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 the Claims
Applicant’s submission filed 09 July 2026 has been entered. Claims 101-106, 109-112, and 114-116 are pending. Claims 101-102, 104-106, 109, and 111-112 have been amended, while claim 113 has been cancelled without prejudice or disclaimer. Therefore, prosecution on the merits continues for claims 101-102, 104-106, 109-112, 114, and 116 as being drawn to the elected invention and species, with claims 103 and 115 withdrawn for reading on the non-elected species. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to the Drawings
Applicant’s petition to accept colored photographs and/or drawings filed 15 December 2025 has been granted on 18 February 2026, thereby obviating the objection of record.
Therefore, the objection is withdrawn.
RE: Objection to claims 101, 104, and 113
Applicant’s amendments to instant claims 101 and 104 obviate the objections of record. With that, instant claim 113 has been cancelled, thereby rendering the objection moot.
Therefore, the objections are withdrawn.
RE: Rejection of claims 104, 114, and 116 under 35 USC 112(b)
Applicant’s amendment to independent claim 104 adding a preamble obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 104, 114, and 116 under 35 USC 101
Applicant’s amendment to independent claim 104 adding a preamble obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 101-102, 104-106, 111-113, and 116 under 35 USC 102(a)(2) over Yivgi-Ohana et al
The cancellation of claim 113 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendments to independent claims 101 and 104 requiring the pharmaceutical composition and method of making thereof to not comprise a CD4 T cell or an NK cell – which is a newly presently limitation – obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 101-102, 104-106, 109-114, and 116 under 35 USC 103 over Yivgi-Ohana et al in view of Han et al
The cancellation of claim 113 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendments to independent claims 101 and 104 requiring the pharmaceutical composition and method of making thereof to not comprise a CD4 T cell or an NK cell – which is a newly presently limitation – obviates the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s amendments are addressed in so far as they are applicable to the claims as amended:
Applicant has traversed the rejection, asserting on Pages 13-14 of the Remarks filed 09 July 2026 that the mitochondrial enrichment of CD8+ T cells unexpectedly reduces T cell exhaustion markers LAG-3 and TIM-3 and increases the percentage of non-exhausted T cells. Applicant cites Figure 6 to support these assertions. In response, the Examiner respectfully reminds Applicant that, in submitting evidence asserted to establish unobvious results, there is a burden on Applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter relative to the prior art subject matter. See MPEP § 2145. It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. See MPEP § 716.02(b). In the instant case, the referenced figure is not commensurate in scope with the instant claims. More specifically, at least independent claims 101 and 104 only broadly require the exogenous mitochondria to be present in an amount effective to increase survival and/or activity of the human CD8+ T cell, whereas the supporting data for the purported unexpected results administers 10 μg, 30 μg, and 100 μg of exogenous mitochondria to CD8+ T cells. As the instant claims are broader than the supporting data, the unexpected results are not commensurate in scope with the instant claims.
In addition, the Examiner notes that the ordinary artisan would have expected the percentage of exhausted T cells and associated markers to decrease with the administration of exogenous mitochondria, as Gojo et al (US 2020/0054682 A1) teach the rejuvenation of exhausted T cells via the administration of exogenous mitochondria. See, for example, Paragraphs [0282]-[0285], [0338], and [0433] of Gojo et al.
New Grounds of Rejection
Specification
The substitute Specification filed 15 December 2025 is acknowledged. Accordingly, because the petition under 37 CFR 1.84(a)(2) for colored drawings is has been granted as of 18 February 2026, the amendments to the Specification regarding the section heading “BRIEF DESCRIPTION OF THE DRAWINGS” have been entered.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all optional limitations are not required.
It is of note that Applicant has defined the term “increase” to refer to an increase of 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 87%, 90%, 95%, 98%, 99%, 100%, 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5-fold, 4-fold, 4.5-fold, 5-fold, 5.5.-fold, 6-fold, 6.5- fold, 7-fold, 7.5-fold, 8-fold, 8.5-fold, 9-fold, 9.5-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-5 fold, 35-fold, 40-old, 45-fold, 50-fold, 55-fold, 60-fold, 65-fold, 70-fold, 75-fold, 80-fold, 85-fold, 90-fold, 95-fold, 100-fold, or greater in a recited variable. See Page 29, Lines 1-6 of the instant Specification filed 03 November 2023.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 101-102, 105-106, and 109-112 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Gojo et al (US 2020/0054682 A1). Gojo et al has a publication date of 20 February 2020.
