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 June 10, 2024 is acknowledged. Claims 1-2, 7, 22, 24, 34, 39, 42-47, 59, 64, 66-67, 69-70 and 73-74 are pending and under examination. Claim Rejections - 35 USC § 112 (b) The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claim s 1-2, 7, 22, 24, 34, 39, 42-47, 59, 64, 66-67 , 69-70, and 73-74 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim s 1 and 69-70 recites “an AAV2 capsid protein comprising an amino acid sequence LGETTRP inserted between position 587 and 588 of the capsid protein, wherein the amino acid res i d u e number corresponds to an AAV 2 capsid protein”. Claim 1 is indefinite because the amino acid numbering isn’t recited in relation to a specific sequence – a SEQ ID NO or an Accession number for the AAV2 capsid protein. “An AAV2 VP1 capsid protein” is a genus of proteins including wild-type, naturally occurring variants , and engineered variants that have inserted or deleted residues that would alter the amino acid numbering . As such the insertion point of LGETTRP in VP1 is undefined and the structure of the AAV2 capsid protein overall is indefinite. Claims 2, 7, 22, 24, 34, 39, 42-47, 59, 64, 66-67 and 73-74 are rejected for depending from claim 1 and not remedying the indefiniteness. Claims 69-70 recite “A unit dos e of… rAAV particles for use in a method for…, the method comprising administering said unit dose to one eye of the individual…” The preamble of both claims recite s “A unit dose” and, as such, the claims are directed to products. H owever, “is administered to” is an active step for the unit dose . A single claim which claims both a product and the method steps of using the product is indefinite. See MPEP 2173.05(p).II. In this case, “administered to” is not merely a capability of the unit dose , but instead is directed to actions of an individual using the unit dose. It is not clear if claims 69 and 70 are to the method or to the unit dose. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim s 69-70 are rejected under 35 U.S.C. 102 (a)(2) as being anticipated by Gelfman ( Gelfman et al., Journal of Ocular Pharmacology and Therapeutics (2021), 37: 181-190, published April 1, 2021) evidenced by Grishanin (Grishanin et al., Molecular Therapy (2019), 27: 118-129 and Supplemental Material), Sigg (US 20140012227 A1), Dalkara (Dalkara et al., Science Translational Medicine (2013), 5: 189, 1-12) and Schaffer (US 20140294771 A1). Regarding claims 69-70, “for use in a method…” is interpreted as intended use. “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” See MPEP 2111.02.II. “For use in a method…” does not define any component of the unit dose or the rAAV2. Therefore claims 69-70 will be examined based on the recited structure of the rAAV particle and, for claim 69, the amount of vector genomes (vg). Regarding claims 69-70, Gelfman teaches a dose of 6 x 10 11 vg/eye (i.e., a unit dose) of ADVM-022 (FIG 6B). Gelfman teaches ADVM-022 is a recombinant AAV-based gene therapy vector for neovascular diseases (page 182, ¶6). Gelfman teaches the AAV2.7m8 capsid protein of ADVM-022 was engineered from AAV2, while the expression cassette w as engineered for strong and ubiquitous expression of a codon-optimized cDNA encoding aflibercept (page 182, ¶6). Gelfman teaches the ADVM-022 vector was described in Grishanin (page 182, ¶6, reference 15). Gelfman is silent regarding the structure of ADVM-022. Regarding (a), Grishanin teaches that the ADVM-022 genome consists of an aflibercept expression cassette flanked by viral inverted terminal repeats from AAV2 (page 125, ¶2). Sigg teaches the amino acid sequence for aflibercept is SEQ ID NO 1 ([0032], top of page 4), which is 100% identical to SEQ ID NO 35 of the present application. Therefore, the unit dose of ADVM-022 taught in Gelfman inherently comprised a polynucleotide encoding an amino acid sequence with at least 95% identity to SEQ ID NO 35 and flanked by AAV2 inverted terminal repeats. Regarding (b), Grishanin teaches that ADVM-022 utilizes the AAV2.7m8 capsid that includes a 10-amino-acid insertion in loop IV of the AAV2 capsid protein, which was first described by Dalkara, reference 18 (page 125, ¶2). Schaffer is a US Patent Application Publication having the same disclosures as the Dalkara non-patent literature cited by Grishanin. Schaffer teaches the AAV2.7m8 capsid comprises LGETTRP inserted between positions 587 and 588 of the AAV2 capsid protein ([0193], [0199]; Table 1). Therefore, the unit dose of ADVM-022 taught in Gelfman inherently comprised an AAV2 capsid protein comprising an amino acid sequence LGETTRP inserted between positions 587 and 588 of the VP1 capsid protein. Claim Rejections - 35 USC § 103 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 -2, 7, 22, 24, 39, 47, 59, 64, 66, 70 and 73-74 are rejected under 35 U.S.C. 103 as being unpatentable over Grishanin (Grishanin et al., Molecular Therapy (2019), 27: 118-129 and Supplemental Material) as evidenced by Sigg (US 20140012227 A1), Dalkara (Dalkara et al., Science Translational Medicine (2013), 5: 189, 1-12) and Schaffer (US 20140294771 A1), and in view of Schaffer (US 20140294771 