CTNF 18/697,521 CTNF 95743 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Restriction Requirement 08-25-01 AIA Applicant’s election without traverse of Group I drawn to claims 1-13 in the reply filed on 03/02/2026 is acknowledged. Claim Status Claims 1-16, 18-26, 28-31 and 35-36 are pending. Claims 14-16, 18-26, 28-31 and 35-36 are withdrawn from consideration for being drawn to non-elected inventions. Claims 1-13 are examined on the merits. Claim Objections Claim 6 is objected to because of the following informalities: the claim recites “wherein said increase in grain yield is an increase in at least one of grain number and/or thousand grain weight”. The use of “one of” in this recitation appears unnecessary and awkward, in order to improve claim syntax the Examiner suggests removing “one of” from the second line of the claim. Appropriate correction is requested. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-8 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The invention of claim 1 is directed to a product of nature without significantly more. The claim recites “A wheat plant having a reduced level of EOD1 (Enhancer of DA1) gene expression and/or reduced activity of the EOD1 polypeptide compared to a wild type or a control plant.” The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not include any additional elements and the broadly claimed genus of wheat plants includes those that are naturally occurring. The claim includes the statement “a reduced level of EOD1 (ENHANCER OF DA1) gene expression and/or reduced activity of the EOD1 polypeptide compared to a wild type of control plant”, this encompasses the natural variation in expression or activity of EOD1 within a population at a given time. The art with respect to EOD1 expression and activity does not describe the exact mechanisms regulating EOD1 expression at all times but does describe interactions between the E3 ligases DA1, DA2 and EOD1 in a variety of plant species. Specifically, Li, states that DA1 can cleave and destabilize EOD1 (which is also known as Big Brother, see Li, Page 438, First line of Last Paragraph) indicating that in plants with greater levels of DA1, EOD1 activity can be reduced by cleavage (Li, Page 441, Last paragraph; Li )(Li, Annual review of plant biology 70.1 (2019): 435-463). Interestingly this peptidase activity of DA1 is activated by monoubiquitination in multiple sites on DA1 by EOD1 (Li, Page 441, Last Paragraph). Given that the claim is drawn to any level of reduced activity or expression of EOD1 in any wheat plant as compared to a wild type or a control plant and that EOD1 activity levels are known to be reduced through cleavage by DA1 peptidase activity, the claimed wheat plant has a naturally occurring counterpart. Specifically, a naturally occurring field comprising a plurality of wheat plants in which slightly different concentrations of EOD1 and DA1 polypeptides results in a greater rate of cleavage of the EOD1 polypeptide in one plant compared to any other. This would result in a naturally occurring wheat plant having reduced EOD1 activity as to a compared to a wild type plant. Given that claim 1 does not provide significantly more than a naturally occurring wheat plant, the claim is rejected as being drawn to a judicial exception without substantially more. Claim 2 is drawn to the plant of claim 1, wherein the EOD1 polypeptide has at least 80% sequence identity to any one of SEQ ID NOs: 1,4, or 7. The only limitation that this claim adds to the scope of claim 1 is the provision that the EOD1 protein have a sequence which is at least 80% identical to a reference sequence of SEQ ID NO: 1, 4 or 7. This limitation does not amount to significantly more than the product of nature because EOD1 sequences from wheat plants, including Einkorn wheat ( Triticum urartu ) having greater than 80% sequence identity to SEQ ID NO: 1 are naturally occurring, see E3 ubiquitin ligase BIG BROTHER [Triticum Urartu], which discloses a sequence having 99.17% identity and 95% query coverage of reference sequence SEQ ID NO: 1 (“E3 Ubiquitin Ligase BIG BROTHER [Triticum Urartu] - Protein - NCBI.” Nih.gov, NCBI, 20 Mar. 2015). Given that claim 2 does not provide significantly more than the plant of claim 1, this plant is naturally occurring and is rejected as being drawn to a judicial exception without substantially more. Claim 3 is drawn to the plant of claim 1, wherein the EOD1 nucleic acid has at least 80% sequence identity to any one of SEQ ID NOs: 3, 6, 9, 2, 5 or 8. The only limitation that this claim adds to the scope of claim 1 is the provision that the EOD1 nucleic acid have a sequence which is at least 80% identical to a reference sequence of SEQ ID NO: 3, 6, 9, 2, 5 or 8. This limitation does not amount to significantly more than the product of nature because EOD1 sequences from wheat plants, including bread wheat ( Triticum aestivum ) having greater than 80% sequence identity to SEQ ID NO: 2 are naturally occurring, see Triticum aestivum cDNA, which discloses a sequence having 100% sequence to the sequence of instant SEQ ID NO: 2 (“Triticum Aestivum CDNA, Clone: WT004_I12, Cultivar: Chinese Spring - Nucleotide - NCBI.” Nih.gov , NCBI, 25 June 2009). Given that claim 3 does not provide significantly more than the plant of claim 1, this plant is naturally occurring and is rejected as being drawn to a judicial exception without substantially