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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07January2026 has been entered.
Election/Restrictions
[Updated to Reflect Claims as Filed 05May2026 →] Applicant’s election without traverse of Group II (claims 10-19) in the reply filed on 22July2025 is acknowledged.
Claims 1-9, 20, 33 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group of invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 22July2025.
Applicant's election with traverse of (B) SEQ ID NO: 1, (C) SEQ ID NO: 88, (D) position -1, and (F) SEQ ID NO: 263 in the reply filed on 22July2025 is acknowledged. For clarity of the record, and as shown within the sequence alignment below, SEQ ID NOs: 94 and 112 comprise SEQ ID NOs: 1 and 88 (SEQ ID NO: 1 having a placeholder “r” seventh nucleotide being either “A” or “G”). SEQ ID NOs: 1, 88, 94, and 112 are examined together.
The requirement is still deemed proper and remains FINAL.
Status of the Claims
The amendments and arguments filed 05May2026 are acknowledged and have been fully considered. Claims 11-12, 15, 17-19, 21-29 were previously canceled and claims 13, 31-32, 34 are now canceled (= claims 11-13, 15, 17-19, 21-29, 31-32, 34 are canceled). Claims 1-10, 14, 16, 20, 30, 33 are pending. Claims 10, 20, 33 are currently amended. Claims 7, 30 was previously presented. Claims 1-6, 8-9, 14, 16 are original. Claims 1-9, 20, 33 remain withdrawn.
Claims 10, 14, 16, 30 are examined on the merits herein.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [US provisional 63209836 filed 11June2021] is acknowledged. Claims 10, 14, 16, 30 maintain an effective filing date of 11June2021.
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.
Claims 10, 14, 16, 30 are rejected under 35 U.S.C. 103 as being unpatentable over ZHANG et al. (“Genome editing of upstream open reading frames enables translational control in plants” 2018 Nature Biotechnology 36(9):894-898 (9 total pages)) as applied to claims 10, 14, and 16 above in view of JOSHI et al. (“Context sequences of translation initiation codon in plants” 1997 Plant Mol. Bio. 35:993-1001) in view of LUEHRSEN & WALBOT (“The impact of AUG start codon context on maize gene expression in vivo” 1994 Plant Cell Reports 13:454-458) as evidenced by HERNANDEZ et al. (“Conservation and Variability of the AUG Initiation Codon Context in Eukaryotes” 2019 Trends in Biochem. Sci. 44(12):1009-1021; of record PTO-892 05September20251) and GenBank FL331574.1 (entitled “1401568 CERES-197 Zea mays cDNA clone 294516 5’, mRNA sequence” dated 07March2011, 1 total page, available at https://www.ncbi.nlm.nih.gov/nuccore/FL331574.1/, last visited 21May2026).
Applicant has amended the claims 05May2026 to remove references to SEQ ID NOs: 1 and 88 so that the claims now require the Kozak sequence be either SEQ ID NO: 94 or 112. These sequences relate to one another in the following way (please note the placeholder “r” in SEQ ID NO: 1 and the start codon “ATG” is underlined throughout):
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The CERES-197 clone sequence published as GenBank FL331574.1 is added here as evidence that this new limitation (the Kozak sequence being either SEQ ID NO: 94 or 112) would have been obvious in view of the prior art.
↓ Rejection of Record Updated to reflect the Claims Filed 05May2026 ↓
As an initial matter, please note that the elected consensus sequence SEQ ID NO: 1 is a maize “strong” consensus sequence (referred to as “Strong-1”) with the seventh nucleotide “R” being either “A” or “G”.2 The elected edited sequence SEQ ID NO: 88 is a species of SEQ ID NO: 1 where “R” is “G” (there are no other differences between SEQ ID NOs: 1 and 88).3
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Claims 10 and 14 are generally directed toward using gene editing (e.g., CRISPR/Cas) to introduce any edit into the endogenous Kozak sequence of any nucleic acid molecule within a corn plant cell so that the resulting Kozak sequence is SEQ ID NO: 94 or 112. Please note the breadth of these claims: the claims do not state that a particular endogenous gene is being edited = there is no starting Kozak sequence which is being edited. All that is required in these claims is that the resulting, edited Kozak sequence be SEQ ID NO: 94 or 112. This means that, for SEQ ID NO: 112, any one or more of -11, -10, -9, -8, -7, -6, -5, -4, -3, -2, -1, +4, +5, +6, +7, +8, +9, +10, +11, and +12 positions within the Kozak sequence4(-1 position being the elected position) of any corn nucleic acid molecule may be edited to arrive at SEQ ID NO: 112. In the case of SEQ ID NO: 94, any one or more of -9, -8, -7, -6, -5, -4, -3, -2, -1, +4, +5, +6, +7, +8, +9, +10, +11, and +12 positions within the Kozak sequence of any corn nucleic acid molecule may be edited to arrive at SEQ ID NO: 94. Claim 16 specifies that an N-terminal residue of the encoded protein is modified (i.e., an edit after the start codon meaning a change at one or more of +4, +5, +6, +7, +8, +9, +10, +11, and +12 positions resulting in a change of the encoded amino acid). Claim 30 adds that, via the edited Kozak sequence, the protein accumulation is increased “by at least 1500%” (i.e., at least 20-fold) as compared to a control plant.
