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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to chiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts thereof; and Compound I-1 (wherein R1 is morpholinyl; R2 is H; R3 is Bn; R4 is Ph; as shown in Embodiment 3) as the elected compound species, in the reply filed on April 20, 2026 is acknowledged. The traversal is on the ground(s) that the groups of inventions shares the “same special technical feature”; and the groups of species share the same general structure formula defined in the Markush form, thus, will not impose a serious search burden. In summary, Applicant argues Inventions I and II are not distinct, and there are no alternative method known in the art to prepare the formula (I) instantly claimed; inventions I and III share the same technical feature, the claimed method drawn to treating depression cannot be practiced using any other compound(s) with significantly different structure, and the “shelf-stability test” stated in the previous Office Action is unrelated without specific use; Invention II and III are not distinct, because without obtaining the compound, one cannot use said compound. This is not found persuasive, because of the following reasons: first, instant application is a continuation of a PCT application, thus, unity of invention is not a standard to determine whether the groups of inventions are independent and distinct under U.S. restriction practice. While the Examiner acknowledged Applicant cited the foreign application CN115368363 A, which applicant indicates said reference is the parent of instant application, it is respectfully noted that the Examiner is not required to provide prior art(s) and search report to demonstrate distinction between the groups of inventions and the groups of species under U.S. restriction practice. As stated in the previous Office Action mailed on January 20, 2026, the groups of inventions I and II, I and III, and I and III are shown to be distinct if one of the recited condition(s) is meet. Applicant’s assertion that one cannot synthesize the claimed compound using any alternative routes known to those skilled in the art, such as using compound having the structure of compound 5 and 6 (see previous Office Action) as a starting material rather than the claimed raw material, this appears to be mere argument without supporting evidence; said evidence is respectfully requested. In addition, Applicant clearly indicates using claimed compound for self-stability test is entirely different from the claimed use (see p. 18, first paragraph in the reply), and that clearly supports the product as claimed can be used in a “materially different” process. It is noted that applicant’s asserts there is no known compound(s) with different structure in the art capable of treating depression, this assertion appears to be mere argument without supporting evidence; said evidence is respectfully requested. Furthermore, the method of preparing the claimed compound, and the method of preventing or treating depression has different effects and mode of operation. For instance, a subject cannot be treated or prevented just by practicing the active steps of preparing the claimed compound, and that clearly indicate they have different mode of operation. If applicant asserts just by practicing the active steps of preparing the claimed compound, preventing or treating depression would necessarily present, said evidence is respectfully requested. In sum, the species and the inventions clearly include distinct characteristics and/or structure, and each method involves different active steps that clearly requires a different filed of search; and that involves searching different classes/successes or electronic resources, or employing different search strategies or search queries. In view of these findings, applicant’s argument is not found persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Please note the chemical structure of Compound I-1, when construed in light of paragraph [00107] of the specification, is a compound having the structure of:
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.
Claims 2 and 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on April 20, 2026.
Please note Applicant indicates claims 1-5 reads on the elected species (see page 19, last paragraph in the reply); However, the Examiner noted that claim 2 is drawn to a nonelected species. In short, claim 2 does not include
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at R2,
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at R4, and Bn at R3.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on April 20, 2026, wherein claims 1-10 are unchanged.
Claims 1-10 are pending.
Claims 2 and 6-10 are withdrawn.
Claims 1 and 3-5 are under examination in accordance with the elected species along with the expanded compounds set forth in the Expansion of Species section below.
