DETAILED ACTION
STATUS OF THE APPLICATION
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 28 August 2025, in the matter of Application No. 17/920,337. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-18 are pending.
Claims 1-15 have been amended.
Claims 16-18 have been newly added.
Thus, claims 1-18 represent all claims currently under consideration.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
Claim Objections
Applicant’s amendments to claims 2, 5, and 12-13 have fully overcome the claim objections.
35 U.S.C.§ 112
Applicant’s amendments to the claims have fully overcome the rejections over instant claims 2-15 under 35 U.S.C.§ 112(b) over claim 13 under 35 U.S.C.§ 112(d).
35 U.S.C.§ 103
The claim rejections under 35 U.S.C.§ 103 from the previous Office Action mailed 28 May 2025 are withdraw in view of Applicant’s amendments to instant claim 1.
Double Patenting
Applicant’s terminal disclaimer filed 28 August 2025 have fully overcome the provisional nonstatutory double patenting rejections over claims 1-8 and 12-14 of copending Application No. 17/920,327, claims 1-4 and 8-14 of copending Application No. 17/919,932, and claims 1-3 and 7-13 of copending Application No. 17/919,939.
Claim Objections
Claim 1 is objected to because of the following informalities:
In line 7, “…α,ω-C4 alkanediol mononitrate….” should read “…α,ω-C4alkanediol mononitrate….” in a manner consistent with the claims and written description.
Claim 5 is objected to because of the following informalities:
In line 8, “…LP-1….” should read “…LP-I….”
In line 11, “…GP-1….” should read “…GP-I….”
In line 11, “…(partial)….” should read “…partial….”
In line 17, “…LP-1….” should read “…LP-I….”
In line 29, “…onto…” should read “…into…”
Claim 12 is objected to because of the following informalities:
In line 4, “…mol ratio….” should read “…mole ratio ….”
In line 6, “…HNO3 in a range of….” should read “…HNO3 is in a range of….”
Appropriate correction is required.
Claim Interpretation
Examination requires claim terms first be construed in terms of the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what Applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III).
The term “inlet stream” recited in claim 1, absent any strict definition in the written description, will be interpreted as any one of the feed streams, boilup streams, or reflux streams entering the distillation column, as evidenced by L. Robbins (c.f., pages 8-9, Section 2.1: Distillation Column Inlet Stream, in Distillation Control, Optimization, and Tuning, 2011, pages 1-134).
The term “inert solvent” will be interpreted according to the instant specification (page 4, paragraph 4) as a solvent which does not take part in a chemical reaction in the reaction medium and under the operating conditions, and which is inert to both the reactants and the reaction products.
The term “evaporator” will be interpreted according to the instant specification (page 5, paragraph 5) as a device used to turn a liquid form of a chemical substance or a mixture of chemical substance into its gaseous form/vapor.
NEW Claim Rejections - 35 USC § 103 – Necessitated by Amendment
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.
Claims 1 and 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Hack et al. (US 2010/0137599 A1; PTO-892 of 05-28-2025; hereinafter “Hack”), in view of Furniss et al. (Vogel’s Textbook of Practical Organic Chemistry (1989), pages 173 and 175; PTO-892 of 05-28-2025; hereinafter “Furniss”) and L. Robbins (Distillation Control, Optimization, and Tuning, 2011, pages 1-134; PTO-892 of 05-28-2025; hereinafter “Robbins”).
Regarding claim 1, Hack teaches a process for the preparation of 4-nitrooxybutan-1-ol via the hydrolysis of 4-nitrooxy-butan-1-ol butyrate, wherein the reaction solvent was completely was removed completely by vacuum distillation. The 4-nitrooxybutan-1-ol compound taught by Hack is a α,ω-C4 alkanediol mononitrate and is thus a species that reads on the instantly claimed genus, a α,ω-C3-10 alkanediol mononitrate (Hack; claim 1; paragraph [0159], Example 3).
Hack fails to teach a distillation comprising partial condensation and continuous back-feeding of fractions comprising mixtures of inert solvent and α,ω-C3-10alkanediol mononitrate into the distillation of step (a) via an inlet stream, as recited in instant claim 1.
However, Furniss teaches that unless the boiling points of the components of a mixture are widely different it is usual to employ a fractionating column to attempt the separation of liquid mixtures by distillation wherein a fractionating column consists essentially of a long vertical tube through which the vapor passes upward and is partially condensed; the condensate flows down the column and is returned eventually to the flask (Furniss; page 173, paragraphs 3-4). In addition, Furniss details the theory of fractionation and the enhancement of efficiency by virtue of increasing the number or theoretical plates, and Furniss further teaches that the ultimate aim in the design of efficient fractionating columns is to reduce the proportion of the intermediate fractions to a minimum (Furniss; page 175, paragraph 4 and page 176, paragraphs 1-2).
Although Furniss does not explicitly recite the term “the continuous back-feeding of fractions into the distillation of step (a) via an inlet stream”, as recited in claim 1, the skilled artisan could reasonably interpret the condensate flowing down the column and returned to the flask as taught by Furniss as an inlet stream, in a manner consistent with the instant claim.
