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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6May2026 has been entered.
Election/Restrictions History and Sequences in Claims
Copied From Election/Restriction section of Nonfinal 23September2025:
“Applicant’s election without traverse of (A) SEQ ID NOs: 72 and 74 for the structure of the endogenous FEA2 gene or protein, (B) the region being SEQ ID NO: 111, (C) a negative to positive substitution at position E447 of SEQ ID NO: 74 (which is within the region SEQ ID NO: 111) and the specific mutant species being E447K with corresponding sequences SEQ ID NOs: 157 and 158 in the reply filed on 29July2025 is acknowledged.
Because Applicant elects a substitution mutation at E447 (specifically, the mutation E447K) which is the sole mutation within “Allele F” of Table 1 of the specification at page 96 (corresponding to the nucleic acid sequence SEQ ID NO: 130 and the amino acid sequence SEQ ID NO: 131), and because Alleles B, C, D, G, K, N, P, R, S, and V (of Table 1 of the specification at pages 95-97) also all comprise the E447K substitution in combination with other mutations (corresponding to nucleic acid sequences SEQ ID NOs: 122, 124, 126, 132, 140, 144, 148, 151, 153, 157 and amino acid sequences SEQ ID NOs: 123, 125, 127, 133, 141, 145, 149, 152, 154, 158), ALL of Alleles B, C, D, F, G, K, N, P, R, S, and V (corresponding to nucleic acid sequences SEQ ID NOs: 122, 124, 126, 130, 132, 140, 144, 148, 151, 153, 157 and amino acid sequences SEQ ID NOs: 123, 125, 127, 131, 133, 141, 145, 149, 152, 154, 158) are being examined together herein.”
Regarding the nucleotide sequences recited in the second “wherein” clause of Claim 57:
These claims, such as claim 57, recite certain “region” nucleotide sequences (some of which encode the elected amino acid “region” sequence SEQ ID NO: 111). See the following paragraph of claim 57, for example:
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The Examiner has aligned those sequences to wild type FEA2 coding sequence SEQ ID NO: 73 as well as to the examined mutant fea2 sequences (see claim 14) that all comprise a mutation at the position corresponding to E447 of SEQ ID NO: 74. That alignment (multiple sequence alignment via ClustalOmega) is provided, in part, below (immaterial sequence has not been copied below to save space in this action). The underlined sequences of SEQ ID NO: 73 are nucleotides 1324-1389 which encode the elected SEQ ID NO: 111 amino acid “region” sequence (SEQ ID NO: 111 corresponds to amino acids 442-463 of wild type FEA2 amino acid sequence SEQ ID NO: 74). The elected codon for mutation (which encodes E447) is boxed (“gag”). As can be seen from the below alignment, SEQ ID NOs: 80, 88, 89, 93, 101, 102, 106, and 110 do not encode the elected “region” sequence SEQ ID NO: 111 (they do not comprise the nucleotides corresponding to 1324-1389 of SEQ ID NO: 73). Please note that SEQ ID NO: 110 does not even encode the elected position for mutation (a substitution at the codon encoding E447 of SEQ ID NO: 74).
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The Examiner has also aligned the spacer sequences recited in claim 74 (to be clear, the reverse complement of those sequences) to wild type FEA2 coding sequence SEQ ID NO: 73. That alignment (multiple sequence alignment via ClustalOmega) is provided, in part, below (immaterial sequence has not been copied below to save space in this action). The underlined sequences of SEQ ID NO: 73 are nucleotides 1324-1389 which encode the elected SEQ ID NO: 111 amino acid “region” sequence (SEQ ID NO: 111 corresponds to amino acids 442-463 of wild type FEA2 amino acid sequence SEQ ID NO: 74). The elected codon for mutation (which encodes E447) is boxed (“gag”). As can be seen from the below alignment, SEQ ID NOs: 114, 117, and 119 are not specific for the elected mutation position (i.e., they cannot direct position-specific gene editing to the elected “gag” codon encoding E447 of SEQ ID NO: 74). To be clear, all of spacer sequences SEQ ID NOs: 113-115 and 117-119 would directed a gene editing CRISPR-cas system to the nucleotides which encode elected “region” sequence SEQ ID NO: 111, but only some of those sequences (SEQ ID NOs: 113, 115, and 118) could result in a mutation at the codon encoding the elected position corresponding to E447 of SEQ ID NO: 74.
