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 claims
Claims 1-19 are original. Claims 3-19 are withdrawn due to a restriction. Claims 1-2 are elected, pending, and under examination.
Priority
This application is a continuation of International Application No. PCT/CN2022/110893, filed on August 8, 2022, which claims priority to Chinese Patent Application No. 202111612903.1. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/12/2024 and 08/11/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of Group I (i.e., claims 1-2) in the response filed on 07/17/2026 is acknowledged. Claims 3-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, here being no allowable generic or linking claim. Per the applicant’s request, the election is treated as without traverse.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamaguchi (Yamaguchi A, Ishikawa KI, Inoshita T, et al. Identifying Therapeutic Agents for Amelioration of Mitochondrial Clearance Disorder in Neurons of Familial Parkinson Disease. Stem Cell Reports. 2020;14(6):1060-1075. doi:10.1016/j.stemcr.2020.04.011).
Yamaguchi aimed to establish an imaging-based, semi-automatic, high-throughput system for the quantitative detection of disease-specific phenotypes in dopaminergic neurons from induced pluripotent stem cells [¶abstract].
Regarding Claim 1: Yamaguchi teaches treating PARK2 and PARK6 iPSC-derived dopaminergic neurons with flunarizine, including repetitive testing with 1-100µM flunarizine, and reports that flunarizine accelerated mitochondrial elimination, decreased mitochondrial area, and promoted lysosomal degradation of the mitochondria––Thereby teaching contacting flunarizine with cells to remove intracellular mitochondria [p. 1066, col. 1, ¶2; Figures 3 and S4A]. Yamaguchi teaches that the treated PARK2 and PARK6 neurons contain intracellular mitochondria and specifically evaluates mitochondrial clearance within those cells [p. 1062, col. 2, ¶2]. Yamaguchi also identifies the PARK2 cells as having homozygous Parkin deletions and PARK6 cells having a PINK1 mutation (which results in mitochondrial dysfunction) [p. 1062, col. 1, ¶1].
Regarding Claim 2: The instant recitation of claim 2 that the mitochondria “comprise mitochondria with a DNA mutation and/or mitochondria without a DNA mutation” encompass mitochondria regardless of mutation status, because the claimed alternative include mitochondria either with or without a DNA mutation. Accordingly, this limitation does not further distinguish the claimed mitochondria from the intracellular mitochondria disclosed by Yamaguchi.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 inventio
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Yamaguchi (Yamaguchi A, Ishikawa KI, Inoshita T, et al. Identifying Therapeutic Agents for Amelioration of Mitochondrial Clearance Disorder in Neurons of Familial Parkinson Disease. Stem Cell Reports. 2020;14(6):1060-1075. doi:10.1016/j.stemcr.2020.04.011) in view of Youle (US20120277286A1).
Yamaguchi teaches all required limitations of claim 1 and 2 as mapped in the 35 U.S.C. 102(a)(1) rejection above.
However, if applicant chooses one option from claim 2, Yamaguchi fails to explicitly teach the non-limiting elements of claim 2 (i.e., wherein the mitochondria comprise mitochondria with a DNA mutation or mitochondria without a DNA mutation).
Youle discloses compositions and methods for the treatment or prevention of diseases associated with a mitochondrial defect [¶abstract].
Regarding Claim 2: Youle teaches that cells affected by mitochondrial disease can contain both mutant and wild-type mitochondrial DNA (i.e., mitochondria with and without DNA mutations), because mutated mtDNA typically coexists with wild-type mtDNA in a hetero-plasmic state [¶4]. Youle teaches selectively eliminating mitochondria having a mutation in mitochondria DNA by increasing mitophagy [¶7]. Youle expressly teaches screening agents for enhancing selective elimination of defective mitochondria, including adding a candidate compound to the culture medium of cells and determining whether the compound reduces defective mitochondria [¶154]. Youle further expressly teaches that these screens may be carried out in cybrid cells comprising mixed populations of wild-type and defective mitochondria, or in cells comprising mtDNA defects [¶159]. Youle also teaches that the test agents can include organic molecules and small chemical compounds [¶157].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to apply Yamaguchi’s flunarizine treatment to the cybrid cells taught by Youle, which comprise mixed populations of wild-type and mutant mtDNA. This is because Youle expressly teaches using such cells to screen candidate compounds for their ability to promote mitophagy and reduce defective mitochondria. Meanwhile, Yamaguchi provides a specific compound (i.e., flunarizine), that was already shown to accelerate mitochondrial elimination and promote lysosomal degradation of mitochondria, while Youle provides a well-known cellular model containing both mutant and wild-type mitochondrial populations for evaluating mitochondrial clearance. A person of ordinary skill in the art would have been motivated to apply the screening method of Youle to the therapy method of Yamaguchi to further test the efficacy of flunarizine via an additional evaluation. Thus, the combination would have amounted to applying a known mitochondrial clearance agent to a known screening system for the same recognized purpose. One of ordinary skill in the art would have had a reasonable expectation of success because both references concern promoting removal of the intracellular mitochondria through induced mechanisms, and Yamaguchi had already demonstrated that flunarizine produces the desired mitochondrial-elimination effect.
Conclusions
No claim is found allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARYA AHMADI BAZARGANI whose telephone number is (571)272-0211. The examiner can normally be reached Monday - Friday 11:00 AM - 5:00 PM.
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Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/ Primary Examiner, Art Unit 1613
Prosecution Insights