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 .
Response to RCE
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible
for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has
been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37
CFR 1.114.
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Acknowledgement is made of previously presented (1, 8, 15-16, 19-20, 25), withdrawn (17), and cancelled (2-7, 9-14, 18, 21-24, 26-30) claims filed on August 3, 2026.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 Claim 17 is withdrawn as being drawn to non-elected species.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.
Examiner Note
While not presently examined, for the purposes of compact prosecution the Examiner notes a typographical error in withdrawn claim 17, “The method of claims 16” (emphasis added) which should read “The method of claim 16”. Claim 17 also states “said oligonucleotide is a small inhibitory RNA (siRNA), a microRNA (miRNA), and a short hairpin RNA (shRNA)” (emphasis added). It is unclear if applicant meant “or” for an alternative list (siRNA, miRNA, or shRNA), or if “a oligonucleotide” is referring to a mix comprising all three (siRNA, miRNA, and shRNA) which is confusing because of the singular “a”.
Response to Arguments
In light of Applicant’s amendment to the specification filed August 3, 2026 the following has been withdrawn:
The objection to the specification
Applicant's arguments filed August 3, 2026 have been fully considered but they are not fully persuasive.
It is the Examiner’s understanding that Applicant repeatedly alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Reply filed August 3, 2026 at “II. The rejection under 35 USC 103 should be withdrawn” and the 8/3/26 Declaration).
However, to establish unexpected results, the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP § 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
If Applicant means to allege the existence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 based upon instant Figure 4C (see, e.g Reply filed August 3, 2026 at “II. The rejection under 35 USC 103 should be withdrawn”, see also 8/3/26 Declaration) this is also not persuasive because the requirements of MPEP § 716.02 have not been satisfied. Specifically, MPEP § 716.02(d) is not satisfied because such proffered evidence is not commensurate in scope with the instant claims with respect to any amount of RocA, any flavivirus, and prevention vs treatment scenarios (see, e.g., instant claim 1; see also MPEP § 716.02(d)(I)-(II)); rather the example is highly limited with RocA; only tested specific strains of poliovirus (a non-flavivirus), Zika virus, and Dengue virus; and fail to establish that the observed results persist within the full scope and ranges of compositions presently claimed (see, e.g., MPEP § 716.02(d)). In regards to unpredictability in the art, the 8/3/26 Declaration states, “although compounds such as RocA and silvestrol act on the same target enzyme, one cannot predict from the fact alone which mRNAs or which viral RNAs would be translationally inhibited by any given drug” (see 8/3/26 Declaration at p. 3 “12.”). Accordingly Applicant’s data regarding RocA against the flaviviruses Zika and Dengue is insufficient to “speak” for all flaviviruses, including instantly claimed West Nile virus, yellow fever virus, or Japanese encephalitis virus. Forat least these reasons, the proffered data at Figure 4C is insufficient to establish unexpected results commensurate in scope with the requirements of MPEP § 716.02. Accordingly, evidence of any unexpected results commensurate in scope with the requirements of MPEP § 716.02 has not been placed on record at this time.
Applicant’s arguments regarding unexpected results is commensurate for the scope of administering a therapeutically effective amount of RocA for treating Zika virus or Dengue virus in a subject, or inhibiting replication of Zika virus or Dengue virus in a cell.
Applicant argues no expectation of success would exist for substituting RocA for silvestrol (see 8/3/26 Remarks at p. 7 ¶1). The Examiner disagrees; while different eIF4A inhibitors may have different binding modes, kinetics, or downstream effects, rocaglate derivatives are known in the art to inhibit Zika virus. Muller et. al.1 teaches rocaglate CR-31-B(-), a structurally similar compound to RocA and silvestrol, inhibits the replication of Zika, Lass, and Crimean Congo hemorrhagic fever viruses (see Muller at Abstract and at Figure 1, shown below).
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As mentioned in the previous office action, silvestrol is known in the art to inhibit Zika virus (as taught by Elgner). An artisan would thus have a reasonable expectation of success for a rocaglate derivative and eIF4A inhibitor to exhibit an anti-Zika virus effect.
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.
Compact prosecution: During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
New Rejections
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.
Claim 25 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 10,085,988 B1 to Wang et. al.2
Regarding claim 25 and a method of inhibiting replication of a flavivirus in a cell with RocA, Wang teaches rocaglamide A has antiviral activity against Dengue virus, reading on instant flavivirus, at low concentrations (see Wang at Figure 5 and col. 8 lines 17-29).
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 are rejected under 35 U.S.C. 103 as being unpatentable over Wang.
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 and a method of treating a flavivirus infection with RocA, Wang teaches rocaglamide A has antiviral activity against Dengue virus at low concentrations (see Wang at Figure 5 and col. 8 lines 17-29).
The prior art differs from the instant claims as follows: while Wang teaches RocA has antiviral properties against Dengue virus, Wang does not specify administering RocA to a subject.
However, 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):
Per MPEP § 2144.07, a prima facie case of obviousness exists for the selection of a known material based on its suitability for its intended use. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). It would have been obvious to an artisan to administer RocA to a subject to treat or prevent a Dengue virus infection because the prior art teaches it has antiviral properties against Dengue virus (as taught by Wang), so RocA would be performing it’s art-recognized intended use as an anti-Dengue agent.
Furthermore, it is well-within the ordinary skill in art to select a known antiviral for the purpose of treating a known viral infection.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 15-16, 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wang as applied to claims 1, 8 above and in further view of Taguwa 20153.
The prior art differs from the instant claims as follows: while Wang teaches RocA for treating Dengue virus infections, Wang does not specify further administering a second therapeutic.
However,
Regarding claims 15-16, 19-20 and an additional therapeutic agent such as JG40, Taguwa teaches JG40 is an allosteric HSP70 inhibitor that blocks infection of Dengue virus, and also blocks replication of other flaviviruses such as West Nile virus, yellow fever virus, and Japanese encephalitis virus (see Taguwa at Abstract).
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 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 Dengue virus infection such as RocA (as taught by Wang) with another known anti-Dengue virus treatment such as an HSP70 inhibitor including JG40 (as taught by Taguwa 2015) in order to treat a Dengue virus infection.
Furthermore, it is well-within the ordinary skill in art to combine two known treatments for Dengue virus infections for same purpose as taught by the prior art (treating a Dengue virus infection).
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Maintained/Modified Rejections & Objections
Claims 1, 8, 15-16, 19-20 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Elgner et. al.4 and as evidenced by Yoder-Hill and in further view of EP3305290 A1 to Grunweller et. al.5, Iwasaki et. al.6, and Taguwa et. al.7
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Cited in the 6/27/24 IDS. Muller et. al. "Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol" Antiviral Research 2020, 175, 104706, 1-10. DOI: 10.1016/j.antiviral.2020.104706. Available online January 10, 2020. Hereinafter Muller.
2 Cite No. 1 in the IDS filed 7/25/23. Patented October 2, 2018. Hereinafter Wang.
3 Cite No. 45 in the IDS filed 7/25/26. Taguwa et. al. "Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection" Cell 2015, 163, 1108-1123. DOI: 10.1016/j.cell.2015.10.046. Herienafter Taguwa 2015.
4 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
5 Published April 11, 2018. Cited in IDS filed 6/27/24. Hereinafter Grunweller.
6 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.
7 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.
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