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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/22/2026 has been entered.
Claims 5, 7-9 have been canceled, claims 1-3 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 4, 6 and 10-13 have been considered on the merits. All arguments have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 12 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 12 was newly added in the claim amendment filed on 8/14/2025. The limitation of claim 12 is directed to the PRF being greater than 5% by volume. The originally filed specification only discloses “5% by volume” or “5vol%” for PRF, and there is no disclosure supporting the limitation of “greater than 5% by volume”. Thus, the amendment filed on 8/14/2025 which is after the OA mailed on 6/25/205, and thus, the amendment introduces new matter to the instant specification.
In amended cases, subject matter not disclosed in the original application is sometimes added and a claim directed thereto. Such a claim is rejected on the ground that it recites elements without support in the original disclosure under 35 U.S.C. 112, first paragraph, Waldemar Link, GmbH & Co. v. Osteonics Corp. 32 F.3d 556, 559, 31 USPQ2d 1855, 1857 (Fed. Cir. 1994); In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981). See MPEP § 2163.06 - § 2163.07(b) for a discussion of the relationship of new matter to 35 U.S.C. 112, first paragraph. New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.
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) 4, 6 and 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over McCully et al. (US20180057610; of record) in view of Ding et al. (2017, Ann. Plast. Surg.; of record) as evidenced by Samson et al. (1960, Am. J. Physiol.; of record).
McCully et al. teach methods of treating a wound in a subject, the method comprising administering a composition comprising isolated mitochondria and/or a
combined mitochondrial agent to the wound area in an amount sufficient to treat the wound. McCully et al. teach that the wound can be any kind of wound, e.g., an open wound, or a bum wound (para. 35). McCully et al. also teach a method of treating skin wrinkles or scars on a subject, and the method includes the steps of administering a composition comprising isolated mitochondria (para. 40). McCully et al. teach that isolated mitochondria or combined mitochondrial agents can be used to improve mitochondrial function in these damaged or aged tissue, thereby removing skin wrinkles, scars, or treating loose skin, burns, wounds, lipoma, etc. (para. 212). Thus, the teachings of McCully et al. meet the limitation of claim 4 directed to step of administering a composition comprising an isolated mitochondria to a wound of a subject.
Regarding the blood product being a growth factor and a PRF, McCully et al. teach that mitochondria can be included in compositions that include blood and/or products derived from blood (para. 132). However, McCully et al. do not teach growth factors and a PRF.
Ding et al. teach that platelet-rich fibrin (PFR) accelerates skin wound healing in diabetic mice (see entire document). Ding et al. teach that PRF contains several cytokines and growth factors (see Abstract).
It would have been obvious to a person skilled in the art to use the PRF taught by Ding et al. along with the mitochondria taught by McCully et al. with a reasonable expectation of success. As McCully et al. teach the use of blood product in combination with mitochondria, and PRF is a blood product useful in treating wounds according to Ding et al., one skilled in the art would have been motivated to combine two teachings for the same purpose of treating wounds.
M.P.E.P. §2144.06 states “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
Regarding the growth factor, as discussed above, Ding et al. teach that PRF contains growth factors, and thus, the use of PRF taught by Ding et al. in the method of McCully et al. inherently apply both growth factor and PRF as claimed.
Regarding the intended outcome of the preamble in the amended claims directed to promoting skin cell proliferation and collagen secretion, the limitation does not require any additional active step to be carried out other then administering a composition comprising an isolated mitochondria, a growth factor and a PRF. As the method steps of the combined teachings of McCully et al. in view of Ding et al. are identical to the claimed steps, the results of the McCully et al. in view of Ding et al. would be inherently identical to the claimed results.
Regarding claims 6 and 10 directed to the dose of the mitochondria being from 1 to 40 mg or 15 to 40 mg, McCully et al. do not teach the limitation. However, McCully et al. teach the quantity of mitochondria to be administered is at least about 1x103 to 1x1014 (para. 151). Considering the weight of a mitochondrion being about 0.3 pg according to Samson et al., 1x103 to 1x1014 of mitochondria would be 0.3 ng to 30 mg. Therefore, the amount of mitochondria taught by McCully et al. would meet the limitation of claims 6 and 10.
Regarding claim 11 directed to the growth factors and their concentration, McCully et al. in view of Ding et al. do not particularly teach the limitation. However, the use of PRF taught by McCully et al. in view of Ding et al. would inherently meet the types of growth factors because the instant specification discloses that platelet-rich fibrin (hereafter as PRF) contains a variety of growth factors, such as PDGF-AA, PDGF-AB, PDGF-BB, TGF-β1, VEGF, EGF, IGF, etc. (para. 23). Thus, the PRF of McCully et al. in view of Ding et al. would inherently contain the claimed growth factors.
Regarding claim 12 directed to the PRF being greater than 5% by volume, McCully et al. in view of Ding et al. do not particularly teach the amount or ratio of the PRF in the composition.
