DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 3 and 10-11 are cancelled.
Claims 1-2, 4-9, and 12-16 are pending.
Claims 1-2, 4-9, and 12-16 are examined herein.
Claims 1-2, 4-9, and 12-16 are rejected.
Claim Rejections - 35 USC § 112
New Subject Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 5 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.
This is a new rejection, necessitated by Applicant’s amendments.
Claim 5 recites “The method of claim 1, wherein a post-transcriptional technique is further used to reduce or abolish enzyme activity.”
That is, the claimed embodiment requires the combination of both a loss-of-function mutation in at least one copy of the 7-DR2 gene and a post-transcriptional technique used to reduce or abolish enzyme activity.
This combination does not appear in the disclosure of the invention and the combination is not a disclosed or described alternative embodiment. The specification only refers to post transcriptional techniques as a complete alternative to other methods of reducing expression or activity (see relevant recitations below).
On p. 3 lines 3-18, the specification recites:
"Reducing activity" may mean reducing or abolishing enzyme activity or expression. In a preferred embodiment, the method comprises introducing a loss of function mutation into5 at least one copy of the 7-DR gene (preferably S17-DR2 gene). The mutation may be in the coding sequence. The mutation may be an insertion, deletion, or alteration. In embodiments loss of function mutations may be introduced into multiple copies of the Sl7-DR2 gene. Preferably, the mutation is introduced by genome editing, preferably ZFNs, TALENs or CRISPR. In some embodiments, mutagens (for example, radiation) may be used to introduce the mutation. In some embodiments, mutations may be introduced into at least one copy of the gene, and conventional breeding techniques used to generate plants with multiple mutations in the genome, eg, homozygous plants.
In other embodiments, post-transcriptional techniques may be used to reduce or abolish enzyme activity. For example, RNAi, CRISPRi, or antisense techniques can all be used to reduce enzyme levels. The method may comprise introducing an siRNA or antisense molecule into the plant; or may comprise introducing a nucleic acid sequence which encodes an siRNA or antisense molecule into the plant. Such nucleic acid sequence may be stably incorporated into the plant genome.
On p. 8 lines 14-21, the specification recites:
In another embodiment, conventional mutagenesis techniques, such as T-DNA insertional mutagenesis or any known physical or chemical mutagen can be used disrupt genes described herein. In a further example, the expression of one or more genes can be reduced at the level of transcription or translation using gene silencing methods known to the skilled person, such as, but not limited to, the use of small interfering nucleic acids (siNAs) against one or more genes. For example, the siNA may include short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), antagomirs and short hairpin RNA (shRNA) capable of mediating RNA interference.
Thus, the specification provides post-transcriptional techniques to reduce enzyme activity as an alternative embodiment/ example to knockout mutations, and does not suggest combining the embodiments. Because the combination is not described in the disclosure, the claimed combination is new subject matter is therefore improper.
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.
Claim(s) 1-2, 5, 8-9, and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Sonawane (Sonawane, P. D., Pollier, J., Panda, S., Szymanski, J., Massalha, H., Yona, M., ... & Aharoni, A. (2016). Plant cholesterol biosynthetic pathway overlaps with phytosterol metabolism. Nature plants, 3(1), 1-13), Meissner (Meissner, R., Jacobson, Y., Melamed, S., Levyatuv, S., Shalev, G., Ashri, A., ... & Levy, A. (1997). A new model system for tomato genetics. The Plant Journal, 12(6), 1465-1472), and Mizutani (PCT Patent Publication No. WO-2019163601-A1).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/28/2025, necessitated by Applicant’s amendments.
Claim 1 is drawn to a method of improving provitamin D₃ levels in a plant wherein said plant is from the Solanaceae family, and wherein the genome of said plant comprises a gene encoding 7-dehydrocholesterol reductase 1 (7-DR1) and a gene encoding 7- dehydrocholesterol reductase 2 (7-DR2), the method comprising introducing a loss of function mutation into at least one copy of the 7-DR2 gene, thereby reducing activity of 7- dehydrocholesterol reductase 2 (7-DR2) in the plant leading to accumulation of 7-DHC, wherein 7-dehydrocholesterol reductase 1 (7-DR1) is not affected and wherein said plant does not have a dwarf phenotype.
