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 .
Restriction Requirements
The amendments received on 10/27/2025 have been entered. Claims 1, 6-7, 14-18 are pending.
Claims 6-7, 14-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/16/2024.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Applicant argues in accordance with the Office's rejoinder procedure under MPEP 821.04, because withdrawn claims 6, 7, and 14-18 depend from claim 1 and require all limitations thereof, therefore Applicant requests that upon allowance of claim 1 that claims 6, 7, and 14-18 be rejoined and examined.
Applicants arguments are fully considered but they are not found persuasive since it would require two copies of the mutant alleles and further sequence search and analysis on mutation, homozygosity and heterozygosity of third mutant allele of SEQ ID NO:1, and mutation in SDP1-L and TT2 genes.
Applicant is reminded that unity of invention is reevaluated at each step of prosecution and when a claim is found to be allowable, then all claims that require the special technical features of the allowable claim will be rejoined because unity of invention will have been restored.
Therefore claim 1 is examined in this Office Action.
Rejection that are withdrawn
35 USC § 103 rejection over Xu et al. and further in view of Abdullah et al. and Joint Genome Institute (JGI) phytozome 14 (https://phytozome-next.jgi.doe.gov/) database and as evidenced by NCBI protein database, has been withdrawn in light of applicant’s amendment of claim 1 to specifically recite the mutated gene corresponds to SEQ ID NO:2 as second homeolog, and first and third homeologs as SEQ ID NO:3 and 1 are wild type allele. Xu et al. does not expressly teach mutation in SEQ ID NO:2 and Abdullah et al. does not strongly suggest involvement of SEQ ID NOs: 1-3 in SDP1 triacylglycerol lipase pathway in C. sativa.
The 35 USC § 103 rejection over Dhankher et al. and further in view of Moreno et al., Joint Genome Institute (JGI) phytozome 14 (https://phytozome-next.jgi.doe.gov/) database and as evidenced by NCBI protein database, has been maintained, see analysis below.
Claim Rejections - 35 USC § 112 – Written Description Requirement
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.
Claims 1 is 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 claim(s) 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.
Following analysis is modified necessitated by the amendment of claim 1, specifically recitation of the term “corresponding” to SEQ ID NOs: 1 and 2 in claim 1 steps b and c raise further written description issue of the structure of genus of alleles corresponding to the recited sequences.
The claim is broadly drawn to a genetically modified Camelina sativa plant comprising: a) a first homeolog of the SUGAR-DEPENDENT1 (SDP1) gene, which in wild-type C. sativa plants has a wild type allele of SEQ ID NO:3,occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 20and being homozygous for a wild- type allele; and (b) a second homeolog of the SDP1 gene, which in wild-type C. sativa plants has a wild type allele of SEQ ID NO:2, the second homeolog occurring in its natural position within the genome of the genetically modified plant on chromosome 13 and being homozygous for a mutant allele wherein the mutant allele does not encode an active SDP1 lipase; and (c) a third homeolog occurring in its natural position of the SDP1 gene, which in wild-type C. sativa plants has a wild type allele of SEQ ID NO:1, in chromosome 8 of the plant.
Analysis of Breadth of Claims
The mutation would be any mutation (i.e. insertion, deletion, replacement etc.) in any wild type allele corresponding to SEQ ID NO:2 in C. sativa in chromosome 13.
A second and third homeolog of a SDP1 gene would have any structure since an allele corresponding to SEQ ID NO:1 and 2 would encompass large number of alleles.
What is Described in the Specification
Applicant describes:
The analysis of amplicon sequencing data from wild-type WT43 plants showed that each sdp1 allele was represented in almost equal numbers (i.e. approximately 33% of sequences correspond to each allele, TABLE 4) (page 35, paragraph 00134).
The sdp1 and sdp1-like genes were selected for editing in Camelina sativa to reduce the turnover of TAGs that occurs in mature seeds, both to prevent yield loss and to prevent the undesirable accumulation of free fatty acids in oil after searching in GenBank for Camelina sativa DH55 genome using Genbank BLAST search tool using Arabidopsis SDP1 and SDP1-like proteins as queries (Spec, page 31, paragraph 127).
A combination of syntenic analysis and sequence alignment was used to identify the three homeologous copies of SDP1 and SDP1-like in the allohexaploid Camelina sativa genome (see FIG. 2A-D, page 32, paragraph 128, Table 2).
The three SDP1 in Camelina are Camelina SDP1_CH_8 (SEQ ID NO: 30); Camelina SDP1_CH_13 (SEQ ID NO: 31); and Camelina SDP1_ CH _20 (SEQ ID NO: 32) (page 10, paragraph 0051) encoded by SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 respectively (page 32, paragraph 00128).
Construct pMBXS1 107 (FIG. 4(A)) was designed with the Guide sequence SDP1-#71 (SEQ ID NO: 4; TABLE 3) fused to DNA encoding the RNA scaffold (FIG. 3) to allow formation of the functional sgRNA for editing all three copies of the sdp1 gene. Guide SDP1 #71 was designed to target all three homeologs of the sdp1 gene in Camelina WT43 germplasm (page 33-34, paragraph 129).
Amplicon sequencing data for the T1 lines transformed with pMBXS 1107 showed edits mostly in the form of 1 to 6 base pair deletions or single base pair insertions in the sdp1 gene (page 35, paragraph 135, Table 5).
In the T3 generation homozygous edits were obtained, however the maximum number of edited alleles in lines was two (TABLE 6) despite having observed heterozygous edits in all three sdp1 gene copies in the T1 generation (TABLE 5) (page 36, paragraph 00137).
T3 lines with homozygous editing in the SDP1 alleles on chromosome 13 or chromosome 8, as well as lines with homozygous editing in SDP1 alleles on chromosomes 13 and 20 were identified (TABLE 6). The sequence of the edited regions is shown for select lines in TABLE 6 (page 36, paragraph 137).
T4 generations best plants showed the highest yielding plants were those that contained edits in only the SDP1 gene located on chromosome 13 (NS14 lines, TABLE 7) leaving the copies on chromosomes 8 and 20 intact. Seed yields in these plants increased by up to 39% over the wild-type unedited control plants while seed oil content was similar (TABLE 7), hence it was increased seed yield that increased the total oil produced per plant by up to 40% compared to the control (page 37, paragraph 138).
Difference Between What was Described and What is Claimed
Applicant has not described second and third homeologs of the SPD1 gene since the wildtype allele corresponding to SEQ ID NOs: 1 and 2 are not described.
Applicant has not described use of any mutation (i.e. insertion, deletion, substitution) in the second homeolog of Camelina sativa plant since increase in seed yield can be obtained with mutating any of the SDP1 gene other than SDP1 gene located on chromosome 13 as SEQ ID NO:2 (page 34, paragraph 00129) using the guide-RNA comprising target sequence of SEQ ID NO:4 along with CRISPR nuclease leading to the deleted plants of NS14, Line 17-0781, and NS14 ,Line 17-0783 , causing the mutation as in SEQ ID NO:111 with the insertion of allele T.
Applicant has not described structure of any inactive SDP1 triacyl glycerol lipase gene.
Applicant has not described any mutation on in the second homeolog of Camelina sativa plant as wildtype allele corresponding to SEQ ID NO:2 would cause the inactive SDP1 triacyl glycerol lipase gene.
