DETAILED ACTION
This office action is in response to applicant’s filing dated March 7, 2025.
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 .
Status of claims
Claims 1, 3, 6, 8, 10 and 15 - 28 are pending in the instant application. Acknowledgment is made of Applicant’s amendments filed March 7, 2025. Acknowledgment is made of Applicant’s cancelation of claims 2, 4, 5, 7, 9, and 11 - 14.
Priority
The present application is a 371 of PCT/US2023/011827, filed January 30, 2023, and claims the benefits of priority to U.S. Provisional Application No. 63/304772 filed January 31, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/31/2024 and 01/28/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 17 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.
The claim recites the term:”[…] “preferably” , (line 2) which is equivalent to phrase “such as”, renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 17 recite “acetic acid in an amount in a range of from about 0.1 eq. to about 10 eq., preferably about 0.5 eq. to about 6 eq.” which is unclear whether the claimed narrower range is a limitation and lead to confusion over the intended scope of the claim. Narrow and broader numerical ranges stated in a single claim render the claim indefinite.
In the interest of compact prosecution, for the purposes of applying art, the broader numerical ranges recited in claim 17 have been considered.
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, 3, 6, 8, 10, 15, 16, 19 – 21 and 23 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Annis (WO 2004/011453 A2, cited in IDS, filed 07/31/2024, hereinafter Annis).
Instant claims are drawn to a method of preparing a compound of Formula (II):
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from compound of formula (I):
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, where Y is N; R5 is a halogen, such as Br; R6 is a halogen, such as Cl in position 3 of heteroaromatic ring, and m is 0 – 3; R7 is a H or C1-C4 alkyl; X is N; R1 is a sulfonate; R2 is a halogen, such as Cl in position 3 of heteroaromatic ring, and m is 0 – 3; R3 is a H or C1-C4 alkyl; such as the method of preparing of compound of formula
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from the compound of formula
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. Said method comprises:
Forming a mixture of compound
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with a solvent and optionally a bromide;
Introducing a bromination agent to the mixture;
Introducing a strong acid to the mixture;
Adding a base to the mixture. The suitable solvent for the above method is e.g. dibromomethane, dichloromethane or acetic acid, the bromination agent and strong acid is an HBr, the base is a sodium bicarbonate.
Annis teaches the method for preparing a compound of formula Ia:
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from compound of formula IIa:
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, where Z is N or CH; R3 is halogen, such as Cl in position 3 of aromatic or heteroaromatic ring, and m is 0 – 3; R4 is a H or C1-C4 alkyl, X1 is Br; X2 is OS(O)2R1, where R1 is methyl, phenyl or 4-methylphenyl. Annis teaches the method according to the scheme:
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(pages 13 – 14). Annis teaches an exemplary method, where the method shows conversion of ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[[(4-methylphenyl)sulfonyl]oxy]-1H-pyrazole-5-carboxylate or ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)oxy]-1H-pyrazole-5-carboxylate (equivalent to a compound
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of instant claims) into ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (equivalent to a compound
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of instant claims) under action of HBr, gaseous or dissolved in acetic acid, optionally in presence of Lewis acid (e.g. aluminum bromide). HBr in the method of Annis acts as both, bromination agent and a strong acid. The solvent used for the process is dibromomethane or acetic acid (pages 20 – 21, Examples 2 and 3).
Thus, Annis teaches an identical method of chemical conversion, conducted under the same conditions as instantly claimed method.
Therefore, teachings of Annis anticipate the instantly claimed method.
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, 17, 27 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Annis (WO 2004/011453 A2, cited in IDS, filed 07/31/2024).
Instant claims are drawn to a method of preparing a compound of Formula (II):
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from compound of formula (I):
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, such as the method of preparing of compound of formula
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from the compound of formula
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, where the solvent is acetic acid in the amount of 0.1 eq to 10 eq, and where the reaction was conducted at temperature range of 0 °C to 5 °C or 8 °C to 12 °C.
Annis teaches the method for preparing a compound of formula Ia:
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, from compound of formula (IIa)
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, according to reaction:
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, where Z is N or CH; R3 is halogen, such as Cl in position 3 of aromatic or heteroaromatic ring, and m is 0 – 3; R4 is H or C1-C4 alkyl, X1 is Br; X2 is OS(O)2R1, where R1 is methyl, phenyl or 4-methylphenyl, such as the method of preparation of compound
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from compound
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, where the solvent is an acetic acid, where 4 mL of acetic acid was added to 2.44 mmol of ethyl 1-(3-chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulfonyl)oxy]-1H-pyrazole-5-carboxylate (
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) (page 21, Example 3). Since acetic acid has a molecular weight of 60.05 g/mol and density 1.0446 g/mL (64-19-7 Substance Detail | CAS SciFinder), 4 ml of acetic acid is approximately 0.069 mol or 69 mmol, representing an approximate 28-fold excess relative to the 2.44 mmol of reactant. Although prior art teaches greater excess of acetic acid than instant claims, this variation represents nothing more than a routine optimization and does not carry patentable weight. Similar conclusion apply to the reaction temperature. Annis teaches, the reaction was conducted at about 0 °C to 100 °C (e.g. at about 10 – 40 °C) (page 12, lines 28 – 30), which falls within the claimed ranges, rendering the selection of this parameter a matter of routine optimization.
