DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/02/2026 has been entered.
Information Disclosure Statement
Initialed and dated copy of Applicant’s information disclosure statement (IDS) filed on
01/02/2026 is attached to the instant Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Claims
The amendments received on 01/02/2026 have been entered. Claims 66, 69-70, 76, 78, 87-88, and 118-130 are pending.
Claims 66, 69-70, 76, 78, and 87 remain withdrawn for being directed to a non-elected invention(s).
Claims 88 and 118-130 are examined in this Office Action.
The text of those sections of Title 35, U.S. Code, not included in this action, can be found in a prior Office action.
Claim Rejections - 35 USC § 103
Claims 88 and 118-130 are rejected under 35 U.S.C. 103 as being unpatentable over Youssef (Youssef et al., 2017, Nature Genetics, Vol. 49(1), pp. 157-161; included on IDS dated 03/14/2023). All dependent claims are included in these rejections unless they include a limitation that overcomes the deficiencies of the parent claim.
Claim 88 recites “[a] guide nucleic acid that binds to a target site in a corn Short Internodes (SHI) transcription factor gene that encodes a SHI transcription factor, wherein the SHI transcription factor is a SIX-ROWED SPIKE 2 (VRS2) transcription factor, and wherein the target site encodes a sequence having at least 80% sequence identity to any one of the amino acid sequences of SEQ ID NOs:88-92”.
Youssef teaches the Six-rowed spike 2 (Vrs2), which encodes a SHORT INTERNODES (SHI) transcriptional regulator (i.e., a Short Internodes (SHI) transcription factor gene that encodes a SHI transcription factor, wherein the SHI transcription factor is a SIX-ROWED SPIKE 2 (VRS2) transcription factor) (Youssef, Abstract). Youssef teaches the SHI protein encoded by Vrs2 features two N-terminal zinc-finger-like motifs (CCCH) with a nuclear localization signal (KRRER) and the C-terminal SHI-family-specific IGGH domain (see sequence comparisons below) (Youssef, page 159, right column, last paragraph; Supplementary Figure 3).
Youssef teaches that based on the IGGH domain, 111 SHI-related proteins were identified, including 6 in the barley genome, 4 in Brachypodium distachyon, 6 in rice (Oryza sativa L.), 5 in Sorghum bicolor and 10 in maize (Zea mays L.) (i.e., a corn Short Internodes (SHI) transcription factor gene that encodes a SHI transcription factor) (Youssef, page 159, right column, last paragraph; Supplementary Figure 4).
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The alignment shows the double-CCCH motif (red stars), the nuclear localization signal (KRRER), the IGGH domain (isoleucineglycine-glycine-histidine sequence) (the recited motifs are in bold in the instant sequence below).
INSTANT SEQUENCE SEQ ID NO: 71(instant sequence SEQ ID NO: 88 in box):
[AltContent: rect]MAGFPLGGGSHTQSRDAPASSVPPVHPSDAASFLYAARAGAGLQLWQQQQQHPFYTSNIIRFSDDPPGPAPSLTGATSPSHRTRASGGSGGGGGVSCQDCGNQAKKDCVHQRCRTCCKSRGFACSTHVKSTWVSAAKRRERQQQLAALAASAGDTAAAAGPSRDPTKRPRARLSVVTPTTTSSGDQQMVTVAERFPREVSSEALFRCVRLGPVDRAEAEVAYQTTVSIGGHVFKGLLHDVGPRSLPAAGGGAAAAAIEYYFRHAADGSPPSTTGAAGEACGAGGVGNVVVSSAVVMDPYPTPGSYAAFLPGAPFFPGGHPRQ
Youssef teaches sequence A0A1I9RHG9_HORVU (UniProt) which shares 96.8% sequence identity with instant sequence SEQ ID NO: 88 (i.e., wherein the target site encodes a sequence having at least 80% sequence identity to SEQ ID NO: 88) (see sequence alignment below).
