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. Priority This application is national stage entry under 35 U.S.C. 371 of PCT/EP2022/060665 (filed on 04/22/2022), which claims priority to SWEDEN 2150516-9 (filed on 04/23/2021). Election/Restrictions Applicant’s election without traverse of FILLIN "Enter claim indentification information" \* MERGEFORMAT Group I in the reply filed on FILLIN "Enter mail date of the reply." \* MERGEFORMAT 02/06/2026 is acknowledged. Claims 1-8, 13-16, and 23-24 read on the elected group. Claim Status Claims 1-16 and 23-26 are pending. Claims 9-12 and 25-26 are withdrawn based on the election without traverse. Claims 1-8,13-16, and 23-24 have been considered on the merits. Claim Rejections - 35 USC § 112 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 appl icant regards as his invention. Claim FILLIN "Enter claim indentification information" \* MERGEFORMAT 13 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 claim 13, the phrase “ the composition is used to coat a support…” renders the claim indefinite because it is unclear what the phrase, specifically the term ‘coating’ encompasses in the context of the claims. When the limitations set forth in claim 13 are read into the independent claim 1, which claim 13 is dependent of, the scope of the claim is unclear and therefore indefinite. Coating support such as cell culture dish, beads, or microcarriers with the composition of human laminin 5α chain is not unclear, but the necessity of doing so in the context of the method of claim 1 and therefore claim 13, is indefinite. There is no basis for needing to coat the support objects with the composition for the method, at least it is not clear in the claims. For examination purposes with respect to prior art, any method that cultures MSCs on culture dishes or any of the support objects in claim 13 that is coated with human laminin 5α chain, in any manner and meeting the recited active method steps will be considered within the metes and bounds of claim 13. Appropriate correction or clarification is required. 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. Claims FILLIN "Pluralize claim, if necessary, and then insert the claim number(s) which is/are under rejection." \d "[ 1 ]" 1-7,13-16, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over FILLIN "Insert the prior art reference(s) relied upon for the obviousness rejection." \d "[ 2 ]" Simonson et al (US 2019/0112578 A1) and in view of FILLIN "Insert the additional prior art reference(s) relied upon for the obviousness rejection." \d "[ 4 ]" De Francisco et al (US 2021/0113625 A1) . Simonson et al disclosed a method for culturing mesenchymal stem (stromal) cells (MSCs), such that the MSCs are multipotent and immunomodulatory potential (See, Abstract). Regarding claims 1,2,14, and 15, Simonson et al disclose d an invention drawn to a method for culturing MSCs with maintained or enhanced multipotency and/or immune-modulatory potential. The method comprises culturing the MSCs under hypoxic or normoxic conditions in the presence of at least one laminin α5 chain and/or at least one laminin α4 chain (See, ¶0023). The method disclosed by Simonson et al can also include an agent with Wnt canonical pathway to generate Isl1 + (See, ¶0026). Simonson et al disclosed that the multipotent Isl1 + cells can produce a population of extracellular vesicles that can have polypeptide abundance (See, ¶0038). Simonson et al further states that the characteristics of Isl1 + of producing extracellular vesicles ( EVs ) and modulate immune response are important for the clinical application of the invention (See, ¶0038). Simonson et al does not teach the isolation of the EVs from cell culture medium. De Francisco et al disclosed a method to prepare extracellular vesicles (EVs) from mesenchymal stem cells (MSCs), a composition of extracellular vesicles obtained from the method and composition comprising EVs that can be used as a medicament (See, Abstract). De Francisco et al teaches that EVs isolated from MSCs have emerged as a novel therapeutic and are much safer to administer than stem cells (i.e. MSCs) (See, ¶0007-0009). De Francisco et al disclosed a method to produce a composition comprising EVs of mesenchymal stem cells. First step is to culture MSCs obtained from biological tissue or fluid to generate undifferentiated mesenchymal stem cells. Second step is to contact the cultured undifferentiated MSCs with culture medium containing growth factors or inflammatory mediators, to generate mesenchymal stem cells of interest to produce EVs (See, ¶0034-0037). De Francisco et al further disclosed 6 methods of isolating the EVs from the MSC culture, including differential centrifugation (See, ¶0094-99), density gradient centrifugation (See, ¶0100-0101), size exclusion chromatography (See,¶0102-0103), ultrafiltration (See,¶0104-0105), polymer based precipitation (See,¶0106-0107), and immunological separation (See,¶0108-0109). It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of Simonson et al to comprise isolating the