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. 1. Claims 1 – 20 are pending. Election/Restrictions 2. Applicant’s election without traverse of Group I (claims 1 – 11 and 16 – 19) in the reply filed on 10/28/2025 is acknowledged. 3. Claims 12 – 15 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/28/2025. 4. Claims 1 – 11 and 16 – 19 are under consideration. Priority 5 . This application claims priority to JP2020-120695 filed on 07/14/2020. 6 . Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application. Information Disclosure Statement 7 . The information disclosure statement (IDS) submitted on 07/08/2025, 08/02/2024 and 01/13/2023 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Drawings 8 . The drawings filed on 01/13/2023 are acknowledged. Specification 9 . The use of the term Accutase , Accumax , TrypLE , Dispase , Trizol , and Countess, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Claim Objections 10 . Claim 1 is objected to because of the following informalities: in line 2, “having a history of stabilization culture” should read “after a period of stabilization culture” to provide antecedent basis for recitation of “the period for the stabilization culture” in claim 4 . Appropriate correction is required. 1 1 . Claim 10 is objected to because of the following informalities: in line 2 – 3, “ as a liquid to be used for the suspension culture medium” should read “a suspension culture medium” because “ the suspension culture medium” lacks antecedent basis . 1 2 . Claim 18 is objected to because of the following informalities: in line 2, “as a liquid to be used for the suspension, culture medium” should read “a suspension culture medium” because “the suspension, culture medium” lacks antecedent basis. 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. 1 3 . Claims 1 , 3, 5 – 11, and 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. 1 4 . Regarding claim 1, the metes and bounds of “having a history of stabilization culture ” are unclear. Applicant’s specification discloses “stabilization culture refers to a culture performed after the thawing of the cells and before the start of the production of cardiomyocyte spheroids” (page 9, 0018) , however it is unclear “having a history” refers to a certain time of stabilization culture. For the purpose of applying prior art, “having a history of stabilization culture” is interpreted as stabilization culture for any period of time prior to suspension culture. Claims 3 and 5 – 11 are also rejected as they depend from claim 1 and do not clarify the grounds of rejection. 1 5 . Claim 5 recites the limitation "the time taken to produce cardiomyocytes" in line 1. There is insufficient antecedent basis for this limitation in the claim. 1 6 . Claim 6 recites the limitation "the container" in 2. There is insufficient antecedent basis for this limitation in the claim. 1 7 . Claim 7 recites the limitation "the container" in line 2. There is insufficient antecedent basis for this limitation in the claim. 1 8 . Claim 9 recites the limitation "the container" in line 2. There is insufficient antecedent basis for this limitation in the claim. 1 9 . Regarding claim 9, it is unclear what “rotated in the range of 10 mm or more” means in relation to “flow under suspension” recited in claim 1. Further, the claim recites “the range” but does not recite a range as “10 mm or more” does not have an upper limit. For the purpose of applying prior art, claim 9 is interpreted as suspension culturing on an orbital shaker where the orbit is 10 mm or more. 2 0 . Claim 16 recites the limitation "the stabilization culture" in line 2. There is insufficient antecedent basis for this limitation in the claim. In claims 1 and 2, “to flow under suspension conditions” might be unclear. I’m not sure what is meant by this. If you understand it, don’t make the rejection. Claim Interpretation 21 . For the purpose of applying prior art, “having a history of stabilization culture” of claim 1 is interpreted as stabilization culture for any period of time prior to suspension culture. 22 . For the purpose of applying prior art, “flow under suspension conditions” of claims 1 and 2 is interpreted as dynamic culturing conditions and not static culturing. 23 . For the purpose of applying prior art, “a non-annular container” of claim 2 is interpreted to include a petri dish, a 6-well plate, a 12-well plate, and a flask as shown in Applicant’s Figure 1 and at page 6, 0013 of Applicant’s specification. 