more. Claims 4-6 are drawn to the plant of claim 1 having increased yield compared to a wild type of control plant (Claim 4), where the increased yield is grain yield (Claim 5) and wherein said increase in grain yield is an increase in grain number or thousand grain weight (Claim 6). These limitations do not add significantly more to the product of nature of claim 1, see 101 analysis above. This is because the claim is not drawn to an requisite degree of increase in yield and Li discloses the role of EOD1 in negatively regulating seed size and correspondingly, seed weight, noting that eod1 mutants have large seeds and organs (Li, Paragraph spanning pages 438 – 441). Therefore, in the example described in the 101 analysis with respect to claim 1 above, the wheat plant in the field having reduced activity of EOD1 due to the protease activity of DA1 would have increased seed size and therefore would also have increased thousand grain weight as compared to the other wild type wheat plant having slightly higher EOD1 activity. Given that claims 4-6 do not provide significantly more than the plant of claim 1, these plants are naturally occurring and are rejected as being drawn to a judicial exception without substantially more. Claims 7-8 are drawn to the plant of claim 1 comprising at least one mutation in at least one nucleic acid sequence encoding the EOD1 polypeptide or at least one mutation in the promoter of at least one of the EOD1 genes (Claim 7), where the mutation is an insertion, deletion and/or a substitution (Claim 8) and where the mutation is a loss of function or partial loss of function mutation (Claim 9). These limitations do not add significantly more to the product of nature of claim 1, see 101 analysis above. This is because there is no reference state provided in the claim, as such the claim is interpreted to refer to a wheat plant which comprises and EOD1 protein or an EOD1 gene which comprise a mutation from any reference state including ancestral genes or homoeologs. In the instant case, Applicant provides the sequences of instant SEQ ID NOs: 3, 6 and 9 which are drawn to the three homoeologs of EOD1 in wheat (Instant Specification, Page 29, Paragraphs 0108, 0111 and 0114). Alignment of SEQ ID NO: 6 to SEQ ID NO: 3 shows that these sequences share a high percentage of sequence identity, they share 4406/4934 identities, however there are 262 gaps in the alignment as well as mismatches. These residues which result in lack of identity appear to be due to the presence of mutations in the sequences that cause them to differ from each other and from a shared common ancestor. As such it appears that wild type wheat plants comprise at least one mutation in at least one nucleic acid sequence encoding the EOD1 polypeptide as compared to the other endogenous wild type EOD1 genes. As such claims 7-8 are rejected as drawn to a judicial exception without substantially more. Claim 13 is drawn to a plant cell, plant part or seed of the wheat plant according to claim 1. The only limitation that this claim adds to the scope of claim 1 is to include plant parts and plant seeds from the plant of claim 1. This limitation does not amount to significantly more than the product of nature because the plants of claim 1 are naturally occurring, see 101 analysis above with respect to claim 1. As such these parts of that plant would also be naturally occurring. Given that claim 13 does not provide significantly more than the plant of claim 1, this plant is naturally occurring and is rejected as being drawn to a judicial exception without substantially more. In order to promote compact prosecution the Examiner notes that even if the plant of claim 1 was required to have a specific non-naturally occurring mutation, modification or other feature, if claim 1 does not recite that the mutation or other modification was homozygous and claim 13 is not amended to recite that the seed comprise this non-naturally occurring element, then, claim 13 would still read on naturally occurring seeds because given Mendelian Inheritance a hybrid parent when self-crossed or crossed to another non-homozygous plant will produce progeny not comprising the modification. Claim Rejections - 35 USC § 112 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 3, 7-10 and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. The rejection includes dependent claims. Claim 3 recites the limitation “The wheat plant of claim 1, wherein the EOD1 nucleic acid comprises a nucleic acid sequence selected from” in the first two lines of the claim. There is insufficient antecedent basis for this limitation in the claim because claim 1 while referring to an EOD1 gene does not refer to any EOD1 nucleic acids. Claim 12 recites “the wheat plant of claim 7, wherein the EOD1 promoter comprises the nucleic acid sequence of SEQ ID NOs: 10 to 12”. First, it is not clear how the promoter of claim 7 can comprise all three of the sequences claimed in claim 12. Should these sequenced by combined end to end, should this be interpreted to be a group of alternatives from which one member should be chosen or is there some other meaning? Second it is unclear if the promoter sequences recited in claim 12 are those before or after the mutation. As such the scope of claim 12 is not clear and it is rejected as indefinite. Claim Rejections - 35 USC § 112 (Written Description) 07-30-01 AIA 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. 