Analysis
The purpose of the written description is to ensure that the inventor had possession at the time the invention was made, of the specific subject claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
Applicant defines "Homeologs" are pluralities of genes (e.g. two, three, or more genes) that originated by speciation and were brought back together in the same genome by allopolyploidization (Glover et al., 2016, Trends Plant Sci., 21, 609) (page17, paragraph 0074) (Included in IDS submitted on 01/19/2022). Applicant defines "Allopolyploidy" is a type of whole-genome duplication by hybridization followed by genome doubling (Glover et al., 2016). Allopolyploidy typically occurs between two related species, and results in the merging of the genomes of two divergent species into one genome (Spec, page17, paragraph 0076). It is clear that there is no requirements of any identity of two homeolog of the SDP1 genes. For this reason, the structure of the second and third homeolog corresponding to SEQ ID NO:2 and 1 cannot be determined. It can be any sugar dependent gene since applicant has not expressly defined the structure required to be retained in “hybridization” of the gene before duplication in their definition that would produce any variants of the original gene and applicant has not defined the variation from the further natural or artificial selection in historical timeline to define them as homeolog of each other. Speciation is random process, for this reason without specifically defining homeolog referencing to speciation in any historical time of evolution of an organism does not describes the term. Furthermore, one would need progenitor genome to confirm the structure of first and second homeolog and it is not clear whether all the progenitor genomes are present to confirm the recited first and second homeolog is homeolog of any SDP1 gene.
Furthermore, Glover et al. (Published: 2016, Journal: Trends in Plant Science, July 2016, Vol. 21, No. 7) (Included in IDS submitted on 01/19/2022) teaches there are structural and functional divergence of homeologs and the chromosomes they reside wherein the definition of homeologs suffers from inconsistent interpretation, usage, and spelling (page 619, concluding remarks, see Table 1 below).
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Glover et al. teaches since homoeology is characterized by an initial speciation event, once the progenitor species of the future allopolyploid begin to diverge, the corresponding genes in each new species that descended from a common ancestral gene start diverging in their genic sequences (Figure 2) along with single-gene duplications, deletions, and rearrangements (page 613, paragraph 5).
Glover et al. teaches conservation of relative genomic location in itself is not a requirement for homoeology, which depends only on the type of event that gave rise to the sequences (page 616, paragraph 3). Therefore, the homeolog would have any structure.
Therefore, the structure of the second and third homeologs on chromosomes 13 and 8 respectively are not described with their structure relating to the function since the wildtype allele corresponding to SEQ ID NOs: 1 and 2 would be any allele. For example, Merriam Webster dictionary defines the term “corresponding” as “related, accompanying” or “having or participating in the same relationship (such as kind, degree, position, correspondence, or function) especially with regard to the same or like wholes (such as geometric figures or sets)” (accessed 01/30/2026, accessed at CORRESPONDING Definition & Meaning - Merriam-Webster). Therefore the wildtype allele corresponding to SEQ ID NOs: 1 and 2 would comprise large variants of sequence (same or like wholes) related to or have some relationships with the SEQ ID NO:1 and 2. Instead applicant has not described any sequences other than SEQ ID NO:1 and 2 in third and second homeologs. Therefore, there is dearth of description of wildtype allele corresponding to SEQ ID NOs: 1 and 2 and mutant allele of the corresponding allele of SEQ ID NO:2 with any mutation that would lead to the mutant allele not encoding an active SDP1 tryacylglycerol lipase.
Furthermore, Applicant has not described any mutation on in the second homeolog of Camelina sativa plant as wildtype allele corresponding to SEQ ID NO:2 would cause the inactive SDP1 triacyl glycerol lipase gene. In figure 5, applicant describes the expression profiles of SDP1s on chromosomes 8, 13 and 20, however there is dearth of description of whether the mutation in SEQ ID NO:2 has inactivated tryacylglycerol lipase.
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Applicant has not described mutation in any of the homeolog corresponding to SEQ ID NO:2 of any of the line from C. sativa would have any use. For example the JGI genome database (accessed on https://phytozome-next.jgi.doe.gov/report/protein/Csativavar_DH55_1_0/Csa13g006100.1, accessed 07/17/2025) showed there is diversity of SDP1 genome homeolog for example in sample of sequenced C. sativa plant the plant from the database of C. sativa Joelle v1.1 has 99.9% identity to the Csa13g006100 which has 100% sequence identity to applicant’s SEQ ID NO: 31 (i.e. SDP1 gene). Therefore, given the variations among the C. sativa lines, applicant has not described any mutation in the any homeolog of the SDP1 in chromosome 13 would have any use other than the specific mutation in SEQ ID NO: 31 that renders the homeolog does not encode an active SDP1 triacylglycerol lipase compared to the wildtype plant.
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The mutation of SDP1 gene would include any mutation from spontaneous mutation or mutation by mutagens such as chemical or gamma rays, or mutation by using CRISPR CAS systems, the mutation would include any number of insertions, and deletions ranging from few nucleotides to any number of nucleotides. Applicant has only described mutation using CRISPR Cas9 with specific guide sequence SDP1-#71 (SEQ ID NO: 4). Since for example applicant showed in Table 7 that the mutation would cause increase in seed yield only when the mutation was in SDP1 gene of Chromosome 13 and has negative effect when SDP1 of chromosome 20 was edited. Applicant in claim 1 only recite first homeolog encodes an active SDP1 triacylglycerol lipase comprising SEQ ID NO:32 and it is not clear whether the third homeolog corresponding to SEQW ID NO:1 would encode an active SDP1 triacylglycerol lipase since it is wildtype allele. However, since it does not specifically recite there is no description whether the allele would encode the active lipase or not.
Furthermore, applicant has only described sdp1 alleles are found in chromosomes 8, 13 and 20 (see Table 4 above) and guide sequence SDP1-#71 has target sequence of SEQ ID NO: 4 that targets SEQ ID NO: 1-3 of the chromosomes 8, 13 and 20 (see Table 3). Therefore, applicant has only showed the mutant allele cause by CRISPR system including guide sequence SDP1-#71 that has target sequence of SEQ ID NO: 4 would cause the SDP1 inactive when specific nucleotides showed in Table 6 (see sequence above) are edited. In chromosome 8 and 13. Applicant has not described any mutation of the homeolog of the SDP1 gene other than using Guide sequence SDP1-#71 (SEQ ID NO: 4).
For this reason, there is a dearth of description of a genetically modified Camelina sativa plant with use as increased seed yield with any kind of mutant alleles with one or more additions, deletions, or substitutions anywhere in second homeolog of SDP1 gene.
Applicant has not described any mutation of any identical wild type allele other than SEQ ID NO: 2 encoding SEQ ID NO: 31 of chromosome 13 that would have use of increasing seed yield of up to 38.8% in Camelina sativa. Applicant showed in Table 7 that the mutation would cause increase in seed yield only when the mutation was in SDP1 gene of Chromosome 13 and has negative effect when SDP1 of chromosome 20 was edited. Furthermore, applicant has only described sdp1 alleles are found in chromosome 8, 13 and 20 (see Table 4) and guide sequence SDP1-#71 has target sequence of SEQ ID NO: 4 that targets SEQ ID NOs: 1-3 of the chromosomes 8, 13 and 20 (see Table 3). Applicant has not described any mutation of any corresponding wild type allele other than SEQ ID NOs: 2 of chromosome 13 would have use of increasing seed yield of up to 38.8% in Camelina sativa. Therefore, there is dearth of description of any homeolog of SDP1 wild-type allele that are kept wild-type and any allele that are mutated.
