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, 4 – 5, 18, 21, 25, 28, 31, 34, 43, 45, 52, 55 – 59, 61 – 62, 65 – 66, and 67 – 69) drawn to a compound of Formula (I)
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and the species election of (2-(4-(N-(4-chloro-7-(2-((S)-1-(2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-4-oxo-7-(3,3,3-trifluoropropoxy)pyrido[2,3-d]pyrimidin-3(4H)-yl-1-methyl-1H-indazol-3-yl)methylsulfonamido)-2-methyl-4-oxobutan-2-yl)-5-methyl-3-(phophonooxy)benzyl)phosphonic acid of structure
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in the reply filed on May 22nd, 2026 is acknowledged.
Claims 73 – 75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II (a method of treating or preventing a human immunodeficiency virus (HIV) infection), there being no allowable generic or linking claim. Moreover, claims 25, 28, 43, 45, 52, 56, 58 – 59, 61, 66, and 67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected compound species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 22nd, 2026.
However, upon the initial search the elected specie
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the search was expanded, to include non-elected species where G1 is a C1-10 alkoxy, RX6 = CF3, and RX4 = CH2CF3. As a result, only non-elected species where Y1 = N; m = 1; W = RX3 = Cl; RX4 = CH3 or CH2CF3; RX5 = CH3; RX6 = CHF2 or CF3; and Y = phenyl substituted with 3 R3 groups where one R3 = Ra = -OP(O)(OH)2; one R3 = CH2-P(O)(OH)2; and one R3 = CH3 as encompassed by claims 58 and 66 are rejoined. Nonetheless, outside of the elected species as delineated above; the election of species required in the Restriction Requirement mailed May 22nd, 2026, is maintained; and the restriction requirement between Groups I and Group II is also maintained.
Hence claims 1, 4 – 5, 18, 21, 31, 34, 55, 57 – 58, 62, 65 – 66, and 68 – 69 are examined of the merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See specification page 135 paragraph 0403. 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: structures of W recitation are blurry. If the claim becomes allowable the quality of the structures in the printer might not be of good enough quality. 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 is 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, 5, 18, 21, 31, 34, 55, and 68 – 69 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2023/102239 A1 to Farand et. al. (Farand’239; cited on IDS dated September 16th, 2024) in view of International Publication Number WO 2018/2003235 A1 to Babu et.al. (Babu’235; cited on IDS dated September 16th, 2024).
Regarding claims 1, 5, 18, 21, 31, 34, 55, and 68 – 69, Farand’239 teach novel compounds and pharmaceutical compositions comprising said compounds for use in the prevention or treatment of a Retroviridae viral infection, including an infection caused by the human immunodeficiency virus (HIV). See page 1 paragraph 0002. Farand’239 teach a compound of Formula I, of structure
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. See page 2 paragraph 0005. In particular, Farand’239 teach an embodiment of the compound of Formula I where the compound is compound 55 of the structure
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where m = 1; RX5 = CH3; RX4 = CH2CF3; W =
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; RX3 = Cl; RX6 = CF3; and X =
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. See page 224. See claim 1 limitation for a compound where m = 1; RX6 = CF3; RX5 = CH3; RX4 = CH2CF3; W =
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; and RX3 = Cl; and X =
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. See claim 5 limitation for a compound where X = isobutyl substituted with Y, where Y = phenyl substituted with 3 R3 groups where one R3 = Ra = -OP(O)(OH)2, one R3 = CH2-P(O)(OH)2, and one R3 =- CH3. See claim 18 limitation for a compound where X = isobutyl substituted with one Y. See claim 21 limitation for a compound where X substituted with Y is
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. See claim 31 limitation for a compound where Y = phenyl and the phenyl is substituted with 3 R3 groups. See claim 34 limitation for a compound where one R3 = Ra = -OP(O)(OH)2, one R3 = CH2-P(O)(OH)2, and one R3 =- CH3.
Additionally, Farand’239 teach an embodiment where the compounds of the disclosure, which include compound 55, is combined with one, two, three, or four additional therapeutic agents selected from ATRIPLA® (efavirenz, tenofovir disoproxil fumarate, and emtricitabine); COMPLERA® (EVIPLERA®; rilpivirine, tenofovir disoproxil fumarate, and emtricitabine); STRIBILD® (elvitegravir, cobicistat, tenofovir disoproxil fumarate, and emtricitabine);TRUV ADA® (tenofovir disoproxil fumarate and emtricitabine. See page 112 paragraph 0340. See claim 69 limitation for a pharmaceutical composition further comprising one, two, three, or four additional therapeutic agents. Furthermore, Farand’239 teach that the oral bioavailability of compound 55 was assay in Sprague Dawley rats and Beagle dogs where the animals were administered an oral dose of the compound in mixture of suspension vehicle of 0.5% hydroxypropyl methylcellulose, high viscosity and 99.5% water with final pH of 2.0 and solution vehicles of either 1) 5 % ethanol, 20% propylene glycol, and 75 % water or 2) 30% 10 mM HCl, 5% ethanol, 45% polyethylene glycol 300, and 20% propylene glycol. See page 275 paragraph 0681 and 0685. See claim 68 limitation for a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
However, Farand’239 fail to teach a compound with a 4-Quinazolinone scaffold where Y1 = N and G1 = OCH3. See claims 1 and 55 limitation.