Claim 2 is drawn the method of claim 1 wherein the method comprises introducing one or more mutations reducing the activity of the enzyme encoded by the 7-DR2 gene in the plant.
Claim 5 is drawn to the method of claim 1, wherein a post-transcriptional technique is further used to reduce or abolish enzyme activity.
Claim 8 is drawn to the method of claim 1, further comprising processing the plant or a part of the plant to obtain 7-DHC and/or vitamin D3.
Claim 9 is drawn to a genetically altered plant, part thereof or plant cell, wherein said plant is from the Solanaceae family, and wherein the plant, part thereof or plant cell has reduced activity of 7-dehydrocholesterol reductase 2 (7-DR2), and 7-dehydrocholesterol reductase 1 (7-DR1) is not affected and wherein said plant does not have a dwarf phenotype.
Claim 12 is drawn to the method of claim 1, wherein the plant is a Solanum spp.
Claim 13 is drawn to a food product produced from the plant or part thereof of claim 9.
Claim 14 is drawn to the plant, part thereof or plant cell of claim 9, wherein the plant is a Solanum spp.
Claim 15 is drawn to the method of claim 12, wherein the plant is tomato (Solanum lycopersicum), potato (Solanum tuberosum), or eggplant (Solanum melongena).
Claim 16 is drawn to the plant, part thereof or plant cell of claim 14, wherein the plant is tomato (Solanum lycopersicum), potato (Solanum tuberosum), or eggplant (Solanum melongena).
Regarding claim 1, Sonawane teaches silencing 7-DR2 in tomato plants using VIGS (p. 9-10). Because Sonawane only teaches silencing 7-DR2, 7-DR1 is reasonably interpreted to be unaffected. Sonawane further teaches the cholesterol pathway intermediate pro-vitamin D3 (7-DHC) is a high value chemical (p. 10, discussion, ¶4), and 7-DR2 but not 7-DR1 catalyzes the last committed step of 7-DHC to cholesterol in the plant cholesterol pathway (Fig. 1, p. 10, ¶2).
Regarding claim 5, Sonawane teaches silencing 7-DR2 in tomato plants using VIGS (p. 9-10) (i.e. a post transcriptional technique used to reduce or abolish enzyme activity).
Regarding claim 9, Sonawane teaches silencing 7-DR2 in tomato plants using VIGS (p. 9-10). Because Sonawane only teaches silencing 7-DR2, 7-DR1 is reasonably interpreted to be unaffected.
Regarding claims 12 and 14-16, Sonawane teaches the plant is Solanum lycopersicum (p. 10, Methods, Plant materials).
However, Sonawane teaches using VIGs to silence the gene, and therefore does not explicitly teach introducing a loss of function mutation into at least one copy of the 7-DR2 gene (required by claims 1 and 9). Sonawane also teaches the tomato is cv. Micro-Tom (p. 10, Methods, Plant materials), and therefore does not teach the plant does not have a dwarf phenotype (required by claims 1 and 9). Sonawane also does not explicitly teach reducing 7-DR2 activity led to accumulation of 7-DHC (required by claim 1).
Regarding the remaining limitations of claim 1 and 9, in analogous art, Mizutani teaches suppressing 7-DR2 in a plant by CRISPR/Cas9 knockout (i.e. reasonably interpreted as a loss-of-function mutation in the 7-DR2 gene) (¶0068-0069, 0084). In other analogous art, Meissner teaches the tomato cultivar Micro Tom is a beneficial model system for tomato genetics, growing at high density, having a short life cycle, easily transformable, and only differs from standard tomato cultivars by two major genes which are recessive (title, abstract, and discussion, ¶1). Meissner teaches mutants, gene knockout and tagging, and transgenes can be produced and studied in Micro Tom (p. 1466, ¶2, p. 1469, discussion, ¶1), and if needed, tested in standard tomato cultivar background (p. 1469, discussion, ¶1).
