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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments, see Pg 5, filed 4/13/2026, with respect to the claim rejections under 35 U.S.C. 102 have been fully considered and are persuasive. The rejections have been withdrawn in view of amendment.
Applicant’s arguments with respect to the claim rejections under 35 U.S.C. 103 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Further, the double patenting rejections have been maintained/modified herein.
Claim Status
Claims 21-33 are pending. Claims 26-33 are new. Claims 23-25 are withdrawn; further, claims 29 and 33 are hereby withdrawn as non-elected species. Claims 1-20 are cancelled.
Priority
The instant application is the 371 national stage entry of PCT/US21/72377, filed 11/12/2021, which claims priority to the provisional application 63115826, filed 11/19/2020. The priority date of 11/19/2020 is acknowledged.
It is noted that the instant specification filed on 11/6/2023 refers to the instant application as a continuation-in-part ([0001]), but this does not appear to be the case per the filing receipt from 5/30/2025.
Drawings
The drawings are objected to because the table depicted in Fig. 17 and the graphs in Fig. 22 use a font size/color that makes them difficult to read; and the legend of Fig. 19 refers to panels A, B, and C but the panels displayed are not annotated as such. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
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(s) 21 and 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Berry et al. (Berry, Brandon et al., “Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance,” bioRxiv, August 2019, 1-34) in view of Chistiakov et al. (Mitochondrial aging and age-related dysfunction of mitochondria. Biomed Res Int. 2014;2014:238463.).
Berry teaches using an engineered mitochondria-targeted light-activated proton pumping protein (mitochondria-ON or “mtON”) to selectively increase the protonmotive force (PMF) in mitochondria to prevent hypoxic precondition (mitochondrial dysfunction; Abstract). mtON comprises a light-activated proton pump from Leptosphaeria maculans (Mac) and the terminal 187 amino acids of the Immt1 gene from mouse cDNA (Pg 4, “Light-activated proton pump mitochondria-ON (mtON) is expressed in mitochondria,” first paragraph, and Pg 15-16, “Molecular biology”); the light-activated proton pump from Mac is equivalent to the instant SEQ ID NO: 10 and the terminal 187 amino acids from Immt1 is equivalent to the instant SEQ ID NO: 6. The instant specification indicates that SEQ ID NO: 6 corresponds to a first moiety that targets the fusion protein to the mitochondrial inner membrane (see instant [0007, 0092, 0203]) and SEQ ID NO: 10 corresponds to a second moiety that comprises a light-activated proton pump (see instant [0008, 0097-0098, 0203]).
Berry further teaches mtON localizes to the mitochondrial inner membrane and orients such that the proton pump pumps from the mitochondrial matrix towards the intermembrane space to increase the PMF in response to light (Pg 5, “mtON activation increases the PMF,” second and third paragraphs; Figure 2).
Berry further teaches that mtON ameliorate mitochondrial dysfunction by promoting organismal survival in response to electron transport chain inhibitors (Pg 9, “mtON increases survival during acute ETC dysfunction”; Figure 3).
Berry does not expressly teach a method of ameliorating age-related mitochondrial dysfunction.
Chistiakov teaches age-related changes in mitochondria are associated with decline in mitochondria function (Abstract). Mitochondrial dysfunction, including decreased oxidative capacity and increased oxidative damage, is thought to substantially contribute to biological aging. A fundamental impact of mitochondria on aging has been suggested several decades ago. One concept considers aging as the result of an accumulation of damage to biomolecules due to the excessive production of highly toxic reactive oxygen species (ROS). This concept was developed as the mitochondrial theory of aging since mitochondria are the major producers of ROS in the cell. According to this theory, with age, mitochondria accumulate ROS-induced damage and become dysfunctional. With time, the function of cells declines causing aging and subsequent death (Pg 1, left column, first paragraph).
In summary, Berry teaches a method of ameliorating mitochondrial dysfunction in a subject comprising expressing a fusion protein comprising a first moiety that targets the fusion protein to the mitochondrial inner membrane and a second moiety that comprises a light-activated proton pump, wherein the fusion protein orients into the mitochondrial inner membrane to pump protons into the intermembrane space and increase the protonmotive force upon activation with light. Chistiakov teaches age-related mitochondrial dysfunction is a type of mitochondrial dysfunction associated with aging.
