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 (RCE) 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06October2025 has been entered.
Status of the Claims
No claim amendments were filed with the RCE on 06October2025, the RCE is only accompanied by two IDSes. Applicant asks that the previous After-Final amendment (filed 04September2025) be examined. The After-Final amendment filed 04September2025 was already entered and considered on the merits (please see the Advisory Action dated 24September2025). Therefore, this action is made Final (see corresponding form paragraph at the bottom of this action).
The claims filed 04September2025 are examined on the merits herein. Claims 1-4 are pending and currently amended.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [US provisional 63000206 filed 26March2020] and 35 U.S.C. 120 [continuation of 17212665, now US PAT NO. 11999946] is acknowledged. Claims 1-4 maintain an effective filing date of 26March2020.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3 and 4 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over BOMMERT et al. (“Quantitative variation in maize kernel row number is controlled by the FASCIATED EAR2 locus” 2013 Nature Genetics 45(3):334-338; of record IDS 25April2024).
[↓ Copied from the Nonfinal Action 16May2025 ↓ ]
For context, the mutant amino acid sequences SEQ ID NOs: 173-177 in these claims are characterized by a single amino acid substitution of the Proline (Pro, or “P”) residue located at position 477 of wild type sequence SEQ ID NO: 74 (see also allele numbers 3-7 at FIG. 3). The specific substitutions are P477F, P477S, P477T, P477V, and P477C (respectively). The amino acid sequences SEQ ID NOs: 173-177 are encoded by, respectively, the polynucleotide sequences SEQ ID NOs: 100-104.
BOMMERT et al. teach mutant corn comprising mutations within the FEA2 sequence, one being (what it calls) a “fea2-1328” mutant allele characterized by a C1430T nucleotide change resulting in a P477L amino acid change within the encoded FEA2 protein.1 BOMMERT et al. teach that the P477L mutation encoded by the fea2-1328 allele negatively affects FEA2 protein function2, presumptively, by altering the binding of FEA2 to ligand, by a change in receptor complex formation, and/or by the ability of the complex to signal3. BOMMERT et al. teach that mutant corn plants comprising the fea2-1328 allele (i.e., reduced FEA2 protein function) have an increased kernel row number (KRN) as compared to wild type plants4. BOMMERT et al. teach increased KRN is an important/desirable agronomic trait in grain crops (e.g., corn)5.
BOMMERT et al. do not teach a mutant FEA2 gene encoding a mutant FEA2 protein characterized by comprising a P477F, P477S, P477T, P477V, or P477C substitution.
At the time this application was filed, a person with ordinary skill in the art (a “POSA”) would have found it obvious in view of the teachings by BOMMERT et al. to try different amino acid substitution mutations at position P477 of the corn FEA2 protein because it would have been no more than the “simple substitution of one known element (leucine as taught by BOMMERT et al.) for another (any of the other 18 standard amino acids) to obtain predictable results (disrupted FEA2 function, as taught by BOMMERT et al., and increased KRN)” (MPEP § 2143(I)(B)) or the “use of a known technique (substitution mutation as taught by BOMMERT et al.) to improve similar products (corn FEA2) in the same way” (MPEP § 2143(I)(C)) or the “applying a known technique (substitution mutation of FEA2 per BOMMERT et al.) to a known product (corn FEA2) ready for improvement to yield predictable results” (MPEP § 2143(I)(D)) or, at the very least “obvious to try” (MPEP § 2143(I)(E)). This would be especially true of nonpolar amino acid substitutions (such as phenylalanine (F, i.e., P477F) and valine (V, i.e., P477V)) given the success BOMMERT et al. had by introducing the nonpolar amino acid leucine (L) into position P477 (i.e., P477L). A POSA would have been motivated to try other amino acid substitution mutations at position P477 because, as BOMMERT et al. show, a substitution mutation at position P477 can have the desirable effect of increasing KRN. A POSA would have had a reasonable expectation of successfully increasing KRN in view of the results achieved by BOMMERT et al. (this would have been especially true of P477F or P477V substitutions which, like the P477L substitution taught by BOMMERT et al., would be a substitution of proline with a nonpolar amino acid). Absent evidence to the contrary from Applicant, it is believed that a POSA would have arrived at the structure/sequence particulars of claims 3 and 4 by having modified BOMMERT et al. in this way (i.e., arrived at one or more of amino acid sequences SEQ ID NOs: 173-177 as well as the nucleic acid sequences SEQ ID NOs: 100-104 encoding them).