EVs generated from the culturing of MSCs as taught by De Francisco et al. One would be motivated to make this modification because Simonson et al teaches there is clinical relevance to EVs produced by their method and De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer than stems cells such as MSCs. Therefore, the isolation of the EVs from cell culture medium is obvious in light of Simonson et al in view of De Francisco et al because De Francisco et al discloses methods of isolation of EVs that can be generated from the method of Simonson et al . Further, one would have a reasonable expectation of success because isolation of the EVs from the cell culture of MSCs from De Francisco et al could be readily done to isolate the EVs generated from the culturing of MSC with laminin α5 of the method of Simonson et al. As Simonson et al teaches the method with MSCs and that the culturing method produces EVs, and De Francisco et al teaches method of isolating EVs that includes ultracentrifugation, claims 2, 14, and 15 are included in this rejection. Therefore, claims 1, 2, 14, and 15 are rendered obvious over Simonson et al in view of De Francisco et al. Regarding claim 3 and 4, following the discussion of claim 2 above, Simonson et al discloses that the method of the invention comprising the step of culturing MSCs and the MSCs are obtainable from bone marrow, Wharton’s jelly, perinatal tissue, cord blood, amniotic tissue, adipose tissue, etc. (See, ¶0025). As Simonson et al discloses where the MSCs can be derived from and where or how the MSCs are differentiated from is included in the rejections because claim 4 is a product by process claim (See, MPEP 2113). Regarding claim 5, 6, and 7, following the discussion above of claim 1, Simonson et al disclosed that the culturing method of the present invention of MSC with at least one laminin comprising α5 chain can be laminin 511, 521,523 or any combination of said laminins (See, ¶0053). Simonson et al also discloses that any cell culture growth substratum or cell culture medium additive comprising laminin 511 or 521 or 523 can be used for the culturing (See, ¶0053). The laminin protocol was tested in the experimentation section of Simonson et al, it was concluded that optimal ratio of laminins α5 for the culturing is 25% α5 to promote attachment and growth (See, ¶0071). This reads on the limitation of claim 5, such that the substratum for cell culture comprises at least 10% of one polypeptide ; limitation of claim 6, such that the polypeptide of human laminin α5 chain is laminin-511, laminin-521, laminin-522 or laminin-523 ; lastly on the limitation of claim 7, such that polypeptide human laminin α5 is either laminin-521 . Regarding claim 13, following the discussion about claim 1 above, Simonson et al discloses that for the context of the invention, the laminins used are coated on the cell/tissue culture equipment (See, ¶0032). This reads on the limitation of claim 13, wherein the composition is used to coat cell culture dishes , since the composition of claim 1 comprising polypeptide human laminin α5 chain. Regarding claim 16, following the discussion of claim 1 above, Simonson et al disclosed that the cells in the invention can be in a pharmaceutical composition comprising the cells per the invention combined with at least one pharmaceutically acceptable excipient for medicinal use, such as solubilized agent (See, ¶0064). Simonson et al does not teach a pharmaceutical composition of extracellular vesicles in combination with at least one pharmaceutically acceptable constituent. De Francisco et al further disclosed that the invention relates to the use of EVs for the manufacture of a medicament intended for treating subjects suffering from ischemic disease or disorder of the circulatory system (See,¶0132). It is disclosed that to enhance the efficacy and facilitate the administration of the medicament of the invention, the composition with the EVs may be mixed with any agent or biologically compatible material or device (See,¶0144). The EVs or the compositions containing EVs may be applied with a medical device such as, a stent, endoscope or syringe (See, ¶0144). Pharmacologically acceptable agents to mix with EVs or compositions containing EVs include, water, alcohols, polyols, glycerol, vegetable oils, etc. (See, ¶0145). It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of Simonson et al to comprise having the pharmaceutical composition to comprise EVs with a pharmacologically acceptable agent as taught by De Francisco et al. One would be motivated to make this modification because Simonson et al teaches there is clinical relevance to EVs produced by their method and De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer than stems cells such as MSCs. Therefore, pharmaceutical composition comprising EVs in combination with at least one pharmaceutically acceptable constituent is obvious in light of Simonson et al in view of De Francisco et al because De Francisco et al discloses methods of isolating EVs that can be generated from the