07-31-01 Claims 1-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement . The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id. Independent claim 1 is broad in the following aspects: The claim is drawn to any wheat plant. The claim is drawn to any level of reduction in activity of any EOD1 sequence, endogenous, exogenous, modified or not or to any level of reduction in expression of any EOD1 gene as compared to a control plant. The dependent claims add additional limitations EOD1 polypeptides having at least 80% sequence identity to SEQ ID NOs: 1,4 or 7 (Claim 2) EOD1 nucleic acid sequences having at least 80% sequence identity to instant SEQ ID NOs: 3, 6, 9, 2, 5 or 8 (Claim 3). Wheat plants which comprise increased yield, grain yield, and increased grain number and/or thousand grain weight (Claims 4, 5 and 6, respectively). Wheat plants which comprise at least one mutation in the promoter or the coding sequence of the EOD1 gene, where these mutations are an insertion, deletion and/or substitution, where the mutations confer a loss of function or partial loss of function and where the mutations are selected from two specific substitutions corresponding to specific positions in the reference sequences of SEQ ID NO: 3 and 9 (Claims, 7, 8, 9 and 10, respectively). Wheat plants comprising a silencing construct that reduces or abolishes EOD1 nucleic acid expression and/or reduces or abolishes the activity of an EOD1 promoter (Claim 11). Wheat plants comprising in a promoter having the sequence of SEQ ID NOs: 10-12 (Claim 12). While these additional limitations appear to narrow down the scope of the independent claim they remain drawn to broad subject matter. For example, while claim 10 limits claim 1 to plants comprising a mutation in one of two specific positions in two reference sequences, the claim is not limited to those exact sequences and remains drawn to plants having any EOD1 sequences whatsoever as long as they have the corresponding mutations at those positions. Given the breadth and variability of the claimed sequences even with this more narrow scope it is not clear that these mutations in all EOD1 sequences would produce reduced level of EOD1 expression or EOD1 activity. In contrast, Applicant describes identifying three homoeologous EOD1 genes from the Chinese Spring survey sequence and reference genome (Specification, Page 31, Paragraph 0133). Then applicant describes EMS mutagenesis of wheat seeds from which plants comprising point mutations in the three homoeologous genes which resulted in STOP codons or amino acid changes were selected (Specification, Pages 31-32, Paragraph 136). While, applicant provides this description as noted below, applicant only describes one nucleic acid substitution mutation which does not produce an amino-acid-change in two of the three homoeologs. The two mutant alleles that were identified had the following characteristics: The first, A1, was a mutation in the Chinese Spring EOD1 A01 homoeolog (SEQ ID NO: 3 with a coding sequence of SEQ ID NO: 2) which was a G-A mutation that did not produce a change in amino acid but did effect a splice site (Specification, Page 32, Paragraph 0137, Table 2; Specification, Page 29, Paragraphs 0107-0108). The second, D3, was a mutation in the Chinese Spring EOD1 D01 homoeolog (SEQ ID NO: 9 with a coding sequence of SEQ ID NO: 8) which was a G-A mutation that did not produce a change in amino acid but did effect a splice site (Specification, Page 32, Paragraph 0137, Table 2; Specification, Page 29, Paragraphs 0113-0114). Applicant, describes identifying eod1 mutant plants and describes a breeding scheme using these plants (Specification, Paragraphs 0140-0141). This breeding scheme involved identifying mutant plants by sequencing. The plants sequenced were M3 plants. M2 plants were produced by self-crossing plants grown from the mutagenized seeds, M3 plants were harvested from the M2 plants, although applicant does not describe if the M2 plants were self-crossed or outcrossed to produce the M3 plants (Specification, Page 31, Paragraph 0136; Specification, Page 33, Paragraph 0140). After sequencing to confirm the presence of the identified eod1 mutation and to determine heterozygosity the breeding scheme used the following steps (Specification, Page 33, Paragraph 0141): An M3 plant containing mutation A1 was crossed to an M3 plant containing mutation D3. F1 progeny plants from this cross were selected that were heterozygous for mutation A1 and mutation D3. The selected F1 plants were intercrossed. F2 progeny were selected that were heterozygous for both mutations A1 and D3. The selected F2 progeny were backcrossed to wild-type plants of the same cultivar for two generations with selection for double heterozygous plants in each generation. After backcrossing the double heterozygous plants were self-crossed. From the progeny of this self -cross the following three homozygous genotypes were selected: Homozygous A1 and homozygous D3 mutant*. Homozygous A1 mutant. Homozygous D3 mutant. *Importantly even the double homozygous mutant retains two wild-type copies of EOD1 on the B genome. Applicant describes all homozygous genotypes occurring at a frequency of 1/16, however applicant does not describe any other mutations that may have been linked to the mutations they were selecting for or may have been carried through the