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 the Nonfinal 03November2025 → ] Applicant’s election without traverse of (A) the FEA2 gene comprises a sequence having at least 90% sequence identity to the nucleotide sequence of SEQ ID NO: 72 or 73 (see part (b) at claims 1,7,14), (B) residues 461-613 of SEQ ID NO: 74 as the FEA2 region for mutating/targeting, (C) SEQ ID NO: 79 as the spacer, (D) & (E) amino acid position 477 of SEQ ID NO: 74 wherein the substitution is P477S (corresponding to nucleotide sequence SEQ ID NO: 101 and polypeptide sequence SEQ ID NO: 174) in the reply filed on 04September2025 is acknowledged. Please note that Applicant’s representative Alice BONNEN kindly clarified the election for (A) in a telephone conversation had 22October2025.
Status of the Claims
The amendments filed 05December2025 are acknowledged and have been fully considered. Claims 4 and 16 are cancelled. Claims 1-3, 5-15, and 17-19 are pending and examined on the merits herein. Claims 1, 3, 7, 9-13, 17-19 are currently amended. Claims 2, 5-6, 8, 15 are original.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [US provisional 63000206 filed 26March2020] and 35 U.S.C. 121 [divisional of 17212665 filed 25March2021] is acknowledged. Claims 1-3, 5-15, and 17-19 maintain an effective filing date of 26March2020.
Examined Sequences
[Copied from the Nonfinal 03November2025 ↓ ]
For clarity of the record,
Elected PAM sequence SEQ ID NO: 79 (cagatccctgcggggcttggggg) corresponds to nucleotides 1506-1528 of genomic FEA2 sequence SEQ ID NO: 72 and corresponds to nucleotides 1423-1445 of coding FEA2 sequence SEQ ID NO: 73. SEQ ID NO: 79 encodes the amino acid sequence “QIPAGLG” which corresponds to residues 475-481 of FEA2 amino acid sequence SEQ ID NO: 74. The target site nucleotide sequence SEQ ID NO: 77 encodes SEQ ID NO: 75 (AGQIPAGLGGMGR) which corresponds to residues 472-485 of SEQ ID NO: 74. The target site nucleotide sequence SEQ ID NO: 78 encodes SEQ ID NO: 76 (CNYLAGQIPAGLGGMGRLHTL) which corresponds to residues 469-489 of SEQ ID NO: 74 and comprises SEQ ID NO: 75 (underlined therein).
For completeness, below is a partial alignment of SEQ ID NOs: 74-76 with the sequence encoded by SEQ ID NO: 79 shown in underline and the elected P477 position (for editing) shaded:
PNG
media_image1.png
187
751
media_image1.png
Greyscale
Withdrawn Objections and/or Rejections
Objections and/or rejections made of record in the nonfinal office action dated 03November2025 that are not otherwise discussed herein are withdrawn. In particular:
RE ¶¶ 6-15: The objections are withdrawn in view of the amendments to the claims;
RE ¶¶ 16, 18: The indefiniteness rejections of claims 10 and 19 are withdrawn in view of the amendments to the claims;
RE ¶ 17: The indefiniteness rejection of claim 13 is withdrawn in view of Applicant’s remarks saying the qualifiers of the term “region” are material (the term region should be read with the 5 or 6 words that follow it, as in not just “region” but “region of a corn FEA2 protein” or “region of an endogenous corn FEA2 gene”)—please also note that the “region of an endogenous corn FEA2 gene” must encode the “region of a corn FEA2 protein” per lines 4-5 of claim 13;
RE ¶ 19: The rejection of claim 16 is withdrawn in view of claim 16 being cancelled;
and
RE ¶ 24: The anticipation rejection over CARGILL et al. is withdrawn because Applicant invoked the “Joint Research Agreement” exception to remove the CARGILL et al. reference (2020/0377900) as prior art (Remarks 05December2025 at part (C) on page 16).
Claim Rejections - 35 USC §§ 101 & 112 - Utility
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.
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.
Claims 1-2 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.
↓ Rejection Copied from the Nonfinal 03November2025 ↓
These claims are directed toward a “guide nucleic acid” with particular binding features. Please note that “guide” is a non-limiting intended use (as used in the art, the nucleic acid will bind a target sequence if or when the guide nucleic acid is put in contact with that target sequence—but that target sequence must be present for the nucleic acid to act as intended, i.e., as a “guide”).
