DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt of the Response and Amendment after Non-Final Office Action filed 06/30/2026 is acknowledged.
The status of the claims upon entry of the present amendment stands as follows:
Pending claims: 26-28, 30, 31, and 33-44
Withdrawn claims: None
Previously canceled claims: 1-25, 29, and 32
Newly canceled claims: None
Amended claims: None
New claims: None
Claims currently under consideration: 26-28, 30, 31, and 33-44
Currently rejected claims: 26-28, 30, 31, and 33-44
Allowed claims: None
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 26-28, 30, and 33-39 are rejected under 35 U.S.C. 103 as being unpatentable over Markosyan et al. (U.S. 2017/0303565 A1) in view of Gerwig et al. (Gerwig, G. J., et al., “Stevia Glycosides: Chemical and Enzymatic Modifications of Their Carbohydrate Moieties to Improve the Sweet-Tasting Quality,” Advances in Carbohydrate Chemistry and Biochemistry, Vol., 73, 1-72 (2016)).
As for claim 26, Markosyan et al. discloses a method for producing a sweetened composition (Abstract), the method comprising contacting a high intensity sweetener glycoside with an enzyme ([0126]-[0128], [0133]-[0134], [0137], [0143]-[0144], [0169]). The composition may further comprise prebiotic functional ingredients ([0277]), such that the composition would constitute a prebiotic composition.
Markosyan et al. does not specifically disclose that the method is effective to galactosylate and/or fructosylate the glycoside in the presence of sucrose and/or lactose or that the method simultaneously produces galactooligosaccharides or fructooligosaccharides.
However, Gerwig et al. discloses galactosylation of a steviol glycoside using E. coli as the enzyme/microorganism and lactose as the donor substrate (p. 48 – p. 49, § 7.5 β-Galactosidase Transglycosylation Systems, ¶1, Table 6, where E. coli β-Galactosidase resulted in 12.5% of No. 99, which shows the glycoside has been galactosylated).
It would have been obvious to one having ordinary skill in the art to perform a galactosylation modification of the steviol glycosides taught in Markosyan et al. according to the instruction of Gerwig et al. Since Markosyan et al. discloses fairly broadly that various target steviol glycosides may be obtained via the use of numerous different carbohydrate starting compositions ([0133]-[0134], [0137]) and different microorganisms ([0168]-[0169]), a skilled practitioner would be motivated to consult Gerwig et al. for more specific instruction in order to clarify the broad teaching in Markosyan et al. Gerwig et al. teaches that galactosylation occurs when using E. coli as the microorganism and lactose as the donor substrate (p. 48 – p. 49, § 7.5 β-Galactosidase Transglycosylation Systems, ¶1, Table 6). Markosyan et al. similarly teaches lactose as a carbohydrate starting composition ([0137]) together with a steviol glycoside ([0144]-[0145]) with E. coli as the microorganism ([0168]-[0169]). As such, a skilled practitioner would reasonably expect that selecting such components as taught in Markosyan et al. would result in the galactosylation of the steviol glycoside. The claimed composition would thus be obvious to a skilled practitioner.
Gerwig et al. also discloses enzymatic modifications of steviol glycosides in the presence of sucrose and lactose resulting in a mixture of glycosylated products (p. 29, ¶3 – p. 30, ¶1). Gerwig et al. further discloses an experiment wherein a steviol glycoside is subjected to enzymatic glucosylation, wherein large amounts of oligosaccharide by-products were produced (p. 33, ¶3).
It would have been obvious to one having ordinary skill in the art to perform the method of Markosyan et al., wherein fructooligosaccharides are produced concurrently with the enzymatic modification of the steviol glycoside. Since Markosyan et al. is relatively broad in terms of the types of starting materials and modifications that may be performed ([0132]-[0145]) and indicates that “residual reaction products” may be produced ([0219]), a skilled practitioner would be motivated to consult Gerwig et al. for additional clarification in terms of what types of residual reaction products may be produced and whether the mixture may need additional treatment/purification before use as a sweetener. Since Gerwig et al. clarifies that oligosaccharides may be produced concurrently with the enzymatic modification of the steviol glycoside and suggests that the oligosaccharides produced are polymers of the carbohydrates that are present in the starting material (p. 33, ¶3) and Markosyan et al. discloses that both fructose and fructooligosaccharides may be in the starting composition ([0137]), the production of fructooligosaccharides as part of the enzymatic modification process would be obvious.
