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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 11/5/2025 has been considered. Claims 17-23 are newly added. Claims 13-15 are canceled. Claims 1, 3-6, 8-9 and 11 are amended. Claims 1-12 and 16-23 are pending and are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application EP19382447.1 and 371 of PCT/EP2020/065018 published 5/31/2019 and 5/29/2020, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 5/31/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/9/2025 were received. The submissions were in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements were considered by the examiner.
Withdrawn Rejections
The 35 U.S.C. 102(a)(1) and 102(a)(2) rejection of claims 1, 7-8 and 11-12 has been withdrawn in light of applicants claim amendments which further describe the encoded insulin as comprising a furin cleavage site.
Similarly, the 35 U.S.C. 102(a)(1) and 102(a)(2) rejection of claims 1-5, 7-10 and 16 has been withdrawn in light of applicants claim amendments which further describe the encoded insulin as comprising a furin cleavage site.
The 35 U.S.C. 103 rejection of claims 1-6, 7-12 and 16 has been withdrawn in light of applicants claim amendments which further describe the encoded insulin as comprising a furin cleavage site.
Claim Interpretation
Insulin as recited in claim 1 will be given its broadest reasonable interpretation consistent with the specification and include insulin and insulin-like growth factors (IGF) given the close functional and sequence homology. It is noted that this interpretation does not apply to claim 6 wherein the nucleotide or amino acid sequence encoding insulin is expressly defined.
It is noted that the preamble “a method for treating and/or preventing neuroinflammation, neurodegeneration and/or cognitive decline” is construed as intended use language. 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 of significant weight, see MPEP 2111.02.
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 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.
Claims 1, 6-8, 11-12 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Ishii et al. US 2008/0248099, published 10/9/2008 (hereinafter Ishii, reference of record) in view of Tang et al. US 2004/0142884, published 4/22/2004 (hereinafter Tang). This rejection is newly applied as necessitated by applicant’s amendments dated 11/5/2025.
Claims 1 and 7-8: Ishii describes a method for treating diseases of the nervous system by administering a viral vector encoding a nucleotide sequence encoding insulin into the central nervous system (CNS) (Ishii, para 29, 39 and claim 17). Ishii found that insulin broadly acts as a neurotrophic factor and can treat a variety of diseases of the CNS (Ishii, para 33).
Claims 11 and 23: Ishii describes treating neurodegenerative diseases like Alzheimer’s (Ishii, claim 1).
Claim 12: Ishii describes delivery into the intra- cerebrospinal fluid (Ishii, para 45).
Ishii does not expressly describe the encoded insulin comprising a furin cleavage site or a nucleotide sequence encoding insulin consisting of the amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 42.
Claim 1: Tang describes a method for engineering non-beta like cells to secrete insulin in a glucose-responsive manner for treating diabetes (Tang, para 12, 102). Tang describes the expression of a mutated pre-proinsulin cDNA that includes a furin cleavage site at the B-C and C-A junctions (Tang, Fig 1 and example 1). Tang describes how incorporating furin cleavage sites into the proinsulin sequence allows the non-beta cells which typically have furin but lack the specific convertases found in pancreatic beta cells to accurately and efficiently cleave the proinsulin precursor to yield biologically active insulin (Tang, para 15, 22, and example 1).
Claim 6: Tang discloses a nucleic acid sequence with 100% sequence similarity to instant SEQ ID NO: 42 (sequence search results shown below). Notably, the furin cleavage site is highlighted in red.
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Sequence alignment for SEQ ID NO: 333 from Tang against instant SEQ ID NO: 42
It would have been prima facie obvious to one of ordinary skill in the art to substitute the specific human insulin cDNA sequence comprising a furin cleavage site as disclosed by Tang for the recombinant cDNA described by Ishii. It would have been a matter of simply substituting one known human insulin cDNA sequence for another to obtain predictable results given that Ishii expressly describes the use of recombinant insulin from humans, but falls short of providing the specific sequence comprising a furin cleavage site as described in claims 1 and 6 (Ishii, para 37). One would have been motivated to make this substitution given that incorporating a furin cleavage sites into the proinsulin sequence allows the non-beta cells which typically have furin but lack the specific convertases found in pancreatic beta cells to accurately and efficiently cleave the proinsulin precursor to yield biologically active insulin (Tang, para 15, 22, and example 1). One would have a reasonable expectation of success given that the substitution of one known cDNA sequence for another in a viral vector is routine in the art and that there are known advantages of incorporating a furin cleavage site into proinsulin precursors to improve therapeutic outcomes as demonstrated by the disclosure of Tang. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 1, 6-8, 11-12 and 23 to have been prima facie obvious to at the time the invention was made.
Claims 1-12 and 16-23 are rejected under 35 U.S.C. 103 as being unpatentable over Ishii (supra) in view of Tang (supra) as applied to claims 1, 6-8, 11-12 and 23 above in further view of Dominguez et al. US 2018/0265893, published 9/20/2018 (hereinafter Dominguez, reference of record). This rejection is newly applied as necessitated by applicant’s amendments dated 11/5/2025.
A description of Ishii and Tang can be found above. Neither Ishii nor Tang describes the use of a ubiquitous CAG promoter, the specific expression vector limitations or the use of a target sequence in the gene construct of a microRNA expressed in the liver and heart tissue in which transgene expression is intended to be prevented.
Claim 1: Dominguez describes gene expression constructs comprising a nucleotide sequence encoding an insulin-like growth factor (IGF) and methods for treating type 1 diabetes (Dominguez, abstract and para 5, 12-22).
Claims 2-3 and 17: Dominguez describes the expression of the nucleotide sequence encoding IGF under the control of the ubiquitous CAG promoter (Dominguez, para 23).
Claims 4-5 and 18: Dominguez describes expression of IGF operably liked to a ubiquitous promoter having a target sequence of a microRNA expressed in the liver and heart tissue in which IGF expression is intended to be prevented (Dominguez, para 12, 40, 41). Dominguez provides embodiments to target sequences of microRNA which share 100% sequence similarity to instant SEQ ID Nos: 7 and 8, respectively (Dominguez, para 71).
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Sequence search results, instant SEQ ID No: 7 as compared to SEQ ID No: 8 from Dominguez
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Sequence search results, instant SEQ ID No: 8 as compared to SEQ ID No: 15 from Dominguez
Claims 7-10, 16 and 19-22: Dominguez describes the use of a viral expression vector including AAV serotype 6 and pharmaceutically acceptable ingredients (Dominguez, para 88-92 and 118). Dominguez provides preferred embodiments to AAV serotype 1 and 9 vectors (Dominguez, para 161).
It would have been prima facie obvious to one of ordinary skill in the art to modify the insulin expressing vector of Ishii in view of Tang to include a ubiquitous promoter having a target sequence of a microRNA expressed in the liver and heart tissue in which insulin expression is intended to be prevented as described by Dominguez. It would have been a matter of combining prior art elements according to known methods to yield predictable results since all expression vector elements were known in the art. Furthermore, the disclosure of Ishii describes how insulin broadly acts as a neurotrophic factor and can treat a variety of diseases of the CNS (Ishii, para 33). Thus, one would have been motivated to make this combination in order to minimize off-target insulin expression in the heart and liver tissue and improve therapeutic efficacy by specifically administering and targeting the CNS (Dominguez, para 15-23). One would have a reasonable expectation of success given that both insulin and IGF are closely related hormones and in the same technical field. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
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