DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/17/2025 has been entered.
3. Applicant’s amendment to the claims filed on 10/17/2025 in response to the Final Rejection mailed on 10/17/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
4. New claims 92 and 93 are added.
5. Claims 1, 67, 79, and 81-93 are pending.
6. Applicant’s remarks filed on 10/17/2025 in response to the Final Rejection mailed on 10/17/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Rejections - 35 USC § 112(b)
7. The rejection of claims 1, 67, 79, and 81-91 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the relative term “substantially” is withdrawn in view of applicants’ amendment to the claims to remove said term.
8. The rejection of claim 89 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the relative term “about” is withdrawn in view of applicants’ amendment to the claims to remove said term.
Claim Rejections - 35 USC § 101
9. The rejection of claims 1, 67, 79, and 81-89 under 35 U.S.C. 101 because the claimed invention is directed to a nature based product without significantly more is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 92 and 93, which is necessitated by applicants’ amendment to the claims to add new claims 92 and 93.
Claims 1, 67, 79, 81-89 and 92-93 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature based product without significantly more. As amended, the claim(s) recite(s) a frozen pharmaceutical composition comprising a population of isolated mitochondria and at least one pharmaceutically acceptable component, wherein the frozen pharmaceutical composition has been cryopreserved for at least one week, wherein, after thawing the frozen pharmaceutical composition: (i) at least 80% of the mitochondria in the population have intact inner and outer membranes, (ii) at least 80% of the mitochondria in the population are polarized as measured by a fluorescence indicator, (iii) at least 80% of the mitochondria in the population maintain functional capability in an extracellular environment at a total calcium concentration of 8 mg/dL, and (iv) at least 80% of the mitochondria in the population have a non-filamentous shape, which is different from filamentous shape of mitochondria inside cells, wherein upon contact of the population of isolated mitochondria with a population of cells, after thawing the frozen pharmaceutical composition, the isolated mitochondria are capable of being incorporated into cells upon contacting the cells and inducing co-localization and/or fusing with endogenous mitochondria in the cells while maintaining the non-filamentous shape. This judicial exception is not integrated into a practical application because the claims encompass naturally occurring mitochondria. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite limitations that define the functional capabilities of the mitochondria; however, these functions are already associated with the innate function of mitochondria. There is no indication that these functions are sufficient to transform the claimed population of mitochondria into something that is markedly different structurally and functionally from its natural counterpart. The limitation “frozen” merely recites the current state of the mitochondria, but when compared to its closest natural counterpart, such as a frozen human cell line, does not transform the mitochondria into something that is markedly different. It still maintains its innate function and ability as demonstrated in the claims with the recitations of “after thawing”. Additionally, the limitation “a pharmaceutically acceptable component” is sufficiently broad to encompass any component such as water. Furthermore, claims drawn to defining the product by how it is made are not sufficient to transform the product into something markedly different because these are “product by process” limitations. MPEP 2113.I states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” In the instant case, there is no evidence of record that the process of isolating the mitochondria to produce the population of isolated mitochondria is sufficient to transform the mitochondria into something that is markedly different structurally and functionally from its natural counterpart. Accordingly, the population of isolated mitochondria recited in the claims are not patent eligible. It is suggested that applicants’ amend the claims to transform the isolated mitochondria into something that is markedly different that its natural counterpart or provide evidence to suggest the claimed functional capabilities are markedly different from its natural counterpart.
RESPONSE TO REMARKS: Beginning on p. 7 of applicants’ remarks, applicants contend that the amendment to a frozen composition is markedly different from naturally occurring mitochondria as they are certainly not in a frozen state. Applicants also contend that the limitation of a pharmaceutically acceptable component is sufficient to transform the mitochondria into something significantly more than the natural product.
These arguments are found to be not persuasive in view of the modified rejection above, the reasons already of record, and the reasons set forth below. As state above, the limitation “pharmaceutically acceptable component” is sufficiently broad so as to encompass a natural component, such as water. The examiner maintains the position that the claims recite limitations that define the functional capabilities of the mitochondria; however, these functions are already innate to the naturally occurring mitochondria. MPEP 2106.04(c)II.C.2 states “In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e., the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). In sum, the claimed genes were different, but not markedly different, from their naturally occurring counterparts (the BRCA genes), and thus were product of nature exceptions. In Ambry Genetics, the court identified claimed DNA fragments known as "primers" as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because "single-stranded DNA cannot be found in the human body". The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence. 774 F.3d at 760, 113 USPQ2d at 1243-44.” The limitation “frozen” merely recites the current state of the mitochondria, but when compared to its closest natural counterpart, such as a frozen human cell line, does not transform the mitochondria into something that is markedly different. It still maintains its innate function and ability as demonstrated in the claims with the recitations of “after thawing”. The ability of the isolated mitochondria to co-localize and fuse with endogenous mitochondria is innate to the natural structure of the mitochondria itself. Furthermore, the existence of the isolated mitochondria in a non-filamentous form is analogous to the isolated DNA and single stranded primers set forth in the Myriad decision above. In the instant case, the isolated mitochondria although different in shape, still maintain the same innate function that occur in nature.