As for claim 27, Markosyan et al. discloses the high intensity sweetener glycoside is a steviol glycoside ([0144], [0130]).
As for claim 28, Markosyan et al. discloses the high intensity sweetener glycoside is galactosylated and/or fructosylated ([0137], where use of galactose or fructose as a starting composition would result in galactosylation or fructosylation of the sweetener glycoside). Markosyan et al. discloses the enzymes used may be from Aspergillus sp. ([0168]-[0171]), which renders the use of carbohydrase mixtures from Aspergillus sp. obvious.
As for claim 30, Markosyan et al. discloses the composition only optionally contains galactose and or fructose ([0137]) such that any galactosylation or fructosylation is effectively disclosed as ranging from 0% to some amount greater than 0%, which renders the claimed limitations of the sweetened prebiotic composition being “up to about 5 % galactosylated and/or up to about 5 % fructosylated” obvious.
As for claim 33, Markosyan et al. discloses the high intensity sweetener glycoside is rebaudioside A ([0147]).
As for claims 34 and 35, Gerwig et al. discloses the glycosides as being modified by up to about 3 units of galactose (claim 34) and up to about 4 units of galactose (claim 35) (p. 48 – p. 49, § 7.5 β-Galactosidase Transglycosylation Systems, ¶1, Table 6, No. 99, where one galactose unit has been added).
As for claim 36, Markosyan et al. discloses the method of claim 26, wherein the steviol glycoside may be fructosylated with fructose ([0137], where use of fructose as a starting composition would result in fructosylation of the sweetener glycoside). Markosyan et al. further discloses that the starting composition may also comprise “steviol glycoside(s)” ([0144]), which is defined as including rubusoside ([0130]) that contains two glucose units ([0131]), which can be glycosylated into rebaudioside M that contains six glucose units ([0131], Fig. 2). Such a glycosylation would constitute a modification of 4 units.
Markosyan et al. does not explicitly disclose steviol glycosides that have been modified by 4 or more units of galactose or fructose.
However, since Markosyan et al. discloses that fructosylation may be one of the modifications that is performed on steviol glycoside starting material ([0137]) and that modification with glucose may be in an amount of up to 4 units, it would be obvious to a skilled practitioner to modify the starting steviol glycoside with up to 4 units of fructose as well.
As for claim 37, Markosyan et al. discloses the composition may comprise a target steviol glycoside and “steviol glycosides and/or residual reaction products” ([0219]), which constitutes “a mixture of steviosides having different modifications” as claimed.
As for claim 38, Markosyan et al. discloses the method of claim 37, as well as that the high intensity sweetener glycoside has been fructosylated ([0133], [0137], where use of fructose as a starting composition would result in fructosylation of the sweetener glycoside) and that the starting composition may also comprise “steviol glycoside(s)” ([0144]), which is defined as including rebaudioside A ([0130]). Markosyan et al. thus effectively discloses rebaudioside A with 1 unit of fructose as claimed.
As for claim 39, Markosyan et al. discloses the method of claim 37, as well as that the high intensity sweetener glycoside has been galactosylated ([0133], [0137], [0144]-[0145], [0169]) and that the starting composition may also comprise “steviol glycoside(s)” ([0144]), which is defined as including rebaudioside A ([0130]). Markosyan et al. thus effectively discloses rebaudioside A with 1 unit of galactose as claimed in option (ii).
Claims 31 and 40-44 are rejected under 35 U.S.C. 103 as being unpatentable over Markosyan et al. (U.S. 2017/0303565 A1) in view of Gerwig et al. (Gerwig, G. J., et al., “Stevia Glycosides: Chemical and Enzymatic Modifications of Their Carbohydrate Moieties to Improve the Sweet-Tasting Quality,” Advances in Carbohydrate Chemistry and Biochemistry, Vol., 73, 1-72 (2016)) as applied to claims 26 and 33 above, and further in view of Prakash et al. (U.S. 2014/0343262 A1).
Regarding claim 31, Markosyan et al. and Gerwig et al. disclose the method of claim 26.
The cited prior art does not disclose the sweetener glycoside as including a mogroside that is enzymatically modified.
However, Prakash et al. discloses mogroside V ([0248]) that may be enzymatically modified ([0249]).