There is no disclosed, nor well-recognized, specific or substantial use a “guide” nucleic acid without a sequence-guided gene editing component. 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” (pages 49-52). Please amend claims 1-2 so that the “guide” nucleic acid is within a CRISPR-Cas editing system (i.e., bring claim 3 up into claim 1).
Claims 1-2 also remain 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:
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 part (E) on page 9). Applicant also provides examples of granted claims directed toward nucleic acids, polypeptides, or guide nucleic acids (Remarks at pages 9-10).
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 guide nucleic acids. Applicant has not done this. In fact, the Office candidly believes that such uses envisioned by Applicant are 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).
Claim 19 REMAINS 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.
↓ Rejection Copied from the Nonfinal 03November2025 ↓
Claim 19 appears to be directed toward a corn plant that comprises only a guide nucleic acid. As understood in the art, and as described within the specification (see pages 49-52), no change would occur to the plant if only a guide nucleic acid is introduced thereinto—the guide nucleic acid would require at least a CRISPR-Cas effector protein in order for a change to occur. For at least this reason, there is no disclosed, nor well-recognized, specific or substantial use of a corn plant that only comprises a “guide” nucleic acid. Please amend claim 19 so that the “guide” nucleic acid is introduced within a CRISPR-Cas editing system (i.e., bring the language of claim 3 into claim 19).
Claim 19 also remains 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:
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 part (F) on page 11). Applicant also provides examples of granted claims directed toward nucleic acids, polypeptides, or guide nucleic acids (Remarks at page 11).
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 transformed corn plant. Applicant has not done this. To be clear, the issue here is that this claim only transforms a guide nucleic acid into a corn plant and, absent evidence to the contrary, a guide nucleic acid alone in a corn plant would not be useful (it would have no functional effect onto the corn plant)—the Office continues to believe that other structures would be needed for the guide nucleic acid to have specific and substantial utility (such as being introduced into the plant within or with a CRISPR-Cas editing system). 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).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 3, 7, 9-11, 13-14 REMAIN rejected under 35 U.S.C. 102(a)(1) as being anticipated by PENNELL et al. (US2019/0032071 published 31January2019, of record IDS 21May2024).
↓ Rejection Copied from the Nonfinal 03November2025 ↓
These claims are generally directed toward a CRISPR-Cas gene editing system and methods of using it for editing the endogenous CLV2/FEA2 gene within a maize plant cell. In particular, modifying an amino acid therein and increasing the Kernel Row Number of a resulting, edited maize plant. Please note that the rejected claims do not specify where FEA2 is edited (e.g., specifying the target site, a PAM sequence, or the amino acid residue(s) which are modified).
PENNELL et al. teach the maize FEA2 nucleotide sequence SEQ ID NO: 36 which as 100% sequence identity to the FEA2 sequence SEQ ID NO: 73 of this application1. PENNELL et al. teach CRISPR-Cas editing2 of an intracellular corn/Zea mays FEA2 sequence SEQ ID NO: 36.3 [claims 3, 7, 13-14] To be clear, PENNELL et al. teach that: plants may be regenerated from a transformed corn plant cell4 [claim 9]; that kernel row number is modified5 [claim 10]; and that the editing results in amino acid variation6 [claim 11].
Response to Applicant’s Remarks 05December2025:
(1) Applicant believes claim 3 should be removed from this rejection because the recitations of now-cancelled claim 4 have been added to claim 3 (Remarks at page 12).
This is not persuasive because those same recitations are within rejected claims 7 and 14 = it looks like claim 4 should have been listed here as a rejected claim in the nonfinal of record (an accident which would be clear to a person of ordinary skill in the art reviewing the recitations of rejected claims 7 and 14).
(2) Applicant traverses this rejection because, according to Applicant, the teachings of PENNELL et al. are “solely prophetic” (Remarks at pages 12-13).
This is not persuasive because even if the teachings by PENNELL et al. are prophetic, prophetic teachings may be anticipatory.
Claims 3, 7, 9-10 REMAIN rejected under 35 U.S.C. 102(a)(1) as being anticipated by LIPPMAN et al. (WO2018/213547 published 22November2018).