MPEP 2144.05 states: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.).
Thus, since Annis teaches the same process using the same solvent, wherein the concentration and a temperature ranges are merely the result of routine experimentation, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to adapt the prior art process to arrive at claimed method. The one of ordinary skills would be motivated to do so in pursuit of improving an efficiency of known process with the reasonable expectation of success.
Claims 1, 18, 22 and 24 - 26 are rejected under 35 U.S.C. 103 as being unpatentable over Annis (WO 2004/011453 A2, cited in IDS, filed 07/31/2024) in view of Yamamoto et al (US 8,481,744 B2, hereinafter Yamamoto).
Instant claims are drawn to a method of preparing a compound of Formula (II):
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from compound of formula (I):
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, such as the method of preparing of compound of formula
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from the compound of formula
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. The method comprises:
Forming a mixture of compound
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with a solvent and optionally a bromide;
Introducing a bromination agent to the mixture;
Introducing a strong acid to the mixture;
Adding a base to the mixture; wherein the base is sodium hydroxide, added to mixture dropwise, bromide is phosphorus oxybromide, phosphorus pentabromide or phosphorus tribromide, strong acid is a sulfuric acid, and wherein reaction mixture was stirred.
Annis teaches the method for preparing a compound of formula Ia:
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, from compound of formula (IIa)
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, according to reaction:
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, where Z is N or CH; R3 is halogen, such as Cl in position 3 of aromatic or heteroaromatic ring, and m is 0 – 3; R4 is H or C1-C4 alkyl, X1 is Br; X2 is OS(O)2R1, where R1 is methyl, phenyl or 4-methylphenyl, such as the method of preparation of compound
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from compound
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, where strong acid is a hydrobromic acid, the base is sodium bicarbonate and bromide is e.g. Aluminum bromide. Although instant claims recite sulfuric acid, sodium hydroxide and phosphorus oxybromide, phosphorus pentabromide or phosphorus tribromide, the skilled artisan would recognize it as a simple substitution of known chemical equivalents, used for the same purpose to achieve predictable results. HBr and H2SO4 are well-established functional equivalents for providing H+ ions, likewise sodium bicarbonate and sodium hydroxide are both used to neutralize acidic reaction conditions, when reaction mixture is “washed” with sodium bicarbonate solution (page 20, line 30), as well as all Lewis acids are the compounds with structural feature capable of accepting an electron pair. Thus, it would have been prima facie obvious to substitute strong acid, bromide (Lewis acid) and base taught by prior art with known equivalents to arrive at claimed method with the reasonable expectation of success (see MPEP2144.05 and 2144.06).
Regarding limitations of claims 25 and 26, which recite adding base to the reaction mixture dropwise and stirring the reaction, these limitations do not carry a patentable weight because stirring the reaction mixture and adding components dropwise constitute standard chemistry laboratory techniques inherent to the art, even if omitted from procedural description.
To support these obviousness conclusions, Examiner cites Yamamoto.
Yamamoto teaches a process for producing compound of formula (III) from compound of formula (II) according to reaction:
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, Z is benzene substituted with nitro group (column 5, step [B]). Although compounds of formula II and III are not structurally identical to instantly claimed compounds, they are structural analogs undergoing identical chemical conversion at the same reaction center (see the circled fragments above). Yamamoto teaches that the reaction was conducted in solvent such as dichloroethane or acetic acid, in presence of brominating agent such as hydrogen bromide, metal bromides (potassium bromide, aluminum bromide), phosphorus tribromide and phosphorus pentabromide, or hydrogen bromide can be generated by reacting a e.g. metal bromide with an acid such as sulfuric acid (column 7). Yamamoto teaches a reaction example, where compound of formula (II) was dissolved in acetic acid, and hydrogen bromide acetic acid solution was dropwise added, followed by stirring for about 1.5 hours. After completion of the reaction (obtaining a compound of formula (III)), ethyl acetate, water and 1.8 mL of 1 N sodium hydroxide were added, followed by stirring and extraction with ethyl acetate (column 15, lines 24 – 30).
Thus, Yamamoto teaches the same chemical reaction conducted under the same conditions, involving identical reaction center of structurally analogous compounds as instantly claimed method, thereby supporting applied above obviousness conclusion about art-recognized equivalents (hydrobromic and sulfuric acids, sodium bicarbonate and sodium hydroxide or choice of bromides) as well as using standard laboratory techniques such as adding reaction components dropwise or stirring the reaction mixture (see MPEP 2144.05 and 2144.06).
Thus, since prior art teaches the same process of chemical conversion of the same or similar compounds, conducted under the same conditions and producing the same or similar product as instantly claimed, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine and modify teachings of prior art to arrive at claimed method with the reasonable expectation of success, since according to teachings of prior art, the claimed method is a predictable application of known chemistry to a known class of compounds.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made,
as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Claims 1, 3, 6, 8, 10 and 15 – 28 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET.
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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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