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 .
Application Status
The Amendments and Remarks filed 13 March 2026 in response to the Office Action 16 December 2026 are acknowledged and have been entered. Claim 1 is amended. Claims 2, 3, 10, and 21 are canceled. Claims 1, 4-9 and 11-20 are pending. Claims 5-9 and 11-20 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Furthermore, introducing a chimeric promoter into the cell is a non-elected species and is withdrawn from consideration. Claims 1 and 4 are pending and under examination on the merits.
Any objection or rejection not reiterated herein has been overcome by applicant’s amendments.
Priority
Applicants claim priority to 371 PCT EP2019/057543 filed 03/26/2019. Acknowledgment is made of applicant’s claim for priority based on applicationsEP18164080.6 filed 03/26/2018. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang et al. Plant Physiology, January 2017, Vol. 173, pp. 715-727) in view and Fauteux (Fauteux et al. BMC plant biology 9.1 (2009): 126), Hernandez (Hernandez-Garcia et al. Plant Science 217 (2014): 109-119) and von Arnim (Von Arnim et al. Plant Science 214 (2014): 1-12). This is a new rejection necessitated by applicant’s claim amendments.
Regarding claims 1 and 4, Zhang teaches a method of where a TATA-box (i.e., a promoter activating nucleic acid sequence (PANAS)) insertion in the IRT1 promoter in the genus Malus increases the expression of IRT1, which accounts for the increase in Fe uptake in various plant Malus species [abstract; pg. 716, col. 1, para 2; Fig. 4A, 6E]. Zhang teaches the introduction of plasmids (i.e., a nucleic acid construct or expression cassette) containing IRT promoters with 0, 1, 2, or 3 copies of the TATA-box into plant cells thereby teaching the introduction of a nucleic acid construct or expression cassette into plant cells, where the nucleic acid construct or expression cassette comprises a promoter activating nucleic acid sequence of ATTATAA into a promoter controlling the expression of a nucleic acid molecule of interest (abstract; pg. 719, col. 1, para 2-720; page 725, col. 2, para 4-6; Fig. 4-5; Supplemental Figure S1). Zhang teaches that the insertion is -363 to -357 bp from the ATG start site (i.e., more than 50 nucleotides upstream of the start codon) [pg. 716, col. 2, para 2]. Zhang teaches at least a 4-fold increase in the expression level of the nucleic acid molecule of interest in cells containing the nucleic acid construct or expression cassette [Fig. 4] (regarding claims 1 and 4). Zhang therefore teaches increasing expression of a plant gene through insertion of a TATA-containing promoter activating sequence into a recipient promoter.
Zhang is silent about the location of the promoter activating nucleic acid sequence in relation to the TSS and a uORF and does not teach to introduce the promoter activating nucleic acid sequence into the recipient promoter at a position 50-500 nucleotides upstream of the TSS of the nucleic acid molecule of interest or where there is no upstream open reading frame (uORF) downstream of the insertion or introduction site. Zhang do not teach wherein the promoter activating nucleic acid sequence is identical to CTATAAATA.
Fauteux teaches the specific promoter motif CTATAAATA. Specifically, Table 1 identifies Fabaceae motif F3 as a TATA-box motif corresponding to CTATAAATA and identifies Poaceae motif P4 as a TATA-box motif corresponding to CTATAAATA. Fauteux further states that “the third motif discovered in Fabaceae (motif F3), and the fourth motif discovered in Poaceae SSP gene promoters (motif P4), are highly similar to a TATA-box motif (CTATAAATA) [pg. 3, last paragraph]” Fauteux additionally teaches that the motif functions as a promoter cis-regulatory element in plant promoters [pg. 2, col. 2].
Kumari teaches that distribution of known core promoter elements (CPEs) motifs, including a TATA box, with respect to transcription start site (TSS) exhibited positional conservation within monocots and dicots with slight differences across eight plant genomes [abstract]. Kumari teaches that the TATA box was conserved across all genomes and could be found up to 70 base pairs upstream from the TSS [pg. 5, col. 2, para 2; Fig. 4].
