CTNF 18/256,548 CTNF 83474 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION 1. This application is a 371 of PCT/GB2021/053131 12/01/2021. FOREIGN APPLICATIONS: UNITED KINGDOM 2019393.4 12/09/2020. Claims 1-7, 9-20 are pending. Response to Restriction Election 08-25-02 AIA 2. Applicant’s election of group I in the reply filed on January 12, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). Claim Rejections - 35 USC § 101 & 35 USC § 112 07-04-01 AIA 07-04 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. 07-30-02 AIA 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 applicant regards as his invention. 3. Claim 13 is rejected under 35 U.S.C. 101 because the claimed invention is directed to nonstatutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because claim 13 is a use claim where “a method comprising the use of flow synthesis” with no steps. Recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, which is not a category of invention under 35 U.S.C. 101. Claim 13 is also rejected under 35 U.S.C. 112(b). Specifically, because the claimed invention does not fall within at least one of the four categories of invention, for the reasons set forth above, one skilled in the art clearly would not know what steps make up the claimed invention since there are no steps. See MPEP 2173.05(Q) “I. A "USE" CLAIM MAY BE REJECTED UNDER 35 U.S.C 101 AND/OR 112 It is appropriate to reject a claim that recites a use but fails to recite steps under 35 U.S.C. 101 and 35 U.S.C. 112(b) if the facts support both rejections.” Claim Rejections - 35 USC § 112 07-30-02 AIA 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 applicant regards as his invention. 4. Claims 1-7, 9-11, 13-20 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. Claims 1 and 14 are drawn to “preparing input flow reagent A, comprising hexamine dissolved in nitric acid with a concentration less than 92%”. It is unclear whether the concentration refers to hexamine or nitric acid. In addition there is no unit in the concentration, which would be molar, weight percent, etc. For purposes of examination the examiner has considered this be a saturated solution methamine solution in nitric acid, where this refers to the amount of methamine in claim 3, such that it is less than 92%. Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA 5. Claim(s) 1-3, 5-7, 9-11, 13-14, 16, 19-20 is/ are rejected under 35 U.S.C. 103 as being unpatentable over Hal e, “Nitration of urotropine using nitric acid”, J. Am. Chem. Soc. 47 (1925) 2754–2757 and Kyprianou “Synthesis of 2,4,6-Trinitrotoluene (TNT) Using Flow Chemistry” Molecules 2020, 25, 3586 1-15, Published: 6 August 2020 in view of Luo “ Evaluations of kinetic parameters and critical runaway conditions in the reaction system of hexamine-nitric acid to produce RDX in a non-isothermal batch reactor.” Journal of Loss Prevention in the Process Industries 15 (2002) 119–127. The factual inquiries set forth in Graham v. John Deere Co. , 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: Det ermining the scope and contents of the prior art Hale teaches the basic reaction of the instant claims used to produce RDX on a large scale on page 2757, Nitration of Hexamethylenetetramine Nitrate.—Table I gives the results of several representative nitrations in which nitric acid at various concentrations and at different temperatures was used. The nitrations were carried out by adding 5g. of the dried hexamethylenetetramine nitrate, obtained as described above, in small portions to the c. p. acid contained in a lOOcc. beaker. The acid was stirred only gently during the addition of the salt, as it was soon found that vigorous agitation caused a hasty reaction which tended toward a violent fuming of the mass. During the addition of the nitrate and for a short time after, the solution showed slight effervescence and the odor of formaldehyde was evident. As soon as the solution became quiet the charge was poured slowly into ice water, whereupon a white crystalline compound separated. PNG media_image1.png 356 729 media_image1.png Greyscale The quenching was performed with ice water to initiate precipitation as in claim 9 which is below 10 o C as in claim 10. Kyprianou demonstrated the feasibility of performing nitration of 2,4-DNT to 2,4,6-TNT using a flow chemistry approach: In recent years, considerable progress has been made in the synthesis of high-energy materials, especially in the field of military high explosives or propellants. Some of these high-energy materials can be obtained by novel eco-friendly methods of synthesis or techniques [3,4]. Nevertheless, the traditional approach is still applied, and it involves the use of hazardous concentrated acid mixtures (typically nitric and sulfuric acid as a nitrating mixture [5]). Nitration processes carried out especially at a larger scale are particularly prone to runaway exothermic reactions, and thus are of high safety concern [6]…..