It would have been obvious to one having ordinary skill in the art to produce the composition of Markosyan et al. comprising an enzymatically modified mogroside. Markosyan et al. discloses that mogrosides may be combined with the enzymatically-modified steviol glycosides produced according to the process disclosed therein ([0268]). Markosyan et al. also discloses broadly that the starting composition may comprise organic compounds generally ([0133]), which would prompt a skilled practitioner to consider how the enzymatic treatment may affect such compounds in the reaction mixture. A skilled practitioner would thus be motivated to consult Prakash et al. for further instruction regarding whether mogrosides may be affected by the enzymatic treatment. Since Prakash et al. discloses that mogrosides may also be modified by enzymatic treatment to achieve compounds having varying numbers of glycosidic residues ([0248]-[0249]), a skilled practitioner would find the incorporation of a mogroside into the reaction mixture of Markosyan et al. to be obvious in order to glycosylate the mogroside compounds. The claimed limitation that the sweetener glycoside comprises a mogroside would thus be obvious to a skilled practitioner.
Regarding claim 40, Markosyan et al. and Gerwig et al. disclose the method of claim 33.
The cited prior art does not disclose the composition as comprising a mixture of mogrosides having different modifications.
However, Prakash et al. discloses mogroside IV and mogroside V ([0248]) that may be enzymatically modified ([0249]).
It would have been obvious to one having ordinary skill in the art to produce the composition of Markosyan et al. comprising a mixture of mogrosides having different modifications. Markosyan et al. discloses that mogrosides may be combined with the enzymatically-modified steviol glycosides produced according to the process disclosed therein ([0268]). Markosyan et al. also discloses broadly that the starting composition may comprise organic compounds generally ([0133]), which would prompt a skilled practitioner to consider how the enzymatic treatment may affect such compounds in the reaction mixture. A skilled practitioner would thus be motivated to consult Prakash et al. for further instruction regarding whether mogrosides may be affected by the enzymatic treatment. Since Prakash et al. discloses that mogrosides may also be modified by enzymatic treatment to achieve compounds having varying numbers of glycosidic residues ([0248]-[0249]), a skilled practitioner would find the incorporation of a mixture of mogrosides into the reaction mixture of Markosyan et al. to be obvious in order to glycosylate the mogroside compounds. The claimed limitation that the composition comprises a mixture of mogrosides having different modifications would thus be obvious to a skilled practitioner.
As for claims 41-43, Prakash et al. discloses the mogrosides as comprising mogroside V ([0248]).
As for claim 44, Prakash et al. discloses that the mogrosides IV and V may be modified by 1-50 glycosides residues that may be galactosyl- or fructosyl- ([0248]-[0249]), which renders obvious the claimed mixture of (i) mogroside IV, (ii) mogroside with 1 unit of galactose, (iii) mogroside V with 2 units of galactose, and (iv) mogroside V with 3 units of galactose.
Response to Arguments
Claim Rejections - 35 U.S.C. § 103 of claims 26-28, 30, and 33-39 over Markosyan et al., and Gerwig et al.; claims 31 and 40-44 over Markosyan et al., Gerwig et al., and Prakash et al.: Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s first asserted that the patentability analysis is “a vast simplification of enzymatic reactions and diminishes Applicant’s contribution to the art” (p. 7, ¶2).
However, the present claim rejections are commensurate in complexity with the present claims, which are claimed broadly in a manner that does not require: a specific high-intensity sweetener substrate, any specific enzyme (beyond having the recited function), any limitation on the location or degree of galactosylation/fructosylation, any limitation on the structure of the produced galactosaccharide/fructooligosaccharide, any process conditions whatsoever, any minimal yield, any effect of the products, or any use of the products (although some dependent claims admittedly provide moderate limitations on some of those parameters individually). The claims are merely directed to the concept of galactosylating/fructosylating a high intensity sweetener glycoside with an enzyme and concurrently producing an oligosaccharide. Examiner maintains that such a generalized concept was adequately deemed obvious in view of the cited combination of prior art. Applicant cannot fairly argue that the claim rejections are overly simplistic when the claims do not necessitate any more complex analysis.
Applicant then argued that the residual reaction products of Markosyan et al. are disclosed only as two specific embodiments (Applicant’s Remarks, p. 7, ¶3 - ¶4).
Examiner maintains that the indication that “residual reaction products” may be produced via the enzymatic reaction ([0219]) is properly interpreted as indicating that such a result may occur generally for other substrates/enzymes disclosed in the reference. Neither the enzymes nor the substrates (whether steviol glycosides or other compounds in the starting composition) would be expected to be sufficiently distinct from the process concluding at paragraph [0219] that a skilled practitioner would expect that residual reaction products would not also be produced when using other enzymes/substrates. That only “two very specific embodiments” are disclosed in the reference does not limit the broader applicability of such instruction to only the specific methods discussed.
