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 .
Status of Claims
The amendments submitted on September 3rd, 2026, have been entered.
Claim 87 has been cancelled.
Claims 66-86 are pending in the application.
Claims 66-70, 77-78, and 80-86 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.
Examiner’s Note
Examiner notes that this is a second Final Office Action. Any inconvenience to the Applicant is regretted.
Applicant has requested that withdrawn claims 71-76 and 79 be rejoined. Examiner notes that these claims introduce unaddressed rejections, such as indefiniteness over the optional steps of claim 77. As such, these claims are not rejoined.
Examiner notes that claim 84 recites “[a] method of preparing a product of claim 83” instead of “[a] method of preparing the product of claim 83”.
Claim Rejections - 35 USC § 101
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.
Claim 83 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim recites a product produced from a plant of claim 66 and/or produced from a seed therefrom, wherein the product is a food product or beverage product.
Broadest Reasonable Interpretation
Claim 83 recites “a product produced from a plant of claim 66 and/or a seed therefrom, wherein the product is a food product or beverage product.” The Examiner has interpreted the claimed product as any food or beverage product produced from any plant or seed of the plant of claim 66. Claim 66 does not specify the type of plant and claim 83 does not specify that the plant or seed comprise the genetic modification of claim 66. Thus, this can be any number of natural products produced from a seed of the plant as the seed would not necessarily comprise the sequences or amino acid positions claimed in claim 66 after reproduction with another parent plant. This could be a product such as sap from a tree, which is a food product. Since claim 83 does not recite characteristics that amount to a difference between naturally-occurring products and the claimed product, the product produced from the plant and/or seed of the plant of claim 66 has been interpreted as a product as seen in nature.
Step 1: Whether the claim is to a statutory category
Under Step 1 of the subject matter eligibility test for products and processes, it must be determined if the claim is to a process, machine, manufacture or a composition of matter. In the instant case, claim 83 is directed to a composition of matter (food product). The claims are therefore directed to a statutory category, a product, and according to the broadest reasonable interpretation, it is also a natural product.
Step 2A: ‘Directed to a judicial exception’ analysis:
Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Markedly different characteristics can be expressed as the product's structure, function, and/or other properties. Non-limiting examples of characteristics that can determine the presence of a marked difference include biological or pharmacological functions or activities; chemical and physical properties; phenotype, including functional and structural characteristics; and structure and form, whether chemical, genetic, or physical.
The Examiner has interpreted the product of claim 83 as any product produced from any plant that can be a food or beverage product. This could be sap from a tree, as suggested above. It could be juice from a fruit grown from a seed of the plant of claim 66. A peanut grown from the plant grown from the seed of the plant of claim 66 (etc.). Furthermore, Applicant has not provided evidence of a markedly different characteristic between the instantly recited product and their naturally-occurring counterparts. As such, claim 83 recites a judicial exception.
Under Revised Step 2A, prong 1 of the analysis (determining the Judicial Exceptions), it must be determined if the claim is directed to a law of nature, a natural phenomenon (product of nature) or an abstract idea. In the instant case, the formulation is a naturally occurring product (product from a plant or seed). Because the products are the same as a product of nature, it falls within a judicial exception.
Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
Under Step 2A, prong 2 of the analysis, it must be determined whether the claim recites additional elements that integrate the judicial exception into a practical application. In the instant case, the claims fail to recite any additional elements that integrate the judicial into a practical application, and therefore the claims remain directed to a judicial exception invoking further analysis under step 2B.
Step 2B: ‘Significantly more’ analysis:
Under Step 2B, it must be determined if the claim recites additional elements that amount to significantly more than the judicial exception. In the instant case, claim 83 fails to recite any additional elements that amount to significantly more than the judicial exception since the claims are recited as product-by-process without reciting any structural features. Therefore, the claims as a whole do not amount to significantly more than the exception.
Therefore, claim 83 is directed to subject matter that is not patent-eligible and are, as a result, rejected under 35 U.S.C. 101.