24 . For the purpose of applying prior art, “substantially flat-bottomed” of claim 6 and 17 is interpreted to exclude round-bottom and V-bottom plates and include a petri dish based on Applicant’s specification at page 6, 0013 and Figure 1. 25 . For the purpose of applying prior art, claim 9 is interpreted as suspension culturing on an orbital shaker where the orbit is 10 mm or more. 26 . For the purpose of applying prior art, claim 10 and 18 are interpreted as suspension culturing for 26 hours or more in a medium that does not contain one or more components selected from the group consisting of insulin, transferrin, selenium, bFGF , EGF, PDGF-BB, and ET-1 based on Applicant’s specification at page 3, para. 4 and page 13, 0026. 27 . For the purpose of applying prior art, the “wherein” limitation of claims 11 and 19 are not given patentable weight as the limitation “derived from a pluripotent stem cell(s)” is a product-by-process limitation (see MPEP 2113). Claim Rejections - 35 USC § 102 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. 28 . Claim(s) 2 and 17 – 19 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Bartholoma ( Bartholomä , P., et al. Journal of biomolecular screening 10.8 (2005): 814-822 ), hereinafter Bartholoma . Claim 2 is drawn to a method for producing cardiomyocyte spheroids, comprising an aggregation step of allowing dissociated cardiomyocytes to flow under suspension conditions in a non-annular container to aggregate the cells. Regarding claims 2 , 17, and 1 9 , Bartholoma teaches a method of forming cardiomyocyte spheroids by reaggregating (“an aggregation step” of claim 2 ) a suspension of cardiomyocytes that were dissociated from hearts of chicken embryos (“ dissociated cardiomyocytes” of claim 2 and 19 ) in petri dishes (“non-annular container” of claim 2 ; “ substantially flat-bottomed” of claim 17 ) on a gyratory shaker (“flow under suspension conditions” of claim 2 ) ( page 814, right col. last para.; page 815, left col. para. 1; page 816, right col. para. 2; Figure 2B – D; page 818, right col. para. 2 and last para.). Regarding claim 18 , Bartholoma teaches culturing in culture medium that does not contain any of the recited components recited in claim 18 for up to 22 days (page 815, left col. para. 1; Figure 1). Therefore, Bartholoma anticipates claims 2 and 17 – 19 . 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. 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 . 29 . Claim (s) 1 – 11 and 16 – 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bartholoma ( Bartholomä , P., et al. Journal of biomolecular screening 10.8 (2005): 814-822 ), hereinafter Bartholoma in view of Xu ( Xu, Chunhui , et al. Regenerative medicine 6.1 (2011): 53-66. ), hereinafter Xu . Bartholoma anticipates claims 2 and 1 7 – 19 as set forth above. Bartholoma does not teach “the stabilization culture is adherent culture” of claim 16 . Regarding claims 1 , 6 – 8 and 11 , Bartholoma teaches a method of forming cardiomyocyte spheroids by reaggregating (“an aggregation step” of claim 1 ) a suspension of cardiomyocytes that were dissociated from hearts of chicken embryos (“ dissociated cardiomyocytes” of claim 1 and 1 1 ) in 35-mm petri dishes (“substantially flat-bottomed” of claim 6 ; claim 7 ) on a gyratory shaker (“flow under suspension conditions” of claim 1 ) at a rotation speed of 75 rpm (claim 8 ) at a 12.3 mm radius (claim 9 ) ( page 814, right col. last para.; page 815, left col. para. 1; page 816, right col. para. 2; Figure 2B – D; page 818, right col. para. 2 and last para.). Bartholoma does not teach “having a history of stabilization culture” of claim 1 . Regarding claim 5 , Bartholoma teaches the cardiomyocytes formed spheroids at 24 hours and day 3 spheroids were used for testing isoproterenol ( Figure 1; page 815, left col. para. 1; page 818, right col. para. 2). Regarding claim 1 0 , Bartholoma teaches culturing in culture medium that does not contain any of the recited components recited in claim 18 for up to 22 days (page 815, left col. para. 1; Figure 1). Bartholoma does not teach “having a history of stabilization culture” of claim 1 or “adherent culture” of claim 3 or “the period of stabilization culture is 4 hours of more” of claim 4 or “the stabilization culture is adherent culture” of claim 16 . However, Bartholoma teaches the method of reaggregation in rotation culture produces a 