Response to Applicant’s Remarks 04September2025, Copied from Advisory Action 24September2025:
The claims are amended to remove the sequences corresponding to a P477F mutation (SEQ ID NOs: 173 and 100) and a P477V mutation (SEQ ID Nos: 176, 103). As discussed of record, "F" and "V" are both nonpolar amino acids.
Applicant asserts that this amendment necessitates withdrawal of the obviousness rejection of record because it would not have been obvious to a POSA for the mutant amino acid to be something other than a nonpolar amino acid and/or one such POSA would not have had a reasonable expectation of successfully obtaining an increase in KRN with the mutant amino acid being something other than a nonpolar amino acid (Remarks dated 04September2025 at the bridge of pages 1-2).
To ensure a clear record, and as evidenced by BOMMERT et al., increasing KRN WITHOUT also having a negative impact on ear morphology and yield (e.g., ear length) via a FEA2 mutation requires the FEA2 mutant to be a weak, partial loss-of-function FEA2 mutant (null FEA2 mutants may have increased KRN but also negative ear morphology and/or yield per TAGUCHI-SHIOBARA et al.).
Applicant's argument is not persuasive because, as said of record, the obviousness rejection is with respect to ANY OF THE OTHER 19 AMINO ACIDS which may substituted in at position P477 and one of the applicable rationales for obviousness here is that it would have been obvious-to-try and of the other 19 standard amino acids at the position P477 in view of BOMMERT et al. Given the teachings of BOMMERT et al., the Office maintains that a POSA would have had a reasonable expectation of OTHER amino acids, substituted into position P477, ALSO causing a weak, partial loss-of-function FEA2 mutant. Regarding the state of the prior art and ease of assaying all standard amino acids at a particular location, please note the teachings of at least MASQUNA et al. who demonstrate the use of site saturation mutagenesis (and commercial kits therefor) to identify protein variants with a particular functional effect (there, gain-of-function mutants) whereby 39 amino acid locations were systematically mutated with every one of the other 19 standard amino acid residues to identify those substitution mutants that increase protein::protein interactions.
The obviousness rejection of record is maintained.
Claims 1 and 2 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over BOMMERT et al. (“Quantitative variation in maize kernel row number is controlled by the FASCIATED EAR2 locus” 2013 Nature Genetics 45(3):334-338; of record IDS 25April2024) and PENNELL et al. (US Pre-grant Pub. No. 2019/0032071 published 31January2019, now US Pat. No. 10,876,129 issued 29December2020, with an effectively filed date of 12February2016 via US provisional appl. No. 62/294,539; of record IDS 25April2024).
[↓ Copied from the Nonfinal Action 16May2025 ↓ ]
For context, please note that claim 1 recites that the FEA2 gene which is/was mutated is endogenous to the corn plant. For at least that reason, claim 1 was not included in the rejection above. Claim 2 is generally directed toward a method of mutating a corn plant’s/part’s endogenous FEA2 gene using a nuclease (e.g., CRISPR/Cas technology). For additional context, the mutant amino acid sequences SEQ ID NOs: 173-177 in these claims are characterized by a single amino acid substitution of the Proline (Pro, or “P”) residue located at position 477 of wild type sequence SEQ ID NO: 74 (see also allele numbers 3-7 at FIG. 3). The specific substitutions are P477F, P477S, P477T, P477V, and P477C (respectively). The amino acid sequences SEQ ID NOs: 173-177 are encoded by, respectively, the polynucleotide sequences SEQ ID NOs: 100-104.
The teachings by BOMMERT et al. are as stated above with respect to claims 3 and 4. The Office’s position as to why it would have been obvious to a POSA to modify the teachings of BOMMERT et al. with the motivation of, and reasonable expectation of, arriving at the mutant nucleic acid of claim 3 and mutant protein of claim 4 are as stated above.
