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 has been considered by the Examiner.
Status of Claims
Claims 11 and 13-20 are under examination.
Claims 1-10 and 12 are cancelled.
Claim Rejections - 35 USC § 103
Rejection to claims 12 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 (Pharm Res., 2013) has been withdrawn in view of the applicant’s amendments filed 03/23/2026.
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.
Claims 11 and 13-20 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 recombinant adenoviral vectors for gene therapy (page 1676, paragraph 3). Sakamoto et al. teach delivery of nucleic acids via replication-defective recombinant adenoviral vectors (Ads) (page 1676, Results paragraph 2). Sakamoto et al. teach vectors including 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 regenerating missing or insufficient β-cells and/or shutting down the underlying autoimmune disease that attacks β-cells as 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 and HGF 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 regenerating 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 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 glucose 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 on day 0 mice were injected in the tail vein with a single dose combination of Ad.HB-EGF and Ad.HGF (page 1674, Materials and methods).
Regarding claim 18, Sakamoto et al. teach an injection into the tail vein with 2x1011 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 2x1011 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).
Response to Arguments
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive.
Applicant’s argument: Applicant argues HB-EGF gene was administered to T1D model mice by systemic administration rather than by topical administration to pancreas, in the mice, elevation of blood glucose was suppressed over a long term of at least 10 weeks after administration.
Examiner’s response: The administration to a T1D model mouse is not a limitation of the current claims. Furthermore, decreased blood glucose is the successful treatment of diabetes.
Applicant’s argument: The combination of Sakamoto et al. and Castillo et al. fails to disclose or reasonably suggest treating diabetes in a mammal by administering both (a) an effective amount of a nucleic acid encoding a HB-EGF and (b) an effective amount of a nucleic acid encoding a HGF, much Less recognize the unexpected benefits, e.g., synergistically improved glucose tolerance over a long period of time, resulting therefrom.
Examiner’s response: As previously recited 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). Sakamoto et al. teach vectors including Ad.HB-EGF and Ad.HGF (page 1674, materials and methods). Sakamoto further teach treatment of mice with HB-EGF and AD.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).
The combination of cited prior art makes obvious treatment of diabetes in a mammal with HB-EGF and HGF. Sakamoto teaches the method is useful in regeneration and inhibition organ injuries. Organ regeneration and inhibiting organ injury specifically the β-cells of the pancreas for treating diabetes in a mammal. The growth factors and hormones involved in β-cell regeneration are crucial to repair a damaged pancreas and long term improvement of diabetes symptoms.
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.
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635
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