However, it would have been obvious to a person skilled in the art to mix the mitochondria of McCully et al. and the PRF taught by Ding et al. at any desired ratio by volume with a reasonable expectation of success. As McCully et al. teach that the mitochondria being included in compositions comprising products derived from blood (para. 132), one skilled in the art would recognize that the ratio of mitochondria and the blood product would be readily modified for the desired outcome of repairing, healing, and/or regenerating wound/tissue by routine experimentations. For example, one skilled in the art would try an 1:1 mixing ratio by volume as it is within the purview of the skilled artisan. By doing so, the volume of PRF would be 50% of the total mixture and it would meet the claimed greater than 5% by volume.
The selection of mixing ratio between the components in a composition would have been a routine matter of optimization on the part of the artisan of ordinary skill. A holding of obviousness over the cited claims is therefore clearly required. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages. See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382.; See also M.P.E.P. § 2144.05.
Regarding claim 13 directed to the source cells of the isolated mitochondria, McCully et al. teach that the mitochondria can be isolated from any source, e.g. isolated from cultured cells or tissue, and the tissue can be liver tissue, skeletal muscle, heart, brain and adipose tissue (para. 135). Thus, it would have been obvious to a person skilled in the art to choose any cells from the liver tissue (i.e. liver cells), or skeletal muscle (i.e. skeletal muscle cell), etc.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Regarding the 112(b) rejection, the claim rejection has been withdrawn due to the instant amendment.
Regarding the 103 rejection, applicant alleged that the specific components and biological mechanisms are not taught by the prior art. Applicant argued that McCully discloses isolated mitochondria for treating wounds or improving skin wrinkles, it fails to teach or suggest the combination as claimed and there is no teaching that mitochondria can actively promote collagen secretion or stimulate cell proliferation. The Examiner acknowledged that McCully does not teach PRF and a growth factor utilized along with mitochondria in their method and the claim rejection stated so. The deficiency has been addressed by combining the teaching of Ding et al. Regarding the intended outcome not being taught by McCully, as discussed in the claim rejection above, the intended outcome does not require any other active step carried out than administering the isolated mitochondria, a growth factor and PRF. Since the combined teaching of McCully and Ding meet the claimed method step, the intended results would be inherently met.
Applicant asserted that there is unexpected synergistic results and enhanced technical effect shown in Examples 3-4 and 6-9, and Figs. 3-6 of the instant specification.
Examples 3-4 of the instant specification does not disclose the combination of mitochondria and PRF.
Example 6 discloses the results of cell migration assay compared between PRF and PRF/mitochondria (15 or 40 mg of mito.) (Fig. 3) on CCD-966SK cells. The specification discloses that CCD-966SK cells are human skin fibroblasts (para. 31). According to Figure 3A and B and Figure 4, there is increase of cell migration and soluble collagen in the group having mitochondria and PRF compared to PRF. The data shown in Fig. 3 and 4 do not provide any evidence that there is any synergistic effect of PRF and mitochondria because the data are compared to PRF only. However, Fig. 2 showed that the amount of soluble collagen secreted from the mitochondria only treated cells was about 15 or 25 mg/ml for mitochondria at 15 mg or 40 mg, respectively. As the combination of mitochondria and PRF shown in Fig. 4 is over 1000 mg/ml for both concentration of mitochondria, it is concluded that there is a synergistic effect of mitochondria at 15 mg or 40 mg along with PRF in collagen secretion from human skin fibroblast in vitro. However, this synergistic effect in vitro is based on the 15 or 40 mg of mitochondria and the amount of PRF utilized in the Examples, which is 5% by volume in the medium using the PRF prepared by the method shown in Example 2. As the instant claims do not particularly disclose the concentration of PRF, the alleged synergistic effect does not support the entire scope of the PRF concentration as the claims do not disclose the concentration.
It is noted that claim 12 discloses that the PRF is greater than 5% by volume. It is understood that the in vitro as well as in vivo examples of the instant specification only utilized 5vol% of PRF according to the specification (para. 35). However, the claimed method in claim 4 does not particularly disclose the concentration, and claim 12 discloses broader scope of “greater than 5% by volume” which excludes 5vol% as shown in the instant specification. There is no evidence supporting the synergism for in vitro as well as in vivo experimentations utilizing the claimed greater than 5%(v/v) PRF.
Therefore, while there appears to be a synergistic effect from combination of mitochondria and PRF at the specific amount in vitro, however, the instant claims disclose the scope broader than the evidence supporting the alleged synergistic effect.
For the synergistic effect for in vivo treatment of wound, Example 8 and Fig. 5 do not provide clear evidence that there is any synergistic effect as the data do not provide data point with mitochondria only. Furthermore, even if there is any synergism present for the in vivo application, however, the synergism appear to require the specific concentration range for mitochondria and PRF. Yet the independent claim 4 discloses a broader scope in terms of the concentration of mitochondria and PRF, and the dependent claims also fail to limit the concentrations of mitochondria and PRF supported by the data shown in Example 8 and Fig. 5.
Based on the above discussion, it is the Examiner’s position that the combined teachings of McCully and Ding in view of Samson render the claimed invention obvious.
Applicant is advised to amend the claims and provide the missing data (e.g. mitochondria only) to substantiate the alleged synergism from in vivo method as claimed.
Conclusion
No claims are allowed.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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