Regarding claim 2, Mizutani teaches suppressing 7-DR2 in a plant by CRISPR/Cas9 knockout (i.e. reasonably interpreted as introducing a mutation reducing the activity of the enzyme encoded by 7-DR2) (¶0068-0069, 0084).
Regarding claim 8, Mizutani teaches 7-DHC produced can be separated from plants and purified as a substantially pure and homogeneous compound (¶0056) (i.e. processing the plant or a part of the plant to obtain 7-DHC).
Regarding claim 13, Mizutani teaches the invention that is plants with increased 7-DHC can be used in food additives, feed additives, pharmaceutical raw materials and intermediates, health foods, and the like (¶0111, abstract).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention taught by Sonawane to include the limitations of Mizutani and Meissner to arrive at the instantly claimed method with a reasonable expectation of success because one having ordinary skill in the art could incorporate the method of silencing 7-DR2 via VIGs in cv Micro Tom as taught by Sonawane into a standard, non-dwarf tomato using a mutation induced by CRISPR-mediated knockout (rather than VIGs silencing) without encountering any special technical obstacles. One having ordinary skill in the art would have been motivated to combine the teachings to reduce 7-DR2 activity in a standard tomato plant because Sonawane teaches silencing 7-DR2 decreased cholesterol content in tomato plants and reduced α-tomatine and esculeoside B in green tissues and red fruit, respectively, and Meissner teaches Micro Tom is a model system for studying tomato genetics, and teaches methods first studied and produced in Micro Tom can also be tested in standard tomato cultivar background (i.e. non dwarf) (p. 1466, ¶2, p. 1469, discussion, ¶1). Therefore, it would be obvious to silence 7-DR2 in a standard tomato cultivar to test if 7-DR2 silencing in a standard tomato cultivar is also observed to have the same results including decreased cholesterol content, α-tomatine, and esculeoside B in the plants and fruit. Furthermore, because Applicant provides evidence that knockout alleles of Sl7-DR2 in non-dwarf tomato plants leads to accumulation of 7-DHC (spec., p. 11, lines 17- p. 12, line 25), the limitation of accumulation of 7-DHC recited in claim 1 is also obvious as a function of inherency because the obvious 7-DR2-silenced non-dwarf tomato produced in view of Sonawane, Meissner, and Mizutani would reasonably be expected to have been observed to comprise the inherent feature of accumulated 7-DHC. Lastly, it would be obvious to combine the teachings of Sonawane with Mizutani because it would be prima facie obvious to i. substitute one known method of reducing gene/ protein expression (VIGS) with another known method of reducing gene/protein expression (CRISPR/Cas9 mediated knockout mutations) for the same purpose (as it applies to claim 1-2), and ii. combine one known method of reducing gene/ protein expression (VIGS) with another known method of reducing gene/protein expression (CRISPR/Cas9 mediated knockout mutations) for the same purpose (as it applies to claim 5).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Sonawane, Meissner, and Mizutani as applied to claims 1 and 2 above, and further in view of Coruzzi (US Patent Application Publication No. US-20120151635-A1).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/28/2025, necessitated by Applicant’s amendments.
Claim 4 is drawn to the method of claim 2, further comprising breeding mutant plants to obtain a plant homozygous for the mutation.
Regarding claim 4, Sonawane, Meissner, and Mizutani teach the limitations of claims 1 and 2 as set forth in the previous obviousness rejections. The teachings of Sonawane, Meissner, and Mizutani as they are applied to claims 1 and 2 are set forth previously herein and are incorporated by reference. Additionally, Mizutani teaches progeny obtained from self- pollinating seed of the TO generation (¶0051).
However, Sonawane, Meissner, and Mizutani do not explicitly teach breeding the mutant plants to obtain a plant homozygous for the mutation, as required by claim 4.