A1) and Inatani (Inatani et al., Advances in Therapy (2021), 38: 1106-1115, published December 16, 2020). Claim 73 is evidenced by Wu (Wu et al., Molecular Therapy (2020), 28: 3, 1-19). Regarding claim s 1 -2 , 22 Grishanin teaches pre-clinical evaluation of using ADVM-022 for treating wet age-related macular degeneration (w A MD) in non-human primates to determine safe and effective options for treating w A MD (Abstract). Regarding (a), Grishanin teaches that the ADVM-022 genome consists of an aflibercept expression cassette flanked by viral inverted terminal repeats from AAV2 (page 125, ¶2). Grishanin is silent regarding the amino acid sequence of aflibercept. Sigg teaches the amino acid sequence for aflibercept is SEQ ID NO 1 ([0032], top of page 4), which is 100% identical to SEQ ID NO 35 of the present application. Therefore, the ADVM-022 taught in Grishanin inherently comprised a polynucleotide encoding an amino acid sequence with at least 95% identity to SEQ ID NO 35 and flanked by AAV2 inverted terminal repeats. Regarding (b), Grishanin teaches that ADVM-022 utilizes the AAV2.7m8 capsid that includes a 10-amino-acid insertion in loop IV of the AAV2 capsid protein, which was first described by Dalkara, reference 18 (page 125, ¶2). Grishanin is silent regarding the amino acid sequence of aflibercept. Schaffer is a US Patent Application Publication having the same disclosures as the Dalkara non-patent literature cited by Grishanin. Schaffer teaches the AAV2.7m8 capsid comprises LGETTRP inserted between positions 587 and 588 of the AAV2 capsid protein ([0193], [0199]; Table 1). Therefore, the ADVM-022 taught in Grishanin inherently comprised an AAV2 capsid protein comprising an amino acid sequence LGETTRP inserted between positions 587 and 588 of the VP1 capsid protein. Regarding methods of treatment, Grishanin teaches that administering ADVM-022 resulted in robust levels of aflibercept in the retina and choroid tissues, which are the sites of neovascularization in wAMD (page 120, ¶1). Grishanin teache s ADVM-022 has the potential to treat neovascularization that precedes vision loss (page 119, ¶2). Grishanin does not teach using ADVM-022 for treating glaucoma in humans. Schaffer teaches the AAV2.7m8 variant capsid vectors can be used for treating glaucoma ([0167]). Schaffer teaches the AAV2.7m8 variant capsid vectors can be used to deliver anti-VEGF polypeptides ([0152]). Inatani teaches a clinical tria l studying the efficacy of using aflibercept to treat neovascular glaucoma (Abstract). Inatani teaches that neovascular glaucoma is characterized by neovascularization of the iris and angle, which prevents normal drainage for the eye leading to elevated intraocular pressure (IOP) (¶ spanning pages 1107-1108). Inatani teaches that intravitreal aflibercept injection was approved in 2020 as a treatment for patients with neovascular glaucoma in Japan (page 1180, ¶2). Inatani teaches aflibercept treatment was associated with statistically significant and clinically meaningful reduction in interocular pressure (IOP), which support using aflibercept as a treatment of patients with neovascular glaucoma (page 1107, Conclusions). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have used Grishanin’s ADVM-022 viral vector comprising the coding sequence for aflibercept and the engineered AAV2.7m8 capsid to treat neovascular glaucoma. It would have amounted to using a known aflibercept viral delivery method known to treat neovascularization in the eye to treat a known disease characterized by neovascularization in the eye. The skilled artisan would have predicted that ADVM-022 could be used to treat neovascular glaucoma, and been motivated to have done so, because 1) Grishanin teaches that it would be useful for treating ocular diseases characterized by neovascularization (i.e., neovascular glaucoma), 2) Schaffer teaches the AAV2.7m8 variant can be used to treat glaucoma, and 3 ) Inatani teaches that aflibercept administration can reduce neovascularization in neovascular glaucoma. Regarding claim 7, Grishanin teaches a dose of 2 x 10 12 vg ADVM-022 administered to eyes of the non-human te s t subjects (Table 1). Grishanin also teaches administration of a similar vector carrying a GFP reporter coding sequence, AAV2.7m8-CMV-GFP (Figure S1; Supp Methods). Grishanin teaches administering AAV2.7m8-CMV-GFP particles at a dose of 5 x 10 11 vg/eye (i.e., between about 2 x 10 10 to about 6 x10 11 vg/eye) is sufficient for deliver y of the transgene to ocular tissues (Figure S1; Supp Methods). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have administered the ADVM-022 particles to human eyes at a range of about 2 x 10 10 to about 6 x10 11 vg/eye. It would have amounted to optimizing AAV-based particle dosing by known means to yield predictable results. The skilled artisan would have predicted that a dose of ~ 5 x 10 11 vg/eye would be sufficient for treatment in human s because Grishanin teaches that dose is sufficient for transgene delivery in related non-human primates. The skilled artisan would have been motivated to optimize dosing since that is a standard procedure in the art for determining therapeutic methods. Regarding claim 24, Grishanin teaches the C11.CO.aflibercept expression cassette comprises in 5’ to 3’ order (a) a human CMV enhancer, (b) a human CMV promoter, (c) a 5’ UTR comprising a TPL eMLP, an synthetic intron, (d) the coding sequence for aflibercept (i.e., encoding an amino acid sequence of SEQ ID NO 35), (e) a human SAR (i.e., a second enhancer region) and (f) a human GH polyA sequence (i.e., a polyadenylation site) (Figure 1). Grishanin teaches the elements (a)-(f) are flanked by AAV2 inverted terminal repeats (Figure 1). Regarding claim 39, Schaffer teaches the GH loop of AAV2.7m8 VP1 amino acid sequence comprises SEQ ID NO 36 (Fig. 18B), which is 100% identical to SEQ ID NO 38 of the present invention. Therefore, the ADVM-022 taught in Grishanin inherently comprised an AAV2 capsid protein comprising a GH loop that comprise the acid sequence of SEQ ID NO 38. Regarding claim s 47 and 74 , Grishanin teaches the unit dose of ADVM-022 is provided in 50 m L (Table 1; page 125, ¶6). Regarding claim s 59 , 64 and 66 , Grishanin teaches that AAV2-based gene therapy can induce ocular inflammation, but that the inflammation was controlled with topical steroid treatment in previous clinical trials with AAV2 vectors (page 124, ¶3). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have additionally provided steroids during or after administration of the ADVM-022 viral vector during the method of treating glaucoma rendered obvious above. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that a topical steroid can be provided with the ADVM-022 treatment because Grishanin teaches that topical steroids have used in combination with other AAV2 gene therapy methods. One would have been motivated to do so to reduce AAV2-inducted inflammation. Regarding claim 70, Grishanin does not teach an ADVM-022 dose specifically for a human. However, it would have been obvious to one skilled in the art to have used the 2 x 10 12 vg in 50 m L as a dose for humans because Grishanin teaches the rAAV do s e is effective for treating neovascular ocular conditions of the eye and reduced interocular pressure at at least one time point after administration (Fig 3F). Regarding claim 73, Grishanin teaches the aflibercept coding sequence is under the control of the CMV promoter (i.e., a strong promoter) (Fig 1). Grishanin is silent regarding whether CMV is active in the ciliary body. Wu teaches delivery of a GFP coding sequence whose expression is driven by the CMV promoter to ciliary bodies extracted from human eyes (Figure 5). Wu teaches detecting CMV-promoter driven GFP expression in cells of the ciliary body (Figure 5). Therefore, the ADVM-022 taught in Grishanin inherently comprised a strong promoter that is active in the ciliary body. Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Grishanin (Grishanin et al., Molecular Therapy (2019), 27: 118-129 and Supplemental Material) as evidenced by Sigg (US 20140012227 A1), Dalkara (Dalkara et al., Science Translational Medicine (2013), 5: 189, 1-12) and Schaffer (US 20140294771 A1), and in view of Schaffer (US 20140294771 A1) and Inatani (Inatani et al., Advances in Therapy (2021), 38: 1106-1115, published December 16, 2020) as applied to claim s 1-2, 7, 22, 24, 39, 47, 59, 64, 66, 70 and 73-74 above, and further in view of Keravala (US 20200010851 A1, published January 9, 2020). The teachings of Grishanin, Sigg, Dalkara, Schaffer and Inatani are recited above and applied as for claims 1-2, 7, 22, 24, 39, 47, 59, 64, 66, 70 and 73-74 . Briefly , Grishanin teaches the ADVM-022 gene therapy vector comprising an expression cassette comprising in 5’ to 3’ order (a) a human CMV enhancer, (b) a human CMV promoter, (c) a 5’ UTR comprising a TPL eMLP, an synthetic intron, (d) the coding sequence for aflibercept (i.e., encoding an amino acid sequence of SEQ ID NO 35), (e) a human SAR (i.e., a second enhancer region) and (f) a human GH polyA sequence (i.e., a polyadenylation site) (Figure 1). Grishanin, Sigg, Dalkara, Schaffer and Inatani do not teaches the nucleic acid sequences of the elements depicted in Figure 1 of Grishanin. Keravala teaches optimized nucleic acid expression cassettes and vectors for expression gene in mammalian cells ([0005] ), including for expression of aflibercept ([0020]). Keravala teaches a polynucleotide cassette comprising a CMV enhancer, CMV promoter, 5’UTR with TPL and eMLP, a coding sequence of a protein of interest, a full EES sequence second enhancer , and an HGH polyadenylation sequence (FIG 1, Cassette No. 11). Keravala teaches construct 11 drove high expression of transgenes, including for aflibercept, in HeLa cells (FIGs 2 and 7-8), HEK293 cells (FIGs. 3, 6 and 9), pig retinal explants (FIG. 4A-B, 10A-B; [0049]), and ARPE19 cells (FIG. 5). Regarding (a), Keravala teaches the sequence of the CMV enhancer is SEQ ID NO 1 ([0032]), which is 100% identical to SEQ ID NO 22 of the examined application. Regarding ( b ), Keravala teaches the sequence of the CMV promoter is SEQ ID NO 4 ([0032]), which is 100% identical to SEQ ID NO 23 of the examined application. Regarding ( c ), Keravala teaches the 5’ UTR comprising the TPL sequence and eMLP sequences comprising SEQ ID NOs 11 and 12 ([0032]), which are 100% identical to SEQ ID NOs 24 and 25, respectively, of the examined application. Regarding ( d ), Keravala teaches the enhancer sequence is the full EES sequence with SEQ ID NO 13 ([0032]), which is 100% identical to SEQ ID NO 26 of the examined application. Regarding ( e ), Keravala teaches the HGH polyadenylation signal sequence has SEQ ID NO 14 ([0032]), which is 100% identical to SEQ ID NO 27 of the examined application. Keravala teaches the AAV expression cassettes can be delivered by AAV particles including the variant comprising the 7m8 variant ([0039], [0049]). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have used Keravala’s Cassette No. 11 for expressing aflibercept delivered by the AAV2.7m8 capsid in the method rendered obvious above for claim 1. It would have amounted to using known expression control elements/sequences by known means to yield predictable results. The skilled artisan would have predicted that Ker a vala’s Cassette 11 could be used in the obvious method to treat glaucoma because 1) Keravala teaches that aflibercept can be delivered in such as cassette, packaged into AAV2.2m8 virions , and delivered to pig ocular cells and 2) the expression cassette of Grishanin has many of the same genetic elements. The skilled artisan would have been motivated to use Keravala’s cassette because of its ability to drive high transgene expression in a variety of cells including in ocular tissues. Claim s 42-46 , 67 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Grishanin (Grishanin et al., Molecular Therapy (2019), 27: 118-129 and Supplemental Material) as evidenced by Sigg (US 20140012227 A1), Dalkara (Dalkara et al., Science Translational Medicine (2013), 5: 189, 1-12) and Schaffer (US 20140294771 A1), and in view of Schaffer (US 20140294771 A1) and Inatani (Inatani et al., Advances in Therapy (2021), 38: 1106-1115, published December 16, 2020) as applied to claim s 1-2, 7, 22, 24, 39, 47, 59, 64, 66, 70 and 73-74 above, and further in view of Gasmi (WO 2021050094 A1, published March 28, 2021). The teachings of Grishanin, Sigg, Dalkara, Schaffer and Inatani are recited above and applied as for claims 1-2, 7, 22, 24, 39, 47, 59, 64, 66, 70 and 73-74 . Briefly, Grishanin teaches the ADVM-022 gene therapy vector comprising the claimed polypeptide coding sequence and claimed AVV capsid protein for the treatment of neovascular diseases of the eye. The obviousness of using ADVM-022 to treat neovascular glaucoma is recited above in paragraph REF _Ref224726838 \r \h 21 . Schaffer also teaches the rAAV virions can be formulated in a pharmaceutical composition with acceptable carriers, diluents, excipients and buffers, including phosphates and emulsifying agents, and which are known in the art ([0161]-[0162]) Grishanin, Sigg, Dalkara, Schaffer and Inatani do not teach the specific formulations for administering ADVM-022 to the eyes of human patients. Regarding claims 42-46 and 69, Gasmi teaches treating ocular neovascular disease in an individual comprising administering a unit dose of rAAV particles encoding SEQ ID NO 35 (i.e., aflibercept) and an AAV capsid having LGETTRP inserted into position 587-588 of VP1 capsid (i.e., AAV2.7m8) (Abstract). Gasmi teaches pharmaceutical formulations for the rAAV particles ([0177]-[0200]). Gasmi teaches a specific pharmaceutical formulation comprises 6 x 10 12 vg/mL or 6 x 10 11 vg/mL rAAV with about 180 mM sodium chloride, about 5 mM monobasic sodium phosphate, about 5 mM dibasic sodium phosphate and about 0.001% (w/v) po l oxamer 188 (i.e., a surfactant) with a pH of 7.3 ([0185]). Gasmi also teaches the formulations can comprise about 2x 10 12 vg/mL of rAAV particles ([0179]). Gasmi uses the formulation s recited in examined claim 44 in a phase I clinical trial for treating the neovascular disease wAMD ([0229], Table 1). Gasmi summarized the results of the phase I clinical trial as “AAV2.7m8-aflibercept provided a clear benefit for improving retinal anatomy and stabilizing vision, while exhibiting an acceptable safety profile. Specifically, patients maintained vision during the study, and AAV2.7m8-aflibercept was shown to be safe and well tolerated, with observed inflammation generally being mild and responsive to steroid eye drops.” ([0290]) It would have be e n obvious to one skilled in the art before the effective filing date of the claimed invention to have used the formulation s and rAAV concentrations reported in Gasmi in the method rendered obvious above for claim 1. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that the formulations would be functional to treat neovascular glaucoma, and been motivated to use the same formulations because Gasmi teaches the formulations for treating another neovascular ocular disease and concluded that the formulations are safe, well tolerated and provide a clear benefit for stabilizing vision. Regarding claim 67, Gasmi teaches combining the AAV2.7m8-aflibercept treatment with a topical steroid comprising difluprednate 0.05% at a dose of about 1 m g to about 3 m g ([0021]). Gasmi also teaches another Phase I study combining the AAV2.7m8-aflibercept treatment with topical steroid s , 0.05% difluprednate drops ([0303]-[0307]-Table 9). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have also provided difluprednate at 0.05% at a dose of about 1 m g to about 3 m g as reported in Gasmi in the method rendered obvious above for claim 1. It would have amounted to simple combination of known elements by known means to render predictable results. The skilled artisan would have predicted that the combination of difluprednate and AAV2.7m8-aflibercept would be functional to treat neovascular glaucoma because Gasmi teaches the formulations for treating another neovascular ocular disease and concluded that the formulations are safe, well tolerated and provide a clear benefit for stabilizing vision. The skilled artisan would have been motivated to use difluprednate for the purpose of treating inflammation which can occur with AAV2 gene delivery to the eye as taught by both Gasmi and Grishanin . 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 . Claim s 1-2, 7, 22, 24, 34, 39, 42-47, 59, 64, 66-67 , 69-70, and 73-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 4-9, 11, 16, 22-30, 32-35, 37-38, 40-41, 44-46, 49-53, 57, 60-61, 63, 72-74, 80, 82, 84-86, 88-89, 91-93, 100, 109-119 and 122 of copending Application No. 17017469 in view of Schaffer (US 20140294771 A1) and Inatani (Inatani et al., Advances in Therapy (2021), 38: 1106-1115, published December 16, 2020) . Copending claim 1 recites A method of reducing inflammation associated with administering recombinant adeno-associated virus (rAAV) particles for treating wet age-related macular degeneration (AMD) in an individual, the method comprising administering a topical steroid and a unit dose of about 1 x 10 10 vector genomes (vg) to about 6 x 10 11 vg of rAAV particles to one eye of the individual by intravitreal administration, wherein the individual is a human, and wherein the rAAV particles comprise: a) a nucleic acid encoding a polypeptide comprising an amino acid sequence with at least about 95 % identity to the amino acid sequence of SEQ ID NO: 35 [which is 100% identical to SEQ ID NO 35 of the examined application] and flanked by AAV2 inverted terminal repeats (ITRs), and b) an AAV2 capsid protein comprising an amino acid sequence LGETTRP (SEQ TD NO: 14) inserted between positions 587 and 588 of the capsid protein, wherein the amino acid residue numbering corresponds to an AAV2 VP1 capsid protein; wherein the timing of the administration of the topical steroid starts at about one week prior to administration of the unit dose of rAAV particles, and wherein the topical steroid treatment is difluprednate. Copending claim 16 recites wherein the unit dose of rAAV particles is:(a) between about 6 x 10 10 to about 6 x 10 11 vector genomes per eye (vg/eye); (b) between about 6 x 10 10 to about 2 x 10 11 vg/eye;(c) between about 2 x 10 11 to about 6 x 10 11 vg/eye;(d) about 2 x 10 11 vg/eye; or (e) about 6 x 10 11 vg/eye. Copending claim 32 recites wherein the polypeptide is aflibercept. Copending claim 34 recites wherein the nucleic acid comprises, in the 5' to 3' order:(a) a first enhancer region;(b) a promoter region;(c) a 5'UTR region;(d) a nucleic acid encoding a polypeptide comprising an amino acid sequence with at least about 95% identity to the amino acid sequence of SEQ ID NO: 35;(e) a second enhancer region; and(f) a polyadenylation site;and flanked by AAV2 inverted terminal repeats (ITRs). Copending claim 44 recites wherein the nucleic acid further comprises (a) a first enhancer region comprising a CMV sequence comprising the sequence of SEQ ID NO: 22 or a sequence having at least 85% identity thereto; (b) a promoter region comprising a CMV sequence comprising the sequence of SEQ ID NO: 23 or a sequence having at least 85% identity thereto; (c) a 5'UTR region comprising, in 5' to 3' order, a TPL sequence comprising the sequence of SEQ ID NO: 24 or a sequence having at least 85% identity thereto, and an eMLP sequence comprising the sequence of SEQ ID NO: 25 or a sequence having at least 85% identity thereto; (d) a second enhancer region comprising a full EES sequence comprising the sequence of SEQ ID NO: 26 or a sequence having at least 85% identity thereto; and (e) a HGH polyadenylation site comprising the sequence of SEQ ID NO: 27 or a sequence having at least 85% identity thereto , wherein each of the recite SEQ ID NOs are identical to the instantly claimed SEQ ID NOs. Copending claims 51-52 recite wherein the unit dose of rAAV particles is in a pharmaceutical formulation [ compris ing] the rAAV particles, sodium chloride, sodium phosphate and a surfactant. Copending claim 53 recites wherein the pharmaceutical formulation comprises:(a) about 150 to about 200 mM sodium chloride, about 1 to about 10 mM monobasic sodium phosphate, about 1 to about 10 mM dibasic sodium phosphate, about 0.0005% (w/v) to about 0.005% (w/v) poloxamer 188, and about 6 x 10 13 to about 6 x 10 10 vector genomes (vg) per mL (vg/mL) of the rAAV particles, wherein the pharmaceutical formulation has a pH of about 7.0 to about 7.5;(b) about 180 