↓ Rejection Copied from the Nonfinal 03November2025 ↓
These claims are generally directed toward a CRISPR-Cas gene editing system and methods of using it for editing the endogenous CLV2/FEA2 gene within a maize plant cell. In particular, modifying an amino acid therein and increasing the Kernel Row Number of a resulting, edited maize plant. Please note that the rejected claims do not specify where FEA2 is edited (e.g., specifying the target site, a PAM sequence, or the amino acid residue(s) which are modified).
LIPPMAN et al. teach using CRISPR-Cas editing to edit the corn/maize FEA2 gene’s endogenous promoter to generate a weak allele (citing BOMMERT et al. 2013, of record IDS 21May2024)7. As evidenced by the sequence alignment below, BOMMERT et al. uses the corn FEA2 sequences published as “GRMZM2G104925”8, the amino acid sequence of which has 100% sequence identity to SEQ ID NO: 74 of this application (also published as UniProtKB Accession No. Q940E8, see version dated 03April2013 and version 102 dated 13February2019; of record IDS 21May2024).9 To be clear, an endogenous promoter is within the meaning of a “gene”10 [claims 3, 7, 9] and LIPPMAN et al. teach generating a weak FEA2 allele to increase kernel row number11 [claim 10].
RESULT 1
FEA2_MAIZE
ID FEA2_MAIZE Reviewed; 613 AA.
AC Q940E8; B4G061;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 115.
DE RecName: Full=Leucine-rich repeat receptor-like protein FASCIATED EAR2;
DE AltName: Full=CLAVATA2-like protein;
DE Flags: Precursor;
GN Name=FEA2; ORFNames=ZEAMMB73_546581;
OS Zea mays (Maize).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Liliopsida; Poales; Poaceae; PACMAD clade;
OC Panicoideae; Andropogonodae; Andropogoneae; Tripsacinae; Zea.
OX NCBI_TaxID=4577;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. B73;
RX PubMed=11641280; DOI=10.1101/gad.208501;
RA Taguchi-Shiobara F., Yuan Z., Hake S., Jackson D.;
RT "The fasciated ear2 gene encodes a leucine-rich repeat receptor-like
RT protein that regulates shoot meristem proliferation in maize.";
RL Genes Dev. 15:2755-2766(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. B73;
RX PubMed=19965430; DOI=10.1126/science.1178534;
RA Schnable P.S., ….;
RT "The B73 maize genome: complexity, diversity, and dynamics.";
RL Science 326:1112-1115(2009).
RN [3]
RP GENOME REANNOTATION.
RG Maize Genome Sequencing Project;
RL Submitted (AUG-2012) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. B73;
RX PubMed=19936069; DOI=10.1371/journal.pgen.1000740;
RA Soderlund C., Descour A., Kudrna D., Bomhoff M., Boyd L., Currie J.,
RA Angelova A., Collura K., Wissotski M., Ashley E., Morrow D., Fernandes J.,
RA Walbot V., Yu Y.;
RT "Sequencing, mapping, and analysis of 27,455 maize full-length cDNAs.";
RL PLoS Genet. 5:E1000740-E1000740(2009).
RN [5]
RP MUTAGENESIS OF GLY-332; MET-367; GLY-405 AND PRO-477, AND FUNCTION.
RX PubMed=23377180; DOI=10.1038/ng.2534;
RA Bommert P., Nagasawa N.S., Jackson D.;
RT "Quantitative variation in maize kernel row number is controlled by the
RT FASCIATED EAR2 locus.";
RL Nat. Genet. 45:334-337(2013).
CC -!- FUNCTION: Receptor-like protein that regulates shoot meristem
CC proliferation. Based on additive and synergistic phenotypes of double
CC mutants, it is probable that unlike CLV1 and CLV2 in A.thaliana, FAE2
CC and TD1 do not function exclusively in a single pathway.
CC {ECO:0000269|PubMed:11641280, ECO:0000269|PubMed:23377180}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in ear primordia, vegetative apex and
CC young leaf tissues. Barely detected in expanded leaf tissues and not
CC expressed in roots. {ECO:0000269|PubMed:11641280}.
CC -!- DISRUPTION PHENOTYPE: Fasciation. Flattened and wider ears with
CC irregular rows of seeds. Thicker rachis of tassels and increased floral
CC organ numbers. {ECO:0000269|PubMed:11641280}.
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DR EMBL; AY055124; AAL17871.1; -; mRNA.
DR EMBL; CM000780; AFW62869.1; -; Genomic_DNA.
