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 .
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.
Response to Amendment
The amendment filed June 15, 2026 has been entered. Claims 1, 5, 8-10, 13, 19, 22, 28 have been amended, claims 2-4, 6-7, 15 have been cancelled. Applicant’s amendments to the claims have overcome the 112(a), 112(b), 102, and the 103 rejections over Shen alone previously set forth in the Non-Final Office Action mailed March 13, 2026. Applicants cancellation of claims 2-4, 6-7, 15 have rendered the corresponding rejections/objections moot. As such, these rejections and objections are hereby withdrawn.
Applicant’s arguments filed June 15, 2026 were fully considered but they were not persuasive. Modified/New rejections necessitated by Applicant’s amendment and response to arguments are addressed below.
Claims 1, 5, 8-14, and 16-30 are pending in this application.
Priority
This application is a track one application. This application is a continuation of PCT/US2024/027749 filed 05/03/2024 and claims the benefit of US provisional applications 63/571,795 filed 03/29/2024, 63/588,255 filed 10/05/2023, 63/534,748 filed 08/25/2023, and 63/500,416 filed 05/05/2023.
Modified/New 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 1, 5, 8-14, 16-26, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over (Shen, WO 2022/218274, cited in previous action, the English translation has been provided by the Examiner) in view of Butora (WO 2007/021610, cited in previous action).
Regarding claims 1, 5, 8-14, 16-26, and 29-30: Shen teaches nucleoside analogs, pharmaceutical compositions thereof for treating and/or preventing diseases caused by coronaviruses, paramyxoviruses, influenza viruses, flaviviruses, filoviruses, bunya viruses, and/or arenaviruses (English translation, abstract). Shen teaches viruses to be treated include, RSV, hepatitis C virus, influenza A, B, or C, SARS-CoV-2, (English translation, pg. 40, paras. 2-10). Shen teaches a pharmaceutical composition comprises a pharmaceutically acceptable carrier and in a preferred embodiment the composition can comprise additional antiviral active ingredients (English translation, pg. 39, middle of page). In a preferred embodiment the preparation includes oral formulations (English translation, pg. 39, second to last sentence). In a preferred embodiment the preparation includes powders or tablets (English translation, pg. 39, last sentence). According to the instant specification an excipient can be a capsule, a tablet, a cachet, a pill, a powder, a granule, an elixir, a tincture, a suspension, a syrup, or an emulsion (pgs. 156-157, bridging para.). Shen specifically teaches the following compound B4:
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has activity against RSV and H3N2 influenza (English translation, pg. 58, Table, row 8, compound B4). Shen also teaches the following compound:
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(English translation, pg. 55, top scheme, compound C54). Shen teaches both
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(B4) and
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are compounds of formula I:
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wherein the B group can be
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as alternatives (English translation, pgs. 14-13, bridging para.).
Taken together, it would have been prima facie obvious to substitute the cyclopropyl in B4 with cyclohexyl arrive at the following compound
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as demonstrated by Shen. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as both features are encompassed by the same formula and explicitly demonstrated in Shen. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities (See MPEP 2144.09 (I)). In short, the following compound is rendered obvious over Shen
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. The compound of Shen is of the following formula:
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wherein R5 is cyclohexyl and R1 and R7 are H (English translation, pg. 16, bottom of page, formula I-V). Shen teaches the compounds are a class of nucleoside prodrugs with good pharmacokinetic properties such as high oral bioavailability and significant antiviral activity (English translation, pg. 40, third para. from bottom of page). Shen teaches viruses to be treated include hepatitis C virus (English translation, pg. 40, para. 6). Shen teaches that nucleoside analogs are an important class of antiviral drugs which interfere with the replication of genetic material (English translation, pg. 14, para. 6). Shen teaches other analogs which are cyclic acetals
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(English translation, pg. 44, bottom of page).
Shen does not explicitly teach wherein R5 is a 4-chlorobenzoyl group as recited by instant claims 5, 8-14, and 16-17 as demonstrated in the following compound:
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.
However, Butora teaches antiviral nucleoside cyclic acetals which precursors or prodrugs of inhibitors of RNA-dependent RNA viral polymerase or RNA-dependent RNA viral replication (abstract). Butora teaches the preparation of the following compound
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wherein R2 is 4-chlorophenyl and R3 is
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(pg. 33, bottom of page, example 27).
Taken together, it would have been prima facie obvious to modify the compound of Shen such that the cycloalkyl group is replaced with a para-chloro group as taught by Butora, arriving at the following compound
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. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as 5’-benzylation is a known tolerable modification in nucleoside prodrugs for the treatment of the viral infections. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities (See MPEP 2144.09 (I)).
Claims 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over (Shen, WO 2022/218274, cited in previous action, the English translation has been provided by the Examiner) and Butora (WO 2007/021610, cited in previous action) as applied to claims 1, 5, 8-14, 16-26, and 29-30 above in view of Ivachtchenko (WO 2018/160088, cited in previous action, the English translation has been provided by the Examiner).
Regarding claims 27-28: As discussed above the prior art renders obvious the method of claim 19.
