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 Priority Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Acknowledgment is made of Applicants’ claim for benefit to foreign applications JP2021-033714 and JP2021-145796 filed 03/03/2021 and 09/07/2021 respectively . This application claims the benefit of priority to Patent Application PCT/JP2022/008898 . Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/JP2022/008898 , filed on 03/02/2022 . Information Disclosure Statement The IDS filed 12/28/2023, 04/28/2025, 07/30/2025 ha s been considered by the Examiner. Status of Claims Claims 11-20 are under examination. Claim 1-10 are cancelled. 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. Claim s 1 1 -20 are rejected under 35 U.S.C. 103 as being unpatentable over Sakamoto et al. (International Journal of Molecular Medicine, 2016) and in further view of Castillo et al. (Pharm Res., 2013) . Regarding claim 11, Sakamoto et al. teach r ecombinant adenoviral vectors for gene therapy (page 1676, paragraph 3) . Sakamoto et al. teach delivery of nucleic acids via r eplication-defective recombinant adenoviral vectors (Ads) (page 1676, Results paragraph 2) . Sakamoto et al . teach v ectors in cluding Ad.HB-EGF and Ad.HGF ( page 1674, materials and methods) . Sakamoto further teach treatment of mice with HB-EGF and HGF gene therapy in mice (page 1676, Results paragraph 2). Sakamoto et al. teach the method is useful in regeneration and inhibition organ injuries (page 1674, paragraph 3). Therefore Sakamoto et al. teach a method of treating a mammal comprising administering an effective amount of a nucleic acid encoding a heparin-binding epidermal growth factor-like growth factor (HIB-EGF). Sakamoto does not teach treating diabetes in a mammal with diabetes. Castillo et al. teach r egenerating missing or insufficient β-cells and/or shutting down the underlying autoimmune disease that attacks β-cells a s recent major research goals (page 2, introduction) . Castillo et al. teach advances in the understanding of growth factors and hormones involved in β-cell regeneration and the development of various agents that are able to modulate the autoimmune disease (page 2, introduction) . Castillo et al. teach methods of treating diabetes in a mammal with diabetes by administering growth factors (page 1, abstract). Castillo et al. teach HB - EGF treatment is responsible for the reduction of insulitis (page 9, paragraph 3). Castillo et al. teach HB-EGF was administered to insulitis / diabetes model (page 1, method). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Sakamoto et al. for a treatment involving the delivery of Ad.HB-EGF for gene therapy with the teachings of Castillo et al. for methods of treating diabetes in a mammal with diabetes by administering growth factors . Castillo et al. provide motivation by teaching that r egenerating missing or insufficient β-cells via the modulation or introduction of growth factors are major research goals . One of skill in the art would have had a reasonable expectation of success at combining Sakamoto et al. and Castillo et al. because both teach delivery of growth factors to a mammal in order to improve condition of the cells in an organ. Regarding claim 12, Sakamoto et al. teach the method of treating further comprises administering to the mammal an effective amount of a nucleic acid encoding HGF a hepatocyte growth factor (page 1681 , paragraph 3 ) Regarding claim 13, Castillo et al. teach insulin staining and fasting blood glucose as reporters for an increase in β -cell mass or regeneration as a result of treatment (page 2, introduction) . Castillo et al. teach the measure β -cell mass correlates positively with and is directly related to insulin staining of the pancreas (page 2, introduction). Therefore, an increase in pancreatic β -cells also increased insulin levels which were responsive to gluco se and decreased overall fasting blood glucose . Regarding claim 14, Sakamoto et al. teach intravenous injection of adenoviral vectors (page 1673, abstract). Regarding claim 15, Sakamoto et al. teach the nucleic acid is carried on a viral vector (page 1673, abstract). Regarding claim 16, Sakamoto et al. teach the viral vector is an adenovirus (ad) vector (page 1674, materials and methods). Regarding claim 17, Sakamoto et al. teach o n day 0 mice were injected in the tail vein with a single dose combination of Ad.HB-EGF and Ad.HGF ( pa ge 1674, Materials and methods). Regarding claim 18, Sakamoto et al. teach an injection in to the tail vein with 2x10 11 total particles of Ad.HB-EGF and Ad.HGF (page 1674, Materials and methods). Castillo et al. teach the growth factors were administered per kg of bodyweight (pages 3-4, Pharmacokinetics). Therefore, a practitioner would arrive at 2x10 11 particles/kg of bodyweight in order to introduce an amount proportional to the body weight of the subject. Regarding claim 19, Castillo et al. teach the diabetes is type 1 diabetes (T1D) (page 8, paragraph 2). Regarding claim 20, Castillo et al. teach the treatment is anticipated for use in humans (page 8, paragraph 2). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Catherine L McCormick whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-5659 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Friday, 8:30 am-5:30 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. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Tracy Vivlemore can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-2914 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /C.L.M./ Examiner, Art Unit 1638 /Anna Skibinsky/ Primary Examiner, AU 1635