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
This office action is in reply to the Response to Election/Restriction filed 05 May 2026 for application 18/684,486 filed 16 February 2024, 371 of PCT/JP2022/031308 filed 19 August 2022, claiming priority from JP2021-134801 filed 20 August 2021. Claim 4-7, 12-13, 15-17 and 19-21 are amended. Currently, claims 1-21 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 May 2024 and 18 September 2025 was filed after the mailing date of the application on 16 February 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of Group I with traverse in the reply filed on 05 May 2026 is acknowledged.
Applicant's election with traverse of Group I in the reply filed on 05 May 2026 is acknowledged. The traversal is on the ground(s) that “Applicant notes the Group II claims depend on the Group I claims and thus can be examined at the same time, and also note In re Ochiai. This is not found persuasive because the Groups are two distinct inventions – Group I being a composition of matter and Group II being method of use. The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election of compound I-078, illustrated below, in the reply filed on 05 May 2026, is acknowledged:
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Applicant’s election of coronavirus as the disclosed species of viral infectious disease, in the reply filed on 05 May 2026, is acknowledged.
The elected species, per Applicant’s Remarks, reads on claims 1-8 and 12-19. As such, claims 9-11 and 20-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or species, there being no allowable generic or linking claim. Election was made in the reply filed on 05 May 2026.
The elected species was searched and found to be free of the prior art.
The search was expanded to the full scope of the claims.
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 non-obviousness.
Claims 1-8 and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Francom et al. (Bycyclic nucleosides and nucleotides as therapeutic agents, WO 2010/002877 A2, 2010; entered into the IDS on 16 May 2024) and Byeon et al. (C-nucleosides, C-nucleotides and their analogs, equivalents and prodrugs thereof for ectonucleotidase inhibition, WO 2021/040356 A1, 2021; entered into the IDS on 16 May 2024) in view of Babu et al. (Antiviral azasugar-containing nucleosides, US 2015/0291596 A1, 2015).
Francom discloses compound 15 (para. 00281) and similar structures, which reads upon formula I except for the aza-sugar, for the purpose of treating or preventing microbial or viral infections, or proliferative disorders (para. 0037):
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They do, however, disclose a structure of the following formula where A is selected from a group including -NR-, where R = H (para. 0016):
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As the disclosed possibilities are narrow, only six members, where A is NR, only eleven disclosed moieties for R, with H being the simplest and elementary, a person of ordinary skill in the art would clearly envisage N-H as being a possible moiety.
Similarly, Byeon discloses compound example 1, incorporating nucleosides and phosphate pro-drug moieties, which also reads upon formula I except for the aza-sugar (para. 243) for the purpose of inhibiting the CD73 enzyme (para. 1):
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Like Francom, they disclose a structure for the following formula where X is selected from a group including -NH (para. 77):
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However, they do not disclose specific examples of aza-sugars while exemplifying other aspects of the claimed invention such as the nucleoside moieties.
Babu rectifies this deficiency by teaching aza-sugars of the formula (para. 0013) for the purpose of inhibiting viral RNA polymerase activity or viral replication, and treating viral infections:
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Here L4 is selected from a group including a bond and R4 is selected from a group including (para. 0254):
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R4 can also be represented by the illustrated formula where L5 is selected from a group including a bond and R4 can be selected from a group consisting of C1-C6 alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C1-C6 acyl, carboxyl, or absent.
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Babu describes that their disclosed aza-sugar compounds are characterized, in part, by favorable pharmacokinetics for the active pharmaceutical ingredients, particularly in conjunction with enteral administration, including in particular, oral administration (abstract). Even if the working structures described by Francom and Byeon are not identical to the claimed/recited structures, it would have nonetheless been obvious to the person of ordinary skill in the art at the time of Applicant’s earliest effective filing date, to incorporate the teachings of Babu to reach similar aza-sugars as both Francom and Byeon describe the concept of aza-sugars for the treatment of viral infections as all three inventions are purposed for treating such, while simultaneously capturing the improved drug-like properties of aza-sugars as described by Babu. A rationale to support a conclusion that a claim would have been obvious is that all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider both aza-sugar moiety as exemplified by Babu for their drug-like properties and taught by both Francom and Byeon, and combining with the nucleoside structures as disclosed by Francom and Byeon.
With regards to the limitations of claim 2, wherein the formula I-1 consists of substituent A represented by formula a1 and a2, are met as Francom and Babu both disclose structures and compounds that embody these substituents including compound 15 from Francom (para. 00281).
With concern to the limitations of claim 3, wherein RA6 and RB6 are each independently hydrogen, hydroxy, or alkylcarbonyl, R3 is hydrogen, and R6 is hydrogen or C1-C3 alkyl, are met as structures and compounds where RA6 = R3 = R6 = H.
With respect to the limitations of claim 4, wherein RA1 and RB1 are each independently hydroxy, amino, an aromatic heterocyclyl optionally substituted with substituent group α, or a group represented by any of the following formulae: -C(=O)-N(Ra1)(Ra2), and -C(=NRa3)-NH2, are met as Francom teaches compound 15 (para. 00281).
