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 .
Priority
This application, filed April 28, 2022, is a national stage application of PCT/JP2020/040975, filed October 30, 2020, which claims priority to foreign priority application JP2019-200257, filed November 1, 2019.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 9, 2026 has been entered.
Status of the Application
Applicant’s communication, received March 9, 2023, wherein claims 1, 10, and 16 are amended and claim 15 is canceled, is acknowledged.
Claims 1-14, 16-17, and 19-23 are pending in this application.
Claims 19-23 are withdrawn from consideration as being drawn to a non-elected invention.
Claims 1-14 and 16-17 are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, received March 9, 2026, with respect to the rejection of claims 1-17 under 35 USC § 112(b) as indefinite over the two steps of claim 1 requiring mixing the roughly purified product in solvent, has been fully considered and found to be persuasive to remove the rejection because claim 15 is canceled and Applicant has amended claim 1 to recite the limitation “to adjust a solution for crystallization” only one time. Accordingly, the rejection of claim 1 under 35 U.S.C. 112(b) is withdrawn. However, claim 1 is now interpreted as described below in the claim interpretation section.
Applicant’s amendment, received March 9, 2026, with respect to the rejection of claims 1-5, 7, 10-11, 13, 15, and 17 under 35 USC § 103 as unpatentable over Markosyan ‘167 in view of Prakash, as evidenced by Perkin Elmer, has been fully considered and found to be persuasive to remove the rejection of claims 10 and 15 because claim 15 is canceled and claim 10 is amended to require the additional methods steps recited in claim 10, which the combination of Markosyan ‘167 and Prakash does not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received March 9, 2026, with respect to the rejection of claims 1-7, 9-13, and 15-17 under 35 U.S.C. § 103 as being unpatentable over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana, as evidenced by Perkin Elmer, has been fully considered and found to be persuasive to remove the rejection of claims 10 and 15 because claim 15 is canceled and claim 10 is amended to require the additional method steps recited in claim 10, which the combination of Markosyan ‘167, Prakash, Abelyan, and Steviana does not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received March 9, 2026, with respect to the nonstatutory double patenting rejection of claims 1-13 and 15-18 over claims 1-15 of copending U.S. patent application 17/772848 in view of Markosyan ‘167, as evidenced by Perkin Elmer, has been fully considered and found to be persuasive to remove the rejection because Applicant has filed a terminal disclaimer disclaiming extension of patent term beyond that of application 17/772848. Therefore the rejection is withdrawn.
The following is a new rejection, necessitated by Applicant’s amendment received March 9, 2026, wherein claims 1, 10, and 16 are amended and claim 15 is canceled.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 17 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 17 depends from claim 1 and requires a ratio of rebaudioside D crystallized to rebaudioside D contained in the roughly purified product, after a single crystallization, is 70 to 99% by mass.
However, claim 1 now requires the recovery rate of rebaudioside D is 55 to 90% by mass after a first crystallization through the production method. The ratio of rebaudioside D crystallized to rebaudioside D contained in the roughly purified product after a single crystallization, as recited in claim 17, is defining the recovery rate of rebaudioside D after a first crystallization. Therefore, because claim 17 requires said ratio is 70 to 99% by mass, which does not fall within the range of 55 to 90% by mass as recited in claim 1, claim 17 fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following are modified grounds of rejection, updated herein to reflect Applicant’s amendments received March 9, 2026. Applicant’s arguments are addressed following these rejections.
Claim Interpretation
Claim 2 requires the total steviol glycoside corresponds to rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, stevioside, rebaudioside F and rebaudioside M. The transitional phrase “corresponds to” is interpreted as synonymous with the inclusive transitional phrase “comprises,” which requires the listed species but permits additional steviol glycoside species as well. See MPEP 2111.03.
Claim 1 recites “mixing the roughly purified product in a solvent containing methanol or ethanol such that a degree of supersaturation at 10°C of rebaudioside D is 10 or more and a degree of supersaturation at 10°C of rebaudioside A is 18 or less,” and “mixing the roughly purified product in a solvent containing ethanol and having a methanol concentration of 1 mg/L or less, to adjust a solution for crystallization.”
Applicant has amended claim 1 herein to remove the limitation “to adjust a solution for crystallization” following “mixing the roughly purified product in a solvent containing methanol or ethanol such that a degree of supersaturation at 10°C of rebaudioside D is 10 or more and a degree of supersaturation at 10°C of rebaudioside A is 18 or less.” Claim 1 was previously rejected under 112(b) because it recited two steps for adjusting a solution for crystallization.
Regarding the previous rejection under 112(b), Applicant argues that claim 1 is now amended for even greater clarity, and Applicant submits that one of skill in the art would immediately know the metes and bounds of the claim including the mixing steps, as well as the solution for crystallization.
Claim 1 is thus interpreted herein as requiring mixing the roughly purified product in a solvent containing methanol or ethanol such that a degree of supersaturation at 10°C of rebaudioside D is 10 or more and a degree of supersaturation at 10°C of rebaudioside A is 18 or less, and mixing the roughly purified product in a solvent containing ethanol and having a methanol concentration of 1 mg/L or less, to adjust a solution for crystallization.
These two mixing steps may the same step, such as if ethanol with less than 1 mg/mL methanol is used in the first step to achieve the required degrees of supersaturation, or these two mixing steps may be separate steps. This interpretation does not require crystallization occurs under the supersaturation conditions recited in the claim, because the claim permits an additional step of mixing the roughly purified product in a solvent containing ethanol and having a methanol concentration of 1 mg/L or less, to adjust a solution for crystallization, after having added solvent to achieve the required degrees of supersaturation.
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 1-5, 7, 11, 13, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Markosyan ‘167 (US 20190133167 Al; cited in IDS received August 2, 2022) in view of Prakash (Publication No. WO 2017059414 A1; of record), as evidenced by Perkin Elmer (Perkin Elmer Application Note, Analysis of United States Pharmacopoeia (USP) Grade Alcohol (Ethyl alcohol) Impurities, 2021; of record).
Claim 1 claims a method for producing a rebaudioside D-containing crystallized product by use of a roughly purified product obtained by roughly purifying an extract from a stevia plant, wherein a total steviol glycoside content of the roughly purified product is 50 to 95% by mass and the roughly purified product contains at least rebaudioside A and rebaudioside D, wherein a
content of rebaudioside A is 20 to 70% by mass in the roughly purified product, the method comprising: mixing the roughly purified product in a solvent containing methanol or ethanol
such that a degree of supersaturation at 10°C of rebaudioside D is 10 or more and a degree of
supersaturation at 10°C of rebaudioside A is 18 or less, to adjust a solution for crystallization, cooling the solution for crystallization with stirring, to precipitate rebaudioside D, mixing the roughly purified product in a solvent containing ethanol and having a methanol concentration of 1 mg/Lor less, to adjust a solution for crystallization, and cooling the solution for crystallization with stirring, to precipitate rebaudioside D, wherein, in the rebaudioside D-containing crystalline product obtained after a first crystallization through the production method, the proportion of rebaudioside D relative to total steviol glycosides is 35 to 95% by mass, and the recovery rate of rebaudioside D is 55 to 90% by mass.