Gojo et al disclose methods and compositions for the generation of mitochondria replaced cells (MirC), and therapeutic methods for using such compositions for treating a subject having an age-related disease or syndrome, mitochondrial disease or disorder, or otherwise in need of mitochondrial replacement (Abstract).
As such, Gojo et al disclose a pharmaceutical composition comprising human CD8+ T cells that are co-incubated with exogenous mitochondria within a pharmaceutically acceptable carrier (Paragraphs [0013], [0032], [0036]-[0038], [0047]-[0048], [0051]-[0052], [0054]-[0059], [0196], [0220], [0230], [0265], [0332]-[0333], [0338], [0342]; Figure 16E).
Gojo et al further disclose an embodiment wherein the T cells are exhaustive T cells (Paragraphs [0269], [0338]). Gojo et al further disclose an embodiment wherein the T cells further comprise a chimeric antigen receptor (Paragraphs [0032], [0048], [0269], [0284]-[0285]).
Gojo et al further disclose that the contacting of the CD8+ T cells with exogenous mitochondria results in a prolonged lifespan – or survival – of the CD8+ T cells that is increased about 1.5 fold (Paragraphs [0051]-[0052], [0182], [0285], [0339]).
Gojo et al further disclose that the mitochondria-contacted cells have an increased basal and maximal rate of oxygen consumption relative to the corresponding level in the cells prior to mitochondrial contact (Paragraphs [0205], [0238]-[0239], [0376]). It is of note that Gojo et al define “increase” as a value which is at least 5%, for example an increase by at least about 10%, or at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90%, or more than 90% higher than the corresponding reference value (Paragraph [0189]).
Accordingly, Gojo et al anticipate the claims as follows:
Regarding claims 101-102: Gojo et al disclose a pharmaceutical composition comprising human CD8+ T cells that are co-incubated with exogenous mitochondria within a pharmaceutically acceptable carrier, such that the amount of exogenous mitochondria is sufficient to increase the survival of the CD8+ T cells by about 1.5 fold (claim 102) when compared to CD8+ T cells that have not been contacted with exogenous mitochondria. As the embodiment of the pharmaceutical composition does not comprise CD4+ T cell or NK cells, this therefore reads on the pharmaceutical composition of instant claim 101.
Regarding claims 105-106: Following the discussion of claim 101, Gojo et al further disclose that the basal and maximal rate of oxygen consumption relative to the corresponding level in the human CD8 T cells prior to mitochondrial contact is increased by at least 10% (claims 105-106). This therefore reads on the pharmaceutical composition of the instant claims.
Regarding claims 109-110: Following the discussion of claim 101, Gojo et al further disclose that the human CD8+ T cells are in an exhaustive state. As Gojo et al disclose that the exhausted CD8+ T cells are rejuvenated via the administration of exogenous mitochondria such that the population doubling level – which is an indicator of T cell exhaustion – is reduced by about 1.5 fold (claim 109), the rejuvenated human CD8+ T cells will necessarily have an associated decrease in T cell exhaustion marker expression (Paragraphs [0189], [0282]-[0285], [0433]-[0436]). See MPEP § 2112.01(II). This therefore reads on the pharmaceutical composition of instant claim 110.
Regarding claims 111-112: Following the discussion of claim 101, Gojo et al further disclose that the human CD8+ T cells are CAR-T cells (claim 111). As the human CD8+ CAR-T cells that have been contacted with exogenous mitochondria have the same structure as the instantly claimed human CD8+ CAR-T cells and interact with target cells, they will inherently have an increased expression of IL-2 mRNA, IFN-γ mRNA, TNF-α mRNA, Granzyme B mRNA, or a combination thereof when compared to a human CD8+ CAR-T cell that has not been treated with exogenous mitochondria. See Paragraph [0338] of Gojo et al, Example 14 on Pages 93-94 of the instant Specification filed 03 November 2025, and MPEP § 2112.01(II). This therefore reads on the pharmaceutical composition of instant claim 112.
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.
Claims 104 and 116 are rejected under 35 U.S.C. 103 as being unpatentable over Gojo et al (US 2020/0054682 A1).
Han et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 20 February 2020.
Regarding claim 104: Gojo et al disclose methods and compositions for the generation of
mitochondria replaced cells (MirC), and therapeutic methods for using such compositions for treating a subject having an age-related disease or syndrome, mitochondrial disease or disorder, or otherwise in need of mitochondrial replacement (Abstract).
