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 .
Status of the Claims
Claims 22 – 37 are pending.
Claims 22 – 26 and 36 – 37 are rejected.
Claims 27 – 35 are withdrawn.
Election/Restriction
Applicant’s election without traverse of Group I, claims 22 – 26 and 36 – 37, in the reply filed on January 23, 2026 is acknowledged. Applicant specifically elected compound HUP1108:
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The compound reads on the structure of general formula (1) (claim 22):
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, wherein:
R1 is –(CH2)n1-Z1-R11,
n1 is 1,
Z1 is O, and
R11 is H.
The compound reads on the structure of formula (1-1) (claim 23):
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, wherein:
R21 is H.
Examination: Applicant’s elected compound HUP1108 reads on claims 22 – 26 and 36 – 37. The elected species is not allowable over the prior art. Examination of the Markush-type claim has not been extended. Claims 27 – 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Priority
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, the filing date of the priority document is not perfected unless Applicant has filed both, a certified copy of the document and an English language translation (if the document is not in English) (see, 37 CFR 1.55(g)(3)). Accordingly, the claims do not receive the filing date of the earlier filed priority document and are examined with an effective filing date of January 20, 2022 (the filing date of the ‘997 PCT Application).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 20, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is 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.
Claims 22 – 26 and 36 – 37 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 22 recites the limitation “… R11 is a hydrogen atom, an alkyl group… six-membered heterocyclic group including a nitrogen atom”. Emphasis added. See, page 2, lines 9-10. Claim 23 recites the limitation “A is a five- or six-membered heterocyclic group including a nitrogen atom”. Emphasis added. See, page 4, line 10. The term “including” is a relative term. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the term creates a level of ambiguity regarding the metes and bounds of the claims and renders the instant claims indefinite. Dependent claims 24 – 26 and 36 – 37 also do not properly define or cure the deficiencies present in claims 22 – 23 and are also considered indefinite.
In order to overcome the rejection, Applicant may amend to replace the term “including” with the term “comprising”.
Claim Rejections - 35 USC § 102
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 22 – 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Uemura et al., iScience, 24 (10), October 22, 2021, 103120, Retrieved on February 20, 2026, https://www.sciencedirect.com/science/article/pii/S2589004221010889?via%3Dihub.
Uemura et al. teach the compound HUP1108 (HMTU), 5-hydroxymethyltubercidin. See, e.g., pg. 2, Figure 1. Compound HUP1108 (HMTU) is presented below:
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Uemura et al. also teaches that the compound exhibits potent antiviral activity against flaviviruses and human coronaviruses, specifically SARS-CoV-2. See, e.g., Title, pg. 3, 1st paragraph, Tables 1-3.
The prior art anticipates the instant claims as presented below:
Claims 22 and 24 – 25, directed to an antiviral agent comprising a compound represented by general formula (1):
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, wherein:
R1 is –(CH2)n1-Z1-R11,
n1 is 1,
Z1 is O, and
R11 is H.
Claim 23, wherein the compound is the compound of formula (1-1):
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, wherein:
R21 is H.
With respect to claim 26, Uemura et al. teaches that the compound exhibits potent antiviral activity against flaviviruses and human coronaviruses, specifically SARS-CoV-2. See, e.g., Title, pg. 3, 1st paragraph, Tables 1-3. The data of Table 3 is presented below:
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Thus, Uemura et al. teaches the pharmaceutical composition comprising the antiviral agent HUP1108 (HMTU), 5-hydroxymethyltubercidin.
Claims 22 – 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Montgomery et al., Biological Methylation and Drug Design (1986), pp. 409-416, as cited in IDS dated July 20, 2023.
Montgomery et al. teach nucleoside analog compounds as antiviral agents. See, e.g., Title. Montgomery et al. also teaches a 7-hydroxymethyl derivative of c7-Ado compound. See, e.g., pg. 413, 1st paragraph. The 7-hydroxymethyl derivative is compound 14 (see, e.g., pg. 411) as presented below:
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Montgomery et al. also teaches that the compound exhibits potent antiviral activity against viruses vaccinia, vesicular stomatitis, parainfluenza type 3, and reo type 1. See, e.g., pg. 409, 1st paragraph, Table 2.