Priority
The instant application 18/512,177 filed on November 17, 2023 is a continuation of PCT/CN2022/092681 filed on May 13, 2022, which claims priority to, and the benefits of Foreign Application No. CN202110534270.0 filed on May 17, 2021, and Foreign Application No. CN202210513147.5 filed on May 12, 2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Accordingly, claims 1-10 are not entitled to the benefits of the Foreign Applications (PCT/CN2022/092681, CN202110534270.0, and CN202210513147.5) written in foreign language and will receive an effective filing date of November 17, 2023, which is the filing date of instant application 18/512,177.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected species conducted by the Examiner
discover a prior art by Jiang et al. that anticipates the claimed invention, wherein the prior art also teaches compound 7q that anticipates the claimed invention. In addition, the Examiner also discovered a prior art by Cuevas-Cordobés et al. that teaches Compound 202 that renders obvious the claimed invention in view of Chen et al. In light of these discoveries (see rejection(s) below), the search is expanded to the subject matter of the compound to include compound 7q and the compound having the structure of:
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in addition to the elected compound species (Compound I-1), such that it does not encompass the full scope of the claims.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/17/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Please note that foreign references without an English translation but have an English
translation of the abstract will only have the abstract considered by the Examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0064]: the text in the reaction scheme is blurry and unreadable. For instance, the recitation of “
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” in the reaction scheme is blurry, and it is not clear what these are.
Paragraph [00104]: the text appears under the chemical structure is blurry and unreadable. For instance, the text indicated as follows (see shaded):
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is blurry and unreadable.
the specification is repleted with the term “novel” (see e.g., [0054]; [0057]). It is suggested that the term “novel” be deleted from the language of the disclosure. Once the determination of the novelty of a claimed invention has been established and the disclosure of the invention made public and/or patented, the claimed invention is no longer novel or new, since the scope of the invention no longer embraces what is considered “novel”. Thus, the incorporation of the term “novel” into the language of the specification is not appropriate.
The references cited in the specification are not cited in the information disclosure statement (IDS), and a legible copy of these references is not provided by the Applicant. For example, “[Kim, D. H.; Santilli, A A. J Af ed Chem.1969, 12, 1121---1122.]” is cited (see page 2 of the specification), but it is not in the IDS. Same logics applies to other references cited therein.
Appropriate correction is required.
Drawings
The drawings are objected to because of the following informalities:
Fig. 2A: the text is blurry and unreadable (e.g.,
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). Said figure also uses the same shade (
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) to label different groups, thus, one cannot distinguish them. For example, these three groups indicated below has the same shade
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(see shaded box):
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;
Fig. 5A-5D: the text on the x-axis is blurry and unreadable (e.g.,
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)
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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 1 and 3-5 are objected to because of the following informalities:
Regarding claims 1 and 3-5, the claim language repeatedly missing a coordinating conjunction (e.g., “and” or “or”) before the very last item in the list of alternated usable members, such coordinating conjunction should be added to indicate the end of series.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 3-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
According to MPEP 2163 I, “[t]o satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116… An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991)”.
Additionally, according to MPEP II-A-3-a-ii, “[t]he written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”; “[a] ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).”; and “’[a] patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”
Instant claim(s) recite a broad genus of chiral or racemic pyrimidine-fused diazepinone derivatives and a broad genus of pharmaceutically acceptable salts thereof that promises a broad genus of R1, R2, R3 and R4 for the formula (I); However, the specification fails to provide a reasonable sampling of them —a representative number of species— to represent the claimed genus fairly.
In the present case, the specification only exemplifies compound species I-1 to I-18 (see e.g., [00107]) and I-19 to I-38 (see e.g., [00130]). Among all of these disclosed compound species, the compound species only has phenyl as the representative species of “aryl group”; the compound species only contains lower alkyl, specifically propyl and t-Bu, as the representative species of “C1-C20 linear or branched alkyl group”; and the compound species only contains
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(see Compound I-34; I-38) as the representative species of “C2-C20 acyl group” at R3 and R4; However, instant claim(s) promises a broad genus of “substituted or unsubstituted aryl group” and a broad genus of “C1-C20 linear or branched alkyl group” at R1, R2, R3 and R4; and a broad genus of “C2-C20 acyl group” at R3 and R4. The specification does not identify any other particular species, synthetic preparation, or representative examples thereof. The specification only identify a few limited number of substitution species. The mere boiler plate reference to “substituted or unsubstituted aryl group”, “C1-C20 linear or branched alkyl group” and “C2-C20 acyl group” does not provide adequate blaze marks to the vast genus encompassed by the claim(s).
While Applicant does not have to exemplify every possible chiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts thereof to satisfy the written description requirement, applicant needs to provide enough representative species from different corners of the range to represent the claimed genus fairly. In other words, applicant should give concrete examples that reflect the diversity of what they are claiming. Since the claims recite a large set of possible R1, R2, R3 and R4 to arrive the Formula (I), applicant must provide a reasonable sampling of them —a representative number of compound species—so that a relevant artisan can see applicant truly envisioned the whole range, i.e., the entire scope of chiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts.
Therefore, in view of the foregoing, applicant is not in the possession of the entire scope of chiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable slats.
This is a written description rejection.
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.
Claims 1 and 3-5 are 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.
The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Regarding claim 1,
the claim recites “[c]hiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts thereof” that lacks an article (e.g., “a”) and uses a plural noun “derivatives” and “salts”. Said recitation lacks clarity and can be interpreted in various ways. For instance, the claim can be interpreted such that the claim is drawn to (i) a mixture of more than one chiral or racemic pyrimidine-fused diazepinone, or more than one pharmaceutically acceptable salt form; or (i) a compound that is one of the many chiral or racemic pyrimidine-fused diazepinone diazepinones or pharmaceutically acceptable salts thereof. The lack of clarity renders the claim indefinite, because one cannot reasonably determine which interpretation applies.
Additionally, the claim recites “[c]hiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts thereof”, and also recites “wherein a structural formula of the pyrimidine-fused diazepinone derivaties is as shown in formula (I)”. It is also unclear whether all of the recited “[c]hiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts thereof” are limited to the formula (I) or whether formula (I) merely represent one structural formula among multiple possible structures encompassed the claimed derivatives. The lack of clarity renders the claim indefinite, because one cannot reasonably determine which interpretation applies.
a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation “[c]hiral or racemic pyrimidine-fused diazepinone derivatives or pharmaceutically acceptable salts thereof”, and the claim also recites “a structural formula of the pyrimidine-fused diazepinone derivatives is as shown in formula (I), * is a chiral carbon atom with a configuration of R, S, or R/S” and “the pyrimidine-fused diazepinone derivatives is a levorotatory form, a dextrorotatory form, or a racemic form” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The claim is repleted with the term “substituted” that is not defined by the claim and the specification also does not provide a standard indicating what substitution(s) are permitted, how many substituents are permitted, and whether there are any structural limitations apply to the substituted moieties. For example, the “substituted” in the phrase “substituted or unsubstituted aryl group” lacks clarity. Can the substitution(s) be a heterocyclic ring fused to or added to the claimed aryl group? How many substation(s) can be added? Given that one cannot reasonably determine the metes and bounds for the term “substituted” accompanied with each and every phrase, one skilled in the art would not be reasonably apprised of the scope of the invention.
Accordingly, claims 3-5 are also rejected based on their dependency on a rejected base claim.
Regarding claim 3-5, the claims recite "the structural formula is the formula (I) with a skeleton structure of the pyrimidine-fused diazepinone" in line 2-3 is circular and renders the claim indefinite. The recitation of “the structural formula is the formula (I) with a skeleton structure of the pyrimidine-fused diazepinone” loops back onto the structural formula set forth in the previous claim. In the present case, claims 3-5 depends on claim 1, and claim 1 already set forth “a structural formula of the pyrimidine-fused diazepinone derivatives is as shown in formula (I)”. Therefore, when claims 3-5 recites the structural formula is the formula (I) with “a skeleton structure of the pyrimidine-fused diazepinone” again, it is not clear if applicant is intending to introduce “a” new skeleton structure to the previous formula (I) or is referring to the very same “formula (I)” set forth in claim 1; and it is like defining a word with a word. Therefore, without a clear sentence structure, one cannot reasonably determine the metes and bounds of the structural formula.
