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 .
Claim Status
Claims 1, 3-21, are pending. Claim 2, is cancelled. Claims 4-5 and 9-19 are withdrawn due to species election and not examined on its merits. Claims 1, 3, 6-8 and 20-21 are examined in the instant application.
All previous rejections not set forth below have been withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Amendments
Status of Objections
Specification objection has been withdrawn.
Status of Rejections from action:
In regard to Claims 1, 3, 6-8 and 21 under 112 (b) is added in view of amendment.
In regard to Claims 1, 3, 6-8 and 20-21 under 112(a) Written Description has been modified in view of amendments.
In regard to Claims 1, 3, 6-8 and 20-21 under 112(a) Enablement has been withdrawn in view of amendments. The Applicant limited the parent plants to specifically the brassica plant having a glucoraphanin content of 5mg/100g (fresh weight) and the Raphanus plant comprising a loss of function of glucoraphasatin synthase gene.
In regard to Claims 1, 3, 6-8 and 21 under 103 is modified in view of amendment.
Claim Rejections - 35 USC § 112(a)(Written Description)
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, 3, 6-8 and 20-21, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The 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.
The written description requirement may be satisfied through sufficient description of a representative number of species by disclosing relevant and identifying characteristics such as structural or other physical and/or chemical properties, by disclosing functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the invention as claimed. See Eli Lilly,119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant’s disclosure is as follows.
Applicant crossed a Brassicaceae plant, a kale line "KK-45" and 4 Japanese radish cultivar "Nishimachi-Risou” (AK0103, AK0108, AKO110, and AKO118), (see page 20 and table 1), to create hybrid plants AKO103xKK-45, AKO110xKK-45, AKO118xKK-45, and AKO108xKK-45 having increased glucoraphanin and decreased glucoraphenin content. Wherein, the glucoraphanin content increase by a “range of 1.97 to 2.56” (spec. pg. 23 para. [269]). Additionally, all four hybrids showed more glucoraphanin content compared to glucoerucin.
Claims encompass crossing Brassica plant wherein the glucoraphanin content is 5 mg/100g (fresh weight) or more and a Raphanus plant that comprises a loss-of-function of glucoraphasatin synthase gene - the specification only describes crossing a Brassicaceae plant, a kale line "KK-45" and 4 Japanese radish cultivar "Nishimachi-Risou” (AK0103, AK0108, AKO110, and AKO118).
The claimed invention lacks adequate written description for the following reasons. Claims 1, 3, 6-8 and 20-21 are directed to crossbreeding any species from the genus of Brassica and Raphanus plants to get a ratio of glucoraphanin content to glucoraphenin content in more than 1.0 or more.
The specification has only described cross breeding Brassicaceae plant, a kale line "KK-45" and 4 Japanese radish cultivar "Nishimachi-Risou” (AK0103, AK0108, AKO110, and AKO118), to get a ratio of glucoraphanin content to glucoraphenin content in more than 1.0 or more.
While the specification has described a glucoraphanin content increase by a “range of 1.97 to 2.56”, the specification has not described a representative number of crosses from the broad genus of plants that may be crossed and which comprise a ratio that is greater than 2.56 or a glucoraphanin content that is greater than 20mg/100g which is critical because there is no upper limit on the claimed ratio or glucoraphanin content.
The specification has not described if crossing other species of Brassica and Raphanus plants will produce a ratio of glucoraphanin content to glucoraphenin content in more than 1.0 or more. The resulting hybrid's glucoraphanin level depends entirely on the specific genetic makeup (genotype) of the parent plants.
For example, Liu et al. (Enriching Glucoraphanin in Brassica rapa Through Replacement of BrAOP2.2/BrAOP2.3 with Non-functional Genes. 2017. Front. Plant Sci. 8:1329. (U)) describes that “in most B. rapa vegetables, glucoraphanin is undetectable or only present in trace amounts, since the glucoraphanin that is present is converted to gluconapin by three functional BrAOP2 genes.”, (see Abstract). This suggests that plants with functional AOP2 genes would convert glucoraphanin (GRA) into gluconapin reducing the desired result.
Additionally, Endo et al. (Large insertion in radish GRS1 enhances glucoraphanin content in intergeneric hybrids, Raphanobrassica (Raphanus sativus L. x Brassica oleracea var. acephala). 2023. Front. Plant Sci. 14:1132302(V)) describe that “GLUCORAPHASATIN SYNTHASE 1 (GRS1) is an enzyme present in radish that synthesizes 4-methylthio-3-butenyl GSL (glucoraphasatin, 4MT3B), a precursor of 4MSO3B, using 4-(methylthio)butyl GSL (glucoerucin, 4MTB) as a substrate”…”We hypothesized that owing to the impaired function of GRS1 in Raphanobrassica, it may be possible to breed Raphanobrassica cultivars containing a high, 4MSOB([glucoraphanin]) content” (see Abstract and figure 1).