The claim 1 limitation “via an inlet stream” as recited in step (b) is further addressed by Robbins, who teaches distillation column control (Robbins; page 8, paragraph 1 and Figure 2.1). Of particular note, Robbins teaches that inlet and outlet stream flow rates are the manipulated variables in distillation column control and is usually the stream that has an automatic valve connected to a controller output signal (Robbins; page 8, paragraph 1 and Figure 2.1). Figure 2.1 of Robbins shows that separate inlet stream from the distillate can be controlled via a valve to adjust the amount recycled back to the distillation column, and the flow rates of the distillate and bottoms streams change as necessary to maintain the material balance and achieve the target compositions (Robbins; page 8, Figure 2.1 and page 25, paragraph 4). Thus, the skilled artisan would recognize from the teachings of Robbins that a separate inlet stream enables an improved method of distillation control.
The prior art taught by both Hack, Furniss, and Robbins described above reside in the overlapping technical fields of synthetic organic chemistry and chemical purification, and the prior art taught by both Furniss and Robbins reside in the overlapping technical field of purification using distillation-based systems. This prior art is therefore deemed analogous art, as described in MPEP § 2141.01(a). Moreover, the methods regarding fractional distillation as taught by Furniss and the methods of controlling the inlet stream of the distillate as taught by Robbins are routinely practiced by the skilled artisan. As such, one of ordinary skill in the art would be sufficiently motivated to incorporate the teachings of Furniss and Robbins into the method of Hack to arrive at the instantly claimed process with a reasonable expectation of success. Such an endeavor would result in combining prior art elements according to known methods to yield predictable results, as described in MPEP § 2143(I)(A) and the use of known techniques to improve similar devices in the same way, as described in MPEP § 2143(I)(C).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the distillation method of Hack to incorporate the teachings of Furniss and Robbins to arrive at the instantly claimed process. The motivation to do so would permit the skilled artisan to pursue, with a reasonable expectation of success, a process that improves the separation efficiency and enables improved distillation control to maintain the material balance and achieve the target compositions, as described above.
Regarding claim 3 depending from claim 1, Hack teaches the preparation of 4-nitrooxybutan-1-ol with a purity according to GC of 99.7% (Hack; paragraph [0159], Example 3). This value resides within the instantly claimed range.
Regarding claim 4 depending from claim 3, Hack teaches the complete removal of methanol solvent by distillation, wherein the methanol amount as checked by GC is 0.04% relative to 4-nitrooxybutan-1-ol. (Hack; paragraph [0159], Example 3). This value resides within the instantly claimed range.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Hack et al. (US 2010/0137599 A1; PTO-892 of 05-28-2025; hereinafter “Hack”), in view of Furniss et al. (Vogel’s Textbook of Practical Organic Chemistry (1989), pages 173 and 175; PTO-892 of 05-28-2025; hereinafter “Furniss”) and L. Robbins (Distillation Control, Optimization, and Tuning, 2011, pages 1-134; PTO-892 of 05-28-2025; hereinafter “Robbins”) as applied to claims 1 and 3-4 above and further in view of W. B. Glover (Chem. Eng. Prog. 2004, 100, 26-33; PTO-892 of 05-28-2025; hereinafter “Glover”) and Kafi et al. (Desalination, 2005, 182, 175-186; PTO-892 of 05-28-2025; hereinafter “Kafi”).
Regarding claim 2, claim 1 is rendered obvious over Hack, Furniss, and Robbins, as detailed above.
Hack, Furniss, and Robbins fail to teach wherein the process is carried out in an evaporator setup, even more preferably in an evaporated setup which comprises 1 to 5 evaporators, as recited in instant claim 2.
However, Glover teaches that evaporators are used in a wide range of processes, including pharmaceuticals, foods and beverages, pulp and paper, chemicals, polymers and resins, inorganic salts, acids, bases, and a variety of materials (Glover; page 26, Col. 1, paragraph 1). Glover further teaches that an evaporator should be designed to provide a clean separation of the vapors from the condensate and the feed, and consists of a heat exchanger or heated bath, valves, manifolds, controls, pumps and condenser; a properly designed evaporator must, at a minimum: be designed to effectively transfer heat at a high rate with minimum surface area to be cost-effective; effectively separate the vapor from the liquid concentrate; produce a product that meets the required quality; be energy efficient; and minimize fouling (Glover; page 26, Col. 1, paragraph 5 and Col. 2, paragraph 1). In addition, Glover teaches that agitated thin-film evaporators have several advantages such as: short residence time, high heat-transfer coefficients, less product decomposition, and high recovery; they are typically used for the purification of sensitive organic chemicals, concentration of foods and pharmaceuticals, and recovery of valuable resources from waste streams, such as solvents (Glover; page 32, Col. 1, paragraphs 2-3).
Although Glover teaches the general utility and advantages of utilizing evaporators in purification processes, Glover fails to explicitly teach an evaporator setup comprising 1 to 5 evaporators, as recited in the instant claim.
However, Kafi teaches an improved cost and energy efficient plate multi-effect distillation (MED) desalination process comprising a three-effect plate evaporator with three evaporator-condenser units in series, wherein brine from each evaporator can be recycled to earlier units (Kafi; page 175, Col. 2, paragraph 1; page 178, Fig. 3; page 179, Col. 1, paragraph 3).