Qy 1 CQDCGNQAKKDCVHQRCRTCCKSRGFACSTH 31
|||||||||||| ||||||||||||||||||
Db 106 CQDCGNQAKKDCQHQRCRTCCKSRGFACSTH 136
It is noted that instant sequence SEQ ID NO: 71 also comprises instant sequences SEQ ID NO: 90 (100% sequence identity to instant sequence SEQ ID NO: 71; instant claim 123); SEQ ID NO: 91 (87.8% sequence identity to instant sequence SEQ ID NO: 71; instant claim 120); and SEQ ID NO: 92 (100% sequence identity to instant sequence SEQ ID NO: 71; instant claim 120).
Youssef teaches mutant barley plants carrying the vrs2.e allele, which comprises an X-ray induced mutation resulting in a single-base-pair deletion at nucleotide position 527 in the first exon resulting in a frameshift mutation (Youssef, page 159, right column, first paragraph; Supplementary Note Table 1).
Additionally, Youssef teaches mutants int-b.3 (deletion identical to that in vrs2.e allele), int-b.6 (a 13-bp deletion in exon 1), and HOR 19366 (a single-base-pair deletion at nucleotide position 504), all of which produce the same premature stop codon (see figure below). In the absence of evidence to the contrary, the deletions taught by Youssef, which introduce a premature stop codon, are capable of disrupting the binding of the SHI family transcription factor to DNA.
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It is noted that it is the position of this Office that any mutation introduced using any guide system in any gene location that disrupts the binding of DNA is rendered obvious by the teachings of Youssef. Although Youssef does not explicitly teach introducing a mutation using an editing system that comprises a guide nucleic acid, there is no way to distinguish a corn plant comprising a mutation introduced using an editing system that comprises a guide nucleic acid from a corn plant comprising a mutation introduced via X-ray, for example. As such, it would have been obvious to one of ordinary skill in the art to introduce a mutation in the location of the VRS2 gene as taught by Youssef to disrupt DNA binding.
At the time the instant application was filed, it would have been obvious and within the scope of one of ordinary skill in the art to utilize the known SHI transcription factor gene from barley as taught by Youssef, to identify a SHI transcription factor gene from maize which encodes the VRS2 transcription factor having at least 80% sequence identity to the amino acid of instant SEQ ID NO: 88, as taught by Youssef. Based on the teachings of Youssef, one of ordinary skill in the art would be motivated to mutate a maize VRS2 transcription factor gene knowing that the vrs2 mutants in barley produced premature stop codons. Thus, one of ordinary skill in the art would have a high expectation of success by following the teachings of Youssef.
The method of mutating an endogenous gene to disrupt DNA binding is a technique that was routine in the art at the time the application was filed, as taught by the cited reference and the state of the art in general.
In regard to claim 118, amino acid sequence A0A1I9RHG9_HORVU (UniProt) taught by Youssef, which shares 96.8% sequence identity with instant sequence SEQ ID NO: 88, is encoded by sequence KX601716.1 Hordeum vulgare mutant SHI (Vrs2) gene, vrs2.e allele, complete cds which shares 94% sequence identity with instant sequence SEQ ID NO: 75 (elected sequence; see alignment below) (i.e., wherein the target site comprises a sequence having at least 80% identity to the nucleotide sequence SEQ ID NO: 75).
Sequence ID: KX601716.1 aligned with instant sequence SEQ ID NO: 75
Query 15 CAGCTGCCAGGACTGCGGCAACCAGGCCAAGAAGGACTGCGTGCACCAGCGCTGCCGCAC 74
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Sbjct 1024 CAGCTGCCAGGACTGCGGCAACCAGGCCAAGAAGGACTGCCAGCACCAGCGCTGCCGCAC 1083
Query 75 CTGCTGCAAAAGCCGCGGCTTCGCCTGCAGCACCCACGTCAAGTCCACCTGGGT 128
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Sbjct 1084 CTGCTGCAAATCCCGGGGCTTCGCCTGCTCCACCCACGTCAAGTCCACCTGGGT 1137
Summary
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MEADOWS whose telephone number is (703)756-1430. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on 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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/CHRISTINA L MEADOWS/Examiner, Art Unit 1663
CHRISTINA MEADOWS
Examiner
Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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