mM sodium chloride, about 5 mM monobasic sodium phosphate, about 5 mM dibasic sodium phosphate, about 6 x10 12 vg/mL of the rAAV particles, and about 0.001% (w/v) poloxamer 188, wherein the pharmaceutical formulation has a pH of about 7.3;(c) about 180 mM sodium chloride, about 5 mM monobasic sodium phosphate, about 5 mM dibasic sodium phosphate, about 2 x10 12 vg/mL of the rAAV particles, and about 0.001% (w/v) poloxamer 188, wherein the pharmaceutical formulation has a pH of about 7.3; or (d) about 180 mM sodium chloride, about 5 mM monobasic sodium phosphate, about 5 mM dibasic sodium phosphate, about 6 x1011 vg/mL of the rAAV particles, and about 0.001% (w/v) poloxamer 188, wherein the pharmaceutical formulation has a pH of about 7.3. Copending claim 80 recites wherein the steroid treatment comprises difluprednate 0.05% at a dose of about 1 m g to about 3 m g. The copending claims do not recite using the compositions and formulations for treating neovascular glaucoma. Schaffer teaches the AAV2.7m8 variant capsid (i.e., the copending claimed AAV2 capsid variant virion) can be used for treating glaucoma ([0167]). Inatani teaches a clinical trial studying the efficacy of using aflibercept to treat neovascular glaucoma (Abstract). Inatani teaches that neovascular glaucoma is characterized by neovascularization of the iris and angle, which prevents normal drainage for the eye leading to elevated intraocular pressure (IOP) (¶ spanning pages 1107-1108). Inatani teaches that intravitreal aflibercept injection was approved in 2020 as a treatment for patients with neovascular glaucoma in Japan (page 1180, ¶2). Inatani teaches aflibercept treatment was associated with statistically significant and clinically meaningful reduction in interocular pressure (IOP), which support using aflibercept as a treatment of patients with neovascular glaucoma (page 1107, Conclusions). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have used the copending AAV2.7m8-aflibercept formulations to treat neovascular glaucoma. It would have amounted to using a known aflibercept viral delivery method known to treat neovascularization in the eye to treat a known disease characterized by neovascularization in the eye. The skilled artisan would have predicted that the copending AAV2.7m8-aflibercept vector could be used to treat neovascular glaucoma, and been motivated to have done so, because 1) Schaffer teaches the AAV2.7m8 variant can be used to treat glaucoma, and 2) Inatani teaches that aflibercept administration can reduce neovascularization in neovascular glaucoma. This is a provisional nonstatutory double patenting rejection. Claims 1-2, 7, 22, 24, 34, 39, 42-47 , 59, 64, 66, 67, 69-70, and 73-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 5-17, 47 and 50-52 of copending Application No. 17479968 in view of Schaffer (US 20140294771 A1) and Inatani (Inatani et al., Advances in Therapy (2021), 38: 1106-1115, published December 16, 2020). Claims 24 and 34 are rejected in further view of Keravala (US 20200010851 A1, published January 9, 2020). Claims 42-46, 59, 64, 66 and 67 are rejected in further view of Gasmi (WO 2021050094 A1, published March 28, 2021). Copending claim 1 recites A method of ameliorating one or more symptoms associated with wet age-related macular degeneration (wAMD), the method comprising administering a unit dose of a pharmaceutical composition by intravitreal injection to an eye of a primate subject in need thereof, wherein the unit dose is between 5E10 vector genomes (vg) to 7E12 vg, wherein the pharmaceutical composition comprises:(a) a rAAV2 variant comprising an amino acid sequence LGETTRP, SEQ ID NO: 4, inserted between positions 587 and 588 of capsid protein VP1, and a nucleic acid sequence encoding a polypeptide having an amino acid sequence with at least 95% homology to SEQ ID NO: 1 (i.e., identical to SEQ ID NO 35 of the examined application) , and(b) a pharmaceutically acceptable excipient. Copending claim 5 recites wherein the unit dose is between 2E12 to 6E12 vector genomes. Copending claim 9 recites wherein the subject is a human. Copending claim 50 recites wherein the nucleic acid sequence encoding a polypeptide having an amino acid sequence with at least 95% homology to SEQ ID NO: 1 is under the transcriptional control of a cytomegalovirus (CMV) promoter. Copending claims 6-7 recite wherein the unit dose is in a volume that is not more than 50 m L or 100 m L. The copending claims anticipate examined claims 69-70 because “for use in a method” is interpreted as intended use that does not limit the structure of the unit dose. The copending claims do not recite using the compositions and formulations for treating neovascular glaucoma. The copending claims do not recite additional regulatory elements of the sequences for the CMV promoter (claims 24 and 34). The copending claims do not recite specific formulations for the AAV2.7m8-aflibercept (claims 42-46). The copending claims do not recite coadministration with a steroid (claims 59, 64, 66, 67) . The teachings of Schaffer and Inatani are recited above in paragraph REF _Ref224735161 \r \h 47 - REF _Ref224735162 \r \h 48 and