Applicant described the T4 generation best plants showed the highest yielding plants were those that contained edits in only the SDP1 gene located on chromosome 13 (NS14 lines, TABLE 7) leaving the copies on chromosomes 8 and 20 intact. Seed yields in these plants increased by up to 39% over the wild-type unedited control plants while seed oil content was similar (TABLE 7) (page 37, paragraph 138).
Applicant has not described use of any of the SDP1 gene other than SDP1 gene located on chromosome 13 as SEQ ID NO:2 (page 34, paragraph 00129) using the guide-RNA comprising target sequence of SEQ ID NO:4 leading to the deleted plants of NS14, Line 17-0781, and NS14, Line 17-0783, causing the mutation as in SEQ ID NO:111 with the insertion of allele T.
Given the virtually large structural variation associated with these embodiments, the claims read on an extremely broad and highly diverse structures of the homeologs of SDP1 genes corresponding to SEQ ID NOs: 1 and 2 in the genetically modified plant that have showed to as use of specific function of increase in seed yield. Thus, in view of the analysis presented above, a skilled artisan would appreciate that the claims are directed to extremely broad and highly diverge genus of sequence variants that are required to have the specific function of increase in seed yield.
Relating to structure vs. function, the claims remain drawn to any unspecified SDP1 gene corresponding to SEQ ID NOs:1 and 2. This leads to a situation where the instantly claimed mutated genes would not possess the necessary structural features needed to accomplish the claimed phenotype that the applicant found them useful. The Specification makes clear that the specific sequences of SEQ ID NOs: mutated and maintained wildtype lend to the phenotype, thus it is necessary to claim the gene as such (i.e. specific gene).
"The test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to one skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharm, Inc, v EH Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Lockwood v. Amer. Airlines, ina, 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). "An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations. Lockwood, 107 F.3d at 1572, 41 USPG2d at 1966". While the written description requirement does not demand either examples or an actual reduction, actual "possession" or reduction to practice outside of the specification is not enough. Ariad Pharm, Inc. v. Eli Lilly & Co., 598 F,3d 1336,1352 (Fed. Cir. 2010). Rather, it is the specification itself that must demonstrate possession. Id.
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Response to Applicant’s Argument
Applicant's arguments filed 10/27/2025 have been fully considered but they are not persuasive.
Applicant argues the disclosure of the present application conveys to the skilled person that the inventors had possession of the genetically modified Camelina sativa plant of claim 1 as amended as of the filing date based on the specification providing detailed examples and actual reductions to practice (response to Rejection, page 6, second paragraph).
Applicant argues the specification teaches the identity of each of these three homeologs based on chromosomal location and wild-type sequence of each. Applicant argues the specification teaches that Camelina sativa is an allohexaploid plant species that contains three subgenomes and thus is expected to contain three homeologous copies, also termed homeologs, of each gene (specification, paragraph [00128]). Applicant argues the specification also teaches that, as expected, Camelina sativa contains three homeologs of the SDP1 gene (specification, paragraph [00128]). Applicant argues the specification teaches that the three homeologs of SDP1 were identified on chromosomes 20, 13, and 8 of Camelina sativa, with wild-type alleles corresponding to SEQ ID NOS: 3, 2, and 1, respectively, as disclosed in the specification, and to GenBank accessions XM_0l0492596.2, XM_0l0453992.2, and XM_0l0425338.2, also respectively, as available from GenBank (see specification, paragraph [00128]). Applicant argue the specification thus teaches that the first homeolog of the SDP1 gene of claim 1, which as recited in claim 1 occurs in its natural position within the genome of the genetically which as recited in claim 1 occurs in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 8 is the homeolog of Camelina sativa SDP1 that in wild-type Camelina sativa plants occurs on chromosome 8 and has a wild-type allele corresponding to SEQ ID NO: 1. (response to Rejection, page 8, second paragraph).
Applicant argues as noted, claim 1 recites that the first homeolog is homozygous for the wild-type allele in the genetically modified Camelina sativa plant, and the second homeolog is homozygous for a mutant allele in the genetically modified Camelina sativa plant. Applicant argues claim 1 further recites that the wild-type allele of the first homeolog encodes an active SDP1 triacylglycerol lipase comprising SEQ ID NO: 32, and that the mutant allele of the second homeolog does not encode an active SDP1 triacylglycerol lipase (response to Rejection, page 9, first paragraph).
Applicant argues regarding the active SDP1 triacylglycerol lipase encoded by the first homeolog, the specification teaches that the Camelina sativa SDP1 gene encoded by SEQ ID NO: 3 encodes the Camelina sativa SDP1 triacylglycerol lipase of SEQ ID NO: 32 (specification, Table 2) (response to Rejection, page 9, third paragraph).
Applicant argues regarding the mutant allele of the second homeolog not encoding an active SDP1 triacylglycerol lipase, the specification teaches that the second homeolog can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of the wild-type allele of the second homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase (see, e.g., specification, paragraph [0011]). Applicant argues this concept would be well known and understood by a skilled person because it is fundamental to understanding and practicing molecular biology. Applicant argues the specification teaches that the disruption can be made by including one or more additions, deletions, or substitutions of one or more nucleotides relative to the wild-type allele of the second homeolog (specification, paragraph [0011]). Applicant argues the skilled person would know that additions and/or deletions can disrupt an open reading frame by introducing a frameshift mutation, and that substitutions can disrupt an open reading frame by introducing stop codons, any of which change can be introduced predictably to change an open reading frame from one that encodes an active protein, such as an active SDP1 triacylglycerol lipase, to one that does not (response to Rejection, page 9, last paragraph).
Applicant argues the specification teaches that this can be done using known transformations to genetically modify the second homeolog of SDP1 of a Camelina sativa plant using transgenic, cis-genic, or genome editing methods (see specification, paragraph [0094]). Applicant argues the specification teaches, for example, that recent advances in genome editing technologies provide an opportunity to precisely remove genes, edit control sequences, introduce frame shift mutations, etc., to significantly alter the expression levels of targeted genes and/or the activities of the proteins encoded thereby (specification, paragraph [00121]) (response to Rejection, page 10, first paragraph).
Applicant argues regarding the third homeolog of the SDP1 gene, the specification teaches that the Camelina sativa SDP1 gene encoded by SEQ ID NO: 1 encodes the Camelina sativa SDP1 triacylglycerol lipase of SEQ ID NO: 30 (specification, Table 2). Applicant argues the specification also teaches that in the genetically modified Camelina sativa plant the third homeolog of the SDP1 gene can be homozygous for a wild-type allele, e.g., homozygous for SEQ ID NO: 1, homozygous for a mutant allele, or heterozygous for a wild-type allele and a mutant allele (see specification, paragraph [0019]). Applicant argues for essentially the same reasons as provided for the second homeolog of SDP1, the specification teaches that the third homeolog can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the third homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase (response to Rejection, page 10, second paragraph).
Applicant argues the specification describes detailed examples of how to make the genetically modified Camelina sativa plant of claim 1. Applicant argues as noted above, the specification discloses that Camelina sativa is a known plant species, that Camelina sativa is an allohexaploid plant species that contains three subgenomes and thus is expected to contain three homeologous copies, also termed homeologs, of each gene, and that, as expected, Camelina sativa contains three homeologs of the SDP1 gene (response to Rejection, page 10, last paragraph).