Claim 2 requires the total Steviol glycoside content as recited therein, claim 3 requires a content of rebaudioside D is 2 to 70% by mass in the roughly purified product, claim 4 requires the concentration of the ethanol in the solvent is 99.9% by mass or less, claim 5 requires the solvent is kept at a temperature of 40 to 80°C in mixing of the roughly purified product, claim 7 requires the solution for crystallization is cooled to a temperature of 35°C or less with stirring, to precipitate rebaudioside D.
Claim 11 requires further separating rebaudioside D precipitated and a liquid phase, and drying rebaudioside D separated, claim 13 requires a methanol content of a rebaudioside D-containing crystallized product is less than 10 ppm, and claim 17 requires ratio of rebaudioside D crystallized, to rebaudioside D contained in a roughly purified product, after a single crystallization, is 70 to 99% by mass.
Markosyan ‘167 teaches an example in which 14 kg of starting stevia extract (referred to as SSE) was added into 112 liters of 75% (v/v) ethanol, the mixture was heated to 80° C for complete dissolution of SSE, the solution was cooled to 25° C, and about 3 g of crystalline Rebaudioside M was added as seed. Markosyan ‘167 teaches that the solution was held at 25° C for 96 hours for crystallization, that the obtained crystals were separated from the mother liquor and washed with pure ethanol, and that the wet crystals were dried in a vacuum drier at 70° C to yield about 4 kg of powdered steviol glycosides composition (referred to as SGC-1) (p. 7, [0072], lines 1-11).
SSE in this case is considered as the roughly purified product. Because it is named as a stevia extract, it is reasonably considered an extract from a stevia plant, and because it contains several different components, the method of producing it is reasonably considered as roughly purifying, as recited in claim 1.
Regarding the requirement that the methanol concentration is less than 1 mg/L as recited in claim 1, because Markosyan ‘167 does not teach the addition of methanol, this is interpreted as evidence that no methanol is present in the crystallization solution.
To further support the requirement that the ethanol includes a concentration of less than 1 mg/L methanol, Perkin Elmer (Perkin Elmer Application Note, Analysis of United States Pharmacopoeia (USP) Grade Alcohol (Ethyl alcohol) Impurities, 2021; of record) serves as an evidentiary reference that ethanol may be free of methanol. Perkin Elmer teaches that runs of ethanol blanks A and B (p. 5, Table 2) showed no methanol present, while a 200 ppm spike of methanol showed a detectable area. Therefore, based on these data from Perkin Elmer, ethanol as a solvent is reasonably considered to be free of methanol, and the product produced by the method of Markosyan ‘167 would be expected to have less than 10 ppm methanol, as required by claim 13.
The 75% v/v ethanol satisfies the limitation regarding ethanol concentration in claim 4, and the temperatures taught by Markosyan ‘167 satisfy the limitations of claim 5 and claim 7. The method requires separating rebaudioside D precipitated and a liquid phase, and drying rebaudioside D separated, as recited in claim 11.
Markosyan ‘167 teaches that HPLC analysis of the SSE showed the composition comprised the following components (% w/w): RebE: 3.42%; Reb O: 7.34%; Reb D: 25.26%; Reb N: 7.26%; Reb M: 10.71%; RebA 11.19%; Stev 1.67%; Reb F 0.08%; Reb C: 0.41%; Dul A 0.1%; Reb B: 0.29%; and Sbio: 0.03%. (pp. 7-8, [0077], Table 1). The total Steviol glycoside content in this composition is 67.76%, which satisfies the limitation regarding total Steviol glycoside content in claim 1 and the amount of Reb D in claim 3. In addition, these glycosides satisfy the limitation regarding the total Steviol glycoside content of claim 2.
Markosyan ‘167 teaches that HPLC analysis of the SGC-1 product showed the composition comprised the following components (% w/w): RebE: 0.84%; Reb O: 1.07%; Reb D: 67.34%; Reb N: 2.3%; Reb M: 22.58%; RebA 1.44%; Stev 0.02%; and Reb B: 0.16% (pp. 7-8, [0077], Table 1). This value of 67.34% Reb D satisfies the limitation of claim 1 requiring the proportion of rebaudioside D relative to total steviol glycosides is 35 to 95% by mass.
Regarding the recovery of Reb D, the mass of Reb D in the SSE used in this example is 3.54 kg (14 kg * 25.26% Reb D). The mass of Reb D in the SGC-1 is 2.69 kg (4 kg * 67.34%). Therefore the ratio of rebaudioside D crystallized to rebaudioside D contained in a roughly purified product is 76.0% by mass, which satisfies claims 1 and 17.
Moreover, Markosyan ‘167 teaches that the solution of starting material may be seeded with a steviol glycoside seed composition to promote crystallization (p. 6, [0057]), and suggests rebaudioside D as one such steviol glycoside that may be used as a seed (p. 6, [0058]). In addition, Markosyan ‘167 teaches that the concentration of aqueous ethanol may vary from 0.05% to 99%, which is taken as teaching the concentration of ethanol may affect the yield and/or products of the process taught by Markosyan ‘167.
Regarding the requirement in claim 1 wherein the degree of supersaturation at 10°C of rebaudioside D is 10 or more and a degree of supersaturation at 10°C of rebaudioside A is 18 or less, although Markosyan ‘167 does not specifically teach the degree of supersaturation in their experiment, the examiner believes that the conditions of Markosyan ‘167 meets this requirement.
The ratio (g/L) of Reb D to 75% ethanol in the experiment taught by Markosyan ‘167 is 31.6 (based on 3536 g of Reb D (25.26% * 14,000 g) in 112 L), and the ratio of Reb A to 75% ethanol is 13.8 (based on 1566 g (11.19% * 14,000 g) in 112 L).
The instant specification discloses in Experimental Example 15 (see specification, p. 76-77) that an approximately 180 g product comprising 49.4% Reb A (88.8 g) and 14.8% Reb D (26.6 g) was dissolved in 1.538 L of 90% ethanol. The ratio (g/L) of Reb D to 90% ethanol in this example is 17.29 (determined from 26.6 g/1.538 L), and the ratio of Reb A to 90% ethanol is 57.7 (determined from 88.8 g/1.538 L). The specification teaches that the degree of supersaturation of Reb A at 10 °C was 5.7, and the degree of supersaturation of Reb D at 10 °C was 160.1 (p. 77, [0170], lines 3-5).
Therefore, in the example taught by Markosyan ‘167, the concentration of Reb D is higher than the concentration of Reb D in Experimental Example 15, and the concentration of Reb A is lower than the concentration of Reb A in Experimental Example 15. Accordingly, one of ordinary skill in the art would have expected Reb D to have a higher degree of supersaturation than in Experimental Example 15 and Reb A to have a lower degree of supersaturation than in Experimental Example 15. These degrees of supersaturation would satisfy the requirements regarding degrees of supersaturation recited in claim 1. Although the solubilities of Reb D and Reb A in 90% ethanol may be different from those concentrations in 75% ethanol, absent evidence showing the degrees of supersaturation of Reb D and Reb A in the experiment of Markosyan ‘176 do not satisfy claim 1, the examiner maintains this method meets the limitations of claim 1.
Finally, Markosyan ‘167 teaches their method may be applied to compositions with other ratios of Steviol glycosides, such as those with higher concentrations of rebaudioside A (p. 4, [0033]), and that the embodiment of their method is not limited to the proportions in the example provided (p. 7, [0071, lines 1-5).
