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. Claim Status Claims 1-10 were filed 8/23/2023 and are pending. Priority The application was filed on 8/23/2023 and claims the benefit of priority to: See filing receipt dated 10/3/2023. Acknowledgment is made of applicant's claim for foreign priority based on two applications filed in China (CN) on 4/13/2022. It is noted, however, that applicant has not filed a certified copy of the applications as required by 37 CFR 1.55. Drawings /Specification The disclosure is objected to because of the following informalities: the specification is objected to because all of the Schemes and compound structures therein are blurry and difficult to read. See p. 2-10. Appropriate correction is required. The drawings are objected to because Figures 4- 5 are blurry and the axes cannot be read. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Objections Claims 4-5 are objected to because of the following informalities: Claim 4 should be rewritten to say “The method of claim 3, wherein in step (S3 ) , the acid is a dilute hydrochloric acid and is added to the reaction system until the reaction system reaches a pH of 3 or less”. In the final line of claim 5 , the limitation “(42)” should be rewritten as “(S42)”. Appropriate correction is required. 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. Claim(s) 1- 6, 9, and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Engell ( US 2010/0087679 , published on 4/8/2010) in view of Grignard ( saved at the wayback machine: https://web.archive.org/web/20210301000000*/https://chem.libretexts.org/Ancillary_Materials/Demos_Techniques_and_Experiments/General_Lab_Techniques/Quenching_reactions/ Quenching_Reactions%3A_Grignards , on 3/7/2021, and downloaded on 3/26/2026) and Martinez ( US 2008/0161593 , published on 7/3/2008) and as evidenced by Ammonium Chloride (downloaded from https://thechemco.com/chemical/ammonium-chloride / on 3/26/ 2026) and Methacrylic Acid (downloaded from https://pubchem.ncbi.nlm.nih.gov/compound/Methacrylic-Acid#section=Dissociation-Constants&fullscreen=true on 3/26/2026). The Applicant claims: A method for synthesizing a labeled pyruvic acid, comprising: (S1) adding an isopropenyl Grignard reagent to a reaction vessel followed by cooling to a preset temperature; (S2) adding a carbon isotope-labeled carbon dioxide to the reaction vessel followed by reaction with the isopropenyl Grignard reagent for a preset time; (S3) adding an acid to a reaction system obtained in step (S2) and adjusting the reaction system to a preset temperature to quench the reaction; (S4) subjecting a quenched reaction system to ozonization to obtain an ozonized product; (S5) reducing the ozonized product obtained in step (S4) with a reducing agent to obtain a reduced product; and (S6) removing impurities from the reduced product to obtain the labeled pyruvic acid. Engell is directed toward a method for producing 13 C 1 -alpha-keto acids and esters, in particular 13 C 1 -pyruvic acid and esters thereof, which are 13 C-enriched (isotopically enriched in carbon-13) at the C1-atom (carboxyl atom). See abstract. Engell teaches that one pathway towards the labeled pyruvic acid includes the production of intermediate methacrylic acid compound (II) from a 2-halopropene of formula (III): . See [0053-0054]. The compound (II) is then subjected to ozonolysis to produce the labeled pyruvic acid (I): . See [0057-0061]. Paragraphs [0062-0070] describe produc ing 13 C 1 -pyruvic acid using the processes of reaction schemes 2 and 3 above. Specific experimental conditions are provided in Fig. 1 and the examples. Example 1a in [0073] corresponds to the reaction sequence in scheme 2 above and Examples 2 and 3 in [0075-0076] correspond to the reaction in scheme 3 above. Also see Fig. 1 from the top of the page until formation until bubble labeled “Methacrylic acid”. Scheme 2 and E xample 1a correspond to instantly claimed steps (S1) (S2) and (S3). Scheme 3 and Examples 2-3 correspond to instantly claimed steps (S4) (S5) (S6). Regarding step (S1), t he reaction of compound (III) of scheme 2 with Mg in reaction 2 corresponds to the in - situ preparation of an isopropenyl Grignard reagent (the intermediate compound of scheme 2 ) in a reaction vessel . Once formed, the reaction vessel is cooled to a preset temperature of -70°C. Regarding step (S2), Engell teaches that carbon dioxide, including 13 CO 2 ( 13 C labeled carbon dioxide - claim 6 ), is