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 .
Restriction/ Election of Species and Status of the Claims
Claims 1-32 are pending. Claims 18-32 have been withdrawn from further consideration as being directed towards nonelected groups. Claims 7-15 have been withdrawn from further consideration as being directed towards nonelected species until a generic claim has been found allowable. Claims 1-6 and 16-17 are examined on their merits.
Information Disclosure Statement
The Information Disclosure Statement filed on September 29th 2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
35 U.S.C. § 103 Rejections Maintained
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 rejections of claims 1-2 and 16-17 under 35 U.S.C. 103 as being unpatentable over Kern (Kern et al., Antimicrob Agents Chemother. 2004 Dec;48(12):4745-53) in view of Sanjay (Sanjay et al, Herpes Zoster Ophthalmicus. Curr Treat Options Neurol 13, 79–91 (2011)) have been maintained.
Applicant’s arguments in the response filed on September 29th 2025 are acknowledged. Applicant argues that:
Kern does not address topical administration of filociclovir, but only systemic administration, and teaches difficulties in treating ophthalmic infections.
The murine model used by Kern is irrelevant to applicant’s method, in which experiments were performed on a white rabbit infection model.
Sanjay is not relevant art because the herpes zoster virus addressed by Sanjay is significantly different than the adenovirus addressed in the application.
Sanjay teaches away from ophthalmic administration.
Substituting filociclovir for acyclovir in Sanjay’s method would be unreasonable, because acyclovir and filociclovir have significantly different antiviral properties.
Hartline’s data cannot be used to predict the antiviral activities of the compounds investigated.
Abelson teaches away from topical ophthalmic administration of filocivlovir, because cidofovir, another nucleoside analog, was found to be toxic when administered ophthalmically.
Abelson teaches away from topical administration to treat ophthalmic adenovirus infections, and specifically addresses the application of topical steroids.
Regarding argument 1, it is acknowledged that Kern does not address topical administration. However, the additional references address this deficiency. Regarding applicant’s claim that Kern teaches difficulties in ophthalmic infections, specifically the presence of the blood-eye barrier that represents a significant barrier for systemic delivery in ophthalmic infections, this blood-eye barrier does not represent any sort of teaching away from topical administration, but in fact a motivation to do so, as topical administration for the treatment of ophthalmic infections would necessarily avoid such a barrier.
Regarding argument 2, mouse models are standard in the art of medicine and constitute evidence towards the merits of pharmacological methods of treatment. Furthermore, applicant’s method of claim 1 describes infection in the eye of a mammal, in which a murine model certainly applies.
Regarding argument 3, Sanjay was not recited for the disclosure of antiviral activity of acyclovir towards herpes zoster, but for the topical administration of nucleoside analogues for the treatment of ophthalmic viral infections, which Sanjay certainly teaches.
Regarding argument 4, applicant shares the passage from Sanjay:
“Topical antiviral medication has not been shown to be effective except for corneal epithelial disease and is thus not routinely recommended.”
and states that Sanjay therefore teaches away from topical administration of antivirals. This is in a section of the paper where Sanjay reviews common treatments for herpes zoster infection. However, Sanjay additionally states:
“We recommend oral acyclovir in conjunction with topical 3% acyclovir ointment, lubricants, and steroids for conjunctival, corneal, and uveal inflammation associated with HZO.”
That is, Sanjay provides a direct recommendation of the topical antiviral, regardless of what is commonly done in the art.
Regarding argument 5, the different antiviral properties of acyclovir and filociclovir are acknowledged. However, this does not negate Sanjay’s demonstration that nucleoside analogues are indeed used in the art to treat ophthalmic viral infections via topical administration. That is, with the knowledge that antiviral nucleoside analogues can be administered topically for the treatment of one viral infection, one of ordinary skill in the art would reasonably topically administer another antiviral nucleoside analogue for the treatment of a viral infection in which it is known to be effective.
Regarding argument 6, The data presented in Hartline would at least be sufficient to demonstrate that, of the drugs investigated, filociclovir was one of the two with the greatest anti-adenoviral activity:
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Regarding argument 7, the toxicity of the ophthalmic formulation of cidofovir is acknowledged, as well as it’s comparable anti-adenoviral activity. However, this is not a claim to the toxicity, or even potential toxicity of filociclovir. In fact, Abelson additionally discloses the topical antiviral compound, NVC-422 for the treatment of viral conjunctivitis (Abelson, pg. 5). Abelson therefore cannot be seen as “teaching away” from topical administration in general, but as stating that such treatments should be evaluated on their antiviral activity as well as their safety.
Regarding argument 8, filociclovir is not a steroid.
Applicant’s arguments are thereby found not persuasive and the 103 rejections are maintained.
103 Rejections Reiterated
Claim 1 is directed towards the treatment of viral infections of the eye, comprising topical administration of filociclovir (often referred to as cyclopropavir in the literature) to the eye.