In analogous art about methods for obtaining transgenic plants (abstract), Coruzzi teaches a homozygous transgenic plant can be obtained by sexually mating (selfing) a heterozygous transgenic plant that contains a single added heterologous nucleic acid (¶0218 and 0220).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Sonawane, Meissner, and Mizutani to include the limitations of Coruzzi to arrive at the instantly claimed method with a reasonable expectation of success because Sonawane, Meissner, and Mizutani reducing 7-DR2 activity in tomato plants, and Mizutani teaches a introducing mutations that reduce the activity of the enzyme encoded by the 7-DR gene in the plant, and Coruzzi teaches a method of obtaining transgenic plants homozygous for mutations, and combining the methods presents no special technical obstacles. One having ordinary skill in the art would have been motivated to do so because Coruzzi teaches the resulting inbred plant produces seed containing the newly introduced foreign gene(s), and these seeds can be grown to produce plants that would produce the selected phenotype (¶0218).
Claims 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Sonawane, Meissner, and Mizutani as applied to claim 1 above, and further in view of Japelt (Japelt, R. B., & Jakobsen, J. (2013). Vitamin D in plants: a review of occurrence, analysis, and biosynthesis. Frontiers in plant science, 4, 136), and Ballester (Ballester, A. R., et al. (2010). Biochemical and molecular analysis of pink tomatoes: deregulated expression of the gene encoding transcription factor SIMYB12 leads to pink tomato fruit color. Plant physiology, 152(1), 71-84).
This is a modified rejection from the previous rejection set forth in the Office Action dated 11/28/2025, necessitated by Applicant’s amendments.
Claim 6 is drawn to the method of claim 1, further comprising exposing the plant or apart of the plant to UV-B radiation.
Claim 7 is drawn to the method of claim 6, wherein the plant carries a mutation which increases the penetration of UV-B light from the exposing step into fruit.
Regarding claims 6 and 7, Sonawane, Meissner, and Mizutani teach the limitations of claim 1 as set forth in the previous obviousness rejection. The teachings of Sonawane, Meissner, and Mizutani as they are applied to claim 1 are set forth previously herein and are incorporated by reference. Additionally, Mizutani also teaches suppressing expression of the gene encoding 7-dehydrocholesterol reductase gene by ultraviolet radiation (claim 7 of Mizutani) (i.e. exposing the plant or part of the plant to UV radiation).
However, Sonawane, Meissner, and Mizutani do not explicitly teach exposing the plant or apart of the plant specifically to UV-B radiation, as required by claim 6. Additionally, Sonawane, Meissner, and Mizutani do not explicitly teach wherein the plant carries a mutation which increases the penetration of UV-B light into fruit, as required by claim 7.
In analogous art, Japelt teaches the content of vitamin D3 in UVB-exposed plants was 18-64 times higher than for non-UVB-exposed plants (p. 10, right column, sentence 2). Additionally, Ballester teaches flavonoids in tomato are involved in protection against ultraviolet light, and further teaches a mutation in tomato fruit that leads to decreased flavonoids in tomato fruit skin which generates pink tomatoes (abstract, p. 72, left column, paragraph 2).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Sonawane, Meissner, and Mizutani to include the limitations of Japelt and Ballester to arrive at the instantly claimed method with a reasonable expectation of success because the teachings of Sonawane, Meissner, and Mizutani, Japelt, and Ballester are directed to increasing vitamin D3 in tomato, which includes exposure of plants to UV light or a method of decreasing UV-protecting flavonoids, and may be combined and achieved without any special technical obstacles. One having in the art would have been motivated to do so because Ballester teaches a method to decrease UV-protecting flavonoids in tomato fruit (abstract, p. 72, left column, paragraph 2), and Japelt teaches explicit motivation that plants with increased of UV-B exposure produce significantly higher vitamin D3 accumulation, and further teaches it would be valuable to increase the food sources of vitamin D in the human diet or to optimize the content by biofortification, especially in plants of the Solanaceae family (p. 15, concluding remarks).
Response to Arguments
Applicant argues beginning on p. 4 of remarks dated 02/27/2026 the
following arguments:
Claims 1-2, 4-9, and 12-16 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre- AIA ), first paragraph, as allegedly failing to comply with the written description requirement.