Applicant argues the specification also discloses that the three copies of SDP1 were identified on chromosomes 20, 13, and 8 of Camelina sativa, corresponding to SEQ ID NOS: 3, 2, and 1, respectively, and to GenBank accessions XM_0l0492596.2, XM_0l0453992.2, and XM_0l0425338.2, also respectively. Applicant argues the specification also describes detailed guidance regarding how to disrupt the open reading frame of a wild-type allele of the second homeolog of the SDP1 gene and optionally the open reading frame of a wild-type allele of the third homeolog of the SDP1 gene so that they no longer encode active SDP1 triacylglycerol lipases (specification, paragraphs [0094]-[00125]) (response to Rejection, page 11, first paragraph).
Applicant argues the specification also provides actual reductions to practice of the genetically modified Camelina sativa plant of claim 1. Applicant argues these include NS14 Line 17-0781 and NS14 Line 17-083, both of which are genetically modified Camelina sativa plants comprising: (a) a first homeolog of the SUGAR-DEPENDENT] (SDP1) gene, which in wild-type Camelina sativa plants has a wild-type allele of SEQ ID NO: 3 and is located on chromosome 20 of the Camelina sativa genome, the first homeolog occurring in its natural position within the genome of the genetically modified Camelina sativa plant; (b) a second homeolog of the SDP1 gene, which in wild-type Camelina sativa plants has a wild-type allele corresponding to SEQ ID NO: 2 and is located on chromosome 13 of the Camelina sativa genome, the second homeolog occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 13 and being homozygous for a mutant allele in the genetically modified Camelina sativa plant; and (c) a third homeolog of the SDP1 gene, which in wild-type Camelina sativa plants has a wild-type allele corresponding to SEQ ID NO: 1 and is located on chromosome 8 of the Camelina sativa genome, the third homeolog occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 8, wherein: (i) the wild-type allele of the first homeolog encodes an active SDP1 triacylglycerol lipase comprising SEQ ID NO: 32; and (ii) the mutant allele of the second homeolog does not encode an active SDP1 triacylglycerol lipase, as claimed (Specification, Tables 6 and 7) (response to Rejection, page 11, last paragraph).
Applicant argues although the Official action contends that the mutation would be any mutation in any homeolog of the SDP1 gene of Camelina sativa in chromosome 13, as discussed above the specification teaches that the second homeolog of the SDP1 gene can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wildtype allele of the second homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase (response to Rejection, page 12, second paragraph).
Applicant moreover, although the Official action contends that a second and third homeolog of a SDP1 gene would have any structure, and that Applicant has not described second and third homeologs of the SDP1 gene, as discussed above the specification teaches that the second homeolog of the SDP1 gene is the homeolog of Camelina sativa SDP 1 that in wild-type Camelina sativa plants occurs on chromosome 13 and has a wild-type sequence corresponding to SEQ ID NO: 2, and that the third homeolog of the SDP1 gene is the homeolog of Camelina sativa SDP1 that in wild-type Camelina sativa plants occurs on chromosome 8 and has a wildtype sequence corresponding to SEQ ID NO: 1 (response to Rejection, page 12, third paragraph).
Applicant argue although the Official action contends that Applicant has not described that an increase in seed yield can be obtained by mutating any of the SDP1 genes other the SDP1 gene located on chromosome 13 as SEQ ID NO: 2 using the guide-RNA comprising target sequence of SEQ ID NO: 4 along with CRISPR nuclease leading to the deleted plants of NS 14 Line 17-0781 and NS14 Line 17-083, causing the insertion as in SEQ ID NO: 111 with the insertion of the nucleotide T, claim 1 does not recite an increase in seed yield (response to Rejection, page 12, last paragraph).
Applicant argues moreover, as discussed above the specification teaches that the second homeolog of the SDP1 gene can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the second homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase (response to Rejection, page 13, first paragraph).
Applicant argues, furthermore, although the Official action contends that Applicant has not described any structure of any inactive SDP triacyl glycerol lipase gene, again as discussed above the specification teaches that the second homeolog of the SDP1 gene can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the second homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase (response to Rejection, page 13, second paragraph).
Applicant argue further still, although the Official action contends that it is clear that there are no requirements of any identity of two homeologs of the SDP1 genes, that for this reason the structures of the second and third homeologs cannot be determined, and that one would need a progenitor genome to confirm the structure of first and second homeologs and it is not clear whether all the progenitor genomes are present to confirm the recited first and second homeologs are homeologs of any SDPI gene, as discussed above the specification teaches that Camelina sativa is a known plant species, that the first homeolog of the SDP1 gene is the homeolog of Camelina sativa SDPI that in wild-type Camelina sativa plants occurs on chromosome 20 and has a wild-type sequence corresponding to SEQ ID NO: 1, that the second homeolog of the SDP1 gene is the homeolog of Camelina sativa SDP1 that in wild-type Camelina sativa plants occurs on chromosome 13 and has a wild-type sequence corresponding to SEQ ID NO: 2, and that the third homeolog of the SDP1 gene is the homeolog of Camelina sativa SDP1 that in wild type Camelina sativa plants occurs on chromosome 8 and has a wild-type sequence corresponding to SEQ ID NO: 1 (response to Rejection, page 13, last paragraph).
Applicant argues although the Official action contends that the second and third homeologs on chromosomes 13 and 8 respectively are not described with their structure relating to their function, regarding chromosome 13 as discussed the specification teaches that the second homeolog of the SDP1 gene can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the second homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase. Applicant argues regarding chromosome 8, as discussed above the specification teaches that the Camelina sativa SDP1 gene encoded by SEQ ID NO: 1 encodes the Camelina sativa SDP1 triacylglycerol lipase of SEQ ID NO: 30, and for essentially the same reasons as provided for the second homeolog of SDP1, the specification teaches that the third homeolog can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the third homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase (response to Rejection, page 13, last paragraph).
Applicant argues although the Official action contends that it is clear that two genes are required to be wild-type and at least SEQ ID NO: 2 needs to be mutated, and that for this reason there is a dearth of description of any mutation of any homeolog of the SDP1 gene that would have any use of the mutation to increase seed yield, again claim 1 does not recite an increase in seed yield. Applicant argues moreover, the specification does not teach that two genes are required to be wild-type. Applicant argues for example, although the specification describes in one example, namely Example 2, that in the T3 generation homozygous edits of this example the maximum number of edited alleles in Camelina sativa lines was two and that T3 lines with homozygous editing in the SDP1 alleles on chromosome 13 or chromosome 8 were identified, as well as lines with homozygous editing in SDP1 alleles on chromosomes 13 and 20 (specification, Example 2, paragraph [00137]), the specification also teaches in another example, namely Example 4, that TS seed were obtained from Camelina sativa plants with complete editing in all three homeologs of SDP1 (specification, Example 4, Table 14) (response to Rejection, pages 13 and 14, last and first paragraph).
Applicant argues although the Official action contends that the second and third homeologs on chromosomes 13 and 8 respectively are not described with their structure relating to their function, regarding chromosome 13 as discussed the specification teaches that the second homeolog of the SDP1 gene can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the second homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase. Applicant argues regarding chromosome 8, as discussed above the specification teaches that the Camelina sativa SDP1 gene encoded by SEQ ID NO: 1 encodes the Camelina sativa SDP1 triacylglycerol lipase of SEQ ID NO: 30, and for essentially the same reasons as provided for the second homeolog of SDP1, the specification teaches that the third homeolog can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele of the third homeolog so that it no longer encodes an active SDP1 triacylglycerol lipase.
