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. 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. Election/Restrictions Applicant's election with traverse of Group I, claims 1-5 and 18-21 in the reply filed on 14 January 2026 is acknowledged. The traversal is on the ground(s) that the special technical feature was not previously known in the art; as such, applicant disagrees with the examiner’s position that Groups II-III do not share a common special technical feature. The examiner does not necessarily disagree with this argument; however, the examiner takes the position that Groups II and III lack a common technical feature with Group I a priori . See MPEP 1850(II), third paragraph for information regarding a priori lack of unity of invention. This is because Group I is drawn to exosomes; however, Groups II and III are drawn to cells; see withdrawn claims 23 and 36. The requirement is still deemed proper, but is not made final because the rationale presented by the examiner for the examiner’s determination of lack of unity presented in this office action differs from the rationale presented by the examiner in the restriction requirement on 30 September 2025. Claims 12-17 and 23-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 14 January 2026. The examiner has addressed applicant’s arguments in greater detail in the section below entitled “Response to Arguments.” Clarification Regarding Potential Rejoinder: The examiner takes the position that even if, purely en arguendo , the examiner was to find claims drawn to the recited exosomes to be allowable (which has not occurred in this office action), there would not appear to be a right of rejoinder of withdrawn claims drawn to cells, or methods of making or using cells. This is because exosomes and cells are separate products. Exosomes and cells differ because of the at least following reasons: Exosomes lack a nucleus and other organelles including but not limited to the endoplasmic reticulum and the Golgi apparatus; in contrast, these are included in cells. Exosomes are generally of a smaller size as compared with cells, and exosomes often have a diameter that is smaller than that of cells by at least two orders of magnitude. In exosomes, as in synthetic liposomes, the structure is that of a lipid bilayer comprising an interior aqueous phase. The interior aqueous phase in exosomes is generally water, often with salts dissolved, and having a viscosity very similar to that of water. In contrast, cells comprise cytoplasm in the interior which has a much higher viscosity than ordinary liquid water. Exosomes are generally made for drug delivery, whereas cells are less likely to be used for this purpose. There is a possibility that the issues related to 35 U.S.C. 101 regarding cells differ from those regarding exosomes. Claim Interpretation For the purposes of examination under prior art, the examiner understands the terms “exosome” to refer to extracellular vesicles of a relatively small size. See e.g. the instant specification on page 18, paragraph 0039. The abbreviation “ Wnt ” is a well-known abbreviation referring to Wingless and Int-1 signaling. The examiner notes that instant claim 1 appears to be a product-by-process claim. The reason for this is that instant claim 1 is drawn to a product formed by the process of (a) first, providing a population of adipocytes comprising at least 30% Wnt + adipocytes, and (b) secondly, forming exosomes from said adipocytes. Product-by-process claims are not limited to the manipulations of the recited steps, only to the structure implied by the steps. See MPEP 2113(I). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product. See MPEP 2113(II). With that being said, in this case, the skilled artisan would have understood that the process of making an exosome from a cell involves retaining the plasma membrane (though reducing the size of the vesicles produced therefrom) and reformulating the plasma membrane into exosomes while removing features in the inside of the cell and the outside of the cell. Consequently, a composition comprising adipocyte exosomes with Wnt present, but either encapsulated in the interior aqueous phase of the liposome or dissolved in the exterior aqueous phase of the liposome is not understood to be within the claim scope. This is because such a structure would not have been produced by obtaining Wnt + cells and forming exosomes therefrom. In order to better clarify this position, the examiner presents the following pictures, with an explanation as to whether what is shown in the picture is within the claim scope. The pictures have been drawn by the examiner ; however, the outline of the structure of an exosome was taken from Khatami et al. (Molecular Neurobiology, Vol. 60, 2023, pages 4659-4678) . The examiner clarifies the following regarding the above figures. First, the outline for the lipid bilayer of the exosome was taken from Khatami et al. (Molecular Neurobiology, Vol. 60, 2023, pages 4659-4678). Khatami et al. (hereafter referred to as Khatami) is not prior art due to having a later filing date; however, it is useful in explaining the claim interpretation because it clearly shows the structure of an exosome which is necessary for the examiner to best explain how the claim is being interpreted. The triangle with “ Wnt ” in the middle was drawn by the examiner, does not appear in Khatami, and represents the Wnt protein. Secondly, for the purposes of explaining the claim interpretation, the examiner makes the assumption that the exosomes described in the above-reproduced figure are derived from a population of adipocytes. As such, the examiner has presented three figures above. Figure ( A ) is understood to be within the claim scope because it has Wnt in the membrane of an exosome. This would have been obtained from the process of preparing an exosome from a Wnt + cell such as a Wnt + adipocyte. A population of exosomes wherein all of the exosomes have the structure of figure (B) is not within the claim scope. This is because this structure would have been prepared by obtaining exosomes from a population of adipocytes lacking Wnt and subsequently adding Wnt later. The reason for this is because the process of making exosomes from cells preserves the cell membranes but removes ingredients inside the cell or outside the membrane. Therefore, the presence of Wnt either outside the exosome or in the interior aqueous space of the exosome indicates that the Wnt was not part of the adipocyte from which the exosome was obtained; but rather, was added following the formation of the exosome from the adipocyte. Similarly, a population of exosomes wherein all of the exosomes have the structure of figure (C) is not within the claim scope. This is because, similar to figure (B), this structure would have been prepared by obtaining exosomes from a population of adipocytes lacking Wnt and subsequently adding Wnt later. The reason for this is because the process of making exosomes from cells preserves the cell membranes but removes ingredients inside the cell or outside the membrane. Therefore, the presence of Wnt either outside the exosome or in the interior aqueous space of the exosome indicates that the Wnt was not part of the adipocyte from which the exosome was obtained ; but rather, was added following the formation of the exosome from the adipocyte. Claim Rejections - 35 USC § 101 – Patent Eligibility 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 1-5 and 18-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a natural product without significantly more. The examiner notes MPEP 2106 as teaching the following flowchart for analysis under 35 U.S.C. 101. Step 2A can be further broken down into the following two prongs, as of MPEP 2106.04(II)(A), as set forth below. Regarding step 1, it is the examiner’s position that the claimed invention is drawn to a composition of matter. Regarding step 2A, P rong O ne, it is the examiner’s position that the instant claims recite a natural product, which is within the scope of the judicial exceptions of a law of nature or natural phenomenon. The examiner presents the following in support of this position. As an initial matter, the examiner takes the position that the instant specification admits that adipocytes comprising Wnt (i.e. Wnt + adipocytes) are naturally occurring. In support of this position, the examiner cites the instant specification as of pages 11-12, paragraph 0023, reproduced below. As such, the specification appears to admit that Wnt + adipocytes exist naturally. Additionally, there would have been a reasonable expectation that the Wnt + adipocytes described in the above-reproduced paragraph would have produced exosomes naturally in the human body or the body of another living organism . In support of this position, the examiner cites Kalluri et al. (Science, Vol. 367 (640), 16 pages (1 page summary and pages 1-15 for the article), 7 February 2020) which indicates that all cells release extracellular vesicles, as of the left column of the summary of Kalluri . The examiner understands the terms “exosome” and “extracellular vesicle” to have essentially the same meaning. As such, the skilled artisan would have expected that adipocyte exosomes released from Wnt + adipocytes would have existed naturally. This is because Wnt + adipocytes exist naturally, as per the instant specification, and all cells release adipocytes, as per Kalluri ; therefore, the skilled artisan would have expected that exosomes derived from Wnt + adipocytes would have existed naturally. In order to provide additional evidence that exosomes derived from adipocytes are natural products, the examiner cites Zhou et al. ( Theranostics , Vol. 10 Issue 18, 2020, pages 8197-8210). Zhou et al. (hereafter referred to as Zhou) is drawn to exosomes derived from brown adipose tissue, as of Zhou, page 8197, title and abstract. As admitted by the instant specification, the skilled artisan would have expected that 20% of these exosomes would have comprised material associated with Wnt + even if that feature was not recognized by Zhou. The examiner further notes here that prohibitions against impermissible hindsight reasoning that exist in anticipation and obviousness analysis (e.g. as per MPEP 2145(X)(A)) do not apply to patent eligibility analysis. Therefore, the instant claims are drawn to the judicial exception of a law of nature and/or natural phenomenon. Regarding step 2A, P rong Two , the examiner takes the position that claim 1 does not appear to recite additional elements beyond the exosomes. As such, the claim does not recite additional elements that integrate the judicial exception into a practical application. Regarding Step 2B, the e xaminer notes that, purely en arguendo , the concentration of adipocytes derived from Wnt + exosomes may differ from what would have been present naturally. Nevertheless, this difference is not sufficient to overcome this patent eligibility rejection. Changing the concentration does would not appear to change the structure or function of the products. All that is being done is removing other products from the composition that have other functions which are not of interest, without changing anything about the products being retained. As such, any difference in concentration is insufficient to render the claimed invention patent eligible. Regarding