As such, Gojo et al disclose a method of making a pharmaceutical composition comprising recipient cells, exogenous mitochondria, and a pharmaceutically acceptable carrier, wherein the method comprises: (a) contacting a recipient cell with an agent that reduces endogenous mtDNA copy number; (b) incubating the recipient cell for a sufficient period of time for the agent to partially reduce the endogenous mtDNA copy number in the recipient cell; and (c) co-incubating (1) the recipient cell from step (b) in which the endogenous mtDNA has been partially reduced, and (2) exogenous mitochondria from a healthy donor, for a sufficient period of time to non-invasively transfer exogenous mitochondria into the recipient cell, thereby generating a mitochondria replaced cell, wherein said mitochondria replaced cell comprises greater than 5% of exogenous mtDNA (Paragraphs [0013], [0032], [0036]-[0048], [0051]-[0052], [0054]-[0059], [0196], [0220], [0230], [0265], [0332]-[0333], [0338], [0342]; Figure 16E).
Gojo et al further disclose that the recipient cells are human CD8+ T cells (Paragraphs [0032], [0048], [0220], [0269], [0282], [0338]). Gojo et al further disclose that the T cells can be autologous (Paragraphs [0213], [0263], [0284]).
However, Gojo et al do not exemplify or reduce to practice the making of a pharmaceutical composition comprising isolated human CD8+ T cells that does not comprise a CD4+ T cell or an NK cell, as required by instant claim 104.
Therefore, it would have been prima facie obvious to have modified the method of Gojo et al such that the human CD8+ T cells are isolated out from an autologous sample of cells. One of ordinary skill in the art before the effective filing date of the invention would have recognized that the CD8+ T cells can be separated from a larger autologous sample of cells, and would have had a reasonable expectation of success given that Gojo et al teach separation techniques and the isolation of primary T cells within embodiments of their invention (Paragraphs [0032], [0165], [0246], [0416]-[0422]). See MPEP § 2143(I)(G).
Consequently, Gojo et al render obvious a method of making a pharmaceutical composition, the method comprising: isolating the human CD8+ T cell cells from an autologous sample of primary cells, co-incubating the human CD8+ T cell cells and exogenous mitochondria for a sufficient period of time to non-invasively transfer exogenous mitochondria into the human CD8+ T cell cells, and formulating the human CD8+ T cell cells comprising the transferred exogeneous mitochondria with a pharmaceutically acceptable carrier. As the resulting pharmaceutical composition does not comprise a CD4+ T cell or an NK cell, this therefore renders obvious the method of the instant claim.
Regarding claim 116: Following the discussion of claim 104, Gojo et al further disclose that the exogenous mitochondria is isolated, intact mitochondria (Paragraphs [0017], [0047], [0212], [0239], [0259], [0272]-[0273]). This therefore reads on the method of the instant claim.
Claims 104, 114, and 116 are rejected under 35 U.S.C. 103 as being unpatentable over Gojo et al (US 2020/0054682 A1) in view of Liao et al (Methods Cell Biol, 2019).
The discussion of Gojo et al regarding claim 104 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Gojo et al render obvious claims 104 and 116. Liao et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 114: As aforementioned in the discussion of claim 104 above, Gojo et al disclose that the mitochondria replaced cell comprises greater than 5% of exogenous mtDNA.
Gojo et al further disclose that the exogenous mitochondria is isolated from donor cells (Paragraphs [0054]-[0055], [0185]-[0186], [0240]-[0241], [0255]-[0259], [0322]).
Gojo et al do not disclose that the amount of exogenous mitochondria in culture with the recipient human CD8+ T cells is about 30 micrograms, as required by instant claim 114.
Liao et al, however, disclose that the crude amount of mitochondria isolated from cultured cells can be from 7 to 50 micrograms of mitochondrial protein per 106 cells (Page 14).
Therefore, it would have been prima facie obvious to have modified the method of Gojo et al such that the amount of exogenous mitochondria cultured with the recipient human CD8+ T cells is about 30 micrograms, as suggested in Liao et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to administer the amount of exogenous mitochondria isolated from the donor cells to effect an appropriate mitochondrial replacement within the recipient cells, and would have had a reasonable expectation of success given that the disclosures of Gojo et al and Liao et al are concerned with the isolation of mitochondria from donor cells. See MPEP § 2143(I)(G).
Consequently, Gojo et al as modified by Liao et al render obvious a method of making a pharmaceutical composition, wherein about 30 micrograms of exogenous mitochondria is cultured with the recipient human CD8+ T cells. This therefore renders obvious the method of the instant claim. See MPEP § 2144.05.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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