DETAILED ACTION
This office action is in response to applicant’s filing dated October 3, 2025.
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 Claims
Claims 1, 2, 5, 7, 9, 10, 35, 38, 50, 72, 83-85, and 87-90 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed October 3, 2025. Acknowledgement is made of Applicant's amendment of claims 1, 7, 9, 10, 84, and 85; cancelation of claims 3, 4, 6, 8, 11-34, 36, 37, 39-49, 51-71, and 73-83; and addition of new claims 88-90.
Applicants elected without traverse Group I, drawn to a compound of Formula (I), (II), (III), or (IV) or a pharmaceutically acceptable salt or prodrug thereof as the elected invention and the compound having the structure (hereinafter referred to as Compound 9):
Compound 9
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as the elected compound of formula (I) species in the reply filed on December 4, 2023. The requirement is still deemed proper. Claims 5, 7, 9, 10, 38, 50, and 72 remain withdrawn.
Compound 9 has been construed as a Na salt of a Compound of Formula (I) wherein RA is
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, wherein R1A is alkyl (-CH2(CH2)6CH3, octyl); RB is
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, wherein R1B is alkyl (-CH2(CH2)6CH3, octyl); and R4, R5, R6, and R7 are H; and wherein RA and RB are the same.
The Examiner notes that the elected compound, Compound 9, no longer reads on the instant claims. Thus, Examination has been expanded to encompass a compound of formula (I) wherein RA is
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and RB is
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; wherein R1A and R1B are substituted C1-10 alkyl substituted with an aryl.
Claims 1, 2, 35, 83-85, and 87-90 read on the expanded species.
Claims 1, 2, 35, 83-85, and 87-90 are presently under examination as they relate to the expanded species.
Priority
The present application is a 371 of PCT/US2019/039943 filed on June 28, 2019, which is which claims benefit of US Provisional Application No. 62/692,479 filed on June 29, 2018.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
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.
Claims 1, 2, 35, 83-85, and 87-90 are rejected under 35 U.S.C. 103 as being unpatentable over Morgan et al (US 2015/0202222 A1, cited in the IDS filed May 15, 2023).
Regarding claims 1, 83-85, 87-90, Morgan teaches a molecular tweezer of formula (I):
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wherein each of X1 and X2 is O; A combined with X1 forms a alkylphosphonate; B combined with X2 forms an alkylphosphonate; and each of R1, R2, R3, and R4 are independently H (claim 12); wherein A and B are independently
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, wherein R5 is alkyl (claim 15 and [0044]). Morgan further teaches the term “alkyl” means a straight or branched saturated hydrocarbon having C1 to C14 [0142]. Morgan does not explicitly teach a substituted alkyl, substituted with an aryl.
However, Morgan teaches compounds wherein A and B are alkylphosphonate or arylphosphonate [0182]. Thus, Morgan suggests that aryl and alkyl groups are both suitable for making molecular tweezers of the disclosed invention. Moreover, Morgan teaches aryl includes phenyl and naphthyl [0143]; an aryl group may be substituted with one or more substituent groups including C1-6 alkyl [0143]. Thus, Morgan teaches arylalkyl groups are suitable for making molecular tweezers of the disclosed invention. It would have been prima facie obvious to one of ordinary skill in the art to arrive at a molecular tweezer compound wherein R5 is a substituted alkyl chain substituted with an aryl from the teachings of Morgan. The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity.
Regarding claim 2, Morgan teaches A and B are the same [0045].
Regarding claim 35, Morgan teaches the molecular tweezer may be combined with a pharmaceutically acceptable carrier (excipient) to form a pharmacological composition (pharmaceutical composition) [0201].
Taken together, all this would result in the composition of claims 1, 2, 35, 83-85, and 87-90 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
A person of ordinary skill in the art would not have been motivated to arrive at a compound of the instantly amended claims in view of Morgan.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Since a modified rejection was issued (see above), it is the Examiner’s belief that arguments regarding the amended compounds presented by Applicant have been considered/answered in the rejection itself.
Applicant argues:
Compounds of amended claim 1 are unexpectedly superior to the only example compound described in Morgan with respect to antiviral activity against the enveloped virus SARS-CoV-2.
