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 without traverse of Group I (claims 1, 3 – 4, 6, 8, 10 – 11, 17, 19, 29 – 32, 36, and 41) drawn to a compound having Formula I:
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wherein R1-7’, and X1-8 are defined and the species election of 2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-4-(4-(1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one with the structure
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in the reply filed on February 9th, 2026 is acknowledged.
Claims 40, 47 – 49, and 61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II (a method of treating cancer), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 2nd, 2024.
However, upon initially searching the elected species 2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-4-(4-(1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl)benzyl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one with the structure
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, the species was found to be free of the prior art. Thus the search was expanded to include all chemical species having Formula I. Therefore, since the search was expanded to include all chemical species having Formula I; all chemical species having Formula I are rejoined and the species election requirement set forth in the Requirement for Restriction/Election dated August 11th, 2025 is withdrawn. However, the restriction set forth in the Requirement for Restriction/Election dated August 11th, 2025 between Group I and Group II is still maintained.
Hence claims 1, 3 – 4, 6, 8, 10 – 11, 17, 19, 29 – 32, 36, and 41 are being examined on the merits herein.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: the word “and” is duplicated on page 3 line 17 of the claim. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: the word “susbstituted,” in line 2 of the claim should be “substituted.” Appropriate correction is required.
Claim 19 is objected to because of the following informalities: the word “susbstituted,” in line 2 of the claim should be “substituted.” Appropriate correction is required.
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.
Claims 1, 8, 10, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stewart et. al. ((2020), An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds, Chem. Commun., 56, 6818 – 6821; cited in the Requirement for Restriction/Election dated August 11th, 2025).
Regarding claims 1, 8, 10, and 30, Stewart et. al. teach the species compound 8m of structure
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(claim 1) (page 6819 column 2 Table 1) which is embraced by general formula (I) wherein instant X1 is N; instant X2 is CH; instant X3 is NH wherein instant R3 is H; instant R1 is phenyl with the substituents on R1 are H (claim 10); instant X4 is CH2 wherein instant R4 and R4’ are H; instant X5 – 8 are CH (claim 30); wherein instant R8 is H (claim 8); instant R2 is H; instant R6 and R6’ are H; instant R7 is H; and instant R7’ is adamantly, that is a cycloalkyl. Additionally, Stewart et. al. teach that partially saturated bicyclic piperazine-based privileged scaffolds are present in a number of drugs for a variety of clinical indications including treatments of malaria, hyperglycaemia, sex-hormone related disorders and cancer (page 6818 column 1 paragraph 4).
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 nonobviousness.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Stewart et. al. ((2020), An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds, Chem. Commun., 56, 6818 – 6821; cited in the Requirement for Restriction/Election dated August 11th, 2025) in view of Chaudhari et. al. ((2012), Pharmaceutical Excipients: A review, IJAPBC, 1, 21 – 34).
The teachings of Stewart et. al. as they relate to claim 1, from which claim 41 depend, are given previously in this office action and are fully incorporated here.
While Stewart et. al. does teach that partially saturated bicyclic piperazine-based privileged scaffolds are present in a number of drugs for a variety of clinical indications including treatments of malaria, hyperglycaemia, sex-hormone related disorders and cancer (page 6818 column 1 paragraph 4); Stewart et. al. fail to teach a pharmaceutical composition comprising compound 8m, and a pharmaceutically acceptable carrier (claim 41).
Nevertheless, Chaudhari et. al. teach that many dosage forms formulated today are complex system containing many other components along with the active pharmaceutical ingredient (API) (page 21 column 1 paragraph 1). Moreover, Chaudhari et. al. teach that many of these components are added to protect, support or enhance stability of the formulation, bulk up the formulation in case of potent drug for assisting in formulation of an accurate dosage form, improve patient acceptance, help improve bioavailability of the active drug, and enhance overall safety and effectiveness of the formula during its storage and use (page 21 columns 1 – 2). Specifically, Chaudhari et. al. teach in Tables 1 – 3 excipients used in solid dosage forms (page 28 Table 1), excipients used in liquid dosage forms (page 29 Table 2), and excipients used in semisolid dosage forms (pages 29 – 30 Table 3).