Therefore, the method of Markosyan ‘167 teaches all limitations of claims 1-5, 7, 11, 13, and 17, except for wherein a content of rebaudioside A is 20 to 70% by mass in the roughly purified product, and cooling the solution for crystallization with stirring to precipitate rebaudioside D, each as required by claim 1.
Prakash teaches methods of preparing compositions comprising Steviol glycosides. In one example, Prakash teaches that a Steviol glycoside concentrate obtained by extraction from stevia leaves was dried with a spray drier to yield an Enriched Stevia Extract powder comprising 1.97% Reb E, 7.82% Reb O, 23.92% Reb D, 6.92% Reb N, 12.17% Reb M, 11.91 % Reb A and about 2% of other steviol glycosides (all percentages are on w/w anhydrous basis) (p. 79, lines 8-11). This extract includes at least 64% steviol glycosides, including 23.92% Reb D and 11.91% Reb A.
Prakash further teaches that a method wherein 100 g of Enriched Stevia Extract obtained according to the procedure in their Example 1 was dissolved in 700 mL of 70% Ethanol (v/v), seeded with 20 mg Reb M crystals and agitated moderately for 4 days at 25 °C for crystallization (p. 79, Example 2, lines 13-17). Prakash teaches the crystals were separated by filtration, washed with ethanol, and dried under vacuum at 80°C for 12 hours, to yield about 30 g of product A95 (p. 79, lines 15-17). Prakash further teaches that HPLC analysis showed this product contained 63.95% rebaudioside D (p. 80, Table 1). Therefore, 23.92 g (23.92% of 100 g) of Reb D was used for crystallization in the method of Prakash, and approximately 19.2 g (63.95% of 30 g) was isolated, corresponding to an approximately 80% yield.
In addition, Prakash teaches and claims a method of preparing a steviol glycoside composition comprising (i) providing enriched stevia extract comprising from about 5% to about 30% rebaudioside M by weight; (ii) combining the enriched stevia extract with a solvent system comprising at least one organic solvent to provide a first solution; (iii) stirring the first solution and/or seeding the solution to promote crystal formation; and (iv) separating the crystals from the first solution to provide the steviol glycoside composition (p. 89, claim 22, lines 1-8) (emphasis added). This is taken as teaching that stirring during crystal formation is an effective form of agitation.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to stir during precipitation in the method of Markosyan ‘167. One of ordinary skill in the art would have been motivated to stir during precipitation in the method of Markosyan ‘167 because Markosyan ‘167 teaches a method of precipitating rebaudioside D, and because Prakash teaches a similar method of precipitating rebaudioside D that involves agitation or stirring during crystal formation. Thus one of ordinary skill in the art would have recognized that stirring maybe effective in promoting crystal formation in the precipitation of rebaudioside D, as taught by Prakash, and would have considered stirring during precipitation of rebaudioside D when practicing the method of Markosyan ‘167.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art to apply the method of Markosyan ‘167 to a stevia extract comprising a higher concentration of rebaudioside A. One of ordinary skill in the art would have been motivated to apply the method of Markosyan ‘167 to a stevia extract comprising a higher concentration of rebaudioside A because Markosyan ‘167 states their method may be applied to compositions with other proportions of components, including those with higher concentrations of rebaudioside A, and accordingly one of ordinary skill in the art would have reasonably recognized that the method of Markosyan ‘167 is not limited to the specific starting composition disclosed by Markosyan ‘167, and may also be used to isolate rebaudioside D from a composition that includes higher concentrations of rebaudioside A. In addition, one of ordinary skill in the art would have contemplated applying the method disclosed by Markosyan ‘167 to other stevia extracts, such as those with higher concentrations of rebaudioside A, because that would permit isolation or enrichment of rebaudioside D from additional stevia extracts, and thus provide alternative sources of starting material from which to isolate rebaudioside D.
Regarding the specific degree of supersaturation of rebaudioside A in such a composition, even with a stevia extract that includes, for example, twice as much rebaudioside A as the composition taught by Markosyan ‘167, said composition used in the method obvious over Markosyan ‘167 in view of Prakash would still have a degree of supersaturation below 18, as required in claim 1, because the degree of supersaturation in the composition taught by Markosyan ‘167 is less than 5.7, as described above.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejections, Applicant presents the following arguments:
1. Applicant argues that the presently claimed subject matter achieves both high yield and high purity in the first crystallization. Further to this, the claims as amended herein specify that in the rebaudioside D-containing crystalline product obtained after a first crystallization through the production method, the proportion of rebaudioside D relative to total steviol glycosides is 35 to 95% by mass, and the recovery rate of rebaudioside D is 55 to 90% by mass. Markosyan '167 in view of Prakash fail to teach or suggest at least these features of the methods as presently claimed. Applicant states that neither Markosyan '167 nor Prakash discloses achieving high yield and high purity in the first crystallization (i.e., primary crystallization), nor would such an effect have been expected from their teachings.
2. Applicant argues that Markosyan '167 fails to teach or suggest the recited
roughly purified product having a Reb A content of 20-70 wt% and that Prakash does not cure
this deficiency, and thus the cited art does not disclose or suggest use of a roughly purified product with a high Reb A content of 20-70 wt% of Reb A as a starting product. Moreover, one of skill in the art would not have any reason to replace the starting material of Markosyan '167 with that of Prakash at least because the object of Markosyan '167 is enrichment for Reb M. Markosyan, when considered as a whole, teaches enrichment for Reb M based on, for example, the use of crystalline Reb M seeds and high content of Reb M in the starting stevia extract (SSE). Notably, had one of skill in the art at the time of filing considered replacing the SSE of Markosyan '167 with the SSE of Prakash, the skilled artisan would actually have expected to lower the yield of the target compound (Reb M), and thus there was a disincentive to use such an SSE in Markosyan '167.
3. Applicant argues the claimed embodiments result in obtaining Reb D in
high purity (>70%) even in a single crystallization step by adjusting the supersaturation levels as
specified in claim 1, and even when using a roughly purified product with a high Reb A content, as embodied in Example 8 of the specification. Applicant argues that the cited art, either singly or in combination, does not disclose or suggest this.
Applicant’s arguments have been fully considered but they are not found persuasive.
Regarding Applicant’s first argument that presently claimed subject matter achieves both high yield and high purity in the first crystallization, as described in the above rejection, the method of Markosyan ‘167 shows high yield and purity after a single crystallization, with both yield and purity of Reb D satisfying the amended claims.
Regarding Applicant’s second argument that the cited art does not disclose or suggest use of a roughly purified product with a high Reb A content of 20-70 wt % of Reb A as a starting product, the examiner maintains that Markosyan ‘167 suggests their method may be applied to alternative extracts, including those with higher concentrations of Reb A. Markosyan ‘167 discloses a broad range of acceptable Reb A levels in the composition, and thus one of ordinary skill in the art would have recognized the method of Markosyan ‘167 may be reasonably applied to compositions with alternative proportions of rebaudiosides.
Regarding Applicant’s argument that the objective of Markosyan ‘167 is solely to enrich Reb M in the specific SSE of Markosyan ‘167, the examiner maintains that this is a narrow reading of Markosyan ‘167, especially when their results show robust enrichment of Reb D by their crystallization method. The examiner maintains that because Markosyan ‘167 suggests extracts with alternative Reb A concentrations may be used in their method, one of ordinary skill in the art would have contemplated said methods for the full scope of stevia extracts from which a rebaudioside may be isolated.
