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 .
Election/Restrictions
Applicant's election with traverse of Group III, claims 20-22, in the reply filed on 01/16/2026 is acknowledged. The traversal is on the ground(s) that there is no undue burden on the examiner. This is not found persuasive because the fusion protein products and the methods of treating would be classified separately in the art. Moreover, the different methods are directed at treating different conditions that would not have the same classifications in the art. Given these separate classifications, there exists undue burden in searching the inventions as originally claimed.
Claims 1-19 and 23-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group of inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/16/2026.
Applicant's election with traverse of SED NO: 6 and SEQ ID NO: 11 for the first and second moieties in the reply filed on 01/16/2026 is acknowledged. The traversal is on the grounds that there is no undue burden on the examiner. This is not found persuasive because, as claimed, the species of fusion protein can comprise a first moiety having any sequence, structure, or composition capable of targeting the fusion protein to the mitochondrial inner membrane in the desired orientation, and the second moiety can have any light-activated proton pump from any species synthetic or natural. As such, the species of targeting sequences and proton pumps are very broad and would be classified differently in the art. Given that widely different sequences or structures (small molecules, amino acid sequences, nucleic acids) used for targeting would be classified differently, there would be a search burden on account of the classifications.
The requirement is still deemed proper and is therefore made FINAL.
Although SEQ ID NO: 11 was elected to represent the second moiety in Applicant’s response to the requirement for restriction and election of species filed on 01/16/0226, the examiner called and confirmed that a typographical error was made and Applicant intended to elect SEQ ID NO: 10 to represent the second moiety. The examiner attempted to contact the Attorneys/Agents at the following provided phone numbers: (202) 741-5635, (202) 662-3008, (202) 662-3042, (703) 770-7571, (202) 662-3075. Voicemail messages were left at the first number on 02/03/2026, 02/04/2026, and 02/05/2026 during standard business hours. In these voicemail messages, the examiner addressed his concern over a potential typographical error. After receiving a call in response and confirming that Applicant intended to elect SEQ ID NO: 10, examination proceeded with examination of SEQ ID NO: 10 in place of SEQ ID NO:11 as the elected species of the second moiety.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/02/2023 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: Paragraph 092 reads “In some embodiments, the first moiety comprises the first 65 amino acids of mouse IMMT (SEQ ID NO:5) or variants thereof. the first moiety comprises the first 187 amino acids of human IMMT (SEQ ID NO:6) or variants thereof.” It is advised that Applicant revise this paragraph to include the phrase “In some embodiments, ” at the beginning of the second sentence.
Appropriate correction is required.
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.
Claim 20 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Berry et al. (Berry, Brandon et al., “Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance,” bioRxiv, August 2019, 1-34).
With regard to claim 20, Berry et al. teach a method comprising amplifying a sequence of a light-activated proton pump from Leptosphaeria maculans (Mac) and the terminal 187 amino acids of the Immt1 gene from mouse cDNA and expressing these in transgenic animals (see page 15, paragraph 2 and page 16, paragraph 1). These sequences correspond to the claimed sequences 10 and 6 of the instant application, moieties 2 and 1, respectively. Berry et al. further teach these sequences/fragments were ligated together into plasmids (which read as follows: (Peft-3::IMMT1(N-terminal 187 amino acids)::Mac::GFP), pBJB16 (Pmyo-3::IMMT1(N-terminal 187 amino acids)::Mac::GFP)) that were then used in transformation of animals by plasmid DNA microinjection (see page 16, paragraph 1). By this fusion of the light-activated proton pump to the N-terminal mitochondrial targeting sequence of the IMMT1 protein, mitochondrial localization was achieved in an orientation that allowed proton pumping from the mitochondrial matrix towards the intermembrane space to increase the PMF in response to light (see page 4, paragraph 3). They further teach that the fusion protein increases survival during acute ETC dysfunction (see page 9, paragraph 2). More specifically, they teach that when the ETC was exposed to inhibitors, the fusion protein improved survival for the organism, suggesting that the fusion protein works to reverse mitochondrial dysfunction (see page 9, paragraph 1). As such, Berry et al. teach a method of ameliorating mitochondrial dysfunction in a subject, comprising the steps of expressing a fusion protein in target cells in the subject, wherein the fusion protein comprises a first moiety (SEQ ID NO: 6) that targets the fusion protein to the mitochondrial inner membrane, and a second moiety that comprises a light-activated proton pump, wherein the first moiety orients the light-activated proton pump in the direction to pump protons from the mitochondrial matrix to the inner membrane space, exposing the target cells to light to activate the proton pump to increase the protonmotive force (PMF) across the mitochondrial inner membrane, wherein increased PMF in the mitochondria of the target cells reverses mitochondrial dysfunction in the target cells.
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 21 is 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), as applied to claim 20 above, and in further view of Zhang et al. (Zhang, Huiliang et al., “Reduction of Elevated Proton Leak Rejuvenates Mitochondria in the Aged Cardiomyocyte,” bioRxiv, August 2020, 1-27).
