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. Election/Restrictions Applicant’s election without traverse of Group 1, claims 20-28 and 54 in the reply filed on 31 December 2025 is acknowledged. Claim s 29, 31-35, 38-42, and 48-51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 31 December 2025 . Applicant added claim 57 after the restriction requirement. This claim is directed to claim 20 and will be included in Group 1. Therefore, Group 1 now includes claims 20-28, 54, and 57. Claim Status Claims 1-19 , 30, 36-37, 43-47, 52-53, and 55-56 were previously cancelled, claim 57 is new, claims 21-22, 26-27, 42, and 54 have been amended, claims 20-28, 54, and 57 have been considered on their merits. Claim Objections Claim 20 is objected to because of the following informalities: The first instance of the acronym TNF should be spelled out. Claim 57 is objected to because of the following informalities: The claim refers to claim 20, yet states “The method of claim 20”. Claim 20 is a composition claim. For the purpose of compact prosecution c laim 57 will be interpreted as “The composition of claim 20, …”. Appropriate correction is required. Claim Rejections - 35 USC § 112 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 applicant regards as his invention. Claims 26 and 57 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. Regarding claim 26, t he claims refer to signal sequences from Tables 2 or 3, which is not found in the claims. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola , 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). See MPEP § 2173.05(s). It is suggested to amend the claims to include the data from Tables 2 and/or 3 into the claims. Regarding claim 57, the claim requires the viral capsid have an amino acid sequence which is at least 95% identical to a list of known AAV serotype capsids, yet the claim does not provide the requisite sequences for comparison. It is understood, some AAV capsid sequences are well - known in the art, however, some of these capsid sequences have variations. Therefore, without the sequence data for comparison the claim is considered indefinite . 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 20-22, 24, 26-27, 54, and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Danos et al. (WO2019/079496 A2, published 25 April 2019, IDS ref.) in view of Lebreton et al. (FR3031112 A1, published 01 July 2016, IDS ref.). Lebreton et al. was provided in the IDS, however, the document is in French. A machine translation was used as a reference. Regarding claim s 20 , 22, 24 , 26 , and 57 , Danos et al. teach vectors for the delivery of a transgene to a target cell, wherein the vectors include viral vectors or plasmids (para. [0041]). Danos et al. teach in some embodiments, the vector is a targeted vector, e.g., a vector targeted to retinal pigment epithelial cells (para. [0041]). Danos et al. teach the recombinant vector used for delivering the transgene includes non-replicating recombinant adeno-associated virus vectors ( rAAV ) ( claim 20 preamble ) or other viral vectors including but not limited to lentiviral vectors , vaccinia viral vectors, non-viral expression vectors referred to as "naked DNA" constructs ; wherein e xpression of the transgene can be controlled by constitutive or tissue-specific expression control elements (para. [0006]). Danos et al. teach the recombinant vector used for delivering the transgene includes AAV based vectors comprising capsid ( claim 20(a) ) components from one or more of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh 1 0 , or AAVrh20 ( claim 57 ) (para. [0031]) . Danos et al. teach a pharmaceutical composition for treating ocular disorders, including age-related macular degeneration, in a human subject in need thereof, comprising an AAV vector comprising: (a) a viral capsid that is at least 95% identical to the amino acid sequence of an AAV8 capsid (SEQ ID NO: 78) or AAV9 capsid (SEQ ID NO: 79); and (b) an artificial genome comprising an expression cassette flanked by AAV ITRs wherein the expression cassette comprises a transgene operably linked to one or more regulatory sequences that control expression of the transgene in human retinal cells ( claim 24 ); wherein said AAV vector is formulated for subretinal, intravitreal, or suprachoroidal administration to the eye of said subject. (Section 3.1 Illustrative Embodiments, 82). An artificial genome comprising an expression cassette flanked by AAV ITR wherein the transgene is operably linked to one or more regulatory sequences that control expression of the transgene in human retinal cells, read as regulatory sequences that promote expression of the transgene in human ocular tissue cells. Danos et al. teach signal sequence MYRMQLLLLIALSLALVTNS (SEQ ID NO: 161) (para. [0066]), which is identical to instant SEQ ID NO: 62 ( claim 26 ). Danos et al. teach signal peptides may also be referred to as leader peptides or leader sequences (para. [0065]), which suggest said signal sequence is present at the N-terminus of the transgene. Additionally, Danos et al. teach a composition wherein the transgene encodes a signal sequence at the N-terminus of a transgene which directs secretion and post translational modifications in human retinal cells ( ocular tissue cells ) (section 3.1 Illustrative Embodiments, 88). While Danos et al. teach the AAV , capsid, regulatory elements , and delivering transgene to human ocular tissue, Danos et al. do not teach the specific expression cassette compris ing a transgene encoding an anti-TNFα F c fusion protein comprising a human soluble TNF α receptor type I ( TNFRl ) or type II (TNFR2) extracellular domain covalently linked through a peptide bond to a polypeptide comprising an Fc domain of an immunoglobulin heavy chain. However, Lebreton et al. teach treatment of uveitis with a DNA construct allowing the targeted intraocular production of therapeutic proteins (p. 1). Lebreton et al. teach a DNA construct intended for the non-viral transfer of nucleic acids into the muscle cells of the ocular sphere of a patient, which comprises an origin of replication, a promoter allowing its expression in the ocular sphere of the patient, one or more sequences promoting the expression of the DNA in the ocular sphere of the patient, and a polynucleotide coding for a therapeutic protein selected for its activity in the treatment of ocular pathologies (p. 3). Lebreton et al. teach the DNA construct comprises a polynucleotide encoding a fusion protein comprising human versions of soluble TNFα type I receptor ( hTNFR -Is) and immunoglobulin G1 heavy chain (hIgG1) and a thrombin cleavage site (p. 5). Lebreton et al. teach in a preferred embodiment the fusion protein corresponds to SEQ ID NO: 4, which is 100% identical to instant SEQ ID NO: 12 ( claim 22 ) . See sequence search results file us-18-034-042a-12.rag, result number 2 for full alignment, see search result header below: Therefore, it would have been obvious for one of ordinary skill in the art to utilize the composition of Danos et al. to deliver a transgene expressing the fusion protein of Lebreton et al. with a reasonable expectation of success because both references teach methods of treating diseases associated with ocular tissue cells . Additionally, MPEP § 2144.06(I) states "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) (citations omitted).” One would be motivated to utilize the composition of Danos et al. to deliver a transgene expressing the fusion protein of Lebreton et al. because Danos et al. teach therapeutic antibodies delivered by gene therapy have several advantages over injected or infused therapeutic antibodies that dissipate over time resulting in peak and trough levels (para. [0008]). Danos et al. teach sustained expression of the transgene product antibody, as opposed to injecting an antibody repeatedly, allows for a more consistent level of antibody to be present at the site of action, and is less risky and more convenient for patients, since fewer injections need to be made (para. [0008]). Thus, suggesting an advantageous delivery method compared to directly delivering the TNFα inhibitor fusion protein taught by Lebreton et al. which could result in a more consistent level of the fusion protein in said ocular tissue cells. Regarding claim 21, Lebreton et al. teach the fusion protein has a sequence in which the human version of the soluble TNFα type I receptor ( hTNFR -Is) is linked to the human immunoglobulin G1 heavy chain (hIgG1) by a thrombin cleavage site (reads as the C-terminus of the human TNFR extracellular domain) (p. 6). Lebreton et al. teach the thrombin cleavage site corresponds to SEQ ID NO: 3 (p. 6). The sequence is disclosed in the untranslated FR3031112, found on page 22 (SEQ ID NO: 3 LVPRGS), which is 100% identical to instant SEQ ID NO: 8 Regarding claim 27, Danos et al. teach a self-complementary vector may be utilized (para. [0056]). Regarding claim 54, Danos et al. teach culturing a host cell containing an artificial genome comprising a cis expression cassette flanked by AAV ITRs, wherein the cis expression cassette comprises a transgene encoding a therapeutic antibody operably linked to expression control elements that will control expression of the transgene in human cells; a trans expression cassette lacking AAV ITRs, wherein the trans expression cassette encodes an AAV rep and capsid protein operably linked to expression control elements that drive expression of the AAV rep and capsid proteins in the host cell in culture and supply the rep and cap proteins in trans; sufficient adenovirus helper functions to permit replication and packaging of the artificial genome by the AAV capsid proteins; and recovering recombinant AAV encapsidating the artificial genome from the cell culture (para. [0040]). Danos et al. teach the means of delivery of a transgene include plasmids (para. [0041]). Therefore, Danos et al. in view of Lebreton et al. read on the limitations of the claim for the same reasons set forth above regarding the rejection of claim 20 Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention. Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Danos et al. (WO2019/079496 A2, published 25 April 2019, IDS ref.) in view of Lebreton et al. (FR3031112 A1, published 01 July 2016, IDS ref.), as applied to claim 20 above, and further in view of Gamache et al. (US2009/0098136 A1, published 16 April 2009). Regarding claim 23, Danos et al. in view of Lebreton et al. are silent to the anti-TNFα Fc fusion protein being etanercept. However, Gamache et al. teach treating dry eye by administering inhibitors of TNFα (Abstract). Gamache et al. teach TNFα inhibitors are soluble dimeric TNFα receptors, such as etanercept, which is a dimeric fusion protein of the extracellular ligand-binding portion of the human TNFα receptor (p75) linked to the Fc portion of human IgG1 (para. [0020]). Therefore, it would have been obvious to one of ordinary skill in the art to utilize the etanercept of Gamache et al. in the composition taught by Danos et al. in view of Lebreton et al. with a reasonable expectation of success because all three references teach methods of treating diseases associated with ocular tissue cells. One would be motivated to utilize the etanercept of Gamache et al. in the composition taught by Danos et al. in view of Lebreton et al. because Gamache et al. teach etanercept is a soluble TNFα inhibitor linked to the Fc portion of human IgG1, which reads the same as the teachings of Lebreton et al. Additionally, MPEP § 2144.06(II) states, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout , 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention. Allowable Subject Matter Claim s 25 and 28 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The following is a statement of reasons for the indication of allowable subject matter: The nucleic acid sequences of SEQ ID NO: 13 and 14 are codon optimized sequences and these optimized sequences were found to be free from the prior art. Accordingly, the nucleic acid sequences corresponding to SEQ ID NOs: 15-18 comprise the codon optimized nucleic acid sequence of SEQ ID NO: 13, as such, these sequences were found to be free from the prior art. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT NICHOLAS A. HUMPHRIES whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-5556 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday, 7:30am - 4:30 pm . 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. /N.A.H./ Examiner, Art Unit 1631 /LAURA SCHUBERG/ Primary Examiner, Art Unit 1631