The prior art taught by both Glover and Kafi are in the overlapping technical field of purification using evaporator-based systems. This technical field further overlaps with the teachings of Hack, Furniss, and Robbins described above, who teach methods relating to synthetic organic chemistry and chemical purification using distillation-based techniques. This prior art is therefore deemed analogous art, as described in MPEP § 2141.01(a). Moreover, the methods regarding distillation as taught by Furniss and Robbins and the methods regarding the use of evaporators for chemical process applications including distillation as taught by Glover and Kafi are routinely practiced by the skilled artisan. As such, one of ordinary skill in the art would be sufficiently motivated to incorporate the teachings of Glover and Kafi into the method of Hack, Furniss, and Robbins to arrive at the instantly claimed process with a reasonable expectation of success. Such an endeavor would result in combining prior art elements according to known methods to yield predictable results, as described in MPEP § 2143(I)(A) and the use of known techniques to improve similar devices in the same way, as described in MPEP § 2143(I)(C).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Hack, Furniss, and Robbins to incorporate the teachings of Glover and Kafi to arrive at the instantly claimed process. The motivation to do so would permit the skilled artisan to pursue, with a reasonable expectation of success, an energy-efficient process with the added benefit of short residence time, high heat-transfer coefficients, less product decomposition, and high recovery, as described above.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Hack et al. (US 2010/0137599 A1; PTO-892 of 05-28-2025; hereinafter “Hack”), in view of Furniss et al. (Vogel’s Textbook of Practical Organic Chemistry (1989), pages 173 and 175; PTO-892 of 05-28-2025; hereinafter “Furniss”), L. Robbins (Distillation Control, Optimization, and Tuning, 2011, pages 1-134; PTO-892 of 05-28-2025; hereinafter “Robbins”), W. B. Glover (Chem. Eng. Prog. 2004, 100, 26-33; PTO-892 of 05-28-2025; hereinafter “Glover”), and Kafi et al. (Desalination, 2005, 182, 175-186; PTO-892 of 05-28-2025; hereinafter “Kafi”) as applied to claim 2 above and further in view of W. L. Luyben (Ind. Eng. Chem. Res. 2004, 43, 6416-6429; PTO-892 of 05-28-2025; hereinafter “Luyben”).
Regarding claim 5 depending from claim 1, Kafi teaches an evaporator setup comprising 3 evaporator-condenser units in series and a first or second liquid fraction that can optionally be recycled back onto the first evaporator or the second evaporator, consistent with every limitation of step (S-1) and several limitation of steps (S-2)-(S-6) of the instant claim (Kafi; page 175, Col. 2, paragraph 1; page 178, Fig. 3; page 179, Col. 1, paragraph 3).
Hack, Furniss, Robbins, Glover, and Kafi fail to explicitly teach the recited evaporator pressures in steps (S-2), (S-4), and (S-6), the recited composition of α,ω-C3-10 alkanediol mononitrate in steps (S-2) and (S-4), and the recited temperatures in steps (S-3) and (S-5) of the instant claim.
In spite of this deficiency, Robbins teaches distillation control variables that include flow rate, pressure, and temperature, and further teaches that the pressure in a distillation column has an overriding influence on the control of the process (Robbins; page 9, Section 2.3, Controlled Variables). In addition, Robbins teaches that if a distillation column is on manual control, then one improvement may be to install a temperature controller for the most responsive temperature point in the column to automatically shed many of the disturbances that come to the column, and online analyzers can be used for direct composition control (Robbins; page 65, paragraph 1, Optimizing Product Quality and Performance). Thus, the teachings of Robbins indicates that the pressures, distillate compositions, and temperatures recited in the instant claim represent fundamental distillation parameters that are routinely optimized by one of ordinary skill in the art and arrived at through routine experimentation. MPEP § 2144.05(II) states that “[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.”
Hack, Furniss, Robbins, Glover, and Kafi fail to teach the use of intermediate partial condensers that correspond to C1 and C3 in steps (S-3) and (S-5) of the instant claim, respectively.
However, this deficiency is remedied by Luyben, who teaches that partial condensers are used in distillations when the distillate product is removed as a vapor stream (Luyben; Abstract). In addition, Luyben teaches that this approach is commonly employed when there are very light components in the feed to the column that would require a high column pressure or a low condenser temperature to completely condense these very volatile components (Luyben; Abstract). Finally, Luyben teaches that the use of a partial condenser can avoid the use of costly refrigeration in the condenser (Luyben; Abstract).
The prior art taught by both Luyben and Robbins are in the overlapping technical field of purification using distillation systems. This technical field further overlaps with the teachings of Hack, Furniss, Glover, and Kafi described above, who teach methods relating to synthetic organic chemistry and chemical purification, including distillation and evaporator-based purification systems. The prior art is therefore deemed analogous art, as described in MPEP § 2141.01(a). As such, the skilled artisan would be sufficiently motivated to incorporate the teachings of Luyben s with that of Hack, Furniss, Robbins, Glover, and Kafi to arrive at an improved process (e.g., avoiding a high column pressure or a low condenser temperature) with a reasonable expectation of success. Such an endeavor would result in combining prior art elements according to known methods to yield predictable results, as described in MPEP § 2143(I)(A) and the use of known techniques to improve similar devices in the same way, as described in MPEP § 2143(I)(C).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Hack, Furniss, Robbins, Glover, and Kafi to incorporate the teachings of Luyben to implement the use of intermediate partial condensers that correspond to C1 and C3 in steps (S-3) and (S-5) of the instant claim, as taught by Luyben, and implement the evaporator pressures recited in steps (S-2), (S-4), and (S-6), the composition of α,ω-C3-10 alkanediol mononitrate recited in steps (S-2) and (S-4), and the temperatures recited in steps (S-3) and (S-5), as taught by Robbins and tractable through routine experimentation by the skilled artisan, to arrive at the claimed invention. The motivation to do so would permit the skilled artisan to pursue, with a reasonable expectation of success, an improved process that avoids a high column pressure or a low condenser temperature to completely condense volatile components and avoids the use of costly refrigeration in the condenser, as described above.
