DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed 04/07/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Ofir et al (US 2023/0190822A1), in view of Von Maltzahn et al (US 2021/0187018 A1), further in view of Ikeda et al (J Am Coll Cardiol, 77(8), 2021, 1073-88), further in view of Pinilla et al (Biology, 2021, 10, 723, 1-28) and further in view of Moon et al (Exp Neurobiol, 2015, 24(2), 103-116).
Ofir taught a method of enhancing a cellular or physiological function in a subject in need thereof, comprising contacting said subject with a pharmaceutical composition comprising a subcellular fraction of a cell, thereby enhancing a cellular or physiological function in a subject, where said pharmaceutical composition was administered [claims 1-2], and wherein said subcellular fraction was a vesicular fraction, selected from an exosome [claims 8-9]. The described subcellular fractions were mitochondria-enriched cellular fractions, administered as a part of the pharmaceutical composition, further comprising one or more pharmaceutically acceptable carriers and/or in combination with an excipient, e.g., a pharmacologically acceptable excipient [074-0175, 0190-0191], and encapsulated within the subcellular fraction [claim 5; ¶ 0043, 0050, 0056].
In an embodiment, Ofir taught incubation of placental adherent stromal cells (ACS) with resveratrol (0066]. Subjects treated by the described methods and compositions included Parkinson’s Disease [0076, 0111]. Typical human dosages were disclosed [0183, 0185-0187], as were dose aliquots [0170] (e.g., reads on unit dose form).
Although Ofir taught incubation of ACS with resveratrol, Ofir was not specific resveratrol in the presence of mitochondria contained in extracellular vesicles, as recited in claim 1. Although Ofir generally taught enhancing a cellular or physiological function, Ofir was not specific treating tissues under hypoxic-induced stress, as recited in claim 1.
Nevertheless, Von Maltzahn taught extracellular vesicles, e.g., exosomes [0311-0312; claim 28i] comprising mitochondria [0614, 0724] and resveratrol, wherein resveratrol was sufficient to increase mitochondrial biogenesis [0386], and wherein comprising included encapsulating [0610, 1136].
Since Ofir taught mitochondria-enriched extracellular vesicles, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Ofir, resveratrol in the presence of mitochondria, as taught by Von Maltzahn. The ordinarily skilled artisan would have been motivated to include an agent sufficient to increase mitochondrial biogenesis, as taught by Von Maltzahn [0386].
The combined teachings of Ofir and Von Maltzahn did not teach treating tissues under hypoxic or agent-induced stress.
Nonetheless, Ikeda taught that extracellular vesicles, rich in mitochondria, facilitate the transfer of mitochondria and their related energy sources, into ischemic cells, in order to enhance cellular function, through the restoration of cellular bioenergetics. This contributes to improved intracellular energetics for mitochondria-related diseases.
Ikeda was drawn to an in vivo model of ischemia, where the cells were hypoxia-injured [abstract].
Pinella taught that hypoxia is pathogenic in the development of Parkinson’s Disease [abstract].
And, Moon taught that Parkinson’s Disease is a mitochondria-related disease [abstract and title].
Since Ofir generally taught enhancing a cellular or physiological function, in the treatment of Parkinson’s Disease, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of Ofir and Von Maltzahn, treating hypoxia-injured cells, as taught by Ikeda [abstract]. Since Pinella taught that hypoxia is pathogenic in the development of Parkinson’s Disease, and Moon taught that Parkinson’s Disease is a mitochondria-related disease, the ordinarily skilled artisan would have been motivated to improve intracellular energetics for mitochondria-related diseases [Pinella at the abstract; and, Moon at the title and abstract].
Ofir, in view of Von Maltzahn, Ikeda, Pinella and Moon, reads on claims 1-4, 6, 8-9.
Claim 5 is rendered prima facie obvious because Von Maltzahn taught that the modulator of mitochondrial biogenesis was included in an amount, and for a time sufficient to increase mitochondrial biogenesis by at least 10-90 % or more [0385]. The motivation to combine Von Maltzahn with Ofir was previously discussed.
The instant claim 5 recites about 10-20 % more mitochondria in the presence of the promoting agent, than without the agent. Von Maltzahn taught that the modulator of mitochondrial biogenesis was included in an amount, and for a time, sufficient to increase mitochondrial biogenesis by at least 10-90 % or more. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claim 7 is rendered prima facie obvious because Ofir taught exosomes sized 100 nm [0031], or 100-400 nm [¶ 0209 at Table 2].
The instant claim 7 recites medium-to-large extracellular vesicles. The instant Specification disclosed [0040] medium-to-large extracellular vesicles as having particle diameters ranging from 100 to 1000 nm [0040], or >200 nm [0045]. The Examiner notes that it appears that the prior art exosomes meets the claimed limitation of medium-to-large extracellular vesicles, based upon the instant Specification definition of medium-to-large extracellular vesicles.
Response to Arguments
Applicant's arguments, filed 04/07/2026, have been fully considered, but they are not persuasive. Declaration under Rule 1.32 (Dr. Devika Manickam), filed 04/07/2026, has been fully considered.
Applicant and Declarant argued that when a promoter is used, together with a human brain endothelial cell line, the endothelial cells manufacture and excrete EVs having 10-20 percent more mitochondrial content than EVs excreted without the presence of the promoting agent [see the Declaration at sections 6-10]. The Applicant and Declarant argues that this evidence is unexpected.
The Examiner acknowledges the evidence relating to this unexpected result. The data show that for human brain endothelial cells, that there is a difference, by 10-20 %, in the mitochondrial content, when the promoter is resveratrol. This effect by the promoter, on human brain endothelial cells, is not recognized by the prior art, and thus, the effect is unexpected.
However, once unexpectedness has been established, the probative value of the evidence as compared to the invention as claimed must be determined, i.e., claims must be “commensurate in scope” with the showing. See MPEP 716.02(d). In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. And this is not considered to be the case with the instant claims. The instant claim 1 does not limit the promoting agent, and only requires a “promoting agent”. And for this limitation, the data is not considered to be commensurate in scope.
The only promoting agent tested was resveratrol. However, other promoting agents that are not able to make the interaction with human brain endothelial cells that resveratrol makes, would be expected to interact differently, and it is unclear whether the effect would be present with promoting agents that act differently than resveratrol. Thus, the data shows that a particular promoting agent influences the mitochondrial content, but the instant claim 1 does not state any additional limitation beyond “promoting agent”. It is noted that claim 3 limits the promoting agent, and is considered commensurate in scope, in this respect.
The Applicant is encouraged to cancel claim 2, amend claim 1 with claim 3, and amend claim 9 to a straight composition claim.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612
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