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 .
Election/Restrictions
[Copied From 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. To that end, the restriction requirement between these alleles (and their corresponding sequences) is withdrawn and are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once a restriction requirement or species election is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim 4 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (“the region” having the sequence SEQ ID NO: 75-110), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 29July2025.
Response to Applicant’s Remarks:
Applicant asserts that claim 4 should not be withdrawn (Remarks 05December2025 at pages 8-10).
The sequence SEQ ID NO: 111 was elected by Applicant and claim 4 does not recite the sequence SEQ ID NO: 111. Therefore, claim 4 remains withdrawn. Relatedly, and further to the recommendations made throughout this action, Applicant should consider limiting these claims to the elected substitution mutation at position E447 (numbered with respect to SEQ ID NO: 74) and, in so doing, Applicant may find an appropriate amendment to claim 4 which would make claim 4 eligible for rejoinder.
Status of the Claims
The amendments and arguments filed 05December2025 are acknowledged and have been fully considered. Claims 2-3, 5-6, 9-10, 13, 15-56, 58-63, 68-73, 75-83, 85-88, 91-100 were previously cancelled, claims 11, 66 are newly cancelled. Claim 102 is newly presented. Claims 1, 4, 7-8, 11-12, 14, 57, 64-67, 74, 84, 89-90, 101-102 are pending. Claim 4 is withdrawn as being directed toward a non-elected region. Claims 1, 7-8, 11-12, 14, 57, 64-67, 74, 84, 89-90, 101-102 are examined on the merits herein. Claims 1, 8, 67, 84, 89 are currently amended. Claims 7, 12, 14, 57, 64-65, 74, 90, 101 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, 11-12, 14, 57, 64-67, 74, 84, 89-90, 101-102 maintain an effective filing date of29June2022.
Withdrawn Objections and/or Rejections
Objections and/or rejections made of record in the nonfinal office action dated 23September2025 that are not otherwise discussed herein are withdrawn. In particular:
RE ¶ 5: The objection to the specification is withdrawn in view of the amendments thereto filed 05December2025;
RE ¶ 6: The objection to claim 8 is withdrawn in view of the amendment to the claim;
RE ¶ 7: The indefiniteness rejection regarding language in claim 1 is withdrawn in view of the amendment to the claim;
and
RE ¶ 8: The indefiniteness rejection regarding language in claims 67, 84, and 89 is withdrawn in view of the amendments thereto.
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.
Claims 57, 67, 74, 84, 89, 90, 101 REMAIN rejected, and new claim 102 is 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).
Please note that new claim 102 corresponds to part (c) of claim 57 (there is an “or” between parts (c) and (d) of claim 57, likewise an “or” recited in claim 102). Therefore, claim 102 is rejected with claim 57.
The claims filed 05December2025 do not contain amendments which address this rejection (Applicant only responds via Remarks). Therefore, the rejection below is copied from the Nonfinal 23September2025 (but-for the additional reference to claim 102) and new content is found within the Response to Applicant’s Remarks section below.
↓ Copied from Nonfinal 23September2025 (but-for reference to 102) ↓
These claims do 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).
To be clear, claim 1 (not rejected here), 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).
Claims 57 and 102 are directed toward a method of making a corn plant/part comprising a mutated endogenous FEA2 gene using, for example, CRISPR/cas gene editing. Materially, claims 57 and 102 only require that the target site is within an endogenous FEA2 gene (the claim does not specify what the target site is). Claim 74 is similar to claim 57 in that the claimed “guide” nucleic acid need only be capable of binding to any target site within an FEA2 gene (wherein, as elected, the FEA2 gene encodes the amino acid sequence SEQ ID NO: 111). Claims 67, 84, and 89 supposedly recite mutant nucleic acid or polypeptide sequences, but as evidenced by the sequence search results of record,1 the recitation of “90% sequence identity” means that wild type sequences are encompassed. To that end, and further to the indefiniteness rejection herein above, it is not clear what “mutation(s)”, if any, are within or outside of these claims; therefore claims 67, 84, and 89 (as well as claims 90 and 101, which refer thereto) are included here.
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.2 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.3 PENNELL et al. teach that the gRNA can include at least one spacer sequence (e.g., a “target spacer”).4 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: 365 and the plant cell is optionally a Zea mays (i.e., corn or maize) cell.6 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)7. 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 in a sequence having at least 90% sequence identity to the sequences SEQ ID NOs: 130 or 157 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 sequence having at least 90% sequence identity to the sequences SEQ ID NOs: 72, 130, or 157 of this application, and at least one non-natural mutation is made within the endogenous gene following cleavage by the nuclease.