Regarding Applicant’s argument that Markosyan ‘167 is drawn to isolating Reb M, one of ordinary skill in the art would have recognized the outcome of said experiment – an increase in Reb D – and recognized the benefit of such recrystallization conditions, even when seeding with Reb M. Furthermore, Markosyan ‘167 teaches that other crystals may be used as seeds. Therefore, one of ordinary skill in the art would have contemplated the method of Markosyan ‘167 and recognized that this method may be utilized for purifying alternative steviol glycosides, such as Reb D as embodied by Markosyan ‘167.
Regarding Applicant’s third argument and the specific supersaturation conditions required by claim 1, although Markosyan '167 does not disclose or suggest adjusting the supersaturation levels of the components, specifically lowering the supersaturation of the major component Reb A and increasing the supersaturation of Reb D in order to enhance the yield of Reb D, as stated, the concentrations of Reb A and Reb D as taught in the experiment by Markosyan '167 are believed to satisfy the requirements regarding degrees of supersaturation required by claim 1, absent evidence to the contrary. In addition, if a composition comprising a higher concentration of Reb A were used in the method of Markosyan ‘167, for example, a composition with twice the level of Reb A, this level of Reb A is believed to still fall below the supersaturation limit required by claim 1, absent evidence to the contrary.
Regarding Applicant’s claim of superior results embodied by Experiment 8, the examiner recognizes these results, but does not believe they are unexpected or superior in view of the prior art. As stated, Markosyan ‘167 teaches robust yield and purity of Reb D in the product crystallized during their method. In addition, Abelyan (Publication no. WO 2011046423 A1; of record) discloses an embodiment in which a composition (which had already been through one step of recrystallization) included Stevioside (1.4%), Rebaudioside A (72.8%), Rebaudioside C (1.5%), Rebaudioside D (21.4%), Rebaudioside B (0.1%), Rebaudioside E (2.1%), and Rebaudioside F (0.7%) (pp. 56-57, [00225]). Abelyan teaches that for further purification of Rebaudioside D, the precipitate was suspended in 50% ethanol at 1:2 w/v ratio and maintained for 12 hours at 35°C with agitation. The suspension was filtered and precipitate was dried. The yield of precipitate was around 23% and contained Stevioside (0.8%), Rebaudioside A (16.2%), Rebaudioside C (0.7%), Rebaudioside D (81.6%), Rebaudioside E (0.5%), and Rebaudioside F (0.2%).
This experiment from Abelyan demonstrates that substantial increases in rebaudioside D content (from 21.4% to 81.6%) may be achieved in a single step based on differential solubility. In addition, significant decreases of Rebaudioside A content (from 72.8% to 16.2%) were achieved. Although the Reb A content of this composition is higher than the range recited in claim 1, and although the yield of this specific recrystallization experiment is relatively low, it serves as another example (in addition to Markosyan ‘167) that in a single step, substantial enrichment of Reb D may be achieved. Moreover, one of ordinary skill in the art would have recognized that the full steps of traditional crystallization, including complete dissolution and cooling of the solution, may reasonably increase the yield achieved from this experiment.
Finally, Abelyan teaches general guidance regarding isolation of rebaudioside A and rebaudioside D by recrystallization. Abelyan teaches that the rebaudioside D content increases with the increase of the concentration of ethanol up to 88-90% and a decrease in the ratio of solvent to extract, and at the same time, the purity of Rebaudioside A increased with more diluted ethanol solutions and higher ratios of solvent to extract (p. 32, [00129]; see also pp. 31-32, Tables 3 and 4). Accordingly, in view of this teaching, one of ordinary skill in the art would have adjusted conditions, including the amount of ethanol used for recrystallization and the amount of solvent relative to stevia extract, to optimize the yield of the rebaudioside compound being isolated. Moreover, the general principle argued by Applicant, that a difference in solubility (e.g., a difference in degree of supersaturation in a single solvent system) may be used to enrich a product in a less soluble component is well-known in the prior art, and one of ordinary skill in the art would have reasonably engaged in routine experimentation to optimize conditions for crystallization.
Therefore, for the reasons described above, the present rejection of claims 1-5, 7, 11, 13, and 17 as unpatentable over Markosyan ‘167 in view of Prakash, as evidenced by Perkin Elmer, is maintained.
Claims 6, 9, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Markosyan ‘167 in view of Prakash, as evidenced by Perkin Elmer, as applied to claims 1-5, 7, 11, 13, and 17 above, and further in view of Abelyan (Publication no. WO 2011046423 Al; of record).
Claim 6 depends from claim 1 and requires rebaudioside D is used as a seed crystal. Claim 9 depends from claim 1 and requires the solution for crystallization is cooled for a period of 1 to 48 hours with stirring, to precipitate rebaudioside D, as required by claim 9. Claim 12 requires the additional steps of crystallization recited therein.
Markosyan ‘167 and Prakash teach as described in the above rejection under 35 U.S.C. § 103. Specifically, Markosyan ‘167 teaches that crystalline Rebaudioside M was added as a seed (p. 7, [0072], lines 5-7), and suggests other Steviol glycosides, including Rebaudioside D, may be added as a seed (p. 6, [0057]-[0058]). Prakash teaches that seeding may be used to promote crystal formation (p. 89, claim 22, step (iii)) and teaches seeding with Reb M crystals (p. 79, lines 14-15).
In addition, Markosyan ‘167 teaches an embodiment wherein the composition is cooled for 96 hours for crystallization (p. 7, [0072], lines 7-8), and Markosyan ‘167 claims holding the solution of starting material at a temperature ranging from about -24°C to about 80°C during a time interval ranging from about 1 minute to about 240 hours, to obtain a crystallized Steviol glycosides composition (p. 9, claim 1).
Neither Markosyan ‘167 nor Prakash teach a specific embodiment wherein Reb D is used a seed crystal, as required by claim 6, or wherein the solution for crystallization is cooled for a period of 1 to 48 hours with stirring, to precipitate rebaudioside D, as required by claim 9. In addition, neither Markosyan ‘167 nor Prakash teach the additional steps of crystallization required by claim 12.
Abelyan teaches a method of isolating both Reb A and Reb D from stevia leaf extracts. Abelyan teaches and claims a method for purifying rebaudioside D from Stevia extract comprising providing an extract of Stevia rebaudiana Bertoni plant; dissolving the extract in a first aqueous solution of organic solvent, inducing crystallization, and filtering the first mixture to obtain a first precipitate and a first filtrate. Abelyan teaches that additional steps of crystallization may be performed by dissolving the first precipitate in a second aqueous solution of organic solvent to result in a second mixture, inducing crystallization, and filtering the second mixture to obtain a second precipitate and a second filtrate, as well as a third step whereby drying the third precipitate yields purified Rebaudioside D (p. 67, claim 1). This method of Abelyan includes two additional crystallization steps for producing purified rebaudioside D.
Abelyan further claims that the purified Rebaudioside D composition comprises rebaudioside D with a purity greater than about 95%, 97%, 98%, and 99% Rebaudioside D (p. 69, claims 16-19).