Specifically, the Examiner asserts that Applicant has not described the full genus of methods to reduce 7-dehydrocholesterol reductase activity in a plant. While the Applicant maintains that the skilled person would understand that any method that reduced the activity of 7-DR2 would lead to 7-DHC accumulation, and would be enabled to do so by the present disclosure, solely to expedite prosecution, Applicant has amended the claims to specify that the activity is reduced by introducing a loss of function mutation into at least one copy of the 7-DR2 gene. This amendment is based on paragraph [0008] of the published application. Given the disclosure in the application of targeted knock out of the 7-DR2 gene using gene editing, and the known sequence of the gene, Applicant respectfully submits that the skilled person would have sufficient information to use other known mutagenesis techniques, and to be able to screen for successful loss of function mutations. Accordingly, the disclosure meets the written description requirement.
Accordingly, Applicant respectfully requests reconsideration and withdrawal of the foregoing rejection.
Examiner’s response:
In view of Applicant’s amendment to claim 1, the previous rejection under 35 USC 112(a) written description has been withdrawn.
Applicant argues beginning on p. 5 of remarks dated 02/27/2026 the
following arguments:
Claims 1, 5, 9, 12, and 14-16 are rejected under 35 U.S.C. § 103 as being unpatentable over Sonawane and Meissner. Claims 2, 8, 10, and 13 are rejected under 35 U.S.C. § 103 as being unpatentable over Sonawane and Meissner, and further in view of Mizutani. Claim 4 is rejected under 35 U.S.C. § 103 as being unpatentable over Sonawane, Meissner, and Mizutani, and further in view of Coruzzi. Claims 6-7 are rejected under 35 U.S.C. § 103 as being unpatentable over Sonawane, Meissner and Mizutani, and further in view of Japelt and Ballester.
Applicant respectfully traverses the rejection for the following reasons.
As acknowledged by the Examiner, Sonawane is limited to plants with a dwarf phenotype. This is a critical distinction from the present invention which specifically requires that the plant does not have a dwarf phenotype. Furthermore, Sonawane does not explicitly describe reducing 7- DR2 activity to accumulate 7-DHC.
Meissner reports that Micro Tom differs from standard cultivars by "two major genes ". Thus, the skilled person would understand that these genetic differences are not insignificant. This is reflected by the reduced brassinosteroid content of Micro Tom, indicating that Micro Tom exhibit metabolic deficiencies. It is known in the art that brassinosteroid and cholesterol synthesis are closely linked. In fact, Sonawane highlights this on page 1, column 1, paragraph 1, where it is stated that "besides their major importance as membrane components, phytosterols serve as precursors for brassinosteroids, signalling molecules involved in growth and development." As such, since the brassinosteroid content of Micro Tom is compromised, it would be logical for the skilled person to assume that sterol content and metabolism is also compromised. On this basis, it would be expected that mutations in these pathways would not show consistent results in dwarf varieties and wild-type cultivars. This is reinforced by Marti et al, 2006 [https://doi.org/10.1093/ixb/eri154] which notes on page 2046, column 2, paragraph 2 that due to the reduced brassinosteroid content of Micro Tom "caution is required when obtaining data using this variety." As such due to the fundamental differences in Micro Tom that affect brassinosteroid synthesis the skilled person could not reasonably use data from Micro Tom to predict what may be expected in non-dwarf cultivars. Furthermore, due to the caution required when obtaining data in Micro Tom, the skilled person would not be motivated to silence 7-DR2 in cultivars on the back of a publication that is limited to a dwarf variety.
While Meissner mentions the possibility of testing mutations developed in Micro Tom in standard cultivars "if needed", this disclosure is mere speculation. Crucially, Meissner fails to:
" Consider the practicalities of transferring a mutation from Micro Tom to standard cultivars.
" Provide any specific motivation to transfer a mutation from Micro Tom to a standard cultivar.
" Provide any example of a mutation being successfully transferred from Micro Tom to a standard cultivar.
