DETAILED ACTION
This office action is in response to applicant’s filing dated June 24, 2026.
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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 24, 2026 has been entered.
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 June 24, 2026. Claims 3, 4, 6, 8, 11-34, 36, 37, 39-49, 51-71, and 73-83 were previously canceled.
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 Claims 5, 7, 9, 10, 38, 50, and 72 remain withdrawn.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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 24, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
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 an 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
The Declaration of Thomas Schrader under 37 CFR 1.132 filed June 24, 2026 is insufficient to overcome the rejection of record and is addressed in the response to arguments set forth below.
Applicant argues:
Morgan’s disclosure does not suggest the instantly claimed compounds. Morgan discloses alkylphosphonate and arylphosphonate. As would be readily recognized by those of skill in the art, alkylphosphonate and arylphosphonate relate to moieties in which alkyl or aryl, respectively, are attached directly, via P-C bond, to the phosphorus atom. The only reference in Morgan to a phosphate ester relates only to alkyl phosphate monoester. The only reference in Morgan to aryl relates to aryl phosphonate, in which the aryl is attached directly to the P atom.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Morgan teaches a molecular tweezer of formula (I). As set forth above, Morgan teaches compounds wherein A and B are alkylphosphonate or arylphosphonate. Thus, Morgan suggests that aryl and alkyl groups are both suitable for making molecular tweezers of the disclosed invention. Morgan teaches A and B can be the same or different and can be
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. Thus, Morgan teaches that attaching R5 directly to the O or to the P is alternatively useful for forming molecular tweezer compounds of formula (I). As set forth above, 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.
Applicant argues:
Morgan’s disclosure would not have prompted introducing hydrophobic substituents such as alkylaryl as claimed. Morgan provides experimental data for exactly one compound – TW1 (CLR01) – which bears unsubstituted phosphate groups. Morgan provides no biological data, such as antiviral data, and no physiochemical data, for any compound bearing a substituted alkyl group or a phosphate monoester oxygen. Morgan does not disclose or provide any guidance regarding structural features of substituents of the molecular tweezers that affect this mechanism of action.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Morgan teaches a molecular tweezer of formula (I). As set forth above, Morgan teaches compounds wherein A and B are alkylphosphonate or arylphosphonate. Thus, Morgan suggests that aryl and alkyl groups are both suitable for making molecular tweezers of the disclosed invention. Thus, Morgan teaches arylalkyl groups are suitable for making molecular tweezers of the disclosed invention. Moreover, as set forth above, Morgan teaches aryl includes phenyl and naphthyl; an aryl group may be substituted with one or more substituent groups including C1-6 alkyl. Morgan teaches A and B can be the same or different and can be
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. Thus, Morgan teaches that attaching R5 directly to the O or to the P is alternatively useful for forming molecular tweezer compounds of formula (I). As set forth above, 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.
Applicant argues:
The Examiner’s refusal to consider post-filing data as published in Weil 2022 is legally flawed.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
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.
Moreover, MPEP 716.01(b) states:
If the evidence is to be given substantial weight in the determination of obviousness or nonobviousness, evidence of secondary considerations must be relevant to the subject matter as claimed, and therefore the examiner must determine whether there is a nexus between the merits of the claimed invention and the evidence of secondary considerations. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 305 n.42, 227 USPQ 657, 673-674 n. 42 (Fed. Cir. 1985), cert. denied, 475 U.S. 1017 (1986). The term "nexus" designates a factually and legally sufficient connection between the objective evidence of nonobviousness and the claimed invention so that the evidence is of probative value in the determination of nonobviousness. Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d 1387, 7 USPQ2d 1222 (Fed. Cir.), cert. denied, 488 U.S. 956 (1988). See also Yita LLC v. MacNeil IP LLC, 69 F.4th 1356, 1363, 2023 USPQ2d 667 (Fed. Cir. 2023). Applicant or patent owner bears the burden of establishing a nexus between the objective evidence of nonobviousness and the claimed invention. See In re Huang, 100 F.3d 135, 140, 40 USPQ 1685, 1689 (Fed. Cir. 1996).
In the instant case, the Weil 2022 reference discloses molecular tweezer compounds and their inhibitory activity against SARS-CoV-2, RSV, IAV, MeV, and HIV-1. Moreover, Weill discloses 7 compounds with aryl substitutions. In a review of the instant specification, disclosure of these compounds was not identified. Disclosure of any aryl substituted molecular tweezer compound in the instant specification was not identified. In a review of the instant specification, disclosure of covid-19 or SARS-CoV-2 was not identified. While the instant specification discloses the molecular tweezers of the instant specification are useful for treating respiratory syncytial virus (RSV), influenza virus (IAV), measles virus (MeV), and human immunodeficiency virus (HIV), none of the aryl substituted tweezer compounds disclosed in Weil are disclosed in the instant specification. Thus, there is no nexus between the data provided in the Weil reference and the claimed invention. The Examiner notes that the same compounds of Weil 2022 are disclosed in Weil 2026. Thus, the disclosures of Weil 2022 or Weil 2026 cannot support an advantage or unexpected result of the claimed invention as described in the Specification.
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. The Weil 2022 and Weil 2026 data establish unexpected results. The instant specification discloses antiviral utility against enveloped viruses expressly identifying Coronaviridae, Retroviridae, Paramyxoviridae, Herpesviridae, Flaviviridae, and Orthomyxoviridae as covered virus families. Weil 2022, of record, establishes the following specific improvements over CLR0 1, which is the experimentally characterized compound in Morgan. The data presented in Weil 2022 and Weil 2026 fill exactly the gap that Morgan leaves entirely open: what biological and physicochemical consequences, if any, follow from varying substituents introduced into the phosphate monoester oxygen of CLR01 (e.g., as variable R5 in Morgan's formula I, which corresponds to RA or RB in the instantly claimed formula I). Morgan is silent on this question because its entire disclosure provides no framework for addressing it.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, the disclosures of Weil 2022 or Weil 2026 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 7 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 2022 or Weil 2026 is insufficient to support unexpected properties of the instantly claimed compounds of formula (I).
Applicant argues:
The commensurate-in-scope requirement is satisfied. The commensurate-in-scope requirement does not demand that every compound within the claim scope be individually tested; it requires that the evidence be representative of the claimed range. In re Lindner, 457 F.2d 506, 508 (CCPA 1972). The seven aromatic tweezers tested in Weil 2022 represent a systematic structure-activity study varying the aryl ring system (phenyl, naphthyl, biphenyl), the alkyl linker length (Cl, C2, C3), and the phenyl ring substitution pattern, covering the structural space of the instant claims. All seven show consistent, marked superiority over CLR01 across this structural range. The Weil 2026 data further extends this showing to additional virus types belonging to families expressly named in the instant specification, further confirming the consistency of the improvement across the claimed structural class. In re Clemens, 622 F.2d 1029 (CCPA 1980).
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
In the instant case, as set forth above, Weil teaches 7 specific compounds having an alkyl substituted with an aryl. 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 of any of the compounds tested in Weil 2022 or Weil 2026 or any aryl substituted molecular tweezer compound. 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 2022 or Weil 2026 is insufficient to support unexpected properties of the instantly claimed compounds of formula (I).
Conclusion
Claims 1, 2, 35, 83-85, and 87-90 are rejected.
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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