Kern teaches oral administration of filociclovir (referred to as cyclopropavir), an antiviral nucleoside analogue known for activity against double-stranded DNA viruses via the inhibition of DNA polymerase1, for the treatment of cytomegalovirus infections of the eye (Kern, pg. 4745). Kern uses a mouse model with implanted human retinal tissue and suggests treatment in humans (Kern, Abstract). While Kern teaches the treatment of cytomegalovirus infections of the eye via oral administration of filociclovir, Kern does not explicitly teach ophthalmic topical administration of the filociclovir.
However, one of ordinary skill in the art would have a reasonable expectation of success in administering filociclovir topically to the eye, because similarly acting antiviral nucleoside analogues are known in the art to be administered topically to the eye. For example, see Sanjay, who administers acyclovir, another nucleoside analogue that similarly inhibits viral DNA polymerase2, topically to the cornea for the treatment of ophthalmic infection by herpes zoster, another double-stranded DNA virus (Sanjay, pg. 79).
One of ordinary skill in the art would reasonably substitute filociclovir for the acyclovir in an analogous treatment of ophthalmic cytomegalovirus infections, and claim 1 is prima facie obvious.
Claim 2 further limits the viral infection of claim 1 to one selected from a group, including cytomegalovirus. Claim 2 is prima facie obvious for the same reasons as claim 1.
Claim 16 requires that, in the method of claim 1, the composition is topically administered to the cornea and/or conjunctiva of the eye. As Sanjay teaches topical administration to the cornea (see the above 103 rejection for claim 1), claim 16 is prima facie obvious.
Claim 17 limits the mammal of claim 1 to a human. As this patient population is obvious to try, claim 17 is prima facie obvious for the same reasons as claim 1.
Claims 3-6 are rejected under 35 U.S.C. 103 as being unpatentable over Kern in view of Sanjay and in further view of Hartline (Hartline et al., Antiviral Res. 2018 Nov;159:104-112) and Abelson (Abelson et al., Review of Opthamology 2010 Mar).
Claims 3-5 further limit the viral infection of claim 1 to adenoviruses, such as adenovirus 3 or adenovirus 5, both of which are known in the art to cause conjunctivitis of the eye3. For the teachings of Kern and Sanjay as they relate to claim 1, see the above 103 rejection for claim 1. Regarding the treatment of adenovirus 5, Hartline teaches filociclovir as a treatment of adenovirus 5 infections (Hartline, pg. 110, Table 7). As these infections are known to occur in the eye, and the topical administration of filociclovir is obvious (see the above 103, rejection for claim 1), one of ordinary skill in the art would reasonably use applicant’s method in the treatment of adenovirus 5 infections, and claims 3-5 are prima facie obvious.
Claim 6 further limits the method of claim 4 to the treatment of adenovirus 3. As one of ordinary skill in the art would reasonably treat ocular adenovirus 5 infections with the described method, and ocular adenovirus 3 infections are known to act in a similar manner3, causing keratoconjunctivitis, the method would be obvious to try for the treatment of adenovirus 3 infections, and claim 6 is therefore prima facie obvious.
Nonstatutory Double Patenting Rejections Maintained
As applicant relied on the arguments regarding Sanjay as they relate to the topical administration of nucleoside analogues, and the arguments have been addressed above, the nonstatutory double patenting rejections over copending Application No. 17/437,236 (‘236 Application) in view of Sanjay (Sanjay et al, Herpes Zoster Ophthalmicus. Curr Treat Options Neurol 13, 79–91 (2011)) are maintained.
Nonstatutory Double Patenting Rejections Reiterated
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 1-6 and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-10, and 31 of copending Application No. 17/437,236 (‘236 Application) in view of Sanjay (Sanjay et al, Herpes Zoster Ophthalmicus. Curr Treat Options Neurol 13, 79–91 (2011)).
The ‘236 Application teaches administration of filociclovir to humans for the treatment of various adenovirus infections. The ‘236 Application does not teach topical ophthalmic administration of the filociclovir, but one of ordinary skill in the art would have a reasonable expectation of success in administering filociclovir topically to the eye, because similarly acting antiviral nucleoside analogues are known to be administered topically to the eye. See the above 103 rejections for claims 1-2 and 16-17 for the teachings of Sanjay as they relate to this subject.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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 Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 For evidentiary support, see Chou (Chou S, Marousek G, Bowlin TL. Cyclopropavir susceptibility of cytomegalovirus DNA polymerase mutants selected after antiviral drug exposure. Antimicrob Agents Chemother. 2012 Jan;56(1):197-201)
2 For evidentiary support, see Mondal (Mondal, Acyclovir, xPharm: The Comprehensive Pharmacology Reference, Elsevier, 2007)
3 For evidentiary support, see Abelson (Abelson et al., Review of Opthamology 2010 Mar) (pg. 1, 3rd paragraph; pg. 5, 5th paragraph)