BOMMERT et al. do not teach mutating an endogenous FEA2 gene within a corn plant/part or the use of a nuclease (e.g., CRISPR/Cas technology) therefor.
PENNELL et al. teach a plant cell into which a CRISPR/Cas gene editing system comprising a Cas gene and a guide nucleic acid (e.g., guide RNA or “gRNA”) has been introduced, wherein the Cas gene encodes an RNA-guided DNA endonuclease enzyme capable of introducing a sequence-specific double- or single-strand break at a target site within a gene and that uses the gRNA to recognize the target site.6 PENNELL et al. teach that the gRNA can include at least one spacer sequence (e.g., a “target spacer”).7 At the claims and Examples, PENNELL et al. teach gRNAs designed to mutate the genomic target, wherein the genomic target is the maize FACIATED EAR2 (FEA2) nucleotide sequence SEQ ID NO: 368 and the plant cell is optionally a Zea mays (i.e., corn or maize) cell.9 PRENNELL et al. teach wherein the cells comprise at least one non-natural mutation within the genomic target (e.g., the FEA2 sequence SEQ ID NO: 36)10.
The target sequence SEQ ID NO: 36 of PENNELL et al. comprises a sequence that has 100% sequence identity to the target gene sequences SEQ ID NOs: 7211 and 7312 and to the region sequences SEQ ID NOs: 7713 and 7814 of this application. Sequence SEQ ID NO: 36 of PENNELL et al. encodes an amino acid sequence with 100% sequence identity to the sequence SEQ ID NO: 74 of this application. So, PENNELL et al.‘s CRISPR/Cas editing system comprises a nucleic acid binding domain that binds to a target site in the endogenous (FEA2) target gene wherein the target site is within a region comprising a sequence having at least 90% sequence identity to the sequences SEQ ID NO: 77 or 78 of this application and/or the region encodes a sequence having at least 95% sequence identity to the sequences SEQ ID NO: 75 or 76 of this application. Further, PENNELL et al.’s CRISPR/Cas editing system comprises a nuclease, (as noted above) the nucleic acid binding domain binds to a target site in the endogenous (FEA2) target gene wherein the target site is within a region comprising a sequence having at least 90% sequence identity to the sequences SEQ ID NO: 77 or 78 of this application, and at least one non-natural mutation is made within the endogenous gene following cleavage by the nuclease.
Absent evidence to the contrary from Applicant, it would have been obvious to a person with ordinary skill in the art at the time this application was filed (a “POSA”) to utilize CRISPR/Cas technology (in view of PENNELL et al.) to modify an endogenous corn plant/part FEA2 gene in the manner taught by BOMMERT et al. (a substitution mutation at position P477 of sequence SEQ ID NO: 74) because it would have been no more than “combining prior art elements (CRISPR/Cas techniques per PENNELL et al. with the FEA2 mutation per BOMMERT et al.) according to known methods to yield predictable results (increased KRN)” (MPEP § 2143(I)(A)) or the “simple substitution of one known element (the TILLING technique used by BOMMERT et al.) for another (the CRISPR/Cas technique by PENNELL et al.) to obtain predictable results” (MPEP § 2143(I)(B)) or the “use of a known technique (CRISPR/Cas per PENNELL et al.) to improve similar methods/products (the TILLING methods and resulting fea2 mutants per BOMMERT et al.) in the same way (i.e., introduce a substitution mutation into the FEA2 coding sequence)” (MPEP § 2143(I)(C)) or “applying a known technique (CRISPR/Cas per PENNELL et al.) to a known method/product (mutation of FEA2 per BOMMERT et al.) ready for improvement to yield predictable results” (MPEP § 2143(I)(D)) or, at the very least “obvious to try” (MPEP § 2143(I)(E)). This would have been true for introducing any of the other 18 standard amino acids at position P477 and especially true of introducing an alternate nonpolar amino acid at position P477 (such as phenylalanine (F, i.e., P477F) and valine (V, i.e., P477V)) given the success BOMMERT et al. had by using the nonpolar amino acid leucine (L, i.e., P477L) for achieving an increased KRN. A POSA would have been motivated to use CRISPR/Cas technology to mutate FEA2 because doing so is/was taught by PENNELL et al. A POSA would have been motivated to modify BOMMERT et al. so as to arrive at a corn plant/part comprising a mutant FEA2 protein having one of the sequences SEQ ID NOs: 173-177 (as well as the nucleic acid sequence selected from SEQ ID NO: 100-104 encoding it) because BOMMERT et al. teach that a single amino acid substitution at position P477 (specifically, P477L) of the protein FEA2 will result in the beneficial agronomic trait of increased KRN. A POSA would have had a reasonable expectation of successfully increasing KRN in view of the results achieved by BOMMERT et al. (this would have been especially true of P477F or P477V substitutions which, like the P477L substitution taught by BOMMERT et al., would be a substitution of proline with an alternate nonpolar amino acid).
