CTNF 18/289,530 CTNF 101524 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application is a national stage entry under 35 U.S.C. 371 of PCT/KR2022/006423 (filed on 05/04/2022), which claims priority to KR 10-2021-0058172 (filed on 05/04/2021). Claim Status Claims 1-11 are pending and have been considered on the merits. Claim Objections 07-29-01 AIA Claim 10 objected to because of the following informalities: In claim 10, line 7 , the term “from” is misspelled (form) . Appropriate correction is required. Claim Rejections - 35 USC § 112 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Regarding claims 1 and 10, the phrase "treating the extracellular vesicles… " renders the claims indefinite because the phrase, specifically what the term ‘treating’ encompasses in the context of the claims. It is not clear what is the scope of ‘treating’ is and any interpretation, leads to the claims being indefinite. It appears this may be a translation error. For examination purposes with respect to prior art, any method that comprises administering the extracellular vesicles derived from 3D spheroid type cell aggregate to a subject in need thereof or to in vitro cells will be considered within the metes and bounds of claim 1 and 10, respectively. Claims 2-9 depending directly from claim 1, inherit the deficiencies, and thus are rejected on the same basis. Regarding claims 5 and 6: The term “highly express” in claim 5-6 is a relative term which renders the claim indefinite. The term “highly express” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Regarding claims 5-6, the phrase “highly express” at least one selected from the group is ambiguous because neither the prior art nor the specification make clear what is included or excluded by the relative term “highly express”. For examination purposes with respect to prior art, any method that comprises promoting angiogenesis and meeting the recited active method steps will be considered within the metes and bounds of claims 5-6. Appropriate correction or clarification is required. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-21-aia AIA Claim s 1-9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Cha et al (KR101991038 B1; as cited in IDS filed on 11/03/2023) and further in view of Makino et al (US 2022/0145241 A1) . Cha et al is in the Korean language. A translation is provided. Citations are to the translation. Cha et al discloses a method for producing extracellular vesicles derived from stem cells using a 3D cell culture, and a pharmaceutical composition containing them (See, ¶0001). Regarding claim 1 and 11, Cha et al discloses a method for producing stem cell derived extracellular vesicles (See, ¶0021). The 3D culturing can be done in cell microwell array, with a cell culture space of 50 to 250μm (See, ¶0039-0041). Cha et al discloses that the method can further include isolating and/ or purifying the extracellular vesicles produced from culturing the stem cell aggregates (See, ¶0055). Cha et al further discloses that extracellular vesicles isolated from the 3D culturing of the stem cells can be a pharmaceutical composition and that the composition can be administered to a subject (See, ¶0064-0065). Cha et al does not disclose that the microwell used for the method has a depth of 100 to 1000 μm. Makino et al teaches a method for producing undifferentiated cell spheroids from stem cells, which can be mesenchymal stem cells (See, Abstract and ¶0124). Makino et al teaches a culturing method to produce cell spheroids on a cell culture sheet with a plurality of recesses or microwells each with an opening of 2000 μm or less in diameter (See, ¶0015). Makino et al teaches an embodiment where the cell culture sheet comprising a plurality of recesses each having an opening of 1000 μm or less in diameter and a depth of 10 to 1500 μm, 10 to 1000 μm, 10 to 800 μm, 10 to 500 μm, or 10 to 300 μm (See, ¶0094-0101 and Figure 1 D11 and D11 a respectively). It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of Cha et al to comprise producing spheroids in cell culture sheets with microwells with diameters of 1000μm or less and depth of 10-1500 μm as taught by Makino et al. One would be motivated to make this modification because Makino et al teach that the use of culture sheet comprising microwells enables easy and efficient production of spheroids (See, ¶0016). Microwells with diameters of 200-800 μm and depth of 100 to 1000 μm are obvious in light of Cha et al in view of Makino et al because Makino et al discloses methods of spheroid formation and culturing in microwells with overlapping ranges of diameter and depth. In case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists (See MPEP 2144.05). Further, one would have a reasonable expectation of success because the cell culture sheet with microwells of Makino et al could readily be used to generate exosome producing MSC spheroids in the method of Cha et al. Therefore, claims 1 and 11 are rendered obvious over Cha et al in view of Makino et al. Regarding claim 2, Cha et al discloses the stem cells used in the disclosed invention can be embryonic stem cells (¶ 0022), induced pluripotent stem cells (¶ 0023), progenitor cells (¶ 0024), or mesenchymal stem cells (¶ 0026). This reads on wherein the stem cells are at least one selected from the group consisting of