[page 1] The objective of this work was to develop a safer process for the manufacturing of high purity TNT (>99%) to be used in the preparation of explosives standards at the European Commission’s Joint Research Centre. These standards are used to verify that various explosives detection devices, like explosives trace detection equipment (ETD) used at airports, perform according to the specifications laid down in the EU Commission Implemented Regulation 2015/1998 [13]. In this regard, flow chemistry was chosen as a safer alternative to the conventional method of preparing TNT. Flow chemistry—also known as continuous flow chemistry—is the process of performing chemical reactions in a reactor, which can be a pipe, tube, or more complex microstructure device. The reagents are pumped to a mixing junction and flow into the temperature-controlled reactor. The large surface area facilitates vigorous mixing due to high rates of mass transfer and fast dissipation of heat, which allows for highly exothermic reactions. Consequently, faster, safer, automated, scalable procedures can be developed, and high purity products can be obtained by applying this form of synthesis [14–16]. In the pharmaceutical sector, several highly exothermic or hazardous nitration reactions were scaled up using flow chemistry processes [17]. Energetic materials have traditionally been prepared in batch reactors. However, on some occasions, flow chemistry was successfully used as an alternative to batch synthesis [18,19]. Among explosive substances, nitroglycerin, which is also a pharmaceutical substance, attracted a significant scientific interest for translating its conventional batch synthesis into flow process [20]. The application of flow chemistry is important for processes associated with large risks. Flow chemistry mainly increases safety with well-controlled pressure, stable temperatures, homogenous mixing, and fast dissipation of heat. Moreover, lesser amounts of energetic materials are present at any time in the reactor due to the continuous flow of reagents and the removal of the synthesis products.[page 2] The benefits of conducting the nitration of 2,4-DNT to 2,4,6-TNT using a flow chemistry approach were shown by Kyprianou. The main advantages of the flow chemistry approach included the use of safer reagents, shorter reaction times, and minimizing the risk of runaway reactions since the mixing steps take place in the reactor under continuous flow conditions. Luo explains that the reaction of Hale, sometimes called the Woolrich process, where hexamine is reacted with nitric acid to produce RDX, is dangerous. Although the RDX has been produced and used by many countries for a long time, its production process is not very safe so far. Numerous thermal runaway incidents and explosion catastrophes have occurred in the past. Unfortunately, its reactive hazard has not been clearly identified. The critical runaway temperature and unstable criterion at its reaction process are still unknown. The industries have to control their operating conditions very carefully to avoid the reaction system becoming a runaway situation. Therefore, we evaluate its reaction kinetic parameters from known production data of RDX in this investigation. Then, we can determine the critical runaway conditions of RDX reaction in a non-isothermal batch reactor using the transient energy and mass balance equations and evaluated kinetic parameters by numerical techniques simultaneously. Consequently, this critical runaway condition can be expressed as a function of kinetic parameters of chemical reaction, physical properties, and ambient temperature etc. Their required heat transfer coefficients in this critical condition can also be estimated. [ Luo Page 119, co. 2] Evaluation of reaction kinetic parameters from batch reaction of RDX The chemical reaction rate is very sensitive and affected by the temperature variation in an exothermic reaction system. Runway reaction or thermal explosion occurs in this exothermic hexamine-nitric acid reaction system in its production process. If we consider this reaction system in a batch reactor, when the total generated heat rate of reactive system exceeds removed heat rate of the ambient cooling medium, the whole system is very easy to accumulate energy and raise temperature. Then, this heat increasing system becomes unbalanced and a self-ignition reaction is triggered off. As soon as the temperature in this batch reactor reaches the critical point, the reactive system becomes a runaway situation or even explosion. [page 121 col. 1] Luo conducts experiments with 98% nitric acid an analyzes the yield of RDX at various times and temperatures in Table 1 on page 121 and determined safe parameters for operating a batch reactor. “The batch reaction system of RDX production being either runaway or safe can be evaluated from the values of f. " Ascertaining the differences between the prior art and the claims at issue. The prior art is directed towards a batch process while the instant claims are drawn to a flow chemistry reaction set up. Resolving the level of ordinary skill in the pertinent art and considering