The prior art anticipates the instant claims as presented below:
Claims 22 and 24 – 25, directed to an antiviral agent comprising a compound represented by general formula (1):
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, wherein:
R1 is –(CH2)n1-Z1-R11,
n1 is 1,
Z1 is O, and
R11 is H.
Claim 23, wherein the compound is the compound of formula (1-1):
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, wherein:
R21 is H.
With respect to claim 26, Montgomery et al. teaches that the 7-hydroxymethyl derivative of c7-Ado compound (compound 14) exhibits significant antiviral activity. See, e.g., pg. 414, 1st paragraph, Table 2. The data of Table 2 is presented below:
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Thus, Montgomery et al. teaches the pharmaceutical composition comprising the antiviral agent 14.
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.
Claims 36 – 37 are rejected under 35 U.S.C. 103 as being unpatentable over Montgomery et al., Biological Methylation and Drug Design (1986), pp. 409-416, as applied to claims 22 – 26 above, in view of Boras et al., bioRxiv, September 13, 2020, https://www.biorxiv.org/content/ 10.1101/2020.09.12.293498v2.full.
Determining the scope and contents of the prior art
Montgomery et al. teach nucleoside analog compounds as antiviral agents. See, e.g., Title. Montgomery et al. also teaches a 7-hydroxymethyl derivative of c7-Ado compound. See, e.g., pg. 413, 1st paragraph. The 7-hydroxymethyl derivative is compound 14 (see, e.g., pg. 411) as presented below:
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Montgomery et al. also teaches that the compound exhibits potent antiviral activity against viruses vaccinia, vesicular stomatitis, parainfluenza type 3, and reo type 1. See, e.g., pg. 409, 1st paragraph, Table 2.
Montgomery does not teach the pharmaceutical composition, further comprising an inhibitor of 3CL protease, specifically PF-07304814.
Boras et al. teach 3CL protease is a “virally encoded protein that is essential to the viral life cycle across a broad spectrum of coronaviruses with no close human analogs”. See, e.g., Abstract. Boras also teaches a phosphate prodrug PF-07304814 which is metabolized to PF-00835231, a potent inhibitor in vitro of the coronavirus family 3CL pro. See, e.g., Abstract. Boras further teaches PF-07304814 exhibits high systemic clearance and short half-life to provide metabolic stability and conversion to its active moiety (PF-00835231). See, e.g., bridging paragraph between page 13-14.
Ascertaining the differences between the prior art and the claims at issue
Compared to claims 36 – 37, Montgomery et al. do not teach that the pharmaceutical composition comprising antiviral compound 14 further comprises an inhibitor of 3CL protease, specifically PF-070304814.
Rationale for a prima face case of obviousness
According to MPEP §2141(III), two of the rationales in the KSR decision states “(A)
Combining Prior Art Elements According to Known Methods To Yield Predictable Results…
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary
skill to modify the prior art reference or to combine prior art reference teachings to arrive at the
claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Boras et al. further teach a potential antiviral combination of the metabolized inhibitor PF-00835231 in combination with another antiviral agent, remdesivir. Boras teaches that the drug combination can be analyzed to understand the additive, synergistic or antagonistic effects. See, e.g., pg. 7, 1st paragraph. MPEP §2144.06(I) further states:
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”.
A person having ordinary skill in the art would have been motivated to co-administer compound 14
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with 3Cl protease prodrug PF-07304814 because Boras teaches that this compound have been generally known to be co-administered with other antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Montgomery et al. and Boras et al. show that compound 14 and 3Cl protease inhibitor PF-07304814 are useful for the same purpose as antiviral agents. The PHOSITA would find it advantageous to co-administer compound 14 and 3Cl protease inhibitor PF-07304814 in the pharmaceutical compositions.
Thus, the prior art renders the instant claims prima facie obvious.
Conclusion
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/Sagar Patel/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626