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Status of the Claims
The amendments and arguments filed 06May2026 are acknowledged and have been fully considered. Claims 2-3, 5-6, 9-11, 13, 15-56, 58-63, 66, 68-73, 75-83, 85-88, 91-100 were previously cancelled, claims 4, 84, 89 are newly cancelled. Claims 1, 7-8, 12, 14, 57, 64-65, 67, 74, 90, 101-102 are pending and examined on the merits herein. Claims 1, 14, 57, 67, 74, 90, 101-102 are currently amended. Claims 7-8, 12, 64-65 were previously presented.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [US provisional 63356524 filed 29June2022] is acknowledged. Claims 1, 7-8, 12, 14, 57, 64-65, 67, 74, 90, 101-102 maintain an effective filing date of29June2022.
Claim Interpretation(s)
As explained throughout the record (e.g., the anticipation and obviousness rejections at ¶6 on page 4 and ¶7 on page 8, respectively, of the final action dated 16January2026), “… claim 1 …, as well as claims that refer thereto, is/are interpreted as specifying that (1) that a mutation be introduced into a particular “region” (elected region being the sequence SEQ ID NO: 111).”
Withdrawn Objections and/or Rejections
Rejections made of record in the final office action dated 16January2026 that are not otherwise discussed herein are withdrawn. In particular:
RE ¶ 7: The obviousness rejection over PENNELL et al. and BOMMERT et al. is withdrawn in view of the claim amendments (e.g., claims 57, 90, 101 now saying that the mutation is in a sequence having at least 90% identity to SEQ ID NO: 111 and claim 74 now saying that the target site is the nucleotide sequence encoding SEQ ID NO: 111 “and/or” the gene editing system comprises a spacer specific for the nucleotide sequence encoding SEQ ID NO: 111); and
RE ¶ 9: The utility rejection of claims 74, 84, and 89 is withdrawn in view of the claim amendments (claims 84 and 89 are now cancelled and claim 74 is amended to be a “gene editing system”).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 74 REMAINS rejected under 35 U.S.C. 102(a)(1) as being anticipated by 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 28November2023).
Comment on Claims Filed 05May2026 and Summary of Issue: Claims 57, 67, 84, 89, 90, 101, and 102 as amended 05May2026 are removed from this rejection because 84 and 89 are canceled and claims 57, 90, and 101 now say that the mutation is in a sequence having at least 90% identity to SEQ ID NO: 111 (which is not believed to be taught by PENNELL et al.). Claim 74 remains rejected here because open-ended “comprising” language is being used to defined the target site. While the sequences recited in claim 74 all appear to be those which were not taught by PENNELL et al. (or mutated by BOMMERT et al., for that matter), claim 74 still says that the target site may “comprise” any of those sequences meaning the entire fea2 sequence SEQ ID NO: 72 or 73 is still encompassed by the claim language. Please note that the “and/or” between the second and third paragraphs of the claim mean that the guide nucleic acid sequences are not mandatory (which, if mandatory, would inherently limit the scope of which sequences may be mutated by the CRISPR/Cas). Please also note that the specification does not provide a limiting definition by which “target site” may be reasonably interpreted as a subsequence of SEQ ID NO: 72 or 73. It would be remedial of this rejection to use closed “consisting of” language such as “… the target site [[comprises]]consists of the nucleotide sequence of any one of SEQ ID NOs: … or consists of a nucleotide sequence that encodes the amino acid sequence of SEQ ID NO: 111 ….”
Rejection →↓: This claim does not require either (1) that a mutation be introduced into a particular location such as by specifying what the target site is (e.g., the elected region sequence SEQ ID NO: 111) or (2) that a particular mutation be introduced (e.g., the elected E447K mutation).
Claim 74 is directed toward a CRISPR/Cas gene editing system comprising an effector protein and a guide nucleic acid that binds to a target site within a FEA2 gene. The claim then further defines either (via “and/or”) the target site or the guide nucleic acid. This rejection is based on the second paragraph of the claim which further defines the target site. There, claim 74 says that the target site comprises (a) “… the nucleotide sequence of any one of SEQ ID NOs: 78-80, 87-89, 92, 93, 100-102, 105, 106, or 110” or that the target site comprises (b) “… a nucleotide sequence that encodes the amino acid sequence SEQ ID NO: 111 ….” Both (a) and (b) read on a full length FEA2 gene sequence such as SEQ ID NO: 72 and 73 because both SEQ ID NOs: 72 and 73 comprise “the nucleotide sequence of any one of SEQ ID NOs: 78-80, 87-89, 92, 93, 100-102, 105, 106, or 110” and comprise “… a nucleotide sequence that encodes the amino acid sequence SEQ ID NO: 111 ….”