objective evidence present in the application indicating obviousness or nonobviousness Since the prior art process for making RDX was known to be dangerous in batch mode, the artisan would naturally look to flow chemistry to make the process safer as well as achieving shorter reaction times. The risk of runaway reactions would be minimized since the mixing steps take place in the reactor under continuous flow conditions. This is a so called exemplary rationale discussed in MPEP 2143, “(C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;” Using flow chemistry was recognized providing improvements in safety in explosives nitration. One of ordinary skill in the art would have been capable of applying this known technique disclosed by to Kyprianou to the known batchwise RDX synthesis that was ready for improvement. The results would have been predictable to one of ordinary skill in the art. Process optimization such as changes in temperature, concentration of reagents are routine. Hale shows a clear dependence of the reaction rate on temperature and acid concentration. According to Kyprianou “The influence of key parameters, such as HNO 3 :DNT molar ratio, residence time, and process temperature were investigated and optimized by applying a design-of-experiments approach. We note the possibility of obtaining a high conversion rate from 2,4-DNT to TNT (>99%) in only 20 min. This significant improvement of reaction performance can be attributed to the use of a flow chemistry set up, which includes the rapid mixing in the reactor that facilitates enhanced mass transfer during the course of the reaction. It is possible to safely apply elevated temperatures due to the fast dissipation of heat, which would not be possible with the batch methods due to high risk of a runaway reaction. By comparison, in similar conditions, the conversion rate of 2,4-DNT to TNT in a batch type reaction did not exceed 58%. Although a thorough economic assessment is beyond the scope of this paper, a provisional cost assessment of reagents indicates the flow chemistry approach might be favorable.” Optimizing time, temperature and concentration is especially critical in light of the potential for runaway reactions . 07-22-aia AIA 6. Claim (s) 4, 15 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hale and Kyprianou in view of Luo as applied to claim s 1-3, 5-7, 9-11, 13-14, 16, 19-20 above, and further in view of Dunning “The Heat of Nitrolysis of Hexamine in Nitric Acid.” Journal of the Chemical Society (1950), 2920-4. Claim 4, 15 and 18 are drawn to using 99% nitric acid as one of the flow reagents. The references above Hale and Luo use up to 98% nitric acid. The use of 99% nitric acid in this reaction is also known as shown by Dunning who used 99% acid in various experiments including Figure 3: PNG media_image2.png 418 629 media_image2.png Greyscale The Table on page 1267 also shows a rapid rate of production of the product (I), RDX, from hexamine with 99% nitric acid. PNG media_image3.png 325 1189 media_image3.png Greyscale The experimental section on page 1268 describes “99% acid (200 g.) was cooled to a predetermined extent below 0" and finely crushed hexamine (2 g.) was added at once to the vigorously stirred acid in a thin-walled flask; the temperature rose rapidly (<30 sec.) to 0 o C” It would be obvious to use 99% nitric acid to increase the reaction rates . 07-21-aia AIA 7. Claim (s) 15 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hale and Kyprianou in view of Luo as applied to claims 1-3, 5-7, 9-11, 13-14, 16, 19-20 above, and further in view of Fischer, Dennis; “Synthesis and Characterization of Guanidinium Difluoroiodate, [C(NH2)3]+[IF2O2]- and its Evaluation as an Ingredient in Agent Defeat Weapons” Zeitschrift fuer Anorganische und Allgemeine Chemie (2011), 637(6), 660-665 (abstract only). The prior art of Hale and Kyprianou in view of Luo does not use 70% nitric acid with sodium nitrite. According to Fischer abstract it is effects the same transformation. Combining two things known for the same purpose is prima facie obvious. Such salts can be added to decompose unwanted by-products in a controlled manner. Conclusion 8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID K O'DELL whose telephone number is (571)272-9071. The examiner can normally be reached on Monday - Friday 9:30 - 7:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form. /DAVID K O'DELL/Primary Examiner, Art Unit 1621 Application/Control Number: 18/256,548 Page 2 Art Unit: 1621 Application/Control Number: 18/256,548 Page 3 Art Unit: 1621 Application/Control Number: 18/256,548 Page 4 Art Unit: 1621 Application/Control Number: 18/256,548 Page 5 Art Unit: 1621 Application/Control Number: 18/256,548 Page 6 Art Unit: 1621 Application/Control Number: 18/256,548 Page 7 Art Unit: 1621 Application/Control Number: 18/256,548 Page 8 Art Unit: 1621 Application/Control Number: 18/256,548 Page 9 Art Unit: 1621 Application/Control Number: 18/256,548 Page 10 Art Unit: 1621 Application/Control Number: 18/256,548 Page 11 Art Unit: 1621