Claim Rejections Under 35 USC § 112(b)
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.
Claims 66-70, 77-78, and 80-86 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. This is a new rejection necessitated by amendments to the claims.
Claim 66 recites a plant having a genetically modified gene encoding an atypical cinnamoyl-CoA dehydrogenase 2 (CAD2) polypeptide, wherein when expressed in the plant the polypeptide confers enhanced resistance to a Fusarium sp. when compared to a corresponding plant lacking the gene, wherein the polypeptide comprises amino acids having a sequence at least 90% identical to the amino acid sequence of any one or more of SEQ ID NOs 1 to 10, and wherein the polypeptide has one or more or all of; i) an alanine at a position corresponding to amino acid number 179 of SEQ ID NO:1, ii) a leucine at a position corresponding to amino acid number 180 of SEQ ID NO:1, iii) a phenylalanine at a position corresponding to amino acid number 181 of SEQ ID NO:1, and iv) a threonine at a position corresponding to amino acid number 182 of SEQ ID NO:1.
As taught in the instant disclosure, SEQ ID NO: 1 is the amino acid sequence of barley CAD2 biotrophic fungal pathogen resistance polypeptide with the positions corresponding to the specified amino acids within claim 66. SEQ ID NO: 2 is the amino acid sequence of a barley CAD2 polypeptide that is susceptible and does not have any of the positions as listed. SEQ ID NOs: 3-10 are amino acid sequences of CAD2 polypeptides from various species, including wheat, rice, maize, sorghum etc. that do not include any of the specific amino acids at the positions listed in instant claim 66.
It appears that the inventive concept of the instant application is the changes to the four consecutive amino acids around the substrate binding site for HvCAD2 that lead to changes in the HvCAD2 enzyme activity and confer enhanced resistance to Fusarium pseudograminearum. As SEQ ID NO: 2 is the susceptible HvCAD2 polypeptide, a change to the positions of SEQ ID NO: 1 as claim in claim 1 would likely result in enhanced resistance. It would not be clear to one of ordinary skill in the art that a modification to a position of SEQ ID NO: 1 would have any impact on SEQ ID NOs: 3-10 such that the resistance to Fusarium is enhanced when the genetically modified gene is expressed in a plant. One would not know what position within SEQ ID NOs: 3-10 need to be modified in order to confer the function as claimed. It is not clear if Applicant intends to claim that the same positions would need to be modified or if the positions would vary across the claimed sequences.
Claim 83 does not require the specified amino acids at the positions according to claim 66. The product can be a seed produced from the plant and does not require the SEQ ID NO. and the amino acids of claim 66. Seeds generally contain genetic material from two parents, meaning the genetic modification of claim 66 would not necessarily be introduced into the product of claim 83. Thus, the product would be indistinguishable from that of a product made with a seed not from the plant of claim 66. It is not clear what the inventor deems the invention in this case. Claim 84 depends from claim 83 and does not clarify the deficiencies.
Claim Rejections Under 35 USC § 112(a)
Claim 66, and claims 67-70, 77-78, and 80-86 depending therefrom, 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. Claims 67-70, 77-78, and 80-86 are also rejected insofar as they depend from claim 66, and do not overcome the stated rejection(s). This is a modified rejection necessitated by amendments to the claims.
The claims are drawn to a plant having a genetically modified gene encoding an atypical CAD2 polypeptide with at least 90% identity to any one or more of SEQ ID NOs: 1-10, which, when expressed in the plant confers enhanced resistance to a Fusarium sp, and wherein the polypeptide has one or more or all of; i) an alanine at a position corresponding to amino acid number 179 of SEQ ID NO:1, ii) a leucine at a position corresponding to amino acid number 180 of SEQ ID NO:1, iii) a phenylalanine at a position corresponding to amino acid number 181 of SEQ ID NO:1, and iv) a threonine at a position corresponding to amino acid number 182 of SEQ ID NO:1.
