METHODS AND COMPOSITIONS FOR IMPROVING RESISTANCE TO FUSARIUM HEAD BLIGHT

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 Final Action Dated 07January2026, Nonfinal Action Dated 08July2025 → ] Applicant's election with traverse of Group I and election without traverse of RPL3B-3, (wild type) SEQ ID NO: 78 and its associated SEQ ID NO: 77, as well as (mutant) amino acid sequence SEQ ID NO: 152 (corresponding to SEQ ID NO: 151), as well as SEQ ID NOs: 110 and 141 in the reply filed on 06May2025 is acknowledged. The traversal as to Group I is on the ground(s) that the subject matter of Groups I and II are so similar that it would not amount to an undue burden if the two were examined together (Remarks at the paragraph bridging pages 2 and 3). This is not found persuasive because, as evidenced of record, there are at least disparate anticipation considerations for Groups I and II in so far as “editing system” at Group II is considered a nuclease system such as CRISPR/Cas. To that end, what constitutes an “editing system” for the purposes of Group II is not relevant to present Group I and would need to be analyzed under 35 U.S.C. § 112(a) and (b). The requirement is still deemed proper and is therefore made FINAL. Claims 42, 45, 50, 51, 53, 75, 81, 83, 89, 91, and 94 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group of invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06May2025. Status of the Claims The claims filed 11August2026 are acknowledged and have been fully considered. Claims 2-4, 6-8, 10-16, 18-19, 21-22, 24-25, 27-31, 33-41, 43-44, 46-49, 50, 52, 54-74, 76-80, 82, 84-88, 90, 92-93, and 95-115 are canceled. Claims 1, 5, 9, 17, 20, 23, 26, 32, 42, 45, 51, 53, 75, 81, 83, 89, 91, and 94 remain pending. Claims 1, 17, 42, 75 are currently amended and claims 5, 9, 20, 23, 26, 32 were previously presented. Following the restriction requirement mailed 07March2025 and Applicant’s election dated 06May2023, claims 42, 45, 51, 53, 75, 81, 83, 89, 91, and 94 remain withdrawn as being directed toward a non-elected group and/or species (rejoinder currently being inappropriate). Claims 1, 5, 9, 17, 20, 23, 26, and 32 are examined on the merits herein. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) [US provisional 63328313 filed 07April2022] is acknowledged. Claims 1, 5, 9, 17, 20, 23, 26, and 32 maintain an effective filing date of 07April2022. Withdrawn Objections and/or Rejections Objections and/or rejections made of record in the nonfinal office action dated 08May2026 that are not otherwise discussed herein are withdrawn. In particular: RE ¶ 6: The rejection under 35 U.S.C. §§ 112(a) and/or 101 is withdrawn in view of both the claim amendments 11August2026 and the Declaration by Dr. Miller (hereinafter “Declaration2”) filed 11August2026. In particular, please note that claim 1 (to which all other rejected claims refer) is now amended to specify the six RPL3 genes present within hexaploid wheat at the first wherein clause and also now specifies that only one or two of those genes are mutated but no more (i.e., the second wherein clause excludes a complete knockout). Declaration2 confirms this meaning of claim 1 and further explains that: PNG media_image1.png 312 600 media_image1.png Greyscale Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 1, 5, 9, 17, 20, 23, 26, 32 REMAIN rejected under 35 U.S.C. 103 as being unpatentable over HARRIS et al. (US PAT. NO. 6855872 issued 15February2005) and DI et al. (“Expression of a truncated form of yeast ribosomal protein L3 in transgenic wheat improves resistance to Fusarium head blight.” 