Applicant next states: “In the Examiner’s opinion, Markosyan broadly teaches enzymatic modifications to high intensity sweetener glycosides, and based on this, the skilled person would know that a high intensity sweetener glycoside could be fructosylated and/or galactosylated and then look to Gerwig to provide adequate instruction of galactosylation and/or fructosylation of high intensity sweetener glycosides.” (Applicant’s Remarks, p. 7, ¶5 – p. 8, ¶1).
However, Applicant’s argument mischaracterizes the claim rejection. Examiner admitted: “Markosyan et al. does not specifically disclose that the method is effective to galactosylate and/or fructosylate the glycoside in the presence of sucrose and/or lactose or that the method simultaneously produces galactooligosaccharides or fructooligosaccharides.” The claim rejection is not based on an assumption, based only on Markosyan et al., that “the skilled person would know that a high intensity sweetener glycoside could be fructosylated and/or galactosylated” as Applicant asserts. The breadth of Markosyan et al. would prompt consultation of Gerwig et al. for clarification regarding expected reaction products for certain starting materials. Only upon consultation of Gerwig et al. would the galactosylation process be clarified. Examiner maintains that adequate motivation is detailed for combining the prior art references.
Applicant then argued that Gerwig et al. does not teach that an oligosaccharide would be produced during galactosylation/fructosylation of a high intensity sweetener glycoside (Applicant’s Remarks, p. 8, ¶2 - ¶4).
Examiner maintains the position in paragraph 40 of the previous Office Action—that the instruction in Gerwig et al. is instructive as to the “residual reaction products” that would be reasonably expected when producing a composition according to Markosyan et al., particularly for a mixture comprising fructose and fructooligosaccharides as starting components. That Gerwig et al. involves different carbohydrates and enzymes does not preclude consultation of the reference in order to determine likely by-products. Examiner maintains that the combined instruction from both references is adequate to deem the concurrent production of fructooligosaccharides obvious.
Applicant again asserted that the present claim rejection relies on improper hindsight (Applicant’s Remarks, p. 8, ¶5).
Examiner maintains that the present claim rejections rely only on knowledge that was within the level of ordinary skill in the art and thus do not rely on improper hindsight rationale.
Applicant next asserted the importance of the claimed invention, asserting various efficiency improvements (Applicant’s Remarks, p. 9, ¶1).
However, Applicant’s arguments are unpersuasive due to being much narrower in scope than the present claims and/or being directed to features which are not claimed. The present claims do not require: any scale of the process, any yield, any particular use of the products, or use of any specific equipment. The claim rejection adequately addressed the limitations that were actually claimed, and Applicant’s arguments regarding ancillary hypothetical effects do not overcome the obviousness rejections.
Applicant asserted “the synergistic improvement of isovaleric acid concentrations in fecal cultures” and the promotion of human health, purporting to show a synergistic effect between a galactosylated/fructosylated high intensity sweetener glycoside and an oligosaccharide in terms of increased isovaleric acid concentrations (Applicant’s Remarks, p. 9, ¶2 – p. 10, ¶1; Kolida Declaration, ¶12-¶18).
However, MPEP 716.02(d) recites: “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range.” Not only is the nature of any prebiotic functionality not claimed (which alone fully undermines Applicant’s argument), the scope of the claims is substantially broader than the data asserted as showing an unexpected result. The claims do not require administration of either product to any subject or administration of any amount of any product. The claims are also broader due to the data apparently being limited to a specific species, specific high intensity sweetener glycosides, and defined production and administration parameters. The data further does not account for process embodiments that would fall within the scope of the claimed method but that would presumably not result in the asserted benefit (e.g., enzymes that may inefficiently produce galactooligosaccharides/fructooligosaccharides, resulting in a process the meets all the claim requirements, but where the GOS/FOS concentration may be too low to actually cause the asserted synergistic effect). Applicant’s assertion of unexpected results is consequently insufficient for overcoming the prima facie showing of obviousness.
The rejections of claims 26-28, 30, 31, and 33-44 have been maintained herein.
Conclusion
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.
Claims 26-28, 30, 31, and 33-44 are rejected.
No claims are allowed at this time.
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/JEFFREY P MORNHINWEG/Primary Examiner, Art Unit 1793
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