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 .
Notice of Priority
This applications claims priority for U.S. Provisional Application 63/046,123 filed 30 June 2020.
DETAILED ACTION
Information Disclosure Statement
The Information Disclosure Statements (IDS) filed on:
28 January 2025
29 April 2025
20 February 2026
30 June 2026
have been considered by the Examiner.
Claim Status
Examiner acknowledges Applicant’s cancellation of Claim(s) 1-21.
Examiner acknowledges Applicant’s introduction of Claim(s) 22-30.
Claim(s) 22-30 are examined on the merits herein.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 29, citing reference to “Formula (1)” and “Formula (2)” are interpreted inasmuch as they pertain to compounds of Formula (1) and Formula (2), below:
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as described in the Specification [pg. 5; lines 06-15].
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 29 is 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.
In regards to Claim 29, the mentioned claim cites reference to “reacting the compound of Formula (1) and the compound of Formula (2)”, but fails to provide the identity of Formula(s) (1) and (2) in the claim. As a result, the metes and bounds of the claim are unclear for which compounds are being referenced. There are found, however, compounds corresponding to Formula(s) (1) and (2) in the Specification [pg. 5; lines 06-15], but it is unclear from the claim language whether those are the compounds being referenced in the claim.
Therefore, Claim 29 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. For the sake of compact prosecution, compounds corresponding to Formula(s) (1) and (2) will be interpreted as they are found in the Specification [pg. 5; lines 06-15].
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(g)(1) during the course of an interference conducted under section 135 or section 291, another inventor involved therein establishes, to the extent permitted in section 104, that before such person’s invention thereof the invention was made by such other inventor and not abandoned, suppressed, or concealed, or (2) before such person’s invention thereof, the invention was made in this country by another inventor who had not abandoned, suppressed, or concealed it. In determining priority of invention under this subsection, there shall be considered not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice, from a time prior to conception by the other.
Claim(s) 22-23, 26, 28, and 30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated Levin (Filed: 18 June 2018; US 2018/0360975 Al; henceforth Levin).
Levin teaches a method to make the drug candidate CV-8972 from two smaller starting materials, 2,3,4-trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol to produce a precursor molecule having free base and salt forms. In context to this molecule, the Instant specification teaches the structure of CV-8814 to be the free base form, below [pg. 7; lines 04-09]:
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and also teaches conversion of the free base form of this molecule to the salt form to be reversible [Specification; pg. 2; lines 09-10] in order to convert back to the free base for subsequent production of CV-8972 [Specification; pg. 2; lines 06-08]. Therefore, free base CV-8814 is not treated as an intermediate in this series, but rather as the final product of the coupling, which is then used for producing the mutually disclosed CV-8972 molecule. Accordingly, in teaching the production of free base CV-8814, Levin meets several requirements of the Instant invention.
On pg. 25 par. [0254], Levin teaches the following synthetic scheme, below:
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Briefly, the compounds (1) and (2) undergo reductive amination in the presence of sodium triacetoxyborohydride (STAB) at room temperature, to produce the free base compound (3) that matches the structure of Formula (IX) of the Instant claims.
In regards to the mentioned claims, this synthetic scheme meets the limitations for the reaction of 2,3,4-trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol to produce a free base form of the compound of Formula (IX) (Inst. Cl. 22) using sodium triacetoxyborohydride (Inst. Cl. 23) and performed at from about 15°C to about 25°C (Inst. Cl. 26), also excluding both the production of a salt form of the compound of Formula (IX) (Inst. Cl. 28) and the use of either dioxane, ethylacetate, or potassium carbonate (Inst. Cl. 30).
Therefore, Claim(s) 22-23, 26, 28, and 30 are rejected under 35 U.S.C. 102(a)(2).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
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) 24-25, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Levin (cited above), as also applied to Claim(s) 22-23, 26, 28, and 30, in view of the Organic Chemistry Portal (Published: 21 September 2019; https://www.organic-chemistry.org/abstracts/literature/717.shtm; accessed via Wayback Machine; henceforth OCP), Pace et al (Published: 07 August 2012; Pace V, et al. 2-Methyltetrahydrofuran (2-MeTHF): A Biomass-Derived Solvent with Broad Application in Organic Chemistry. ChemSusChem 2012, 5, 1369 – 1379; henceforth Pace) and Anderson (Published: 2012; Anderson NG, Practical Process Research and Development: A guide for Organic Chemists, 2nd ed., Academic Press, 2012).
Levin teaches as described above. However, Levin does not teach the use of acetic acid or 2-methyltetrahydrofuran (MeTHF) in the synthesis of Formula (IX). Levin also does not teach the exclusion of dichloromethane (DCM) from the synthesis of Formula (IX) or the solvent exchange and recrystallization of Formula (IX) in the presence of MTBE and heptane.
The OCP provides reaction schematics and an abstract for Abdel-Magid et al (Published: 1996; Abdel-Magid AF, et al. Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures. J. Org. Chem., 1996, 61, 3849-3862; provided), wherein Abdel-Magid teaches reaction conditions for various reductive amination reactions between aldehydes/ketones and amines, utilizing STAB, acetic acid, and tehtrahydrofuran (THF). In their schematics, OCP teaches the following scheme, below:
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For reactions involving methoxybenzaldehydes and anilines, below:
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In doing so, OCP meets several requirements of the Instant invention. In regards to Claim 24, OCP meets the limitation of the reductive amination reaction comprising acetic acid. In regards to Claim 27, OCP meets the limitation of the reductive amination reaction not comprising dichloromethane by teaching the use of THF as a solvent to couple the m-methoxybenzaldehyde to aniline at over 85% yield [pg. 1]. Yet, while teaching the use of THF, the OCP reference does not cite the use of MeTHF in the reaction.
