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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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Action dated 08January2026 is restated here if relevant (e.g., restating that certain objections or rejections are withdrawn via the filing 22December2025).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 1-21 and 23 were previously canceled. Claims 22, 24-31 are pending and are examined on the merits herein. Claims 22, 27-28 are currently amended. Claims 24-26, and 29-31 were previously presented.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [10 US provisionals including 63059860 filed 31July2020]; 35 U.S.C. 365(c) [PCT/US2021/043483 filed 28July2021]; and 35 U.S.C. 120 [CON of 18058081, now US Pat. No. 11773397] is acknowledged. Claims 22, 24-31 are supported by at least US provisional application 63059860 and, therefore, MAINTAIN an effective filing date of 31July2020.
Claim Interpretations
The following claim interpretations have been made by the Examiner and relied upon for examination:
[Copied from the Final Action 19November2024 & Nonfinal Action 20June2024 →] “DAS59122-7” maize plants and the “DAS59122-7” transgenic loci (see claims 22, 28) are well-known in the field. In particular, while the specification describes “DAS59122-7” with respect to issued patents and representative deposited seed (see screenshot below, from page 7 ¶27 of the specification); please note that “DAS59122-7” maize plants are known commercially under the trade name HERCULEX® and publicly available by the DOW AGROSCIENCES family of companies.1
PNG
media_image1.png
179
524
media_image1.png
Greyscale
Regarding the subject matter of claims 29-31, 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 22, 24-26. 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 29 (which, if present, suggests that the commercialized maize plant/product comprises or originated from the subject matter of this application’s claims 22, 24, 25, or 26. Such uses are encompassed by the description of “detection/detecting” throughout ¶9 on page 3 of the specification; ¶60 on page 15 of the specification; and ¶62 on page 17 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 27 is withdrawn in view of the amendment to the claim (adding “maize” as requested by the Office);
and
RE ¶ 6: The rejection of claims 27-28 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 22 (and, therefore, claims 24-31 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 ↓
Please note that the amendments to claim 22 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 5' junction sequence SEQ ID NO: 19. Based on sequence alignment of SEQ ID Nos: 1, 2, and 19; the sequence SEQ ID NO: 2 only has a PARTIAL deletion of the sequences SEQ ID NO: 19. 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: 19. The following amendment would remedy this issue: "... comprises a deletion of part [[or all]] of the 5' junction polynucleotide sequence ... and wherein the deletion [[of the 5' 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 22, 24-31 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 12September2023); 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 12September2023); D’HALLUIN (US PAT No. 10538774 issued 21January2020 to BASF AGRICULTURAL SOLUTIONS SEED, US LLC); BING et al. (US Pat No. 7956246 published 07June2011 to PIONEER HI-BRED INTERNATIONAL, INC.; of record IDS 12September2023); and SASTRY-DENT et al. (US Pat. No. 10093940 issued 09October2018 to DOW AGROSCIENCES LLC).
With the amendment filed 21August2025, claims 27-28 are 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 22). Because it is unclear if one must use the recited guide RNA sequence SEQ ID NO: 4 to perform the methods of claims 27-28 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 DAS59122-7 loci sequence SEQ ID NO: 1) (see the nonfinal 21April2025 at the top of page 14)—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 DAS59122-7 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 DAS59122-7 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 maize plant cell comprising a modified DAS59122-7 transgenic loci comprising SEQ ID NO: 2 has that a maize plant cell comprising a DAS59122-7 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 DAS59122-7 loci cannot?
These claims are now limited to making a particular deletion in the 5’ junction polynucleotide of the DAS59122-7 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 5’ junction sequence of the DAS59122-7 transgenic locus as compared to the original DAS59122-7 locus sequence SEQ ID NO: 1:
PNG
media_image2.png
227
694
media_image2.png
Greyscale
;
The “DAS59122-7” transgenic locus as depicted at FIG. 1 of this application’s drawings is provided below for ease of review:
PNG
media_image3.png
223
713
media_image3.png
Greyscale
For clarity, simply deleting a part of the “DAS59122-7 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 “5’ junction polynucleotide” which, as is shown at FIG. 1, is far upstream of the phosphinothricin acetyltransferase (PAT) selective marker sequence that is within the “DAS59122-7 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 “DAS59122-7 transgenic loci” for a later insertion of at least one new transgene whilst maintaining the original genes encoded by the “DAS59122-7 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 subsequent insertion (and expression) of a transgene via gene editing technology (therein using CRISPR/Cas technology):7
PNG
media_image4.png
538
878
media_image4.png
Greyscale
PNG
media_image5.png
362
870
media_image5.png
Greyscale
PNG
media_image6.png
517
943
media_image6.png
Greyscale
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”,8 DANILO et al. do not specifically teach this technique within a maize plant or plant part (and, therefore, do not teach the maize plants being “DAS59122-7 maize” plants and, therefore, also do not teach the “landing pad”/”safe harbor” being the “DAS59122-7 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”.9 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.”10 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”.11 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).12
PNG
media_image7.png
395
785
media_image7.png
Greyscale
D’HALLUIN suggest targeting the flanking/junction polynucleotides (5’ or 3’) of the maize “DAS51922-7” elite event (referred to as a “preselected site” or “predefined site”, see Table 1 therein) with nucleases to modify polynucleotides in or around the elite loci to cause, for example, gene deletion (e.g., deletion of selectable markers), gene or regulatory element replacement, gene insertion (= “gene stacking”), etc.13 D’HALLUIN specifically emphasize that polynucleotides in and around known elite loci (including 5’ flanking/junction polynucleotides) are chosen (called “existing elite event(s)” therein) for efficiency.14 For clarity and consistency, it is the Office’s position that D’HALLUIN identify the “DAS51922-7 transgenic loci” as a “landing pad”/”safe harbor”. D’HALLUIN also suggest that inbred (plants obtained by selfing) of hybrid plants may be obtained that comprise the modification within the “preselected/predefined site” [relevant to claims 27-28].15 Claims 1, 17, 19 and Table 1 of D’HALLUIN provide:
PNG
media_image8.png
452
524
media_image8.png
Greyscale
PNG
media_image9.png
73
515
media_image9.png
Greyscale
PNG
media_image10.png
49
528
media_image10.png
Greyscale
PNG
media_image11.png
172
700
media_image11.png
Greyscale
BING et al. teach sequences of “the DAS59122-7 event”, including sequences for the plasmid insert and 5’ and 3’ flanking sequences of the insertion site.16 Absent evidence to the contrary, BING et al.’s “DAS51922-7 event” language is interpreted as being synonymous with the “DAS51922-7 transgenic locus” language of these claims and, it follows that, BING et al. is assumed to teach the sequence SEQ ID NO: 1 of these claims. BING et al. obtained the sequence for “the DAS51922-7 transgenic locus” by isolating the DNA from a maize leaf sample.17 Because leaf tissue is within the description of what constitutes a “biological sample”18 and “processed transgenic maize plant product”19 of these claims; BING et al. is also relevant to the subject matter of claims 30 and 31.
SASTRY-DENT et al. is cited because it evidences (like DANILO et al.), that it was previously appreciated that polynucleotides at the “landing pad”/”safe harbor” loci can be deleted/excised before introducing a new transgene of interest into the “landing pad”/”safe harbor” (notably, SASTRY-DENT et al. is specifically talking about maize “landing pads”/”safe harbors” here)20:
PNG
media_image12.png
184
339
media_image12.png
Greyscale
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 “DAS51922-7 transgenic locus” information taught by D’HALLUIN and BING 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 (maize DAS51922-7 transgenic plants and its DAS51922-7 loci via D’HALLUIN and BING 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 DAS51922-7 loci in DAS51922-7 maize via D’HALLUIN and BING 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] (DAS51922-7 maize via D’HALLUIN and BING 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 (DAS51922-7 maize and its DAS51922-7 transgenic loci via D’HALLUIN and BING 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, D’HALLUIN, BING et al., and SASTRY-DENT et al. evidence that choosing to place a deletion “in the 5’ junction polynucleotide” comprising SEQ ID N: 19 of “the DAS51922-7 transgenic locus” comprising SEQ ID NO: 2 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 22, 24-26 and 29-31 at least because D’HALLUIN identify the “DAS51922-7 transgenic loci” as a maize “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 “DAS51922-7 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 maize starting materials (ready for transgene insertion by gene editing) that facilitate the benefits of more efficient, more durable, and cheaper generation of maize transgenic “event” plants as compared to traditional (random insertion) transformation or biolistic methods.21 To be clear, and absent evidence to the contrary, D’HALLUIN evidence that it would have been obvious to a POSA to practice the methods of claims 27 and 28 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).22 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, 24-26].
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 DAS59122-7 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 DAS59122-7 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 20 to page 6, line 6). 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 BING et al. (see Column 1, lines 20-30; Column 2, lines 13-40; Column 4, lines 9-18; Column 5, lines 29-51).
II.) Claims 22, 24-31 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over D’HALLUIN (US PAT No. 10538774 issued 21January2020 to BASF AGRICULTURAL SOLUTIONS SEED, US LLC); BING et al. (US Pat No. 7956246 published 07June2011 to PIONEER HI-BRED INTERNATIONAL, INC.; of record IDS 12September2023); and SASTRY-DENT et al. (US Pat. No. 10093940 issued 09October2018 to DOW AGROSCIENCES LLC).
With the amendment filed 21August2025, claims 27-28 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 22). Because it is unclear if one must use the recited guide RNA sequence SEQ ID NO: 4 to perform the methods of claims 27-28 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 DAS59122-7 loci sequence SEQ ID NO: 1) (see the nonfinal 21April2025 at the top of page 14)—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 DAS59122-7 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 DAS59122-7 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 maize plant cell comprising a modified DAS59122-7 transgenic loci comprising SEQ ID NO: 2 has that a maize plant cell comprising a DAS59122-7 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 DAS59122-7 loci cannot?
These claims are now limited to making a particular deletion in the 5’ junction polynucleotide of the DAS59122-7 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 5’ junction sequence of the DAS59122-7 transgenic locus as compared to the original DAS59122-7 locus sequence SEQ ID NO: 1:
PNG
media_image2.png
227
694
media_image2.png
Greyscale
;
The “DAS59122-7” transgenic locus as depicted at FIG. 1 of this application’s drawings is provided below for ease of review:
PNG
media_image3.png
223
713
media_image3.png
Greyscale
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).
D’HALLUIN suggest targeting the flanking/junction polynucleotides (5’ or 3’) of the maize “DAS51922-7” elite event (referred to as a “preselected site” or “predefined site”, see Table 1 therein) with nucleases to modify polynucleotides in or around the elite loci to cause, for example, gene deletion (e.g., deletion of selectable markers), gene or regulatory element replacement, gene insertion (= “gene stacking”), etc.23 D’HALLUIN specifically emphasize that polynucleotides in and around known elite loci (including 5’ flanking/junction polynucleotides) are chosen (called “existing elite event(s)” therein) for efficiency.24 For clarity and consistency, it is the Office’s position that D’HALLUIN identify the “DAS51922-7 transgenic loci” as a “landing pad”/”safe harbor”. D’HALLUIN specifically suggest and demonstrate “gene stacking” (simply referred to as “stack(s)” or “gene stack” therein).25 D’HALLUIN also suggest that inbred (plants obtained by selfing) of hybrid plants may be obtained that comprise the modification within the “preselected/predefined site” [relevant to claims 27-28].26 Claims 1, 17, 19 and Table 1 of D’HALLUIN provide:
PNG
media_image8.png
452
524
media_image8.png
Greyscale
PNG
media_image9.png
73
515
media_image9.png
Greyscale
PNG
media_image10.png
49
528
media_image10.png
Greyscale
PNG
media_image11.png
172
700
media_image11.png
Greyscale
BING et al. teach sequences of “the DAS59122-7 event”, including sequences for the plasmid insert and 5’ and 3’ flanking sequences of the insertion site.27 Absent evidence to the contrary, BING et al.’s “DAS51922-7 event” language is interpreted as being synonymous with the “DAS51922-7 transgenic locus” language of these claims and, it follows that, BING et al. is assumed to teach the sequence SEQ ID NO: 1 of these claims. BING et al. obtained the sequence for “the DAS51922-7 transgenic locus” by isolating the DNA from a maize leaf sample.28 Because leaf tissue is within the description of what constitutes a “biological sample”29 and “processed transgenic maize plant product”30 of these claims; BING et al. is also relevant to the subject matter of claims 30 and 31.
SASTRY-DENT et al. supplement D’HALLUIN by specifically evidencing that the prior art appreciated that polynucleotides at the “landing pad”/”safe harbor” loci can be deleted/excised before introducing a new transgene of interest into the “landing pad”/”safe harbor” (notably, SASTRY-DENT et al. is specifically talking about maize “landing pads”/”safe harbors” here)31:
PNG
media_image12.png
184
339
media_image12.png
Greyscale
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 “gene stack/-ing” teachings of D’HALLUIN by adding a deletion step before gene insertion at the “landing pad”/”safe harbor” “DAS51922-7 transgenic loci” (as evidenced by SASTRY-DENT 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:
the “simple substitution of one known element (the “landing pad”/”safe harbor” “DAS51922-7 transgenic loci” taught by D’HALLUIN and BING et al.) for another (the “highly desirable location for inserting polynucleotide donor sequences” discussed by SASTY-DENT et al. at Column 36, lines 3-13.) to obtain predictable results (i.e., the claimed subject matter) (MPEP § 2143(I)(B));
the “use of known technique (that taught by SASTY-DENT et al. whereby gene insertion is preceded by a deletion of one or more polynucleotides at the “landing pad”/”safe harbor”) to improve similar [methods] (“gene stacking” at the “DAS51922-7 transgenic loci” as taught by D’HALLUIN and BING et al.) in the same way” (MPEP § 2143(I)(C));
and/or
“applying a known technique (that of SASTY-DENT et al. including a deletion step before a gene insertion step) to a known [method] ready for improvement (the “gene stacking” at the “DAS51922-7 transgenic loci” as taught by D’HALLUIN and BING 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, D’HALLUIN, BING et al., and SASTRY-DENT et al. evidence that choosing to place a deletion “in the 5’ junction polynucleotide” comprising SEQ ID N: 19 of “the DAS51922-7 transgenic locus” comprising SEQ ID NO: 2 would have been “an obvious matter of design choice” (MPEP § 2144.04(VI)(C)). To be clear, and absent evidence to the contrary, D’HALLUIN evidence that it would have been obvious to a POSA to practice the methods of claims 27 and 28 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 modify D’HALLUIN for the purpose of arriving at the subject matter of these claims at least because adding a precedent deletion step (to remove one or more polynucleotides in the “DAS51922-7 transgenic loci” including at the 5’ junction polynucleotide sequence) would be understood as useful to, for example, make room for a large new transgene expression construct and/or to swap out regulatory sequences (e.g., if the ones present within the existing “DAS51922-7 transgenic loci” are not desirable for whatever transgene is being inserted and/or not desirable for whatever downstream manipulation is planned such as if a cut site is within the original loci that a POSA would like to remove and, thereby, prevent certain cleavages).
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad ABRAHAM can be reached on (571) 270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/REBECCA STEPHENS/Examiner, Art Unit 1663
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
1 See US Environmental Protection Agency letter 25September2015 regarding the Protection Label for HERCULEX®/DAS-59122-7 corn (5 total pages); available at https://www3.epa.gov/pesticides/chem_search/ppls/068467-00005-20150928.pdf.
2 BING et al. (US Pat. No. 7956246) 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 Abstract, at page 3, and at Fig. 1(A) on page 6 (including legend); respectively.
8 DANILO et al. at Abstract.
9 RUDGERS&SASTRY-DENT at page 6.
10 RUDGERS&SASTRY-DENT at page 6.
11 RUDGERS&SASTRY-DENT at page 6.
12 RUDGERS&SASTRY-DENT at pages 6-8.
13 See D’HALLUIN at Column 12, line 9-Column 20, line 60 (including Table 1); Column 21, lines 9-16; Column 25, line 55-Column 27, line 25; issued claims 1, 17, and 19.
14 See D’HALLUIN at Column 3, lines 41-50; Column 9, lines 55-67; Column 12, line 9-Column 20, line 60 (including Table 1)
15 D’HALLUIN at Column 41, lines 2-38.
16 See Abstract; FIGs 1-3 as well as the description thereof at Column 8, line 54 to Column 7, line 16; Column 28, lines 4-20.
17 See BING et al. at Example 3 at Column 22, lines 60-63 and then sequences was as described at Example 4 (Columns 23-29).
18 ¶21 bridging pages 5-6 of this application’s specification.
19 See the sentence at ¶93 on page 49 of this application’s specification (namely, “(f) raw … biomass ….”).
20 Column 36, lines 3-13.
21 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.").
22 D’HALLUIN at Column 41, lines 2-38.
23 See D’HALLUIN at Column 12, line 9-Column 20, line 60 (including Table 1); Column 21, lines 9-16; Column 25, line 55-Column 27, line 25; issued claims 1, 17, and 19.
24 See D’HALLUIN at Column 3, lines 41-50; Column 9, lines 55-67; Column 12, line 9-Column 20, line 60 (including Table 1)
25 Column 3, lines 42-49; demonstrated at Examples 5-7.
26 D’HALLUIN at Column 41, lines 2-38.
27 See Abstract; FIGs 1-3 as well as the description thereof at Column 8, line 54 to Column 7, line 16; Column 28, lines 4-20.
28 See BING et al. at Example 3 at Column 22, lines 60-63 and then sequences was as described at Example 4 (Columns 23-29).
29 ¶21 bridging pages 5-6 of this application’s specification.
30 See the sentence at ¶93 on page 49 of this application’s specification (namely, “(f) raw … biomass ….”).
31 Column 36, lines 3-13.
Prosecution Insights