Applicant argues although the Official action contends that it is clear that two genes are required to be wild-type and at least SEQ ID NO: 2 needs to be mutated, and that for this reason there is a dearth of description of any mutation of any homeolog of the SDP1 gene that would have any use of the mutation to increase seed yield, again claim 1 does not recite an increase in seed yield. Applicant argues Moreover, the specification does not teach that two genes are required to be wild-type. Applicant for example, although the specification describes in one example, namely Example 2, that in the T3 generation homozygous edits of this example the maximum number of edited alleles in Camelina generation homozygous edits of this example the maximum number of edited alleles in Camelina chromosome 13 or chromosome 8 were identified, as well as lines with homozygous editing in SDP1 alleles on chromosomes 13 and 20 (specification, Example 2, paragraph [00137]), the specification also teaches in another example, namely Example 4, that TS seed were obtained from Camelina sativa plants with complete editing in all three homeologs of SDP 1 (specification, Example 4, Table 14) (response to Rejection, page 14, first paragraph).
Applicant's arguments have been fully considered but they are not persuasive since:
Regarding argument on specification teaches specification teaches that the three homeologs of SDP1 were identified on chromosomes 20, 13, and 8 of Camelina sativa, with wild-type alleles corresponding to SEQ ID NOs: 3, 2, and 1, the argument was not found persuasive since the term “corresponding” would mean any structure of the recited sequences of SEQ ID NOs: 1 and 2. Therefore there is death of description of any wild type allele corresponding to SEQ ID NOs: 2 and 1 are recited in amended claims.
Regarding argument on activity of SDP1 triacylglycerol lipase after mutation in second homeolog of SEQ ID NO:2, the argument was not found persuasive since there is dearth of description of the SDP1 triacylglycerol lipase was inactive by virtue of example. Applicant has not described the level of activity of SDP1 triacylglycerol lipase upon mutation of the second homeolog.
Regarding argument on introducing stop codons would have predictable effect on the function of the second and third homeolog is not found persuasive since for example There are examples where such stop codon readthrough (SCR) are common in plants. For example, Zhang et al. (Published: 2024, Journal: Cell Reports, 43(2):1-21) showed the evidence for presence of substantial SCR in plants as maize, rice, soybean and Arabidopsis (Zhang et al., page 7, right paragraph 1). Zhang et al. further describes SCR events are commonly present in plant species and found unprecedented plasticity of stop codons (page 11, right paragraph 3). Therefore, there is dearth of description of any change to any stop codon in anywhere in the allele corresponding to SEQ ID NOs:2 and 1 would inactivate the SDP1 triacylglycerol lipase gene, leading to change in phenotypes.
Regarding argument on third homeolog can be made to not encode an active SDP1 triacylglycerol lipase based simply on disrupting the open reading frame of a wild-type allele, applicant has not described any mutation in third homeolog would have any use other than when the mutation in both second and third homeolog in specific place, using specific guide RNA would cause the decrease in seed yield and oil content (see Spec, page 47, table 7). Therefore, there is death of description of third homeolog with any allele corresponding to SEQ ID NO: 1 and its mutation anywhere would cause any change in function of the gene.
Regarding argument on claim 1 does not recite an increase in seed yield, the argument was not found persuasive since the analysis is based on the use of the mutants described by the Applicants for either increase or decrease in seed yield and oil content. Furthermore, applicant has not described there will be use of any mutation in SEQ ID NO:2 in the C. sativa plant wherein applicant has only showed the SDP1 gene located on chromosome 13 as SEQ ID NO: 2 using the guide-RNA comprising target sequence of SEQ ID NO: 4 along with CRISPR nuclease leading to the deleted plants of NS 14 Line 17-0781 and NS14 Line 17-083, causing the insertion as in SEQ ID NO: 111 with the insertion of the nucleotide T, would lead to use of plant as increase in seed yield and oil content (see Table 7).
Regarding argument on requirement on two genes to be wild-type and at least SEQ ID NO: 2 needs to be mutated is not requirements as sowed in Table 14 was found partially persuasive. However, the mutant lines in Table 14 have only been described to have higher oil content when the other genes Sdp1-like and tt2 were edited found in chromosomes 4, 69 and 10, 11 and 12 respectively wherein applicant has not described, the use of any mutation that would only cause mutation in the SDP1 genes.
Therefore, the written description requirements rejection has been maintained.
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.
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 non-obviousness.
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.
Obvious over Dhankher et al. in view of Moreno et al. and JGI phytozome 14
Claims 1 is rejected under 35 U.S.C. 103 as being unpatentable over Dhankher et al. (US Pub. No.: US 2018 / 0237792 A1, Pub. Date: Aug. 23, 2018), and further in view of Moreno et al. (Published Year: 2016, Journal: Plant Cell Physiol. 58(7): 1260–1267 (2017) doi:10.1093/pcp/pcx058), and further in view of Joint Genome Institute (JGI) phytozome 14 (https://phytozome-next.jgi.doe.gov/) database and as evidenced by NCBI protein database.
The claim is drawn to a genetically modified Camelina sativa plant comprising: a) a first homeolog of the SUGAR-DEPENDENT1 (SDP1) gene; and (b) a mutated second homeolog of the SDP1 gen, (c) a third homeolog of the SDP1 gene.
Regarding claim 1, Dhankher et al. teaches transgenic Camelina sativa cv. Suneson transformed with three constructs made in pCambia RedSeed (FIG. 2A) wherein one was for overexpression of MGAT1 (FIG. 11 upper construct, a contract for overexpression of PDCT1 and construct for expression of SDP1 RNAi to reduce expression of the SDP1 gene (FIG. 11, bottom construct) (page 16, paragraph 0159). Dhankher et al. teaches RNAi knockdown of the SDP1 gene in Camelina caused more than 30% increase in seed size, 6 - 15 increase in oil contents, and more than 2 - fold increase (double) in total seed yield per plant basis (page 16, paragraph 0162). Dhankher et al. teaches SDP1 gene were identified as significant in regulating oilseed yield produce almost a three - fold increase in total per plants energy yield in the Camelina sativa (page 16, paragraph 0162).
Dhankher et al. teaches SPD1 has a sequence of SEQ ID NO:5, wherein the Dhankher et al.’s SEQ ID NO: 5 encodes the protein of applicant’s SEQ ID NO: 31 from chromosome 13 (see encoded PDF) and see below for alignment of Dhankher et al.’s SEQ ID NO: 5 to the NCBI nucleotide database (see included alignment in PDF). Therefore, Dhankher et al. teaches reducing expression of SEQ ID NO: 31 from chromosome 13 would cause more than 30% increase in seed size, 6 - 15 increase in oil contents, and more than 2 - fold increase (double) in total seed yield per plant basis (page 16, paragraph 0162).
Dhankher et al. teaches T3 seeds having RNAi knockdown of SDP1 gene expression in FIG. 14 (page 16, paragraph 0161).
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Furthermore, Dhankher et al. teaches an endogenous SPD1 of a plant can be modified to be non-functional (i. e., knocked out) or to have reduced activity using known methods, for example, the CRISPR / Cas system (page 14, paragraph 0127).
Dhankher et al. teaches methods are provided for producing a transgenic plant by suppressing the plant’s endogenous SPD1 using, for example, by modifying or engineering an endogenous SPD1 gene by, for example, genome editing or mutation, so that the activity of the endogenous SPD1 is reduced, or eliminated (page 14, paragraph 0128).
Dhankher et al. however, does not produced a Camelina sativa plant that has mutation in an endogenous SDP1 gene.