method of Simonson et al and generating a pharmaceutical composition with a pharmacologically acceptable agent. Further, one would have a reasonable expectation of success because De Francisco et al teaches that EVs are a safer therapeutic to administer than stem cells such as MSCs . Therefore, claim 16 are rendered obvious over Simonson et al in view of De Francisco et al. Regarding claim 23 and 24, following the discussion about claim 15 above, Simonson et al disclosed that stents or other medical devices for implantation into a human or animal body can be coated with laminin α5 or α4, and the stent may be implanted with or without MSCs, progenitor cells to be further differentiated (See, ¶0062). Simonson et al does not teach a medical device coated with EVs or what the medical device is. De Francisco et al further disclosed that the invention relates to the use of EVs for the manufacture of a medicament intended for treating subjects suffering from ischemic disease or disorder of the circulatory system (See,¶0132). It is disclosed that to enhance the efficacy and facilitate the administration of the medicament of the invention, the composition with the EVs may be mixed with any agent or biologically compatible material or device (See,¶0144). The EVs or the compositions containing EVs may be applied with a medical device such as, a stent, endoscope or syringe (See, ¶0144). It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of Simonson et al to comprise coating a medical device with extracellular vesicles as taught by De Francisco et al because a stent is a type of graft and therefore a medical device . One would be motivated to make this modification because Simonson et al teaches there is clinical relevance to EVs produced by their method and De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer or use as a coating than stems cells such as MSCs. Therefore, a medical device coated with EVs and the medical device such that it is a graft is obvious in light of Simonson et al in view of De Francisco et al because De Francisco et al discloses methods of isolating EVs that can be generated from the method of Simonson et al and coating a medical device with the composition comprising EVs . Further, one would have a reasonable expectation of success because De Francisco et al teaches that EVs are a safer therapeutic to administer or use as a coating than stem cells such as MSCs. Therefore, claims 1-7, 13-16, and 23-24 are rendered obvious over Simonson et al in view of De Francisco et al. Claim FILLIN "Pluralize claim, if necessary, and then insert the claim number(s) which is/are under rejection." \d "[ 1 ]" 8 is rejected under 35 U.S.C. 103 as being unpatentable over FILLIN "Insert the prior art reference(s) relied upon for the obviousness rejection." \d "[ 2 ]" Simonson et al and De Francisco et al as applied to claims FILLIN "Pluralize claim, if necessary, and then insert the claim number(s) which is/are under rejection." \d "[ 3 ]" 1-7,13-16, and 23-24 above, and further in view of FILLIN "Insert the additional prior art reference(s) relied upon for the obviousness rejection." \d "[ 4 ]" Doi et al (The journal of biological chemistry, 2002) . The teachings of Simonson et al and De Francisco et al are set forth above. Regarding claim 8, following the discussion of claim 1 above, Simonson et al teaches a method comprises culturing the MSCs under hypoxic or normoxic conditions in the presence of at least one laminin α5 chain and/or at least one laminin α4 chain (See, ¶0023) and De Francisco et al teaches 6 methods of isolating the EVs from the MSC culture, including ultrafiltration (See,¶0104-0105) , which rendered claim 1 obvious. Simonson et al and De Francisco et al do not teach where the polypeptide of laminin α5 comprises amino acid SEQ ID NO: 1. Doi et al teaches the roles of laminin 10 with endothelial cells and how the molecule could be useful in improving the biocompatibility and reendothelialization of vascular grafts (See, Abstract) . Doi et al submitted laminin α5 to GenBank with accession number AF443072 (See, Methods) . The amino acid sequence of accession number AF443072 is a 100% match with SEQ ID NO: 1 when aligned (See, appendix). It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of Simonson et al and De Francisco et al to comprise laminin α5 with amino acid sequence of AF443072 as taught by Doi et al. One would be motivated to make this modification because it would be advantageous to use a sequence that is well known in the art. Therefore, the method of claim 1, wherein the polypeptide comprising human laminin α5 chain with amino acid sequence SEQ ID NO: 1 is obvious in light of Simonson et al and of De Francisco et al in view of Doi et al because it is advantageous to use a sequence known in the art. Further, one would have a reasonable expectation of success because Doi et al teaches that the molecule of human laminin α5 could be useful in improving biocompatibility and reendothelialization of vascular grafts. Therefore, claim 8 is rendered obvious over Simonson et al and De Francisco et al in view of Doi et al. Double Patenting 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 . Claim FILLIN "Pluralize \“Claim\” if necessary, insert \“is\” or \“are\” as appropriate, and insert the claim number(s) which are under rejection." s 1- 4, 6-8 , 14 -16,23-24 a re rejected on the ground of nonstatutory double patenting as being unpatentable over claim FILLIN "Pluralize \“Claim\” if necessary, and insert the claim number(s) of the U.S. Patent." s 1,2,3 of U.S. Patent No. FILLIN "Insert the number of the primary reference patent." 