Pace teaches the use of MeTHF as a sustainable substitute for common organic solvents (i.e. THF) in acidic conditions. In doing so, Pace addresses several limitations of the Instant invention. In regards to Claim 25, Pace meets the limitation for the reductive amination to comprise the MeTHF by teaching that water-miscible cyclic-ether-based solvents (e.g., THF) are not stable in acidic aqueous conditions, as and degraded by ring opening, further adding teaching that replacing THF with MeTHF is advantageous due to the low miscibility of MeTHF with water, creating a biphasic system and preserving MeTHF from the acidic hydrolytic action [pg. 1370; Section 2: Stability of 2-MeTHF in Acidic Conditions].
Anderson teaches industrial-scale methods of recrystallizing ketones that utilizes MTBE and heptane. In doing so, Anderson meets several limitations of the Instant invention. In regards to Claim 29, Anderson teaches the “solvent chasing” of a rich acetonitrile extract of ketones using MTBE as a low boiling point solvent to effectively replace the solvent acetonitrile with MTBE prior to recrystallization of the free base [pg. 224-225; Section VII: SIMPLE PROCEDURES; par. 2; also Figure 8.10], followed by 2:1 addition of heptane to the rich MTBE extract of ketones, below:
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A prima facie case of obviousness can be made for one of ordinary skill in the art to start with Levin’s reaction scheme that produces the free base compound in DCM/STAB, and replace that system with AcOH/THF/STAB as taught by the OCP for reductive amination reactions. Next, in anticipating hydrolysis of the THF solvent in the presence of AcOH, as well as the poorer aqueous miscibility of the free base compound as compared to the salt, the artisan may include the teachings of Pace to solve both of these problems by simply replacing THF with MeTHF. Furthermore, the artisan may include the teachings of Anderson to recrystallize the free base form by “solvent chasing” replacement using MTBE and recrystallization from MTBE/heptane. One of the ordinary skill in the art would be motivated to combine these teachings as they are cited to be effective methods for conducting/purifying reductive amination reactions and isolating free base product forms, and would be met with a high expectation of success given the over 85% yields for both THF-based reactions of methoxybenzaldehydes and recrystallization of free bases using MTBE/heptane. As a result, the reproduction of the Instant invention would already be possible before the effective filing date the Instant application.
Therefore, Claim(s) 24-25, 27, and 29 are rejected under 35 U.S.C. 103.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim(s) 22-30 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-6 and 20 of U.S. Patent No. 11,780,811 (Published: 10 October 2023; henceforth ‘811) and claims 1, 9-11, and 13-14 of U.S. Patent No. 12,110,275 (Published: 08 October 2024 ; henceforth ‘275).
In regards to Claim 22, reacting 2,3,4-trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol to produce a free base form of the compound of Formula (IX) is claimed by both ‘811 [Col. 20; Cl.1; lines 02-14] and ‘275 [Col. 20-21; Cl. 1; lines 46-67, 1-14].
In regards to Claim 23, the step of reacting 2,3,4- trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol comprising sodium triacetoxyborohydride is claimed by both ‘811 [Col. 20; Cl.2; lines 20-22] and ’275 [Col. 20-21; Cl. 1; lines 46-67, 1-14].
In regards to Claim 24, the step of reacting 2,3,4- trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol comprising acetic acid is claimed by both ‘811 [Col. 20; Cl.3; lines 23-25] and ‘275 [Col. 20-21; Cl. 1; lines 46-67, 1-14].
In regards to Claim 25, the step of reacting 2,3,4- trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol comprising 2-methyltetrahydrofuran is claimed by both ‘811 [Col. 20; Cl.4; lines 26-28] and ‘275 [Col. 20-21; Cl. 1; lines 46-67, 1-14].
In regards to Claim 26, the step of reacting 2,3,4- trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol being performed at from about 15°C to about 25°C is claimed by both ‘811 [Col. 20; Cl.5; lines 29-31] and ‘275 [Col. 22; Cl. 9; lines 18-20].
In regards to Claim 27, the step of reacting 2,3,4- trimethoxybenzaldehyde and 2-(piperazin-1-yl)ethan-1-ol not comprising dichloromethane is claimed by both ‘811 [Col. 20; Cl.6; lines 32-34] and ‘275 [Col. 22; Cl. 10; lines 21-23].
In regards to Claim 28, the method not comprising the production of a salt form of the compound of Formula (IX) is claimed by ‘275 [Col. 22; Cl. 13; lines 34-36].
In regards to Claim 29, the further comprisal of a solvent exchange to Methyl tert- Butyl Ether (MTBE), and recrystallization from MTBE/n-heptane after the step of reacting the compound of Formula (1) and the compound of Formula (2) is complete to form the free base form of a compound of Formula (IX) is claimed by ‘275 [Col. 22; Cl. 11; lines 24-29].
In regards to Claim 30, exclusion of dioxane, ethylacetate, or potassium carbonate from the method is claimed by both ‘811 [Col. 21; Cl.20; lines 17-19] and ‘275 [Col. 22; Cl. 14; lines 37-39].
Although the claims at issue are not identical, they are not patentably distinct from each other because the process of producing Formula (IX) of the Instant claims is embedded within the processes of producing Formula (X) in the referenced patents, and is similarly claimed therein.
Therefore, Claim(s) 22-30 are rejected as double patenting.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STANLEY BRAM whose telephone number is (571)272-8779. The examiner can normally be reached 7:30 - 5:00.
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/STANLEY BRAM/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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