2010 Plant Science 178:374-380; of record IDS 17August2023) and BRAUER et al. (“Expression of a truncated form of yeast ribosomal protein L3 in transgenic wheat improves resistance to Fusarium head blight” 2020 MPMI 33(3):553-560) and LEE et al. (“Impaired Plastid Ribosomal Protein L3 Causes Albino Seedling Lethal Phenotype in Rice” 2019 J. Plant Biol. 62:419-428; of record PTO-892 08July2025). ↓Materially Copied from the Final 07January2026 and Nonfinal 08May2026, See Response to Applicant’s Remarks for New Content↓ The claims were amended 08December2025 to specify that the plant is a wheat plant and that “the mutation is an out-of-frame deletion and/or an out-of-frame insertion” (taken from claim 9). LEE et al. (formerly used in an anticipation rejection) is added to the list of cited reference here in view of the claim amendments. LEE et al., which regard rice plants, teach mutating (by base insertion and deletion) the endogenous Plastid Ribosomal Protein L3 (PRPL3) gene sequence of rice using CRISPR/Cas to obtain plants with PRPL3 knocked out. [relevant to claims 1, 5, 9, 23] To be clear, rice plants with PRPL3 knocked out are “seedling lethal”,1 meaning those mutant plants/parts have resultant “no detectable RPL3 polypeptide” as well as “reduced binding to a … mycotoxin” [relevant to claim 1] such as DON as well as “increased resistance to FHB”, and/or a “decreased amount of F. graminearum” and/or an ‘increased tolerance to DON” [relevant to claim 23]. Absent evidence to the contrary, and based on the highly conserved nature of RPL3 sequences2, the rice RPL3 gene sequence of LEE et al. is presumed to have at least “80% sequence identity to … SEQ ID NO: 78” and/or “and least 80% sequence identity to … SEQ ID NO: 110 or 141” and/or encode an amino acid sequence with “at least 80% sequence identity to … SEQ ID NO: 77”. [relevant to claim 20] ↓Materially Copied from the Nonfinal 08July2025, See Response to Applicant’s Remarks for New Content↓ HARRIS et al. is cited for teaching a wheat RPL3 amino acid sequence that has 100% sequence identity to this application’s SEQ ID NO: 77 (= SEQ ID NO: 16 of HARRIS et al.)3 and, therefore, making the RPL3 gene sequences that encode one such amino acid sequence obvious.4 For clarity of the record, please also note that SEQ ID NO: 78 of this application is an RPL3 genomic sequence and has at least 84% sequence identity to the RPL3 coding sequence SEQ ID NO: 13 of HARRIS et al.5 DI et al. is considered the primary reference and is cited for teaching transgenic (hexaploid) wheat plants and plant parts expressing both its endogenous RPL3 genes as well as a transgenic, mutant RPL3 sequence (referred to therein as “L3Δ”) which encodes a truncated RPL3 protein that only has the first 99 amino acids from the wild type wheat RPL3 protein (i.e., N’-1 … 99*).6 DI et al. teach that when wheat plants/parts express both its endogenous (wild type) RPL3 sequence as well as a truncated form of RPL3 (“L3Δ”), plants/seeds are protected from FHB and show reduced DON accumulation.7 For clarity of the record, this application’s (elected) mutant sequence SEQ ID NO: 151 encodes the amino acid sequence SEQ ID NO: 152 [see claim 32] and the sequence SEQ ID NO: 152 consists of the first 105 amino acids from the wild type wheat RPL3 protein (corresponding to amino acids 1-105 of SEQ ID NO: 16 from HARRIS et al.8). There is nothing of record to suggest that the 6 amino acid extension in SEQ ID NO: 152 (as compared to the “L3Δ” truncated RPL3 protein taught by DI et al.) has a material effect on the protein function. Therefore, the sequence SEQ ID NO: 152 (amino acids 1-105) of claim 32 is considered a range of amino acids that overlap with those of the “L3Δ” sequence taught by DI et al. (amino acids 1-99) and, absent evidence to the contrary (such as a showing of functional differences), the sequence SEQ ID NO: 152 is considered prima facie obvious in view of the “L3Δ” sequence taught by DI et al.9 DI et al. do not teach editing an endogenous RPL3 gene. BRAUER et al. is cited for teaching the use of CRISPR/Cas gene editing of an endogenous gene in wheat (there, the DON-induced gene referred to as “TaNFXL1”) to introduce deletion mutations and increase the wheat plant’s/part’s resistance to F. graminearum.10 Therefore, while BRAUER et al. do not regard RPL3 sequences; they nonetheless demonstrate successful use of CRISPR/Cas to edit an endogenous gene (including by deletion mutations) in wheat and regarding F. framinearum/FHB resistance. Without more information from Applicant, it is believed that a person with ordinary skill in the art at the time this application was filed (a “POSA”) would have been motivated to combine the prior art