DR EMBL; BT042749; ACF87754.2; -; mRNA.
DR RefSeq; NP_001105662.1; NM_001112192.2.
DR AlphaFoldDB; Q940E8; -.
DR SMR; Q940E8; -.
DR IntAct; Q940E8; 1.
DR STRING; 4577.GRMZM2G104925_P01; -.
DR PaxDb; Q940E8; -.
DR EnsemblPlants; Zm00001eb184050_T001; Zm00001eb184050_P001; Zm00001eb184050.
DR GeneID; 542675; -.
DR Gramene; Zm00001eb184050_T001; Zm00001eb184050_P001; Zm00001eb184050.
DR KEGG; zma:542675; -.
DR MaizeGDB; 493979; -.
DR eggNOG; KOG0619; Eukaryota.
DR HOGENOM; CLU_000288_18_4_1; -.
DR OMA; KWSNLRY; -.
DR OrthoDB; 826997at2759; -.
DR Proteomes; UP000007305; Chromosome 4.
DR ExpressionAtlas; Q940E8; baseline and differential.
DR Genevisible; Q940E8; ZM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:EnsemblPlants.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001653; F:peptide receptor activity; IEA:EnsemblPlants.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0009908; P:flower development; IMP:UniProtKB.
DR GO; GO:0010078; P:maintenance of root meristem identity; IEA:EnsemblPlants.
DR GO; GO:0010088; P:phloem development; IEA:EnsemblPlants.
DR GO; GO:0045595; P:regulation of cell differentiation; IEA:EnsemblPlants.
DR GO; GO:0048509; P:regulation of meristem development; IMP:UniProtKB.
DR GO; GO:0010075; P:regulation of meristem growth; IEA:EnsemblPlants.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR013210; LRR_N_plant-typ.
DR Pfam; PF12799; LRR_4; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF08263; LRRNT_2; 1.
DR SMART; SM00369; LRR_TYP; 8.
DR PROSITE; PS51450; LRR; 13.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Differentiation; Glycoprotein;
KW Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..613
FT /note="Leucine-rich repeat receptor-like protein FASCIATED
FT EAR2"
FT /id="PRO_0000422039"
FT TOPO_DOM 29..573
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 574..597
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 598..613
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 79..103
FT /note="LRR 1"
FT REPEAT 104..128
FT /note="LRR 2"
FT REPEAT 130..150
FT /note="LRR 3"
FT REPEAT 151..176
FT /note="LRR 4"
FT REPEAT 178..199
FT /note="LRR 5"
FT REPEAT 202..226
FT /note="LRR 6"
FT REPEAT 227..250
FT /note="LRR 7"
FT REPEAT 251..274
FT /note="LRR 8"
FT REPEAT 276..297
FT /note="LRR 9"
FT REPEAT 298..322
FT /note="LRR 10"
FT REPEAT 324..346
FT /note="LRR 11"
FT REPEAT 347..370
FT /note="LRR 12"
FT REPEAT 372..394
FT /note="LRR 13"
FT REPEAT 435..459
FT /note="LRR 14"
FT REPEAT 460..483
FT /note="LRR 15"
FT REPEAT 484..507
FT /note="LRR 16"
FT REPEAT 508..531
FT /note="LRR 17"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
Query Match 100.0%; Score 3138; DB 1; Length 613;
Best Local Similarity 100.0%;
Matches 613; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLTATPLPHQLLATFLLVLASATQPAVPASTDRAALLAFRASLSPPSRAALSSWSGPLSP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLTATPLPHQLLATFLLVLASATQPAVPASTDRAALLAFRASLSPPSRAALSSWSGPLSP 60
Qy 61 SWLGVSLHPATAPAPSVTTPSVAELSLRGLNLTGVIPAAPLALLRRLRTLDLSANALSGE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SWLGVSLHPATAPAPSVTTPSVAELSLRGLNLTGVIPAAPLALLRRLRTLDLSANALSGE 120
Qy 121 LPCSLPRSLLALDLSRNALSGAVPTCLPSSLPALRTLNLSANFLRLPLSPRLSFPARLAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LPCSLPRSLLALDLSRNALSGAVPTCLPSSLPALRTLNLSANFLRLPLSPRLSFPARLAA 180
Qy 181 LDLSRNAISGAVPPRIVADPDNSALLLLDLSHNRFSGEIPAGIAAVRSLQGLFLADNQLS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LDLSRNAISGAVPPRIVADPDNSALLLLDLSHNRFSGEIPAGIAAVRSLQGLFLADNQLS 240