Claims 6-15 are rejected under 35 U.S.C. 103 as being unpatentable over Hack et al. (US 2010/0137599 A1; PTO-892 of 05-28-2025; hereinafter “Hack”), in view of Furniss et al. (Vogel’s Textbook of Practical Organic Chemistry (1989), pages 173 and 175; PTO-892 of 05-28-2025; hereinafter “Furniss”) and L. Robbins (Distillation Control, Optimization, and Tuning, 2011, pages 1-134; PTO-892 of 05-28-2025; hereinafter “Robbins”) as applied to claims 1 and 3-4 above and further in view of Thalluri et al. (RSC Adv. 2012, 2, 6838-6845; PTO-892 of 05-28-2025; hereinafter “Thalluri”), Howard et al. (US 3,214,347; PTO-892 of 05-28-2025; hereinafter “Howard”), N. G. Anderson (Practical Process & Research Development, 5th ed, 2000, pages 117-118; PTO-892 of 05-28-2025; hereinafter “Anderson”), Luyben et al. (Ind. Eng. Chem. Res. 2004, 43, 384-396; PTO-892 of 05-28-2025; hereinafter “Luyben-2”), Wuts et al. (Greene’s Protective Groups in Organic Synthesis, 4th ed, 2007, page 554; PTO-892 of 05-28-2025; hereinafter “Wuts”), and Wernik et al. (Org. Proc. Res. Dev. 2019, 23, 1359-1368; PTO-892 of 05-28-2025; hereinafter “Wernik”).
Regarding claim 6 depending from claim 1, Hack teaches a process for the preparation of 4-nitrooxybutan-1-ol (a α,ω-C4 alkanediol mononitrate), as detailed above (Hack; claim 1; paragraph [0159], Example 3), wherein the process further comprises the preceding consecutive steps of acylation of 1,4-butanediol (a α,ω-C4 alkanediol) with butyric acid, continuous nitrate ester formation via reaction of 1,4-butanediol monobutyrate (a α,ω-C4 alkanediol monoacylate) with a nitrating agent (H2SO4 and HNO3), and hydrolysis of 4-nitrooxybutan-1-ol butyrate (a α,ω-C4 alkanediol mononitrate monoacylate) by continuously feeding a base into a solution of 4-nitrooxybutan-1-ol butyrate and aqueous methanol to obtain a solution comprising aqueous methanol and 4-nitrooxybutan-1-ol (Hack; paragraph [0154], Example 1; paragraph [0160], Example 4; paragraph [0161], Example 5).
Regarding step (A) of the instant claim, Hack fails to teach an acylation comprising the step of re-feeding recycled reaction components comprising α,ω-C3-10alkanediol, α,ω-C3-10alkanediol monoacylate and α,ω-C3-10alkanediol diacylate back into said acylation reaction and with the proviso that in the acylation reaction per mole recycled acylate groups 0.5 to 1.5 mole of water is added and that the molar ratio of the (molar) sum of the acylating agent, α,ω-C3-10alkanediol monoacylate and 2 times of α,ω-C3-10alkanediol diacylate to the sum of the α,ω-C3-10alkanediol, α,ω-C3-10alkanediol monoacylate and α,ω-C3-10alkanediol diacylate is selected in the range from 0.5 to 1.1 mol per mol of α,ω-C3-10alkanediol to obtain a α,ω-C3-10alkanediol monoacylate.
However, Thalluri teaches waste reduction in amide synthesis based on recycling of the reaction mixture, wherein a major portion of the product is separated out and the homogeneous reaction mixture as a whole is reused in the same pool, resulting in drastic waste reduction (Thalluri; Title; Abstract; page 6838, Col. 1, paragraph 1). Thus, one of ordinary skill could deduce that the teachings of Thalluri could be applied to the method of Hack with a reasonable expectation of success to realize a process with improved waste reduction by re-feeding recycled reaction components.
Regarding the addition of water to the recycled reaction components as recited in step (A) of the instant claim, the acylation method taught by Hack utilizes butyric acid as the acylation reagent (Hack; paragraph [0154], Example 1). To this end, Howard teaches an azeotropic distillation process comprising water-miscible carboxylic acids which form azeotropes with water (Howard; Title; Col. 1, lines 20-23). Of particular note, Howard teaches that the boiling point of an azeotropic mixture of n-butyric acid (pure boiling point = 164.0 ºC) and water (pure boiling point = 100.0 ºC) is 99.4 ºC (Howard; Col. 5 and Col. 6, Table). Thus, one of ordinary skill could deduce that the teachings of Howard could be applied to the method of Hack to introduce water with the recycled reaction components such that the subsequent purification step could be facilitated at a lower temperature due to a lower boiling point of the butyric acid/water mixture.
Regarding the molar ratio recited in step (A) of the instant claim corresponding to the amount of added acylation agent to the recycled reaction mixture, Anderson teaches that the charges of reagents, starting materials, and solvents to reactions are minimized to decrease the cost of inputs and to optimize vessel throughput (Anderson; page 117; paragraph 3). Anderson further teaches that minimizing these charges also decreases operating times by decreasing the amount of time needed to add these components, to remove solvents by distillation, and to neutralize reactive components, and waste disposal costs are also decreased by minimizing charges of reaction components; thus, this consideration can have considerable impact on overall product cost and productivity (Anderson; page 117; paragraph 3). Finally, Anderson teaches that undercharging reagents can lead to increased impurities; in general, 1.02-1.2 equivalents are often charged in order to reach suitably rapid reactions, and additional equivalents will be needed if there is more than one reactive group in the molecules (Anderson; page 117; paragraph 4; page 118, paragraph 1). Overall, the teachings of Anderson indicates that the recited molar ratio could reasonably be surmised through routine optimization of synthetic processes by one of ordinary skill in the art. MPEP § 2144.05(II) states that “[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.”
