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 June 16th, 2026 have been entered.
New claims 86-87 have been added.
Claims 66-87 are pending in the application.
Claims 66-70, 77-78, and 80-87 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 Interpretation
The instant specification defines the term "atypical cinnamoyl-CoA dehydrogenase polypeptide 2" or "CAD2" refer as members of the short-chain dehydrogenase/reductase (SDR) family and states that examples of the CAD2 polypeptide family include polypeptides which share high primary amino acid sequence identity, for example at least 40%, at least 50%, at least 60%, at least 70%, least 80%, at least 90%, or at least 95% identity with the amino acid sequence of any one or more of SEQ ID NO's 1 to 10. This is taken to mean that the CAD2 is a member of the SDR family with >40% identity to the amino acid sequence of SEQ ID NOs 1-10.
Withdrawn/Modified Objections and Rejections
The objection to the drawings is withdrawn in light of amendments to the specification.
The objection to the specification is withdrawn in light of amendments to the specification.
The rejection of claims 66-70, 77-78, and 80-85 under 35 USC § 112(a) is modified in light of amendments to the claims.
The rejection of claim 66 and 67 under 35 USC § 102 is moot in light of the claim amendments and is thus withdrawn.
The rejection of claims 66, 68-79, 77-78, and 80-81 under 35 USC § 103 is modified in light of amendments to the claims.
Modified Rejections
Claim Rejections - 35 USC § 112(a)
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.
Claim 66, and claims 67-70, 77-78, 80-85, and 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 80-85 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.
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 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.
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 any sequence with 90% identity or more to SEQ ID NOs. 1-10 to still confer enhanced resistance to Fusarium without the presence of one or both of these amino acids.
For example, SEQ ID NO. 1 is 372 amino acids long. 90% identity would allow for 37 mismatches to SEQ ID NO. 1. This may or may not include mutations of the necessitated two amino acids that were highly conserved across CAD2 homologs in other plants. A sequence with 90% identity to SEQ ID NO. 1 may or may not carry the same amino acids that were indicative of an altered function to provide the resistance phenotype to Fusarium. The specification does not provide enough evidence that the structure of such a sequence would provide the same function of enhanced resistance to a Fusarium pathogens. Undue experimentation would be required to ensure that the difference in structure would still perform the function as claimed. Although 95% sequence identity to the claimed sequences as recited in claim 67 improves the specificity, it does not ensure that the structure would have the required amino acids to provide Fusarium resistance.
Examiner notes that defining the CAD2 polypeptide sequence with more specificity may help to overcome this rejection.
New Rejections
Claim Rejections - 35 USC § 103
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.
Claims 66-70, 77-78, and 80-81 are rejected under 35 U.S.C. 103 as being unpatentable over Pan, H. et al. (2014), "Structural Studies of Cinnamoyl-CoA reductase and Cinnamyl-Alcohol Dehydrogenase, Key Enzymes of Monolignol Biosynthesis," The Plant Cell, 26:3709-3727 (as cited in IDSs filed 8/18/2025 and 9/24/2025), in view of Sawbridge, T. et al., “Manipulation of plant cell walls,” (AU 2011202252 B2, published 2/21/2013, as cited in IDS filed 9/23/2024), Powell, J. et al. (2017), “The Fusarium crown rot pathogen Fusarium pseudograminearum triggers a suite of transcriptional and metabolic changes in bread wheat (Triticum aestivum L.)”, Annals of Botany, 119:853-867, and Alexandrov, N. (2012). “Sequence-Determined DNA Fragments and Corresponding Polypeptides Encoded Thereby”, (US 20120159672 A1). This is a new rejection necessitated by the claim amendments.
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.
Claim 67 recites the plant of claim 66, wherein the polypeptide comprises amino acids having a sequence at least 95%identical to the amino acid sequence of any one or more of SEQ ID NOs 1 to 10.
Claim 68 recites the plant of claim 66, wherein the genetically modified gene is an exogenous polynucleotide encoding the polypeptide.
Claim 69 recites the plant of claim 66, wherein the Fusarium sp. is Fusarium pseudograminearum.
Claim 70 recites the plant of claim 66 which is a cereal plant or a legume plant.
Claim 77 recites a method of producing a plant with a genetic modification(s) of claim 66, comprising i) introducing a genetic modification(s) to a plant cell such that the cell is capable of producing an atypical cinnamoyl-CoA dehydrogenase 2 (CAD2) polypeptide that confers upon the plant comprising the cell enhanced resistance to Fusarium sp. when compared to a corresponding plant lacking the genetic modification(s), 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; ii) regenerating a plant with the genetic modification(s) from the cell.