Claim 64 is not rejected here because it specifies that the substitution is to F, K, N, or I. Claim 66 is not rejected here because the inherent function recited by claim 66 is believed to flow from a weak, partial loss-of-function fea2 mutant allele and PENNELL et al. does not appear to teach a weak, partial loss-of-function fea2 mutant allele.
Response to Applicant’s Remarks 05December2025:
(1) Applicant traverses this rejection because, according to Applicant, the teachings of PENNELL et al. are “solely prophetic” (Remarks at pages 18-19).
This is not persuasive because even if the teachings by PENNELL et al. are prophetic, prophetic teachings may be anticipatory.
(2) Applicant traverses this rejection because, according to Applicant, PENNELL et al. do not teach or suggest how to improve a phenotype of a [corn] plant, particularly increasing yield (Remarks at page 19).
This is not persuasive because these claims do not require a particular phenotype.
Applicant should consider limiting these claims to the elected substitution mutation at position E447 (numbered with respect to SEQ ID NO: 74).
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 57, 64, 67, 74, 84, 89, 90, 101 REMAIN rejected, and new claim 102 is rejected, under 35 U.S.C. 103 as being unpatentable 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) as applied to claims 57, 67, 74, 84, 89, 90, 101, 102 as above and in view of 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).
Please note that new claim 102 corresponds to part (c) of claim 57 (there is an “or” between parts (c) and (d) of claim 57, likewise an “or” recited in claim 102). Therefore, claim 102 is rejected with claim 57.
The claims filed 05December2025 do not contain amendments which address this rejection (Applicant only responds via Remarks). Therefore, the rejection below is copied from the Nonfinal 23September2025 (but-for the additional reference to claim 102) and new content is found within the Response to Applicant’s Remarks section below. In addition, please note that at page 11 of the Nonfinal 23September2025, the Office stated that neither claims 1 or 67 (or claims referring thereto) were not being rejected here. That is true with respect to claim 1, but not with respect to claim 67. Claim 67 should not have been referenced there (which is corrected herein below).
↓ Copied from Nonfinal 23September2025 (but-for reference to 102 and removing 66) ↓
These claims do 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).
To be clear, claim 1 (not rejected here), 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).
Claims 57 and 102 are directed toward a method of making a corn plant/part comprising a mutated endogenous FEA2 gene using, for example, CRISPR/Cas gene editing. Materially, claims 57 and 102 only requires that the target site is within an endogenous FEA2 gene (the claim does not specify what the target site is). Claim 74 is similar to claim 57 in that the claimed “guide” nucleic acid need only be capable of binding to any target site within an FEA2 gene (wherein, as elected, the FEA2 gene encodes the amino acid sequence SEQ ID NO: 111). Claim 64 simply adds that the mutation (at any location in the FEA2 gene) is a substitution to F, K, N, or I. Claims 67, 84, and 89 supposedly recite mutant nucleic acid or polypeptide sequences, but as evidenced by the sequence search results of record,8 the recitation of “90% sequence identity” means that wild type sequences are encompassed. To that end, and further to the indefiniteness rejection herein above, it is not clear what “mutation(s)”, if any, are within or outside of these claims; therefore claims 67, 84, and 89 (as well as claims 90 and 101, which refer thereto) are included here.
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.9 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.10 PENNELL et al. teach that the gRNA can include at least one spacer sequence (e.g., a “target spacer”).11 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: 3612 and the plant cell is optionally a Zea mays (i.e., corn or maize) cell.13 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)14. 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 in a sequence having at least 90% sequence identity to the sequences SEQ ID NOs: 130 or 157 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 sequence having at least 90% sequence identity to the sequences SEQ ID NOs: 72, 130, or 157 of this application, and at least one non-natural mutation is made within the endogenous gene following cleavage by the nuclease.
PENNELL et al. does not appear to teach that the substitution is to F, K, N, or I (claim 64). PENNELL et al. does not appear to teach a weak, partial loss-of-function fea2 mutant allele (now cancelled claim 66).
BOMMERT et al. teach a corn plant/part comprising a weak, partial loss-of-function fea2 mutant allele referred to as “fea2-0881” having a G-to-A nucleotide change at position 1101 which causes a Met367Ile amino acid substitution mutation in the encoded FEA2 polypeptide. BOMMERT et al. teach that a corn plant comprising a weak, partial loss-of-function fea2 mutant allele is expected to have increased Kernel Row Number (KRN) via increased meristem size without a deleterious and substantial impact on yield (such as ear length)15.