Regarding step (B) of the instant claim, Hack fails to teach an inert solvent in a group of pieces of equipment comprising at least two reactors in series by simultaneously feeding said solution into the first and the second reactor to obtain the respective α,ω-C3-10alkanediol mononitrate monoacylate. Instead, Hack teaches a continuous nitrate ester formation step that is run under neat conditions, without inert solvent (Hack; paragraph [0160], Example 4). However, the analogous batch reaction for nitrate ester formation taught by Hack uses dichloromethane solvent (paragraph [0155], Example 2). Furthermore, Hack teaches that the nitration is preferably carried out by contacting the nitration mixture in a chlorinated solvent at -10 C with a solution of 1,4-butanediol monoester in the same chlorinated solvent or even neat in continuous processing (Hack; paragraphs [0040] and [0089]). Therefore, one of ordinary skill in the art could reasonably apply the batch nitrate ester formation reaction conditions comprising dichloromethane as inert solvent taught by Hack to the corresponding continuous process taught by Hack to arrive at this claim limitation.
Regarding the claim limitation of at least two reactors in series by simultaneously feeding said solution into the first and the second reactor to obtain the respective α,ω-C3-10alkanediol mononitrate monoacylate recited in step (B) of the instant claim, Hack teaches a continuous nitration process comprising the addition of nitrating agent (approx.. 10-12 l/h) and 1,4-butanediol monobutyrate (approx. 2.4 kg/h) as two reaction streams that are mixed in a static mixer and cooled in a heat exchanger, but fails to teach the addition of nitrating agent and monoacylate into a first and second reactor in series. However, Luyben-2 teaches that advocates of inherently safer process design have promoted “intensification” as a way to reduce the amounts of dangerous chemicals contained in a process; the idea is to design equipment to minimize the inventory of hazardous material so that the safety and environmental consequences of loss of containment are reduced in the event of a large leak from the process equipment (Luyben-2; Abstract). Of particular note, Luyben-2 teaches a benzene nitration reactor process example that compares one large continuous stirred tank reactor (CSTR) with two smaller CSTR reactors in series, wherein the feed streams and the product streams leaving the two systems are exactly the same (Luyben-2; page 387, Col. 2, paragraph 3; page 389, Figure 5). Luyben-2 teaches that the two-CSTR process is much superior because: (1) the inventory of hazardous materials is smaller; (2) the size of the equipment is much smaller, which results in a lower capital cost; and (3) less coolant is required although the total heat removal is the same (Luyben-2; page 390, Col. 1, paragraph 1). Therefore, one of ordinary skill in the art would be reasonably motivated to incorporate the two-reactor system taught by Luyben-2 to the continuous nitrate ester formation method of Hack to arrive at this claim limitation.
Regarding step (C) of the instant claim, Hack fails to teach a two-phase hydrolysis, continuously feeding a base and a solution comprising the α,ω-C3-10alkanediol mononitrate monoacylate and an inert solvent into a stirred cascade reactor. However, Wuts teaches that under normal circumstances, methyl esters are readily cleaved by alkali metal hydroxides or carbonates in an aqueous/organic solvent mixture (Wuts; page 554, last paragraph). Thus, given the ubiquitous nature of this reaction method in the prior art, as taught by Wuts, one of ordinary skill could arrive at a two-phase hydrolysis method from the teachings of Hack through routine optimization. MPEP § 2144.05(II) states that “[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.”
Regarding the claim limitation of continuously feeding a base and a solution comprising the α,ω-C3-10alkanediol mononitrate monoacylate recited in step (C) of the instant claim, Hack teaches continuously feeding a base into a solution of 4-nitrooxybutan-1-ol butyrate and aqueous methanol to obtain a solution comprising aqueous methanol and 4-nitrooxybutan-1-ol (Hack; paragraph [0161], Example 5). One of ordinary skill would reasonably deduce that the method of Hack and the instantly claimed method provide the same results but merely differ by their order of process steps. MPEP § 2144.04(IV) states that the “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results.”
Regarding the claim limitation of a stirred cascade reactor as recited in step (C) of the instant claim, Wernik teaches the design and optimization of a continuous stirred tank reactor (CSTR) cascade for the production of diazomethane for the synthesis of α-chloroketones (Wernik; Title; page 1363, Scheme 4; page 1365, Scheme 5). Wernik further teaches that the CSTR cascade entails the advantage of a dramatically decreased residence time in each CSTR, and compared to a tube-in-tube reactor, the productivity could be increased by a factor of 4.2, and the use of CSTR cascades is among the cheapest and best-understood ways to provide the required contact time (Wernik; page 1365, Col. 1, paragraph 1; page 1366, Col. 1, paragraph 2 and Col. 2, paragraph 2). Therefore, one of ordinary skill in the art would be motivated to apply the CSTR cascade reactor set up to the corresponding continuous process taught by Hack with a reasonable expectation of success and arrive at this claim limitation.