Qy 241 GDIPPGIGNLTYLQVLDLSNNRLSGSVPAGLAGCFQLLYLQLGGNQLSGALRPELDALAS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GDIPPGIGNLTYLQVLDLSNNRLSGSVPAGLAGCFQLLYLQLGGNQLSGALRPELDALAS 300
Qy 301 LKVLDLSNNKISGEIPLPLAGCRSLEVVDLSGNEISGELSSAVAKWLSLKFLSLAGNQLS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LKVLDLSNNKISGEIPLPLAGCRSLEVVDLSGNEISGELSSAVAKWLSLKFLSLAGNQLS 360
Qy 361 GHLPDWMFSFPLLQWLDLSSNKFVGFIPDGGFNVSEVLNGGGGQGTPSESVLPPQLFVSA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GHLPDWMFSFPLLQWLDLSSNKFVGFIPDGGFNVSEVLNGGGGQGTPSESVLPPQLFVSA 420
Qy 421 SVDTVSWQLDLGYDVQATTGIDLSGNELCGEIPEGLVDMKGLEYLNLSCNYLAGQIPAGL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 SVDTVSWQLDLGYDVQATTGIDLSGNELCGEIPEGLVDMKGLEYLNLSCNYLAGQIPAGL 480
Qy 481 GGMGRLHTLDFSHNGLSGEVPPGIAAMTVLEVLNLSYNSLSGPLPTTKFPGALAGNPGIC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GGMGRLHTLDFSHNGLSGEVPPGIAAMTVLEVLNLSYNSLSGPLPTTKFPGALAGNPGIC 540
Qy 541 SGKGCSENARTPEGKMEGSNHRGWLGGWHGENGWVSLGAFCISTMTSFYVSLATLLCSSN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SGKGCSENARTPEGKMEGSNHRGWLGGWHGENGWVSLGAFCISTMTSFYVSLATLLCSSN 600
Qy 601 ARNFVFRPVRVEY 613
|||||||||||||
Db 601 ARNFVFRPVRVEY 613
Response to Applicant’s Remarks 05December2025:
(1) Applicant believes claims 9 and 10 should be removed from this rejection because claim 7, to which claims 9-10 refer, was not listed in this rejection (Remarks at page 12).
This is not persuasive because, as Applicant pointed out, claims 9 and 10 require the recitations of claim 7 (= claim 7 just wasn’t listed in the rejection statement, an accident which would be clear to a person of ordinary skill in the art reviewing the recitations of claims 9 and 10). As a specific example, discussion of sequences within the rejection of record would not be necessary if claim 7 weren’t being considered (none of the claims listed in the rejection statement recited sequences, only claim 7 did/does).
(2) Applicant traverses reliance on LIPPMAN et al. because, per Applicant, LIPPMAN et al. does not teach or suggest editing an fea2 gene (LIPPMAN et al. regarding promoters and regulatory regions) (Remarks at page 14).
This is not persuasive in view of the breadth of these claims (the claims encompass the teachings of LIPPMAN et al.).
(3) Applicant also traverses this rejection because, according to Applicant, LIPPMAN et al. do not teach editing a specific site (Remarks at page 15).
This is not persuasive because of the breadth of these claims (Applicant is making arguments about supposed claim requirements that are not actually required by these claims). These claims are very broad with most of the text talking about the targeted FEA2 gene structure and not the guide nucleic acid structure, or target site structure, or specific edit being introduced therewith. Applicant should consider narrowing the claim language to overcome the prior art rejections of record.
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 1-3, 5-15, 17-19 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over BOMMERT et al. (“Quantitative variation in maize kernel row number is controlled by the FASCIATED EAR2 locus” 2013 Nature Genetics 45(3):334-338 including supplemental information available at https://www.nature.com/articles/ng.2534#Sec8 , of record IDS 21May2024) as evidenced by the sequence(s) published as UniProtKB Accession No. Q940E8 (see version dated 03April2013 and version 102 dated 13February2019; of record IDS 21May2024); in view of PENNELL et al. (US2019/0032071 published 31January2019, of record IDS 21May2024); and LIPPMAN et al. (WO2018/213547 published 22November2018).