Weil discloses several molecular tweezers encompassed by amended claim 1 that have antiviral activity against SARS-CoV-2 that is unexpectedly superior to CLRO1, the only example compound tested in Morgan.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The Examiner notes that obviousness is based on the state of the art prior to the effective filing date of the invention. The Weil reference, cited by the Applicant, has a publication date of September 6, 2022 and thus does not constitute prior art. It is unclear if the data provided would have been available to the public prior to the effective filing date of the invention. Thus, the cited reference cannot establish what was known at the time of the effective filing date. Moreover, allowing post-filing date data that is entirely unsupported by the Specification to serve as evidence of unexpected results subverts the quid pro quo inherent in the patent system. 35 U.S.C. § 112, first paragraph (2012) sets the expectation that the “specification shall contain a written description of the invention . . . and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.” It is inconsistent with the patent statute itself to advantage an unexpected result not described in the Specification, whose best mode is therefore not revealed until well after the application is filed. In the instant case, in a review of the instant specification, disclosure of covid-19 or SARS-CoV-2 was not identified. Moreover, Weill discloses 7 compounds with aryl substitutions. In a review of the instant specification, disclosure of these compounds was not identified. Thus, the disclosure of Weil cannot support an advantage or unexpected result of the claimed invention as described in the Specification.
Moreover, MPEP 716.02(d) states:
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
In the instant case, as set forth above, Weil teaches 8 specific compounds having an alkyl substituted with an aryl:
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. This is insufficient to support unexpected properties for the full scope of the claims which encompasses compounds wherein R1A and R1B are any substituted C1-10 alkyl or substituted C2-10 alkenyl substituted with any unsubstituted or substituted aralkyl or any unsubstituted or substituted aryl. As noted previously, the instant specification does not provide any teaching that the instant compounds are useful for treating covid-19 or SARS-CoV-2. The instant specification discloses antiviral activity of compounds with unsubstituted alkyl against Zika Virus (ZIKV) and HIV1. Thus, the data provided is not commensurate with the instant claims and is also not commensurate with the disclosed invention.
Thus, the data provided in Weil is insufficient to support unexpected properties of the instantly claimed compounds of formula (I).
Applicant argues:
The specification describes "A method of inhibiting the growth, and/or the proliferation, and/or the infectivity, of an enveloped virus, said method comprising contacting said virus with an effective amount of a compound (molecular tweezers) . .. ." SARS-CoV-2 is an enveloped virus. The specification further states that, in some embodiments, "said virus is a member of a family selected from the group consisting of Herpesviridae, Poxviridae, Hepadnaviridae, Coronaviridae, Flaviviridae, Togaviridae, Retroviridae, Orthomyxoviridae, Arenaviridae, Bunyaviridae, Filoviridae, Paramyxoviridae, and Rhabdoviridae." SARS-CoV-2 is a member of the Coronaviridae family. Therefore, the specification teaches that the disclosed compounds (molecular tweezers) are useful for the treatment of members of the Coronaviridae family of viruses (e.g., SARS-CoV-2). Accordingly, Weil, which teaches molecular tweezers with activity against SARS-CoV-2, can support an unexpected result associated with the amended claims.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Disclosure of the genus, enveloped virus, is insufficient to provide written description support for the species SARS-CoV-2. Enveloped virus encompasses numerous subgenus of viruses (e.g. Herpesviridae, Poxviridae, Hepadnaviridae, Coronaviridae, Flaviviridae, Togaviridae, Retroviridae, Orthomyxoviridae, Arenaviridae, Bunyaviridae, Filoviridae, Paramyxoviridae, and Rhabdoviridae as disclosed in the response, which encompasses a variety of different species of viruses within each subgenus. Disclosure of Coronaviridae is insufficient to provide written description support for the species SARS-CoV-2. Coronaviridae encompasses numerous viruses which are sorted into three groups. Group 1: Canine coronavirus, Feline coronavirus, Feline infectious peritonitis virus, Human coronavirus 229E, Porcine epidemic diarrhea virus, Transmissible gastroenteritis virus, and Human Coronavirus NL63. Group 2: Bovine coronavirus, Canine respiratory coronavirus, Human coronavirus OC43, Human enteric coronavirus, Mouse hepatitis virus, Murine hepatitis virus, Puffinosis coronavirus, Porcine hemagglutinating encephalomyelitis virus, Rat coronavirus, Sialodacryoadenitis virus, and Severe Acute Respiratory Syndrome Coronavirus (SARS). Group 3: Avian infectious bronchitis virus, Rabbit coronavirus, Infectious bronchitis virus, and Turkey coronavirus (Bluecomb disease virus). Disclosure of the genus is insufficient to provide written description support possession of a method of inhibiting SARS-CoV-2. Thus, the disclosure of Weil cannot support an advantage or unexpected result of the claimed invention as described in the Specification.
Conclusion
Claims 1, 2, 35, 83-85, and 87-90 are rejected.
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628