BOMMERT et al. utilized TILLING to generate fea2 mutants and do not teach or suggest the use of site-directed gene editing (such as CRISPR/Cas) to generate fea2 mutants.
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 M367 of sequence SEQ ID NO: 74) to introduce a substitution to Ile (I) and, thereby, introduce a weak, partial loss-of-function fea2 allele 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 given the success BOMMERT et al. had by introducing a weak, partial loss-of-function mutation into FEA2 for achieving an increased KRN without a substantial negative impact on yield (e.g., ear length). A POSA would have been motivated to use CRISPR/Cas technology to mutate FEA2 because doing so is/was taught by PENNELL et al.
Regarding claim 1 (as well as claims that refer thereto), which are not rejected here, the claims are interpreted as requiring a mutation within the region consisting of one of SEQ ID NOs: 75-111 (SEQ ID NO: 111 being elected here). It appears as though none of SEQ ID NOs: 75-111 correspond to the nucleotides encoding Met367. Therefore, specifying that the mutant fea2 contains a mutation (1) within the region defined by one of SEQ ID NOs: 75-111 or (2) that is/encodes E447K would appear to distinguish these claims from the teachings of PENNELL et al. and BOMMERT et al.
Response to Applicant’s Remarks 05December2025:
(1) Applicant traverses this rejection because, according to Applicant, the teachings of PENNELL et al. are “solely prophetic” (Remarks at page 20).
This is not persuasive because even if the teachings by PENNELL et al. are prophetic, prophetic teachings may be anticipatory.
(2) Applicant traverses this rejection because, according to Applicant, BOMMERT et al. regarding EMS-induced mutagenesis and do not teach the CRISPR/Cas particulars of these claims (Applicant repeatedly pointing toward a guide nucleic acid) (Remarks at the bridge of pages 20-21).
This is not persuasive because Applicant’s argument is based on the technologies used by the respective references (which was already addressed in the rejection of record). Please note that PENNELL et al. teach CRISPR/Cas technology (which would include guide nucleic acids).
Applicant should consider limiting these claims to the elected substitution mutation at position E447 (numbered with respect to SEQ ID NO: 74)—as was said in the Nonfinal 23September2025 (page 11), such an amendment would appear to overcome rejections over PENNELL et al. and BOMMERT et al.
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, 84, 89, 90, 101 REMAIN rejected, and claim 102 is 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.
Please note that new claim 102 corresponds to part (c) of claim 57 (there is an “or” between parts (c) and (d) of claim 57, likewise an “or” recited in claim 102). Therefore, claim 102 is rejected with claim 57.
The claims filed 05December2025 do not contain amendments which address this rejection (Applicant only responds via Remarks). Therefore, the rejection below is copied from the Nonfinal 23September2025 (but-for the additional reference to claim 102) and new content is found within the Response to Applicant’s Remarks section below. In addition, please note that at page 11 of the Nonfinal 23September2025, the Office stated that neither claims 1 or 67 (or claims referring thereto) were not being rejected here. That is true with respect to claim 1, but not with respect to claim 67. Claim 67 should not have been referenced there (which is corrected herein below).
↓ Copied from Nonfinal 23September2025 (but-for reference to 102 and removing 11,66) ↓
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, 84, 89, 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 within the Election section hereinabove, please note that 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).
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 specification16 as well as the prior art17 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)18.
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.19 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 herein above 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 mutants20 as well as null, total loss-of-function fea2 mutants21 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.
To ensure clarity of the action, claims 74, 84, and 89 are separately rejected below for a lack of utility due to a different issue (i.e., they are rejected here for lack of enablement based upon the data in the specification and then also below for a lack of utility due to the nature of the claim language—the suggested claim amendments within the utility rejection below would not overcome this enablement issue).
Response to Applicant’s Remarks 05December2025:
(1) Applicant traverses this rejection because the claims are not limited to a “partial loss-of-function (weak allele) fea2 mutant” (Remarks at the paragraph bridging pages 12-13).
This is not persuasive because the Office agrees—these claims remain very broad and are not currently limited to a partial loss-of-function (weak allele) fea2 mutant (hence the anticipation and obviousness rejections maintained herein above). The elected partial loss-of-function (weak allele) fea2 mutant is encompassed by these claims, though, and so this rejection is tailored to the elected subject matter.
