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 .
DETAILED ACTION
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 03 Mar 2026 has been entered.
Claims 1, 3-11 and 20 remain pending in the application.
Claims 1 and 8 are amended.
Claims 2 and 12-19 are cancelled.
Claims 3, 4, 11 and 20 are withdrawn from further consideration by the examiner, pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention / species.
Claims 1 and 5-10 are under consideration to the extent of the elected species, i.e., that the disorder is heart failure.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03 Mar 2026 is in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Rejections Maintained
Claim Rejections - 35 USC § 103
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 1 and 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over von Maltzahn et al. (US 2017/0151287, published 01 June 2017, listed on IDS filed 15 Nov 2021) as evidenced by Britannica (mitochondrion, definition, function, structure and facts) and evidenced by the instant specification and in view of Kim et al. (Stem Cells Int.;2016:1329459, published 2016 Aug 4).
Von Maltzahn teaches chondrisomes derived from mitochondria and methods of the chondrisome preparations that have beneficial bioenergetic or biological function for use in therapeutic applications ([0003]). As evidenced by Britannica, a chondrisome is another term for mitochondria (page 1). Von Maltzahn teaches that the chondrisome composition is administered to the subject in an amount and for a time sufficient to improve function in the subject of a cell or tissue that is in an injured state ([0830]). Von Maltzahn teaches treatments for a cardiovascular disorder such as heart failure ([0342]), rendering obvious the disorder characterized by intracellular bioenergetics imbalance in a cardiomyocyte of claims 1 and 5 and the injured cell of claim 10. Von Maltzahn teaches that the parent cell source for the chondrisomes may be prepared from muscle cells such as cardiomyocytes ([0499], [0570]) or are derived cardiomyocytes ([0568]) and that they may target cardiomyocytes ([0632]). Von Maltzahn teaches that the mitochondria may be encapsulated in naturally occurring vesicles such as exosomes ([0613]-[0617]). As evidenced by the instant specification, an exosome is an extracellular vesicle ([0037] of the instant specification). Von Maltzahn teaches that the mitochondrial preparations of the invention are isolated from blood or blood fractions such as peripheral blood mononuclear cells (PBMCs) ([0554], [0559]). Von Maltzahn teaches that cells may be cultured induced pluripotent stem cells (iPS cells) [0567]) and specifically teaches iPS derived cardiomyocytes ([0568]). Von Maltzahn teaches mitochondria may be encapsulated in naturally occurring vesicles such as exosomes ([0613]-[0617) and teaches isolating chondrisomes from the parent cell or tissue source ([0391]). Von Maltzahn teaches that chondrisomes are isolated from cells in culture ([0561]) and Von Maltzahn teaches that the tissue or cellular source may be manipulated or activated to release chondrisomes or mitochondria-containing vesicles ([0607]) rendering obvious culturing the cardiomyocytes in a culture medium and isolating from the culture medium mitochondria-containing vesicles released from the cardiomyocytes into culture medium as in claim 1.
Regarding claims 6 and 9, von Maltzahn teaches that the chondrisomes have a mean average size between 150-1500 nm ([0005]), rendering obvious that the extracellular vesicles are greater than 150 nm in order to contain the mitochondria, and thus rendering obvious the 200-600 nm size. Regarding claim 7, von Maltzahn teaches that the source mitochondria or chondrisomes of the composition are autologous to the subject ([0377]). Regarding claim 8, von Maltzahn teaches that the method of delivering the chondrisome preparations includes contacting the cell or tissue for a time and in an amount sufficient to enhance a function and viability of the cell or tissue ([0238]-[0239]) and teaches targeting cardiomyocytes ([0632]).
Von Maltzahn does not teach that the iPS cells are produced by inducing pluripotency of the PBMCs. This deficiency is made up for in the teachings of Kim.