PENNELL et al. teach the FEA2 gene sequence SEQ ID NO: 36 which has 100% sequence identity to the FEA2 gene sequence SEQ ID NO: 73 of this application.1 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. 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.2 PENNELL et al. teach that the gRNA can include at least one spacer sequence (e.g., a “target spacer”).3 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: 364 and the plant cell is optionally a Zea mays (i.e., corn or maize) cell.5 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)6. 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. 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 sequence having at least 90% sequence identity to the sequence SEQ ID NO: 72 of this application, and at least one non-natural mutation is made within the endogenous gene following cleavage by the nuclease.
Response to Applicant’s Remarks 06May2026:
(1) Applicant traverses this rejection because they believe that the target site is limited to that consisting of any one of SEQ ID NOs: 78-80, 87-89, 92, 93, 100-102, 105, 106, or 110 (Remarks at the bridge of pages 7-8).
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The Office disagrees with this interpretation of the claim—please see the recommended amendments provided above.
Claim Rejections - 35 USC § 112 – Enablement
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 1, 7-8, 12, 14, 57, 64-65, 67, 74, 90, 101-102 REMAIN rejected, under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for subject matter that is taught or suggested by BOMMERT et al. (i.e., enabling for partial loss-of-function (weak allele) fea2 mutants such as a substitution mutation at Met367 of SEQ ID NO: 74), does not reasonably provide enablement for how to MAKE and/or USE a partial loss-of-function (weak allele) fea2 mutant comprising an E447K substitution mutation numbered according to SEQ ID NO: 74 (nor, it follows, a polypeptide encoded thereby, a guide nucleic acid or method for making the same, or a corn plant/part comprising the same). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to MAKE and/or USE the invention commensurate in scope with these claims.
Like the claims filed 05December2025, the claims filed 06May2026 do not contain amendments which address this rejection (Applicant only responds via Remarks). Therefore, the rejection below is materially copied from that within the Nonfinal 23September2025 but-for (1) updates to claim numbering, (2) minor amendments to reflect the content and format of this action (such as removing reference to an “Election/Restriction” section being herein), (3) an additional paragraph to point out the breadth of these claims and (4) edited summaries of the data from Tables 3 and 4 of the specification (the ones previously provided by the Office had irrelevant X-axis labels and misalignments, which are now corrected; the illustrations hereinbelow now also have lines at the wild type data to better illustrate that the KRNs of almost all experimental embodiments are encompassed by the KRN range of the wild type controls, showing that, per the specification, the claimed mutations do not have a material impact on at least KRN).
The factors used (and weighed) to determine whether a specification satisfies the enablement requirement (and, thus, whether any necessary experimentation would be ‘undue’) include, but are not limited to, the following: (A) the breadth of the claims; (B) the nature of the invention; (C) the state of the prior art; (D) the level of one of ordinary skill; (E) the level of predictability in the art (“if one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art” (MPEP § 2164.03); (F) the amount of direction provided by the specification; (G) the existence of working or prophetic examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the specification read in view of the prior art (including whether “one would expect to be able to extrapolate [the example(s)] across the entire scope of the claims” (MPEP § 2164.02(I); MPEP § 2164.01(a), citing In re Wands 858 F.2d 731 at 737; 8 USPQ2d 1400 at 1404 (Fed. Circ. 1988)).
Regarding (A) the breadth of the claims:
The claims rejected here include those that do recite a functional effect (claim 12—regarding a lack of enablement for how to make the claimed invention) as well as claims that do not recite a functional effect (claims 1, 7-8, 14, 57, 64-65, 67, 74, 90, 101, 102—regarding a lack of enablement for how to use the claimed invention).
In particular, these claims are rejected to the extent they require an fea2 mutant (weak, partial loss-of-function) allele characterized by having/encoding an E447K substitution (numbered according to SEQ ID NO: 74) (i.e., “Allele F” in Table 1 of the specification at page 96 corresponding to the nucleic acid sequence SEQ ID NO: 130 and the amino acid sequence SEQ ID NO: 131). As is noted hereinabove, Alleles B, C, D, G, K, N, P, R, S, and V (of Table 1 of the specification at pages 95-97) also all comprise the E447K substitution in combination with other mutations (corresponding to nucleic acid sequences SEQ ID NOs: 122, 124, 126, 132, 140, 144, 148, 151, 153, 157 and amino acid sequences SEQ ID NOs: 123, 125, 127, 133, 141, 145, 149, 152, 154, 158).