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This suggests that only through a very specific cultivar carrying an impaired heterozygous GRS1 gene (see page 3 left column first sentence) makes it even possible to achieve said phenotype. Therefore, the specification has only described plants with mutations that can be crossed to arrive at the phenotype and has not described that any plant from the genus as claimed can produce the phenotype.
Furthermore, the claim encompasses the production of an unlimited amount of glucoraphanin. However, the specification only describes “[t]he ratio of loss-of-function type glucoraphanin content/functional type glucoraphanin content is in a range of 1.97 to 2.56” (spec. pg. 23 para. [269]).
Endo et al. also describes that the glucoraphanin “content in leaves of the defective-type populations was higher than that in the functional type population, and the defective/functional ratio ranged from 2.02 to 2.51-fold” meaning that there is a limited increase of glucoraphanin (Abstract, fig.5, and table 5). Therefore, the specification has not adequately described an unlimited amount of glucoraphanin production.
This demonstrates that not all genera of Brassica or Raphanus plants as broadly encompassed by the claims hybridize and achieve the desired phenotype, further highlighting the unpredictable nature of intergeneric crossbreeding all genus of Brassica or Raphanus plants. Therefore, specification has not described a representative number of species of Brassica or Raphanus plants that may be crossed to yield the claimed trait of glucoraphanin content to glucoraphenin.
Accordingly, there is lack of adequate description to inform a skilled artisan that Applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/ Vol.66, No. 4/ Friday, January 5, 2001/ Notices; p. 1099-1111
Response to Arguments
Applicant's arguments filed 03/12/2026 have been fully considered but they are not persuasive. While Applicants argument rely on the narrow examples in the specification, the actual language of claim 1 broadly encompasses any Brassica and Raphanus cross and having no upper limit on the ratio of glucoraphanin to glucoraphenin and no upper limit on glucoraphanin content. Thus, Applicant’s arguments are not commensurate in scope with what is claimed, and the specification fails to adequately describe possession of the invention as broadly claimed.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 6-8 and 21, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the glucoraphanin content" in line 2. There is insufficient antecedent basis for this limitation in the claim. Applicant is advised to amend claim to wherein the Brassica plant comprises --a-- glucoraphanin content of 5 mg/100 g (fresh weight) or more.
Claims 2-3, 6-8 and 21 are rejected for depending upon a rejected base claim and for failing to remedy the issues of indefiniteness.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3, 6-8 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Niimi et al. “Amiprophosmethyl-induced efficient in vitro production of polyploids in raphanobrassica with the aid of aminoethoxyvinylglycine (AVG) in the culture medium”, Breeding Science. 2015 Dec;65(5):396-402 (U), in view of Yamada et al. (Inhibitory effect of Raphanobrassica on Helicobacter pylori-induced gastritis in Mongolian gerbils. 2014. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association vol. 70: 107-13.(previously cited)) and further in view of Kakizaki et al. (A 2-Oxoglutarate-Dependent Dioxygenase Mediates the Biosynthesis of Glucoraphasatin in Radish, March 2017, Plant Physiology, Volume 173, Issue 3, Pages 1583–1593,(previously cited)).
In regard to claims 1, 6-8 and 21, Niimi et al. teaches that “Inter-generic hybrid between radish (Raphanus sativus L., 2n = 2x = 18, RR genome) and kale (Brassica oleracea L. var. acephala D.C., 2n = 2x = 18, CC genome) categorized as Raphanobrassica, has been recognized to have two glucosinolates (GSL), i.e., kale specific component glucoraphanin (GRA) and radish specific component glucoraphenin (GRE) (Matthäus and Luftmann 2000, Takahata et al. 2006) (pg. 396 col.1 and 2).
Niimi et al. teach “GSL contents in polyploid plants. GSL: glucoraphanin (GRA) and glucoraphenin (GRE) contents were measured with leaves of 3 month-old plants by LC-MS/MS” (fig.4). Niimi et al. also teaches “demand for new Brassicaceae crops with higher amounts of GSL has now become one of the major concerns of the breeders” (pg. 396 col.2).
Niimi et al. does not teach a raphanobrassica plant with a ratio of glucoraphanin content to glucoraphenin content that is 1.0 or more and does not teach glucoraphanin measured in 20 mg/100g fresh weight.
In regard to claims 1, 6-8 and 21, Yamada et al. teaches on “Raphanobrassica (RB), an intergeneric hybrid between the genera Raphanus (radish) and Brassica (cabbage), contains large amounts of glucoraphanin (GR) and glucoraphenin (GRe)” (i.e. intergeneric crossbred plant from a Brassica plant and a Raphanus plant) (see page 107 introduction).
Specifically, Yamada et al. teaches that glucoraphanin is “an inert glucosinolate precursor of sulforaphane (1-isothiocyanato-4-methylsulfinylbutane), is actively hydrolyzed by the enzyme myrosinase to sulforaphane (Fahey et al., 2001), which exerts antimicrobial, antioxidative, anti-inflammatory and antitumorigenic effects mediated largely via the transcription factor Nrf2” (see page 107 introduction) showing that Raphanobrassica produce these anti-tumorigenic compounds, and that glucoraphanin in particular is important.
In regard to claims 1, 6-8 and 21, Kakizaki et al. teaches the radish Glucoraphasatin Synthase 1 (GRS1) is involved in the biosynthetic pathway of glucoraphenin (see figure 5).
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Specifically, the data demonstrates that radish plants deficient in GRS1 exhibit inhibited glucoraphenin production to non-detectable levels, while glucoraphanin content increases significantly (see table 1 below). This shift results in a glucoraphanin ratio of greater than one. The concentration of glucoraphanin is directly limited by the activity of the GRS1 gene.
In Raphanobrassica, both glucoraphanin and glucoraphenin share a common precursor: glucoerucin. Since GRS1 competes with FMO GS-OXs for this shared substrate to produce glucoraphenin, it creates a metabolic diversion that restricts the total yield of glucoraphanin.
By knocking out or lacking the GRS1 gene, effectively eliminates the competing pathway. This ensure that shutting down the alternative pathway, the precursor glucoerucin is made fully available to FMO GS-OXs, facilitating a significant and unobstructed increase in glucoraphanin synthesis (see table 1).
Kakizaki et al. teach measuring in µmol g-1 dry weight, as seen in the calculations below 3.9 µmol g-1 dry weight of glucoraphanin converts to 170.63 mg/100g.
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Table 1.
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Therefore, prior to the effective filing date it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Niimi et al. and Yamada et al in view of Kakizaki et al. because to do so would result in a Raphanobrassica plant with increases glucoraphanin content, of more that 20mg/100g in fresh weight, which is an important trait for cultivars and has beneficial properties as noted above.
One would have a reasonable expectation of success in this approach because Kakizaki et al. teaches a predictable method for modifying glucoraphanin content by knocking out GRS1 in radish. Consequently, one would reasonably expect that inhibiting the expression of an GRS1 gene in a radish plant and crossing it with Brassica would predictably increase glucoraphanin levels and enhance desired anti-tumorigenic properties.
Measuring in fresh/dry weight would be clearly a design choice obvious to a person of ordinary skilled in the art, because fresh plant material is primarily water, the compound is heavily diluted. Dehydrating the material first gives you a significantly higher concentration of the compound per unit of extracted weight. Overall, Kakizaki et al. teaches knocking out the gene responsible to make glucoraphenin and to increase glucoraphanin. Therefore since, glucoraphanin is being exclusively produced then it is expected to have more than 20 mg/100g (fresh weight).
In regard to claim 3, Kakizaki et al. clearly teaches that knocking out GRS1 would inhibit glucoraphenin production therefore glucoraphenin content would be less than 50 mg/100 g fresh weight since levels were non-detectable (see table 1).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 3, 6-8 and 21 have been considered but are unpersuasive. To the extent Applicant’s traversals apply to the above rejection, Applicant traverses primarily that (1) there is no motivation to combine Yamada et al. and Kakizaki et al’s radish; (2) that one skilled in the art would have not expected the specific cross of cultivars to give the unexpected results; and (3) that the examiner written description contradicts the 103 rejection. (Remarks, 03/12/2026, pages 10-12).
This argument has been fully considered but not found persuasive.
MPEP says, "the Board stated that when there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. KSR, 550 U.S. at 402-03, 82 USPQ2d at 1390” (MPEP, 2143/section E).
In regard to the 1st argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, the combination of Niimi et al., Yamada et al. and Kakizaki et al. render the claimed invention obvious. The claims are written so broadly that it encompasses Kakizaki et al’s. radish. Claim 1 just asks for any Raphunus plant with a nonfunctioning GRS1 gene, it reads directly on the prior art, and the cited references clearly contemplate producing Brassicaraphunus plants with increased glucoraphanin.
Applicant’s arguments (2) and (3) are unpersuasive because claim 1 doesn’t actually limit the invention to any specific cultivar or special breeding process. Because the claims is broad enough to encompass any plant that happens to have these basic genetic traits, it is expected to result in the claimed plant.
Applicant’s argument is also not persuasive because obviousness does not require a predictable result but rather a reasonable expectation of success. One has a reasonable expectation of success because Kakizaki teaches a radish plant as claimed, and because the art provides clear motivation for crossing this radish plant with a Brassica plant.
As is it known that the radish plant does not produce glucoraphanin but rather glucoraphanin, one would reasonably expect to see increases in glucoraphanin in the resulting hybrid. Thus, in the absence of some unexpected result or other secondary consideration, the rejection is maintained.
Conclusion
No claims are 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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/C.J.O./Examiner, Art Unit 1663
/JASON DEVEAU ROSEN/Primary Examiner, Art Unit 1662
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