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 .
Status of the Claims
Claims 1-20 are pending (claim set as filed on 08/04/2026).
Applicant’s election without traverse of Group I directed to the method claims is again acknowledged. Claims 9-14 stand withdrawn as being directed to the non-elected product claims.
Therefore, only claims 1-8 and 15-20 are under examination.
Priority
This application is a CIP of PCT/JP2022/015780 filed on 03/30/2022, which has a foreign application to JP 2021-059860 filed on 03/31/2021.
Withdrawal of Rejections
The response and amendments filed on 07/08/2026 and 08/04/2026 (supplemental response) are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s response to arguments section.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Maintained Rejections
Claim Rejections - 35 USC §102, Anticipation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yoshida (US 2021/0054406 A1 - cited in the IDS filed on 09/29/2023).
Yoshida’s general disclosure relates to a method for producing cells having the desired substance introduced therein (see ¶ [0001], [0007]).
Regarding claim 1, Yoshida teaches “A method for producing cells having the desired substance introduced therein, the production method comprising the step of forming an aggregate of cells under conditions that permit transfection of the cells with the substance in a non-cell-adhesive container (step 1)” (see ¶ [0009] & Examples 1-2: Production of Cardiomyocytes from iPSCs-1). Yoshida teaches the cells are cardiomyocytes (see ¶ [0017], [0132]).
Regarding claims 2-3 pertaining to the container, Yoshida teaches “the non-cell adhesive container that can be used is a container with its surface not artificially treated (e.g., by coating with extracellular matrix or the like) for the purpose of improving adhesiveness to cells. … The term ‘non-cell-adhesive’ means that adherent cells do not adhere or rarely adhere to the container (e.g., less than 20%, preferably less than 10%, more preferably less than 1 % cells based on the total number of cells inoculated to the container adhere to the container) … The container can be a microplate, a petri dish (dish), a cell culture flask (a stirring flask, a shaker flask, etc.), a cell culture bag, a roller bottle, a bioreactor or a culture tank, etc. and is appropriately selected according to a production scale (e.g., 1 mL to 2000 L). In the present invention, particularly, a large-capacity (e.g., 100 mL to 2000 L) container may be suitably used” (see ¶ [0085]-[0087]).
Regarding claims 4-5 pertaining to the stirring, Yoshida teaches wherein the step C is performed under static culture of the cells (see ¶ [0037]). Yoshida further teaches “After the static culture, stirring culture may be performed in order to maintain the formed aggregate. The static culture period is not particularly limited, and can be, for example, on the order of 12 to 48 hours and is preferably on the order of 24 hours. The culture conditions are not particularly limited and can involve culture at approximately 37°C in the presence of 5% CO2. The stirring rate and time are appropriately set according to a cell density and the size of the culture container. Typically, the cells are left standing for 4 to 6 hours and then stirred at 25 rpm for 12 hours or longer. Excessive stirring or shaking places physical stress on the cells and also inhibits the maintenance of the aggregate. Thus, it is desirable to control the stirring rate so as to be able to uniformize medium components and the internal oxygen concentration of the medium and so as not to inhibit the maintenance of the aggregate” (see ¶ [0111]-[0112]).
Regarding claim 6 pertaining to the stem cell, Yoshida teaches pluripotency means the ability to be able to differentiate into tissues and cells having various different shapes and functions and to be able to differentiate into cells of any lineage of the 3 germ layers (see ¶ [0056]). Examples of the stem cells include pluripotent stem cells (see ¶ [0058]-[0063]).
Regarding claim 7 pertaining to the cell strainer, Yoshida teaches “the cell solution thus pipetted was passed through a cell strainer (Sterile Cell Strainer 40 μm, Thermo Fisher Scientific Inc.) to recover single cells” (see ¶ [0167], [0184], [0188]).