Hernandez-Garcia teaches that promoters comprise core, proximal, and distal promoter regions containing cis-acting regulatory elements that regulate transcription [pg. 110, col.1, para 2-3]. Hernandez-Garcia teaches that cis-acting elements located upstream of the transcription start site regulate gene expression and that promoter activity depends upon the type, number, position, and combination of regulatory elements present in promoter regions [pg. 110, col.1, para 2-3]. Hernandez-Garcia further teaches that distal promoter elements positioned substantial distances from the transcription start site can regulate transcription [pg. 110, col. 2, para 1]. Thus, Hernandez-Garcia teaches placement and engineering of regulatory elements throughout upstream promoter regions, including promoter regions extending well beyond the core promoter.
von Arnim teaches that upstream open reading frames (uORFs) are located within 5′ untranslated regions and that when translation initiates at a uORF, the efficiency of translation of the downstream major coding region is typically reduced. von Arnim further teaches that uORFs commonly function as regulatory elements affecting expression of the downstream coding sequence [abstract; pg. 10, col. 1; see section 1.3]. Accordingly, von Arnim teaches that the presence of a downstream uORF is generally detrimental to efficient expression of a downstream coding sequence.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to employ the known plant TATA-box motif CTATAAATA taught by Fauteux in the promoter modification approach of Zhang because Zhang teaches that insertion of TATA-containing promoter elements increases expression of a plant gene, Kumari teaches that TATA motifs are recognized plant promoter activation elements involved in transcription initiation, and Fauteux teaches CTATAAATA as a known plant TATA-box promoter motif. One of ordinary skill in the art would have reasonably expected that substitution of one known plant TATA-box motif for another known plant TATA-box motif in the promoter engineering approach of Zhang would predictably increase promoter activity and expression of the associated gene.
It would have further been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify to position the promoter activating sequence, or any fragment, region, or cis element thereof, within an upstream region as taught by Hernandez, ~50-70 nucleotides, upstream of the transcription start site, thereby generating a PANAS that is inserted 50-500 nucleotides upstream of the transcription start site of the nucleic acid molecule of interest and more than 50 nucleotides upstream of the start codon (as taught by Zhang). The art recognized that promoter regulatory activity is governed by the position and arrangement of cis-acting elements within promoter regions and that functional regulatory elements may be positioned throughout proximal and distal promoter regions upstream of the transcription start site. Furthermore, Kumari’s teaches that a plant promoter can contains a TATA box up to 70 base pairs upstream of the transcription start site. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since Zhang, Kumari, Fauteux and Hernandez each teach plant promoter sequences used in transgene expression.
It would have been further obvious to select an insertion site lacking an intervening downstream uORF because von Arnim teaches that uORFs reduce translation of the downstream coding sequence. A person of ordinary skill seeking the increased expression expressly taught by Zhang would have been motivated to avoid known sequence features that reduce downstream expression and therefore would have selected a promoter context lacking an intervening downstream uORF.
Response to Arguments
Applicant's arguments (see pages 8-10), filed 03/13/2026, with respect to the rejection(s) of claims 1-4 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn in view of the applicant’s arguments and amendment to the claims to require that the PANAS is identical to any one of the sequences of SEQ ID NOs: 2 to 8, 10, or 12 to 30, GTATAAAAG (E59), CTATAAATA (E59a), CTATATATA (E59b), CTATAAAAA (E59c) and CTATATAAA (E59d)”. However, upon further consideration, a new ground of rejection is made in view of Kumari, Fauteux, Hernandez, and von Arnim as discussed above.
Applicant argues that the cited references fail to teach or suggest the presently claimed promoter activating nucleic acid sequences. This argument is moot in view of the new rejection set forth above.
Applicant argues that Kumari does not disclose any preference for positioning a TATA box within the claimed range because Figure 4 identifies a peak ranging from -60 to -20 relative to the TSS. This argument is not persuasive. Claim 1 requires insertion of the promoter activating nucleic acid sequence at a location 50 to 500 nucleotides upstream of the transcription start site. Kumari expressly teaches that the TATA-box distribution exhibits a sharp peak ranging from -60 to -20 relative to the TSS, and in certain species from -70 to -20 relative to the TSS. Accordingly, Kumari teaches positions at -50, -55, -60, and -70 nucleotides upstream of the TSS, which fall within or overlap the presently claimed upstream region. The fact that Kumari also discloses positions outside the claimed range does not negate its teaching of positions that fall within the claimed range.
Further, obviousness does not require that the prior art teach only the claimed values or that every disclosed embodiment fall within the claimed range. It is sufficient that the prior art teaches or suggests values overlapping the claimed range and would have reasonably suggested the claimed positioning to one of ordinary skill in the art.
Applicant further argues that TATA-containing promoters represent only a subset of plant promoters. However, obviousness does not require that an element be present in a majority of naturally occurring promoters. Zhang expressly teaches that insertion of a TATA-containing sequence into a promoter increases expression, while Fauteux teaches CTATAAATA as a recognized plant TATA-box motif. The cited art therefore provides both the claimed promoter motif and a reason to employ it to increase gene expression.
Applicant’s arguments have been fully considered but are not persuasive because the cited prior art teaches the claimed promoter activation motif CTATAAATA and provides a reason to employ that motif in promoter engineering to increase expression of a plant gene.
Conclusion
No claims allowed.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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