In the absence of any data showing that mutations can successfully be transferred from Micro Tom to a standard cultivar, the skilled person would not have any reasonable expectation of success if they were to attempt this. Furthermore, since Sonawane completely overlooks the significance of a dwarf phenotype, the skilled person would have no incentive to silence 7-DR2 in a standard cultivar. The Examiner is relying on hindsight to declare that silencing 7-DR2 in a standard cultivar would be obvious despite there being an absence of any incentive to do this in either Sonawane or Meissner.
Examiner’s response:
Applicant has argued there is no reasonable expectation of success transferring mutations successfully from Micro Tom to a standard cultivar. This is not persuasive because, as stated in the 103 rejection, Meissner teaches the tomato cultivar Micro Tom is a beneficial model system for tomato genetics, growing at high density, having a short life cycle, easily transformable, and only differs from standard tomato cultivars by two major genes which are recessive (title, abstract, and discussion, ¶1). Meissner teaches mutants, gene knockout and tagging, and transgenes can be produced and studied in Micro Tom (p. 1466, ¶2, p. 1469, discussion, ¶1), and if needed, tested in standard tomato cultivar background (p. 1469, discussion, ¶1). It is also generally known and routine in the field of plant biotechnology to use Micro Tom as a model system, and standard cultivars are tested after initial work in Micro Tom (for the reasons described by Meissner). Thus, one of ordinary skill in the art actually would have a reasonable expectation of success of transferring mutations successfully from Micro Tom to a standard cultivar.
Furthermore, even though Micro Tom has some genetic differences from standard, non dwarf cultivars, the prior art still provides motivation to move the mutation into a standard cultivar. Sonawane teaches silencing 7-DR2 decreased cholesterol content in tomato plants and reduced α-tomatine and esculeoside B in green tissues and red fruit, respectively, and Meissner teaches Micro Tom is a model system for studying tomato genetics, and teaches methods first studied and produced in Micro Tom can also be tested in standard tomato cultivar background (i.e. non dwarf) (p. 1466, ¶2, p. 1469, discussion, ¶1). Therefore, it would be obvious to silence/knockout 7-DR2 in a standard tomato cultivar to test if 7-DR2 silencing in a standard tomato cultivar is also observed to have decreased cholesterol content, α-tomatine, and esculeoside B in the plants and fruit. By doing so, the non-dwarf plant would inherently have the 7-DHC accumulation as evidenced by the instant disclosure. It is also noted that the plant of claim 9 does not require accumulated 7-DHC, and only requires the structure of a non-dwarf tomato plant with a loss-of-function mutation in 7-DR2 of which, as described herein, is obvious in view of the prior art. For this reason, Applicant’s argument that the skilled person would have no incentive to silence 7-DR2 in a standard cultivar is not persuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Sonawane teaches silencing 7-DR2 in Micro Tom tomato plants, and teaches the result was decreased cholesterol content, α-tomatine, and esculeoside B in the plants and fruit. Meissner teaches what is also generally known in the field that is Micro Tom is a model system for studying tomato genetics, and teaches methods first studied and produced in Micro Tom can also be tested in standard tomato cultivar background. It would be obvious to move the mutation into a standard cultivar for the purpose of testing for the same results as observed in Micro Tom including decreased cholesterol content, α-tomatine, and esculeoside B in the plants and fruit. Based on this published and also known, routine knowledge, the reconstruction to move the mutation into a non-dwarf tomato does not include knowledge gleaned only from the applicant's disclosure and is therefore proper.
Applicant argues beginning on p. 6 of remarks dated 02/27/2026 the
following arguments:
Furthermore, the Examiner's remark that 7-DHC accumulation would have been an inherent result of silencing 7-DR2 in a standard cultivar is flawed:
" As discussed above, there is no motivation in the prior art for the skilled person to attempt silencing 7-DR2 in a standard cultivar.
" As noted in our previous response, Mizutani reported that "it was found that the
accumulation of 7-DHC requires knockout of both LeDWFSH and LeDWF5" (see
[0104] of Mizutani).