The instant disclosure describes changes to the four consecutive amino acids around the substrate binding site of HvCAD2 that likely lead to changes in the enzyme activity and thus enhanced resistance to Fusaruim psudograminearum in barley. The disclosure reduces to practice a resistance phenotype to Fusarium pathogens with two highly conserved amino acids in the CAD2 polypeptide causing the resistance phenotype to Fusarium pathogens. The instant disclosure reduces to practice gene editing of barley CAD2 based on the native amino acid positions at 179-182 of the Hordeum vulgare susceptible allele sequence.
The instant disclosure does not reduce to practice that the expressed CAD2 polypeptide with any of SEQ ID NOs: 1-10 will confer resistance to a Fusarium sp, wherein the polypeptide has one or more or all of; i) an alanine at a position corresponding to amino acid number 179 of SEQ ID NO:1, ii) a leucine at a position corresponding to amino acid number 180 of SEQ ID NO:1, iii) a phenylalanine at a position corresponding to amino acid number 181 of SEQ ID NO:1, and iv) a threonine at a position corresponding to amino acid number 182 of SEQ ID NO:1.
FCR resistance was evaluated in the instant specification using a highly aggressive strain of Fusaruim psudograminearum isolated from infected wheat crowns. FCR assessments were carried out in recombinant lines identified from fine-mapping the gene underlying FCR resistance at the 4HL locus Qcrs.cpi-4H. Transformation constructs were created from the full-length CDSs for each of the two candidate genes obtained from the predicted genes model of WBR1 for the resistant and susceptible lines. Barley was transformed with Agrobacterium-mediated transfer. The genes were cloned and characterized to find that, compared to the known protein structure of Mt-CAD2, which shares 64.15% sequence identity with the barley CAD2, there were four consecutive amino acid changes around the substrate binding site that likely led to changes in enzyme activity and thus resistance to FCR. Orthologs in other plant species, including wheat, rice, maize, and sorghum, were analyzed to provide resistance genes for these plant species, as well.
The instant disclosure describes HvCAD2, the Hordeum vulgare atypical CAD2 gene, encoding a predicted protein of 372 amino acids belonging to the SDR family [Example 3]. Within HvCAD2, four missense variants were detected at positions 542, 544, 547, and 551 between R and S alleles in the coding region of HvCAD2, which gave rise to four consecutive amino acid changes in polypeptides. These changes result in a change of amino acids from a conserved valine to alanine (position 179, V179A), isoleucine to leucine (position 180, I180L), valine to phenylalanine (position 181, V181F) and asparagine to threonine (position 182, N182T). The instant specification describes that the four consecutive amino acid changes around the substrate binding site would very likely lead to changes in enzyme activity of HvCAD2. The instant specification shows that the homologs of the gene in other plants had a valine at the position corresponding to amino acid 197 and an asparagine at position 182, demonstrating that these two amino acids were highly conserved in other CAD2 polypeptides. The Applicant concedes that, “these two amino acids were therefore highly conserved in other CAD2 polypeptides, and the sequence difference in either one, or both, amino acids indicative of an altered function that is the cause of the resistance phenotype to Fusarium pathogens” (see pg. 66 of the instant specification, as referenced below).
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The instant disclosure does not reduce to practice that a single amino acid position as recited in claim 66 would result in the enhanced resistance as claimed. Table 4 shows different plants/lines containing the targeted gene. It appears that the full-length CDS for a candidate gene was transformed into barley by Agrobacterium transformation to obtain lines containing the R allele. It appears that the lines containing the R allele have the nucleotide changes to result in the combination of the amino acid modifications claimed in claim 66. Even still, the Applicant concedes that small number of the transgenic lines did not show the expected FCR resistance as expected [Example 4; Table 4]. It is not clear that a plant with only one of the changes in amino acid at the claimed positions would function as claimed.