Abelyan claims wherein the step of (c) inducing crystallization in the first mixture comprises adding high purity Rebaudioside A to promote crystallization (p. 67, claim 5), and additionally claims that high purity Rebaudioside D is added to promote crystallization in a later step of crystallization to produce purified Rebaudioside D (p. 68, claim 8).
Finally, Abelyan teaches an embodiment wherein a Stevia extract was dissolved in 95% ethyl alcohol and maintained at 80°C for 35 min, and then at l5°C for 12 hours with agitation (p. 56, [0056], lines 1-5). This experiment used 1.0% of highly purified Rebaudioside A as a starter to initiate crystallization (p. 56, [0056], lines 5-7), and after isolation, yielded a product that included rebaudioside A and rebaudioside D (p. 56, [00223], lines 1-3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to substitute the Reb M used as a seed crystal in the experiments of Markosyan ‘167 and Prakash with a Reb D seed crystal. One of ordinary skill in the art would have been motivated to substitute the Reb M used as a seed crystal in the experiments of Markosyan ‘167 and Prakash with Reb D because Prakash teaches generally that addition of a seed crystal may be used to promote crystal formation in their method of producing a steviol glycoside composition, because Abelyan claims that Reb D may be used as a seed crystal to produce highly purified rebaudioside, and because Markosyan ‘167 expressly suggests that Reb D may be used as a seed crystal. Thus one of ordinary skill in the art would have considered Reb D as a seed in the method obvious over Markosyan ‘167 in view of Prakash, because the use of Reb D as a seed would reasonably be expected to produce a purified rebaudioside D product, as taught in the method of Abelyan.
Regarding the crystallization time, because Markosyan ‘167 teaches a range of crystallization times, and because Abelyan teaches a related crystallization method wherein crystals were allowed to form for 12 hours, one of ordinary skill in the art would have considered other times for crystallization, such as the 12 hours taught by Abelyan, because shorter times may also effectively yield a crystallized product with rebaudioside A and rebaudioside D that satisfy the yield and purity requirements of present claim 1, as demonstrated in the method taught by Markosyan ‘167.
Regarding the additional steps of crystallization recited in claim 12, wherein the rebaudioside D is separated, dried, and then subjected to an additional round of crystallization with separation and drying to isolate additional rebaudioside D, one of ordinary skill in the art would have been motivated to perform the additional steps of crystallization because the method obvious over of Markosyan ‘167 in view of Prakash teaches the method of claim 1, including separating and drying precipitated rebaudioside D to obtain a primary crystallized product, and because Abelyan teaches additional steps of crystallization may be performed to improve the purity of rebaudioside D. Therefore one of ordinary skill in the art would have considered the additional steps of crystallization as means to increase the purity of rebaudioside D.
With respect to the degrees of supersaturation of Reb D and Reb A as required by claim 12, because Markosyan ‘167 teaches conditions for the crystallization of Reb D from a solvent of 75% ethanol, one of ordinary skill in the art would have considered these conditions when performing additional recrystallization steps of the Reb D product. As discussed in the above rejection, these conditions are believed to satisfy the required degrees of supersaturation recited in claim 12, absent evidence to the contrary.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection of claims 6, 9, and 12 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash and Abelyan, Applicant argues that claims 6, 9 and 12 are patentable at least due to their dependency on claim 1.
For the same reasons described above regarding the rejection of claim 1, the rejection of claims 6, 9, and 12 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash and Abelyan is maintained.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Markosyan ‘167 in view of Prakash, as evidenced by Perkin-Elmer, as applied to claims 1-5, 7, 11, 13, and 17 above, and further in view of Pnita (U.S. pre-grant publication no. US 20130164434 A1; of record).
Claim 8 depends from claim 1 and requires the solution for crystallization is cooled at a rate of 0.002 to l.37°C/min with stirring, to precipitate rebaudioside D.
Markosyan ‘167 and Prakash teach as described in the above rejections under 35 U.S.C. 103. Specifically, Markosyan ‘167 teaches cooling to induce crystallization, but does not teach a rate of cooling.
Markosyan ‘167 and Prakash do not teach the solution for crystallization is cooled at a rate of 0.002 to l.37°C/min, as required by claim 8.
Pnita teaches processes for the purification of rebaudioside A from Steviol glycoside compositions, such as Stevia extracts (cover page, Abstract, lines 1-3). In one embodiment, Pnita teaches that 470 grams of the dried Stevia extract was mixed with 2 liters of 99.5% (v/v) ethanol, heated to reflux temperature of 78°C over a period of 30 minutes and held at 78°C for 30 minutes, sonicated to initiate nucleation and cooled to 5°C over 6 hours and held at this temperature for 15 hours to allow crystals to develop and mature ([0072], lines 1-8; [0073], lines 1-3). The cooling from 78°C to 5°C over 6 hours corresponds to a rate of cooling of 12°C/hour, or 0.2°C/minute.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to cool the solution of steviol glycosides in the method obvious over Markosyan ‘167 in view of Prakash at a rate of 0.2°C/minute. One of ordinary skill in the art would have been motivated to cool the solution of steviol glycosides in the method obvious over Markosyan ‘167 in view of Prakash at a rate of 0.2°C/minute because Markosyan ‘167 in view of Prakash each teach methods of isolating Steviol glycosides, such as rebaudioside A and rebaudioside D, using crystallization, and because Pnita teaches a method of isolating rebaudioside A by crystallization and teaches a method wherein the solution of Steviol glycosides is cooled at a rate of 0.2°C/minute. Therefore, one of ordinary skill in the art, when practicing the method obvious over Markosyan ‘167 in view of Prakash, would have considered rates of cooling taught in the prior art, including in the related method of Pnita, as guidance when selecting the rate of cooling for the method obvious over Markosyan ‘167 in view of Prakash, and would have adjusted this rate of cooling as necessary depending on the conditions and desired outcome of this method.
One of ordinary skill in the art would have had a reasonable expectation of success applying the method of cooling of Pnita to the method obvious over Markosyan ‘167 in view of Prakash because each method is directed to isolating a Steviol glycoside product by crystallization, and because the method obvious over Markosyan ‘167 in view of Prakash requires cooling to promote crystal formation but provides no guidance to select a rate of cooling. Thus one of ordinary skill in the art would have reasonably considered rates of cooling taught in the prior art, including the rate of cooling taught by Pnita, as guidance when practicing the method obvious over Markosyan ‘167 in view of Prakash.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection of claim 8 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash and Pnita, Applicant argues that claim 8 is patentable at least due to its dependency on claim 1.
For the same reasons described above regarding the rejection of claim 1, the rejection of claim 8 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash and Pnita is maintained.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Markosyan ‘167 in view of Prakash, as evidenced by Perkin-Elmer, as applied to claims 1-5, 7, 11, 13, and 17 above, and further in view of Abelyan (Publication no. WO 2011046423 Al; of record) and Steviana (Publication no. CN109645432A; cited in the restriction requirement mailed March 25, 2025).
Steviana was published in a language other than English. The original document and an English language machine translation were included with the restriction requirement mailed March 11, 2025. Citations below refer to the English language machine translation document.
Claim 16 depends from claim 1 and requires a ratio of rebaudioside A to the total steviol glycoside in the rebaudioside D-containing crystallized product is 10 to 50% by mass.
Markosyan ‘167 and Prakash teach as described in the above rejections under 35 U.S.C. 103.