Therefore, regarding claim 21, it would be prima facie obvious to use the method of treating mitochondrial dysfunction taught by Berry to also treat age-related mitochondrial dysfunction. One skilled in the art would be motivated to do so in order to treat additional types of mitochondrial dysfunction. One would have a reasonable expectation of success given that age-related mitochondrial dysfunction is a species of mitochondrial dysfunction.
Regarding claim 26, as stated above, Berry teaches a fusion protein comprising a first moiety comprising the instant SEQ ID NO: 6.
Regarding claim 27, as stated above, Berry teaches a fusion protein comprising a first second comprising the instant SEQ ID NO: 10.
Regarding claim 28, as stated above, Berry teaches a fusion protein wherein the first moiety is 100% identical to the instant SEQ ID NO: 6 and the second moiety is 100% identical to the instant SEQ ID NO: 10.
Claim(s) 22 and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Berry et al. (Berry, Brandon et al., “Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance,” bioRxiv, August 2019, 1-34) in view of Singh et al. (Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function. Cell Death Dis 9, 735 (2018).).
The teachings of Berry have been set forth above. Berry does not expressly teach a method of ameliorating mitochondrial dysfunction wherein the target cells are hair follicles or keratinocytes.
Singh teaches mitochondrial DNA (mtDNA) depletion is involved in mtDNA depletion syndromes, mitochondrial diseases, aging, aging-associated chronic diseases, and other human pathologies. Singh further teaches that depleting mtDNA in mice leads to a reduction in mitochondrial activity and causes them to develop skin wrinkles and visual hair loss (Abstract; Pg 2, left column, “Development of mtDNA-depleter mouse,” first paragraph).
Singh further teaches that the skin from wild-type animals showed typical morphology of telogen skin in which the epidermis was thin and composed of 1-2 layers of keratinocytes whereas the mice with mtDNA depletion had hyperplastic and hyperkeratotic epidermis, with 4-6 layers of keratinocytes (Pg 4, left column, second paragraph; Figures 3a, 4a, 5, and 6). Additionally, mtDNA depletion led to gray hair, reduced hair density, hair loss, kyphosis, progeroid head (Pg 2, right column, “mtDNA-depleter mice show inflamed wrinkled skin with the hyperplastic and hyperkeratotic epidermis and alopecia secondary to defective hair loss,” first paragraph; Figures 3a, 4a, and 6).
In summary, Berry teaches a method of ameliorating mitochondrial dysfunction in a subject comprising expressing a fusion protein comprising a first moiety that targets the fusion protein to the mitochondrial inner membrane and a second moiety that comprises a light-activated proton pump, such that the fusion protein orients into the mitochondrial inner membrane to pump protons into the intermembrane space and increase the protonmotive force upon activation with light. Singh teaches that mitochondrial dysfunction is associated with skin wrinkles and hair loss.
Therefore, regarding claim 22, it would be prima facie obvious to use the method of treating mitochondrial dysfunction taught by Berry to treat symptoms associated with mitochondrial dysfunction, including keratinocytes and hair follicles. One skilled in the art would be motivated to do so in order to treat any and all symptoms of mitochondrial dysfunction. One would have a reasonable expectation of success given Berry had established a method of treating mitochondrial dysfunction, which would necessarily treat additional symptoms that arise as a result of mitochondrial dysfunction.
Regarding claim 30, as stated above, Berry teaches a fusion protein comprising a first moiety comprising the instant SEQ ID NO: 6.
Regarding claim 31, as stated above, Berry teaches a fusion protein comprising a first second comprising the instant SEQ ID NO: 10.
Regarding claim 32, as stated above, Berry teaches a fusion protein wherein the first moiety is 100% identical to the instant SEQ ID NO: 6 and the second moiety is 100% identical to the instant SEQ ID NO: 10.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21, 22, 27, and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 17-32 of copending Application No. 18/249,497 (reference application, claim set filed 4/8/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application recites the same active steps as the instant application; additionally, the peptide species recited in the reference application read on the genera of peptides recited in the instant application and vice versa.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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