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 .
Priority
The instant application is a 371 National Stage Entry of PCT/PCT/US21/35824 filed on June 4, 2021 which claims benefit to domestic provisional application No. 63/035,185 filed on June 5, 2020.
Status of Claims
Acknowledgement is made of amended (1, 8, 15-16, 19-20, 25), withdrawn (17), and cancelled (2-7, 9-14, 18, 21-24, 26-30) claims filed on January 14, 2026. Claims 1, 8, 15-17, 19-20, 25 are pending in instant application. Claim 17 is withdrawn as being drawn to non-elected species. Claims 1, 8, 15-16, 19-20, 25 are presently examined.
Response to Arguments
Applicant's arguments filed January 14, 2026 have been fully considered but they are not persuasive.
Applicant argues the Title is now descriptive. The Examiner disagrees, the Title is still broadly referencing “compositions” which is not descriptive.
Applicant argues the 35 USC § 102(a)(1) rejection should be withdrawn. The Examiner has modified the rejection under 35 USC § 103 in light of Applicant’s amendments. The prior art still teaches RocA as an eiF4A inhibitor (as taught by Iwasaki), and eiF4A inhibitors are known to treat the flavivirus ZIKA (as taught by Elgner).
Applicant argues the 35 USC § 103 rejection should be withdrawn and that claim 13 was not rejected under 35 USC § 103 and its limitations incorporated into claim 1 render the claim novel. The Examiner notes claim 13 was rejected in the previous Office Action under 35 USC § 103 (see 10/16/25 Office Action at p. 7).
Applicant argus that substitution of silvestrol for RocA yields unpredictable results and references Elgner Figure 3F and instant Figure 4C. The Examiner notes the figures are comparing apples to oranges:
the y-axes are different units (instant viral production in Log10(pfu/mL) compared to Elgner relative titer, a normalized value)
the x-axes are different (instant line graph hpi compared to Elgner’s bar graph three concentrations at three time points)
the concentrations of the active species are different (instant 15 nM, 30 nM, and 60 nM of RocA compared to Elgner’s 5 nM, 10 nM, and 50 nM silvestrol)
One skilled in the art would not be able to determine if silvestrol or RocA is better, just that they both inhibit eiF4A. Absent unexpected results in an experiment directly comparing silvestrol and RocA for treating ZIKA, Applicant’s invention can not be viewed as novel.
Election/Restrictions
Claim 17 remains 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. Election was made without traverse in the reply filed on August 27, 2025.
Maintained/Modified Rejections & Objections
Specification
The title of the invention is still not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The Examiner suggests the title should describe a defined class of inhibitors or species and a defined class of disease or disease species for treatment. For example, ROCALGAMIDE A FOR TREATING FLAVIVIRUS INFECTIONS.
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.
Claims 1, 8, 15-16, 19-20 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Elgner et. al.1 and as evidenced by Yoder-Hill and in further view of EP3305290 A1 to Grunweller et. al.2, Iwasaki et. al.3, and Taguwa et. al.4
Claim interpretation: The instant specification states the terms "patient" or "subject" are used interchangeably and refer to mammals such as human patients and non-human primates, as well as veterinary subjects such as rabbits, rats, and mice, and other animals (see instant spec. at p. 14 ¶5).
Regarding claims 1, 8, 25 and an inhibitor of viral replication, Elgner teaches the compound silvestrol is an inhibitor of eIF4A which is required to unwind 5'-UTRs, and because of this property treats ebola, corona, and picornavirsues. Elgner teaches Zika virus harbors 5'-UTR, and silvestrol has antiviral effects on Zika infections (see Elgner at Abstract). Elgner teaches administering silvestrol to A549 cells to inhibit a Zika infection (see Elgner at p. 6 ¶1).
The prior art differs from the claims as follows: While Elgner and Yoder-Hill teach silvestrol is an inhibitor of eIF4A1 and treatment for Zika viral infections, they do not specify (i) RocA for Zika treatment or (ii) with an additional therapeutic agent such as JG40 or (iii) administering to a subject.
However,
Regarding RocA, Iwasaki teaches RocA is known to reduce eiF4A activity (see Iwasaki at p. 558 right col ¶1).
Regarding claims 15-16, 19-20 and an additional therapeutic agent such as JG40, Taguwa teaches HSP70 inhibitors are refractory to the emergence of drug-resistance viruses and candidates for treating Zika virus infections (see Taguwa at Abstract). Taguwa also teaches JG40 is an HSP70 inhibitor (see Taguwa at Figure 2).
Regarding administering to a subject, Grunweller teaches administering silvestrol to treat a virus in a human (see Grunweller at p. 7 ¶[0046]) such as Zika (see Grunweller at p. 9 ¶[0058]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding RocA for silvestrol, per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to one skilled in the art to substituted RocA for silvestrol to treat Zika because the prior art teaches they are both eIF4A inhibitors (as taught by Elgner and Iwasaki), and that eIF4A inhibition is a mechanism for treating Zika infections (as taught by Elgner).
Regarding a second therapeutic agent, per MPEP § 2144.06(I), "[i]t 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” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). It would have been been obvious to one skilled in the art to combine a known treatment for Zika such as silvestrol or RocA (as taught by Elgner and Iwasaki) with another known Zika treatment such as an HSP70 inhibitor including JG40 (as taught by Taguwa) in order to treat Zika.
Regarding administering, it would have been obvious to administer an eIF4A inhibitor to a subject to treat a flavivirus such Zika because the prior art teaches administering eIF4A inhibitor silvestrol to treat a virus in a human (as taught by Elgner, Grunweller).
Furthermore, it is well-within the ordinary skill in art to combine known Zika treatments for the same purpose as taught by the prior art (treating Zika). Furthermore, it is well-within the ordinary skill in art to incorporate one eIF4A inhibitor for another.
Accordingly, claims 1, 8, 15-16, 19-20 and 25 are obvious over Elgner as evidenced by Yoder-Hill in further view of Grunweller, Iwasaki, and Taguwa.
Conclusion
Claims 1, 8, 15-16, 19-20, 25 are rejected.
Claim 17 stands withdrawn.
THIS ACTION IS MADE FINAL. 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.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Elgner et. al. "Inhibition of Zika Virus Replication by Silvestrol" Viruses 2018, 10, 4, 149. DOI: 10.3390/v10040149. Cite No. 11 in the IDS filed 7/25/23
2 Published April 11, 2018. Cited in IDS filed 6/27/24. Hereinafter Grunweller.
3 Iwasaki et. al. "Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor" Nature 2016, 534, 558-561. DOI: 10.1038/nature17978. Cite No. 22 in the IDS filed 7/25/23.
4 Taguwa et. al. "Zika Virus Dependence on Host Hsp70 Provides a Protective Strategy against Infection and Disease" Cell Reports 2019, 26, 4, 906-920. DOI: 10.1016/j.celrep.2018.12.095. Cite No. 46 in the IDS filed 7/25/23.