Markosyan ‘167 and Prakash do not teach the ratio of rebaudioside A to the total steviol glycoside in the rebaudioside D-containing crystallized product is 10 to 50% by mass, as required by claim 16.
Abelyan teaches as described in the above rejection under 35 U.S.C. 103. In addition, Abelyan teaches that the amount of rebaudioside A present in a crystallized product prepared by a similar method to the method obvious over Markosyan ‘167 and Prakash is dependent on the amount of rebaudioside A present in the initial extract (p. 32, [00130], lines 1-4). As shown in Table 5, the yield of rebaudioside A increased from 22-25% to 32-36% as the amount of rebaudioside A in the initial extract increases from 42-43% to 60-62% (p. 32, [00130], Table 5).
Steviana teaches a method for preparing stevioside-type table candy by crystallization to produce a product with rebaudioside A and rebaudioside D crystals (document p. 2, Abstract, lines 1-4). Steviana teaches that by compounding stevioside ingredients (rebaudioside A and rebaudioside D), the bitter taste of rebaudioside A is reduced and the taste of stevioside is improved (document p. 5, [0023]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to produce a product that includes 10-50% rebaudioside A by modifying the amount of rebaudioside A present in the extract used for the method of Markosyan ‘167 in view of Prakash. One of ordinary skill in the art would have been motivated produce a product that includes 10-50% rebaudioside A by modifying the amount of rebaudioside A present in the extract used for the method obvious over Markosyan ‘167 in view of Prakash because Abelyan teaches that the amount of rebaudioside A in the starting extract is proportional to the amount of rebaudioside A present in the final crystallized product, and because Steviana teaches that compounding the stevioside ingredients improves the taste of stevioside. Therefore, one of ordinary skill in the art would have recognized that producing a product with differing amounts of rebaudioside A and rebaudioside D, including those with a higher concentration of rebaudioside A, may affect the taste of stevioside, and would have reasonably considered modifying the amount of rebaudioside A present in the starting extract to achieve a product with a higher concentration of rebaudioside A in their product, in view of Abelyan teaching that the proportion of rebaudioside A precipitated is proportional to the amount in the original extract.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection of claim 16 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash, Abelyan, and Steviana, Applicant argues that claim 16 is patentable at least due to its dependency on claim 1.
For the same reasons described above regarding the rejection of claim 1, the rejection of claim 16 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash, Abelyan, and Steviana is maintained.
Claims 1-7, 9, 11-13, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Markosyan ‘167 (Publication no. US 20190133167 Al; cited in IDS received August 2, 2022) in view of Prakash (Publication No. WO 2017059414 A1; of record), Abelyan (Publication no. WO 2011046423 A1; of record), and Steviana (Publication no. CN109645432A; cited in the restriction requirement mailed March 11, 2025), as evidenced by Perkin Elmer (Perkin Elmer Application Note, Analysis of United States Pharmacopoeia (USP) Grade Alcohol (Ethyl alcohol) Impurities, 2021; of record).
As described in the above rejections under 35 U.S.C. § 103, the examiner believes that claims 1-5, 7, 11, 13, and 17 are obvious over Markosyan ‘167 in view of Prakash. However, for the sake of argument, if, for example, the conditions regarding degrees of supersaturation disclosed by Markosyan ‘167 were applied to a composition with an increased amount of rebaudioside A do not satisfy present claim 1, then these claims would have been obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana.
Markosyan ‘167 and Prakash teach as described in the above rejections under 35 U.S.C. § 103. Specifically, Prakash teaches stirring to promote crystal formation (p. 89, claim 22). In addition, based on data from Perkin Elmer discussed in the above rejection under 35 U.S.C. § 103, ethanol as a solvent is reasonably considered to be free of methanol, and the product produced by the method of Markosyan ‘167 would be expected to have less than 10 ppm methanol, as required by claim 13.
Markosyan ‘167 and Prakash do not teach wherein the content of rebaudioside A is 20 to 70% by mass in the roughly purified product or the degree of supersaturation of rebaudioside A or D in their experiment, each as recited in claim 1. In addition, Markosyan ‘167 and Prakash do not teach the ratio of rebaudioside A to the total steviol glycoside in the rebaudioside D-containing crystallized product is 10 to 50% by mass, as required by claim 16. Finally, neither Markosyan ‘167 nor Prakash teach a specific embodiment wherein Reb D is used a seed crystal, as required by claim 6, wherein the solution for crystallization is cooled for a period of 1 to 48 hours with stirring, to precipitate rebaudioside D, as required by claim 9, or the additional steps of crystallization required by claim 12.
Abelyan teaches as described in the above rejection under 35 U.S.C. § 103. Specifically, Abelyan teaches that the amount of rebaudioside A present in a crystallized product prepared by a similar method to that of Markosyan ‘167 and Prakash is dependent on the amount of rebaudioside A present in the initial extract (p. 32, [00130], lines 1-4). As shown in Table 5, the yield of rebaudioside A increased from 22-25% to 32-36% as the amount of rebaudioside A in the initial extract increases from 42-43% to 60-62% (p. 32, [00130], Table 5).
Abelyan further discloses an embodiment in which a composition (which had already been through one step of recrystallization) included Stevioside (1.4%), Rebaudioside A (72.8%), Rebaudioside C (1.5%), Rebaudioside D (21.4%), Rebaudioside B (0.1%), Rebaudioside E (2.1%), and Rebaudioside F (0.7%) (pp. 56-57, [00225]).
Abelyan teaches that for further purification of Rebaudioside D, the precipitate was suspended in 50% ethanol at 1:2 w/v ratio and maintained for 12 hours at 35°C with agitation. The suspension was filtered and precipitate was dried. Abelyan teaches the yield of precipitate was around 23% and contained Stevioside (0.8%), Rebaudioside A (16.2%), Rebaudioside C (0.7%), Rebaudioside D (81.6%), Rebaudioside E (0.5%), and Rebaudioside F (0.2%). Around 15.2 g of dry material was obtained at this stage (p. 57, [00227]).
Therefore, Abelyan demonstrates that substantial increases in rebaudioside D content (from 21.4% to 81.6%) may be achieved in a single step based on a different in solubility between rebaudioside A and rebaudioside D. In addition, significant decreases of Rebaudioside A (from 72.8% to 16.2%) were achieved. Although the Reb A content of this composition falls outside of the range recited in claim 1, and although the yield of the experiment is relatively low, it demonstrates that substantial enrichment of Reb D may be achieved based on a difference in solubility between rebaudioside A and rebaudioside D.
Finally, Abelyan teaches general guidance regarding isolation of rebaudioside A and rebaudioside D by recrystallization. Abelyan teaches that the rebaudioside D content increases with the increase of the concentration of ethanol up to 88-90% and a decrease of the ratio of solvent to stevia extract, and at the same time the purity of Rebaudioside A increased with more diluted ethanol solutions and higher ratios of extract to solvent (p. 32, [00129]; see also pp. 31-32, Tables 3 and 4).
Accordingly, this is taken as teaching that one of ordinary skill in the art would have adjusted conditions of crystallization, including the amount of ethanol used for recrystallization and the amount of solvent relative to stevia extract, to optimize the yield of the rebaudioside compound being isolated.
