for them to target the 5’ or 3’ junction/flanking sequences in doing so (i.e., delete polynucleotides there).
[ Copied from the Final 19November2024 to Ensure a Clear Record → ]Please note that while the claims previously recited a change to the 5’ junction and Applicant now clarifies that SEQ ID NO: 2 comprises a change to the 3’ junction, this does not materially change the analysis of record at least because the cited references already teach targeting the 3’ junction (e.g., DANILO et al. at the last full paragraph on page 5 discussing targeting the 3’ end of the DFR gene for deletion of 1,013 base pairs there and De FRAMOND et al. at Example 8 at ¶141 on page 41 to ¶143 on page 42 and Example 9 at ¶145 on page 43 who teach targeting the 3’ junction sequence).
Response to Applicant’s Remarks:
Applicant’s Remarks filed 22December2025 were understood to be responsive to both obviousness rejections. To that end, please see the “Response to Applicant’s Remarks” section hereinabove.
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
1 See MARQUES et al. “Field evaluation of soybean transgenic event DAS-81419-2 expressing Cry1F and Cry1Ac proteins for the control of secondary lepidopteran pests in Brazil” 2017 Crop Protection 96:109-115.
2 See BARD et al. at FIG. 2.
3 See “gene stacking” as explained by RUDGERS&SASTRY-DENT at pages 6-8.
4 What is also referred to as gee “stacking” in the art.
5 DANILO et al. at page 2, first full paragraph on the page.
6 See the Abstract of DANILO et al. as well as the paragraph bridging pages 2-3 through the first paragraph on page 3.
7 See DANILO et al. at the last full paragraph on page 5.
8 See DANILO et al. at the Abstract, at page 3, and at Fig. 1(A) on page 6 (including legend); respectively.
9 DANILO et al. at Abstract.
10 RUDGERS&SASTRY-DENT at page 6.
11 RUDGERS&SASTRY-DENT at page 6.
12 RUDGERS&SASTRY-DENT at page 6.
13 RUDGERS&SASTRY-DENT at pages 6-8.
14 BARD et al. at Column 4, lines 11-41; Column 10, line 4-Column 11, line 2; Column 20, lines 4-22.
15 BARD et al. Column 10, lines 24-40; Column 20, lines 4-22.
16 BARD et al. at Column 3, lines 36-55; Column 7, lines 45-59; Column 8, lines 20-26; Column 21, lines 64-67 (backcrossing).
17 As evidenced by the fact that at Column 20, lines 15-22 BARD et al. specifically say that the resulting insert may comprise “all or a recognizable part of the flanking sequences” (thus, a part of the 5’ junction/flanking sequence is deleted).
18 BARD et al. at Column 4, lines 11-15 (plants and plant parts); Column 4 at line 60 to Column 5 line 6 (deposit); Column 2, lines 18-57; Column 3, lines 30-67 (sequences as well as detecting progeny with the event); Column 13, lines 17-30 (junction sequences); Examples 3-4 and 7 (especially Example 7 at Column 34, lines 1-17).
19 ¶21 bridging pages 5-6 of this application’s specification.
20 See the sentence bridging pages 48 and 49 of this application’s specification (namely, “(f) raw … biomass ….”).
21 DE FRAMOND et al. at Example 8 on pages 41-43, in particular Example 8 at ¶ 141 on page 41 to ¶143 on page 42 and Example 9 at ¶145 on page 43.
22 See MPEP § 2143(I)(G) (citing DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360 (Fed. Cir. 2006)) which explains that “[t]he motivation to combine may be implicit and may be found in the knowledge of one of ordinary skill in the art, or, in some cases, from the nature of the problem to be solved. … an implicit motivation to combine … exists when the ‘improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal—and even common-sensical—we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves. In such situations, the proper question is whether the ordinary artisan possesses knowledge and skills rendering him capable of combining the prior art references.").
23 BARD et al. at Column 4, lines 11-41; Column 10, line 4-Column 11, line 2; Column 20, lines 4-22.
24 BARD et al. Column 10, lines 24-40; Column 20, lines 4-22.
25 BARD et al. at Column 3, lines 36-55; Column 7, lines 45-59; Column 8, lines 20-26; Column 21, lines 64-67 (backcrossing).
26 As evidenced by the fact that at Column 20, lines 15-22 BARD et al. specifically say that the resulting insert may comprise “all or a recognizable part of the flanking sequences” (thus, a part of the 5’ junction/flanking sequence is deleted).
27 BARD et al. at Column 4, lines 11-15 (plants and plant parts); Column 4 at line 60 to Column 5 line 6 (deposit); Column 2, lines 18-57; Column 3, lines 30-67 (sequences as well as detecting progeny with the event); Column 13, lines 17-30 (junction sequences); Examples 3-4 and 7 (especially Example 7 at Column 34, lines 1-17).
28 ¶21 bridging pages 5-6 of this application’s specification.
29 See the sentence bridging pages 48 and 49 of this application’s specification (namely, “(f) raw … biomass ….”).
30 DE FRAMOND et al. at Example 8 on pages 41-43.
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