DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I, claim 2, in the reply filed on March 10, 2026 is acknowledged. Claim 1 links groups I-XI and XVII-XX.
The traversal is on the ground(s) that all of the claims are drawn to the same gene located on different chromosomes such that no separate search is required.
This is not found persuasive because the search of each group is not limited to the search of the ASN2 gene. While the search of the different groups may overlap with respect to the ASN2 gene, they are not coextensive, as the different groups of invention require additional search queries, for example searches directed to breeding methods, or the use of DNA primer pairs.
Applicant’s request for the rejoinder of claims 4-12, which are now amended to depend from claim 2, is however granted. Because claims 4-12 as currently amended depend from claim 2, they are rejoined and considered to be part of group I.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3, 13-29 and 31 are withdrawn from consideration.
Claim Rejections - 35 USC § 112
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.
Claim 2, and claims 4-12 dependent thereon, 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. Claim 2 is indefinite because it is unclear whether and how the phrase “comprises a loss-of-function mutation in the ASN-A2 gene and the ASN-B2 gene; the ASN-A2 gene and the ASN-D2 gene; or the ASN-B2 gene and the ASN-D2 gene” is intended to limit the claim, because “comprise” is open claim language that allows for the inclusion of additional mutated genes. If Applicant intends to limit the claim to the specific gene combinations listed, it is suggested that claim 2 be amended to recite closed claim language before the list of alternatives, such as “wherein the plant has a loss-of-function mutation in two endogenous ASPARAGINE SYNTHETASE 2 (ASN2) genes selected from the group consisting of the ASN-A2 gene and the ASN-B2 gene; the ASN-A2 gene and the ASN-D2 gene; and the ASN-B2 gene and the ASN-D2 gene”.
Claim 8 is 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. Claim 8 is indefinite because it is unclear what constitutes a germination rate of about 70% to about 100% relative to the germination rate of grain without the mutation, since neither the claim nor the specification indicates how close to 70% or 100% a germination rate would be to be included in, or excluded from, this range.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim(s) 1 and 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oddy et al. Reduced free asparagine in wheat grain resulting from a natural deletion of TaASN-B2: investigating and exploiting diversity in the asparagine synthetase gene family to improve wheat quality. BMC plant Biol. 2021 Jun 29;21(1):302.
Claim 1 is drawn to a modified wheat plant, or a progeny thereof, comprising a loss-of- function mutation in at least one endogenous ASPARAGINE SYNTHETASE 2 (ASN2) gene selected from ASN-A2, ASN-B2, and ASN-D2, wherein the mutation confers reduced free asparagine concentration in the grain of the wheat plant.
Claim 7 is drawn to the modified wheat plant of claim 2, wherein the free asparagine
concentration of the grain is reduced by at least 30% relative to the free asparagine concentration
of grain without the mutation.
Oddy et al. teach a modified wheat plant, or a progeny thereof, comprising a loss-of- function mutation in the endogenous ASPARAGINE SYNTHETASE 2 (ASN2) gene ASN-B2. The mutation confers reduced free asparagine concentration in the grain of the wheat plant, including wherein the free asparagine concentration of the grain is reduced by at least 30% relative to the free asparagine concentration of grain without the mutation (page 11 column 2 first full paragraph). Accordingly, Oddy et al. anticipates claims 1 and 7.
Claim(s) 1-2 and 4-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Raffan et al. Wheat with greatly reduced accumulation of free asparagine in the grain, produced by CRISPR/Cas9 editing of asparagine synthetase gene TaASN2 Plant Biotechnol. J. 2021 Aug;19(8):1602-1613. Epub 2021 Mar 28.
Claim 1 is drawn to a modified wheat plant, or a progeny thereof, comprising a loss-of- function mutation in at least one endogenous ASPARAGINE SYNTHETASE 2 (ASN2) gene selected from ASN-A2, ASN-B2, and ASN-D2, wherein the mutation confers reduced free asparagine concentration in the grain of the wheat plant.
Claim 2 is drawn to the modified wheat plant of claim 1, wherein the plant comprises a loss-of-function mutation in the ASN-A2 gene and the ASN-B2 gene; the ASN-A2 gene and the ASN-D2 gene; or the ASN-B2 gene and the ASN-D2 gene.
Claim 4 is drawn to the modified wheat plant of claim 2, wherein the mutation
introduces a frameshift mutation or a pre-mature stop codon in the ASN2 gene.
Claim 5 is drawn to the modified wheat plant of claim 2, wherein the mutation is in
the first exon encoding the glutamine amidotransferase (GATase) domain of the ASN2 gene.
Claim 6 is drawn to the modified wheat plant of claim 2, wherein the mutation is an
insertion, a deletion, or a substitution of one or more nucleotides from position 172 to 192 with reference to SEQ ID NO: 1, 2, or 3.