Please note that the claims (including those filed 06May2026) remain quite broad. Regarding the structures (mutations) being claimed: while the Office has been focused throughout examination on the elected subject matter, the claims are not actually limited to the elected subject matter. For example, claims 1 and 57 encompass any one or more mutations that cause a substitution mutation within the FEA2 “region” sequence SEQ ID NO: 111 (recall that SEQ ID NO: 111 is 22 amino acids long = encoded by 66 nucleotides). Note, for example, that these claims encompass introducing a stop codon within SEQ ID NO: 111. Given the discussions of record regarding null, loss-of-function fea2 mutations versus weak, partial loss-of-function fea2 mutations (see BOMMERT et al., TRUNG et al., and TAGUCHI-SHIOBARA et al.) 7 and that one nucleic acid change (or one amino acid change) is sufficient to cause either a null, loss-of-function fea2 mutation or a weak, partial loss-of-function fea2 mutation; the breadth of these claims remains highly material to this rejection. Regarding the phenotype changes being claimed (see claim 12): note that an increase in any yield characteristic is being claimed (the references to KRN and ear length in claim 12 are optional). “Yield” is described broadly in the specification (pages 15-16) as:
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Regarding (B) the nature of the invention, (F) the amount of direction provided by the specification; and (G) the existence of working or prophetic examples:
It is understood from the specification8 as well as the prior art9 that weak, partial loss-of-function alleles of FASCIATED EAR2 (“FEA2”, also known as the CLAVATA2 or “CLV2” corn ortholog) increase maize Kernel Row Number (via increased meristem size) without having a substantial negative impact on yield (usually measured by the fea2 mutant plant not having a substantial change in ear length as compared to control) whereas null, total loss-of-function fea2 alleles cause an increase in Kernel Row Number (via increased meristem size) but with negative impact on ear morphology (is disordered) and yield (usually via a substantial decrease in ear length as compared to control).
The elected fea2 substitution mutant under examination here is E447K (within Alleles B, C, D, F, G, K, N, P, R, S, and V of the specification)10.
The specification provides Tables 3 and 4 that summarize certain experiments using fea2 mutant Alleles B, C, D, F, G, K, N, P, R, S, and V.11 At Tables 3 and 4, Kernel Row Number (KRN) range information and KRN mean information is supposedly given (please note the objection to the specification of record regarding Allele D—because the Allele D data contained a sample size (n) of 1, there are no ranges provided and it is misleading to suggest there can be a “mean”/average value because calculating a mean requires a sample size of at least two). Table 3 (but not Table 4) also supposedly provides ear length range information and ear length mean information. In view of the specification and the prior art, it is understood that the KRN information and ear length information is given as a proxy for the mutant alleles being weak, partial loss-of-function mutations (i.e., if a mutant allele causes increased KRN without a substantial decrease in ear length; that is evidence that the mutant allele is a weak, partial loss-of-function allele).
The problem with the information in the specification (i.e., the information at Tables 3 and 4), and the reason that this rejection is being made, is that the information in Tables 3 and 4 appears to be incomplete: Applicant does not provide the raw data or any information as to medians, p-values, error ranges, or standard deviations; and the information at Tables 3 and 4 does not otherwise show that an E447K mutation has a substantial (i.e., statistically significant) positive impact on KRN (with no substantial decrease of ear length). One should note, for context, that the sample sizes at Tables 3 and 4 are so small (all much less than thirty) that mean/average values are not informative (a fact that is evidenced by comparing the supposed KRN values for Allele G (heterozygous) given at Table 3 (n=4, mean 16.9, range 16.3-17.7) to those at Table 4 (n=10, mean 17.6, range 16-19)—there is material variance between those values with nothing to suggest the variance is due to experimental conditions). Furthermore, and to that end, the raw data is not given so one cannot determine the medians of the data sets, P-values, error ranges, or standard deviations—any of which would be helpful in determining whether the E447K mutation actually has a material positive impact on KRN without a material negative impact on ear length. Without more information from Applicant, one is left with only the range information at Tables 3 and 4 for comparing the mutant Allele data to that of wild type control. When comparing the KRN range values at Tables 3 and 4, one can see that the mutant Alleles encoding an E447K mutation all cause KRN ranges that overlap with that of the wildtype/control—therefore, there is no indication within the specification that the claimed mutant fea2 alleles have a substantial positive impact on KRN (please see below, sample sizes given in parenthesis). As a reminder, the allele with only the E447K mutant is “Allele F”, all other alleles have the E447K mutation in combination with at least one other mutation.
