DETAILED ACTION The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Status of Claims Claims 1-24 as preliminarily amended are currently pending and subject to an election requirement. Election/Restrictions During a telephone conversation with Janice Kugler DeYoung on 2/19/2026, a provisional election was made without traverse to prosecute the invention of Group I and presently clams 1, 2, and 4-16 . Affirmation of this election must be made by applicant in replying to this Office action. Claim s 3 and 17-24 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. REQUIREMENT FOR UNITY OF INVENTION As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art. The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e). When Claims Are Directed to Multiple Categories of Inventions: As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories: (1) A product and a process specially adapted for the manufacture of said product; or (2) A product and a process of use of said product; or (3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or (4) A process and an apparatus or means specifically designed for carrying out the said process; or (5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process. Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c). Restriction is required under 35 U.S.C. 121 and 372. This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1. In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted. Group I , claims 1, 2, and 4-16 , drawn to a method of generating pre-epicardial cells. Group II , claim 3 , drawn to drawn to a method of generating pre-epicardial cells and cardiomyocytes. Group III , claim s 17 and 1 9 , drawn to a composition comprising pre-epicardial cells. Group IV , claim 1 8 , drawn to a composition comprising pre-epicardial cells and cardiomyocytes. Group V , claims 20-24 , drawn to a method of treating a subject who has or is at risk of developing cardiovascular disease by administering pre-epicardial cells made from induced pluripotent stem cells. Claims 17-19 are product-by-process claims. The patentability of product-by-process claims depends only on the structure of the claimed composition or a ny struct ural differences imparted to the final product by method steps in a product-by-process claim. See M.P.E.P. § 2113. In the instant case and absent evidence to the contrary , a prima facie case exists that the cells claimed in the product-by-process claims is substantially or completely identical to the cells made by other methods. For the purposes of restriction, claims 18 and 19 are read as composition of matter claims for the statutory class of invention. See M.P.E.P. § 2106. The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: Groups I - V lack unity of invention because even though the inventions of these groups require the technical feature of a composition comprising pre-epicardial cells , this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Bao et al. ( Nat Biomed Eng (2016), 1:0003, 24 page author manuscript + appended supplemental information; Reference U) (see p5, subheading “Molecular characterization of hPSC-derived epicardial cells” ). Therefore, restriction is necessitated between Groups I-V. Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention . The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention. Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention. Joint Inventors Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i). Rejoinder The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined. In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01. 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. Claims 1, 2, and 4-16 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. The term “ about ” in claim s 1, 2, and 7-12 is a relative term which renders the claim indefinite. The term “ about ” 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. Correction is required. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim s 1, 2, and 7-11 recites several instances of ranges but then also recites “preferable” ranges which are the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In so much that claims 2 and 4-16 depend from claim 1 and do not resolve the point of confusion, these claims must be rejected with claim 1 as indefinite. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim s 1, 2, 4 - 8, 10- 12, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Bao et al. ( Nat Biomed Eng (2016), 1:0003, 24 page author manuscript + appended supplemental information ; Reference U ) Bao teaches a method of generating a population of pre-epicardial cells (e.g. pro-epicardium or pro-epicardial cells ), the method comprising: providing a population of induced pluripotent stem cells (iPSCs), culturing the population of cells at a density of about 10 0,000-250,000 cells per c m 2 (i.e. 1-2.5 x 10 7 cells per mm 2 ) (p9 -10 , paragraph starting “Cardiac progenitor induction via modulation of canonical Wnt signaling”), performing the following steps in order: (a) treating the cells with a first RPMI medium comprising a Wnt signaling activator and lacking serum (i.e. 1-9 µM CHIR99021 ) for about 1 day in the absence of insulin, (b) replacing the first medium of step (a) with a second medium comprising insulin for about 24 hours (p10, paragraph starting “Epicardial cell generation via activation of canonical Wnt signaling” ), and (c) treating the cells with up to 100 ng/ml Bone Morphogenetic Protein 4 (BMP4) or 2 µM Retinoic Acid ( RA ) (p3, subheading “Wnt/β-catenin signaling regulates epicardial specification” and Table S1 , reading in-part on claim 1 , and reading on claims 4, 5, 7, 8, and 12. Bao teaches adding a 2.5-5 µM WNT inhibitor (i.e. IWP2) (p9-10, paragraph starting “Cardiac progenitor induction via modulation of canonical Wnt signaling”), reading on claims 2 and 11. Ba o teaches RPMI/B27 medium (p9-10, paragraph starting “Cardiac progenitor induction via modulation of canonical Wnt signaling”), reading on claim 6. Bao teaches that pro-epicardium is WT1+, TBX18+, and ALDH1A2+ ( p5, “Molecular characterization of hPSC-derived epicardial cells”), reading on claims 14 and 15. Bao teaches that the pro-epicardial cells are capable of forming functional cardiomyocyte (CM) aggregates (the paragraph spanning p4-5), reading on claim 16. Regarding claim 1, Bao does not teach a cell density of about 5,000-500,000 cells per mm 2 . However, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, Bao teaches that a cell density of about 100,000-250,000 cells per c m 2 (i.e. 1-2.5 x 10 7 cells per mm 2 ) is effective to generate cardiac progenitor cells and pro-epicardial cells Bao’s methods of differentiating iPSCs. Thus, the burden is shifted back to establish criticality of the claimed cell density range by objective evidence. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed. Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Bao as applied to claim 1 above, and further in view of Jennbacken et al. ( Int. J. Mol. Sci. 2019, 20, 6037; 16 pages; Reference V ). The teachings of Bao are relied upon as set forth above. Regarding claim 9, Bao does not teach adding VEGF at a concentration of about 2-7 ng/ml. Jennbacken teaches VEGF-A enhances the proliferation of iPSC- derived cardiac progenitor cells in a dose-dependent manner and with a maximal effect observed at about 1 x 10 -7 M (i.e. 100 nM) (Fig. 2E and p3, paragraph starting “Active proteins, based on…”), reading on claim 9. Regarding claim 8, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the VEGF-A of Jennbacken to the methods of generating pro-epicard i al cells of Bao. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because iPSC-derived cardiac progenitor cells and methods of differentiation therein. The skilled artisan would have been motivated to do so because Jennbacken teaches that the addition of VEGF-A would be predictably advantageous to improve the proliferation Bao’s iPSC-derived cardiac progenitor cells and which are an intermediate cell type in Bao’s methods of generating pro-epicardial cells. Regarding the VEGF concentration of claim 8, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, Jennbacken teaches that a VEGF-A concentration up to about 1 x 10 -7 M (i.e. 100 nM) is effective to improve the proliferation of iPSC-derived cardiac progenitor cells. Thus, the burden is shifted back to establish criticality of the claimed VEGF concentration range by objective evidence. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Bao as applied to claim s 1 and 2 above, and further in view of Ya n et al. ( Scientific Reports (201 9) 9:1295, 12 pages ; Reference W ). The teachings of Bao are relied upon as set forth above. Regarding claim 13, Bao does not teach IWP4. Yan teaches methods of differentiating induced pluripotent stem cells (iPSCs) into cardiovascular spheroids, the method comprising contacting the iPSCs with IWP4 (i.e. a species of WNT inhibitor) (Fig. 1B), reading on claim 13. A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the IWP2 of Bao with the IWP4 of Yan, because IWP2 and IWP4 are both explicitly taught as being useful for THE SAME PURPOSE as species of WNT inhibitors in methods of iPSC differentiation into cardiac cells . Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc. , 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout , 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”). Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed. Conclusion No claims are allowed. No claims are free of the art. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT SEAN C BARRON whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-5111 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 7:30am-3:30pm EDT/EST (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 Sharmila Landau can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-0614 . 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. /Sean C. Barron/ Primary Examiner, Art Unit 1653