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:
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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.
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:
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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. See the 103 rejection below. 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.
Claim interpretation
Claim 1 recites the limitation, “additive”. The term “additive” is not explicitly defined in the disclosure, but the specification suggests the term “additive” is equivalent to a metal halide selected from copper iodide, copper bromide, copper chloride, and copper acetate (para [00030] and claim 6). Thus, the limitation, “additive” is currently being interpreted as copper iodide, copper bromide, copper chloride, or copper acetate.
Claim 1 recites the limitation, “ammonia source”. Similar to above, the term “ammonia source” is not explicitly defined in the disclosure, but the specification and claim 6 suggest the “ammonia source” may be selected from ammonia, ammonium chloride, ammonium acetate, ammonium carbonate, and ammonium formate (para [00046] and claim 6). Thus, the limitation “ammonia source” is currently being interpreted as ammonia, ammonium chloride, ammonium acetate, ammonium carbonate, and ammonium formate.
Claim Objections
Claims 1 and 2 recite, “preparation of compound of”, but should read, “preparation of a compound of”. Appropriate correction is required.
Claim 1 recites the alternatives of each variable as a conjunctive requirement by the use of the term “and”, which indicates each alternative must be present in the formulae. In order to overcome this objection, each “and” in the series of alternatives of each variable must be changed to “or”. Appropriate correction is required.
Claim 2 is objected to for a minor informality. Specifically claim 2 recites, “formula (I)”, but should read “Formula (I)”, in an effort to be consistent. Appropriate correction is required.
Claim 4 is objected to for a minor informality. Similar to above, claim 4 recites, “formula (I)” and “formula (II)”, but should read, “Formula (I)” and “Formula (II)”, respectively, in an effort to be consistent. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 4-6 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.
Claim 1 recites the limitation where X is C. However, unless C is an unmarked anion, X cannot be C and needs to be substituted with a hydrogen or another substituent. Thus, the limitation is unclear. For art purposes, the limitation is currently being interpreted as CH. Dependent claims 4-6 do not resolve this issue by defining this variable and are thus also rejected. 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):
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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:
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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:
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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):
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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):
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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.
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.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621