Claim Rejections - 35 USC § 102
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 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.
Claims 1 and 3-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jiang et al. (Adv. Synth. Catal, 2021. Vol. 363: 3227-3232. First Published on May 21, 2021).
Please note the Examiner noticed the publication date written in the legible copy of Jiang et al. provided by the Applicant has been cross-out; therefore, the Examiner has provided another legible copy of Jiang et al. published on May 21, 2021 (also cited in PTO-892). The specific portions cited in this instant office action will refer to the sections of the legible copy cited in PTO-892.
Jiang et al. teaches a compound 7q having the structure of:
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(see e.g., Scheme 3). Jiang et al. further teaches pyrimidine-fused diazepinones, as structural analogues of benzodiazepinones, are important and privileged N-heterocyclic scaffolds in drug discovery; and these compounds exhibits a broad spectrum of pharmacological properties, such as, inter alia, VGCC [Symbol font/0x61]2[Symbol font/0x64]-1 inhibitor (see e.g., p. 1, 1st paragraph). Please note the compound 7q of Jiang et al. is a compound of formula (I) instantly claimed
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, wherein R1 is
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; R2 is hydrogen; R3 is Bn; R4 is phenyl; reading on claims 1 and 3-5.
Jiang et al. teaches Compound 7a having the structure of:
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(see e.g., Scheme 2).- Please note the compound 7a of Jiang et al. is a compound of formula (I) instantly claimed
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, wherein R1 is
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; R2 is hydrogen; R3 is Bn; R4 is phenyl; reading on claims 1 and 3-5.
Therefore, the claimed invention is being anticipated by Jiang et al.
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.
Claims 1 and 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Cuevas-Cordobés et al. (US 10,590,140 B2), in view of Chen et al. (J. Org. Chem, 2020. Vol. 85: 5146−5157).
Cuevas-Cordobés et al. teaches compound Ex 202, having the structure of:
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is an exemplary compound of general formula (I) (see e.g., Col. 205, Ex 202). Cuevas-Cordobés et al. further teaches the compounds represented by the formula (I) may include enantiomers depending on the presence of chiral center or isomers depending on the presence of double bonds (e.g., Z, E). The single isomer, enantiomers or diastereoisomers and mixtures thereof fall within the scope of the present invention (see e.g., Col. 20, line 36-41); If there are chiral centers, the compounds may be prepared in racemic form (see e.g., Col. 54, line 60-61). Cuevas-Cordobés et al. further teaches the compounds of formula (I) are suitable for the treatment and/or prophylaxis of disease and/or disorders mediated by the subunit [Symbol font/0x61]2[Symbol font/0x64], especially [Symbol font/0x61]2[Symbol font/0x64]-1 subunit of voltage-gated calcium channels and/or noradrenaline transporter (NET); in this sense, compounds of formula (I) are suitable for the treatment and/or prophylaxis of pain, especially other pain conditions involving, inter alia, anxiety and depression (see e.g., Col. 69, line 7-15; claim 44). Cuevas-Cordobés et al. further teaches NET is a target of drugs treating a variety of mood and behavior disorder, such as depression and anxiety (see e.g., [0008]). Cuevas-Cordobés et al. further teaches the compounds of general formula (I):
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, wherein: R3 is, inter alia, hydrogen atom, a –(CH2)q-NR5R5 (see e.g., Col. 5, line 66 to Col. 6, line 43).
Cuevas-Cordobés et al. does not teach the formula (I).