mesenchymal stem cells, pluripotent stem cells, induced pluripotent stem cells and embryonic stem cells , of claim 2. Regarding claim 3, Cha et al discloses a method for preparing the stem cell derived extracellular vesicles that includes generating cell aggregate of a 3D culture under normal culture conditions of 37°C and 5% CO 2 (See, ¶0045-0050). This reads on wherein the 3D culture in step (a) is static culture , of claim 3. Regarding claim 4, Cha et al discloses in example 1 the 3D cell culture of mesenchymal cell to generate extracellular vesicles. In example 1, the mesenchymal stem cells are inoculated onto PEG microwell array at a concentration of 600-700 cells per microwell (See, ¶0075). This reads on wherein the 3D culture in step (a) is performed by dispersing and culturing the mesenchymal stem cells in a microwell at a density of 200 to 600 cells/well of claim 4. Regarding claims 5 and 6, following the discussion above about claim 1, Cha et al teaches a method of producing EVs from 3D stem cell culture in microwells, isolating them and administering them to subject. Therefore, it would be inherent that the extracellular vesicles highly express at least one miR from the group in claim 5 and / or at least one growth factor from the group in claim 6. This reads on …of claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of … of claim 5 and …wherein the extracellular vesicles highly express at least one selected from the group consisting of .. of claim 6. Cha et al teaches that the content of the stem cell derived extracellular vesicles contained in the culture method described is characterized as being significantly increased compared to the culture obtained from 2D cell culture (See, ¶0053, ¶0061 and Figure 1). Due to the reference disclosing all claimed steps, the effect will necessarily be achieved, even if not explicitly recognized by the reference (See, MPEP 2112.02). Regarding claim 7, following the discussion above about claim 1, Cha et al discloses that the pharmaceutical composition comprising the extracellular vesicles is used for diseases such as stroke, which is a cerebrovascular disease (See, ¶0064). This reads on wherein the pharmaceutical composition for promoting angiogenesis is for prevention or treatment of…cerebrovascular diseases of claim 7. Regarding claim 8, following the discussion above about claim 1, Cha et al teaches a method of producing EVs from 3D stem cell culture in microwells, isolating them and administering them to subject. Therefore, it would be inherent that the method would promote angiogenesis and in part promote brain angiogenesis. Due to the reference disclosing all claimed steps, the effect will necessarily be achieved, even if not explicitly recognized by the reference (See, MPEP 2112.02). Regarding claim 9, following the discussion above about claim 1, Cha et al further discloses that extracellular vesicles isolated from the 3D culturing of the stem cells can be a pharmaceutical composition and that the composition can be administered to a subject (See, ¶0064-0065). This reads on, wherein the extracellular vesicles derived from a three-dimensional spheroid-type cell aggregate is contained in food composition or pharmaceutical composition of claim 9. Therefore claims 1-9 and 11 are rejected as being rendered obvious by Cha et al in view of Makino et al . 07-22-aia AIA Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Cha et al in view of Makino et al as applied to claim s 1-9 and 11 above, and further in view of Shabbir et al (Stem cells and development, 2015) . The teachings of Cha et al and Makino et al are set forth above. Cha et al and Makino et al rendered obvious 3D culturing stem cells in microwell array that has a diameter of 200-800 μm and depth of 100-1000 μm to produce extracellular vesicles. Cha et al discloses that the method can further include isolating and/or purifying the extracellular vesicles produced from culturing the stem cell aggregates (See, ¶0055). Cha et al further discloses that extracellular vesicles isolated from the 3D culturing of the stem cells can be a pharmaceutical composition and that the composition can be administered to a subject (See, ¶0064-0065). Cha et al does not teach the administering of the extracellular vesicles isolated from 3D culturing to in vitro cells. Shabbir et al examined the role of exosomes derived from mesenchymal stem cells (MSCs) in wound healing and gained insight in how exosomes and MSCs may mediate wound healing (See, Abstract). Shabbir et al utilized human MSCs cultured them, isolated the exosomes with an ultracentrifugation protocol, and fluorescent labeled the exosomes. Then the MSCs were co-cultured human umbilical vein endothelial cells (HUVECs) with increasing concentration of MSC exosomes. This in vitro culturing of HUVECs and MSC exosomes formed extensive tubular network in a dose dependent manner (See, Figure 5B,C p1641). Shabbir et al also teaches that MSC exosomes activate expression of various signaling pathways and genes, such as VEGF (See, Figure 6 C, p1642). Therefore, given that the in vitro method of promoting angiogenesis of Cha et al is to be administered in a subject, it would have been obvious to have modified the method of Cha et al to administer the composition to cells in vitro . This is achieved by isolating the exosomes as