This Office Action supersedes the non-final Office Action mailed on January 7, 2026.
DETAILED ACTIONNotice 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 and Election
Claims 1, 3, and 5-16 are currently pending. Applicant’s election without traverse of group I (claims 1-7) remains acknowledged. Applicant elected the species of Group A: “inhibiting expression and influencing the protein” and Group B: “siRNA”. Claims 5 and 8-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim.
Claim 1 is amended. Claims 2 and 4 are canceled.
Examination on the merits commences on claims 1, 3, and 6-7. Applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and, therefore, the finality of that action is withdrawn.
Applicants are informed that the rejections and/or objections of the previous Office action not stated below have been withdrawn from consideration in view of the Applicant' s arguments and/or amendments. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 103 – NEW
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.
Claim 1 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Kipnis of record (Kipnis, J., US-20210311076-A1, published 10/7/21), in view of Han (Han, Jihoon, et al. "Alzheimer's disease-causing presenilin-1 mutations have deleterious effects on mitochondrial function." Theranostics 11.18 (2021): 8855. (Year: 2021)),(published August 17, 2021).
Regarding claim 1, Kipnis teaches a method of diagnosing and treating neurodegenerative disorders by detecting and/or inhibiting an upregulated target gene (claim 1 and [0006]) specifically related to Alzheimer’s disease (AD) (claim 66 and [0021]), where the fold change of the upregulated target gene relative to control is measured (Table 2). Kipnis teaches a list of suspected gene targets such as wherein the agent or inhibitor targets Atlastin GTPase2 gene (ATL2) (Table 2, pg 88 line 3, claim 52). Kipnis teaches wherein the agent or inhibitor for treating the neurodegenerative disease is an siRNA for the upregulated target (pg 88 line 3, claim 52).
Kipnis does not provide working examples of ATL2 inhibition to treat Alzheimer’s Disease. However, Han teaches the gene the Atlastin 2 (ATL2) gene has an integral pathological role in Alzheimer’s disease where down-regulation of ATL2 after PS1 mutant induction rescued abnormally elevated ER-mitochondria interactions back to the normal level (abstract). Specifically, Han teaches expression profiling in the hippocampus samples from wild-type and PS1M146V knock-in mice revealed a critical role of Atlastin 2 (ATL2) in the formation of ER-mitochondria contact sites (pg 8856 col 2 para 2). Han teaches significantly elevated ATL2 expression levels observed in the brains of both 3xTg-AD mice and Alzheimer’s Disease patients where findings suggest a deleterious effect of PS1 mutations identified in Familial AD on mitochondrial functions (pg 8856 col 2 para 2).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention for the gene targeting method of Kipnis to treat Alzheimer’s Disease by specifically targeting the ATL2 gene with inhibitory RNA therapeutics. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that the ATL2 gene, described as a potential target within Table 2 of Kipnis, plays a significant role in the pathology of Alzheimer’s Disease because Han teaches significantly elevated ATL2 expression levels observed in the brains of both 3xTg-AD mice and where down-regulation of ATL2 after PS1 mutant induction rescued AD phenotypes back to normal level. Thus, it would have been predictable that a skilled artisan would employ RNAi therapeutics to target ATL2 within Kipnis’ method in order to enhance treatment of subjects with Alzheimer’s Disease.
Regarding claim 6, Han teaches ATL2 increase ER-mitochondria contacts (abstract). Han teaches ATL2 is involved in ER membrane fusion and tethering, which is critical in forming ER-mitochondrial contacts (pg 8866 col 1 para 1). Han teaches down-regulation of ATL2 after PS1 mutant induction rescued that abnormally elevated ER-mitochondria interactions back to the normal level (abstract). Therefore, the inhibitor of the expression of the ATL2 gene or protein lowers the binding between endoplasmic reticulum (ER) and mitochondria in the brain.
Regarding claim 7, Han teaches that ATL2 knockdown rescues the abnormally elevated mitochondrial superoxide present in AD (pg 8866 col 1 para 1, Figure 6G). Therefore, the inhibitor of the expression or activity of the ATL2 gene inhibits the production of mitochondrial superoxide.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Kipnis of record (Kipnis, J., US-20210311076-A1, published 10/7/21), in view of Han (Han, Jihoon, et al. "Alzheimer's disease-causing presenilin-1 mutations have deleterious effects on mitochondrial function." Theranostics 11.18 (2021): 8855. (Year: 2021)),(published August 17, 2021), as applied to claim 1, and in further view of GenBankATL2 of record (GenBankATL2, atlastin-2 isoform 5 [Homo sapiens], accession NP_001317388 XP_011531321, https://www.ncbi.nlm.nih.gov/protein/1060099103?sat=49&satkey=12143486, retrieved 12/29/25, revision 10/11/20, printed as pg 1/2 to 2/2).
Regarding claim 3, the teachings of Kipnis and Han as applied above for claim 1 are incorporated here. Kipnis is silent as to the sequence of the ATL2 gene being inhibited, however, GenBankATL2 teaches instant SEQ ID NO: 1 sequence is the ATL2 gene in homo sapiens (pg 1-2). It would have been obvious to one skilled in the art before the effective filing date of the claimed invention for the ATL2 gene targeted to comprise a base sequence encoding the amino acid sequence of instant SEQ ID NO: 1, given the teachings of GenBankATL2 and the §103 rejection applied above for claim 1.
Response to Arguments
Applicant’s arguments (Remarks pages 6-10) are directed to the withdrawn §§§ 112b, 112a, and 102 rejections of record. Therefore, the arguments are moot.
Conclusion
No Claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN CHARLES MCKILLOP whose telephone number is (703)756-1089. The examiner can normally be reached Mon-Fri 8:30-5:30.
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/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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