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 in the reply filed on 5/26/2026 is acknowledged. The traversal is on the ground that “the common technical feature of a plant comprising a genetically modified FAD2-1 gene with "at least some FAD 2-1 protein activity, wherein the FAD2-1 activity is reduced when compared to a wild type cereal grain" and a genetically modified LOX3 gene with "reduced LOX3 protein activity when compared to the wild type cereal grain"”. This is not found persuasive because the Examiner interprets the common technical feature comprises a (fertile) plant comprising a genetically modified FAD2-1 gene and a genetically modified LOX3 gene, as described in the previous Office action (p.4, para 2) dated 3/26/2026. The plants comprising FAD2-1 and LOX3 mutations produce fertile plants and fertile grains, as evident from the cited references, as discussed below as well. Specific features of the FAD2-1 and LOX3 genes and/or its expression/activity pattern(s) associated with specific trait(s) would be examined during detail examination of the claims on its merits, as discussed below.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-2, 4-7, 9, 13, 20, 22, 33, 37, 41, 44, 50-51, 53, 55, 58 and 61 are pending.
Claims 20, 22, 37, 41, 44, 50-51, 53, 55, 58 and 61 are withdrawn from examination being part of non-elected groups.
Claims 1-2, 4-7, 9, 13 and 33 are being examined.
Claim Objections
Claim 1 is objected to because of the following informalities:
It is suggested to insert an “A” before “fertile” in claim 1 (line 1).
Appropriate correction is required.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Instant specification contains an embedded hyperlinks and/or other form of browser-executable codes (p. 37, line 8-10; p. 63, line 14; p. 84, line 5).
It is noted here that the specification has misnumbered pages. After a ‘first’ page 66, the next few pages are numbered 64, 65, 67. There are 90 total pages, but the last page is numbered 88. Appropriate correction is required.
Claim Rejections - 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 4 recites the broad recitation “between 50% and 80%”, and the claim also recites “between 55% and 75%, between 55% and 70%”, which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 33, line 1 recites, “A cell, preferably a rice cell”. It is unclear whether the claimed cell is limited to being a rice cell, or encompasses any cell type. See MPEP § 2173.05(d). The claim is considered indefinite because there is a question or doubt as to whether the rice cell (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim.
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.
Written Description
Claims 1-2, 4-7, 9, 13 and 33 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 contains 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.
Claim 1 recites “… wherein the grain comprises i) at least some FAD 2-1 protein activity, wherein the FAD2-1 activity is reduced when compared to the wild type cereal grain…”.
The Applicant describes two FAD2-1 mutant lines (V1-4 and V1-13) which are biallelic heterozygous for FAD2-1 (and LOX3 loci) (spec, p.65, line 1-2). The gene edits in V1-7 line resulted in premature stop codon in the FAD2-1 gene (spec, p.65, line 6-7). On the other hand, FAD2-1 editing in the V1-13 line resulted in a small deletion in Allele 1 and single nucleotide insertion in Allele 2 resulting in the deletion of between 1 to 10 amino acids in fad2-1 (designated as the fad2 knock down (KD) or fad2-KD) encoding a truncated protein with a deletion of the first six amino acid residues from the N terminus and a mutation of N182/P183 to T182 (spec, p.65, line 18-25).
The Applicant describes transforming a yeast strain to measure enzymatic activity of different fad2-1 mutant proteins (spec, Example 10, p.82-83) and a reduction of enzymatic “activity resulting from the frame-shift mutations in the yeast model” (spec, p. 83, last 2 lines). It is noted here that a frameshift mutation inherently results in an entirely different protein sequence.