Claim 7 is drawn to the modified wheat plant of claim 2, wherein the free asparagine
concentration of the grain is reduced by at least 30% relative to the free asparagine concentration
of grain without the mutation.
Claim 8 is drawn to the modified wheat plant of claim 2, wherein the grain has a
germination rate of about 70% to about 100% relative to the germination rate of grain without
the mutation.
Raffan et al. teach modified wheat plants, or a progeny thereof, comprising a loss-of- function mutation in the endogenous ASPARAGINE SYNTHETASE 2 (ASN2) genes ASN-A2, ASN-B2, and ASN-D2. The mutations confers reduced free asparagine concentration in the grain of the wheat plant, including wherein the free asparagine concentration of the grain is reduced by at least 30% relative to the free asparagine concentration of grain without the mutation (abstract; page 1607 Column 1 second paragraph and Figure 3). The germination rate of the grain is about 70% to about 100% relative to the germination rate of grain without the mutation (page 1608 column 2 last paragraph). The modified wheat plants of Raffan et al. “comprise” a loss-of-function mutation in the ASN-A2 gene and the ASN-B2 gene; the ASN-A2 gene and the ASN-D2 gene; or the ASN-B2 gene and the ASN-D2 gene, because “comprise” is open claim language that allows for the inclusion of additional mutated genes. The mutations of Raffan et al introduce a frameshift mutation or a pre-mature stop codon in the ASN2 gene, ; Figure 2are in the first exon encoding the glutamine amidotransferase (GATase) domain of the ASN2 gene, and include an insertion, a deletion, or a substitution of one or more nucleotides from position 172 to 192 with reference to SEQ ID NO: 1, 2, or 3 (page 1603 column 1 last paragraph; Figure 1; page 1604-1606; Table 1). Accordingly Raffan et al. anticipate claims 1-2 and 4-8.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 1-2 and 4-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rommens (U.S. Patent Application Publication No.2007/0074304, published Mar. 29, 2007) in view of Xu et al. (Genomic, Biochemical, and Modeling Analyses of Asparagine Synthetases from Wheat. Front. Plant Sci. 2018 Jan 15:8:2237. eCollection 2017), Gao et al. (U.S. Patent Application Publication No. 2017/0114361, published Apr. 27, 2017) and Yang et al. (U.S. Patent Application Publication No. 2015/0067922, published Mar. 5, 2015).
Claim 1 is drawn to a modified wheat plant, or a progeny thereof, comprising a loss-of-function mutation in at least one endogenous ASPARAGINE SYNTHETASE 2 (ASN2) gene selected from ASN-A2, ASN-B2, and ASN-D2, wherein the mutation confers reduced free asparagine concentration in the grain of the wheat plant.
Claim 2 is drawn to the modified wheat plant of claim 1, wherein the plant comprises a loss-of- function mutation in the ASN-A2 gene and the ASN-B2 gene; the ASN-A2 gene and the ASN-D2 gene; or the ASN-B2 gene and the ASN-D2 gene.
Claim 4 is drawn to the modified wheat plant of claim 2, wherein the mutation
introduces a frameshift mutation or a pre-mature stop codon in the ASN2 gene.
Claim 5 is drawn to the modified wheat plant of claim 2, wherein the mutation is in
the first exon encoding the glutamine amidotransferase (GATase) domain of the ASN2 gene.
Claim 6 is drawn to the modified wheat plant of claim 2, wherein the mutation is an
insertion, a deletion, or a substitution of one or more nucleotides from position 172 to 192 with reference to SEQ ID NO: 1, 2, or 3.
Claim 7 is drawn to the modified wheat plant of claim 2, wherein the free asparagine
concentration of the grain is reduced by at least 30% relative to the free asparagine concentration
of grain without the mutation.
Claim 8 is drawn to the modified wheat plant of claim 2+, wherein the grain has a
germination rate of about 70% to about 100% relative to the germination rate of grain without
the mutation.
Claim 9 is drawn to the modified wheat plant of claim 2, wherein the ASN-A2 gene
comprises the nucleotide sequence of SEQ ID NO: 52, 54, or 59.
Claim 10 is drawn to the modified wheat plant of claim 2, wherein the ASN-B2 gene
comprises the nucleotide sequence of SEQ ID NO: 57.
Claim 11 is drawn to the modified wheat plant of claim 2, wherein the ASN-D2 gene
comprises the nucleotide sequence of SEQ ID NO: 53, 55, 56, or 58.
Claim 12 is drawn to the modified wheat plant of claim 2, wherein the wheat plant is
of the variety Bobwhite, Denali, Ripper, Snowmass 2.0, or Steamboat.