Steviana teaches as described in the above rejection under 35 U.S.C. § 103. In addition, Steviana teaches and claims a method of co-crystallizing rebaudioside A and rebaudioside D that requires preparing a certain amount of stevioside raw materials and preparing an ethanol solvent with a concentration of 85-95% (document p. 9, claim 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to substitute the stevia extract in the method obvious over Markosyan ‘167 in view of Prakash with a starting material with a higher concentration of rebaudioside A. One of ordinary skill in the art would have been motivated to substitute the stevia extract in the method taught by Markosyan ‘167 in view of Prakash with a starting material that includes a higher concentration of rebaudioside A because Markosyan ‘167 suggests that their starting extract may include higher concentrations of rebaudioside A, because Abelyan teaches that the amount of rebaudioside A in the starting extract is proportional to the amount of rebaudioside A present in the final crystallized product, and because Steviana teaches that compounding the stevioside ingredients improves the taste of stevioside. Therefore, one of ordinary skill in the art would have recognized that producing a product with differing amounts of rebaudioside A and rebaudioside D, including those with a higher concentration of rebaudioside A, may affect the taste of stevioside, and would have reasonably considered modifying the amount of rebaudioside A present in the starting extract to achieve a product with a higher concentration of rebaudioside A, because Abelyan teaches that the proportion of rebaudioside A precipitated is proportional to its amount in the original extract.
Moreover, by starting with a higher concentration of rebaudioside A in the initial experiment, one of ordinary skill in the art would have reasonably produced a product with a ratio of rebaudioside A to the total steviol glycoside in the rebaudioside D-containing crystallized product of 10 to 50% by mass as recited in claim 16, because such a ratio may provide an optimal improvement in taste of stevioside.
In addition, as described by Abelyan, roughly purified compositions comprising about 20-70% rebaudioside A by mass (e.g., approximately 72% rebaudioside A by mass) are disclosed in the prior art. Therefore, one of ordinary skill in the art would have reasonably contemplated applying the method obvious over Markosyan ‘167 in view of Prakash to one of these compositions. In addition, because Abelyan provides guidance for optimizing the yield of both rebaudioside A and rebaudioside D, one of ordinary skill in the art would have contemplated modifying the conditions disclosed by Markosyan ‘167 in accordance with guidance from Abelyan to identify conditions that enable robust isolation of the product of interest. Finally, as taught by Steviana, one of ordinary skill in the art would have reasonably selected an appropriate starting material to achieve the desired final ratio of rebaudioside D to rebaudioside A, which may improve the flavor of stevioside.
As one such change to the crystallization conditions, one of ordinary skill in the art would have contemplated substituting the 70% or 75% ethanol taught in the methods of Markosyan ‘167 and Prakash with alternative ethanol concentrations, such as the 85-95% ethanol, as taught by Steviana, because Markosyan ‘167 suggests that other concentrations of ethanol may be used in their method, and because Steviana teaches a similar method for producing rebaudioside A and rebaudioside D that uses 85-95% ethanol for improving the flavor of stevioside. Therefore one of ordinary skill in the art would have considered this recrystallization solvent when practicing the method obvious over Markosyan ‘167 in view of Prakash, because this solvent composition may provide a rebaudioside D-containing product with improved taste compared to the product produced by the solvent in the method obvious over Markosyan ‘167 in view of Prakash. The examiner notes that a concentration of 85-95% ethanol, as taught by Steviana, when used in the method obvious over Markosyan ‘167 in view of Prakash would satisfy the required degrees of supersaturation recited in claim 1, as evidenced by Experiment Example 15 recited in the specification and discussed in the above rejection.
More generally, because Markosyan ‘167 and Prakash teach crystallization methods for isolating enriched compositions comprising rebaudioside D, and because Abelyan teaches that the Rebaudioside D content increases with the increase of the concentration of ethanol up to 88-90%, one of ordinary skill in the art would have recognized that the exact recrystallization conditions, including the composition and volume of solvent, may be optimized to improve the enrichment and isolation of the rebaudioside of interest, including the rebaudioside A and rebaudioside D taught by Abelyan. In addition, when identifying said optimal conditions for recrystallization, one of ordinary skill in the art would have contemplated conditions in which the requirement that a degree of supersaturation at 10°C of rebaudioside D is 10 or more and a degree of supersaturation at l 0°C of rebaudioside A is 18 or less, absent a showing of unexpected or superior results that require these specific conditions compared with recrystallization conditions known in the art that do not satisfy these requirements.
Regarding claim 6, one of ordinary skill in the art would have been motivated to substitute the Reb M used as a seed crystal in the experiments of Markosyan ‘167 and Prakash with Reb D because Prakash claims generally that addition of a seed crystal may be used to promote crystal formation in their method of producing a steviol glycoside composition, because Abelyan claims that Reb D may be used as a seed crystal to produce highly purified rebaudioside D, and because Markosyan ‘167 suggests Reb D may be used as a seed crystal. Thus one of ordinary skill in the art would have considered Reb D as a seed, because the use of Reb D as a seed is suggested by Abelyan.
Regarding the crystallization time, because Markosyan ‘167 teaches a range of crystallization times, and because Abelyan teaches a related crystallization method wherein crystals were allowed to form for 12 hours, one of ordinary skill in the art would have considered other times for crystallization, such as the 12 hours taught by Abelyan, because shorter times may also effectively yield a crystallized product with rebaudioside A and rebaudioside D, as taught by Markosyan ‘167.
Regarding the additional steps of crystallization as recited in claim 12, wherein the rebaudioside D is separated, dried, and then subjected to an additional round of crystallization with separation and drying to isolated additional rebaudioside D, one of ordinary skill in the art would have been motivated to perform the additional steps of crystallization because Markosyan ‘167 and Prakash render obvious the method of claim 1, including separating and drying precipitated rebaudioside D to obtain a primary crystallized product, and because Abelyan teaches additional steps of crystallization may be performed to improve the purity of rebaudioside D. Therefore, one of ordinary skill in the art would have considered the additional steps of crystallization as means to increase the purity of rebaudioside D. With respect to the degrees of supersaturation of Reb D and Reb A as required by claim 12, because Markosyan ‘167 teaches conditions for the crystallization of Reb D from a solvent of 75% ethanol, one of ordinary skill in the art would have considered these conditions when performing additional recrystallization steps of the Reb D product, and would have further adjusted the recrystallization conditions to optimize yield and purity of the desired product following recrystallization guidance available in the prior art, including the guidance provided in Abelyan and Steviana.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the above rejection of claims 1-7, 9, 11-13, and 16-17 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash, Abelyan, and Steviana, Applicant argues that claim 1 is patentable over the cited art for reasons noted above.
For the same reasons described above regarding the rejection of claim 1 as unpatentable over Markosyan '167 in view of Prakash, the present rejection of claims 1-7, 9, 11-13, and 16-17 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash, Abelyan, and Steviana is maintained.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana, as evidenced by Perkin-Elmer, as applied to claims 1-7, 9, 11-13, and 16-17 above, and further in view of Pnita (U.S. pre-grant publication no. US 20130164434 A1; of record).
Claim 8 depends from claim 1 and requires the solution for crystallization is cooled at a rate of 0.002 to l.37°C/min with stirring, to precipitate rebaudioside D.
Markosyan ‘167, Prakash, Abelyan, and Steviana teach as described in the above rejections under 35 U.S.C. § 103. Specifically, Markosyan ‘167 teaches cooling to induce crystallization, but does not teach a rate of cooling.