incorporated here. The obviousness of using the copending AAV2.7m8-aflibercept virion to treat neovascular glaucoma is recited above in paragraph REF _Ref224735184 \r \h 49 . Regarding claims 24 and 34, Keravala teaches optimized nucleic acid expression cassettes and vectors for expression gene in mammalian cells ([0005]), including for expression of aflibercept ([0020]). Keravala teaches a polynucleotide cassette comprising a CMV enhancer, CMV promoter, 5’UTR with TPL and eMLP, a coding sequence of a protein of interest, a full EES sequence second enhancer, and an HGH polyadenylation sequence (FIG 1, Cassette No. 11). Keravala teaches construct 11 drove high expression of transgenes, including for aflibercept, in HeLa cells (FIGs 2 and 7-8), HEK293 cells (FIGs. 3, 6 and 9), pig retinal explants (FIG. 4A-B, 10A-B; [0049]), and ARPE19 cells (FIG. 5). Regarding (a), Keravala teaches the sequence of the CMV enhancer is SEQ ID NO 1 ([0032]), which is 100% identical to SEQ ID NO 22 of the examined application. Regarding (b), Keravala teaches the sequence of the CMV promoter is SEQ ID NO 4 ([0032]), which is 100% identical to SEQ ID NO 23 of the examined application. Regarding (c), Keravala teaches the 5’ UTR comprising the TPL sequence and eMLP sequences comprising SEQ ID NOs 11 and 12 ([0032]), which are 100% identical to SEQ ID NOs 24 and 25, respectively, of the examined application. Regarding (d), Keravala teaches the enhancer sequence is the full EES sequence with SEQ ID NO 13 ([0032]), which is 100% identical to SEQ ID NO 26 of the examined application. Regarding (e), Keravala teaches the HGH polyadenylation signal sequence has SEQ ID NO 14 ([0032]), which is 100% identical to SEQ ID NO 27 of the examined application. Keravala teaches the AAV expression cassettes can be delivered by AAV particles including the variant comprising the 7m8 variant ([0039], [0049]). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have used Keravala’s Cassette No. 11 for expressing aflibercept delivered by the AAV2.7m8 capsid in the copending method rendered obvious to use as a treatment for neovascular glaucoma. It would have amounted to using known expression control elements/sequences by known means to yield predictable results. The skilled artisan would have predicted that Keravala’s Cassette 11 could be used in the obvious variation of the copending method to treat glaucoma because 1) Keravala teaches that aflibercept can be delivered in such as cassette, packaged into AAV2.2m8 virions and delivered to pig ocular cells and 2) the copending claims require at least a CMV promoter. The skilled artisan would have been motivated to use Keravala’s cassette because of its ability to drive high transgene expression in ocular tissues. Regarding claims 42-46, Gasmi teaches treating ocular neovascular disease in an individual comprising administering a unit dose of rAAV particles encoding SEQ ID NO 35 (i.e., aflibercept) and an AAV capsid having LGETTRP inserted into position 587-588 of VP1 capsid (i.e., AAV2.7m8) (Abstract). Gasmi teaches pharmaceutical formulations for the rAAV particles ([0177]-[0200]). Gasmi teaches a specific pharmaceutical formulation comprises 6 x 10 12 vg/mL or 6 x 10 11 vg/mL rAAV with about 180 mM sodium chloride, about 5 mM monobasic sodium phosphate, about 5 mM dibasic sodium phosphate and about 0.001% (w/v) poloxamer 188 (i.e., a surfactant) with a pH of 7.3 ([0185]). Gasmi also teaches the formulations can comprise about 2x 10 12 vg/mL of rAAV particles ([0179]). Gasmi uses the formulation recited in claim 44 in a phase I clinical trial for treating the neovascular disease wAMD ([0229], Table 1). Gasmi summarized the results of the phase I clinical trial as “AAV2.7m8-aflibercept provided a clear benefit for improving retinal anatomy and stabilizing vision, while exhibiting an acceptable safety profile. Specifically, patients maintained vision during the study, and AAV2.7m8-aflibercept was shown to be safe and well tolerated, with observed inflammation generally being mild and responsive to steroid eye drops.” ([0290]) It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have used the formulation and rAAV concentrations reported in Gasmi in the obvious variant in the copending method to treat glaucoma . It would have amounted to simple combination of known elements by known means to render predictable results. The skilled artisan would have predicted that the formulations would be functional to treat neovascular glaucoma, and been motivated to use the same formulations because Gasmi teaches the formulations for treating another neovascular ocular disease and concluded that the formulations are safe, well tolerated and provide a clear benefit for stabilizing vision. Regarding claim s 59, 64, 66 and 67, Gasmi teaches combining the AAV2.7m8-aflibercept treatment with a topical steroid comprising difluprednate 0.05% at a dose of about 1 m g to about 3 m g ([0021]). Gasmi also teaches another Phase I study combining the AAV2.7m8-aflibercept treatment with topical steroids, 0.05% difluprednate drops ([0303]-[0307]-Table 9). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have also provided difluprednate at 0.05% at a dose of about 1 m g to about 3 m g as reported in Gasmi in the obvious variant of the copending method to treat glaucoma . It would have amounted to simple combination of known elements by known means to render predictable results. The skilled artisan would have predicted that difluprednate could be provided and the combination with be AAV2.7m8-aflibercept functional to treat neovascular glaucoma because Gasmi teaches the formulations for treating another neovascular ocular disease and concluded that the formulations are safe, well tolerated and provide a clear benefit for stabilizing vision. The skilled artisan would have been motivated to use difluprednate for the purpose of treating inflammation which can occur with AAV2 gene delivery to the eye. Claims 1-2, 7, 22, 24, 34, 39, 42-47 , 59, 66, 69-70, and 73-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-9, 11, 17, 19-21, 29-37, 39- 64, 101-102, 107-108 and 114-123 of copending Application No. 18834864 in view of Schaffer (US 20140294771 A1) and Inatani (Inatani et al., Advances in Therapy (2021), 38: 1106-1115, published December 16, 2020). Copending claims 1 and 3 recite A method for treating [for reducing retinal fluid in an individual with] an ocular neovascular disease in an individual, the method comprising administering a unit dose of about 1 x 10 10 vector genomes(vg) to about 2 x 10 11 vg of recombinant adeno-associated virus (rAAV) particles to one eye of the individual, wherein the individual is a human, and wherein the rAAV particles comprise: a) a nucleic acid encoding a polypeptide comprising an amino acid sequence with at least about 95 % identity to the amino acid sequence of SEQ ID NO: 35 (i.e., 100% identical to SEQ ID NO 35 of the examined application) and flanked by AAV2 inverted terminal repeats (ITRs), and b) an AAV2 capsid protein comprising an amino acid sequence LGETTRP (SEQ TD NO:14) inserted between positions 587 and 588 of the capsid protein, wherein the amino acid residue numbering corresponds to an AAV2 VP1 capsid protein an wherein the method further comprises administering an implant containing a steroid for the one eye. Copending claim 17 recites wherein the unit dose of rAAV particles is between about 6 x 10 10 to about 2 x 10 11 vector genomes per eye (vg/eye). Copending claim 32 recites wherein the polypeptide is aflibercept. Copending claim 34 recites wherein the nucleic acid comprises, in the 5' to 3' order:(a) a first enhancer region;(b) a promoter region;(c) a 5'UTR region;(d) a nucleic acid encoding a polypeptide comprising an amino acid sequence with at least about 95% identity to the amino acid sequence of SEQ ID NO: 35;(e) a second enhancer region; and(f) a polyadenylation site;and flanked by AAV2 inverted terminal repeats (ITRs). Copending claims 44 recites wherein the nucleic acid further comprises (a) a first enhancer region comprising a CMV sequence comprising the sequence of SEQ ID NO: 22; (b) a promoter region, comprising a CMV sequence comprising the sequence of SEQ ID NO: 23; (c) a 5'UTR region comprising, in 5' to 3' order, a TPL sequence comprising the sequence of SEQ ID NO: 24, and an eMLP sequence comprising the sequence of SEQ ID NO: 25; (d) a second enhancer region comprising a full EES sequence comprising the sequence of SEQ ID NO: 26; and (e) a HGH polyadenylation site comprising the sequence of SEQ ID NO: 27 , which are 100% identical to the same SEQ ID NOs in the examined application. Copending claims 51-52 recites wherein the unit dose of rAAV particles is in a pharmaceutical formulation compris ing the rAAV particles, sodium chloride, sodium phosphate and a surfactant. Copending claims 52-56 recite wherein the pharmaceutical formulation comprises about 180 mM sodium chloride, about 5 mM monobasic sodium phosphate, about 5 mM dibasic sodium phosphate, about 6 x 10 12 vg/mL , 2 x 10 12 vg/mL or 6 x z 10 11 vg/mL of the rAAV particles, and about 0.001% (w/v) poloxamer 188, wherein the pharmaceutical formulation has a pH of about 7.3. Copending claims 57-59 recite wherein the unit dose of rAAV particles administered to the one eye isand/or to the contralateral eye in a volume of about 25 m L to about 250 m L , including about 30 m L . The copending claims anticipate examined claims 69-70 because “for use in a method” is interpreted as intended use that does not limit the structure of the unit dose. The copending claims do not recite using the compositions and formulations for treating neovascular glaucoma. The teachings of Schaffer and Inatani are recited above in paragraph REF _Ref224735161 \r \h 47 - REF _Ref224735162 \r \h 48 and incorporated here. The obviousness of using the copending AAV2.7m8-aflibercept virion to treat neovascular glaucoma is recited above in paragraph REF _Ref224735184 \r \h 49 . Conclusion No claims are allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT CATHERINE KONOPKA whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0330 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon - Fri 7- 4 . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CATHERINE KONOPKA/ Primary Examiner, Art Unit 1635