With regard to claim 21, Berry et al. teach the method of ameliorating mitochondrial dysfunction discussed above, but they do not explicitly teach that the method is directed at treating age-related mitochondrial dysfunction. Specifically, Berry et al. teach the method comprising locating a light-activated proton pump to the mitochondrial inner membrane in order to pump protons from the matrix to the intermembrane space (see page 4, paragraph 3). This works to ameliorate the effects of proton leak by building a relatively high concentration of protons in the intermembrane space. Zhang et al. teach that age-related mitochondrial dysfunction is directly connected to proton leak, the movement of protons from the intermembrane space to the matrix without driving ATP synthesis (see Abstract). Given that age-related mitochondrial dysfunction is directly connected to proton leak, it would have been obvious before the effective filing date of the claimed invention to one having ordinary skill in the art to try to use the aforementioned method, which pumps protons back into the intermembrane space, thereby ameliorating proton leak, to treat age-related mitochondrial dysfunction. There would be a reasonable expectation of success because age-related mitochondrial dysfunction is characterized by a insufficient concentration of protons in the intermembrane space, specifically caused by proton leak, as discussed above, and Berry et al. teach a method of ameliorating proton leak, specifically by moving protons from the matrix into the intermembrane space. In short, Berry et al. teach a method of ameliorating proton leak, and age-related mitochondrial dysfunction is characterized by proton leak. As such, there would be a reasonable expectation of success in applying the method of Berry et al. to treat age-related mitochondrial dysfunction because age-related mitochondrial dysfunction is characterized by proton leak, the process that the method of Berry et al. is directed at treating. Given this, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to apply the method of Berry et al. to treat proton leak in age-related mitochondrial dysfunction.
Claim 22 is 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), as applied to claim 20 above, and in further view of Boulton et al. (Boulton, Sarah Jayne et al., “Skin manifestations of mitochondrial dysfunction: more important than previously thought,” Experimental dermatology vol. 24,1 2015).
With regard to claim 22, Berry et al. teach the method of ameliorating mitochondrial dysfunction discussed above, but they do not explicitly teach that the target cells are hair follicles or keratinocytes. Specifically, Berry et al. teach the method comprising locating a light-activated proton pump to the mitochondrial inner membrane in order to pump protons from the matrix to the intermembrane space (see page 4, paragraph 3). As discussed above, this works to reverse the effects of proton leak or uncoupling by building a relatively high concentration of protons in the intermembrane space. Boulton et al. teach that mitochondrial uncoupling induces programmed cell death or apoptosis in keratinocytes (see page 13, paragraph 2). Given that mitochondrial uncoupling is connected to apoptosis of keratinocytes, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to try to use the aforementioned method, which pumps protons back into the intermembrane space, thereby ameliorating uncoupling, to combat programmed death of keratinocytes.
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.
Claim 20 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-20 and 23 of copending Application No. 18/249,497 (using the claims as filed 04/18/2023), hereinafter Wojtovich et al., in view of Berry et al. (Berry, Brandon et al., “Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance,” bioRxiv, August 2019, 1-34).
This is a provisional nonstatutory double patenting rejection.
With regard to claim 20, Wojtovich et al. claim a method comprising the steps of expressing a fusion protein in target cells in a subject, wherein the fusion protein comprises 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 first moiety orients the light-activated proton pump in the direction to pump protons from the inner membrane space to the mitochondrial matrix, exposing the target cells to light to activate the proton pump to decrease the PMF across the mitochondrial inner membrane, wherein decreased PMF in the mitochondria of the target cells prevents or ameliorates symptoms of neurodegenerative disease (see claim 18). Wojtovich et al. do not, however, teach the method comprising pumping protons from the matrix to the inner membrane space to increase the PMF and reverse mitochondrial dysfunction in target cells. Berry et al. provide a clear motivation to use the method of Wojtovich et al. to increase, rather than decrease, the PMF, as it allows for the creation of ATP and experimentally increased mitochondrial resistance to toxins, thereby treating mitochondrial dysfunction rather than neurodegenerative diseases (see Abstract). Instead of using a targeting sequence to orient the light-activated proton pump to move protons from the inner membrane to the matrix, Berry et al. teach the use of a sequence that orients the pump to move protons from the matrix to the inner membrane, establishing a relatively high concentration of protons to drive ATP synthesis (see Abstract and page 4, paragraph 3). Berry et al. further motivate this method particularly drawn to treating mitochondrial dysfunction on account of its ability to compensate for acute electron transport chain dysfunction (see page 9, paragraph 2). As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Wojtovich et al. and Berry et al. to make and use a method comprising the steps of expressing a fusion protein in target cells in a subject, wherein the fusion protein comprises 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 first moiety