The prior art taught by Thalluri, Howard, Anderson, Luyben-2, Wuts, and Wernik are in the overlapping technical fields of chemical synthesis, process development, and purification using distillation systems. These technical fields further overlap with the teachings of Hack, Furniss, and Robbins described above, who teach methods relating to synthetic organic chemistry and chemical purification via distillation-based techniques. The prior art is therefore deemed analogous art, as described in MPEP § 2141.01(a). As such, the skilled artisan would be sufficiently motivated to incorporate the teachings of Thalluri, Howard, Anderson, Luyben-2, Wuts, and Wernik with the method of Hack, Furniss, and Robbins to arrive at an improved process (e.g., decreasing costs and increasing productivity) with a reasonable expectation of success. Such an endeavor would result in combining prior art elements according to known methods to yield predictable results, as described in MPEP § 2143(I)(A) and the use of known techniques to improve similar devices in the same way, as described in MPEP § 2143(I)(C).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Hack, Furniss, and Robbins to incorporate the teachings of Thalluri, Howard, Anderson, Luyben-2, Wuts, and Wernik to implement an acylation comprising the step of re-feeding recycled reaction components comprising α,ω-C3-10alkanediol, α,ω-C3-10alkanediol monoacylate and α,ω-C3-10alkanediol diacylate back into said acylation reaction and with the proviso that in the acylation reaction per mole recycled acylate groups 0.5 to 1.5 mole of water is added and that the molar ratio of the (molar) sum of the acylating agent, α,ω-C3-10alkanediol monoacylate and 2 times of α,ω-C3-10alkanediol diacylate to the sum of the α,ω-C3-10alkanediol, α,ω-C3-10alkanediol monoacylate and α,ω-C3-10alkanediol diacylate is selected in the range from 0.5 to 1.1 mol per mol of α,ω-C3-10alkanediol to obtain a α,ω-C3-10alkanediol monoacylate, in a manner consistent with step (A) of the instant claim; implement an inert solvent in a group of pieces of equipment comprising at least two reactors in series by simultaneously feeding said solution into the first and the second reactor to obtain the respective α,ω-C3-10alkanediol mononitrate monoacylate, in a manner consistent with step (B) of the instant claim; and implement a two-phase hydrolysis, continuously feeding a base and a solution comprising the α,ω-C3-10alkanediol mononitrate monoacylate and an inert solvent into a stirred cascade reactor, in a manner consistent with step (C) of the instant claim. The motivation to do so would permit the skilled artisan to pursue, with a reasonable expectation of success, a process with improved waste reduction, facilitating a simpler purification via the introduction of a lower boiling butyric acid/water mixture, decreasing the cost of inputs and optimizing vessel throughput, reducing the inventory of hazardous materials and lowering capital cost, and obtaining a highly productive cascade reactor system with dramatically reduced residence time that is cost-effective, as described above.
Regarding claim 7 depending from claim 6, Wernik teaches a continuous stirred tank reactor (CSTR) cascade with one or two vessels that impart the advantage of a dramatically reduced residence time with high productivity, as detailed above (Wernik; Title; page 1363, Scheme 4; page 1365, Scheme 5; page 1365, Col. 1, paragraph 1; page 1366, Col. 1, paragraph 2). Therefore, as with claim 6, it would have been prima facie obvious to combine Hack, Furniss, and Robbins with Thalluri, Howard, Anderson, Luyben-2, Wuts, and Wernick to implement a vessel cascade set-up to the acylation step (A) and arrive at the claimed invention.
Regarding claim 8 depending from claim 6, Hack teaches the preparation of a 1,4-butanediol monoester, wherein the isolated 1,4-butanediol monoester contains a percentage of 1,4-butanediol below 1%, preferably below 0.5% (Hack; paragraphs [0026] and [0037]). Furthermore, Hack teaches that the ratio of monoester/diester in the crude mixture is higher than 95% (Hack; paragraph [0025]); this can also be interpreted as an amount of diacylate of less than 5 wt.%. Both of these recited ranges overlap with the ranges recited in the instant claim. MPEP § 2144.05(I) states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”
Regarding claim 9 depending from claim 6, teaches the preparation of a 1,4-butanediol monoester comprising reacting an excess of 1,4-butanediol with an acid of formula R-C(O)OH wherein R is a linear or branched (C3-C5) alkyl chain (Hack; claim 1). Furthermore, Hack teaches reaction examples with several different acylation agents, including butyric acid, acetic acid, and propionic acid (Hack; paragraphs [0154] and [0163]-[0164]).
Regarding claim 10 depending from claim 6, Hack teaches hydrolysis of 4-nitrooxybutan-1-ol butyrate (a α,ω-C4 alkanediol mononitrate monoacylate) by continuously feeding a base into a solution of 4-nitrooxybutan-1-ol butyrate and aqueous methanol to obtain a solution comprising aqueous methanol and 4-nitrooxybutan-1-ol, as detailed above (Hack; paragraph [0161], Example 5). Furthermore, the utilization of two reactors is rendered obvious in view of the teachings of Luyben-2 as detailed in the rejection of instant claim 6 above. Although Hack fails to teach the mass flow of the solution into the first reactor is selected in the range of 40 to 60% of the total mass flow of the solution, while the remaining solution is fed into the second reactor, Hack does teach that the hydrolysis reaction comprises the portionwise addition of the aqueous solution of the base to a solution of the 4-nitrooxybutan-1-ol monoester (Hack; paragraph [0056]). Therefore, one of ordinary skill could arrive at similar mass flows through routine experimentation. MPEP § 2144.05(II) states that “[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.”