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Regarding (C) the state of the prior art; (D) the level of one of ordinary skill; and (E) the level of predictability in the art:
As noted above, the prior art taught weak, partial loss-of-function fea2 mutants12 as well as null, total loss-of-function fea2 mutants13 and their impacts on corn KRN (e.g., via meristem size) as well as yield (e.g., via ear length). The prior art does not appear to have discussed a mutation at position E447 (numbered according to SEQ ID NO: 74), though, and in that regard cannot supplement the deficiencies of this specification. To be clear, the Office believes that which residue positions within the FEA2 sequence (i.e., SEQ ID NO: 74) may be mutated to generate a weak, partial loss-of-function mutant (which is different in kind to a null, total loss-of-function mutation) would have been, and remains, unpredictable (i.e., achieving a weak allele mutation result at one location of the amino acid sequence is not informative for what will happen when mutating a different location of the amino acid sequence). Due to this unpredictability, it is important for the data within this specification to clearly show a substantial positive impact on KRN (without a substantial negative impact on ear length) sufficient to evidence that the claimed fea2 mutant alleles (comprising or encoding an E447K mutation) are weak, partial loss-of-function fea2 alleles.
Regarding (H) the quantity of experimentation needed to make or use the invention based on the content of the specification read in view of the prior art:
Without more information from Applicant, the current specification shows that the claimed E447K mutation does not have a substantial positive impact on KRN without a substantial negative impact on ear length and, therefore, the specification shows that the claimed E447K mutation is not a weak, partial loss-of-function fea2 mutant. Therefore, it is not currently believed that any amount of trial and error experimentation by a skilled artisan would facilitate them making and using the full scope of the invention being claimed. This also means that, without more information from Applicant, a skilled artisan would not (and cannot) make a corn plant/part with “increased KRN, optionally wherein ear length is not substantially reduced” via the claimed (elected) fea2 mutant and would not recognize a specific and substantial use for the claimed nucleic acids, polypeptides, or plants/parts comprising the claimed (elected) fea2 mutant because, based on the current specification, that fea2 mutant does not have an at least substantial positive impact on KRN.
As this is an enablement rejection (as opposed to, for example, a Written Description rejection), Applicant is highly encouraged to submit a complete data set that supplements Tables 3 and 4 (including medians, p-values, error ranges, and/or standard deviations) via declaration practice that shows a substantial positive impact on KRN (with no substantial negative impact on ear length) when a corn plant/part comprises the E447K fea2 mutant. As Applicant no doubt knows, the declaration should be accompanied by an explanation (remarks) as to how and why the data shows a substantial positive impact on KRN (with no substantial negative impact on ear length). As stated above, it is understood that KRN and ear length values are being used as a proxy for whether or not the fea2 mutant allele is a weak, partial loss-of-function allele.
The breadth of these claims (including those dated 06May2026) remains highly material to this rejection. For example, even if the KRN data within the specification was accepted as sufficient to show that an E447K mutation causes an increased KRN, that data could not be reasonably extrapolated out to the full breadth of mutations or phenotype changes (see claim 12) being claimed in view of the prior art (see BOMMERT et al., TRUNG et al., and TAGUCHI-SHIOBARA et al.) and the resultant unpredictability around which changes/mutations (i.e., the specific location of the change and the nature of the change) will cause a null, loss-of-function fea2 mutation, a weak, partial loss-of-function fea2 mutation, or have no functional impact at all.