Moreno et al. teaches Camelina sativa possesses a relatively undifferentiated hexaploid genome, up to three gene homeologs can code for any particular enzymatic activity, wherein specifically designed guide RNA identical to all three homeologs would specifically target CsDAT1 or CsDAT1 homeologous genes for triacylglycerol (TAG) synthesis in developing seeds leading to mutant phenotypes with phenotypic difference in seeds and altered oil content and fatty acid compositions (page 1260, Abstract).
Furthermore, JGI genome database (accessed on https://phytozome-next.jgi.doe.gov/report/protein/Csativavar_DH55_1_0/Csa13g006100.1, accessed 07/17/2025) showed the Csa13g006100.1 (i.e. found in chromosome 13) has 100% sequence identity to applicant’s SEQ ID NO: 31 (i.e. the applicant described second homeolog of SDP1) (see Figure above)(encoded by nucleotide sequence of SEQ ID NO:2, see page 32, Table 2). The alignment of SEDQ ID NO: 32 (i.e. has 32 has the applicant described first homeolog of SDP1) has 100% identity to Csa20g005210.1 (see alignment below) (encoded by nucleotide sequence of SEQ ID NO:3, see page 32, Table 2). Furthermore, JGI genome showed line cultivar DH55 has Csa08g060480.1 as SDP1 homeolog on chromosome 8. Furthermore, JGI phytozome 14, teaches the sequence were available in phytotomzome and NCBI in 2014 (see included PDF).
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Furthermore, SEQ ID NO: 32 has 100% sequence identity to the locus XP_010490898 as triacylglycerol lipase SDP1 isoform X1 of Camelina sativa (see enclosed PDF). Therefore, the locus is an endogenous homeolog in Camelina sativa of triacylglycerol lipase SDP1.
Alignment of SEQ ID NO: 32 to NCBI protein database:
Query: unnamed protein product Query ID: lcl|Query_9649028 Length: 830
>PREDICTED: triacylglycerol lipase SDP1 isoform X1 [Camelina sativa]
Sequence ID: XP_010490898.2 Length: 830
>PREDICTED: triacylglycerol lipase SDP1 isoform X2 [Camelina sativa]
Sequence ID: XP_019097840.1 Length: 830
Range 1: 1 to 830
Score:1721 bits(4457), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:830/830(100%), Positives:830/830(100%), Gaps:0/830(0%)
Query 1 MDISNEASVDPFSIGPTSIMGRTIAFRVLFCRSMAQLRRDLFRFLLHWFLRFKLTVSPFV 60
MDISNEASVDPFSIGPTSIMGRTIAFRVLFCRSMAQLRRDLFRFLLHWFLRFKLTVSPFV
Sbjct 1 MDISNEASVDPFSIGPTSIMGRTIAFRVLFCRSMAQLRRDLFRFLLHWFLRFKLTVSPFV 60
Query 61 SWFHPRNPQGILAVVTIIAFVLKRYTNVKIKAEMAYRRKFWRNMMRTALTYEEWAHAAKM 120
SWFHPRNPQGILAVVTIIAFVLKRYTNVKIKAEMAYRRKFWRNMMRTALTYEEWAHAAKM
Sbjct 61 SWFHPRNPQGILAVVTIIAFVLKRYTNVKIKAEMAYRRKFWRNMMRTALTYEEWAHAAKM 120
Query 121 LEKETPKLNESDLYDEELVKNKLQELRHRRQEGSLRDIMFCMRADLVRNLGNMCNSELHK 180
LEKETPKLNESDLYDEELVKNKLQELRHRRQEGSLRDIMFCMRADLVRNLGNMCNSELHK
Sbjct 121 LEKETPKLNESDLYDEELVKNKLQELRHRRQEGSLRDIMFCMRADLVRNLGNMCNSELHK 180
Query 181 GRLQVPRHIKEYIDEVSTQLRMVCNSDSEELSLEEKLSFMHETRHAFGRTALLLSGGASL 240
GRLQVPRHIKEYIDEVSTQLRMVCNSDSEELSLEEKLSFMHETRHAFGRTALLLSGGASL
Sbjct 181 GRLQVPRHIKEYIDEVSTQLRMVCNSDSEELSLEEKLSFMHETRHAFGRTALLLSGGASL 240
Query 241 GAFHVGVVRTLVEHKLLPRIIAGSSVGSIICAVVASRSWPELQSFFENSLHSLQFFDQLG 300
GAFHVGVVRTLVEHKLLPRIIAGSSVGSIICAVVASRSWPELQSFFENSLHSLQFFDQLG
Sbjct 241 GAFHVGVVRTLVEHKLLPRIIAGSSVGSIICAVVASRSWPELQSFFENSLHSLQFFDQLG 300
Query 301 GVFSIVKRVMTQGALHDIRQLQCMLRNLTSNLTFQEAYDMTGRILGITVCSPRKHEPPRC 360
GVFSIVKRVMTQGALHDIRQLQCMLRNLTSNLTFQEAYDMTGRILGITVCSPRKHEPPRC
Sbjct 301 GVFSIVKRVMTQGALHDIRQLQCMLRNLTSNLTFQEAYDMTGRILGITVCSPRKHEPPRC 360
Query 361 LNYLTSPHVVIWSAVTASCAFPGLFEAQELMAKDRSGEIVPYHPPFNLGPEVGTKSSGRR 420
LNYLTSPHVVIWSAVTASCAFPGLFEAQELMAKDRSGEIVPYHPPFNLGPEVGTKSSGRR
Sbjct 361 LNYLTSPHVVIWSAVTASCAFPGLFEAQELMAKDRSGEIVPYHPPFNLGPEVGTKSSGRR 420
Query 421 WRDGSLEVDLPMMQLKELFNVNHFIVSQANPHIAPLLRLKDLVRAYGGRFAAKLAHLVEM 480
WRDGSLEVDLPMMQLKELFNVNHFIVSQANPHIAPLLRLKDLVRAYGGRFAAKLAHLVEM
Sbjct 421 WRDGSLEVDLPMMQLKELFNVNHFIVSQANPHIAPLLRLKDLVRAYGGRFAAKLAHLVEM 480
Query 481 EVKHRCNQVLELGFPLGGLAKLFAQEWEGDVTVVMPATLAQYSKIIQNPTHLDLQKAANQ 540
EVKHRCNQVLELGFPLGGLAKLFAQEWEGDVTVVMPATLAQYSKIIQNPTHLDLQKAANQ
Sbjct 481 EVKHRCNQVLELGFPLGGLAKLFAQEWEGDVTVVMPATLAQYSKIIQNPTHLDLQKAANQ 540
Query 541 GRRCTWEKLSAIKSNCGIELALDDSVAILNHMRRLKKSAERAASATSSSHHGLASTTRFN 600
GRRCTWEKLSAIKSNCGIELALDDSVAILNHMRRLKKSAERAASATSSSHHGLASTTRFN
Sbjct 541 GRRCTWEKLSAIKSNCGIELALDDSVAILNHMRRLKKSAERAASATSSSHHGLASTTRFN 600
Query 601 ASRRIPSWNVIARENSTGSLDDLAADNNNLHASSGRNLSDSETESVELSSSWTRTGGPLM 660
ASRRIPSWNVIARENSTGSLDDLAADNNNLHASSGRNLSDSETESVELSSSWTRTGGPLM
Sbjct 601 ASRRIPSWNVIARENSTGSLDDLAADNNNLHASSGRNLSDSETESVELSSSWTRTGGPLM 660
Query 661 RTASANKFIDFVQSLDIDIALARGFSSSPNSPAVPPGGPFSPSARSMSAHSDSEPNSNSN 720
RTASANKFIDFVQSLDIDIALARGFSSSPNSPAVPPGGPFSPSARSMSAHSDSEPNSNSN
Sbjct 661 RTASANKFIDFVQSLDIDIALARGFSSSPNSPAVPPGGPFSPSARSMSAHSDSEPNSNSN 720
Query 721 NNTTSRITVTEGDLLQPERTSNGFVLNVVKRENLGMSSIGGNQNTELPESVQLEIPEKEM 780
NNTTSRITVTEGDLLQPERTSNGFVLNVVKRENLGMSSIGGNQNTELPESVQLEIPEKEM
Sbjct 721 NNTTSRITVTEGDLLQPERTSNGFVLNVVKRENLGMSSIGGNQNTELPESVQLEIPEKEM 780
Query 781 DNSSVSEHEVDDDDEHEQEDNNGATVSSPVTESSEDSGLQEPVSGSVIDG 830
DNSSVSEHEVDDDDEHEQEDNNGATVSSPVTESSEDSGLQEPVSGSVIDG
Sbjct 781 DNSSVSEHEVDDDDEHEQEDNNGATVSSPVTESSEDSGLQEPVSGSVIDG 830
Furthermore, alignment of SEQ ID NO:1 to the NCBI database showed the sequence has 100% identity to the coding region of Camelina sativa triacylglycerol lipase SDP1-like (LOC104708721), mRNA, from the C. sativa cultivar DH55, see enclosed alignment in PDF, Published in 2016. Therefore the C. sativa cultivar DH55 comprise the first homeolog of SEQ ID NO:1.