claim 21, the examiner notes that the claim additionally recites a pharmaceutically acceptable carrier or excipient. However, the scope of the phrase “pharmaceutically acceptable carrier or excipient” includes water and saline, which are both natural products themselves, and unlikely to result in marked differences when combined with the cells. Relevant Prior Art – No Rejection As relevant prior art over which the claims have not been rejected, the examiner cites Zhou et al. ( Theranostics , Vol. 10 Issue 18, 2020, pages 8197-8210). Zhou et al. (hereafter referred to as Zhou) is drawn to exosomes derived from brown adipose tissue, as of Zhou, page 8197, title and abstract. Zhou differs from the claimed invention because Zhou is silent as to whether the taught exosomes are from Wnt + adipocytes. With that being said, the instant specification discloses the following, as of pages 11-12, paragraph 0023, reproduced below. As such, the skilled artisan would have expected that in the composition of Zhou, only a maximum of about 20% of the adipocytes would have been Wnt + adipocytes. The examiner must provide rationale or evidence to show inherency, as per MPEP 2112(IV); in this case, the evidence provided by the specification would appear to go against the idea that the required amount of Wnt + adipocytes would have been inherent in the composition of Zhou. Additionally, there would have been no motivation for the skilled artisan to have increased the proportion of exosomes in Zhou that are Wnt + exosomes because this concept is not taught by Zhou. This is at least because the issue of whether exosomes are Wnt + has not been identified as a result-effective variable by Zhou , nor would there have been a design need or market pressure to solve the problem of Wnt + concentration in the exosome population of Zhou by increasing the Wnt + concentration. See MPEP 2144.05(II)(B), second paragraph in section, and MPEP 2144.05(III)(C). Additionally, even if, purely en arguendo , there were motivation for increasing the Wnt + concentration in the exosome population of Zhou, it is unclear that there would have been a reasonable expectation that this could have been successfully achieved. See MPEP 2144.05(II)(B), first paragraph in section. The examiner further notes that according to MPEP 2144.05(II)(A), generally, differences in concentration between the claimed invention and the prior art will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. In support of this position, MPEP 2144.05(II)(A) cites In re Aller , 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) . In the cited case, a claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10% . With that being said, it is the examiner’s position that the instant claims, drawn to Wnt concentration on adipocyte membranes, differs substantially from the cited case. In the cited case, the relevant issue is the acid concentration, and the skilled artisan would have been able to have optimized the acid concentration by adding more acid or less acid. In contrast, in the instant case, Wnt is not added as a reagent (like the acid in the cited case), but is present in cells. As such, to increase or decrease the concentration of Wnt , the skilled artisan would need to separate cells comprising Wnt from those not comprising Wnt . There would have been no motivation for the skilled artisan to have done this, nor would there have been a reasonable expectation that this could have been done successfully. As such, the issue of optimizing the Wnt concentration in the instantly claimed invention and in the Zhou reference difers substantially from the issue of optimizing acid concentration of reagents such as acid in the cases cited in MPEP 2144.05(II)(A). The examiner further clarifies that the presence of Wnt + in a cell would have been expected to have resulted in a structural difference in the membrane of said cell as compared with a non- Wnt + cell . The structural difference would appear to be the presence of palmitoylated Wnt proteins in the Wnt + cell that would not have been present in the non- Wnt + cell. This is described by Zhai et al. (The Journal of Biological Chemistry, Vol. 279 No. 32, August 2004, pages 33220-33227), as of at least the title and abstract of this reference. These palmitoylated proteins are present at the plasma membrane, as of Zhai, page 33220, right column, first full paragraph. As exosomes are obtained from retaining the cell membrane but removing the internal contents of the cell, the skilled artisan would have expected that the exosomes derived from Wnt + adipocytes would have comprised palmitoylated Wnt proteins that would not have been present in the non- Wnt + adipocytes. Therefore, the skilled artisan would have expected that there would have been a structural difference between the Wnt + adipocyte exosomes and the non- Wnt + adipocyte exosomes. Response to Arguments Applicant presented arguments in applicant’s response on 14 January 2026. These arguments relate to differences between the claimed invention and the prior art cited by the examiner in the restriction requirement mailed on 30 September 2025. The examiner has taken applicant’s arguments into account in the examiner’s decision not to reject the instant claims as anticipated or obvious. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ISAAC SHOMER whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-7671 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 7:30 AM to 5:00 PM Monday Through Friday . 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. FILLIN "Examiner Stamp" \* MERGEFORMAT ISAAC . SHOMER Primary Examiner Art Unit 1612 /ISAAC SHOMER/ Primary Examiner, Art Unit 1612