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 .
DETAILED ACTION
Status of 18/042,570
Claims 1-10 are currently pending.
Priority
Instant application 18/042,570, filed 2/22/2023, claims priority as follows:
PNG
media_image1.png
88
396
media_image1.png
Greyscale
Receipt of the foreign priority application is acknowledged.
Information Disclosure Statement
All references from the IDS submitted on 2/22/2023 have been considered unless marked with a strikethrough.
Response to Arguments/Amendments
The amendment filed 5/28/2026 has been entered. Claims 1-3 and 7-9 have been amended. No claims have been added and no claims have been cancelled.
In the Non-Final dated 3/4/2026, claims 1, 2, and 4 were objected to for minor grammatical informalities. In response, Applicant has amended the claims to correct some informalities, which overcome some of the objections. However, claim 2 still recites, “preparation of compound of”, but should read, “preparation of a compound of”. Thus, the objections of claims 1 and 4 have been withdrawn, but the objection of claim 2 is maintained.
Claims 1 and 4-6 were rejected under 35 U.S.C. 112(b) in the Non-Final dated 3/4/2026. In response, Applicant has amended claim 1 to recite “CH” instead of “C”, which overcomes the rejection. Thus, the rejection is withdrawn.
In the Non-Final dated 3/4/2026, claims 1-2 and 4-6 were rejected under 35 U.S.C. 103. In response, Applicant has argued that the substitution of ammonia of Soldatov into the copper mediated cyclization in Bernini would not yield predictable results because chemistry and biological sciences are generally unpredictable, and the presently claimed chemical reaction is particularly unpredictable. Specifically, Applicant argues that the 23 examples of Table 2 of Bernini contain yields of 36% to 93%, and three reactions completely failed, which is not predictable. These arguments have been considered, and are not considered persuasive because the three failed reactions and the two lowest yielding reactions of Table 2 of Bernini use t-BuONa as the base in the reaction, whereas the other reactions in Table 2 of Bernini use K2CO3 as the base. This change in variable directs a skilled artisan to reasoning as to why the reactions were unsuccessful. The Examiner notes K2CO3 is a base recited in instant claim 5. Reactions with K2CO3 as the base range from 70%-90% yield, which directs one of ordinary skill to combine the teachings of Soldatov and Bernini to yield a predictable result. Thus, the rejection is maintained.
Election/Restriction
Applicant’s election of Group I, claims 1-2, 4-6, 9, and 10, drawn to processes for preparing a compound of Formula I from a compound of Formula II, in the reply filed 10/27/2025 is acknowledged. Applicant’s elections of the following compounds and conditions:
PNG
media_image2.png
286
448
media_image2.png
Greyscale
in the same the reply filed 10/27/2025, is also acknowledged. The Examiner acknowledges that the reagents and conditions as disclosed in Example 1 are a polar aprotic solvent such as DMF, an ammonia source such as ammonia or ammonium carbonate, and a metal halide such as copper iodide heated at 100°C for 12 hours. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and no embodiment with all components of the process was identified. Thus, the Examiner expanded her search to compounds of Formula I where X is CH, R1 is phenyl, R2 is phenyl, R3 is H, R4 is H, R5 is H, and R6 is H, and thus compounds of Formula II where X is CH, R2 is phenyl, R4 is H, R5 is H, and R6 is H, and additionally to other polar aprotic solvents. The 103 rejection of the Non-Final dated 3/4/2026 was not overcome. The full scope of the claims has not yet been searched in accordance with Markush search practice. Specifically, the Examiner notes that the scope of the claims where R1 is CH3 has not yet been searched. Claims 1-2 and 4-6 read on the elected species. Claims 3 and 7-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species and/or group, there being no allowable generic or linking claim.
MAINTAINED OBJECTIONS AND REJECTIONS
Claim Objections
Claim 2 recites, “preparation of compound of”, but should read, “preparation of a compound of”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Bernini (Bernini, R. et. al., Synthesis, 2009, 7, 1209-1219.) and further in view of Soldatov (Soldatov, D. V. et. al., Journal of Structural Chemistry, 2005, 46, S158-S164). This rejection applies to the expanded species.
Determining the scope and contents of the prior art
The reference Bernini teaches the synthesis of 1,2-disubstituted 4-quinolones by copper-mediated cyclization from ynones (abstract). Specifically, Bernini teaches the copper-mediated cyclization of 1-(2-Bromophenyl)-3-phenyl-2-propyn-1-one with aniline to generate 1,2-Diphenyl-4(1H)-quinolinone (page 1211, Scheme 4):
PNG
media_image3.png
173
352
media_image3.png
Greyscale
And teaches the reaction in a single pot to make the reaction more attractive from a synthetic point of view (page 1211, left column). The starting material of Bernini, 1-(2-Bromophenyl)-3-phenyl-2-propyn-1-one, maps to a compound of instant Formula II:
PNG
media_image4.png
120
157
media_image4.png
Greyscale
When X is CH, R2 is phenyl, R4 is H, R5 is H, and R6 is H, and the product of Bernini, 1,2-Diphenyl-4(1H)-quinolinone, maps to a compound of instant Formula I:
PNG
media_image5.png
127
148
media_image5.png
Greyscale
When X is CH, R1 is phenyl, R2 is phenyl, R3 is H, R4 is H, R5 is H, and R6 is H. Furthermore, Bernini teaches an additive, copper iodide, and aniline as the nitrogen source for the quinolone (Scheme 4). The mechanism of the reactions is also taught by Bernini (Scheme 5):
PNG
media_image6.png
252
367
media_image6.png
Greyscale
and indicates the reaction pathway goes through compound 1, which when X is Br and R is phenyl, maps to Scheme 4 of Bernini. With respect to claims 4 and 5, Bernini teaches the reaction of the ynone starting material with the inorganic base K2CO3 in the polar solvent DMSO at 80°C for a total of 4 hours to obtain the quinolone.
The reference Soldatov teaches the nucleophilic addition of ammonia to 1,1′-(1,3-Phenylene)bis[3-phenyl-2-propyn-1-one] (page S159, Experimental Section):
PNG
media_image7.png
328
1098
media_image7.png
Greyscale
to generate the enaminone, which is similar to compound 1 taught in the mechanism of Bernini.
Ascertaining the differences between the prior art and the claims at issue
Bernini fails to teach an ammonia source where R1 of the product can be H and the total reaction time of 8-15 h.
Soldatov fails to teach the copper-mediated cyclization of a compound of Formula II to a compound of Formula I.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the synthesis of quinolones. An artisan possess the technical knowledge necessary to make adjustments to the syntheses to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said synthesis of quinolones and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (B), it would have been prima facie obvious for one skilled in the art to substitute the aniline of Bernini with the ammonia of Soldatov because the addition of each compound to a 1-Phenyl-2-propyn-1-one moiety generates an enaminone intermediate, which then can undergo the copper-mediated cyclization of Bernini. The similar compounds are expected to have similar properties. The artisan would have been expected before the effective filing date to use the teachings of Bernini and Soldatov to yield a predictable, successful result from the substitution.
With respect to the reaction time limitation of 8-15 hours recited in claim 4, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the reaction time recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the individual time of each reaction to provide optimal efficiency and yield. The reaction time of each individual reaction is a result effective parameter that will affect the physical properties of the final reaction. The time is clearly a result effective parameter that a person of ordinary skill would routinely optimize. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the reaction times disclosed by Bernini above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal time of the reaction to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the reaction time as disclosed above and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. See MPEP § 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Conclusion
Claims 1-2 and 4-6 are rejected. Claims 3 and 7-10 are withdrawn.
Applicant's amendment necessitated 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights