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
This application is a national stage entry of PCT/US2020/021548 filed on 03/06/2020 which claims priority to U.S. Provisional Application No. 62/815,630 filed on 03/08/2019.
Response to Amendment
No amendments to the claims were made by Applicant’s reply filed on January 5, 2026. Claims 1-10 and 31 are currently pending. Claims 11-30 are canceled.
Response to Arguments
Applicant's arguments filed January 5, 2026 have been fully considered but they are not persuasive. With respect to the double patenting rejection Applicant argues that claim 1 of the '613 application recites, "a viral infection of the eye in a mammal" and "topically administering to said eye" whereas claims 1-10 and 31 of the present application do not recite that the viral infection is of the eye or that the method comprises topically administering the composition to the infected eye. Applicant further argues that independent claim 1 of the present application recites an "adenovirus infection", whereas independent claim 1 of the '613 application does not recite that its viral infection is an adenovirus infection. Applicant further argues that claim 31 of the present application recites the composition further comprises a second antiviral agent and none of claims 1-17 of the '613 application recites a second antiviral agent.
These arguments are found not persuasive since claims 1-10 and 31 of the instant application claim a method of preventing or treating adenovirus infection in a mammal comprising administering to said mammal an effective amount of a composition comprising filociclovir. The claims of copending ‘613 specifically claim a method of treating or preventing a viral infection of the eye, wherein the viral infection is caused by adenovirus (claims 2-15). The claims of the instant application do not specifically claim any particular type of adenovirus infection and thus a prior art which discloses the treatment of any adenovirus infection will meet the limitations of the claims. In the instant case, copending ‘613 specifically claims the treatment of a viral infection caused by adenovirus, thus the cited claims of the instant application would be anticipated by the cited claims of copending ‘613. Furthermore, with respect to claim 31 of the instant application which broadly claims combining filociclovir with a second antiviral agent, combining another antiviral agent to filociclovir to treat an adenovirus infection is rendered obvious since copending ‘613 claims filociclovir is useful in the treatment of adenovirus and thus adding another antiviral agent to achieve improved results is prima facie obvious. Thus claim 31 is rendered obvious over the cited claims of copending ‘613. Accordingly, the previous double patenting rejection is hereby maintained as this rejection is not the only rejection remaining.
Please note that the “provisional” double patenting rejection will continue to be made in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications. Therefore, the provisional double patenting rejection is maintained, as said rejection is not the only remaining rejection in either application.
If a “provisional” nonstatutory obviousness-type double patenting (ODP) rejection is the only rejection remaining in the earlier filed of the two pending applications, while the later-filed application is rejectable on other grounds, the examiner should withdraw that rejection and permit the earlier-filed application to issue as a patent without a terminal disclaimer. If the ODP rejection is the only rejection remaining in the later-filed application, while the earlier-filed application is rejectable on other grounds, a terminal disclaimer must be required in the later-filed application before the rejection can be withdrawn.
With respect to the rejection under 35 USC 103, Applicant argues that Zemlicka does not teach treating adenovirus infection. Applicant further argues that Hartline only alluded to the possibility that filociclovir may be an adenovirus inhibitor, however, without more, one of ordinary skill in the art would not have interpreted the Hartline in vitro assay results as a teaching, or even as a reasonable expectation, that filociclovir would be an actual effective adenovirus inhibitor, as even Hartline specifically cautions against reaching such a conclusion. Applicant argues that the in vitro assay demonstration in Hartline shows human foreskin fibroblasts incubated with filociclovir and virus express more cellular ATP than do human foreskin fibroblasts incubated with virus alone does not teach or suggest Applicant's discovery, as taught in the present specification, that filociclovir actually functions as an effective in vivo treatment for an actual adenovirus infection. Applicant argues that Hartline only describes the initial development and preliminary results of a high throughput assay for the quick screening of compounds to indirectly analyze, i.e., analyze a cellular function affected by a viral infection, as opposed to directly analyzing which step in the virus life cycle, itself, the reference compound interrupts, to quantitate their antiviral potential and cellular cytotoxicity.
Applicant further argues that the human foreskin fibroblasts used in Hartline, being dermal cells, have a number of valuable scientific applications including studies related to wound healing, dermatological research, tissue regeneration, etc., however, adenovirus does not infect dermal cells and, instead, primarily infects the cells of the respiratory tract, the gastrointestinal tract, and the eyes of an individual. Therefore, Applicant argues that while dermal cells may provide valuable in vitro data, they are not the preferred cell type for testing the effectiveness of a compound as an adenovirus inhibitor. Applicant argues that demonstrating the actual in vivo effectiveness of treating an adenovirus infection with filociclovir cannot be predicted or assumed based on the results of a CellTiter Glo fluorescent assay quantitating the level of cellular ATP expressed by human foreskin fibroblasts in an assay plate and is an assumption that can only be reached after analyzing Applicant's novel data demonstrated for the first time in the present specification.
These arguments are found not persuasive since Zemlicka et al. teaches the antiviral compound filociclovir as well as a method of treating a mammal infected with a virus comprising the administration of filociclovir and further administering an additional compound such as the antiviral compounds acyclovir, ganciclovir, etc. Thus Zemlicka et al. specifically teaches that filociclovir is an antiviral compound effective against may types of viruses. The rejection of record recognizes that Zemlicka et al. does not teach that the compounds are useful against adenovirus. However, Zemlicka et al. teaches that the compounds disclosed therein are useful against viruses such as herpes virus, HIV, hepatitis B, and human cytomegalovirus (page 4 and claim 9). Similarly, the data of Hartline confirm the teachings of Zemlicka et al. since the data of Hartline demonstrate antiviral activity of filociclovir against the herpes virus varicella-zoster virus (VZV) (Table 3 page 108), and cytomegalovirus (CMV) (Table 4 page 109). Thus there is no reason to doubt the accuracy of the data shown in Hartline for filociclovir against adenovirus and furthermore there is no reason to doubt that said data would predict whether or not filociclovir would inhibit adenovirus in vivo based on the in vitro data of Hartline.
Obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O ’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988). Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1198 (Fed. Cir. 2014). Proof sufficient “to obtain approval” for a drug by a regulatory agency, such as by a randomized, placebo-controlled, double-blinded design is not necessary to establish obviousness. Hoffmann—La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014) (“[c]onclusive proof of efficacy is not necessary to show obviousness.”). “Scientific confirmation of what was already believed to be true may be a valuable contribution, but it does not give rise to a patentable invention.” PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1363-64 (Fed. Cir. 2007).
Applicant’s arguments with respect to the techniques used in the Hartline reference are found not persuasive since Applicant does not provide any evidence to support their arguments. It is noted that “prior art printed publication cited by an examiner is presumptively enabling barring any showing to the contrary by a patent applicant.” In re Morsa, 713 F.3d 104, 109 (Fed. Cir. 2013). The prior art is enabling if “a person of ordinary skill in the art could make or use the claimed invention without undue experimentation based on the disclosure of that particular document.” Id. at 110. Here, Applicant provides no specific evidence or persuasive reasoning as to why undue experimentation would have been required for an ordinary skilled artisan to follow the disclosures of Zemlicka et al. and Hartline and administer filociclovir for the treatment of an adenovirus infection given that Zemlicka already discloses the use of filociclovir for the treatment of other viral infections. All Applicant presents is attorney argument, but “attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Thus for reasons of record, and for the reasons detailed above, the previous rejection under 35 USC 103 is hereby maintained and reproduced below. This action is FINAL.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 17/622,613 (U.S. Publication No. 2022/0370464 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘613 are drawn to the method of treating or preventing a viral infection caused by an adenovirus comprising administering filociclovir or a pharmaceutically acceptable salt thereof. Therefore claims 1-10 of the instant application would be anticipated over the cited claims of ‘613.