Claim 78 recites a method of producing a plant with a genetic modification(s) of claim 66, the method comprising the steps of i) screening one or more progeny plants from a cross of two parental plants, wherein at least one plant comprises the genetic modification(s), for the presence or absence of the genetic modification(s), and ii) selecting a progeny plant which comprise the genetic modification(s), thereby producing the plant.
Claim 80 recites a seed of the plant of claim 66, wherein the seed comprises the genetic modification(s).
Claim 81 recites a method of producing a plant part, the method comprising, a) growing a plant of claim 66, and b) harvesting the plant part.
Regarding claim 66, Pan teaches a functional and structural analysis of the enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD). Pan teaches that these enzymes catalyze the two key reactions in the conversion of cinnamic acid derivatives into monolignol building blocks for lignin polymers in plant cell walls [Abstract]. Pan teaches that lignin is a major structural component of cell walls and that it plays an important role in defense against pathogens [pg. 1, col. 1, ¶1]. Pan teaches that the polymeric structure of lignin forms from monolignols. The three prominent monolignols p-hydroxycinnamyl, coniferyl, and sinapyl alcohol, give rise to the lignin subunits hydroxycinnamyl (H), guaiacyl (G), and syringyl (S), respectively [pg. 1, col. 2, ¶1]. Pan teaches that atypical CAD has been shown to be involved in lignin biosynthesis in tobacco in prior studies, but belongs to the SDR family, unlike classic CAD enzymes [pg. 2, col. 2, ¶1].
Pan teaches atypical Medicago truncatula CAD2 mutants and the potential utility of engineered variants of Mt-CAD2 in modifying lignin content and composition in plants (i.e., a plant having a genetically modified gene encoding an atypical CAD2 polypeptide) [pg. 3722, col. 1, ¶4]. Pan teaches that atypical Mt-CAD2 may compensate functionally upon the loss of the classic CAD enzyme as the classic CAD1 and the atypical CAD2 can catalyze the same reactions for lignin biosynthesis, but CAD2 has lower activity with the same substrates [pg. 3722, col. 2, ¶3]. For example, Pan teaches that engineered variants of Mt-CAD2 that exhibited enhanced activity with sinapaldehyde but decreased activity with coumaraldehyde and coniferaldehyde [pg. 3720, col. 1, ¶1]. Pan teaches the Mt-CAD2 binding site for the phenylpropene-aldehyde substrate and teaches that replacements of Mt-CAD2 large residues Tyr-136 and Ph2-226 with smaller residues Phe and Ala, resulted in increased catalytic activity against sinapaldehyde [pg. 3720, col. 1, ¶1]. This property could potentially be useful for promoting the production of sinapyl lignin (S-lignin) over guaiacyl lignin (G-lignin) [pg. 3722, col. 1, ¶4]. Pan teaches that such mutants could be introduced back into plants, particularly those harboring knockouts of the classic CAD enzyme to alter lignin composition.
Pan does not explicitly teach the atypical CAD2, wherein a plant having a genetically modified gene encoding the atypical CAD2 which, when expressed, confers enhanced resistance to a Fusarium sp..
However, Sawbridge teaches manipulation of plant cell walls though the modification of lignin biosynthesis [Abstract]. Sawbridge teaches that it is the final two reduction/dehydrogenation steps of the pathway, catalyzed by cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) that are considered to be specific to lignin biosynthesis [pg. 1, ¶1]. Sawbridge teaches that altered lignin composition may be desirable to improve disease resistance (i.e. enhanced resistance) [pg. 1, ¶1]. Sawbridge teaches CAD and CAD-like proteins and nucleic acids or nucleic acid fragments encoding amino acid sequences [pg. 1, ¶1] and introduction of genes encoding the polypeptides into perennial ryegrass for the production of transgenic plants, seeds or plant parts thereof (i.e. a plant having a genetically modified gene) [Example 6].
Although Pan and Sawbridge teach that atypical CAD2 may be mutated to modify lignin biosynthesis and a plant having a genetically modified gene encoding a CAD or CAD-like polypeptide which may confer disease resistance when expressed in the plant, Pan and Sawbridge do not explicitly teach that the atypical CAD2 confers enhanced resistance to a Fusarium sp.