Nevertheless, Babu’235 teach compounds, compositions, and methods for the treatment of human immunodeficiency virus (HIV) infection. See page 1 lines 4 – 5. Babu’235 teach a compound of Formula I
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. See page 2 lines 26 – 28. In particular, Babu’235 teach compound example 13.1 of structure
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with a 4-Quinazolinone core scaffold where Y1 = N; G1 = OCH3; m = 1; RX5 = CH3; RX4 = CH3; W =
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; and RX3 = Cl. See page 494 Table 1 row 1. See claim 1 limitation for a compound where Y1 = N; G1 = OCH3; m = 1; RX5 = CH3; RX4 = CH3; W =
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; and RX3 = Cl. See claim 55 limitation for a compound where Y1 = N.
Both the prior art of Farand’239 and Babu’235 teach compounds useful in methods of treating HIV. Moreover, both the prior art of Farand’239 and Babu’235 teach compounds of overlapping structural features such prior art compound 55 of Farand’239 of the structure
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where m = 1; RX5 = CH3; RX4 = CH2CF3; W =
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; RX3 = Cl; RX6 = CF3; and X =
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and compound example 13.1 of structure
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with a 4-Quinazolinone core scaffold where Y1 = N; G1 = OCH3; m = 1; RX5 = CH3; RX4 = CH3; W =
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; and RX3 = Cl. In particular, the prior art compounds share similar W, RX3, RX5,
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, and
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.
Therefore, it would have been obvious before the effective filing date of the instant application to modify compound 55 of Farand’239 in view of Babu’235 that is to substitute the 4-Quinazolinone core scaffold of compound example 13.1. One of ordinary skill in the art would have been motivated to make this modification since both compounds of Farand’239 and Babu’235 have use in method for treating HIV infections. One of ordinary skill in the art would have had a reasonable expectation of success because both prior art compounds having overlapping structural features that were found to be beneficial for treating HIV infections.
Claims 4, 57 – 58, 62, and 65 – 66 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2023/102239 A1 to Farand et. al. (Farand’239; cited on IDS dated September 16th, 2024) and International Publication Number WO 2018/2003235 A1 to Babu et.al. (Babu’235; cited on IDS dated September 16th, 2024) as applied to claims 1, 5, 18, 21, 31, 34, 55, and 68 – 69 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Farand’239 and Babu’235 as they relate to claim 1, from which claims 4, 57 – 58, 62, and 65 – 66, depend, are given previously in this office action and are fully incorporated here.
However, the prior art of Farand’239 and Babu’235 fails to teach a compound where G1 is either
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. See claims 4, 57 – 58, 62, and 65 – 66 limitations.
Nevertheless, as taught above, Babu’235 teach compound example 13.1 of structure
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with a 4-Quinazolinone core scaffold where Y1 = N; G1 = OCH3; m = 1; RX5 = CH3; RX4 = CH3; W =
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; and RX3 = Cl. See page 494 Table 1 row 1. One of the main difference between the G1 of prior art compound example 13.1 and the G1 recited in examined claims 4, 57 – 58, 62, and 65 – 66 is the addition of two methyl units, that is -CH2-CH2-, between the O and the CH3. Moreover, the secondary difference between the G1 of prior art compound example 13.1 and the G1 recited in examined claims 4, 57 – 58, 62, and 65 – 66 is the substitution of two or three H atoms on the C3 alkyloxy for F atoms. Regarding the difference between prior art compound 13. 1 and a compound of examined claims 4, 57 – 58, 62, and 65 – 66 being that of the additional -CH2-CH2- group between the O and the CH3 both compounds would be considered structural homologs of each other. As such compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) 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). See MPEP 2144.09(II).
Nevertheless, regarding the difference between prior art compound 13. 1 and a compound of examined claims 4, 57 – 58, 62, and 65 – 66 being that of the substitution of two or three H atoms on the C3 alkyloxy for F atoms Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that F and H are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute F for H with a reasonable expectation that compounds with either F or H would have similar biological properties.
Therefore, it would have been obvious before the effective filing date of the instant application to modify compound 55 of Farand’239 and Babu’235 that is to substitute the 4-Quinazolinone core scaffold of compound example 13.1 along with the G1 of OCH3 and to add an additional -CH2-CH2- group between the O and the CH3 in further view of Meanwell, that is to substitute the 2 or 3 H atoms for F atoms. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both F and NH2 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties. Moreover, one of ordinary skill in the art would have been motivated to make this modification since both compounds of Farand’239 and Babu’235 have use in method for treating HIV infections. One of ordinary skill in the art would have had a reasonable expectation of success because both prior art compounds having overlapping structural features that were found to be beneficial for treating HIV infections.
Conclusion
Claims 1, 4 – 5, 18, 21, 31, 34, 55, 57 – 58, 62, 65 – 66, and 68 – 69 are rejected.
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
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