steps of this breeding scheme (Specification, Page 33, Paragraph 0141). This is important given the nature of EMS mutagenesis which produces non-targeted mutations at varying rates depending on specific treatment conditions including the type of plant being mutagenized and the length of treatment (Chen, Page 2, Paragraph Spanning Columns 1-2)(Chen, Frontiers in Plant Science 13 (2023): 1052569.). Applicant then describes yield trials of the mutants where the following four genotypes were tested; wild type for all alleles (EOD1 (-/-/-); eod1 mutant homozygous for A1 and D3 alleles (EOD1 (A1/-/D3); eod1 mutant homozygous for A1 alleles (EOD1 (A1/-/-); and eod1 mutant homozygous for D3 alleles (EOD1 (-/-/D3) (Specification, Page 34, Table 3; Specification, Page 35, Paragraph 0151). Importantly, only two of the three genotypes tested showed differences in yield as compared to the wild type plants and only one showed increases across all of the testing locations. Applicant summarizes these findings, stating that “of the four different genotypes tested, one genotype (EOD1 (A1/-/D3) showed a significant yield increase across all 10 testing locations” (Specification, Page 35, Paragraph 0151). This increase in yield is described as resulting from an increase of thousand grain weight (TGW) (Specification, Page 35, Paragraph 0152; Specification Page 35, Final Entry of Table 4). While Applicant describes one other genotype as showing increased yield (EOD1 (-/-/D3), this yield was not statistically significant. Although, this genotype did demonstrate a statistically significant increase in grain weight (TKW) which appears to mean thousand kernel weight although the specification does not provide a definition for this acronym (Specification, Page 35, Paragraph 0153). This description is limited in comparison to the scope of the claims. Certain aspects of Applicant’s description which are limited in comparison to the claim scope are summarized as follows: Applicant only describes three wild-type endogenous wheat EOD1genes and proteins. The EOD1 sequences described in the specification are the exact sequences of SEQ ID NOs: 3,6 and 9. Applicant provides no assessment of mutations in SEQ ID NO: 6 which corresponds to the EOD1 homoeolog from the B genome. Applicant provides no assessment of the activity of the wild type or mutant EOD1 proteins, instead a yield phenotype is assessed. Importantly, there is no complementation or other assay which demonstrates that this phenotype is due to the described mutations in EOD1 and not some other EMS or other mutation. Applicant provides no assessment of the expression of the mutant or wild type EOD1 genes. Applicant does not describe a relationship between any mutations (including those in the promoter of the EOD1 genes) and reduced expression of EOD1. Nor does applicant provide a correlation between expression of these genes and the phenotypes claimed in claims 4-6. Applicant does not make clear what degree of reduction differentiates the expression from that of a wild-type or control plant which would exhibit natural variation and therefore even claim 11 which requires a specific silencing construct does not limit the independent claim to scope having been adequately described because the amount of reduction in expression of EOD1 as compared to a control plant is not clear. One aspect of Applicant’s description of the two eod1 mutants which show yield related phenotypes and their relationship to the claimed subject matter is summarized and addressed below: In the examples of eod1 mutants which show yield related phenotypes, applicant only describes homozygous mutants and the only mutant which showed a significant increase in yield was a double homozygous mutation. In contrast, Applicant’s most narrow claim appears to be claim 10. Claim 10 does not require double homozygous mutations instead it only requires a single a G to A substitution corresponding to position 3873 of SEQ ID NO: 3 or a G to A substitution corresponding to position 2992 of SEQ ID NO: 9 in any EOD1 gene in wheat as long as this mutation produces a partial loss of function and the activity or expression of EOD1 is reduced compared to a wild type plant. While claim 10 does not require the plant to have a yield related phenotype, it does require the activity and or expression of EOD1 to be reduced and for there to be a partial loss of function mutation. It does not appear that applicant’s specification describes either of these. As such it does not appear that Applicant has sufficiently described at least the following necessary structural features: The features that must be retained by any sequence to be the claimed EOD sequence. The features that must be retained or modified in order to produce the claimed yield related phenotypes. The features that must be retained or modified in order to reduce expression of the claimed genus of EOD1 genes. The degree to which EOD1 expression must be reduced in order to differentiate the claimed plants from wild type plants and their inherent variation in expression of EOD1. Additionally, the state of the art at the earliest effective filing date of the instant application was such that while some of the genetic and enzymatic interactions of EOD1 were known any modification, environmental input, or any other factor which would influence EOD1 activity or expression was not known, nor was the regulatory