Claim 31 is rejected since "It 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 ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980). Thus adding another antiviral compound to filociclovir as claimed in claim 31 is rendered obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
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 1-10 and 31 are rejected under 35 U.S.C. 103 as being obvious over Zemlicka et al. WO 03/104440 A2 (of record) in view of Hartline et al. (2018, Antiviral Research, Volume 159, pages 104-112-Provided on IDS).
Claims 1-10 and 31 of the instant application claim a method of preventing or treating adenovirus infection in a mammal comprising administering to said mammal an effective amount of a composition comprising filociclovir having the following structure:
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or a pharmaceutically acceptable salt thereof.
Zemlicka et al. teaches compounds of formula I or II which are active against viruses (abstract). Formula I and II have the following structures:
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wherein B is a purine or pyrimidine heterocyclic ring or base wherein the purine is selected as guanine
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(abstract, page 1 lines 10-11, page 4 lines 1-20). Zemlicka et al. teaches compound (Z)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl}guanine (compound 1c)
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(page 5 line 32; Example 11 page 22 line 24-page 23 line 7; Figure 5).
Claim 4 of Zemlicka et al. claims an antiviral compound including (Z)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl}guanine (compound 1c). Claims 7 and 8 of Zemlicka et al. claim a method of treating a mammal such as a human infected with a virus comprising administering a compound such as compound 1c. Claims 10 and 11 of Zemlicka et al. claim further administering an additional compound such as the antiviral compounds acyclovir, ganciclovir, etc.
Thus Zemlicka et al. teaches the antiviral compound filociclovir as well as a method of treating a mammal infected with a virus comprising the administration of filociclovir and further administering an additional compound such as the antiviral compounds acyclovir, ganciclovir, etc.
However, Zemlicka et al. teaches that the compounds disclosed therein are useful against viruses such as herpes virus, HIV, hepatitis B, and human cytomegalovirus (page 4 and claim 9), but Zemlicka et al. does not teach that the compounds are useful against adenovirus.
Hartline teaches antiviral activity for a set of reference compounds against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), vaccinia virus (VACV), cowpox virus (CPXV), and adenovirus (AdV) and facilitates a broad assessment of activity against this set of viruses revealing novel activities (page 104). The adenovirus strain tested is AdV5 (VR-1516) (page 105). One of the compounds tested is filociclovir (FCV, cyclopropavir) (page 105). Hartline evaluates the antiviral activity against adenovirus (AdV) (page 109). Hartline teaches that the studies detected antiviral activity against adenovirus with FCV which has not been tested previously or reported in the literature (page 109).
Thus Hartline teaches that in addition to the antiviral effects against the known cytomegalovirus and herpes virus, FCV also has antiviral effects against adenovirus and specifically adenovirus-5.
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Zemlicka et al. which teaches the antiviral compound filociclovir as well as a method of treating a mammal infected with a virus comprising the administration of filociclovir, with the teachings of Hartline which specifically demonstrates that filociclovir has adenovirus inhibitory action. Thus a person of ordinary skill in the art would reasonably expect filociclovir to be useful in a method of treating a mammal infected with a virus comprising the administration of filociclovir, wherein the virus is adenovirus since Hartline demonstrates the antiviral activity of filociclovir against adenovirus. Claim 4 of the instant application is rendered obvious since Hartline specifically teaches adenovirus-5. Claims 2-3 and 5-9 are rendered obvious since Hartline teaches that filociclovir has adenovirus activity and thus a person of ordinary skill in the art would reasonably expect the compound to be useful against other strains of adenovirus in the absence of a demonstration to the contrary. Thus treating multiple strains of adenovirus including those as claimed is rendered obvious in view of the cited prior art teachings.
Claim 31 is rendered obvious since "It 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 ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980). Thus adding another antiviral compound to filociclovir as claimed in claim 31 is rendered obvious.
Thus the cited claims of the instant application are rendered obvious in view of the cited claims of the instant application.
Conclusion
Claims 1-10 and 31 are rejected. Claims 11-30 are canceled. No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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