teachings and with a reasonable expectation of successfully arriving at the claimed subject matter. It is believed that a POSA would have been motivated to do so because it is/was desirable to obtain wheat plants/parts having increased resistance to F. graminearum (and FHB) and/or decreased accumulation of DON.11 Given the results by DI et al. when expressing both the endogenous RPL3 genes and a transgenic, truncated “L3Δ” RPL3 sequence within wheat plants/parts; a POSA would have viewed it as at least “obvious to try” to use a gene editing method like CRISPR/Cas to introduce mutations (e.g., deletion mutations) into at least one of the six RPL3 alleles (e.g., one of the three RPL3B alleles) to arrive at a truncated RPL3 protein similar in structure to DI et al.’s “L3Δ” (i.e., the sequence SEQ ID NO: 152 consisting of amino acids 1-105) and thereby obtain a wheat plant/part expressing both wild type endogenous RPL3 sequences as well as a mutant, truncated RPL3 sequence (which, per the results of DI et al., a POSA would reasonably expect to have increased protection from FHB and show reduced DON accumulation). MPEP § 2143(I)(E). To be clear, it is the Office’s position that the sequence particulars of claims 20 and 32 are taught (claim 20) or suggested (claim 32) by HARRIS et al. and DI et al., respectively. Response to Applicant’s Remarks 11August2026: Applicant asserts that the Utility rejection of record is contradictory to this obviousness rejection and that the Utility rejection of record evidences a lack of motivation to combine the cited references (bridge of pages 10-11). This argument is based on a misunderstanding of the issues. Prior to the claim amendments filed 11August2026, these claims encompassed both a partial and a complete knockout of RPL3. The recitation of a complete knockout of RPL3 was the foundation upon which the Utility issue was based. These claims no longer encompass a complete knockout of RPL3 (discussed above) and, therefore, only encompass a partial knockout of RPL3. This obviousness rejection was made (and is maintained) because these claims continue to encompass a partial knockout of RPL3. Applicant asserts that the cited references do not independently, or together, teach all of the elements of the claims (page 11 of the Remarks): PNG media_image2.png 206 539 media_image2.png Greyscale Applicant’s argument against the references individually is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Conclusion [Copied from Nonfinal 08May2026 → ] As a courtesy to Applicant and in the interest of preserving both temporal and monetary resources, please note that the Office does not currently see a path toward patentability for the examined claims. 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. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /REBECCA STEPHENS/Examiner, Art Unit 1663 /MATTHEW R KEOGH/Primary Examiner, Art Unit 1663 1 LEE et al. at the right column on page 422 to the left column on page 423, as well as figure 4 on page 423. 2 See FIG8A and 8B, as well as the description thereof, of HARRIS et al. (US Pat. No. US6855872 at column 4). 3 See Result 1 of the sequence search results file of record entitled “20250515_125153_us-18-296-392b-77.rai” as well as Result 2 therein for alignment to SEQ ID NO: 17 of HARRIS et al. See also FIGs 7 and 8 of HARRIS et al. as well as the descriptions thereof at column 4, lines 38-53. 4 MPEP § 2143 citing In re Kubin, 561 F.3d 1351 (Fed. Cir. 2009). 5 See Result 1 of the sequence search results file of record entitled “20250515_125107_us-18-296-392b-78.rni”. 6 DI et al. at the left column of page 379; see also figure 2 on page 377 showing sequence alignments to various RPL3 sequences. 7 DI et al. at the left column of page 379; see generally DI et al. at the Abstract, left column on page 375, right column on page 376-379. 8 See Result 3 of the sequence search results file of record entitled “20250515_125153_us-18-296-392b-152.rai”. 9 MPEP 2144.05(I). 10 BRAUER et al. at Abstract, left column on page 554, left column on page 555, left column on page 556. 11 As is discussed generally by at least HARRIS et al. and DI et al.