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. Election/Restrictions Applicant's election with traverse of the invention of Group IV, claims 5-9, in the reply filed on 03/03/2026 is acknowledged. The traversal is on the ground(s) that the Examiner has not demonstrated a serious search and/or examination burden. This argument is not found persuasive because the instant application is a national stage entry of an international patent application under 35 U.S.C. 371, and the standard for restriction in national stage entries is that of unity of invention, not search and/or examination burden. As discussed in the previous Office action, the inventions do not share unity of invention. As such, restriction is proper, regardless of any showing of search and/or examination burden. The requirement is still deemed proper and is therefore made FINAL. Claim Status The amendment of 03/03/2026 has been entered. Claims 1-9 are pending in this US patent application. Claims 1-4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/03/2026. Claims 5-9 are currently under examination and were examined on their merits. Information Disclosure Statement The information disclosure statements filed in this application on 01/08/2024 and 11/25/2024 have been received and considered. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.— The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claims 5-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The term s “ low temperature ” and “high temperature” in claim 5 are relative term s which render the claim indefinite. The term s “ low temperature ” and “high temperature” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree s , and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Which temperatures are “low,” and which temperatures are “high”? As such, claim 5 is indefinite. Because claims 6-9 depend from claim 5 and do not provide further clarification of the indefinite language therein, these claims are also indefinite. Therefore, claims 6-9 are rejected under 35 U.S.C. 112(b). In the interest of compact prosecution, the Examiner has interpreted the “low temperature” and “high temperature” of claim 5 to be any temperatures. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or 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 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over international patent application WO 2020/249138 filed by Wang et al ., published 12/17/2020, in view of Ho et al ., Process Biochemistry 41 : 1829-1834 (2006) . Please note: the corresponding US patent application 2022/0235335 is used herein as an English translation of WO 2020/249138. Paragraph numbers for the Wang reference cited in this Office action correspond to the paragraph numbers in US 2022/0235335. Wang teaches glycosyltransferase UGT76G1 mutants that exhibit increased production of rebaudioside M (see entire document, including paragraphs 0007-0008). Recombinant enzymes may be produced by transforming a suitable host cell with a polynucleotide containing the mutant, culturing the host cell in a suitable medium, and isolating and purifying proteins from the medium or cell (paragraphs 0101-0105). The host cell may also contain an enzyme for recycling UDP glucose, such as AtSUS3 (paragraph 0054; the Examiner notes that AtSUS3 is a sucrose synthase enzyme). In certain embodiments, the UGT76G1 and AtSUS3 genes are cloned into the same recombinant plasmid (paragraph 0147 ; cf. part 1 of claim 5 ), which was then transformed into E. coli BL21 (DE3) , inoculated into LB medium and cultured prior to a 20-hr induction with 0.1 mM IPTG (paragraph s 0136 and 0149; cf. claim 6 and parts 2-3 of claim 5 ). To isolate recombinant enzymes, the cells were collected, resuspended in a buffer, lysed, and then centrifuged to obtain an enzyme-containing supernatant (paragraph 0128; cf. part 3 of claim 5 ; the Examiner notes that any buffer may be a “predetermined buffer” ). The enzymes may be reacted in the presence of 5 g/L rebaudioside substrate, 400 g/L sucrose, and buffer at 37°C for 30 minutes, quenched with methanol, and centrifuged, producing a supernatant that contains the rebaudioside M product (paragraphs 0150 and 0157-0158; cf. claims 7-8 and part 4 of claim 5 ; the Examiner notes that any temperature may be a “predetermined temperature” and that any enzyme composition that contains at least one molecule of one substance that is not the enzyme may be interpreted as “crude” ). The substrate for the enzyme may be rebaudioside D or rebaudioside E (paragraph 0119 ; cf. claims 7-8 and part 4 of claim 5 ). The method for preparing rebaudioside M may be performed outside of cells (paragraph 0117). However, Wang does not teach that the cells are harvested by centrifugation and lysed by ultrasonication as recited in part 3 of instant claim 5. Ho teaches that recombinant E. coli cells cultured in LB medium may be harvested by centrifugation and disrupted using an ultrasonic homogenizer (see entire document, including page 1830, left column, paragraphs 3 and 5; cf. part 3 of claim 5). While Wang does not teach that the cells are harvested by centrifugation and lysed by ultrasonication as recited in part 3 of instant claim 5 , it would have been obvious to one of ordinary skill in the art to do so because Ho teaches that these are functional steps for processing E. coli cells to harvest recombinant proteins. One of ordinary skill in the art would have a reasonable expectation that using the centrifugation and ultrasonication of Ho in the method of Wang would successfully result in the production of a crude enzyme solution that could be further utilized in the method of Wang. Wang and Ho do not teach amounts of the enzymes, rebaudioside substrate, and sucrose or a reaction time that fall within the ranges for these values recited in instant claims 7-8. However, the instantly recited ranges would be within the realm of routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller , 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 part II A. It would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal concentrations of reactants and reaction times for the enzymatic reaction rendered obvious by Wang and Ho because the concentrations of the reactants and the amount of time that the reactants are allowed to react with one another are art-recognized, result-effective variables known to affect the yield of an enzymatic reaction, which would have been optimized in the art to provide the desired yield. Therefore, claims 5-8 are rendered obvious by Wang in view of Ho and are rejected under 35 U.S.C. 103. Claims 5- 9 are rejected under 35 U.S.C. 103 as being unpatentable over international patent application WO 2020/249138 filed by Wang et al ., published 12/17/2020, in view of Ho et al ., Process Biochemistry 41 : 1829-1834 (2006) , and Chinese patent application CN 109750072 filed by Li et al. , published 05/14/2019 (cited on the IDS filed 01/08/2024) . As discussed above, claims 5-8 are rendered obvious by Wang in view of Ho . However, these references do not teach that the sucrose synthase used with the UDP-glycosyltransferase is StSUS1 as recited in instant claim 9. Li teaches that StSUS1 is a sucrose synthase that may be used with glycosyltransferases for the production of rebaudiosides (see entire document, including page 4, paragraph 0010; cf. claim 9). While Wang and Ho do not teach that the sucrose synthase used with the UDP-glycosyltransferase in the method rendered obvious by their teachings is StSUS1 , it would have been obvious to one of ordinary skill in the art to do so because Li teaches that StSUS1 is a sucrose synthase that may be used with UDP-glycosyltransferases for the production of rebaudiosides . One of ordinary skill in the art would have a reasonable expectation that using the sucrose synthase enzyme StSUS1 of Li in the method of using solutions of UGT76G1 and a sucrose synthase to synthesize rebaudioside M rendered obvious by Wang and Ho would successfully result in the production of rebaudioside M. Therefore, claims 5-9 are rendered obvious by Wang in view of Ho and Li and are rejected under 35 U.S.C. 103. T he Supreme Court has acknowledged: When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable vari a tion … 103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obviou s unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions …… the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Erin M. Bowers whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-2897 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Friday, 7:30-5:00 . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Sharmila Landau , can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571)272-0614 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Erin M. Bowers/ Primary Examiner, Art Unit 1653 03/26/2026