10226487B2 in view of FILLIN "Insert the secondary reference." De Francisco et al (US 2021/0113625 A1) . The teachings of De Francisco et al are set forth above. Regarding claims 1 -4,6 - 8, 14 and 15 , the reference claim 1 recites, a method for deriving a multipotent Is11+ cell, comprising the step of:(i) culturing a mesenchymal cell in the presence of at least one laminin comprising an a5 chain, and in a medium comprising at least one agent which activates the Wnt canonical pathway . Reference claim 2 recites, wherein the mesenchymal cell is a cardiac mesenchymal cell, a bone marrow mesenchymal cell … . Reference claim 3 recites, wherein the at least one laminin comprising an a5 chain is selected from the group consisting of laminin 511, laminin 521, and a combination of laminin 511 and laminin 521 . These claims read on the method of claim 1 of the instant application but are missing the step of isolating the EVs generated from culturing MSCs of the method. De Francisco et al further disclosed 6 methods of isolating the EVs from the MSC culture, including ultrafiltration (See,¶0104-0105) . It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of reference patent (US 10226487B2 ) to comprise isolating the EVs generated from the culturing of MSCs as taught by De Francisco et al. One would be motivated to make this modification because De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer than stems cells such as MSCs. Therefore, the isolation of the EVs from cell culture medium is obvious in light of reference claims in view of De Francisco et al because De Francisco et al discloses methods of isolation of EVs that can be generated from the method of Reference patent . Further, one would have a reasonable expectation of success because isolation of the EVs from the cell culture of MSCs from De Francisco et al could be readily done to isolate the EVs generated from the culturing of MSC with laminin α5 of the method of reference patent . Regarding the sequence of human laminin 5α chain of instant claim 8, the sequence is well known in the art and it would be advantageous to use that with the method, therefore is included in the rejection. Therefore, claims 1-4,6,7,8,14 and 15 are rendered obvious over U.S. Patent No. 10226487B2 in view of De Francisco et al (US 2021/0113625 A1). Regarding claim 16, 23, and 24, following the discussion above about claim 15, De Francisco et al further disclosed that the invention relates to the use of EVs for the manufacture of a medicament intended for treating subjects suffering from ischemic disease or disorder of the circulatory system (See,¶0132). It is disclosed that to enhance the efficacy and facilitate the administration of the medicament of the invention, the composition with the EVs may be mixed with any agent or biologically compatible material or device (See,¶0144). The EVs or the compositions containing EVs may be applied with a medical device such as, a stent, endoscope or syringe (See, ¶0144). Combined with the reference claims 1,2, and 3, it would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of reference patent (US 10226487B2) to comprise isolating the EVs generated from the culturing of MSCs and creating a pharmaceutical composition or coating a medical device with the isolated EVs as taught by De Francisco et al. One would be motivated to make this modification because De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer than stems cells such as MSCs. Therefore, the isolation of the EVs from cell culture medium is obvious in light of reference claims in view of De Francisco et al because De Francisco et al discloses methods of isolation of EVs that can be generated from the method of reference patent. Therefore, claims 1-4, 6-8,14-16,23-24 are unpatentable over U.S. Patent No. FILLIN "Insert the number of the primary reference patent." 10226487B2 in view of FILLIN "Insert the secondary reference." De Francisco et al (US 2021/0113625 A1) . Claim FILLIN "Pluralize \“Claim\” if necessary, insert \“is\” or \“are\” as appropriate, and insert the claim number(s) which are under rejection." s 1-8,1 3 -16, and 23-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. FILLIN "Insert the number of the primary reference patent." 