Therefore, it would have been obvious to one of ordinary skill in the art to modify compound 8m of Stewart et. al. in view of Chaudhari et. al., that is to combine compound 8m with any of the excipients taught in Tables 1 – 3 as pharmaceutically acceptable carriers, in pharmaceutical composition. One of ordinary skill in the art would have been motivated to make this modification since the prior art of Stewart et. al. taught that compounds with similar scaffolds that is with partially saturated bicyclic piperazine-based scaffolds had clinical indications which include treating malaria, hyperglycaemia, sex-hormone related disorders, and cancer. One of ordinary skill in the art would have had a reasonable expectation of success because since pharmaceutical formulations is well understood within the pharmaceutical arts.
Claims 3 – 4, 6, 11, and 31 – 32 are rejected under 35 U.S.C. 103 as being unpatentable over Stewart et. al. ((2020), An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds, Chem. Commun., 56, 6818 – 6821; cited in the Requirement for Restriction/Election dated August 11th, 2025) in view of Ali et. al. ((2014), Input of Isosteric and Bioisosteric Approach in Drug Design, J. Chem. Soc. Pak., 36, page 150-169).
The teachings of Stewart et. al. as they relate to claim 1, from which claims 3 – 4, 6, 11, and 31 – 32 depend, are given previously in this office action and are fully incorporated here.
However, Stewart et. al. fail to teach a compound of claim 1 wherein
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independently selected from a group consisting of
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(claim 3); wherein X4 is CR4R4' and X2 is N (claim 4); wherein one or more of X5, X6, X7, and X8 is N (claim 6); wherein R1 is an optionally substituted 5- or 6-membered nitrogen-containing heteroaryl, wherein nitrogen is the only heteroatom (claim 11). Moreover, Stewart et. al. fail to teach the compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, having Formula V
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(claim 31) or more specifically having Formula XV
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(claim 32).
Nevertheless, given that the only difference between the prior art compound 8m of Stewart et. al. of structure
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and a compound of claim 1 wherein
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independently selected from a group consisting of
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(claim 3) wherein X4 is CR4R4' and X2 is N (claim 4); Formula V
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(claim 31) or more specifically having Formula XV
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(claim 32) is the position of the N atom in the structure, that is instant X3 as the N instant of X2, both the prior art compound 8m and species of the instant claims are positional isomers. Therefore, compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)(MPEP 2144.09(II)).
However, Stewart et. al. fail to teach a compound of claim 1 wherein one or more of X5, X6, X7, and X8 is N (claim 6); or wherein R1 is an optionally substituted 5- or 6-membered nitrogen-containing heteroaryl, wherein nitrogen is the only heteroatom (claim 11).
Nevertheless, Ali et.al. teach isosterism or bioisosterism is one of the approaches most frequently used in the design of new molecules (page 150 column 1 paragraph 1). Moreover, Ali et. al. teach that in a broad sense bioisosteres may be identified as any two compounds or structures that show similar biological activities and share analogous topology, volume, electronic arrangements or physicochemical properties (page 150 column 1 paragraph 1). Furthermore, Ali et.al. teach that bioisosterism is a well-established technique in modern drug design, extensively studied for modification of drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile (page 150 column 1 paragraph 1). Specifically, Ali et. al. teach that pyrimidine, a 6-membered nitrogen-containing heteroaryl wherein nitrogen is the only heteroatom and a ring wherein one or more of X5, X6, X7, and X8 is N, is a bioisostere to the benzene rings, on compound 8m of the prior art as shown here
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.
Thus in regards to claim 11 recitation for a compound of claim 1 wherein R1 is an optionally substituted 5- or 6-membered nitrogen-containing heteroaryl, wherein nitrogen is the only heteroatom (claim 11) and a compound wherein one or more of X5, X6, X7, and X8 is N (claim 6); it would have been obvious to one of ordinary skill in the pharmaceutical arts before the effective filing date of the instant application to modify the prior art compound 8m from Stewart et. al. of structure
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in view of Ali et. al., that is to replace both of the benzene rings with pyrimidines. One of ordinary skill in the art would have been motivated to make this modification to improve drug target selectivity, bioactivity, efficacy, potency, membrane permeability, biotransformation pathways and toxicity profile. One of ordinary skill in the art would have had a reasonable expectation of success because bioisosterism is a well-established technique in modern drug design.
Conclusion
Claims 1, 3 – 4, 6, 8, 10 – 11, 30 – 32, and 41 are rejected. Claims 17, 19, 29, and 36 are objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627