Markosyan ‘167, Prakash, Abelyan, and Steviana do not teach cooling the solution for crystallization at a rate of 0.002 to l.37°C/min, as required by claim 8.
Pnita as described in the above rejections under 35 U.S.C. § 103.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to cool the solution of steviol glycosides in the method obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana at a rate of 0.2°C/minute. One of ordinary skill in the art would have been motivated to cool the solution of steviol glycosides in the method obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana at a rate of 0.2°C/minute because Markosyan ‘167 in view of Prakash, Abelyan, and Steviana render obvious methods of isolating Steviol glycosides, such as rebaudioside A and rebaudioside D, using crystallization, and because Pnita teaches a method of isolating rebaudioside A by crystallization and teaches a method wherein the solution of Steviol glycosides is cooled at a rate of 0.2°C/minute. Therefore, one of ordinary skill in the art, when practicing the method obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana, would have considered rates of cooling taught in the prior art, including in the related method of Pnita, as guidance when selecting the rate of cooling when crystallizing rebaudioside A and rebaudioside D, and would have adjusted this rate of cooling as necessary depending on constraints of the method and desired outcome.
One of ordinary skill in the art would have had a reasonable expectation of success applying the method of cooling of Pnita to the method obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana because each method is directed to isolating a Steviol glycoside product by crystallization, and because the method obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana requires cooling to promote crystal formation but provides no guidance to select a rate of cooling. Thus one of ordinary skill in the art would have reasonably considered the rate of cooling taught by Pnita as guidance when practicing the method obvious over Markosyan ‘167 in view of Prakash, Abelyan, and Steviana.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection of claim 8 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash, Abelyan, and Steviana, Applicant argues that claim 8 is patentable at least due to its dependency on claim 1.
For the same reasons described above relating to the rejection of claim 1, the rejection of claim 8 under 35 U.S.C. 103 as unpatentable over Markosyan '167 in view of Prakash, Abelyan, Steviana, and Pnita is maintained.
Allowable Subject Matter
Claims 10 and 14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 10 depends from claim 1 and requires the method of claim 1, further comprising
extracting a dry leaf of a stevia plant with a solvent to obtain an extract, subjecting the extract to a solid-liquid separation treatment to obtain a clarified liquid, adding a coagulant to the clarified liquid for flocculation, to obtain a treatment liquid, treating the treatment liquid with a hydrophobic porous resin, and concentrating a solution after purification with the resin to obtain the roughly purified product.
The closest prior art to the method of claim 10 is considered Prakash (Publication No. WO 2017059414 A1; of record), who teaches a method of producing their Enriched Stevia Extract used in the crystallization discussed in the above rejections. Prakash teaches that two kg of Stevia rebaudiana dried leaves were extracted with water at pH 6.5 at 40 °C for 160 minutes using a continuous extractor, and that the filtrate was collected (p. 78, lines 13-17). Prakash teaches the filtrate was treated with calcium oxide at pH 9 and FeSO4 at pH 3, and the precipitate was removed by filtration. Although these reagents are not expressly taught as coagulants and this step is not explicitly referred to as flocculation by Prakash, because the precipitate was removed by filtration following treatment with calcium oxide and FeSO4, one of ordinary skill in the art would have reasonably considered these reagents as coagulants, because they produced a precipitate, and would reasonably consider this step flocculation, because a precipitate is formed during this treatment.
After treatment of the filtrate with ion-exchange resins, Prakash teaches that the product was treated with macroporous polymeric adsorbent YWD-03, the resin washed with water, and the absorbed Steviol glycosides were eluted with 52% ethanol (p. 78, line 25 to p. 79, line 2). Macroporous polymeric adsorbent YWD-03 is interpreted herein as a hydrophobic porous resin, because it is described as porous, is referred to by Prakash as a resin, and because the absorbed Steviol glycosides are eluted with a less polar solvent than they are washed with, the resin is reasonably considered as hydrophobic (because it required a less polar solvent to elute the adsorbed compounds).
Prakash then teaches that the elution was treated with activated carbon, subjected to cation-exchange resin, distilled using a vacuum evaporator, and spray dried to yield a product that comprises the Enriched Steviol Extract, containing the Steviol glycosides recited above. This extract includes at least 64% w/w steviol glycosides, as stated above. However, the Enriched Stevia Extract disclosed by Prakash includes 11.91 % Reb A, and it is unclear if the method of Prakash may be used to successfully produce a roughly purified product with the proportion of Reb A required by claim 1. In addition, Prakash does not teach or suggest their method as intending to produce a roughly purified product with a 20-70% Reb A, as recited in claim 1, and thus one of ordinary skill in the art would not have been motivated to modify the method of Prakash in such a way as to increase the concentration of Reb A in the roughly purified product.
Accordingly, the method of claim 10, which requires all limitations of claim 1 and further limits the method of making the roughly purified product, is novel and nonobvious over the prior art of record.
Claim 14 depends from claim 1 and requires a ratio MeOH/EtOH of methanol to ethanol contained in a rebaudioside D-containing crystallized product is 0.00010 to 0.00080. As taught by Perkin Elmer and discussed in the above rejections under 35 U.S.C. 103, ethanol may be reasonably considered to be free of methanol. Perkin Elmer teaches that runs of ethanol blanks A and B (p. 5, Table 2) showed no methanol present, while a 200 ppm spike of methanol showed a detectable area. Therefore, based on these data from Perkin Elmer, ethanol as a solvent is reasonably considered to be free of methanol, and the product produced by the method of Markosyan ‘167 would be expected to have less than 10 ppm methanol. However, claim 14 requires a ratio of methanol to ethanol contained in the rebaudioside D-containing crystallized product is 0.00010 to 0.00080, which corresponds to a ratio of greater than 10 ppm methanol. Accordingly, because Perkin Elmer teaches ethanol is free of methanol, one of ordinary skill in the art would have had no reason to prepare a rebaudioside D-containing crystallized product with a ratio of methanol to ethanol of 0.00010 to 0.00080, and would not have reasonably the product prepared by the method obvious over Markosyan ‘167 in view of Prakash to have this ratio of methanol to ethanol.
Rejoinder
Applicant requests rejoinder of the previously withdrawn claims. In the response to Restriction requirement received April 8, 2025, Applicant elected without traverse the invention of Group I, drawn to a method for producing a rebaudioside D-containing crystallized product.
Group II, drawn to a rebaudioside D-containing crystallized product, having a methanol content of less than 10 ppm and a rebaudioside D-containing crystallized product produced by the method of claim 1, were withdrawn as being due to a non-elected invention.
As stated in the Restriction/Election requirement mailed March 11, 2025: “The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.” (pp. 6-7)
In this instance, because Applicant elected the process (method) claim and not the product claim, there is no right to rejoinder. The product claims do not include all limitations of the methods claims, and thus are not eligible for rejoinder. Although claim 21 depends from claim 1, claim 21 is a product-by-process claim, and thus is considered satisfied by a product that satisfies the requirements of the product of claim 1, even if that product were produced by another method.
MPEP 2113 at I states: "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Therefore, the products of claims 19-23 do not contain all limitations of the methods claims, and are not eligible for rejoinder.
Conclusion
Claims 10 and 14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1-9, 11-13, and 16-17 are rejected.
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/B.M.B./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693
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