3D model of embryonic cardiomyocytes that are electrophysiologically active and allows for testing of the effects of β-adrenergic receptor agonists (page 814, right col. para. 2; page 816, right col. para. 2; page 817, right col. para. 2; page 818, right col. para. 2; page 820 , right col. para. 2 – 3 ). Bartholoma teaches therapeutically directed studies profit from the use of 3D cell aggregates, allowing the investigation of the effects of various novel drug-mediated therapies (page 814, left col. para. 1 ; page 8 20 , right col. para. 3 ). Regarding “having a history of stabilization culture” of claim 1 and “adherent culture” of claims 3 and 16 , and “the period of stabilization culture is 4 hours of more” claim 4 , Xu teaches a method of differentiating human embryonic stem cells ( hESCs ) to cardiomyocytes , cryopreservation of the cardiomyocytes, thawing of the cryopreserved cardiomyocytes, and culture of the thawed cardiomyocytes on Matrigel (“adherent culture” of claim 3 and 16 ) where the majority of the thawed cells attached and recovered their contractility 1 – 2 days post-thawing ( “having a history of stabilization culture” of claim 1 and claim 4 ) (page 3, para. 1; page 4, para. 1 ; Figure 5 ). Xu teaches the thawed and cultured cardiomyocytes showed the expected electrophysiological phenotype and predicted AP responses to all of the evaluated pharmacological inhibitors (page 7, para. 4). Xu teaches the cardiomyocytes contained beating cells appearing as both 3D cell clumps and as flat contracting regions (page 5, para. 2). Xu teaches hESCs represent a novel cell source to treat diseases such as heart failure and for use in drug screening (Abstract). Xu teaches the method produces cardiomyocytes of high quality that can be efficiently generated and cryopreserved, which represents a step forward in the application of these cells to human clinical use or drug discovery (Abstract). Xu teaches hESC -derived cardiomyocytes may help prevent progression of heart diseases and/or restore contractile function in damaged hearts, and serve as cellular models for drug testing (page 2, para. 1 – 2). Xu teaches because of limited supplies of human cardiomyocytes, assessment of cardiotoxicity is traditionally carried out in models that use nonhuman cardiac cells (page 2, para. 2). Xu teaches hESCs represent a more appropriate and reliable cell resource for cardiotoxicity testing and they have the ability to differentiate in large quantities to cardiomyocytes with relevant physiological phenotypes, which may translate to reproducible and accurate evaluations of targets in a more cost-effective manner (page 2, para. 2). Xu teaches the method achieves high yields of viable cardiomyocytes that can be cryopreserved and thawed, and that successfully survive in vitro as well as after transplantation in infarcted hearts (page 2, last para.). It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to substitute the chicken cardiomyocytes of Bartholoma with the hESC -derived cardiomyocytes of Xu that had been cryopreserved, thawed, and adherent cultured to arrive at the claimed method where the dissociated cardiomyocytes have a history of stabilization adherent culture. One would have been motivated to make such a substitution as Xu teaches because of limited supplies of human cardiomyocytes, assessment of cardiotoxicity is traditionally carried out in models that use nonhuman cardiac cells and Xu teaches hESCs represent a more appropriate and reliable cell resource for cardiotoxicity testing and they have the ability to differentiate in large quantities to cardiomyocytes with relevant physiological phenotypes, which may translate to reproducible and accurate evaluations of targets in a more cost-effective manner. One would have a reasonable expectation of success in carrying out the substitution as Bartholoma teaches the method of reaggregation in rotation culture produces a 3D model of embryonic cardiomyocytes that are electrophysiologically active and allows for testing of the effects of β-adrenergic receptor agonists. Conclusion No claims allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ZANNA M BEHARRY whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0411 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 8:45 am - 5:45 pm . 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. /Z.M.B./ Examiner, Art Unit 1632 /PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632