Regarding claim 8 pertaining to the cell concentration, Yoshida teaches “the number of microcarriers for use in cell culture is not particularly limited and is, for example, one microcarrier per ten cells. The amount of the microcarrier used in cell culture is not particularly limited and is, for example, 0.1 g of the microcarrier per 1x106 to 5x107 cells, preferably 0.1 g of the microcarrier per 2x107 to 3x107 cells” (see ¶ [0096]-[0097], [0156], [0168], [0174]).
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 07/08/2026 and 08/04/2026 (supplemental response) have been fully considered but they are not persuasive and deemed insufficient to overcome the prior art of record.
In response to Applicant’s argument (addressing page 7 of the remarks filed on 07/08/2026) that Yoshida teaches “After the static culture, stirring culture may be performed in order to maintain the formed aggregate” whereas the instant claims require stirring to cause formation of aggregates: this argument is not persuasive because first note that the prior art’s static culturing prequel step is allowed because of the claim’s transitional phrase of “comprising” which is open-ended and does not exclude additional, unrecited elements or method steps (MPEP 2111.03(I)). Moreover, Yoshida’s recitation of “stirring culture” infers that a cultivation step is still being performed because Yoshida’s ¶ [0052] discloses “The term ‘culture’ or ‘culturing’ means maintaining cells and/or allowing the cells to proliferate (grow) and/or differentiate out of tissue or the body, for example, in a dish, a petri dish, a flask, or a culture tank”. Thus, while the cell aggregates are being maintained, it will inherently continue to grow or proliferate as the stirring duration progresses. In other words, Yoshida’s maintenance of cell aggregates also includes further growth and aggregation of the cells.
In response to Applicant’s argument (addressing page 8 of the remarks filed on 07/08/2026) that claim 1 of the present application is very specific regarding the starting material for aggregate formation (single cell cardiomyocytes): this argument is not persuasive because Yoshida’s cells are subjected in a dispersed state to culture and, if necessary, detached from the microcarrier and dispersed in a step prior to step 1. The detachment treatment can adopt chemical treatment with an enzyme and a chelating agent, etc., physical treatment by pipetting, etc., and a combination thereof (see Yoshida at ¶ [0083]-[0084). Therefore, Yoshida teaches the starting material for aggregate formation.
New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC §103, Obviousness
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Yoshida.
Yoshida’s teachings are discussed above as it pertains to a method of producing cardiomyocyte spheroids.
Note that Yoshida teaches “the ‘cardiomyocytes’ mean cells expressing at least cardiac troponin (cTnT) or αMHC” (see ¶ [0132]).
However, Yoshida does not teach: wherein 70-95% or more of the cells in the suspension at the time of starting the culture are single cells (claims 15-18); or wherein cardiomyocytes separated into single cells are 50-95% or more cardiac troponin T positive cells (claims 19-20).
It would have been obvious to one of ordinary skill in the art to select and optimize the starting amount of single cells from the teachings of Yoshida. In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious (MPEP 2141.02(I)). Both the instant application and prior art are directed to mass-production or large scale production of cardiomyocyte at a commercial level (see background arts). Yoshida is not particularly limited nor restricted in regards to the amount of cells used for production (see, e.g., ¶ [0091]-[0103]). Therefore, the amount of starting material of single cells is within the purview of the ordinary artisan to select based upon the desired result of aggregates as Yoshida discloses the dispersion treatment can also be performed by an approach known in the art and can adopt, for example, chemical treatment with an enzyme and a chelating agent, etc., physical treatment by pipetting, etc., and a combination thereof (see Yoshida at ¶ [0084]). This is motivation for someone of ordinary skill in the art to practice or test the parameter values widely to find those that are functional or optimal which then would be inclusive or cover that values as instantly claimed. Absent any teaching of criticality by the Applicant concerning the amount of single cells, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable which can be met as a matter of routine optimization.
Conclusion
No claims were allowed.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGHI V NGUYEN whose telephone number is (571)270-3055. The examiner can normally be reached Mon-Fri: 9 - 3 pm (EST).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
