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 .
Application Status
The preliminary amendment filed on 3/20/2024 is acknowledged. Claims 1-5, 8-12, 20-25, 28-32 and 40 are currently pending and under consideration.
Information Disclosure Statement
The listing of references in the PCT international search report is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, “the list ... must be submitted on a separate paper.” Therefore, the references cited in the international search report have not been considered. Applicant is advised that the date of submission of any item of information in the international search report will be the date of submission of the IDS for purposes of determining compliance with the requirements for the IDS with 37 CFR 1.97, including all timing statement requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
There are numerous uses of trade names or marks within the specification. For example, the use of the term ATPLITETM, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 5, 8-12, 20-23, 25, 28-32 and 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grunweller et al. (EP3305289A1, 2018-11-04) in view of Wendel et al. (US2015/0219624A1, 2015-08-06) and Muller et al. (Antiviral Research 2018; 150: 123-129).
Grunweller et al. teach the use of Silvestrol, Episilvestrol, Silvestrol analoga and other Rucaglamates for treating infections with viruses whose protein translation requires a cap-structure at the 5’-end of viral mRNAs (paragraph 1). With regards to the viruses, the EP document teaches that viruses include all types of RNA viruses which also perform cap-dependent protein translation, e.g. Coronaviridae, Flaviviridae, and Togaviridae (paragraph 0026). With regards to Coronaviridae, the EP document teaches that Silvestrol is an effective inhibitor of MERS-CoV (high pathogenic) and HCoV-229E (low pathogenic) replication in primary MRC-5 lung cells (paragraph 0022). Moreover, Grunweller et al. teach a medicament comprising a therapeutic effective amount of Silvestrol, Episilvestrol, Silvestrol analoga and other Rucaglamates for the treatment of virus infections of humans and/or mammals, wherein the medicament further comprises a pharmacological carrier substance (paragraph 0026 and 0041).
Grunweller et al. does not teach that the other rucaglamate is CR-31-B.
Wendel et al. teach a method preventing in a subject the translation of mRNA comprising an eIF4A-dependent translation-controlling motif, the method comprising administering to the subject an agent that blocks eIF4a helicase activity, thereby inhibiting translation of mRNA (claim 78 of Wendel et al.). With regards to the agent, Wendel teach that the agents include a rocaglamide such as silvestrol or CR-31-B (+/-) (Paragraph 0086). Moreover, Wendel et al. teach that (+/-) CR-31-B binds the same site on eIF4A as Silvestrol (paragraph 0146).
Muller et al. teach that the EIF4A inhibitor Silvestrol has broad-spectrum antiviral activity against corona and picornaviruses (Title). Specifically Mullet et al. teach that silvestrol-mediated eIF4A inhibition is a promising strategy for combating pathogenic RNA viruses (page 128, 2nd column, 1st full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute silvestrol as taught Grunweller et al. with CR-31-B in view of the teachings of Wendel et al. and Muller et al. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Wendel et al. teach that CR-31-B is a rocaglamide analog similar to silvestrol, wherein CR-31-B binds to the same site on eIF4A as Silvestrol, and
-Muller et al teach inhibition of eIF4A inhibition is a promising strategy for combating pathogenic RNA viruses.
Regarding a racemic mixture of CR-31-B, Wendel et al. teach (+/-) CR-31-B so it is presumed that the CR-31-B is a racemic mixture comprising both the (+) and (-) isoforms of CR-31-B.
Regarding the properties as recited in claims 5, 8-10, 25 and 28-30, it is noted that the combination teaches administering the same compound to the claimed patient population. As such, the property as claimed would appear to be necessarily present by the combination. The office does not have the facilities or resources to determine whether such property is necessarily present. Burden is on Applicants to show that such a property is not present by performing the same active steps, with the same compound and same patient population.
Claim(s) 4 and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grunweller et al. (EP3305289A1, 2018-11-04) in view of Wendel et al. (US2015/0219624A1, 2015-08-06) and Muller et al. (Antiviral Research 2018; 150: 123-129), as applied to claims 1-3, 5, 8-12, 20-23, 25, 28-32 and 40 above, in further view of Liu et al. (J. Med. Chem. 2012; 55:8859-8878).
The combination of Grunweller et al., Wendel et al. and Muller et al. have been described above and incorporated herein. In short, the combination teach a method of treating a viral infection comprising administering (+/-) CR-31-B.
The combination does not teach administering only (-) CR-31-B.
Liu et al. teach synthetic silvestrol analogues as potent and selective protein synthesis inhibitors (Title). In particular, Liu et al. teach the synthesis and evaluation of at least 20 silvestrol analogues all of which are in Silvestrol’s (-) confirmation (Table 1 and Table 2). Interestingly, Liu et al. teach the isolation of the (+) isomer for cmpd 4 referred to as ent-4, but this compound was never tested (Scheme 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the racemic mixture of CR-31-B as taught by the combination with only (-)CR-31-B in view of the teachings of Liu et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Liu et al. teaches that the silvestrol is in the (-) isomer and further all compounds synthesized and tested contained the (-) isomer only.
Conclusion
Therefore, No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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/BRANDON J FETTEROLF/ Primary Examiner, Art Unit 1626