The Applicant reduces to practice the construction of single target gRNAs that directly target the four consecutive amino acids differing between the Resistant and Susceptible alleles of barley [Example 6]. The Applicant describes alignment of the resistant HvCAD2R1 sequence against Triticum aesitivum [Example 7]. The coding domain sequences were aligned with HvCAD2R1 and the homologous regions aligned. Although the Applicant specifies that the peptide sequence indicates that the amino acid positions 179 and 182 are the same as that of the susceptible barley amino acid region for all of the wheat sequences, one of skill in the art would not know where within the wheat gene to modify to result in the amino acid changes that confer enhanced resistance.
The Applicant has not reduced to practice that the gene editing results in enhanced resistance and further teaches that two of the variants are missing 6 amino acids downstream of the substrate binding site and that there is no indication if these variants are functional or not. Modifying a homologous region in another gene does not always result in the same function because the exact phenotypic and regulatory outcomes of a genetic modification can be species specific. For example, genes with conserved protein sequence, function, and expression pattern over time often exhibit extremely divergent cis-regulatory sequences. Mutation of CLV3 in Arabidopsis and tomato displayed distinct differences in response to disruption of regions upstream and downstream of the coding sequence, suggesting regulatory changes and evolutionary divergence can alter functionality (Ciren, D. et al. (2024). “Extreme restructuring of cis-regulatory regions controlling a deeply conserved plant stem cell regulator.” PLoS Genet 20(3): e1011174) [Abstract]. Thus, there is unpredictability in mutating a homologous sequence in wheat, particularly because two of the wheat cds variants are missing 6 amino acids downstream of the substrate binding site and have not been explored for functionality.
The specification does not provide enough evidence that mutations of such a sequence would reliably provide the same function of enhanced resistance to a Fusarium pathogens, especially given that SEQ ID NOs: 3-10 are from variable species beyond wheat and barley. Undue experimentation would be required to locate the positions to target and ensure that the targeting would still perform the function as claimed.
Response to Applicant’s Arguments:
The Applicant’s arguments filed September 3rd, 2026, with respect to the rejection of claim 66-70, 77-78, and 80-86 have been carefully considered but are moot in light of the modified rejection above.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 83 and 84 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Haynes, L. et al. “Production of stabilized whole grain flour and products thereof.” US Patent No. US 8173193 B2. Published 2012. This is a new rejection necessitated by amendments to the claims.
Claim 83 recites a product produced from a plant of claim 66 and/or a seed therefrom, wherein the product is a food product or beverage product.
Claim 84 recites method of preparing a product of claim 83, the method comprising mixing seed, or flour, wholemeal or starch from the seed, with another food ingredient.
Haynes teaches a process for making stabilized whole grain wheat flours containing natural proportions of bran, germ, and endosperm, with low degrees of starch damage due to abrasion and low degrees of starch gelatinization due to heat and moisture treatment [¶19]. The stabilized whole wheat flours of the present invention have dough and baking functionalities approaching those of white refined wheat flour. They may be used in the consistent production of highly machinable, sheetable doughs for making baked goods such as cookies, crackers, and snacks with excellent oven spread and appearance, and a non-gritty mouthfeel.
Given that claim 83 teaches a method of preparing a product from either the plant or the seed of claim 66 and does not require the genetic modifications of the plant of claim 66. Further, claim 66 does not specify the plant species. A wheat plant bred from the plant of claim 66 does not require the modifications of claim 66 because it contains genetic material from another plant parent and may not have the modifications. It would thus be indistinguishable from a wheat plant without the modifications and can be found in the cookie that can be prepared by the flour of Haynes, as detailed above (i.e., a product from the seed of the plant of claim 66).
Additionally, claim 84 does not remedy the lack of specified modifications and thus a cookie (as taught by Haynes) reads on a product and a process of making would be mixing the whole wheat flour of Haynes with another food ingredient, such as salt and baking soda.
Claim Rejections Under 35 USC § 103
The rejections of claims 66-70, 77-88, and 80-85 are withdrawn in light of Applicant’s amendments to the claims.
Summary
Claims 66-70, 77-78, and 80-86 are rejected.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY K. JOHNSON whose telephone number is (571)272-5761. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bratislav Stankovic can be reached at 571-270-0305. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY K JOHNSON/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
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