orients the light-activated proton pump in the direction to pump protons from the matrix to the inner membrane, exposing the target cells to light to activate the proton pump to increase the PMF across the mitochondrial inner membrane to treat mitochondrial dysfunction. With regard to the elected species of fusion protein of the instant application, as discussed above, Berry et al. teach a method comprising amplifying a sequence of the terminal 187 amino acids of the Immt1 gene from mouse cDNA and expressing this in transgenic animals (see page 15, paragraph 2 and page 16, paragraph 1). This sequence corresponds to the claimed and elected sequence 6 of the instant application, moiety 1. Berry et al. further teach this sequences/fragment was ligated into plasmids with SEQ ID NO: 10 of the instant application (which read as follows: (Peft-3::IMMT1(N-terminal 187 amino acids)::Mac::GFP), pBJB16 (Pmyo-3::IMMT1(N-terminal 187 amino acids)::Mac::GFP)) that were then used in transformation of animals by plasmid DNA microinjection (see page 16, paragraph 1). By this fusion of the light-activated proton pump to the N-terminal mitochondrial targeting sequence of the IMMT1 protein, mitochondrial localization was achieved in an orientation that allowed proton pumping from the mitochondrial matrix towards the intermembrane space to increase the PMF in response to light (see page 4, paragraph 3). They further teach that the fusion protein increases survival during acute ETC dysfunction, providing a clear motivation for the use of the aforementioned sequences for the fusion protein (see page 9, paragraph 2). As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to use the aforementioned sequences of the instant application in the fusion protein, particularly in light of the fact that Wojtovich et al. claim SEQ ID NO: 10 of the instant application (see claims 1, 5).
Claim 21 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-20 and 23 of copending Application No. 18/249,497 (using the claims as filed 04/18/2023), hereinafter Wojtovich et al., in view of Berry et al. (Berry, Brandon et al., “Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance,” bioRxiv, August 2019, 1-34) and in further view of Zhang et al. (Zhang, Huiliang et al., “Reduction of Elevated Proton Leak Rejuvenates Mitochondria in the Aged Cardiomyocyte,” bioRxiv, August 2020, 1-27).
This is a provisional nonstatutory double patenting rejection.
With regard to claim 21, Wojtovich et al. claim the method discussed above (see claim 18), but they do not explicitly claim the use of said method directed at treating age-related mitochondrial dysfunction. As discussed above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Wojtovich et al. and Berry et al. to use a light-activated proton pump and targeting sequence to treat mitochondrial dysfunction by pumping protons from the matrix to the inner membrane of the mitochondria. Wojtovich et al. and Berry et al. do not, however, teach or claim that this mitochondrial dysfunction is age-related. As discussed above, Berry et al. teach the method comprising locating a light-activated proton pump to the mitochondrial inner membrane in order to pump protons from the matrix to the intermembrane space (see page 4, paragraph 3). This works to ameliorate the effects of proton leak by building a relatively high concentration of protons in the intermembrane space. Zhang et al. teach that age-related mitochondrial dysfunction is directly connected to proton leak (see Abstract). Given that age-related mitochondrial dysfunction is directly connected to proton leak, it would have been obvious to one having ordinary skill in the art to try to use the aforementioned method, which pumps protons back into the intermembrane space, thereby ameliorating proton leak, to treat age-related mitochondrial dysfunction.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-20 and 23 of copending Application No. 18/249,497 (using the claims as filed 04/18/2023), hereinafter Wojtovich et al., in view of Berry et al. (Berry, Brandon et al., “Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance,” bioRxiv, August 2019, 1-34) and in further view of Boulton et al. (Boulton, Sarah Jayne et al., “Skin manifestations of mitochondrial dysfunction: more important than previously thought,” Experimental dermatology vol. 24,1 2015).
This is a provisional nonstatutory double patenting rejection.
With regard to claim 22, Wojtovich et al. claim the method discussed above (see claim 18), but they do not explicitly claim the use of said method has hair follicles or keratinocytes as the target cells. As discussed above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references of Wojtovich et al. and Berry et al. to use a light-activated proton pump and targeting sequence to treat mitochondrial dysfunction by pumping protons from the matrix to the inner membrane of the mitochondria. Wojtovich et al. and Berry et al. do not, however, teach or claim that the method has hair follicles or keratinocytes as the target cells. As discussed above, Berry et al. teach the method comprising locating a light-activated proton pump to the mitochondrial inner membrane in order to pump protons from the matrix to the intermembrane space (see page 4, paragraph 3). As discussed above, this works to reverse the effects of proton leak or uncoupling by building a relatively high concentration of protons in the intermembrane space. Boulton et al. teach that mitochondrial uncoupling induces programmed cell death or apoptosis in keratinocytes (see page 13, paragraph 2). Given that mitochondrial uncoupling is connected to apoptosis of keratinocytes, it would have been obvious to one having ordinary skill in the art to try to use the aforementioned method, which pumps protons back into the intermembrane space, thereby ameliorating uncoupling, to combat programmed death of keratinocytes.
Conclusion
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654