Regarding the limitations of claim 5, wherein RA1 and RB1 are hydroxy, a 5-membered aromatic heterocyclyl, or a group represented by either one of the following formulae: -C(=O)-NH2, and -C(=NOH)-NH2, are met as Francom teaches compound 15 (para. 00281).
Concerning the limitations of claim 6, wherein substituent A is a group represented by either formula a1 or a2 along with associated limitations, are met as Francom teaches compound 15 (para. 00281).
With regards to the limitations of claim 7, wherein RA1 and RB1 are fluorine, a 5- or 6-membered aromatic heterocyclyl, cyanomethyl, or a group represented by the following formula: -C(=NOH)-H, are met as Francom discloses compound 11 where RA1 = F (para. 00272):
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With concern to the limitations of claim 8, where a compound is selected from the formulae wherein R1 is hydrogen, a group forming a prodrug or selected from a group bi- or tri-phosphate, are met by the rationale of obviousness outlined above in paragraphs 12-16.
With respect to the limitations of claim 12, wherein the groups forming the prodrugs are described within, are met as Byeon discloses several prodrug-containing compounds including example 1 (para. 243) or in table 2 (pgs. 79-80).
Regarding to the limitations of claim 13, wherein R3, R6, RA5, RB5, RC5, RA6, RB6, and RC6 are groups other than the group forming the prodrug and R1 is hydrogen or another group described, are met by the same rationale outlined in paragraphs 12-16 where R1 = H and paragraph 24 where several examples of R1 = prodrug-moieties.
Concerning the limitations of claim 14, wherein R3, R6, RA5, RB5, RC5, RA6, RB6, and RC6 are groups other than the group forming the prodrug and R1 is hydrogen or another group described, are met by the same rationale outlined in paragraphs 12-16 where R1 = H and paragraph 24 where several examples of R1 = prodrug-moieties.
With regards to the limitations of claim 15, wherein R1, R3, R6, RA6, RB6, and RC6 are groups other than the group forming a prodrug and RA5, RB5, RC5 are each independently hydrogen or a group selected from those represented by -C(=O)-PR0; wherein PR0s are independently alkyl, are met as the rationale of obviousness outlined above in paragraphs 12-16 embody compounds where RA5 = H.
With concern to the limitations of claim 16, wherein R1, R3, RA5, RB5, RC5, RA6, RB6, and RC6 are groups other than the group forming a prodrug and R6 are each independently hydrogen or a group selected from -C(=O)-PR0 wherein PR0 is alkyl, are met as rationale of obviousness outlined above in paragraphs 12-16 embody compounds where R6 = H and Babu teaches where the formula contains structures where L4 is a bond and R4 is selected from a group consisting of H, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 acyl, phosphoryl, aryl, aralkyl, heteroaryl, and heteroaralkyl:
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Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Francom, Byeon and Babu as applied to claims 1-8 and 12-16 above, and further in view of P. L. Gould (Salt selection for basic drugs, Int. J. Pharamceutics 1986, 33, 201-217) and Allen et al. (Ansel’s pharmaceutical dosage forms and drug delivery systems 10th edition, Wolters Kluwer Health 2005).
Francom, Byeon, and Babu disclose and teach nucleosides, associated nitrogenous bases, and free base or pro-drug forms and their use in anti-viral treatment.
They do not, however, teach more about pharmaceutical salt forms or compositions.
Gould addresses this oversight by teaching that salt forms can change and/or improve various important physicochemical properties including melting point, aqueous solubility, dissolution rate, stability, and hydrophobicity. They establish trends to assist the chemist in selecting the right salt form to overcome a particular problem with a basic drug, teaching that salt forms are often a comprise in properties and should be tailored to the situation at hand (abstract).
Allen extensively covers many topics within the field of drug formulation, including, but not limited to, typical properties of select excipients, incompatibilities, safety, related substances, along with numerous other examples in categories such as disintegrants, adhesives, and surfactants (select reading; pg. 1 – section I: introduction to drugs, drug dosage forms, and drug delivery systems; pg. 101 – section II: drug dosage form and drug delivery system design).
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider the use of salt forms as taught by Gould to fix or improve upon the drug-like properties found in any target compound, or to incorporate the teachings of Allen to develop an appropriate formulation for a structure according to claim 1 for use in the desired method of treatment utilizing well established literature that is exemplified by Allen.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: elected species I-078 was found to be free of the prior art:
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The closest match is compound 15 disclosed by Francom et al. (Bycyclic nucleosides and nucleotides as therapeutic agents, WO 2010/002877 A2, 2010; entered into the IDS on 16 May 2024):
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The structures encompassed within claim 8 are also not described in the prior art in 100% manner. However, the 1,2,4-triazine moiety is well-covered by the literature along with hydrogen and pro-drug substitution at R1 and therefore do not overcome the prior rejections. In contrast, 1,3,5-triazine moiety is not well-described in the nucleoside literature compared to the other possible hetero-isomers.
Summary
Claims 1-8 and 12-19 are rejected under 35 U.S.C. 102 and 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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