Response to Applicant’s Remarks 04September2025, Copied from Advisory Action 24September2025:
The claims are amended to remove the sequences corresponding to a P477F mutation (SEQ ID NOs: 173 and 100) and a P477V mutation (SEQ ID Nos: 176, 103). As discussed of record, "F" and "V" are both nonpolar amino acids.
Applicant asserts that this amendment necessitates withdrawal of the obviousness rejection of record because it would not have been obvious to a POSA for the mutant amino acid to be something other than a nonpolar amino acid and/or one such POSA would not have had a reasonable expectation of successfully obtaining an increase in KRN with the mutant amino acid being something other than a nonpolar amino acid (Remarks dated 04September2025 at the bridge of pages 1-2).
To ensure a clear record, and as evidenced by BOMMERT et al., increasing KRN WITHOUT also having a negative impact on ear morphology and yield (e.g., ear length) via a FEA2 mutation requires the FEA2 mutant to be a weak, partial loss-of-function FEA2 mutant (null FEA2 mutants may have increased KRN but also negative ear morphology and/or yield per TAGUCHI-SHIOBARA et al.).
Applicant's argument is not persuasive because, as said of record, the obviousness rejection is with respect to ANY OF THE OTHER 19 AMINO ACIDS which may substituted in at position P477 and one of the applicable rationales for obviousness here is that it would have been obvious-to-try and of the other 19 standard amino acids at the position P477 in view of BOMMERT et al. Given the teachings of BOMMERT et al., the Office maintains that a POSA would have had a reasonable expectation of OTHER amino acids, substituted into position P477, ALSO causing a weak, partial loss-of-function FEA2 mutant. Regarding the state of the prior art and ease of assaying all standard amino acids at a particular location, please note the teachings of at least MASQUNA et al. who demonstrate the use of site saturation mutagenesis (and commercial kits therefor) to identify protein variants with a particular functional effect (there, gain-of-function mutants) whereby 39 amino acid locations were systematically mutated with every one of the other 19 standard amino acid residues to identify those substitution mutants that increase protein::protein interactions.
The obviousness rejection of record is maintained.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad ABRAHAM can be reached at (571) 270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA STEPHENS/Examiner, Art Unit 1663
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
1 Table 1 of BOMMERT et al. at page 336.
2 Page 336, left column.
3 Page 336, left column.
4 See, e.g., BOMMERT et al. at page 335 (left and right columns).
5 Page 336, right column.
6 See, in particular, PENNELL et al. at ¶48 on page 7.
7 PENNELL et al. at ¶50 on pages 7-8.
8 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
9 PENNELL et al. at claims 3 and 20 on page 61; see also PENNELL et al. at Example 4 ¶101 on page 14.
10 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
11 In the file wrapper for parent application 17212665, see Result 1 of the 03August2022 sequence search results file entitled “20220802_154905_us-17-212-665-72.rni”.
12 In the file wrapper for parent application 17212665, see Result 1 of the 03August2022 sequence search results file entitled “20220802_154905_us-17-212-665-73.rni”.
13 In the file wrapper for parent application 17212665, see Result 2 of the 03August2022 sequence search results file entitled “20220802_154905_us-17-212-665-77.rni”
14 In the file wrapper for parent application 17212665, see Result 2 of the 03August2022 sequence search results file entitled “20220802_154905_us-17-212-665-78.rni”