The conversion of oleic acid to linoleic acid in plants is facilitated by fatty acid desaturase 2 (FAD2) enzyme that is further classified into FAD2-1, FAD2-2, FAD2-3, and FAD2-4. (Dar et al., The FAD2 Gene in Plants: Occurrence, Regulation, and Role, 2017, Front. Plant Sci., 8:1789; abstract, line 2-4). The genes encoding FAD2-1, FAD2-2, FAD2-3 and FAD2-4 enzymes have high sequence similarity, but differ mostly in their expression patterns. The seed-specific FAD2 genes in plants (that affect grain/seed fatty acid composition) are effectively regulated by temperature, light and wounding (Dar et al. 2017; abstract, line 4-7). The desaturation of stearic acid (C18:0) to oleic acid (C18:1) is catalyzed by stearoyl-acyl carrier protein desaturase (SAD). Further desaturation of oleic acid to linoleic acid (18:2) is catalyzed by FAD2 in the ER and FAD6 in the plastid, whereas linoleic acid desaturation to γ-linolenic acid (C18:3, n6) is catalyzed by FAD3 in the ER and FAD7/FAD8 in the plastid (Dar et al. 2017; p.1, last 5 lines). Yeast cells are not known to have plastids. Post-translational modifications of proteins and regulation of gene expression mainly depending on light, temperature and/or wounding are either not present or work very differently in yeast as compared to plant cells. The Applicant does not describe if any of the fad2-1 mutant proteins retain same or (“some”) enzymatic activities in plant cells as observed in yeast cells.
Moreover, the Applicant does not describe any structure function relationship for FAD2-1. There is no specific domain and/or amino acid sequence responsible for the enzymatic activity of FAD2-1 protein is described by the Applicant. Current status of the art also does not teach any structure/function relationship between FAD2-1 structure and its function as an enzyme converting oleic acid to linoleic acid.
The Applicant does not describe if any of the fad2-1 mutant proteins retain “some” of the enzymatic function of converting oleic acid to linoleic acid in any plant cell including in rice (in seed) (Zaplin et al., bridging paragraph between p.2-3).
A skilled artisan would not be able to mutate the FAD2-1 protein in a way to retain some of its enzymatic activity to convert oleic acid to linoleic acid in plant/rice cells. Thus, it would not be possible for a skilled artisan to mutate the FAD2-1 protein in a way not to totally abolish its function as an enzyme converting oleic acid to linoleic acid.
An invention described solely in terms of a method of making and/or its function would lack written descriptive support where there is no described (in the specification) or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP § 2163.
Considering the breadth of the claims, lack of structure function relationship of the broad genus claimed, and unpredictability of the art, the Applicant does not appear to have been in possession of the claimed genus at the time this application was filed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-7, 9 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Zaplin et al. (Production of high oleic rice grains by suppressing the expression of the OsFAD2-1 gene, 2013, Functional Plant Biology, 40:996–1004) in view of Ma et al. (TALEN-Based Mutagenesis of Lipoxygenase LOX3 Enhances the Storage Tolerance of Rice (Oryza sativa) Seeds, 2015, PLoS ONE, 10:e0143877).
Claim 1 is drawn to a fertile cereal grain comprising a genetically modified FAD2-1 gene with reduced protein activity and a genetically modified LOX3 gene with reduced protein activity when compared to a wild type cereal grain.
Zaplin et al. describes the need to increase the storage/shelf life of brown rice and rice bran (p.1, bridging para between left column and right column), increase the value of rice bran oil (whether for human consumption or for use as a stock for biodiesel) by increasing the proportion of oleic acid while reducing the palmitic and linoleic acid content (p.1, right column, para 1, last 5 lines). Zaplin et al. describes transformed rice grains (as recited in claim 2) containing reduced FAD2-1 gene expression, and thus, reduced FAD2-1 activity, using RNAi suppression (abstract). The FAD2-1 RNAi lines produce fertile seeds that develops subsequent T1-T3 generations (Abstract; p.2; right column, para 2, line 3-4). Several mutated FAD2-1 RNAi lines show increased oleic acid content to the tune of 55.9 to 63.7% (as recited in claim 4), 15.0-17.3% of palmitic acid (as recited in claim 5), and less than 20% of linolic acid (as recited in claim 6) of total fatty acid content while an untransformed control rice grain contains 35% Oleic acid, 37.4% Linoleic acid, and 17.5% Palmitic acid (p.6, Table 3).
However, Zaplin et al. does not describe any LOX3 gene or LOX3 protein.