network(s) controlling expression of EOD1 known such that it could be readily predicted if a modification or mutation would result in the claimed reduction of expression ((Li, Annual review of plant biology 70.1 (2019): 435-463). The analysis will now turn to the second element of the court’s decision in Eli Lilly; namely, the description of a representative number of species. The genus of wheat plants of the independent claim is remarkably large in size and even the plants of the dependent claims remain broad. Given the virtually infinite structural variable associated with these embodiments, the claims read on an extremely broad and highly diverse structures. Thus, in view of the analysis presented above, a skilled artisan would appreciate that the claims are directed to extremely broad and highly diverge genus of plants that are required to have the specific function of reduced activity and/or expression of EOD1 and in some claims certain yield related phenotypes. In contrast, as described above, Applicant has only described two specific mutant wheat plants having a yield related phenotype, has not described any wheat plants having reduced activity of EOD1 nor has applicant described any wheat plants having reduced expression of EOD1. Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed and claims 1-13 are rejected as lacking adequate written description. Claim Rejections - 35 USC § 112 (Enablement) 07-31-02 AIA Claim s 1-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the enablement requirement . The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Applicant claims wheat plants comprising reduced activity and/or expression of EOD1. Independent claim 1 is broad in the following aspects: The claim is drawn to any wheat plant. The claim is drawn to any level of reduction in activity of any EOD1 sequence, endogenous, exogenous, modified or not or to any level of reduction in expression of any EOD1 gene as compared to a control plant. The dependent claims add additional limitations EOD1 polypeptides having at least 80% sequence identity to SEQ ID NOs: 1,4 or 7 (Claim 2) EOD1 nucleic acid sequences having at least 80% sequence identity to instant SEQ ID NOs: 3, 6, 9, 2, 5 or 8 (Claim 3). Wheat plants which comprise increased yield, grain yield, and increased grain number and/or thousand grain weight (Claims 4, 5 and 6, respectively). Wheat plants which comprise at least one mutation in the promoter or the coding sequence of the EOD1 gene, where these mutations are an insertion, deletion and/or substitution, where the mutations confer a loss of function or partial loss of function and where the mutations are selected from two specific substitutions corresponding to specific positions in the reference sequences of SEQ ID NO: 3 and 9 (Claims, 7, 8, 9 and 10, respectively). Wheat plants comprising a silencing construct that reduces or abolishes EOD1 nucleic acid expression and/or reduces or abolishes the activity of an EOD1 promoter (Claim 11). Wheat plants comprising in a promoter having the sequence of SEQ ID NOs: 10-12 (Claim 12). While these additional limitations appear to narrow down the scope of the independent claim they remain drawn to broad subject matter. For example, while claim 10 limits claim 1 to plants comprising a mutation in one of two specific positions in two reference sequences, the claim is not limited to those exact sequences and remains drawn to plants having any EOD1 sequences whatsoever as long as they have the corresponding mutations at those positions. Given the breadth and variability of the claimed sequences even with this more narrow scope it is not clear that these mutations in all EOD1 sequences would produce reduced level of EOD1 expression or EOD1 activity. Applicant provides the following enabled guidance. Applicant provides guidance on identifying three homoeologous EOD1 genes from the Chinese Spring survey sequence and reference genome (Specification, Page 31, Paragraph 0133). Then applicant provides guidance on EMS mutagenesis of wheat seeds from which plants comprising point mutations in the three homoeologous genes which resulted in STOP codons or amino acid changes were selected, although as noted below, in the examples applicant only provides guidance on a single nucleic acid substitution mutation in two out of the three homoeologous genes and neither of these nucleic acid substitutions produces an amino acid change (Specification, Pages 31-32, Paragraph 136). The two mutant alleles that were identified had the following characteristics: The first, A1, was a mutation in the Chinese Spring EOD1 A01 homoeolog (SEQ ID NO: 3 with a coding sequence of SEQ ID NO: 2) which was a G-A mutation that did not produce a change in amino acid but did effect a splice site (Specification, Page 32, Paragraph 0137, Table 2; Specification, Page 29, Paragraphs 0107-0108). The second, D3, was a mutation in the Chinese Spring EOD1 D01 homoeolog (SEQ ID NO: 9 with a coding sequence of SEQ ID NO: 8) which was a G-A mutation that did not produce a change in amino acid but did effect a splice site (Specification, Page 32, Paragraph 0137, Table 2; Specification, Page 29, Paragraphs 0113-0114). Applicant, provides guidance on identifying eod1 mutant plants and includes a breeding scheme using these plants (Specification, Paragraphs 0140-0141). This breeding scheme involved identifying mutant plants by sequencing. The