However, Powell teaches that Fusarium crown rot of wheat, primarily caused by the hemi-biotrophic fungal pathogen F. pseudograminearum, has become increasingly important globally [pg. 853, col. 1 & 2]. Powell teaches that upon F. pseudograminearum infection, phenylalanine-derived metabolic pathways are upregulated. Phenylalanine is an important precursor to lignins [pg. 862, col. 2, ¶4]. Powell teaches that lignin deposition is a known common defense response to pathogen infection, particularly against biotrophic fungal pathogens as a barrier to haustorial penetration, such as F. pseudograminearum (i.e., enhances resistance to a Fusarium sp.). Powel teaches that the molecular mechanisms of Fusarium crown rot infection can aid in efforts to improve Fusarium crown rot resistance [pg. 854, col. 2, ¶2].
Pan, Sawbridge, and Powell do not teach that the CAD2 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 1-10.
However, Alexandrov teaches SEQ ID NO: 29061 with 100% identity to SEQ ID NO: 7 of the instant application (see alignment below). SEQ ID NO: 29061 is annotated as a cinnamyl-alcohol dehydrogenase (CAD). This polypeptide aligns with the claim interpretation of as detailed above and thus is taken to read on instant claim 66 (i.e., 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: 1-10).
Query Match 100.0%; Score 1719; Length 332;
Best Local Similarity 100.0%;
Matches 332; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MASAAATATMGTGKVVCVTGASGYIASWIVRLLLDRGYTVRATVRDTADPKKTLHLTALD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MASAAATATMGTGKVVCVTGASGYIASWIVRLLLDRGYTVRATVRDTADPKKTLHLTALD 60
Qy 61 GAKDRLHLFKASLLEEGSFDAAVHGCDTVFHTASPFYHNVKDAKAELLDPAVKGTLNVLG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GAKDRLHLFKASLLEEGSFDAAVHGCDTVFHTASPFYHNVKDAKAELLDPAVKGTLNVLG 120
Qy 121 SCKKASIKKVVVTSSMAAVAYNGRPRTPEVTVDETWFSDPQICETNQQWYILSKTLAEEA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SCKKASIKKVVVTSSMAAVAYNGRPRTPEVTVDETWFSDPQICETNQQWYILSKTLAEEA 180
Qy 181 AWKFSRDNGLEIVTINPAMVIGPLLQPTLNTSAEAILKLINGSSSTYPNFCFGWVNVKDV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AWKFSRDNGLEIVTINPAMVIGPLLQPTLNTSAEAILKLINGSSSTYPNFCFGWVNVKDV 240
Qy 241 ALAHILAYEVPSSNGRYCMVERVVHYSELVNIIRNMYPTLPLPDKCADDKPFVPPYQVSK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ALAHILAYEVPSSNGRYCMVERVVHYSELVNIIRNMYPTLPLPDKCADDKPFVPPYQVSK 300
Qy 301 EKIKSIGIELIPLETSVKETIESLKEKGFASF 332
||||||||||||||||||||||||||||||||
Db 301 EKIKSIGIELIPLETSVKETIESLKEKGFASF 332
Given that Pan teaches mutant atypical CAD2 polypeptides which can modify the lignin content and composition, particularly S-lignin; given that Sawbridge teaches genetically modified plants having modified lignin biosynthesis-related genes, including CAD and CAD-like proteins and nucleic acids or nucleic acid fragments encoding amino acid sequences; given that Powell teaches that lignin is a primary components of pathogen defense, such as F. pseudograminearum; and given that Alexandrov teaches a CAD polypeptide with 100% sequence identity to SEQ ID NO: 7 of the instant application, it would have been prima facie obvious to one of ordinary skill at the time of filing to combine these teachings to create a genetically modified plant with enhanced resistance to F. pseudograminearum using the CAD sequence of Alexandrov. One would have been motivated to do so as Pan teaches that CAD and CAD-like genes have utility in modifying lignin content and composition in plants, that CAD and CAD-like proteins exhibit enhanced activity with sinapaldehye, which promotes the production of S-lignin, and that lignin plays a large role in plant stress responses, such as pathogen attacks. Sawbridge additionally teaches that modifying lignin biosynthesis and the disclosed modifications may be used for disease resistance. Powell teaches that lignin plays a large role defense response against biotrophic fungal pathogens and that lignin precursors are upregulated under F. pseudograminearum infection. In addition, Powell teaches the importance of managing Fusarium crown rot by F. pseudograminearum infection, providing motivation for modifying lignin-related genes for increased resistance to Fusarium crown rot. Lastly, Alexandrov provides a CAD sequence with 100% identity to SEQ ID NO: 7 of the instant application, which fits the instant specification’s definition of an atypical CAD2 polypeptide. It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to choose a sequence such as this from a finite number of available and defined polypeptide sequences for the plant having a genetically modified gene encoding an atypical CAD2 polypeptide to confer enhanced resistance to a Fusarium sp.