Rommens teach methods for reducing acrylamide levels in plants, which methods include reducing free asparagine levels in plants by downregulating the expression of asparagine synthetase genes by gene silencing, including wheat asparagine synthetase genes, for the purpose of mitigating the negative toxicological effects of acrylamide in food products (abstract; paragraphs [0003]-[0013], [0015], [0021], [0025], [0190], [0202]). Rommens also teach methods of mutagenesis as alternative means for downregulating the expression of asparagine synthetase genes (paragraphs [0225]-[0227]).
Rommens do not teach a modified wheat plant, or a progeny thereof, comprising a loss-of-function mutation in at least one endogenous ASPARAGINE SYNTHETASE 2 (ASN2) gene selected from ASN-A2, ASN-B2, and ASN-D2.
Xu et al. teach the endogenous wheat ASPARAGINE SYNTHETASE 2 (ASN2) genes ASN-A2, ASN-B2, and ASN-D2. Xu et al. teach that because ASN2 is the major enzyme synthesizing asparagine in wheat grain, it is an appropriate target for genetic interventions to reduce free asparagine accumulation (last paragraph).
Gao et al. teach methods for producing mutant wheat plants by introducing loss of function mutations such as deletions, insertions and substitutions into endogenous wheat genes, including endogenous genes of Bobwhite wheat, using targeted genome modification (paragraphs [0010], [0060]-[0061], [0188], [0193]; claim 9).
Yang et al. teach a method for introducing loss of function mutations, including deletions and insertions, into an endogenous potato asparagine synthetase gene using targeted genome modification for the purpose of reducing asparagine content and acrylamide levels in the plant (paragraphs [0157]-[0171]).
Given the teachings of Rommens that free asparagine levels in plants, including wheat plants, can be reduced by downregulating the expression of asparagine synthetase genes, thus reducing acrylamide levels and mitigating the negative toxicological effects of acrylamide in food products, given the further teachings of Rommens that methods of mutagenesis are an alternative means for downregulating the expression of asparagine synthetase genes, given the teachings of Xu et al. that the structure of endogenous wheat ASPARAGINE SYNTHETASE 2 (ASN2) genes ASN-A2, ASN-B2, and ASN-D2 is known, given the further teachings of Xu et al. that ASN2 is an appropriate target for genetic interventions to reduce free asparagine accumulation because it is the major enzyme synthesizing asparagine in wheat grain, given the teachings of Gao et al. that mutant wheat plants can be made by introducing loss of function mutations such as deletions, insertions and substitutions into endogenous wheat genes, including endogenous genes of Bobwhite wheat, using targeted genome modification, and given the teachings of Yang et al. that loss of function mutations, including deletions and insertions, can be introduced into an endogenous potato asparagine synthetase gene using targeted genome modification for the purpose of reducing asparagine content and acrylamide levels in the plant, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to make a modified wheat plant of a known wheat variety comprising a loss-of-function mutation in at least one endogenous ASPARAGINE SYNTHETASE 2 (ASN2) gene selected from ASN-A2, ASN-B2, and ASN-D2, wherein the mutation confers reduced free asparagine concentration in the grain of the wheat plant.
One skilled in the art would have been motivated to do so in order to reduce the acrylamide levels in the wheat plant, thus mitigating the negative toxicological effects of acrylamide in the food products made therefrom.
One skilled in the art would have had a reasonable expectation of success, in light of the knowledge that downregulating the expression of asparagine synthetase was known to reduce free asparagine and acrylamide levels in plants, in light of the knowledge that methods of mutagenesis including targeted genome modification were known and used in the art as alternative means for downregulating plant gene expression, including the expression of endogenous wheat genes and a potato asparagine synthetase gene, in light of the knowledge that ASN2 is an appropriate target for genetic interventions to reduce free asparagine accumulation because it is the major enzyme synthesizing asparagine in wheat grain, and in light of the knowledge that that the structure of endogenous wheat ASPARAGINE SYNTHETASE 2 (ASN2) genes ASN-A2, ASN-B2, and ASN-D2 was known.
Further, the type and location of the loss-of-function mutations produced would be determined by the specific method employed, and the experimental design chosen. Similarly, the degree of the effect of the loss-of-function mutations on the free asparagine concentration and germination rate would be determined by the number and type of loss-of-function mutations produced. Likewise, the specific nucleotide sequence of the ASN2 gene would be determined by the particular wheat variety in which the loss-of-function mutations are made.
Thus, the claimed invention would have been prima facie obvious as a whole to a person having ordinary skill in the art before the effective filing date of the claimed invention.
Remarks
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA E COLLINS whose telephone number is (571)272-0794. The examiner can normally be reached M-F 8:30 am - 5:00 pm.
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/CYNTHIA E COLLINS/Primary Examiner, Art Unit 1662
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