It would have been obvious from teaching, suggestion, and motivation in the Dhankher et al. to mutate one of the homeolog of the SDP1 gene as SEQ ID NO:2 that would be knocked out or will not encode an active SDP1 triacylglycerol lipase and that would include one or more additions, deletions, or substitutions of one or more nucleotides by using CRISPR Cas9 method in Camelina sativa SDP1 homeologs as taught by Moreno et al., furthermore, the active SDP1 would be the endogenous Camelina sativa SDP1 homeolog as SEQ ID NO: 32 as taught by JGI phytozome 14 database, that would have led one of ordinary skill to mutate the homeolog of SDP1 as SEQ ID NO:2 and SEQ ID NO: 1 and 3 would be the wild type homeologs of the SDP1 gene as showed by NCBI database and JGI genome database, to arrive at the genetically modified plant that exhibit an increase in seed yield relative to a parental plant and the genetic modified plant would have a knocked out mutant SDP1 allele.
Response to Applicant’s Argument
Applicant's arguments filed 10/27/2025 have been fully considered but they are not persuasive.
Applicant argues Dhankher, in view of Aznar-Moreno and JGI database, as evidenced by NCBI protein database, does not render claim 1 obvious for at least the reason that Dhankher, in view of Aznar-Moreno and JGI database, as evidenced by NCBI protein database, fails to teach or suggest all the limitations of claim 1 (response to rejection, page 20, paragraph 3).
Applicant argues Considering Dhankher first, Dhankher does not teach or suggest a genetically modified Camelina sativa plant comprising: (a) a first homeolog of the SD Pl gene occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 20 and being homozygous for the wild-type allele in the genetically modified Camelina sativa plant; and (b) a second homeolog of the SDP1 gene occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 13 and being homozygous for a mutant allele in the genetically modified Camelina sativa plant (response to rejection, page 20, paragraph 4).
Applicant argues this is because to the extent that Dhankher teaches plants having increased oil content and seed yield based on modifying expression of sugar dependent 1 (SDP 1), Dhankher teaches that suppression of collective SDP1 expression results in an increase in oil content and/or seed yield (Dhankher, paragraph [0035]), not for example that reducing or eliminating expression of one SDP1 triacylglycerol lipase, while maintaining expression of another, results in an increase in oil content and/or seed yield. Applicant argues Dhankher appears to be silent regarding the possibility that reducing or eliminating expression of one SDP1 triacylglycerol lipase, while maintaining expression of another, could result in an increase in oil content and/or seed yield (response to rejection, page 21, paragraph 2).
Applicant asserts although the official action contends that Dhankher's DNA SEQ ID NO: 5 encodes an SDP1 triacylglycerol lipase that is 100% identical to Applicant's protein SEQ ID NO: 31, and therefore that Dhankher teaches that reducing expression of the SDP1 triacylglycerol lipase of Applicant's SEQ ID NO: 31 from chromosome 13 would cause more than a 30% increase in seed size, a 6-15% increase in oil content, and a more than two-fold increase in total seed yield per plant, it does not follow from Dhankher's DNA SEQ ID NO: 5 encoding an SDP1 triacylglycerol lipase that is 100% identical to Applicant's protein SEQ ID NO: 31 that Dhankher teaches that reducing expression of the SDP1 triacylglycerol lipase of Applicant's SEQ ID NO: 31 from chromosome 13 would cause more than a 30% increase in seed size, a 6-15% increase in oil content, and a more than two-fold increase in total seed yield per plant (response to rejection, page 21, paragraph 3).
Applicant asserts Rather, this is consistent with Dhankher teaching that suppression of collective SDP1 expression results in an increase in oil content and/or seed yield (Dhankher, paragraph [0035]). Applicant argues this is because Dhankher's DNA SEQ ID NO: 5, which corresponds to Applicant's DNA SEQ ID NO: 2 and thus the wild-type allele of the second homeolog of SDP1 on chromosome 13, based on being 100% identical to Applicant's DNA SEQ ID NO: 2, also is 97.58% identical to Applicant's DNA SEQ ID NO: 3, which corresponds to the wild-type allele of the first homeolog of SDP1 on chromosome 20 (response to rejection, pages 21 and 22, last and first paragraphs).
Applicant argues Considering that Dhankher's DNA SEQ ID NO: 5, i.e., Applicant's DNA SEQ ID NO: 2, is 97.58% identical to Applicant's DNA SEQ ID NO: 3, reducing expression of the SDPI triacylglycerol lipase of Applicant's SEQ ID NO: 31 from chromosome 13 by targeting Dhankher's DNA SEQ ID NO: 5, i.e. Applicant's DNA SEQ ID NO: 2, without also reducing expression of the SDP1 triacylglycerol lipase of Applicant's SEQ ID NO: 32 from chromosome 20 by targeting Applicant's DNA SEQ ID NO: 3, would have required careful comparison of the DNA sequences to identify potential suitable target sites, if there are any, to accomplish reducing the expression of the one SDP1 triacylglycerol lipase without inadvertently reducing the expression of the other (response to rejection, page 24, last paragraph).
Applicant argues Dhankher does not teach or suggest anything like this. other.
Applicant argues Rather, as noted above, Dhankher appears to be silent regarding the possibility that reducing or eliminating expression of one SDP1 triacylglycerol lipase, while maintaining expression of another, could result in an increase in oil content and/or seed yield (response to rejection, page 25, second paragraph).
Applicant argues thus, to the extent that Dhankher's DNA SEQ ID NO: 5 encoding an SDP1 triacylglycerol lipase that is 100% identical to Applicant's SEQ ID NO: 31 suggests that Dhankher teaches reducing expression of Applicant's SEQ ID NO: 31 from chromosome 13 in a Camelina sativa plant, it also suggests that Dhankher teaches reducing expression of Applicant's SEQ ID NO: 32 from chromosome 20 in the same Camelina sativa plant (response to rejection, page 25, paragraph 3).