Regarding claim 11 depending from claim 6, Hack teaches a continuous nitrate ester formation step that is run under neat conditions, without inert solvent (Hack; paragraph [0160], Example 4). However, the analogous batch reaction for nitrate ester formation taught by Hack uses 0.624 mol of 1,4-butanediol monobutyrate and 100 mL of dichloromethane (paragraph [0155], Example 2). These quantities correspond to 100 grams of 1,4-butanediol monobutyrate and 133 grams of dichloromethane, respectively, from which a 43 wt.-% concentration of monoacylate can be calculated. This value resides squarely within the concentration range recited in the instant claim. Furthermore, Hack teaches that the nitration is preferably carried out by contacting the nitration mixture in a chlorinated solvent at -10 C with a solution of 1,4-butanediol monoester in the same chlorinated solvent or even neat in continuous processing (Hack; paragraphs [0040] and [0089]). Therefore, one of ordinary skill in the art could reasonably select the 43 wt.-% concentration of monoacylate taught by Hack in the batch nitrate ester formation reaction comprising dichloromethane as an inert solvent and readily apply it to the corresponding continuous process also taught by Hack. Therefore, as with claim 6, it would have been prima facie obvious to combine Hack, Furniss, and Robbins with Thalluri, Howard, Anderson, Luyben-2, Wuts, and Wernick and arrive at the claimed invention.
Regarding claim 12 depending from claim 6, Hack teaches a ratio of equivalents of HNO3 to 1,4-butanediol monoester of 1.1 to 1.6:1 (Hack; paragraph [0092]). This range overlaps with the range recited in the instant claim. MPEP § 2144.05(I) states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.” Furthermore, Hack teaches a ratio of equivalents of H2SO4 and HNO3 of preferably from 5.6:1 to 3:1. The latter range 3:1, also interpreted as a mole ratio of 3, is reasonably close to the instantly claimed range of 1.5 to 2.5 as to render the instant claim obvious. MPEP § 2144.05(I) states that “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
Regarding claim 13 depending from claim 6, Wernik teaches that the continuous stirred tank reactor(s) (CSTR) are operated in a vertical arrangement (Wernik; page 1363, Scheme 4; page 1365, Scheme 5).
Regarding claims 14-15 depending from claim 6, Hack teaches a hydrolysis step of 4-nitrooxy-butan-1-ol butyrate wherein the inorganic base is an aqueous solution of sodium hydroxide or potassium hydroxide or lithium hydroxide; preferably a solution of sodium hydroxide 10% to 30% (Hack; paragraph [0106]). This range of concentration of base overlaps significantly with the range recited in the instant claim. MPEP § 2144.05(I) states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”
Claims 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Hack et al. (US 2010/0137599 A1; PTO-892 of 05-28-2025; hereinafter “Hack”), in view of Furniss et al. (Vogel’s Textbook of Practical Organic Chemistry (1989), pages 173 and 175; PTO-892 of 05-28-2025; hereinafter “Furniss”).
Regarding claim 16 and claim 17 depending from claim 16, Hack teaches a process for the preparation of 4-nitrooxybutan-1-ol via the hydrolysis of 4-nitrooxy-butan-1-ol butyrate, wherein the reaction solvent was completely was removed completely by vacuum distillation. The 4-nitrooxybutan-1-ol compound taught by Hack is a α,ω-C4 alkanediol mononitrate and is thus a species that reads on the instantly claimed genus, a α,ω-C3-10 alkanediol mononitrate (Hack; claim 1; paragraph [0159], Example 3). In addition, Hack teaches the complete removal of methanol solvent by distillation, wherein the methanol amount as checked by GC is 0.04% relative to 4-nitrooxybutan-1-ol, and the 4-nitrooxybutan-1-ol has a purity according to GC of 99.7%. (Hack; paragraph [0159], Example 3). These values reside within the ranges recited in instant claims 16-17. MPEP § 2144.05(I) states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”
Hack fails to teach a distillation comprising partial condensation and continuous back-feeding of fractions comprising mixtures of inert solvent and α,ω-C3-10alkanediol mononitrate into said distillation. However, Furniss teaches that unless the boiling points of the components of a mixture are widely different it is usual to employ a fractionating column to attempt the separation of liquid mixtures by distillation wherein a fractionating column consists essentially of a long vertical tube through which the vapor passes upward and is partially condensed; the condensate flows down the column and is returned eventually to the flask (Furniss; page 173, paragraphs 3-4). In addition, Furniss details the theory of fractionation and the enhancement of efficiency by virtue of increasing the number or theoretical plates, and Furniss further teaches that the ultimate aim in the design of efficient fractionating columns is to reduce the proportion of the intermediate fractions to a minimum (Furniss; page 175, paragraph 4 and page 176, paragraphs 1-2).
The prior art taught by both Hack and Furniss described above are in the overlapping technical fields of synthetic organic chemistry and chemical purification. The prior art is therefore deemed analogous art, as described in MPEP § 2141.01(a). Moreover, the methods regarding fractional distillation as taught by Furniss are routinely practiced by the skilled artisan. As such, one of ordinary skill in the art would be sufficiently motivated to incorporate the teachings of Furniss into the distillation method of Hack to arrive at the instantly claimed process with a reasonable expectation of success. Such an endeavor would result in combining prior art elements according to known methods to yield predictable results, as described in MPEP § 2143(I)(A) and the use of known techniques to improve similar devices in the same way, as described in MPEP § 2143(I)(C).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the distillation method of Hack to incorporate a fractionating column to enable partial condensation and continuous back-feeding of fractions comprising mixtures of inert solvent and α,ω-C3-10alkanediol mononitrate into said distillation. The motivation to do so would permit the skilled artisan to pursue, with a reasonable expectation of success, a process that improves the separation efficiency and reduces the proportion of intermediate fractions to a minimum, as described above.