Regarding claim 67, SEQ ID NO: 29061 of Alexandrov has 100% identity to SEQ ID NO: 7 of the instant application (i.e., wherein the polypeptide comprises amino acids having a sequence at least 95% identical to the amino acid sequence of any one or more of SEQ ID NOs: 1-10).
Regarding claim 68, Sawbridge teaches transformation vectors with chimeric lignin biosynthesis-related genes, such as CAD and CAD-like, using full-length open reading frame cDNAs of perennial ryegrass [Example 6]. Direct gene transfer experiments to tobacco protoplasts were performed using the transformation vectors under the control of the constitutive CaMV 35S promoter for production of transgenic tobacco plants (i.e. wherein the genetically modified gene is an exogenous polynucleotide encoding the peptide).
Regarding claim 69, as detailed above, Powell teaches that lignin deposition is a known common defense response to pathogen infection, particularly against biotrophic fungal pathogens as a barrier to haustorial penetration, such as F. pseudograminearum (i.e., enhances resistance to a Fusarium sp.).
Regarding claim 70, Sawbridge teaches that the vectors may be incorporated into a variety of plants, including monocotyledons (such as grasses from the genera Lolium, Festuca, Paspalum, Pennisetum, Panicum and other forage and turfgrasses, corn, oat, wheat and barley), dicotyledons (such as Arabidopsis, tobacco, 5 white clover, red clover, subterranean clover, alfalfa, eucalyptus) and gymnosperms (i.e. wherein the plant is a cereal or legume plant) [pg. 19, ln. 1-5].
Regarding claim 77, Sawbridge teaches that cells incorporating the vectors of the modified lignin genes may be selected and then cultured in an appropriate medium to regenerate transformed plants (i.e. a method of producing a plant with a genetic modification of claim 1) [pg. 19, ln. 16-20]. It would be routine optimization for one of ordinary skill to introduce the genetic modifications of the CAD2 polypeptide as detailed above to a plant cell, regenerate a plant from the plant cell, and produce progeny, as these methods are well known in the art and taught throughout the cited references.
Regarding claim 78, Sawbridge teaches that the plants resulting from the genetic transformation may be reproduced, either sexually or asexually, using methods known in the art to produce successive generations of transformed plant (i.e. a method of producing a plant with a genetic modification of claim 66; a cross of two parental plants, wherein at least one plant comprises the genetic modifications) [pg. 19, ln. 22-25]. Sawbridge teaches that plants may be screened by methodology known to those skilled in the art and that nucleic acids or nucleic acid fragments according to the present invention and/or nucleotide sequence information thereof may be used as a molecular genetic marker for quantitative trait loci (QTL) tagging, QTL mapping, DNA fingerprinting and in marker assisted selection (screening one or more progeny plants for the presence or absence of the genetic modifications and selecting a progeny plant which comprises the genetic modifications, thereby producing the plant) [pg. 9, ln. 10; pg. 15, ln. 15-20].
Regarding claims 80 and 81, Sawbridge teaches a plant seed or other plant part may be derived from the transgenic plant with the genetic modifications [pg. 20, ln. 10-15]. This indicates that the plant with the genetic modification is grown and a seed or plant part harvested therefrom.
By the rationale above for the plant of claim 66 having a genetically modified gene encoding a CAD2 polypeptide wherein when expressed in the plant, the polypeptide confers enhanced resistance to one or more biotrophic fungal pathogens, Pan, Sawbridge, Powell, and Alexandrov read on claims 67-70, 77-78, and 80-81. Although Pan, Sawbridge, Powell and Alexandrov do not explicitly disclose screening or the progeny plants from a cross with the genetically modified plant, selecting the progeny, or harvesting the plant part, these aspects are implied and generally routine in the prior art.
Claims 82-85 are rejected under 35 U.S.C. 103 as being unpatentable over Pan, Sawbridge, Powell and Alexandrov, as applied to claims 66-70, 77-78, and 80-81 above, and further in view of Palyi, L. Method and device for treating cereals and the like, (EP 0193840 A2, published 9/10/1986). This is a modified rejection necessitated by the claim amendments.
Claim 82 recites a method of producing flour, wholemeal, starch or other product obtained from seed, the method comprising; a) obtaining seed of a) obtaining seed of b) extracting the flour, wholemeal, starch or other product.
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 a 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.
Claim 85 recites a method of preparing malt, comprising the step of germinating seed of claim 80.