Applicant invoked the “Joint Research Agreement” exception to remove the CARGILL et al. reference (2020/0377900) as prior art. Therefore, CARGILL et al. is now removed from the rejection. Please note that the disclosures by PENNELL et al. and LIPPMAN et al. are sufficient to address CRISPR/Cas technology (“As applied to claims 3, 7, 9-11. 13-14; PENNELL et al., LIPPMAN et al., and CARGILL et al. all teach using CRISPR-Cas technology to edit a corn/Zea mays/maize FEA2 gene” Nonfinal 03November2025 at the second paragraph on page 16). The rejection below is otherwise copied from the Nonfinal 03November2025.
↓ Rejection from Nonfinal 03November2025 but-for removal of 4, 16, CARGILL et al. ↓
As elected, these claims are generally directed toward using CRISPR-Cas technology to edit corn FEA2 protein residue Pro477 (numbered according to UniProtKB Accession No. Q940E8 and SEQ ID NO: 74).12 While these claims do not currently specify how Pro477 is edited, Applicant has elected introducing an amino acid substitution at Pro477 (in particular, editing Pro477 to Ser477 (P477S)). To ensure a clear record, and as explained within the summary of sequences section at the top of this action, sequences SEQ ID NOs: 75-79 all encompass Pro477 of SEQ ID NO: 74.
So as compared to the anticipation rejections hereinabove, this rejection regards the extent to which the claims specify what the FEA2 target site is and which FEA2 nucleotide sequence(s) and/or encoded FEA2 amino acid residue(s) are changed.
BOMMERT et al. teach EMS-mutagenesis-induced weak alleles of corn CLV2/FEA2 and resulting increased kernel row number. One such weak allele encodes a Pro477Leu substitution mutation (therein called “fea2-1328”).13 As noted above, BOMMERT et al. use the corn FEA2 sequences published as “GRMZM2G104925”14, the amino acid sequence of which has 100% sequence identity to SEQ ID NO: 74 of this application (also published as UniProtKB Accession No. Q940E8).
BOMMERT et al. do not teach generating a fea2-1328 using CRISPR-Cas technology. Therefore, BOMMERT et al. do not teach the “target site”, “guide nucleic acid”, “spacer” sequence, “gene editing system”, “CRISPR-Cas effector protein”, and other recitations of these claims which are specific for use of the CRISPR-Cas technology).
As applied to claims 3, 7, 9-11. 13-14; PENNELL et al., and LIPPMAN et al. teach using CRISPR-Cas technology to edit a corn/Zea mays/maize FEA2 gene. The difference between these three references and BOMMERT et al. is that none of these three references specifically suggest targeting the region encompassing Pro477 (or targeting Pro477 itself). But please note that at least LIPPMAN et al. evidence that the work of BOMMERT et al. was well known to persons of ordinary skill in the art at the time this application was filed (a “POSA”)—LIPPMAN et al. specifically cite BOMMERT et al. and teach an alternate method of generating a weak FEA2 allele (LIPPMAN et al. targeting the FEA2 promoter instead of its coding sequence, as is taught by BOMMERT et al.).
It would have been obvious to a POSA to recreate the work of BOMMERT et al. (i.e., obtain a maize cell/plant comprising a weak FEA2 mutant allele characterized by a Pro477 substitution mutation) utilizing CRISPR-Cas technology because it would have been no more than “combining prior art elements [mutants of BOMMERT et al. with the CRISPR-Cas techniques of PENNELL et al., and LIPPMAN et al.] according to known methods to yield predictable results” MPEP § 2143(I)(A), the “simple substitution of one known element for another [CRISPR-Cas technology for EMS-mutagenesis] to obtain predictable results” MPEP § 2143(I)(B), the “use of a known technique [CRISPR-Cas] to improve similar products [the weak FEA2 allele of BOMMERT et al.] in the same way” MPEP § 2143(I)(C), “applying a known technique [CRISPR-Cas] to a known product [the weak FEA2 allele of BOMMERT et al.] to yield predictable results” MPEP § 2143(I)(D), or at the very least “obvious to try” with a reasonable expectation of successfully utilizing CRISPR-Cas technology to arrive at a weak FEA2 allele from BOMMERT et al. MPEP § 2143(I)(E).
To be clear regarding elected spacer sequence SEQ ID NO: 79 in view of Applicant’s election of a substitution mutation at P477, there is nothing of record to suggest that SEQ ID NO: 79 would not have also been obvious to a POSA using CRISPR-Cas technology to generate a corn plant/part having a mutation at P477.