(2) Applicant summarizes the information within the specification and traverses this rejection because, according to Applicant, the specification evidences a material change in KRN (without a substantial reduction in mean ear length) when the corn plant/part comprises an fea2 allele encoding a substitution mutation at E447 (Remarks at pages 13-14).
This is not persuasive because Applicant has not provided evidence (data analysis) showing the supposed material change and Applicant has not otherwise provided the raw data needed to do this analysis. As said of record, Applicant is encouraged to provide such information via declaration practice. For clarity, and as said of record, please note that Table 4 of the current specification does not provide any information about ear length (= current Table 4 is of limited value for showing an increase in KRN without a substantial reduction in mean ear length).
Claim Rejections - 35 USC §§ 101, 112 - Utility
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
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 74, 84, 89 REMAIN rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility.
The claims filed 05December2025 do not contain amendments which address this rejection (Applicant only responds via Remarks). Therefore, the rejection below is copied from the Nonfinal 23September2025 and new content is found within the Response to Applicant’s Remarks section below.
↓ Copied from Nonfinal 23September2025 ↓
Separate from the enablement issues discussed hereinabove, these claims are rejected because they are directed to a nucleic acid encoding a mutant fea2 polypeptide (claim 84) or a modified fea2 polypeptide (claim 89), or to just a nucleic acid that may bind to fea2 sequence (claim 74, please note that “guide” is a non-limiting intended use and the reference to a spacer is optional). To that end, an amendment that may overcome this rejection would not be sufficient to overcome the enablement issue(s) discussed above.
The specification explains that when a corn plant or plant part comprises a nucleic acid encoding a weak, partial loss-of-function mutant fea2 nucleic acid (or the mutant fea2 polypeptide encoded thereby), the corn plant is reasonably expected to have increased Kernel Row Number (KRN) with no substantial negative change to yield (as measured by at least no substantial decrease in ear length). There is no disclosed, nor well-recognized, specific or substantial use for one such mutant fea2 nucleic acid (or the mutant fea2 polypeptide encoded thereby) when outside of a corn plant/part. Please amend claims 84 and 89 so that the nucleic acid or polypeptide is within a corn plant/part. Please note that claims 90 and 101 are not rejected here.
Furthermore, the specification explains that a corn plant cell comprising an editing system (wherein the editing system comprises (a) a CRISPR-Cas effector protein and (b) a guide nucleic acid comprising a spacer sequence with complementarity to an endogenous target gene encoding a FEA2 protein) may be used to “generate a mutation in the endogenous target gene encoding an FEA2 protein”22. There is no disclosed, nor well-recognized, specific or substantial use a “guide” nucleic acid without a sequence-guided gene editing component and when outside of a corn plant cell. Please amend claim 74 so that the “guide” nucleic acid is within a CRISPR-Cas editing system that is within a corn plant cell (i.e., Applicant should consider amending claim 74 so that it is directed toward “a corn plant cell comprising a gene editing system” as is described at, for example, lines 3-10 on page 49 of the specification).
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To ensure clarity, use of a mutant nucleic acid or protein to, for example, identify a corn plant/part is a general utility applicable to a broad class of corn nucleic acids or proteins (respectively). Thus, use of the claimed nucleic acid or polypeptide in a manner that any other corn nucleic acid or polypeptide is used is not a specific utility under 35 U.S.C. 101) (MPEP § 2107.01(A)). Further, the claimed nucleic acid or polypeptide must be useful as disclosed—the fact that a desirable characteristic/use may be identified at some future date following further research/analysis is not sufficient for meeting the substantial utility requirement of 35 U.S.C. 101 (MPEP § 2107.01(B)).
As summarized at MPEP § 2103 (I)(A): “the claimed invention as a whole must be useful. The purpose of [the Utility] requirement is to limit patent protection to inventions that possess a certain level of ‘real world’ value, as opposed to subject matter that represents nothing more than an idea or concept, or is simply a starting point for future investigation or research” (internal citations omitted). See MPEP §§ 2164.01(c) and 2107.01-.03, e.g., 2107.02(III)(A) (“… a specification which contains a disclosure of utility which corresponds in scope to the subject matter sought to be patented must be taken as sufficient to satisfy the utility requirement of § 101 for the entire claimed subject matter unless there is a reason for one skilled in the art to question the objective truth of the statement of utility or its scope.”).
Claims 74, 84, 89 are also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
Response to Applicant’s Remarks 05December2025:
(1) Applicant traverses this rejection by asserting that there is no basis for requiring that the claimed subject matter be within a particular context (Remarks at page 15). Applicant also provides examples of granted claims directed toward nucleic acids, polypeptides, or guide nucleic acids (Remarks at pages 15-18).