Kim teaches the generation of induced pluripotent stem cells from PBMCs (abstract). Kim teaches that healthy iPSC colonies are formed even from a small number of PBMCs and that the generated iPSCs expressed pluripotent markers and differentiated into all three germ layer lineages (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have administered cardiomyocyte chondrisome (mitochondria) encapsulated in vesicles such as exosomes for treating heart failure and to have formed the cardiomyocyte chondrisome (mitochondria) vesicles, through inducing pluripotency of PBMCs to produce induced pluripotent stem cells and differentiating the iPS cells to produce cardiomyocytes and to isolate mitochondria containing vesicles secreted from the cardiomyocytes into cell culture medium. Mitochondrial preparations from PBMCs and iPS derived cardiomyocytes are taught by von Maltzahn and it is known that PBMCs can be used to form induced pluripotent stem cells from the teachings of Kim. Induced pluripotent stem cells produced from PBMS are healthy and are able to differentiate into all three germ layers, as taught by Kim. As the elements of PBMCs and iPS cells are taught by Von Maltzahn as suitable for the invention and it is known that PBMCs can be used to produce healthy iPS cells, as taught by Kim, one of ordinary skill in the art would have a reasonable expectation of success in deriving cardiomyocytes from iPS cells produced from PBMCs as each of these components are suitable for the invention and the process of forming healthy iPS cells from PBMCs is known in the art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 03 Mar 2026 have been fully considered but they are not persuasive. Applicant states von Maltzahn’s teachings with respect to cellular sources which can be manipulated or activated to release mitochondria-containing extracellular vesicles does not render obvious the claimed invention (page 5 of remarks). Applicant argues that von Maltzahn provides a broad list of possible source cells from which to prepare chondrisomes but the teachings with respect to cells known to release mEVs is much more limited and does not include chondrisomes (page 5 of remarks). Applicant notes that von Maltzahn mentions teachings from Boudreau and Phinney as providing examples of sources known to release mitochondria in membrane bound vesicles but these sources don’t include cardiomyocytes (page 5 of remarks). Applicant argues that there is nothing in von Maltzahn pointing to the selection of iPS-derived cardiomyocytes from the list of source cells for preparing chondrisomes and that there would need to be a reasonable expectation of success is extrapolating methods for releasing vesicles to all the possible source cells of von Maltzahn (pages 6 and 7 of remarks). Applicant argues that Boudreau and Phinney indicate that the release of mEVs occurs only under defined conditions specialized for each cell type (page 6 of remarks).
The examiner does not find this persuasive as von Maltzahn teaches iPS derived caridomyocytes ([0568]) and renders it obvious to attain chondrisomes released from cells (e.g. [0607]) and based on the evidence at hand it is understood that it would be within the reach of one of ordinary skill in the art to determine the proper conditions for achieving the release. The applicant has spoken to the difficulty of achieving release but has not pointed to clear evidence that it would be outside the normal realm of experimentation for one of ordinary skill in the art. Further, the claims are broad in merely requiring “culturing iCM cells in a culture medium.” Is there a specific culture medium or culturing conditions that provide release of active mitochondria? The examiner notes that the breadth of the claims do not reflect the unexpected nature of achieving release of suitable mitochondria as asserted by the applicant. The applicant points to the limited cell types and phrases in Boudreau and Phinney as suggesting a lack of expectation in achieving suitable release from cardiomyocytes (page 6 of remarks), but the examiner does not agree with conclusions drawn by the applicant. The lack of teaching regarding cardiomyocytes by Boudreau and Phinney does not lead one of ordinary skill in the art away from pursuing release from cardiomyocytes. Instead, Boudreau and Phinney are presented by von Maltzahn as indications that release is known and possible and in the context of the teachings, one would have a reasonable expectation of success in pursuing release from cardiomyocytes. Applicant argues that to arrive at the claimed cmEVs one must select both iPS cell and cardiomyocytes from two different lists of von Maltzahn (page 7 of remarks). The examiner notes however that von Maltzahn explicitly teaches from one list “iPS derived caridomyocytes” ([0568]), providing a reasonable expectation of success in using iPS derived cardiomyocytes as a source cell for chondrisomes (mitochondria). As von Maltzahn additionally teaches procuring the chondrisomes through cell release, as noted above, the examiner maintains that there is a prima facie case of obviousness over the method as claimed.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
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/E.C.M./Examiner, Art Unit 1619 /ANNA R FALKOWITZ/Primary Examiner Art Unit 1600
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