Response to Applicant’s Remarks 06May2026:
(1) Because the Office says that the teachings of BOMMERT et al. would be enabling, Applicant asserts that it is unclear “what undue experimentation would allegedly be needed to carry out and use the subject matter as claimed.” (Remarks at page 12):
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BOMMERT et al. did the work to not only (1) make certain fea2 mutants, but also (2) test them for impact on at least Kernel Row Number (KRN) (see Abstract thereof on page 334) (3) using statistical analysis, (4) confirm which mutations have a material impact on at least KRN (note page 338 thereof which summarizes statistical analysis). BOMMERT et al. had positive results, meaning some of the fea2 mutants that BOMMERT et al. tested actually have a material impact on at least KRN (as compared to a control). Points (3) and (4) are the differences between BOMMERT et al. and the present application: the Office maintains that (3) the specification does not provide sufficient statistical analysis (hence, the Office’s continued efforts to provide its own analysis of the data from Tables 3 and 4 of the specification and the Office’s continued request for declaration evidence) and, based on the information/data currently of record, (4) plants comprising the elected E447K mutation do not have a material impact on at least KRN. To be clear, and absent additional data and analysis from Applicant, it remains the Office’s position that a plant comprising the elected E447K fea2 mutation does not have an increased KRN as compared to a control plant (see Tables 3 and 4 in the specification as well as the Office’s summary thereof captured hereinabove and copied below for ease of review). As stated of record, allele “F” is the fea2 mutant consisting of only the E447K substitution (all other alleles comprise E447K and at least one additional substitution mutation, see Table 2 of the specification). Please also note that, with respect to claim 12 and “… wherein ear length is not substantially reduced”, Table 3 provides some ear length information (Table 4 does not) meaning we do not have information for all E447K alleles on both KRN and ear length. Further, as emphasized of record, the specification does not provide the raw data for Tables 3 or 4 or otherwise provide information about deviation, error, p-values, statistical significance, medians, quartiles, or similar benchmarks for showing statistically significant change. For example, mean/average KRN values are given at Tables 3 and 4, but mean/average values, alone, are meaningless because they are sensitive to outliers. The lack of information in this application means that neither the Office nor the public can tell whether, for example, the 18.7 maximum KRN value reported for allele “F” is greater, by a statistically significant degree, than the 17.7 maximum KRN value reported for wild type plants. This remains the problem (4) underlying this enablement rejection because, when looking at Tables 3 and 4 (including as summarized by the Office below), the KRN values for E447K mutants shows that plants comprising E447K do not have an increased KRN as compared to control plants (note the minimum and maximum KRNs for experimental/E447K mutant alleles being within the minimum and maximum KRN values for wild type plants—note also that while only “F(het)” and “G(het)” allele KRNs were tested twice (i.e., are reported in both Tables 3 and 4), the KRN values of wild type, “F(het)”, and “G(het)” plants differs between Table 3 versus Table 4 showing that there is variation in the data and also showing that the variation is material to whether or not (4) a particular fea2 mutation may be said to materially change KRN. Note that per Table 3, without more information, one may argue that the “F” allele consisting of only the E447K mutation has an increased KRN (18.7) compared to wild type plants (17.7) but per Table 4 and without more information, this is not the case: Table 4 may be interpreted as showing that the “F” allele caused no increase in KRN (18) as compared to control (20). The results for “G(het)” likewise raise unanswered questions around KRN: at both Tables 3 and 4, the “G(het)” allele (comprising the E447K, V457I, and D458N mutations) is shown to have no material change to KRN as compared to control plants (note that the “G(het)” minimum and maximum KRN is within the range of the wild type plant). This fact raises questions about E447K being necessary and sufficient for a material change to KRN because even if the “F(het)” allele data is accepted as showing that a plant consisting of only an E447K fea2 mutation causes an increase in KRN, then the “G(het)” allele data is showing that the E447K mutation cannot be combined with V457I and D458N substitutions or else KRN is not increased (i.e., a plant must consist of only the E447K mutation to increase KRN). This is material in view of the breadth of these claims—these claims remain open-ended (“comprising”) and encompass a variety of substitution mutations (e.g., “F(het)” and “G(het)”, amongst other, mutant alleles are both within the claims).
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In summary, the difference between BOMMERT et al. being enabling for particular fea2 mutants and this specification is point (4): this specification does not show positive results with the elected E447K mutation (plants comprising the elected E447K mutation do not have a material impact on at least KRN). BOMMERT et al. do provide positive results and show that specific fea2 mutants have a material impact on KRN (conclusions which are supported by statistical analysis). With respect to enablement, this means that the claims are directed toward plants, or methods of making plants, comprising E447K and their appears to be no specific and substantial use for such plants (i.e., “how to use” enablement issue). The claims (e.g., claim 12) are otherwise directed toward plants comprising E447K and that have an “increased yield” compared to a control plant, but the specification appears to show that, in fact, that is not possible (plants comprising the E447K fea2 mutation will not have an “increased yield”, i.e., “how to make” enablement issue). To be clear, claims that do not recite a phenotype/function (e.g., claim 1) have a “how to use” enablement issue whereas claims that do recite a phenotype/function (e.g., claim 12) have a “how to make” enablement issue.