Regarding claim 18 depending from claim 17, although Example 3 of Hack does not expressly teach wherein the inert solvent is a halogenated solvent, Hack does teach that the residual solution containing 4-nitroxybutan-1-ol can be subjected to a subsequent purification process comprising one or more extractive cycles with a chlorinated organic solvent immiscible with water (Hack; claim 11; paragraphs [0063]-[0067]). Thus, one of ordinary skill in the art could reasonably select a chlorinated solvent (preferably dichloromethane; c.f., Hack, paragraph [0052]) as an inert solvent and readily apply it to the corresponding distillation process of Hack. Therefore, as with claim 16, it would have been prima facie obvious to combine Hack and Furniss to arrive at the claimed invention.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success of arriving at the instantly claimed method. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Response to Arguments
Claim Rejections - 35 USC § 103
Applicant's arguments filed 28 August 2025, asserting that the pending claims are patentably distinguishable over all applied references of record, have been fully considered but they are not persuasive.
Applicant argues the following:
“Applicant notes in this regard that pending independent claim 1 requires that the fractions comprising mixtures of the inert solvent and α,ω-C3-10 alkanediol mononitrate are back-fed into the distillation of step (a) via an inlet stream. Thus, claim 1 clarifies that there is no condensate returned to the evaporator via the outlet, as would occur in a reflux system.
By recycling the mixture back to the evaporator via the inlet stream according to the claimed invention, the residence time of the mixture in a heated environment is minimized thereby improving the safety of the process and the stability of the product. In contrast, Furniss et al describe a batch process in which the condensation is performed by reflux using a column, which returns the mixture to the flask via the outlet and thereby prolongs the exposure of the mixture to elevated temperature.
Thus, an ordinarily skilled person in this art would not reasonably arrive at the presently claimed invention by combining Furniss et al with Hack et al. The remaining applied references fail to cure the deficiencies of the combination of Hack et al and Furniss et al as noted above. As such, withdrawal of all rejections advanced against the prior pending claims under 35 USC §103 is therefore in order.”
This argument has been fully considered, but is not found to be persuasive. In particular, Applicant’s claim that amended “claim 1 clarifies that there is no condensate returned to the evaporator via the outlet, as would occur in a reflux system” is not persuasive. Although Applicant refers to Figure 4 for support of the amendment in the response filed 28 August 2025, the written describes Figure 4 as an exemplary, non-limiting evaporator setup for the removal and recovery of the inert solvent (Specification; page 20, paragraph 3). Furthermore, the term “inlet stream” is not clearly defined in the written description, and therefore the broadest reasonable interpretation of the term “inlet stream” is being be interpreted as any one of the feed streams, boilup streams, or reflux streams entering the distillation column, as evidenced by L. Robbins (c.f., pages 8-9, Section 2.1: Distillation Column Inlet Stream, in Distillation Control, Optimization, and Tuning, 2011, pages 1-134). See MPEP § 2111. Thus, as detailed in the new 103 rejection above, although Furniss does not explicitly recite the term “the continuous back-feeding of fractions into the distillation of step (a) via an inlet stream”, as recited in claim 1, the skilled artisan could reasonably interpret the condensate flowing down the column and returned to the flask as taught by Furniss as an inlet stream, in a manner consistent with the instant claim.
Regardless, Applicant’s alleged interpretation of “inlet stream” in amended claim 1 is sufficiently addressed by Robbins, as detailed in the new 103 rejection above. Robbins teaches that inlet and outlet stream flow rates are the manipulated variables in distillation column control and is usually the stream that has an automatic valve connected to a controller output signal (Robbins; page 8, paragraph 1 and Figure 2.1). Figure 2.1 of Robbins shows that separate inlet stream from the distillate can be controlled via a valve to adjust the amount recycled back to the distillation column, and the flow rates of the distillate and bottoms streams change as necessary to maintain the material balance and achieve the target compositions (Robbins; page 8, Figure 2.1 and page 25, paragraph 4). Thus, the skilled artisan would recognize from the teachings of Robbins that a separate inlet stream enables an improved method of distillation control. The methods regarding fractional distillation as taught by Furniss and the methods of controlling the inlet stream of the distillate as taught by Robbins are routinely practiced by the skilled artisan. As such, one of ordinary skill in the art would be sufficiently motivated to incorporate the teachings of Furniss and Robbins into the method of Hack to arrive at the instantly claimed process with a reasonable expectation of success. Such an endeavor would result in combining prior art elements according to known methods to yield predictable results, as described in MPEP § 2143(I)(A) and the use of known techniques to improve similar devices in the same way, as described in MPEP § 2143(I)(C). Therefore, the new claim rejections are maintained for the reasons of record and the reasons set forth above.
Conclusion
No claims are allowed.
Applicant’s amendment under 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p) on 28 August 2025 necessitated and prompted 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 extension fee 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 Derek Rhoades whose telephone number is (703)-756-5321. The Examiner can normally be reached Monday–Thursday, 7:30 am-5:00 pm EST; Friday, 7:30 am-4:00 pm EST.
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/D.R./Examiner, Art Unit 1692
/AMY C BONAPARTE/Primary Examiner, Art Unit 1692
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