plants sequenced were M3 plants. M2 plants were produced by self-crossing plants grown from the mutagenized seeds, M3 plants were harvested from the M2 plants, although applicant does not describe if the M2 plants were self-crossed or outcrossed to produce the M3 plants (Specification, Page 31, Paragraph 0136; Specification, Page 33, Paragraph 0140). After sequencing to confirm the presence of the identified eod1 mutation and to determine heterozygosity the breeding scheme used the following steps (Specification, Page 33, Paragraph 0141): An M3 plant containing mutation A1 was crossed to an M3 plant containing mutation D3. F1 progeny plants from this cross were selected that were heterozygous for mutation A1 and mutation D3. The selected F1 plants were intercrossed. F2 progeny were selected that were heterozygous for both mutations A1 and D3. The selected F2 progeny were backcrossed to wild-type plants of the same cultivar for two generations with selection for double heterozygous plants in each generation. After backcrossing the double heterozygous plants were self-crossed. From the progeny of this self -cross the following three homozygous genotypes were selected: Homozygous A1 and homozygous D3 mutant*. Homozygous A1 mutant. Homozygous D3 mutant. *Importantly even the double homozygous mutant retains two wild-type copies of EOD1 on the B genome. Applicant notes that all homozygous genotypes occurring at a frequency of 1/16, however applicant does not provide guidance on other mutations that may have been linked to the mutations they were selecting for or may have been carried through the steps of this breeding scheme (Specification, Page 33, Paragraph 0141). This is important given the nature of EMS mutagenesis which produces non-targeted mutations at varying rates depending on specific treatment conditions including the type of plant being mutagenized and the length of the treatment time (Chen, Page 2, Paragraph Spanning Columns 1-2)(Chen, Frontiers in Plant Science 13 (2023): 1052569.). Applicant provides guidance on yield trials of the mutants where the following four genotypes were tested; wild type for all alleles (EOD1 (-/-/-); eod1 mutant homozygous for A1 and D3 alleles (EOD1 (A1/-/D3); eod1 mutant homozygous for A1 alleles (EOD1 (A1/-/-); and eod1 mutant homozygous for D3 alleles (EOD1 (-/-/D3) (Specification, Page 34, Table 3; Specification, Page 35, Paragraph 0151). Importantly, only two of the three genotypes tested showed differences in yield as compared to the wild type plants and only one showed increases across all of the testing locations. Applicant summarizes these findings, stating that “of the four different genotypes tested, one genotype (EOD1 (A1/-/D3) showed a significant yield increase across all 10 testing locations” (Specification, Page 35, Paragraph 0151). This increase in yield is described as resulting from an increase of thousand grain weight (TGW) (Specification, Page 35, Paragraph 0152; Specification Page 35, Final Entry of Table 4). While Applicant states that one other genotype as showing increased yield (EOD1 (-/-/D3), this yield was not statistically significant. Although, this genotype did demonstrate a statistically significant increase in grain weight (TKW) which appears to mean thousand kernel weight although the specification does not provide a definition for this acronym (Specification, Page 35, Paragraph 0153). This guidance is limited in comparison to the scope of the claims. Certain aspects of Applicant’s guidance which are limited in comparison to the claim scope are summarized as follows: Applicant only provides guidance on three wild-type endogenous wheat EOD1genes and proteins. The EOD1 sequences of the specification are the exact sequences of SEQ ID NOs: 3,6 and 9. Applicant provides no guidance on mutations in SEQ ID NO: 6 which corresponds to the EOD1 homoeolog from the B genome. Applicant provides no guidance on the activity of the wild type or mutant EOD1 proteins, instead a yield phenotype is assessed. Importantly, there is no complementation or other assay which demonstrates that this phenotype is due to the described mutations in EOD1 and not some other EMS or other mutation. Applicant provides no guidance on the expression of the mutant or wild type EOD1 genes. Applicant does not describe a relationship between any mutations (including those in the promoter of the EOD1 genes) and reduced expression of EOD1. Nor does applicant provide a correlation between expression of these genes and the phenotypes claimed in claims 4-6. Applicant does not make clear what degree of reduction differentiates the expression from that of a wild-type or control plant which would exhibit natural variation and therefore even claim 11 which requires a specific silencing construct does not limit the independent claim to scope having been adequately described because the amount of reduction in expression of EOD1 as compared to a control plant is not clear. One aspect of Applicant’s guidance drawn to the two eod1 mutants which show yield related phenotypes and their relationship to the claimed subject matter is summarized and addressed below: In the examples of eod1 mutants which show yield related phenotypes, applicant only provides guidance on homozygous mutants and the only mutant which showed a significant increase in yield was a double homozygous mutation. In contrast, Applicant’s most narrow claim