Pan, Sawbridge, Powell, and Alexandrov teach the plant having a genetically modified gene encoding an atypical CAD2 polypeptide with at least 90% identity to SEQ ID NO: 7, wherein when expressed in the plant the polypeptide confers enhanced resistance to a Fusarium species. Sawbridge teaches obtaining a seed or plant part from a plant with the genetic modification. Pan, Sawbridge, Powell, and Alexandrov do not teach a metho of producing flour or other product, food product or beverage product, or a method of preparing malt from the seed of claim 80.
However, Palyi teaches a method for peeling and grinding grain which is applicable to a wide variety of grains and seeds, including soft and hard wheat, durum wheat, barley, rye, malt barley, millet, African millet, milo, mung bean, sorghum and so on [pg. 1, ¶10]. Palyi teaches that, with the claimed apparatus, the lower disc, which rotates, has the advantage that the grains are not broken open during grinding, but rather a fractional treatment, which leads to an easy separation of the flour (i.e. a method of producing flour comprising extracting the flour) [pg. 3, ¶9].
Palyi additionally teaches that the casing left behind from the removal of the pericarp throughout the process can also be used for 100% germination for malt wheat (i.e. a method of preparing malt comprising the set of germinating the seed) [pg. 3, ¶5]. This has potential application in laboratories, in the baking industry and in brewing beer (i.e. a product produced from the plant of claim 66 or seed therefrom, wherein the product is a food product or beverage product).
Response to Applicant’s Arguments
The Applicant’s arguments filed June 16th, 2026, with respect to the rejection of claim 66-67 under 35 USC § 102 and claims 66, 68-70, 77-78, and 80-81 under 35 USC § 103 have been carefully considered but are moot in light of Applicant’s amendments to the claims. With respect to the rejection of claims 66-70, 77-78, and 80-85, the Applicant’s arguments have been carefully considered but were not found persuasive.
With regard to the claim of “enhanced resistance to one or more biotrophic fungal pathogen”, the arguments are moot in light of Applicant’s amendments to the claims.
With regard to the sequence specificity, the Applicant contends that the genus recited in claim 66 meets the written description requirement through a sufficient description of a representative number of species by actual reduction to practice and that the level of detail required varies depending on the scope and predictability of the claims and technology at hand. The Applicant contends that CAD2 is a member of a well-defined class of polypeptides and that the specification describes how variant polypeptides encompassed by the amended claims can be readily identified. The Applicant contends that the instant application identified new members of a well-defined family of proteins which are involved in lignin biosynthesis and can enhance resistance to Fusarium sps., including considerable details such as experimental results. The Applicant contends that one of ordinary skill in the art could readily identify variants encompassed within the scope of the claims.
The Examiner respectfully disagrees with Applicant’s arguments. Initially, it is noted that these are currently new rejections necessitated by the claim amendments.
The Applicant provides only one sequence, SEQ ID NO: 1 by actual reduction to practice, specifying that 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 (see Office Action filed 03/16/2026; pg. 6, ¶6). Orthologs in other plant species, including wheat, rice, maize, and sorghum, were analyzed to provide resistance genes for these plant species, as well. In the production and evaluation of transgenic plants, the inventors analyzed orthologs in different plant species including wheat, rice, maize and sorghum [pg. 67, Example 5]. The Applicant states that “the mutated plants were screened for the modification at the amino acid positions corresponding to the valine at position 179, and/or the isoleucine at position 180, and valine at position 181, and/or the asparagine at 182 to convert them into resistant polypeptide” [pg. 67, lns. 14-16]. Though the Applicant provides sufficient written description for gene editing with the specific mutations in multiple plant species, the Applicant still does not reduce to practice the genus of the sequences as claimed, even given that CAD2 polypeptides are known in the art.
As stated in the previous Office Action (filed 03/16/2026), SEQ ID NO. 1 is 372 amino acids long. 90% identity would allow for 37 mismatches to SEQ ID NO. 1. This may or may not include mutations of any of the necessitated amino acids that were highly conserved across CAD2 homologs in other plants and required for Fusarium sp. resistance. A sequence with 90% identity to SEQ ID NO. 1 may or may not carry the same amino acids that were indicative of an altered function to provide the resistance phenotype to Fusarium. The specification does not provide enough evidence that the structure of such a sequence would provide the same function of enhanced resistance to one or more biotrophic fungal pathogens. Undue experimentation would be required to ensure that the difference in structure would still perform the function as claimed.
Summary
New claims 86 and 87 are deemed free of the prior art given the failure of the prior art to teach or reasonably suggest a 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 SEQ ID NO: 1, and further, wherein the polypeptide has one or more 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.
Claims 66-70, 77-78, and 80-86 are rejected.
Claim 87 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claim(s).
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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
Prosecution Insights