described in Cha et al and administering them to cells in vitro. One of ordinary skill in the art would have reasonable expectation of success of promoting angiogenesis because Shabbir et al co cultures HUVECs with exosomes derived from MSCs and saw extensive tubular networking or angiogenesis. This conclusion of obviousness is based on the 'teaching, suggestion, or motivation rationale'; one would be motivated to do so because administering the composition to cells would aid in understanding the dosage need for the pharmaceutical composition to be administered to a subject in need of. Double Patenting 08-33 AIA The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 1-6 and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3,5,9,11,and 19 of copending Application No. 18/035,500. Regarding claim 1, the reference claim 1 recites a method for producing extracellular vesicles derived from a three-dimensional spheroid-type cell aggregate comprising:(a) preparing the three-dimensional spheroid-type cell aggregate by 3 dimensionally (3D)-culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; and (b) isolating the extracellular vesicles from the three-dimensional spheroid-type cell aggregate . Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on those of the instant application claim1. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 2111.02). Therefore, instant claim 1 is anticipated by co-pending application. Regarding claim 2, the reference claim 2 recites the method for producing the extracellular vesicles derived from the three- dimensional spheroid-type cell aggregate of claim 1, wherein the stem cells are at least one selected from the group consisting of mesenchymal stem cells, pluripotent stem cells, induced pluripotent stem cells and embryonic stem cells . Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations provided in the reference application of which stem cell population to choose from, reads on those of the instant application claim 2. Therefore, instant claim 2 is anticipated by co-pending application Regarding claim 3, the reference claim 3 recites the method for producing the extracellular vesicles derived from the three- dimensional spheroid-type cell aggregate of claim 1, wherein the 3D culture in step (a) is static culture Although the claims at issue are not identical, they are not patentably distinct from each other because the limitation on step (a) provided in the reference application of static culture reads on those of the instant application claim 3. Therefore, instant claim 3 is anticipated by co-pending application. Regarding claim 4, the reference claim 5 recites …of claim 1, wherein the 3D culture in step (a) is performed by dispersing and culturing the mesenchymal stem cells in the microwell at a density of 100 to 1000 cells/well . Although the claims at issue are not identical, they are not patentably distinct from each other because the range provided in the reference application for the density of the cells per microwell read on those of the instant application claim 4. Therefore, instant claim 1 is anticipated by co-pending application. Regarding claim 5, the reference claim 9 recites …of claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of miR-146a, miR-27a, miR-132, miR- 184, miR-210 and miR-301b, as compared with extracellular vesicles derived from a spheroid- type cell aggregate obtained by 3D-dynamic culture of mesenchymal stem cells . Although the claims at issue are not identical, they are not patentably distinct from each other because the expression of the group consisting of various miRs provided in the reference application read on those of the instant application claim 5. Therefore, instant claim 5 is anticipated by co-pending application. Regarding claim 6 , the reference claim 11 recites … of claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of Integrin 1/2 and Vascular Endothelial Page 4 of 8 Growth Factor Receptor 2 (VEGF/R2), as compared with extracellular vesicles derived from a spheroid-type cell aggregate obtained by 3D-dynamic culture of mesenchymal stem cells. Although the claims at issue are not identical, they are not patentably distinct from each other because the expression of genes provided in the reference application group reads on those of the instant application claim 6. Therefore, instant claim 6 is anticipated by co-pending application. Regarding claim 11, the reference claim 19 recites a method for reducing a donor variation of extracellular vesicles derived from a cell aggregate comprising:(a) preparing a three-dimensional spheroid-type cell aggregate by 3 dimensionally (3D)- culturing stem cells in a microwell with a diameter of 200 to 800 pm and a depth of 100 to 1000 pm; and (b) isolating the extracellular vesicles from the three-dimensional spheroid-type cell aggregate . Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on those of the instant application claim 11. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 52111.02). Therefore, instant claim 11 is anticipated by co-pending application. This is a provisional nonstatutory double patenting rejection. Claims 1-6,9, and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,4-6,10, and 11 of copending Application No. 18/289,532. Regarding claims 1 and 3 , the reference claim 1 recites a method for treating neurological diseases and damage comprising; (a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 m and a depth of 100 to 1000 m; and (b) 3D static culturing of the prepared three-dimensional spheroid-type cell aggregate in the microwell; c)preparing extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (b) by isolating extracellular vesicles from the three- dimensional spheroid-type cell aggregate; and (d) administering the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (c) to a subject in need thereof . Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on those of the instant application claim 1. Reference claim 1 recites static culturing of claim 3. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 52111.02). Therefore, instant claim 1 and 3 is anticipated by co-pending application. Regarding claim 2, the reference claim 2 recites … of claim 1, wherein the stem cells are at least one selected from the group consisting of mesenchymal stem cells, pluripotent stem cells, induced pluripotent stem cells and embryonic stem cells . Although the claims at issue are not identical, they are not patentably distinct from each other because the population of stem cells provided in the reference application read on those of the instant application claim 2. Therefore, instant claim 2 is anticipated by co-pending application. Regarding claim 4, the reference claim 4 recites … of claim 1, wherein the 3D culture in step (a) is performed by dispersing and culturing the mesenchymal stem cells in a microwell at a density of 200 to 600 cells/well. Although the claims at issue are not identical, they are not patentably distinct from each other because the density of cells per microwell for culturing provided in the reference application read on those of the instant application claim 4. Therefore, instant claim 4is anticipated by co-pending application. Regarding claim 5, the reference claim 5 recites …of claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of miR-27a, miR-132, miR- 146a, and miR-146b as compared with extracellular vesicles derived from spheroidal cell aggregates obtained by 3D dynamic culture of mesenchymal stem cells and extracellular vesicles derived from mesenchymal stem cells obtained by 2D culture. Although the claims at issue are not identical, they are not patentably distinct from each other because the expression of the an miR selected from the specific group provided in the reference application read on those of the instant application claim 5. Therefore, instant claim 5 is anticipated by co-pending application. Regarding claim 6, the reference claim 6 recites …of claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of vascular endothelial growth factor (VEGF), a brain-derived neurotrophic factor (BDNF), a brain-derived neurotrophic factor (FGF) and a brain-derived neurotrophic factor (NGF) as compared with extracellular vesicles derived from spheroidal cell aggregates obtained by 3D dynamic culture of mesenchymal stem cells and extracellular vesicles derived from mesenchymal stem cells obtained by 2D culture. Although the claims at issue are not identical, they are not patentably distinct from each other because the expression of the factors in the group provided in the reference application read on those of the instant application claim 6. Therefore, instant claim 6 is anticipated by co-pending application. Regarding claim 9, the reference claim 10 recites … wherein the extracellular vesicles derived from a three-dimensional spheroid-type cell aggregate are contained in food composition or pharmaceutical composition. Although the claims at issue are not identical, they are not patentably distinct from each other because the pharmaceutical composition of extracellular vesicles provided in the reference application read on those of the instant application claim 9. Therefore, instant claim 9 is anticipated by co-pending application. Regarding claim 10, the reference claim 11 recites an in vitro method for promoting neurogenesis comprising: (a) preparing three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm (b) 3D static culturing of the prepared three-dimensional spheroid-type cell aggregate in the microwell (c)preparing extracellular vesicles from the three-dimensional spheroid-type cell aggregate prepared in step (b); and(,d) administering the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (c) to in vitro cells. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on those of the instant application claim 10. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 52111.02). Therefore, instant claim 10 is anticipated by co-pending application. This is a provisional nonstatutory double patenting rejection. Claims 1,2,3,4,5,9,11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,3,4,5,9,10 of copending Application No. 18/862,694. Regarding claim 1, the reference claim 1 recites a method for wound healing or wound recovery comprising:(a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm;(b) preparing extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate by isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate; and(c) treating the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate prepared in step (b) to a subject in need thereof. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on those of the instant application claim 1. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 52111.02). Therefore, instant claim 1 is anticipated by co-pending application. Regarding claim 2 , the reference claim 2 recites … of claim 1, wherein the stem cells are at least one selected from the group consisting of mesenchymal stem cells, pluripotent stem cells, induced pluripotent stem cells, and embryonic stem cells . Although the claims at issue are not identical, they are not patentably distinct from each other because the limitations, including the population of stem cells provided in the reference application reads on those of the instant application claim 2. Therefore, instant claim 2 is anticipated by co-pending application. Regarding claim 3, the reference claim 3 recites …of claim 1, wherein the 3D culture in step (a) is a static culture. Although the claims at issue are not identical, they are not patentably distinct from each other because the limitation of step (a) as static culture provided in the reference application read on those of the instant application claim 3. Therefore, instant claim 3 is anticipated by co-pending application. Regarding claim 4, the reference claim 4 recites … of claim 1, wherein the 3D culture in step (a) is culturing mesenchymal stem cells dispensed into microwells at a density of 100 to 1,000 cells/well. Although the claims at issue are not identical, they are not patentably distinct from each other because the step (a) and the density of cells per microwell provided in the reference application read on those of the instant application claim 4. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 52111.02). Therefore, instant claim 4 is anticipated by co-pending application. Regarding claim 5, the reference claim 5 recites … of claim 1, wherein the extracellular vesicles highly express at least one selected from the group consisting of miR-146a, miR-27a, miR-132, miR-184, miR-210, and miR-301…. Although the claims at issue are not identical, they are not patentably distinct from each other because the expression of a at least one selected from group of miRs provided in the reference application read on those of the instant application claim1. Therefore, instant claim 5 is anticipated by co-pending application. Regarding claim 9 , the reference claim 9 recites … wherein the extracellular vesicles derived from the three-dimensional spheroid-type cell aggregate is contained in cosmetic composition, quasi-drug composition or pharmaceutical composition. Although the claims at issue are not identical, they are not patentably distinct from each other because the pharmaceutical composition limitation provided in the reference application read on those of the instant application claim 9. Therefore, instant claim 9 is anticipated by co-pending application. Regarding claim 11, the reference claim 10 recites a method for producing a composition for wound healing or wound recovery comprising extracellular vesicles derived from a three-dimensional spheroid-type cell aggregate comprising: (a) preparing a three-dimensional spheroid-type cell aggregate by 3-dimensionally (3D) culturing stem cells in a microwell with a diameter of 200 to 800 μm and a depth of 100 to 1000 μm; and (b) isolating extracellular vesicles from the three-dimensional spheroid-type cell aggregate. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on those of the instant application claim 1. The preamble of the co-pending claim does not structurally limit the invention and therefore lacks patentable weight (See, MPEP 52111.02). Therefore, instant claim 1 is anticipated by co-pending application. This is a provisional nonstatutory double patenting rejection. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 3:00pm M-F. 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. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. 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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. /CAROLINE M LARA/Examiner, Art Unit 1633 /ALLISON M FOX/Primary Examiner, Art Unit 1633 Application/Control Number: 18/289,530 Page 2 Art Unit: 1633 Application/Control Number: 18/289,530 Page 3 Art Unit: 1633 Application/Control Number: 18/289,530 Page 4 Art Unit: 1633 Application/Control Number: 18/289,530 Page 5 Art Unit: 1633 Application/Control Number: 18/289,530 Page 6 Art Unit: 1633 Application/Control Number: 18/289,530 Page 7 Art Unit: 1633 Application/Control Number: 18/289,530 Page 8 Art Unit: 1633 Application/Control Number: 18/289,530 Page 9 Art Unit: 1633 Application/Control Number: 18/289,530 Page 10 Art Unit: 1633 Application/Control Number: 18/289,530 Page 11 Art Unit: 1633 Application/Control Number: 18/289,530 Page 12 Art Unit: 1633 Application/Control Number: 18/289,530 Page 13 Art Unit: 1633 Application/Control Number: 18/289,530 Page 14 Art Unit: 1633 Application/Control Number: 18/289,530 Page 15 Art Unit: 1633 Application/Control Number: 18/289,530 Page 16 Art Unit: 1633 Application/Control Number: 18/289,530 Page 17 Art Unit: 1633 Application/Control Number: 18/289,530 Page 18 Art Unit: 1633 Application/Control Number: 18/289,530 Page 19 Art Unit: 1633 Application/Control Number: 18/289,530 Page 20 Art Unit: 1633 Application/Control Number: 18/289,530 Page 21 Art Unit: 1633 Application/Control Number: 18/289,530 Page 22 Art Unit: 1633