appears to be claim 10. Claim 10 does not require double homozygous mutations instead it only requires a single a G to A substitution corresponding to position 3873 of SEQ ID NO: 3 or a G to A substitution corresponding to position 2992 of SEQ ID NO: 9 in any EOD1 gene in wheat as long as this mutation produces a partial loss of function and the activity or expression of EOD1 is reduced compared to a wild type plant. While claim 10 does not require the plant to have a yield related phenotype, it does require the activity and or expression of EOD1 to be reduced and for there to be a partial loss of function mutation. It does not appear that applicant’s specification provides enabled guidance on either of these. As such it does not appear that Applicant has provided sufficient enabled guidance of at least the following structural features which are necessary to make and use the claimed invention without undue experimentation: The features that must be retained by any sequence to be the claimed EOD sequence. The features that must be retained or modified in order to produce the claimed yield related phenotypes. The features that must be retained or modified in order to reduce expression of the claimed genus of EOD1 genes. The degree to which EOD1 expression must be reduced in order to differentiate the claimed plants from wild type plants and their inherent variation in expression of EOD1. Therefore, one of ordinary skill in the art would be unable to make and use the claimed wheat plants without undue experimentation, i.e., it would be necessary use trial and error experimentation to at least unravel the gene regulatory networks regulating expression of EOD1, determine how any mutation in the promoter of EOD1 relates to expression of that gene, determine the scope of the activity of EOD1 and map the relationship between any mutation and that function with the exception of the two modifications to which applicant has provided enabled guidance. Further the ordinary artisan would be required to do all of this analysis in a genus of EOD1 sequences which include any sequence having that name and in more limited aspects any sequence having at least 80% sequence identity to SEQ ID NOs: 1,4, 7, 3, 6, 9, 2, 5, 8, 10 or 12. The prior art does not provide resolution for the lack of guidance provided by Applicant. Specifically, there is insufficient teaching in the art for the ordinary artisan to be able to determine if any environmental input, genetic modification or any other condition or action would reduce EOD1 expression or activity. Therefore, the specification fails to provide sufficient enabled guidance such that a skilled artisan would be able to make and use the full scope of the claimed invention at the time of filing. The lack of predictability in the art and the lack of guidance provided by Applicant would not have enabled one of ordinary skill in the art to predictably make and use the full scope of the claimed invention without undue experimentation and therefore claims 1-13 are rejected as lacking enablement . Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 1, 4-9, 11 and 13 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Li, WO 2015/022192, Published February 19, 2015 . With respect to claim 1, Li discloses wheat plants having reduced expression or activity of EOD1 polypeptides, including plants wherein the expression or activity of the EOD1 polypeptide is reduced by introducing a mutation into the nucleotide sequence of the plant cell which encodes the EOD1 polypeptide or which regulates its expression (Li, Page 21, Lines 29-33; Li, Page 79, Claim 8; Li, Page 83, Claim 42). With respect to claim 4, Li discloses all of the limitations of claim 1, see above. Further, Li discloses that making these modifications in plants produces plants having increased yield (Li, Page 79, Claim 1; Li, Page 40, Lines 21-25). With respect to claim 5, Li discloses all of the limitations of claim 4, see above. Further, Li discloses that increased yield includes grain yield (Li, Page 79, Claim 1; Li, Page 40, Lines 21-25). With respect to claim 6, Li discloses all of the limitations of claim 5, see above. Further, Li discloses that increased grain yield can include increased seed/grain weight (Li, Page 79, Claim 1; Li, Page 40, Lines 21-25). Increasing seed weight would increase lead to increased thousand grain weight and therefore increased thousand grain weight is an implicit property of the plants of Li. With respect to claim 7, Li discloses all of the limitations of claim 1, see above. With respect to claim 8, Li discloses all of the limitations of claim 7, see above. Further, Li discloses that mutations include insertions, deletions and substitutions of one or more nucleotides (Li, Page 24, Lines 28-32). With respect to claim 9, Li discloses all of the limitations of claim 7, see above. Further, Li discloses that mutations may disrupt the function of the EOD1 polypeptide and that the mutations include knock-out mutations (Li, Page 24, Lines 8-10). With respect to claim 11, Li discloses all of the limitations of claim 1, see above. Further, Li discloses plants where the expression or activity of the EOD1 polypeptide is reduced by incorporating a heterologous nucleic acid which expresses a suppressor nucleic acid which reduces expression of the EOD1 polypeptide (Li, Page 79, Claim 9). This suppressor heterologous nucleic acid appears to be another term for silencing construct which the instant specification describes as “capable of suppressing specifically the expression of the endogenous EOD1 gene” (Instant Specification, Page 2, Paragraph 0009). With respect to claim 13, Li discloses all of the limitations of claim 1, see above. Further, Li discloses seed from the plants (Li, Page 81, Claim 24) . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Li in view of E3 Ubiquitin Ligase BIG BROTHER [Triticum Urartu] - Protein - NCBI. Nih.gov, NCBI, 20 Mar. 2015 . With respect to claim 2, Li teaches all of the limitations of claim 1, see anticipation rejection above. With respect to claim 2, Li does not teach an EOD1 sequence having at least 80% sequence identity to instant SEQ ID NO: 1, 4 or 7. With respect to claim 2, E3 Ubiquitin Ligase BIG BROTHER teaches a wheat EOD1 protein having 99.17% identity and 95% query coverage of reference sequence SEQ ID NO: 1 (E3 Ubiquitin Ligase BIG BROTHER). At the time of filing it would have been obvious to modify the wheat plant having reduced activity of EOD1 of Li in order to generate this mutation in the sequence encoding the EOD1 sequence of E3 Ubiquitin Ligase BIG BROTHER. This would have been obvious because the wheat plant of Li comprises a mutation in an EOD1 polypeptide and E3 Ubiquitin Ligase BIG BROTHER teaches a wheat EOD1 polypeptide. The ordinary artisan would have been motivated to modify this sequence in order to produce larger yields and superior grain from plants comprising the EOD1 sequence of E3 Ubiquitin Ligase BIG BROTHER. This would allow for the production of wheat plants with increased yields which are agronomically and economically valuable and would therefore have been motivating to the ordinary artisan. Therefore, claim 2, is rejected as obvious under Li in view of E3 Ubiquitin Ligase BIG BROTHER . 07-21-aia AIA Claim s 3 are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Triticum Aestivum CDNA, Clone: WT004_I12 , Cultivar: Chinese Spring - Nucleotide - NCBI. Nih.gov , NCBI, 25 June 2009 . With respect to claim 3, Li teaches all of the limitations of claim 1, see anticipation rejection above. With respect to claim 3, Li does not teach an EOD1 sequence having at least 80% sequence identity to instant SEQ ID NO: 3, 6, 9, 2, 5 or 8. With respect to claim 3, WT004_I12 teaches a wheat EOD1 gene having 100% sequence identity to reference sequence SEQ ID NO: 2 (WT004_I12). At the time of filing it would have been obvious to modify the wheat plant having reduced activity of EOD1 of Li in order to generate this mutation in the EOD1 sequence of WT004_I12. This would have been obvious because the wheat plant of Li comprises a mutation in an EOD1 gene and WT004_I12teaches a wheat EOD1gene. The ordinary artisan would have been motivated to modify this sequence in order to produce larger yields and superior grain from plants comprising the EOD1 sequence of WT004_I12. This would allow for the production of wheat plants with increased yields which are agronomically and economically valuable and would therefore have been motivating to the ordinary artisan. Therefore, claim 3, is rejected as obvious under Li in view of WT004_I12. Conclusion No claims are allowed. Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN JAMES SULLIVAN whose telephone number is (571)272-0561. The examiner can normally be reached 7:30 to 5:00. 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /BRIAN JAMES SULLIVAN/Examiner, Art Unit 1663 /Amjad Abraham/SPE, Art Unit 1663 Application/Control Number: 18/697,521 Page 2 Art Unit: 1663 Application/Control Number: 18/697,521 Page 3 Art Unit: 1663 Application/Control Number: 18/697,521 Page 4 Art Unit: 1663 Application/Control Number: 18/697,521 Page 5 Art Unit: 1663 Application/Control Number: 18/697,521 Page 6 Art Unit: 1663 Application/Control Number: 18/697,521 Page 7 Art Unit: 1663 Application/Control Number: 18/697,521 Page 8 Art Unit: 1663 Application/Control Number: 18/697,521 Page 9 Art Unit: 1663 Application/Control Number: 18/697,521 Page 10 Art Unit: 1663 Application/Control Number: 18/697,521 Page 11 Art Unit: 1663 Application/Control Number: 18/697,521 Page 12 Art Unit: 1663 Application/Control Number: 18/697,521 Page 13 Art Unit: 1663 Application/Control Number: 18/697,521 Page 14 Art Unit: 1663 Application/Control Number: 18/697,521 Page 15 Art Unit: 1663 Application/Control Number: 18/697,521 Page 16 Art Unit: 1663 Application/Control Number: 18/697,521 Page 17 Art Unit: 1663 Application/Control Number: 18/697,521 Page 18 Art Unit: 1663 Application/Control Number: 18/697,521 Page 19 Art Unit: 1663 Application/Control Number: 18/697,521 Page 20 Art Unit: 1663 Application/Control Number: 18/697,521 Page 21 Art Unit: 1663 Application/Control Number: 18/697,521 Page 22 Art Unit: 1663 Application/Control Number: 18/697,521 Page 23 Art Unit: 1663 Application/Control Number: 18/697,521 Page 25 Art Unit: 1663 Application/Control Number: 18/697,521 Page 26 Art Unit: 1663 Application/Control Number: 18/697,521 Page 27 Art Unit: 1663 Application/Control Number: 18/697,521 Page 28 Art Unit: 1663 Application/Control Number: 18/697,521 Page 29 Art Unit: 1663 Application/Control Number: 18/697,521 Page 30 Art Unit: 1663 Application/Control Number: 18/697,521 Page 31 Art Unit: 1663 Application/Control Number: 18/697,521 Page 32 Art Unit: 1663
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