Shen does not teach wherein the patient is administered a loading dose in a first treatment period, and the subject is administered a treatment dose in the second treatment period, wherein the first treatment period is 1-5 days following diagnosis of the viral infection.
However, Ivachtchenko teaches analogous antiviral nucleotide compounds useful for the treatment of viral infections (English translation, abstract). Ivachtechenko teaches treatment is started with a large initial “loading dose” to quickly reduce or eliminate the virus accompanying the decreasing dose to a level sufficient to prevent an outbreak of infection (English translation, pg. 14, para. 4).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Shen by incorporating a loading dose in the initial treatment immediately following diagnosis (i.e. day 1) as suggested by Ivachtchenko. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to quickly reduce or eliminate the virus accompanying the decreasing dose to a level sufficient to prevent an outbreak of infection and to effectively treat the subject as early as possible.
Allowable Subject Matter
Claim 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The closest prior art is (Shen, WO 2022/218274, cited on PTO-892, the English translation has been provided by the Examiner) in view of Butora (WO 2007/021610, cited on PTO-892).
As discussed above, the prior art render obvious the following compound:
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wherein chlorine is in a para position.
They do not teach wherein the chlorine is in the meta position.
It would be improper hindsight to suggest it would have been prima facie obvious to a person of ordinary skill in the art to further modify the references by moving the chlorine to the meta position to arrive at the instantly claimed compound. A person of ordinary skill in the art would lack the motivation to do so as there is no clear teaching that there is a benefit in doing so, or demonstrates it as a tolerable modification in the art of nucleoside prodrugs.
Response to Arguments
Applicant’s arguments filed June 15, 2026 with respect to the claims as they currently apply have been fully considered but they are not persuasive.
On page 12 of Applicant’s response, Applicant argues an obviousness rejection based on similarity in structure in function requires that the skilled artisan would expect the compounds to have similar properties and showing that the skilled artisan would be motivated to make the claimed compound (para. 3). Applicant argues obviousness based on structural similarity requires clear and convincing evidence that a person of ordinary skill in the art would have been motivated to select and modify a prior art chemical to arrive at a claimed compound with a reasonable expectation of success (para. 4). On page 13 of Applicant’s response, Applicant argues there are no particularly interesting features of B4 and that B1, B38, and B41 all exhibit superior activity against RSV and influenza (para. 1). Applicant argues a person of ordinary skill in the art would not have selected B4 when considering the teachings of Shen as the starting point for further development efforts (para. 2). Applicant argues Shen fails to supply a reason or motivation for modifying B4 with any reasonable expectation of success, and modifying the ester substituents can have wide ranging effect on inhibitory activity (para. 3). On page 14 of Applicant’s response, Applicant argues a person of ordinary skill in the art would understand the teachings of Shen that minor modifications in chemical structures can lead to potentially drastic alterations in their observed antiviral activity.
However, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (See MPEP 2123 (II)). There is no requirement for a person of ordinary skill in the art to select the “best” compound for further modification, Shens teaching of a compound with antiviral activity warrants its starting point for further modification. Furthermore, Shen establishes that modification of the ester moiety in nucleoside antivirals is a known technique for optimizing a lead compound for antiviral activity. Butora further reinforces this notion it that it similarly explores ester modification of nucleoside antivirals. A person of ordinary skill in the art would have the requisite motivation to modify the nucleoside antivirals with modifications taught by Butora as they are a recognized class of compounds (i.e. nucleoside drugs) known for the same purpose of acting as an antiviral for the purpose of optimizing for increased therapeutic success, a known technique in the art. Additionally neither Shen or Butora teach away from ester modifications that are instantly claimed. In short, given that Shen and Butora are directed to nucleoside antivirals, a person of ordinary skill in the art would have the motivation to incorporate features from Butora into the compounds of Shen, given that they are a comparable class of molecules for treating viral infections.
On page 14 of Applicant’s response, Butora is silent to any data with respect to any of the compounds regarding antiviral data (para. 2). Butora merely discusses a large variety of potential modifications that could be made without any clear guidance regarding what specific modifications to make (para. 2). On pages 14-15 of Applicant’s response, Applicant argues a person of ordinary skill would have to perform thousands of experiments just to arrive in proximity to the compounds presently claimed (bridging para.). On page 15 of Applicant’s response, Applicant argues there would be no expectation of success in arriving at the claimed compounds from those in Shen in combination of Butora (para. 2). Applicant argues only improper hindsight would have resulted in arriving at the claimed compounds (para. 2).
However, as discussed above, Shen and Butora are directed to a comparable class of compounds for the same purpose, cyclic acetal nucleoside antivirals. Both Shen and Butora explore various ester substitutions, establishing such modifications as a known technique in the art. Given explicit disclosure of the chloro phenyl substituent on the ester group, a person of ordinary skill in the art would have the motivation to incorporate such a feature from Butora into the compounds of Shen, given that they are a comparable class of molecules for treating viral infections, absent a showing of unexpected results.
On pages 15-16 of Applicant’s response, Applicant argues Ivachtechenko does not cure the deficiencies described above (bridging para.).
See response to arguments above.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 103 rejections are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693
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