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 .
Response to Amendment
This action is written in response to applicant’s amendments received on 9/8/25.
All rejections and objections regarding claims 1-20 are moot due to the cancellation of claims 1-20.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 21-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 21, there is no support in the specification for the limitation “so as to remove phosphate byproducts”.
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.
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 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over) Zhang (US20210246476A1). While Zhang has a later publishing date than the filing date of instant application it claims priority to 1/31/20 and therefore is valid prior art under 35 U.S.C. 102(a)(2).
Regarding claim 21, Zhang teaches methods to make NMN (abstract). Zhang teaches that their method can comprise using NR and ATP react to product NMN and ADP using NRK (fig 2). Zhang teaches their method can be used in engineered organisms ([0242-0245]). Zhang teaches ADP can be used to generate ATP (claim 1), and that ATP can regenerated by ATP-generating permeabilized living microorganisms comprising Saccharomyces cerevisiae (claim 12). Zhang teaches by-products are removed in situ (claim 1). Zhang teaches their system can be “one pot” (same reaction system) (abstract). Zhang teaches the engineered microbial cells can utilize (metabolize) carbohydrates ([0244]), and the permeabilized yeast cells serving as the ATP-generation system would inherently undergo oxidative phosphorylation metabolism (in which adenosine, phosphate, and carbohydrate metabolizable by yeast cells react under catalysis of the yeast cells) under such conditions. Zhang teaches their methods including microorganisms containing the claimed enzymes, leads to higher production of products (NMN, inclusion of adenosine, phosphate, carbohydrate, yeast cells, NR and NRK) ([0019]).
It is obvious to one of ordinary skill in the arts to experiment within the inventive confines of Zhang to arrive at instant invention. All of the claimed components were known in the arts at the time of filing of instant invention and would be yield nothing more than predictable results with a reasonable expectation of success to one of ordinary skill in the arts.
Regarding claim 22, Zhang teaches the ATP regenerating yeast can use glucose (example 31).
Regarding claim 23, Zhang teaches that host organism used can be Saccharomyces cerevisiae (claim 4).
Regarding claims 24-25, Zhang teaches a Mg2+ ions can be added (magnesium) (claim 1).
Claims 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over) Zhang (US20210246476A1) and Akiyama (EP3690057A1). While Zhang has a later publishing date than the filing date of instant application it claims priority to 1/31/20 and therefore is valid prior art under 35 U.S.C. 102(a)(2).
Regarding claim 26, Zhang teaches the concentrations of substrates can be optimized ([0240-0241]). Zhang does not explicitly teach the molar ratios.
Akiyama teaches methods for producing NMN (abstract). Akiyama teaches ATP (adenosine) at a concentration 1 µg/L to 100 g/L ([0097]). Akiyama teaches these concentrations can be adjusted as appropriate ([0097-0098]). Therefore, this is a result effective variable and one of ordinary skill in the arts would be motivated to experiment and find the optimal concentration. See MPEP 2144.05 II. B. Akiyama teaches the ribose (NR from claim 1 rejection above) can be 1 µg/L to 100 g/L ([0095-0097]). Akiyama teaches that the substrate ribose (NR) concentration can be 30 mM ([0161]). This can yield a molar ratio of 1 when combined with 15 g/L ATP as taught by Akiyama above, rendering the claimed range obvious. Generally, differences in concentration 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) (MPEP 2144.05).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use substrate concentration of Akiyama in the invention of Zhang above. One of ordinary skill in the art would be motivated to do so because Zhang teaches their the substrate concentrations can be optimized. Further, one of ordinary skill in the art would be motivated to do so because these enzymes and cellular systems have been successfully used to produce NMN and ATP, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as both Akiyama and Zhang are in the same field of endeavor of producing NMN using microorganisms.
Regarding claim 27, Akiyama teaches that the ratio of the phosphate to the substrate ribose (NR) can be 30 mM to 5mM (ratio of 6, rendering the claimed range obvious) ([0161]). Akiyama teaches that these ratios are important for concentrations to be set to maximize production and that altering the ratios changes the product concentration ([0151]). Therefore, this is a result effective variable and one of ordinary skill in the arts would be motivated to experiment and find the optimal concentration. See MPEP 2144.05 II. B.
Regarding claim 28, Akiyama teaches the cells can be frozen in buffer (wet yeasts once being stored cryogenically) ([0074).
Response to Arguments
Applicant's arguments filed 9/8/25 have been fully considered but they are not persuasive.
Applicant argues that the cited references do not teach a reaction system where ATP is generated, consumed, and regenerated in situ (paragraphs 10 and 11). Zhang teaches that their method can comprise using NR and ATP react to product NMN and ADP using NRK (ATP consumed) (fig 2), and that the system can be a one-pot reaction system that includes an ATP-regeneration system comprising permeabilized yeast cells (claim 12).
Applicant argues that phosphate accumulation is eliminated (13). Zhang teaches by-products (which would include phosphate) are removed in situ (claim 1).
Applicant argues that Zhang requires continuous supply of ATP (12). Zhang teaches that yeast cells can be used for the regeneration of ATP (claim 12).
Applicant argues that a one-pot system and by-product metabolism is not taught by the references (15). Zhang teaches by-products are removed in situ (claim 1). Zhang teaches their system can be “one pot” (same reaction system) (abstract).
Applicant argues that the combination of the art would not result in instant invention (17). Both arts teach yeast can be used in their invention, see the rejection above. As yeast is used by both prior references, the use of the yeast oxidative phosphorylation system would be used.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TREVOR L KANE whose telephone number is (571)272-0265. The examiner can normally be reached M-F 7:00 am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TREVOR KANE/Examiner, Art Unit 1657
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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