This is not persuasive in view of the laws or rules cited within the rejection itself. The one productive thing Applicant may do is describe a specific and substantial utility for the claimed nucleic acids, polypeptides, and guide nucleic acids. Applicant has not done this. In fact, the Office candidly believes that such uses envisioned by Applicant are only when the nucleic acids or polypeptides are within a plant/plant part and only when the guide nucleic acid is within a CRISPR-Cas editing system or in contact with a target nucleic acid sequence (i.e., the only specific and substantial uses envisioned by Applicant are the same as those which the Office has already suggested be recited in these claims). The Office remains interested in Applicant’s evidence to the contrary (= please explain how the subject matter as claimed has a specific and substantial utility, otherwise, please amend the claims).
Warning, Obvious-Type Double Patenting
[Copied from the Nonfinal 23September2025 →] These claims recite many “regions” of a corn FEA2 nucleotide sequence within which a mutation may be made. While non-elected here, these claims recite region sequences SEQ ID NOs: 76-86, 90-91, 94-99, 103-104, 107-108 which appear to contain the codon for Pro477. A substitution mutation at Pro477 is the subject of the claims and examination for co-pending application number 18645465 (Attny. Dkt. No. 1499.26CT). SEQ ID NOs: 174, 175, and 177 of application 18645465 comprise a Pro477Ser, Pro477Thr, and Pro477Cys mutation (respectively), which are mutants that appear to be encompassed by claims 57, 66, and 74 (i.e., the claims of 18645465 appear to anticipate claims 57, 66, 74 of this application). Please note that while claims 1 and 64 of this application say the substitution is to an “F, K, N, or I” residue, that would appear to be obvious in view of SEQ ID NOs: 174, 175, and 177 of 18645465 because a person with even ordinary skill in the art at the time the application was filed would view it as obvious to substitute Pro477 for any of the other nineteen standard amino acids (note that at least “site saturation” mutagenesis techniques were well-known and widely utilized before the filing of either of these applications23). To that end, claims 1, 11-12, 14, 64, 67, 84, 89, 90, 101 appear to be obvious in view of the claims of 18645465.
Again, while these examined claims are currently limited to the elected region sequence SEQ ID NO: 111, for at least the reasons set forth above (and in the event of any rejoinder), Applicant is encouraged to review the non-elected subject matter being recited in the claims of this application and encouraged to delete reference to, for example, region sequences SEQ ID NOs: 76-86, 90-91, 94-99, 103-104, 107-108.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Rebecca STEPHENS whose telephone number is (571)272-0070. The examiner can normally be reached Monday through Friday 8:30-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad ABRAHAM can be reached 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 See the indefiniteness rejection herein above and screenshots therein.
2 See the ABSS sequence search Result 3 in the sequence search file entitled “20250616_121124_us-18-342-761-73.rni”.
3 See, in particular, PENNELL et al. at ¶48 on page 7.
4 PENNELL et al. at ¶50 on pages 7-8.
5 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
6 PENNELL et al. at claims 3 and 20 on page 61; see also PENNELL et al. at Example 4 ¶101 on page 14.
7 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
8 See the indefiniteness rejection herein above and screenshots therein.
9 See the ABSS sequence search Result 3 in the sequence search file entitled “20250616_121124_us-18-342-761-73.rni”.
10 See, in particular, PENNELL et al. at ¶48 on page 7.
11 PENNELL et al. at ¶50 on pages 7-8.
12 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
13 PENNELL et al. at claims 3 and 20 on page 61; see also PENNELL et al. at Example 4 ¶101 on page 14.
14 PENNELL et al. at claim 1 on page 61; see also PENNELL et al. at Example 4 at ¶101 on page 14.
15 See BOMMERT et al. at Figure 3 on page 336.
16 See the various “aspects” of the invention described at pages 4-7.
17 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).
18 See Table 2 of the specification at pages 95-97.
19 See pages 98-99 of the specification.
20 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).
21 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).
22 See the specification at lines 3-10 on page 49.
23 See MOSQUNA et al. (“Potent and selective activation of abscisic acid receptors in vivo by mutational stabilization of their agonist-bound conformation” 2011 PNAS 108(51): 20838-20843) demonstrating 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 nineteen standard amino acid residues to identify those substitution mutants that increase protein::protein interactions.
Prosecution Insights