Regarding the elected Pro477Ser mutation which is encompassed by these claims, albeit not explicitly claimed, it remains the Office’s position15 that a POSA would have found it obvious-to-try any of the other standard nineteen amino acids at position 477 (numbered according to UniProtKB Accession No. Q940E8 and SEQ ID NO: 74) with a reasonable expectation of successfully generating a weak FEA2 allele (and, thereby, increasing kernel row number). To that end, please note that before the filing of this application, techniques such as site saturation mutagenesis were used in the field to do just that (test all 19 of the other standard amino acids at a particular location within an amino acid sequence to assess impact on function).16 Therefore, the elected Pro477Ser mutation would have been obvious too (i.e., an amendment to specify that the mutation is Pro477Ser will not overcome obviousness).
In the interest of compact prosecution, the Office does not see a path toward patentability for the claimed (and elected) subject matter.
Response to Applicant’s Remarks 05December2025:
(1) Applicant invokes the “Joint Research Agreement” exception to remove CARGILL et al. as prior art (Remarks at the last two paragraphs on page 16).
CARGILL et al. has been removed from this rejection.
(2) Applicant traverses reliance on BOMMERT et al. because, per Applicant, BOMMERT et al. regards EMS-mutagenesis (which is not targeted/specific mutagenesis) (Remarks at page 17).
This is not persuasive in view of the other references within this rejection (see PENNELL et al. and LIPPMAN et al.).
(3) Applicant traverses this rejection because, according to Applicant, the teachings of PENNELL et al. are “solely prophetic” (Remarks at page 17).
This is not persuasive because even if the teachings by PENNELL et al. are prophetic, prophetic teachings may be anticipatory.
(4) Applicant also asserts that PENNELL et al. does not teach or suggest a particular target site within an FEA2 gene (Remarks at page 17).
This is not persuasive because these claims are not limited to a particular target site (note the use of “and/or” or “or” throughout the claims) and at least BOMMERT et al. provides teachings and suggestions with respect to what part of the FEA2 may be targeted and what modifications may be made.
(5) Applicant also traverses this rejection because, according to Applicant, LIPPMAN et al. do not teach editing a specific site (Remarks at pages 17-18).
This is not persuasive because of the breadth of these claims (Applicant is making arguments about supposed claim requirements that are not actually required by these claims) and because LIPPMAN et al. is not applied in a vacuum—BOMMERT et al. provides teachings and suggestions with respect to what part of the FEA2 gene may be targeted and what modifications may be made.
(6) Finally, Applicant takes issue with the Office’s statements regarding the spacer sequence SEQ ID NO: 79 (that “there is nothing of record to suggest that SEQ ID NO: 79 would not have also been obvious to a POSA using CRISPR-Cas technology to generate a corn plant/part having a mutation at P477”) (Remarks at page 18).
The Office has established why using CRISPR/Cas technology to arrive at the claimed and elected subject matter would have been obvious—there remains no information in the record to suggest that use of a particular spacer sequence for applying CRISPR/Cas technology would not also be obvious (if Applicant has such information, they should make it of record). It is important to note here that the Office has established why the specifically elected position being claimed would have been obvious (i.e., this is not a vague or otherwise “hand-wavy” prior art rejection).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-15, 17-19 REMAIN provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of copending Application No. 18645465 (Attny. Dkt. No. 1499.26CT, published as US20240279640A1) in view of PENNELL et al. (US2019/0032071 published 31January2019, of record IDS 21May2024); and LIPPMAN et al. (WO2018/213547 published 22November2018). This is a provisional nonstatutory double patenting rejection.
This application 18669588 and 18645465 share a priority claim to provisional application 63000206 (filed 26March2020), and this application 18669588 purports to be a divisional of 17212665 whereas 18645465 is a continuation of 17212665. Otherwise, this application 18669588 and 18645465 are not related (e.g., this application is not a continuation or divisional application of 18645465).