added to the reaction vessel comprising the Grignard reagent. The carbon dioxide and Grignard reagent were placed under heavy stirring and reacted until the temperature reached room temperature (such that the “preset time” is the time taken for the reaction to warm to room temperature). Regarding step (S3), Engell teaches that an acid, saturated ammonium chloride (see evidentiary Ammonium Chloride reference), is added to the reaction system at room temperature to quench (terminate) the reaction. Solvent and unreacted 2-halopropene is then removed in vacuo under heat (30°C), the remaining aqueous phase of the reaction mixture is further acidified with dilute hydrochloric acid (3M HCl, a second acid), and then the methacrylic acid product of formula (II) is extracted into dichloromethane (methylene chloride). Regarding step (S4), Engell teaches that the methacrylic acid (II) can be optionally purified before ozonolysis. According to the “one-pot” and “two-step” preparations discussed on p.11-15 of the specification as filed, any mixture comprising the methacrylic acid product of step (S3) ; or the isolated methacrylic acid compound from step (S3) both meet the limitations of “a quenched reaction system”. Examples 2 and 3 of Engell teach that isolated methacrylic acid is dissolved in dichloromethane/methanol (to form a “quenched reaction system” ) which is subjected to ozonolysis conditions to produce an unstable ozonized product ( ozonoid ). Regarding step (S5), the unstable ozonoid is contacted with a reducing agent to obtain a reduced product comprising labeled pyruvic acid. Regarding step (S6), the pyruvic acid generated at the end of the reduction can be purified to remove impurities and produce a purified labeled pyruvic acid product. Engell does not explicitly teach : adding an isopropenyl Grignard reagent to a reaction vessel followed by cooling to a pre-set temperature (the Grignard reagent is instead formed in situ in the reaction vessel ) in step (S1); or “adjusting the reaction system temperature to a preset temperature to quench the reaction” in step (S3). Grignard is an online general chemistry resource which details how to quench Grignard reactions. The paragraph on the page teaches that Grignard reagents are highly reactive toward water and that they should be quenched at lower temperatures with dropwise addition of water and dilute acids. See whole document (single paragraph on a single page). Martinez teaches an analogous process for producing labeled pyruvic acid. See abstract and claims. The process of Martinez also includes the reaction between a Grignard reagent and labeled CO 2 to produce a methacrylic acid intermediate. See [0077-0084]. In [0128-0129] Martinez teaches a detailed experimental method: . Martinez t eaches that isopropenyl magnesium bromide ( isopropenyl Grignard reagent) is added to an oven dried round bottom flask (RBF) and cooled to -78°C with a dry ice/acetone bath. The 13 CO 2 was bubbled into the Grignard over 55 minutes. After addition, the reaction was stirred for 15 minutes and then diluted HCl (dilute acid) was added as a steady stream over 10 minutes. After acid addition, the cold bath was removed and replaced with water to warm the reaction to room temperature. Therefore, the process of Martinez teaches “adding an isopropenyl Grignard reagent to a reaction vessel” in instant step (S1) and “adding an acid to a reaction system obtained in step (S2) and adjusting the reaction system to a present temperature (room temperature) to quench the reaction” of instant step (S3). It would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Engell , Grignard, and Martinez to arrive at the instantly claimed process with a reasonable expectation of success before the effective filing date of the claimed invention. A person of ordinary skill would have been motivated to add the Grignard reagent to the reaction vessel in instant step (S1), rather than form the reagent in situ as taught by Engell because Martinez explicitly teaches as much. Thus, the slight difference in the order of addition of the first reagent to the first reaction vessel does not appear to be critical. Also see MPEP 2143(I)(A) and MPEP 2144.04(IV)(C). Further, the skilled artisan would be motivated to use the order of addition in Martinez in order to optimize the process. A person of ordinary skill would understand that if a series of Grignard reactions are going to be carried out simultaneously using