(2) Applicant again asserts that there is no requirement for Applicant to provide raw data or even a working example (page 12). Applicant also continues to argue that, in any event, Tables 3 and 4 show that a plant with an FEA2 comprising “one or more amino acid substitutions in … SEQ ID NO: 111 can provide an overall positive contribution to yield” (page 12):
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These arguments remain unpersuasive because Applicant’s assertion (i.e., that the full scope of these claims and/or that the elected E447K mutation are enabled by the specification) is not supported by evidence in the prior art or the specification itself. The prior art shows that whether or not an fea2 mutation may increase corn yield is not predictable and this specification (as discussed above) does not even show that the elected E447K mutation increases corn yield (specifically, KRN and more specifically, KRN without a substantial reduction in ear length). The conclusion of nonenablement remains based on the evidence as a whole (including the prior art and Tables 3-4 in the specification), as is required by the MPEP (see MPEP § 2164.01(a)).
(3) Applicant asserts that it is conclusory to say that “whether or not a particular fea2 mutation will impact yield (particularly KRN) is unpredictable” (Remarks at page 13). Applicant further asserts that there is no “explanation or support” for asserting that it would be unpredictable that a mutation within SEQ ID NO: 111 of FEA2 will impact yield (particularly KRN) (page 13):
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This is not persuasive. As Applicant will note, this rejection has and continues to say that the Office’s conclusion of unpredictability is based on the teachings by the prior art which show disparate yield results using disparate FEA2 mutants. There remains no clear structure::function relationship by which one may reasonably predict which mutations will be weak, partial-loss-of-function mutations and, thereby, positively impact yield (particularly KRN). This is also true of the “region” sequence SEQ ID NO: 111: there is no known structure::function relationship by which one may reasonably predict which mutations in SEQ ID NO: 111 will be weak, partial-loss-of-function mutations and, thereby, positively impact yield (particularly KRN). There is no evidence to suggest that the impact of a mutation within the region SEQ ID NO: 111 will be more predictable than the impact of a mutation elsewhere in the FEA2 sequence. If Applicant has a reason to suggest that SEQ ID NO: 111 is unique, please submit evidence to that effect. Lastly, Applicant should be careful with arguments regarding predictability (here, that a mutation in SEQ ID NO: 111 would predictably cause an increase in KRN as compared to control plants) because Applicant is arguing the opposite in copending, related applications (that it would be unpredictable whether mutations, such as at position 477, would increase KRN) (see copending application 18645465 and the declaration filed 18May2026, for example). Applicant will want to keep nuanced differences clear in the respective records (e.g., that the location within the FEA2 sequence being mutated matters and that predictability is tethered to the location being mutated).
(4) Applicant continues to argue that the Office is imposing an unduly high standard for enablement and that “it is inappropriate for the Office to require additional data” (pages 13-14). Applicant also characterizes the information provided at Tables 3 and 4 of the specification (pages 13-14):
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These arguments remain unpersuasive. It remains the Office’s position that the enablement laws and rules as set forth in the MPEP are being applied and this numerous citations to evidence are made throughout the rejection to justify the conclusion of nonenablement (both prior art citations and Tables 2-4 of the specification). The underlined text within Applicant’s Remarks (screenshot above) is material and requires a response. In particular, the underlined text may illustrate the disagreement between the Applicant’s and Office’s position: the Office is of the position (for reasons discussed above with respect to argument (1) and the Tables 3-4) that the underlined statements are not true. It remains the Office’s position that, even if the sample sizes were of sufficient size, no, the “mean”/average values in Tables 3-4 do not show that plants comprising E447K have an increased KRN compared to control plants because a mean/average value without additional information (such as deviation or medians) is not useful for comparison between data sets and determining whether a material change/difference exists.
To explain by example, Data set A (68, 69, 70, 71, 72) has a mean of 70, median of 70 and standard deviation of 1.58 ; Data set B (55, 62, 70, 78, 85) has a mean of 70, median of 70 and standard deviation of 11.70 = Data sets A and B have the same mean but a lower standard deviation means that the values in Data set A all stay closer to the mean/average (= a value, such as a KRN measurement, needs to be less different than 70 to be significantly different from the mean of Data set A)—the larger standard deviation of Data set B means that a value, such as a KRN measurement, needs to be more different than 70 to be significantly different from the mean of Data set B). As a specific example, let’s say the value is a KRN change of 4, meaning a value of 74: 74 in the context of Data set A would be more than two standard deviations away from the mean of Data set A and would, therefore, be considered a statistically significant change (p<0.05) as compared to Data set A mean 70. A KRN change of 4, meaning a value of 74 in the context of Data set B would not be more than two standard deviations away from the mean of Data set B and would, therefore, not be considered a statistically significant change as compared to the Data set B mean 70. i.e., just having the mean of “70” is meaningless for determining significant differences (more information, such as the standard deviation, is required).