Applicant argues Moreover, although the Official action contends that Dhankher teaches repressing or suggests mutating DNA SEQ ID NO: 5, which encodes the SDP1 triacylglycerol lipase of Applicant's SEQ ID NO: 31 from chromosome 13, that there is a clear indication from Dhankher that reducing expression would increase seed yield in Camelina sativa, that Dhankher teaches that T3 seeds having RNAi knockdown of SDP1 gene expression in FIG. 14, that by using CRISPR-Cas system the activity of the modified endogenous SDP1 in a plant cell is reduced by at least about 10% to about 100% or about 20-80%, and that a gene knockdown usually stops or decreases the expression of the targeted gene, for the reasons provided above, as well as the reasons provided in Applicant's previous response, these teachings are consistent with suppression of collective SDP1 expression, not reducing or eliminating expression of one SDP1 triacylglycerol lipase, while maintaining expression of another (response to rejection, page 25, paragraph 4).
Applicant argues Turning to Aznar-Moreno, the teachings of Aznar-Moreno as cited, which are directed to Camelina sativa possessing a relatively undifferentiated hexaploid genome, and that up to three gene homeologs can code for any particular enzymatic activity, wherein a specifically designed guide RNA identical to all three homeologs would specifically target CsDGATl or CsPDATl homeologous genes for triacylglycerol synthesis in developing seeds leading to mutant phenotypes with a phenotypic difference in seeds and altered oil content and fatty acid compositions, do not cure the deficiency of Dhankher. Applicant argues This teaching is consistent with suppression of collective SDP1 expression, not reducing or eliminating expression of one SDP1 triacylglycerol lipase, while maintaining expression of another. Applicant argues This is because Aznar-Moreno teaches that the purpose of using the specifically designed guide RNA identical to all three homeologs of either CsDGAT1 or CsPDAT1 homeologous genes is to introduce mutations into all three homeologs of the CsDGATl or CsPDATl homeologous genes (Aznar-Moreno, abstract), not to reduce or eliminate expression of one homeolog, while maintaining expression of another (response to rejection, page 26, first paragraph).
Applicant argues Turning to JGI database, as evidenced by NCBI protein database, the teachings of these references as cited, which are directed to a showing that Csal3g006100.l has 100% sequence identity to applicant's SEQ ID NO: 31, that Csa20g005210. l has 100% identity to SEQ ID NO: 32, that cultivar DH55 has Csa08g060480. l as an SDPI homeolog on chromosome 8, that these sequences were available in JGI database and NCBI protein database in 2014, and that SEQ ID NO: 32 has 100% sequence identity to the locus XP _010490898 as triacylglycerol lipase SDPI isoform XI of Camelina sativa, and that therefore the locus is an endogenous homeolog in Camelina sativa of triacylglycerol lipase SDP1, do not cure the deficiency of Dhankher, in view of Aznar-Moreno (response to rejection, page 26, last paragraph).
Applicant argues these teachings do not explain why a skilled person would have made a genetically modified Camelina sativa plant comprising (a) a first homeolog of the SDPI gene occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 20 and being homozygous for the wild-type allele in the genetically modified Camelina sativa plant, and (b) a second homeolog of the SDP I gene occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 13 and being homozygous for a mutant allele in the genetically modified Camelina sativa plant (response to rejection, page 27, first paragraph).
Applicant argues for at least these reasons, Dhankher, in view of Aznar-Moreno and JGI database, as evidenced by NCBI protein database, does not teach or suggest a genetically modified Camelina sativa plant comprising (a) a first homeolog of the SDPI gene occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 20 and being homozygous for the wild-type allele in the genetically modified Camelina sativa plant, and (b) a second homeolog of the SDPI gene occurring in its natural position within the genome of the genetically modified Camelina sativa plant on chromosome 13 and being homozygous for a mutant allele in the genetically modified Camelina sativa plant (response to rejection, page 26, paragraph 2).
Applicant argues although the Official action notes that where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to an argument that attacks the references individually, Applicant's reply is not limited to what a subset of the applied references teach or fail to teach, and does not fail to address the combined teachings of the applied references. Applicant argues Rather, Applicant has addressed the teachings of the applied references broadly, by addressing what the Official action contends that the references teach, and by discussing what the references further teach and fail to teach. Applicant also has discussed the teachings of the applied references in relation to each other (response to rejection, pages 27 and 28, last and first paragraphs).
Applicant's arguments have been fully considered but they are not persuasive since:
Regarding argument on Dhankher appears to be silent regarding the possibility that reducing or eliminating expression of one SDPl triacylglycerol lipase, while maintaining expression of another, could result in an increase in oil content and/or seed yield, was not found persuasive since the reducing or eliminating expression of one SDPl triacylglycerol lipase would have maintained the remaining homeolog not effected or would be active.
Regarding argument on considering the homeologs of applicant’s SEQ ID NO:2 and 3 has 97.58% it would require to identify potential suitable target sites to accomplish reducing the expression of the one SDP1 triacylglycerol lipase without inadvertently reducing the expression of the other. The argument was not found persuasive since finding the specific target site to reduce off target effect is within the skill of the art. Furthermore, Dhankher et al. teaches reducing the activity of SDP1 gene by knocking out the endogenous SDP1 gene using for example genome editing by CRISPR/Cas system by RNA guided editing (page 14, paragraph 0127). Therefore Dhankher et al. targeting specific SEQ ID NO:5 which is applicant’s SEQ ID NO:2.
Regarding argument on Aznar-Moreno does not teach specific guide RNA targeted to specific homeologs was not found persuasive since applicant does not claim specific guide RNA that would be useful for targeting specific homeologs and no other homeologs, wherein applicant has used SEQ ID NO:14 to target SEQ ID NOs:1-3 (see page 43, Table 11) and SEQ ID NO:4 to target SEQ ID NOs:1-3 (page 34, Table 3). Furthermore, Aznar-Moreno teaches designing gene editing in C. sativa to introduce mutations into specific targeted genomic sites. Furthermore, Aznar-Moreno is a supporting art wherein the Dhankher teaches repressing or suggests mutating DNA SEQ ID NO: 5, which encodes the SDP1 triacylglycerol lipase of Applicant's SEQ ID NO: 31 from chromosome 13.
Regarding argument maintaining activity of another, Dhankher teaches repressing or suggest mutating SEQ ID NO: 5 which encodes applicant’s SEQ ID NO: 31 from chromosome 13. Furthermore, there is clear indication from Dhankher et al. that reducing expression would increase seed yield in Camelina sativa. Dhankher et al. teaches T3 seeds having RNAi knockdown of SDP1 gene expression in FIG. 14 (page 16, paragraph 0161). Dhankher et al. teaches using CRISPR-Cas system the activity of the modified endogenous SPD1 in a plant cell is reduced by at least about 10 % to about 100 % (i.e. 20-80%) (page 14, paragraph 0129). A gene knockdown usually stops or decrease the expression of the targeted gene. For this reason, SDP1 does not encode the active SDP1 gene.
Therefore, the rationale to modify or combine the prior art are expressly stated in the prior art and the rationale is reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles that would lead to the recited invention.
Furthermore, where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because the test for obviousness is what the combined teachings of the references would have suggested to a person having ordinary skill in the art (PHOSITA).”
Summary
No claim is allowed.
Applicant's 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.
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/SANTOSH SHARMA/ Examiner, Art Unit 1663
/DAVID H KRUSE/ Primary Examiner, Art Unit 1663