Ma et al. teaches that LOX3 deficiency (which reads on to “no LOX3 activity”, as recited in claim 7), achieved by mutating endogenous LOX3 gene, improved seed storability in rice while the rice seeds/grains are fertile to produce next generation plants (abstract, line 13-16). Ma et al. describes a point mutation in the LOX3 gene in rice “Daw Dam” variety resulting in a premature stop codon (stopping translation), as recited in claim 9, and producing LOX3-null mutant (p.2, para 2, line 10-12).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to undertake genetic modifications in a grain/rice cell (as recited in claim 1 and in claim 33) to reduce the FAD2-1 gene expression and, thus, the activity of the FAD2-1 protein, as described by Zaplin et al., while reducing the activity of the endogenous LOX3 protein by knocking out the endogenous LOX3 gene encoding LOX3 protein activity in rice, as described by Ma et al.
Before the effective filing date, the ordinarily skilled artisan would have been motivated to increase oleic acid content while reducing palmitic acid and linolic acid content in rice to increase the value of rice bran and/or rice bran oil by reducing the activity of endogenous FAD2-1 protein. The ordinarily skilled artisan also would have been motivated to reduce the activity of LOX3 protein by reducing the expression of endogenous LOX3 gene to improved storability of the rice grains/seeds. Stacking different traits in commercially important crops including rice is well known in the art that improve its commercial value ((Hathwaik et al., Efficient Gene Stacking in Rice Using the GAANTRY System, 2021, Rice (NY), 14:17 (Published on February 6 2021); abstract)).
It is noted here that specific fatty acid (oleic acid, palmitic acid and linoleic acid) content in the grain is expressed as a ratio or percentage of total fatty acid content which would not depend on moisture content (or “dry weight”, as recited in claims 4-6) in the grain. That is, a percentage of a component would still be the same whether measured as “wet” or dry weight basis.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Zaplin et al. in view of Ma et al. as applied to claims 1-2, 4-7, 9 and 13 above, and further in view of Abe et al. (Production of high oleic/low linoleic rice by genome editing, 2018, Plant Physiology and Biochemistry 131:58–62).
Claim 13 depends from claim 1 and is drawn to the grain comprising a genetically modified FAD2-1 gene encoding a mutant FAD2-1 protein.
Zaplin et al. in view of Ma et al. describe a fertile rice grain comprising a genetically modified FAD2-1 and LOX3 genes to reduce its activities resulting in increased oleic acid content while reducing palmitic acid and linolic acid content in rice and at the same time improving commercial value and storability of the rice grains/seeds, as discussed above.
However, Zaplin et al. in view of Ma et al. do not describe any modified FAD2-1 gene encoding a mutant FAD2-1 protein.
Abe et al. describes creating mutations comprising either 1-base insertion or an 8-base deletion in the rice FAD2-1 gene (OsFAD2-1) (p.59, right column, last para, line 9-11) using CRISPR-Cas9 gene editing technique (abstract; p.59, right column, last para, line 9-11). The indel mutant alleles encode mutant FAD2-1 proteins with C-terminal truncations and the mutated proteins are non-functional (p.59, right column, last para, last 3 lines; Fig. 2). In the fad2-1(-/-) homozygous mutant rice, the content of oleic acid increased to more than twice that of wild type (~80% of total fatty acid) while the linoleic acid was significantly reduced and could not be detected (p.61, left column, para 1, line 9-12). Thus, targeted mutagenesis of OsFAD2-1 using the CRISPR/Cas9 system produced significantly higher oleic acid and lower linoleic rice as compared to silencing the OsFAD2-1 gene using RNAi as described by Zaplin et al (p.61, left column, para 1, line 14-20).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to modify the method of mutating the OsFAD2-1 and LOX3 genes, as described by Zaplin et al. in view of Ma et al., by replacing RNAi mediated gene silencing with targeted genome editing using CRISPR-Cas9 to downregulate (including knocking out) OsFAD2-1 gene, as described by Abe et al.
Before the effective filing date, an ordinarily skilled artisan would have been motivated to significantly improve commercial value and storability of the rice grains/seeds by reducing the activities of FAD2-1 and LOX3 proteins to significantly increase oleic acid content while significantly reducing palmitic acid and linolic acid content (as compared to what described by Zaplin et al.) by knocking out OsFAD2-1 protein activity in rice, which is a commercially important grain crop.
Conclusion
No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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J.C.
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
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