" Neither Sonawane nor Mizutani report 7-DHC accumulation in dwarf varieties
where 7-DR2 is silenced.
No effect is reported on 7-DHC accumulation when 7-DR2 is silenced in dwarf varieties, and the skilled person would have no reason to believe that silencing 7-DR2 in a standard wild-type cultivar would yield a different result. The Applicant was the first to find that reducing the activity of 7-DR2 results in 7-DHC accumulation in Solanaceae plants that do not have a dwarf phenotype, and the Examiner has not provided any credible reasoning why this could have been predicted with any reasonable expectation of success. In fact, given that the prior art shows no effect on 7-DHC when 7-DR2 is silenced in dwarf varieties, but the Applicant surprisingly showed 7-DHC accumulation in non-dwarf varieties with reduced 7-DR2 activity demonstrates that this result was not inherent.
Sonawane reports that "7-DR2 but not 7-DR1 catalyses the last committed step in the plant cholesterol pathway." However, despite this, Sonawane fails to demonstrate that silencing 7-DR2 results in 7-DHC accumulation in a dwarf variety, nor does it suggest that this could be achieved in a standard non-dwarf cultivar. The prior art does not provide any rationale that the skilled person could plausibly follow to arrive at claim 1 of the present invention. The present invention specifically requires a non-dwarf phenotype and achieves 7-DHC accumulation by reducing the activity of 7-DR2 alone, this is neither disclosed nor reasonably predictable when considering any of the prior art either alone or together, therefore an inventive step must be acknowledged for claim 1 and all dependent claims thereon by virtue of their dependency.
Mizutani, Coruzzi, Japelt and Ballester also fail to cure the deficiencies of Sonawane and Meissner, and therefore fail to render the claimed invention obvious.
Accordingly, Applicant respectfully requests reconsideration and withdrawal of the foregoing rejection.
Examiner’s response:
As previously stated: Sonawane teaches silencing 7-DR2 decreased cholesterol content in tomato plants and reduced α-tomatine and esculeoside B in green tissues and red fruit, respectively, and Meissner teaches Micro Tom is a model system for studying tomato genetics, and teaches methods first studied and produced in Micro Tom can also be tested in standard tomato cultivar background (i.e. non dwarf) (p. 1466, ¶2, p. 1469, discussion, ¶1). Therefore, it would be obvious to silence/knockout 7-DR2 in a standard tomato cultivar to test if 7-DR2 silencing in a standard tomato cultivar is also observed to have decreased cholesterol content, α-tomatine, and esculeoside B in the plants and fruit. Thus, there is motivation to move the mutation into a standard tomato cultivar. By doing so, the non-dwarf plant produced by the method would inherently have the accumulated 7-DHC.
Applicant argues against this, stating the claimed plant produced by the method of claim 1 would not inherently have accumulated 7-DHC. Applicant supports this argument with the Mizutani reference who reported knockout of 7-DR2 alone did not produce accumulated 7-DHC, and Sonawane who was silent to 7-DHC accumulation. However, both of the experiments by Mizutani and Sonawane were performed in a dwarf tomato cultivar (Micro Tom), and therefore the use of these examples does not rebut the position regarding inherency in the claimed subject matter. Because the instant claims are drawn to non-dwarf cultivars and the rejection is directed to a non-dwarf plant identical to a plant that instantly claimed, the result produced by the mutant 7-DR2 in the non-dwarf plant must be the same (the result being accumulated 7-DHC). The instant disclosure also provides evidence that a non-dwarf tomato plant with mutated 7-DR2 alleles accumulates 7-DHC. For these reasons, Applicant’s argument is not persuasive.
Should Applicant still insist 7-DHC accumulation is not inherent to a loss-of-function mutation in 7-DR2 of a non-dwarf tomato plant, then Applicant should consider that the instantly claimed invention is not enabled and another factor that is not claimed or argued is responsible for the 7-DHC accumulation.
Conclusion and Inquiries
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA N STOCKDALE whose telephone number is (703)756-5395. The examiner can normally be reached M-F 8:30-5:00 CT.
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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
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