the same Grignard reagent, or if a commercial source of Grignard were used, that a larger batch of the Grignard reagent would be formed in one reaction vessel (or purchased) and then separated and fed to each individual reaction vessel of the series. This would avoid the need to carry out multiple identical Grignard formation reactions. Further, this would help to standardize all of the series of compounds for better comparison because the same source of Grignard would be used. Also see MPEP 2144.05. A person of ordinary skill would have been motivated to adjust the reaction system temperature to a preset temperature to quench the reaction in the quenching step of Engell (instant step (S3)) after the acid is added because Grignar d advises caution when adding aqueous acids to quench Grignard reagents, which includes the use a slow and controlled rate of addition and carrying the quench out at a low temperature. Engell teaches that the quenching step is carried out at room temperature, though the reaction temperature of the carbon dioxide addition is at -70°C. Based on the teachings of Grignard, the skilled artisan would be motivated to add the quenching acid to a cold reaction system of Engell , before the reaction is warmed to room temperature, in order to increase the safety of the reaction. The skilled artisan could also envision that this might also enhance the selectivity and/or yield of the reaction because the quench is controlled at a lower temperature, as opposed to a “violent” quench at room temperature. Further, this sequence is explicitly taught in the process of Martinez , wherein the acid is added at -78°C, and the resulting mixture is then warmed to room temperature (the pre-set temperature) without adversely affecting the outcome of the reaction . Therefore, modifying the process of Engel to add the acid at a cooler temperature before the source of cooling is removed to allow the reaction to warm to room temperature, as suggested by Grignard and Martinez would predictably increase the safety of the quenching step. Also see MPEP 2143(I)(A). Regarding claim 2 , Engell teaches that the ozonolysis can be carried out continuously for an amount of time (until the reaction turns blue) . See “oxidation by ozonolysis” step of Fig. 1 and [0042], which refers back to a continuous Grignard reactor in [0036]. Also see examples 2-3 in [0075-0076] and [0057]. Regarding claim s 3 and 5 , Engell teaches that the quenched reaction system containing the methacrylic acid product is extracted with dichloromethane (3 x 50 mL), the three organic layers were combined, dried and evaporated to obtain an oily product. See [0073]. Examples 2 and 3 in [0075-0076] then teach that the oily product is transferred to another vessel and dichloromethane and methanol are added to the oil product, and the resulting system is cooled to -78°C (preset temperature) and contacted with ozone to carry out the ozonolysis until a blue color is observed (preset time). Regarding claim 4 , both Engell [ 0073] and Martinez [0128-0129] teach adding dilute HCl until the aqueous phase is made acidic, and then extracting the desired product, methacrylic acid, into an organic layer. Though neither reference explicitly teaches a pH range, “acidic” encompasses that claimed. Further, as evidenced by Methacrylic Acid , the pKa of methacrylic acid is 4.65. Therefore, any pH below that will predictably protonate methacrylic acid to be extracted into the organic phase. Also see MPEP 2144.05. Regarding claim 9 , Engell teaches that the reducing agent includes dimethyl sulfide. See [0057] and [0075-0076]. Regarding claim 10 , Engell teaches that the reduced product (pyruvic acid) can be obtained by evaporating the solvent (removing an organic phase) followed by distillation (step S61) . See [0057] and [0075-0076]. However, Engell teaches that the purification process is not limited to that embodiment. Engell teaches that after evaporation of the solvent, that water and a base can be added to the residue to produce a pyruvate salt, which may then be left for crystallization. See [0058]. Engell further teaches that the pyruvate can be converted into free pyruvic acid in a subsequent step and that the method for this conversion are known in the art. See [0059]. Engell does not explicitly teach that the aqueous alkaline product mixture (comprising pyruvate salt) is extracted and separated to produce multiple aqueous phases which are combined in step (S62). Nor does Engell explicitly teach steps (S63) and (S64). However, all of steps (S62), (S63), and (S64) describe routine reaction work-up steps that would be known to those of ordinary skill in the art. Furthermore, examples of all are present elsewhere in Engell and Martinez . For example, Example 1a in [0073] of Engell teaches steps (S63) and (S64), of acidifying the reaction mixture to produce an aqueous acidic phase which is extracted multiple times with an organic solvent, dried over magnesium sulfate and evaporated (concentrated) to give the title compound as an oil. As the magnesium sulfate is not present in the final product, the skilled artisan would understand that it has been removed. Paragraph [0077] specifically teaches that solids can be removed from liquids by filtration. Further, Martinez also describes extraction of an aqueous acidic phase with an organic solvent in [0100] to separate pyruvic acid. Martinez also teaches than a basic aqueous solution comprising a pyruvate salt c an be extracted with an organic solvent multiple times and the aqueous layer separated and evaporated to dryness, which is analogous to instant step (S62). Therefore, the steps set forth in claim 10 are all routine, predictable, and well-known to those of ordinary skill in the art. Though the references do not teach the specific sequence of (S62) to (S64), the skilled artisan could easily arrive at the claimed steps with a reasonable expectation of success based on Engell and Martinez. From the teachings of the references as a whole, it would be inferred by the skilled artisan that step (S61) would produce a crude residue containing inorganic impurities, organic impurities, and pyruvic acid, all expected from the ozonolysis reaction, especially if the intermediate methacrylic acid is not purified before ozonolysis; step (S62) would transform pyruvic acid to its salt which is soluble in the aqueous layer and would separate organic impurities from the pyruvic acid via extraction into the organic layer; step (S63) would convert the pyruvate back to pyruvic acid, soluble in the organic layer, which will separate the pyruvic acid from inorganic impurities; and that step (S64) is isolating the purified product from the twice extracted mixture. All of these techniques are discussed in the references and combining them in the order claimed would be a prima facie obvious and predictable substitute for the purification processes explicitly taught in the examples of the references. Also see MPEP 2144.05; MPEP 2144.04(IV)(C); and MPEP 2143(I)(B). Claim(s) 7 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Engell ( US 2010/0087679 , published on 4/8/2010) in view of Grignard (saved at the wayback machine on 3/7/2021; full citation above) and Martinez ( US 2008/0161593 , published on 7/3/2008) and as evidenced by Ammonium Chloride (full citation above) and Methacrylic Acid (full citation above), as applied to claims 1-6, 9, and 10 above and further in view of Jove (dated 2017, downloaded from https://moodle2.units.it/pluginfile.php/378235/mod_resource/content/1/Conducting%20Reactions%20Below%20Room%20Temperature.pdf on 3/ 26/2026) and Felton (“Baths and Circulators”, 2004, Today’s Chemist at Work, p. 49). The Applicant claims the method of claim 6, wherein in step (S1), before the isopropenyl Grignard reagent is added to the reaction vessel, a magnetic stirring bar is added to the reaction vessel and argon is introduced into the reaction vessel, and the reaction is cooled to -30 to -78°C in an ethanol bath using a cryogenic recirculation pump and then reacted with the carbon isotope-labeled carbon dioxide for 1 hour in step (S2). The Applicant also claims that in step (S3), the temperature is -10 to 0°C. Regarding step (S1), Engell teaches forming the Grignard in situ under nitrogen gas (inert gas) in the presence of a stir-bar and cooling to -70°C. See [0073]. This temperature falls within the claimed range. See MPEP 2144.05. Martinez teaches that the Grignard reagent is added to an oven-dried round bottom flask (RBF) containing a stirrer and under argon (inert gas) and cooled to -78°C, which also falls within the claimed range. See [0129]. Thus, both Engell and Martinez teach cryogenic reaction temperatures. Regarding step (S2), Engell teaches that the reaction is stirred under CO 2 for the length of time it takes for the reaction to warm from -70°C to room temperature. No specific time is recited. See [0073]. Martinez