Chen et al. teaches the construction of 1,4-benzodiazepine-5-one derivatives has practical application value in the development of new drugs; compounds containing a benzodiazepine nucleus
are of great significance in the study of pharmacochemistry, these compounds have explicitly exhibited fascinating biological activities, such as, inter alia, anti-anxiety, broad-spectrum antitumor antibiotics, and BRD4 inhibitors; and bioactive molecules containing a benzodiazepine nucleus includes:
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598
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(see e.g., p. 5146, left column, 1st paragraph; Figure 1). Chen et al. further teaches a series of 1,4-benzodiazepine-5-one derivatives that can be obtained in moderate to high yield (see e.g., abstract)
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205
967
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, including
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120
126
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(see e.g., Table 2; p. 5155, right column, 4th paragraph; Scheme 1); and teaches the antineoplastic activity of these compounds are explored, which could be important intermediates in the synthesis of some biologically active seven-membered nitrogen heterocycle compounds; and this approach could be widely used in the formation of various heterocyclic frameworks (see e.g., p. 5150, right column, “conclusions”, 1st paragraph).
According to MPEP 2144.09, “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. ‘An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.’ In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)”. In the present case, the difference between the compound Ex 202 of Cuevas-Cordobés et al. and the claimed compound is that the prior art compound does not contain an ethenyl (-CH=CH2) group instantly claimed as shown below (see shaded):
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365
532
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selectively choosing the compound 202 of Cuevas-Cordobés et al., and then modifying said compound by incorporating an ethenyl (-CH=CH2) at the 8-position of the pyrimido[4,5-e][1,4]diazepin-5-one core, because Chen et al. teaches 1,4-benzodiazepine-5-one derivatives exhibit various biological activities, including antianxiety and BRD4 inhibiting effect, and the construction of 1,4-benzodiazepine-5-one derivatives that added an ethenyl (-CH=CH2) at the position indicated as follows (see shaded):
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110
146
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, including
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120
126
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, are explored for antineoplastic activity and suggest this approach could be widely used in the formation of various heterocyclic frameworks. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the pyrimido[4,5-e][1,4]diazepin-5-one core of compound 202 of Cuevas-Cordobés et al. is a heterocyclic framework similar to the 1,4-benzodiazepine-5-one core of Chen et al., and they are each taught to have anti-anxiety activity; and therefore, by incorporating an ethenyl (-CH=CH2) at the 8-position of the pyrimido[4,5-e][1,4]diazepin-5-one core of Cuevas-Cordobés et al. (see shaded:
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226
200
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of Cuevas-Cordobés et al.), which is the same position taught by Chen et al. (see shaded:
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146
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of Chen et al.), one would have reasonably expected to arrive at a derivative that exerts the same or substantially similar anti-anxiety effect as compound 202 of Cuevas-Cordobés et al. Please note the modified compound 202 of Cuevas-Cordobés et al. in view of Chen et al. is a compound of formula (I) instantly claimed
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129
146
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, wherein R1 is
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16
6
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; R2 is hydrogen; R3 is
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6
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; R4 is methyl; and a racemic mixture, and that renders obvious claims 1 and 3-4.
Regarding the limitation of “wherein R3 and R4 are independently selected from….methyl… benzyl” in claim 5, the difference between the modified compound 202 of Cuevas-Cordobés et al. in view of Chen et al. set forth above and the claimed compound is that the modified compound 202 contains a substituted benzyl (
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16
6
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) rather than unsubstituted benzyl. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by further modifying the modified compound 202 of Cuevas-Cordobés et al. and Chen et al. set forth above by replacing the -CH2-NH-CH3 with a hydrogen as taught by Cuevas-Cordobés et al. One would have been motivated to do so, because Cuevas-Cordobés et al. teaches a list R3, including hydrogen atom and –(CH2)q-NR5R5, that can arrive at the compounds of general formula (I). One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by replacing the -CH2-NH-CH3 with a hydrogen at R3 of general formula (I) of Cuevas-Cordobés et al. would have successfully arrive at a derivative that exerts the same or substantially similar anti-anxiety effect as compound 202 of Cuevas-Cordobés et al.
Therefore, the claimed invention is prima facie obvious to one of orindary skill in the art at the time the application was filed.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
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