The claims of 18645465 regard corn plants/parts, and methods of generating them, comprising a mutant FEA2 gene including a substitution mutation at residue Pro477 (numbered according to SEQ ID NO: 74, which is the same amino acid sequence in both this application 18669588 and 18645465). The claims of 18645465 are agnostic for the manner in which Pro477 is mutated (= the corn plant/part may be mutated via EMS mutagenesis, CRISPR-Cas gene editing, or another methodology). For completeness, the specification of 18645465 does say that CRISPR-Cas may be used. As of 06October2025, the claims of 18645465 specifically recite a mutant corn FEA2 characterized by having a P477S mutation (SEQ ID NO: 101 therein), P477T mutation (SEQ ID NO: 102 therein), or P477C mutation (SEQ ID NO: 104 therein).
For the sake of clarity, please note that the claims of this application do not presently specify the elected Pro477Ser mutation, but elected P477S corresponds to the sequence SEQ ID NO: 101 of 18645465.
PENNELL et al., and LIPPMAN et al. teach using CRISPR-Cas technology to edit a corn/Zea mays/maize FEA2 gene. The difference between these three references and 18645465 is that none of these three references specifically suggest targeting the region encompassing Pro477 (or targeting Pro477 itself).
It would have been obvious to a POSA to generate a corn plant/part of 18645465 (i.e., obtain a maize cell/plant comprising a weak FEA2 mutant allele characterized by a Pro477 substitution mutation) utilizing CRISPR-Cas technology because it would have been no more than “combining prior art elements [mutants of 18645465 with the CRISPR-Cas techniques of PENNELL et al., and LIPPMAN et al.] according to known methods to yield predictable results” MPEP § 2143(I)(A), the “simple substitution of one known element for another [CRISPR-Cas technology for EMS-mutagenesis] to obtain predictable results” MPEP § 2143(I)(B), the “use of a known technique [CRISPR-Cas] to improve similar products [the weak FEA2 allele of 18645465] in the same way” MPEP § 2143(I)(C), “applying a known technique [CRISPR-Cas] to a known product [the weak FEA2 allele of 18645465] to yield predictable results” MPEP § 2143(I)(D), or at the very least “obvious to try” with a reasonable expectation of successfully utilizing CRISPR-Cas technology to arrive at a weak FEA2 allele from 18645465 MPEP § 2143(I)(E).
Response to Applicant’s Remarks 05December2025:
Applicant has not addressed this rejection in their response filed 05December2025.
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.
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/REBECCA STEPHENS/Examiner, Art Unit 1663
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
1 See Result 4 in the ABSS sequence search result in parent application 17212665 dated 03August2022 entitled “20220802_154906_us-17-212-665-73.rnpbm”.
2 PENNELL et al. at ¶¶6-7 on page 1, ¶¶14-15 on page 2, ¶23 on page 3-4, ¶¶32-35 on page 5, ¶¶41 on page 6 ¶61 on page 9, ¶90 on page 13, Example 4 on page 14, and the claims on pages 61-62.
3 PENNELL et al. at claims 1, 3-4, 8, 11-20 at page 62 as well as Example 4 at page 14.
4 PENNELL et al. at ¶¶57, 61 at page 9.
5 PENNELL et al. at ¶90 on page 13.
6 PENNELL et al. at ¶¶32-35 on page 5.
7 LIPPMAN et al. at lines 21-30 on page 67, row 1 at the table on page 32.
8 See BOMMERT et al. listed within the alignment herein and see also the Supplemental Table 4 of BOMMERT et al.
9 See the ABSS sequence search result entitled “20220802_154858_us-17-212-665-74.rup” dated 03August2022 in the file wrapper for parent application 17212665.
10 See this specification at lines 23-25 on page 19.
11 LIPPMAN et al. at lines 12-14 on page 69, row 1 at the table on page 32,
12 Note the election of 477 (recited in claim 12) and election of spacer sequence SEQ ID NO: 79 (recited in claims 2, 5, 15, 19).
13 See BOMMERT et al. at page 336 (including Table 1) as well as pages 334-336 in general.
14 See BOMMERT et al. listed within the alignment herein and see also the Supplemental Table 4 of BOMMERT et al.
15 See the prosecution history for co-pending application 18645465 (Attny Dkt. No. 1499.26CT, published as US20240279640A1).
16 MASQUNA 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) who demonstrate the use of site saturation mutagenesis (and commercial kits therefor) to identify protein variants with a particular functional effect (there, gain-of-function mutants) whereby 39 amino acid locations were systematically mutated with every one of the other 19 standard amino acid residues (741 mutations) to identify those substitution mutations that increase protein::protein interactions.
Prosecution Insights