This rejection is based on the fact that these broad claims read on using known CRISPR/Cas technology to edit a Kozak sequence of any endogenous maize/corn nucleic acid molecule within a maize/corn plant cell to arrive at the known Kozak sequence of SEQ ID NO: 94 or 112.
ZHANG et al. is cited for teaching and suggesting the use of gene editing (CRISPR/Cas) to modify the Kozak sequence of a nucleic acid molecule within a plant cell (there, Arabidopsis). With respect to the elected -1 position and editing the N-terminal amino acid(s) of the encoded protein, ZHANG et al. teach “Del2” which is a 14 base pairs deletion including 7 base pairs within the open reading frame.5 [relevant to claims 10, 14, 16]
JOSHI et al. is cited because they discuss consensus plant Kozak sequences and teach a consensus Kozak sequence (“CON”) for monocotyledons such as maize/corn (see part D on page 996):
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Materially, the monocot consensus sequence by JOSHI et al. teaches or suggests SEQ ID NOs: 1 and 88 of these claims. Please note that JOSHI et al. cites LUEHRSEN & WALBOT6 (reference 16 therein) which regards a maize/corn Kozak consensus sequence consistent with that of JOSHI et al. (below being Figure 4 from LEUHRSEN & WALBOT7):
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Please note that both JOSHI et al. and LUEHRSEN & WALBOT teach “GCG” at +4-+6 (encoding an Alanine (A)).
The sequence published as GenBank FL331574.1 is cited to show that Applicant’s amendment to require SEQ ID NO: 94 or 112 is not sufficient to make the claims nonobvious. As is shown within the below screenshots, GenBank FL331574.1 is a sequence that comprises SEQ ID NOs: 1, 88, and 94 except for a guanine (g) at position -9 (in the below alignment8 and mark-up of the GenBank FL331574.1 sequence, the start codon is double-underlined and positions -9 to +12 are underlined for ease of review). In particular, GenBank FL331574.1 has a thymine (t) at position -9 (not a guanine (g) as is present within SEQ ID NOs: 1, 88, 94, and 112). Because JOSHI et al. already teaches SEQ ID NOs: 1 and 88, thereby teaching a guanine (g) at position -9, the sole nucleotide difference between GenBank FL331574.1 and SEQ ID NO: 94 appears to be an obvious change of GenBank FL331574.1 in view of JOSHI et al. (specifically, changing the -9 thymine (t) to a guanine (g) because a guanine (g) at position -9 is encouraged by JOSHI et al. and is, at the very least, considered immaterial “N” by LEUHRSEN & WALBOT).
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Absent evidence to the contrary, it is believed that a person with ordinary skill in the art at the time this application was filed (a “POSA”) would have found it obvious to edit a Kozak sequence such as at -9 to +12 of GenBank FL331574.1 using CRISPR/Cas (as taught or suggested by ZHANG et al.) so that the edited Kozak sequence comprises SEQ ID NO: 94 or 112 in view of the consensus maize Kozak sequence taught or suggested by JOSHI et al. and LUEHRSEN & WALBOT. Given the knowledge within the art regarding Kozak sequences, a POSA making one such edit would reasonably expect one of the three possible outcomes: no change to accumulation of the encoded protein, an increased accumulation of the encoded protein, or a decreased accumulation of the encoded protein. Therefore, an increase in protein accumulation would be one of three reasonably expected results. [claims 10, 14, 16] Given the knowledge within the art regarding Kozak sequences, a POSA would also reasonably expect that, if an increase in protein accumulation were achieved, it may be “by at least 1500%” (i.e., at least 20-fold) as compared to a control plant because, as evidenced by at least HERNANDEZ et al. (cited of record within the Written Description rejection), the art already knew that editing the Kozak sequence can impact protein accumulation by at least 20-fold9 [claim 30].
Especially for a commercially valuable encoded protein, one such POSA would have been motivated to edit its Kozak sequence because that may increase the accumulation (yield) of that protein. MPEP § 2143(E) (“Obvious to try”).
Response to Applicant’s Remarks:
(1) Applicant proactively asserts that the obviousness rejection of record does not address how the prior art teaches or suggests every element of the newly amended claims (namely, SEQ ID NO: 94 or 112). (Remarks at pages 6-7).
This is not persuasive in view of the rejection hereinabove.
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 10, 14, 16, 30 REMAIN rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims now require that the edited plant cell is a maize/corn plant cell, that protein accumulation is increased, and that the edited (resulting) Kozak sequence is either SEQ ID NO: 94 or 112 (the relationship to each other and to the elected sequences SEQ ID NO: 1 and 88 is shown below).
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Please note the breadth of these claims: the claims do not state that a particular endogenous gene is being edited = there is no starting Kozak sequence which is being edited. All that is required in these claims is that the resulting, edited Kozak sequence be SEQ ID NO: 94 or 112. This means that, for SEQ ID NO: 112, any one or more of -11, -10, -9, -8, -7, -6, -5, -4, -3, -2, -1, +4, +5, +6, +7, +8, +9, +10, +11, and +12 positions within the Kozak sequence10(-1 position being the elected position) of any corn nucleic acid molecule may be edited to arrive at SEQ ID NO: 112. In the case of SEQ ID NO: 94, any one or more of -9, -8, -7, -6, -5, -4, -3, -2, -1, +4, +5, +6, +7, +8, +9, +10, +11, and +12 positions within the Kozak sequence of any corn nucleic acid molecule may be edited to arrive at SEQ ID NO: 94.
The specification provides only one example of changing expression with the Kodak sequence SEQ ID NO: 112 and three examples using SEQ ID NO: 94. As emphasized of record, the identity of the genes which are edited and their encoded proteins is not given by the specification (they are referred to as “Protein of Interest (POI)”. As is also said of record, the specification shows that the identity of the gene/protein matters: the three examples given for SEQ ID NO: 94 (“POI1-10”, “POI2-9”, and “POI3-9”) show that protein accumulation may increase or decrease depending upon what the gene/protein actually is (SEQ ID NO: 94 is affiliated with an increase of 106%, an increase of 4%, and a decrease of 46%, respectively). This issue is amplified with respect to claim 30 (reciting an “at least 1500%” increase in protein accumulation) because the specification only provides one example of that level of protein accumulation increase being achieved (using SEQ ID NO: 94 as the Kozak sequence) but, there again, the specific gene/protein that was edited is not identified and it is clear from the three results using SEQ ID NO: 94 that the identity of the gene/protein is material.
Based on the information provided within the specification (e.g., the three results for SEQ ID NO: 94 as the Kozak sequence), a skilled artisan would understand that an increase in protein accumulation will only be achieved using a particular corn gene and, likewise, that an at least 1500% increase in protein accumulation will only be achieved using a particular corn gene. To that end, it remains the Office’s position that a skilled artisan would not reasonably recognize Applicant to be in possession of the full metes and bounds of these claims at the time this application was filed.
At least because the specification does not specifically identify the edited genes and the results in the specification (e.g., with using SEQ ID NO: 94 as the Kozak sequence) show that either an increase or a decrease in protein accumulation may be achieved therewith, the still Office cannot see a path toward patentability for these claims. There are no foreseeable claim amendments or arguments which may remedy this Written Description issue.
↓ From the “Response to Applicant’s Remarks” at Pages 12-13 of the Final Action 07January2026 ↓
For ease of review, the following is a screenshot of Table 6 from the specification (edited to only show “strong-1” edited Kozak sequences. Below that is Applicant’s summary of SEQ ID NOs: 1, 8, 94, and 112 (Remarks at part IV on page 7). Applicant’s argument is not persuasive because neither the claim amendments nor the Remarks remedy the structure-specific-nature of the results at Tables 6 and 7 of the specification. As said of record, and as shown within the screenshot of Table 6 below, whether or not protein accumulation increases or decreases with a particular Kozak edit depends upon what gene is being edited and the particular structure of the expression construct. Note the positive and negative percentage changes at the far right column below.
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Response to Applicant’s Remarks:
Applicant argues that because the specification shows an actual reduction-to-practice of at least one embodiment within the claims, the specification shows possession across the entirety of the claims. (Remarks at page 10).
This is not persuasive in view of the three examples in the specification using SEQ ID NO: 94 as a Kozak sequence: the “POI3-9” data show that protein accumulation may be decreased using SEQ ID NO: 94 as the Kozak sequence = protein accumulation is not reliably increased as suggested by Applicant across all corn genes/proteins as is being claimed. There is reason to believe that protein accumulation for “POI1” and “POI2” may be increased using SEQ ID NO: 94, but those genes/proteins are not identified in the specification, so it would amount to New Matter to recite them in the claims at this time. For at least these reasons, the Office has no suggestions for how to remedy this Written Description issue (= no suggestions for how to put these claims in condition for allowance).
Conclusion
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 For clarity of the record, HERNANDEZ et al. was and is cited within the Written Description rejection.
2 Specification at ¶245 on page 47, Table 1 on page 48; see also ¶272 on page 60.
3 Specification at Table 5 on page 61.
4 “Kozak sequence” being the nucleotides around the translation initiation site, i.e., upstream and downstream of the ATG/AUG start codon.
5 ZHANG et al. at Figure 1 on page 895.
6 JOSHI et al. at the left column on page 999.
7 LUEHRSEN & WALBOT at Fig. 4 on page 457.
8 See Result 1 of the ABSS sequence search results file entitled “20260514_124359_us-17-836-783a-94.rst” dated 14May2026.
9 HERNANDEZ et al. at page 1010 (the second to the last paragraph on the page).
10 “Kozak sequence” being the nucleotides around the translation initiation site, i.e., upstream and downstream of the ATG/AUG start codon.
Prosecution Insights