Claim Rejections - 35 USC § 102
10. The rejection of claims 1, 67, 79, and 81-91 under 35 U.S.C. 102(a)(1) as being anticipated by Fisher et al. (Placenta, May 2019; cited on IDS filed on 05/10/2022) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 92 and 93, which is necessitated by applicants’ amendment to the claims to add new claims 92 and 93.
Claims 1, 67, 79, and 81-93 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fisher et al. (Placenta, May 2019; cited on IDS filed on 05/10/2022).
11. With respect to claim 1, Fisher et al. teach a population of isolated mitochondria, wherein at least 80% of the mitochondria in the population have intact inner and outer membranes, at least 80% of the mitochondria in the population are polarized as measured by a fluorescence indicator, and/or at least 80% of the mitochondria in the population maintain functional capability in an extracellular environment [see p. 1, column 2 bridging to p. 2; Figure 1-2]. Fisher et al. teach wherein the isolated mitochondria are snap frozen and stored at -80oC for up to five months [see p. 1 column 2]. After thawing, Fisher et al. teach the population of isolated mitochondria in the population have a non-filamentous shape [see Figure 1]. Fisher et al. teach a population of isolated mitochondria, wherein at least 80% of the mitochondria in the population have intact inner and outer membranes, at least 80% of the mitochondria in the population are polarized as measured by a fluorescence indicator, and/or at least 80% of the mitochondria in the population maintain functional capability in an extracellular environment [see p. 1, column 2 bridging to p. 2; Figure 1-2]. Fisher et al. teach compositions of the isolated mitochondria comprising 0.5 mM EGTA, 3 mM MgCl2*6H2O, 60 mM K-lactobionate, 20 mM taurine, 10 mM KH2PO4, 20 mM HEPES, 110 mM sucrose, 1 g/L fatty acid free BSA (interpreted as pharmaceutically acceptable carrier) [see p. 2, column 1]. It is noted that the limitations “wherein the population of isolated mitochondria are obtained by a process comprising…” are “product by process” limitations. MPEP 2113.I states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” In the instant case, given that Fisher et al. meet the structural limitations of claim 1, it is the examiner’s position that the mitochondria of Fisher et al. are structurally and functionally identical to the mitochondria obtained by the process of claim 1.
With respect to claims 67 and 79, Fisher et al. teach a population of isolated mitochondria from placenta cells, wherein at least 80% of the mitochondria in the population have intact inner and outer membranes, at least 80% of the mitochondria in the population are polarized as measured by a fluorescence indicator, and/or at least 80% of the mitochondria in the population maintain functional capability in an extracellular environment [see p. 1, column 2 bridging to p. 2; Figure 1-2]. Fisher et al. teach wherein the isolated mitochondria are snap frozen and stored at -80oC for up to five months [see p. 1 column 2]. Fisher et al. teach the population of mitochondria comprising densely folded cristae [see Figure 1]. Fisher et al. teach the population of isolated mitochondria in the population have a non-filamentous shape [see Figure 1]. ]. Fisher et al. teach a population of isolated mitochondria, wherein at least 80% of the mitochondria in the population have intact inner and outer membranes, at least 80% of the mitochondria in the population are polarized as measured by a fluorescence indicator, and/or at least 80% of the mitochondria in the population maintain functional capability in an extracellular environment [see p. 1, column 2 bridging to p. 2; Figure 1-2]. Fisher et al. teach compositions of the isolated mitochondria comprising 0.5 mM EGTA, 3 mM MgCl2*6H2O, 60 mM K-lactobionate, 20 mM taurine, 10 mM KH2PO4, 20 mM HEPES, 110 mM sucrose, 1 g/L fatty acid free BSA (interpreted as pharmaceutically acceptable carrier) [see p. 2, column 1]. It is noted that the limitations “wherein the population of isolated mitochondria are obtained by a process comprising…” are “product by process” limitations. MPEP 2113.I states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” In the instant case, given that Fisher et al. meet the structural limitations of claim 67, it is the examiner’s position that the mitochondria of Fisher et al. are structurally and functionally identical to the mitochondria obtained by the process of claim 67.