The Data sets A and B example herein is provided to illustrate why the present record is deficient and simply stating mean values (without more information such as standard deviation) is insufficient to support Applicant’s claim that the E447K mutation causes a material change (increase) to KRN. All information taken together, no, Applicant has not shown that the KRN for plants comprising the elected E447K mutation is higher than that of wild type plants (and, further that such plants have an increased KRN “without a substantial reduction in ear length”). In summary, Applicant’s assertion that the means in Tables 3 and 4 show a material difference in at least KRN remains unpersuasive because more information is needed to show that a material difference was, in fact, achieved. For clarity of the record, Table 4 does not even provide ear length information and the information at Table 3 is flawed for the same reasons as the information regarding KRN (Table 3 only provides ranges for ear length and means/averages without additional information such as standard deviation which is required to understand whether E447K has a material change to KRN “without a substantial” reduction in ear length).
(5) Applicant asserts that the Examiner should assume the specification is enabling “unless there is reason to doubt the objective truth of the statements contained therein which must be relied on for enabling support” (remarks at page 14):
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The Office agrees with the premise that the specification is assumed to be enabling, but the Office also maintains, for the reasons discussed voluminously hereinabove and of record, that there is sufficient evidence (both in the prior art and this specification) to show that the claims are not enabled. Applicant is also reminded of the breadth of claims here—the arguments around enablement have focused on the elected E447K mutation and the specific alleles comprising the E447K mutation, but the claims are not limited to the elected E447K mutation (note, for example, that claim 1 encompasses a substitution mutation that introduces a stop mutation into SEQ ID NO: 111). It is unreasonable to suggest that the information within the specification enables how to make and use a plant comprising the elected E447K mutation and especially unreasonable to suggest that the specification enables the full scope of these claims.
Conclusion
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/REBECCA STEPHENS/Examiner, Art Unit 1663
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
1 See the ABSS sequence search Result 3 in the sequence search file entitled “20250616_121124_us-18-342-761-73.rni”.
2 See, in particular, PENNELL et al. at ¶48 on page 7.
3 PENNELL et al. at ¶50 on pages 7-8.
4 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
5 PENNELL et al. at claims 3 and 20 on page 61; see also PENNELL et al. at Example 4 ¶101 on page 14.
6 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
7 See, e.g., TRUNG et al. (“A Weak Allele of FASCIATED EAR 2 (FEA2) Increases Maize Kernel Row Number (KRN) and Yield in Elite Maize Hybrids” 2020 Agronomy 10(1774): 17 total pages (doi:10.3390/agronomy10111774 of record IDS 28November2023); 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 28November2023); and TAGUCHI-SHIOBARA et al. (“The fasciated ear2 gene encodes a leucine-rich repeat receptor-like protein that regulates shoot meristem proliferation in maize” 2001 Genes&Development 15:2755-2766, of record IDS 28November2023).
8 See the various “aspects” of the invention described at pages 4-7.
9 See, e.g., TRUNG et al. (“A Weak Allele of FASCIATED EAR 2 (FEA2) Increases Maize Kernel Row Number (KRN) and Yield in Elite Maize Hybrids” 2020 Agronomy 10(1774): 17 total pages (doi:10.3390/agronomy10111774 of record IDS 28November2023); 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 28November2023); and TAGUCHI-SHIOBARA et al. (“The fasciated ear2 gene encodes a leucine-rich repeat receptor-like protein that regulates shoot meristem proliferation in maize” 2001 Genes&Development 15:2755-2766, of record IDS 28November2023).
10 See Table 2 of the specification at pages 95-97.
11 See pages 98-99 of the specification.
12 See TRUNG et al. (“A Weak Allele of FASCIATED EAR 2 (FEA2) Increases Maize Kernel Row Number (KRN) and Yield in Elite Maize Hybrids” 2020 Agronomy 10(1774): 17 total pages (doi:10.3390/agronomy10111774 of record IDS 28November2023); 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 28November2023).
13 TAGUCHI-SHIOBARA et al. (“The fasciated ear2 gene encodes a leucine-rich repeat receptor-like protein that regulates shoot meristem proliferation in maize” 2001 Genes&Development 15:2755-2766, of record IDS 28November2023).
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