10240124B2 in view of FILLIN "Insert the secondary reference." De Francisco et al (US 2021/0113625 A1) . The teachings of De Francisco et al are set forth above. Regarding claims 1, claim 1 of the reference patent recites, a method for maintaining stem cells, comprising: plating the stem cells on a substrate comprising a laminin and a cadherin, wherein the laminin is an intact protein or a protein fragment; and exposing the stem cells to a cell culture medium comprising at least 0.3 mM of albumin-wherein the laminin islaminin-521;wherein the cadherin is e-cadherin; and wherein the weight ratio of the laminin-521 to the e-cadherin is from 5:1 to 10:1 or from 5:1-15:1 . The limitations of reference claim 1 read on the method of claim 1 of the instant application because laminin-521 is a human laminin α5 chain polypeptide and MSCs are stem cells but are missing the step of isolating the EVs generated from culturing MSCs of the method. De Francisco et al further disclosed 6 methods of isolating the EVs from the MSC culture, including ultrafiltration (See,¶0104-0105) . It would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of reference patent (US FILLIN "Insert the number of the primary reference patent." 10240124B2 ) to comprise isolating the EVs generated from the culturing of MSCs as taught by De Francisco et al. One would be motivated to make this modification because De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer than stems cells such as MSCs. Therefore, the isolation of the EVs from cell culture medium is obvious in light of reference claims in view of De Francisco et al because De Francisco et al discloses methods of isolation of EVs that can be generated from the method of Reference patent. Further, one would have a reasonable expectation of success because isolation of the EVs from the cell culture of MSCs from De Francisco et al could be readily done to isolate the EVs generated from the culturing of MSC with laminin α5 (laminin 521) of the method of reference patent. The combination of the teachings of reference claim 1 and De Francisco et al set forth read on instant claims 1-2,4, 6-7, and 14-15. Regrading claim 3, where MSCs are derived from, does not change the properties of MSCs, therefore it is included in the rejection and read on by the teachings set forth. Regarding claim 5, the reference claim provides a ratio of laminin 5α for culturing, that reads on instant claim 5. Regarding the sequence of human laminin 5α chain of instant claim 8, the sequence is well known in the art and it would be advantageous to use that with the method, therefore is included in the rejection. Regarding claim 13, reference claim 1 recites that the substrate on plating for stem cell culturing have laminin 521, which reads on the instant claim 13 of the composition of human laminin 5α chain to be coated on to cell culture dish. Regarding claim 16, 23, and 24, following the discussion above about claim 15, De Francisco et al further disclosed that the invention relates to the use of EVs for the manufacture of a medicament intended for treating subjects suffering from ischemic disease or disorder of the circulatory system (See,¶0132). It is disclosed that to enhance the efficacy and facilitate the administration of the medicament of the invention, the composition with the EVs may be mixed with any agent or biologically compatible material or device (See,¶0144). The EVs or the compositions containing EVs may be applied with a medical device such as, a stent, endoscope or syringe (See, ¶0144). Combined with the reference claim 1, it would have been prima facie obvious to a person having ordinary skill in the art to have modify the method of reference patent (US FILLIN "Insert the number of the primary reference patent." 10240124B2 ) to comprise isolating the EVs generated from the culturing of MSCs and creating a pharmaceutical composition or coating a medical device with the isolated EVs as taught by De Francisco et al. One would be motivated to make this modification because De Francisco et al teaches that EVs isolated from MSC culturing has emerged as a therapeutic, as they are safer to administer than stems cells such as MSCs. Therefore, the isolation of the EVs from cell culture medium is obvious in light of reference claims in view of De Francisco et al because De Francisco et al discloses methods of isolation of EVs that can be generated from the method of reference patent. Therefore, claims 1-8,1 3 -16, and 23-24 are unpatentable over U.S. Patent No. FILLIN "Insert the number of the primary reference patent." 10240124B2 in view of FILLIN "Insert the secondary reference." De Francisco et al (US 2021/0113625 A1) . Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Caroline M Lara whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-4262 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 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, FILLIN "SPE Name?" \* MERGEFORMAT Christopher Babic can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (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. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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 APPENDIX SEQUENCE ALIGNMENT Query, ‘Qy’ (SEQ ID NO 1) vs Database, ‘Db’ (GenBank Accession No. AF443072)