With respect to claim 81, Fisher et al. teach a population of isolated mitochondria, wherein at least 80% of the mitochondria in the population have intact inner and outer membranes, at least 80% of the mitochondria in the population are polarized as measured by a fluorescence indicator, and/or at least 80% of the mitochondria in the population maintain functional capability in an extracellular environment [see p. 1, column 2 bridging to p. 2; Figure 1-2]. Fisher et al. teach the population of mitochondria comprising densely folded cristae [see Figure 1]. Although Fisher et al. does not explicitly teach wherein at least 80% of the mitochondria in the population are not undergoing dynamin-related protein 1-dependent division, wherein the mitochondria exhibit decreased association with mitochondria-associated membrane (MAM) as measured by glucose regulated protein 75 (GRP75) expression, wherein the polydispersity index (PDI) of the population is about 0.2 to about 0.8, and/or wherein the zeta potential of the population of mitochondria is between about -15 mV and about -40 mV, the isolated mitochondria of Fisher et al. meet the structure required by claim 1. It is the examiner’s position that these features are inherent to the isolated mitochondria of Fisher et al. Since the Office does not have the facilities for examining and comparing applicants’ mitochondria with the mitochondria of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the mitochondria of the prior art does not possess the same material structural and functional characteristics of the claimed mitochondria). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claims 82-88, Fisher et al. teach the population of isolated mitochondria of claim 1, wherein at least 70% of the isolated mitochondria in the population are polarized as measured by a fluorescence indicator, after the population undergoes one or more freeze-thaw cycle [see p. 2]. Given the indefiniteness of the phrase “substantially” in claims 83-88, it is the examiner’s position that the teachings of Fisher et al. meet the structural requirements as recited in the claims. Since the Office does not have the facilities for examining and comparing applicants’ mitochondria with the mitochondria of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the mitochondria of the prior art does not possess the same material structural and functional characteristics of the claimed mitochondria). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 89, Fisher et al. teach the population of mitochondria comprising densely folded cristae [see Figure 1]. Given the indefiniteness of the phrase “about” in claims 83-88, it is the examiner’s position that the teachings of Fisher et al. meet the structural requirements as recited in the claims. Since the Office does not have the facilities for examining and comparing applicants’ mitochondria with the mitochondria of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the mitochondria of the prior art does not possess the same material structural and functional characteristics of the claimed mitochondria). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claims 90-91, Fisher et al. teach compositions of the isolated mitochondria comprising 0.5 mM EGTA (divalent chelator), 3 mM MgCl2*6H2O, 60 mM K-lactobionate, 20 mM taurine, 10 mM KH2PO4, 20 mM HEPES, 110 mM sucrose, 1 g/L fatty acid free BSA [see p. 2, column 1].
With respect to claims 92-93, Fisher et al. teach wherein the isolated mitochondria are snap frozen and stored at -80oC for up to five months [see p. 1 column 2].
RESPONSE TO REMARKS: Beginning on p. 9 of applicants’ remarks, applicants in summary continue to contend that Fisher does not disclose whether both inner as well as outer mitochondrial membranes are intact after isolation. Applicants contend that Fisher utilizes homogenization which is a process that is excluded from the present claims and does not show mitochondria with clearly defined cristae and most of the observed mitochondria lack clear internal structure.
This argument is found to be not persuasive for the reasons already of record and the reasons set forth below. Fisher et al. explicitly teach on p. 2, column 1, bottom that isolation by differential centrifugation yielded mitochondrial subpopulations of high purity (85-85%), which maintained morphology similar to mitochondria in situ, with no apparent damage induced by centrifugation, and Fisher et al. further shows that the recovery respiratory rates between 83% and 93% [see p. 2, column 2]. Additionally, Fisher et al. teach that cryopreservation did not have any significant effect on mitochondrial outer membrane integrity and showed clearly defined cristae [see p. 2, columns 1-2]. As such, absent evidence otherwise, these high recovered respiratory rates would be indicative of undamaged mitochondria with intact membranes given that intact membranes would be necessary for active respiration. Taken together, this data would suggest that the inner and outer membranes of the mitochondria were predominantly intact and did not result in substantial damage to the mitochondria.
Conclusion
12. Status of the claims:
Claims 1, 67, 79, and 81-93 are pending.
Claims 1, 67, 79, and 81-93 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656