teaches that the CO 2 is bubbled into the Grignard at -78°C, over 55 minutes and stirred for 15 more minutes. See [0129]. Regarding step (S3), Engell does not teach adjusting to the preset temperature after acid addition. Martinez teaches that the acid is added at -78°C and that the reaction is warmed to room temperature. See [0129]. Grignard teaches that a Grignard reaction can be quenched at 0°C. Therefore, the combined process of Engell , Martinez, and Grignard meets all of the claimed limitations except that the cooling is performed in an ethanol bath using a cryogenic recirculation pump in (S1); that the carbon dioxide is reacted for 1 h in (S2); and that the preset temperature in (S3) is -30 to 0°C. Regarding the time of reaction in (S2), Martinez teaches that the reaction is completed in about 70 minutes (55+15) when kept at -78°C. This value is so close to the claimed value of 60 minutes that a difference of 10 min would not be expected to drastically change the result of the reaction. Further, the time of reaction does not appear to be critical as long as it is long enough for the reaction to be complete. If the reaction is not complete the skilled artisan would predictably lengthen the time of reaction. Thus, the claimed time could also be arrived at through routine optimization. See MPEP 2144.05. Regarding the preset temperature of (S3), as argued in the prior rejection, the skilled artisan would have been motivated to quench the reaction with the acid at a low temperature and then warm the reaction to complete the quench in order to predictably improve the safety of the quench. Martinez teaches that the reaction is gradually warmed from -78°C to room temperature, Engell teaches quench at room temperature, and Grignard teaches that the quench can be carried out at 0°C. Therefore, though the references do not explicitly teach adjusting the temperature of the claimed (S3) mixture to within the claimed range of -30 to 0°C, the combination of teachings indicates that the quench can take place anywhere in the range of -78°C to room temperature, which encompasses the claimed range. The skilled artisan could predictably arrive at the claimed temperature range through routine experimentation. If the quench proceeds too slowly, then the skilled artisan would raise the temperature. If the quench appears to be too reactive, then the skilled artisan would lower the temperature. There does not appear to be anything critical about the claimed range. Also see MPEP 2144.05. Regarding the cooling apparatus of (S1): Felton is a product profile in a magazine for chemists which describes baths and circulators for heating and cooling reactions. See p. 49-50. Felton teaches that known apparatus include circulators which comprise pumps and can be used for heating or cooling by pumping a heating or cooling liquid out of a storage reservoir to laboratory instruments . See p. 49, bottom of second column to top of the third and Table on p. 50. Jove is a review on conducting reactions below room temperature. See p. 1. Jove teaches that for temperatures down to -78°C, dry ice (CO 2 ) baths in different solvents can be employed and that for temperatures below -78°C to -196°C that liquid nitrogen (liq. N 2 ) can be employed as the coolant . See “principles” on p. 1. Table 2 on p. 2 and Table 3 on p. 3 list combinations of dry ice or nitrogen with various solvents for cooling baths and the temperatures which are produced. Both Table 2 and Table 3 teach that ethanol (ethyl alcohol) can be used as a cryogenic solvent. With dry ice, the temperature is about -72°C and with liquid nitrogen the temperature is about -116°C. It would have been prima facie obvious to combine the teachings of Engell , Grignard, Martinez, Felton, and Jove to arrive at the instantly claimed process with a reasonable expectation of success before the effective filing date of the claimed invention. A person of ordinary skill would have been motivated to carry out step (S1) of the combined process of Engell , Grignard, and Martinez using the claimed apparatus because Felton teaches that pump recirculating coolers are known in the art and Jove teaches that ethanol is a suitable solvent to provide the cryogenic temperature requires for step (S1). Therefore, using known apparatus and solvents to predictably cool a reaction mixture to a desired temperature is prima facie obvious. Also see MPEP 2143(I)(B). 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