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 .
Claim status
In the reply filed 27 March 2026, Applicant has amended claims 1 and 8. Claim 7 is stand withdrawn. Therefore, claims 1-8 are herein pending.
Election/Restrictions
Applicant previously elected of Group I, claims 1-6 and 8 drawn to a method for producing a cell population comprising cardiomyocytes in the reply filed on 18 November 2025. Applicant did not distinctly and specifically point out the hypothetical errors in the restriction requirement with an election that mailed on 18 November 2025. Therefore, the election response filed on 18 November 2025 will be treated without traverse (MPEP § 818.01(a)).
Claims 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-6, and 8 are under current examination.
Priority
This application was filed 09/16/2022, 201X and is a 371 application of PCT/ JP2021/011232, filed March 18, 2021, which claims the benefit of Japanese Patent Application No. 2020-050269, filed March 19, 2020, and Japanese Application No. 2020-145097, filed August 28, 2020. Thus, the earliest possible priority for the instant application is March 19, 2020.
Maintained Title Objection
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. See MPEP 606.01
The following title is suggested:
“Method For Producing and Purifying Cardiomyocytes.”
Modified Claim Rejections - 35 USC § 102
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.
Claims 1, 5, 6, and 8 are stand rejected in modified form under 35 U.S.C. 102(a)(1) as being anticipated by Hajjar et al.et al., (US20160271183A1; published on Sep. 22, 2016; cited in PTO892; hereinafter “Hajjar”). This rejection is maintained for reasons of record and current applicant’s amendments.
Regarding claims 1, 5, 6, and 8, Hajjar discloses a method for producing cardiomyocyte cell population (abstract) comprising:
(1) a step of bringing a histone deacetylase inhibitor into contact with a cell population containing cardiomyocytes and cells other than cardiomyocytes (e.g., endothelial and smooth muscle ([0011], [0017], claim 15, of Hajjar) and the cell population being obtained by culturing induced pluripotent stem cells in a medium for cardiomyocyte differentiation ([0011], [0013] of Hajjar). Hajjar further teaches that at least 70 ventricular cardiomyocytes (hPSC-VCM) are obtained from each non-terminally differentiated human pluripotent stem cell ([0013], claim 6 of Hajjar). Therefore, POSTA would have reasonably anticipated the cell population comprise cardiomyocytes and undifferentiated pluripotent stem cells, and
(2) a step of culturing the cell population ([0013] of Hajjar).
Hajjar further discloses this method is generate ample quantities of highly purified autologous, or heterologous, cardiomyocytes from iPSCs, wherein this protocol is producing 80-98% purity CM without any enrichment and/or purification step (limitation of instant claim 8) ([0006], [0009], [0012] of Hajjar).
Accordingly, Hajjar anticipates the instant claims 1, 5, 6, and 8.
Modified 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 of this title, 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 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.
Claims 1-6, and 8 are stand rejected in modified under 35 U.S.C. 103 as being unpatentable over Hajjar et al.et al., (US20160271183A1; published on Sep. 22, 2016; cited in PTO892; hereinafter “Hajjar”), in view of Ping et al., (JP2017104091A, published on: June 15, 2017; cited in PTO892; see attached translated copy; hereinafter “Ping”). This rejection is maintained for reasons of record and further explained below.
Regarding claims 1, 5, 6, and 8, Hajjar discloses a method for producing cardiomyocyte cell population (abstract) comprising:
(1) a step of bringing a histone deacetylase inhibitor into contact with a cell population containing cardiomyocytes and cells other than cardiomyocytes (e.g., endothelial and smooth muscle ([0011], [0017], claim 15, of Hajjar) and the cell population being obtained by culturing induced pluripotent stem cells in a medium for cardiomyocyte differentiation ([0011], [0013] of Hajjar). Hajjar further teaches that at least 70 ventricular cardiomyocytes (hPSC-VCM) are obtained from each non-terminally differentiated human pluripotent stem cell ([0013], claim 6 of Hajjar). Therefore, POSITA would have reasonably expected that the cell population comprise cardiomyocytes and undifferentiated pluripotent stem cells, and
(2) a step of culturing the cell population ([0013] of Hajjar).
Hajjar further discloses this method is generate ample quantities of highly purified autologous, or heterologous, cardiomyocytes from iPSCs, wherein this protocol is producing 80-98% purity CM without any enrichment and/or purification step (limitation of instant claim 8) ([0006], [0009], [0012] of Hajjar).
With respect to claim 2, Hajjar is silent to the cell population is contacted with the histone deacetylase inhibitor in the step (1) on or after 7 days, However, such was known in the prior art.
Regarding claims 2-4, Ping discloses a method of differentiating cardiomyocyte comprising the step of culturing cell population for 8 to 20 days under specific condition ([0040] of Ping) and for cardiomyocyte induction contacting cell population with HDAC inhibitor (i.e., FK228, an inhibitor against class I histone deacetylase) [0072] at least after 8 days of differentiation ([0074] of Ping).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the cardiomyocyte culture method of Hajjar and include HDAC inhibitor FK228 in the medium as taught by Ping with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Ping because it will produce cTnT-positive cardiomyocytes (example 4, [0072] of Ping), cardiomyocytes can be separated by using a property characteristic thereof, or a marker specific thereto (paragraph [0048] of Ping), therefore, pure cardiomyocyte cells population can be used to treating heart diseases such as heart failure ([0055] of Ping). The POSITA would have had a reasonable expectation of success in combining the teachings of Hajjar and Ping because each of these teachings both successfully generated cardiomyocyte. Therefore, the products and method as taught by Hajjar view of Ping would have been prima facie obvious over the products and method of the instant application.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 27 March 2026 are acknowledged.
Regarding the rejection under 35 U.S.C. §102, the Applicant argues that Hajjar's experimental data demonstrate that pluripotency markers are eliminated well before the maturation protocol involving HDAC inhibitor treatment begins. Hajjar states that "transcript expression of the pluripotency markers OGT4 and Nanog decreased time-dependently, and rapidly became undetectable by days 4-5 (FIG. 2)" during the course of its differentiation protocol. This is significant because Hajjar conveys that its differentiation protocol continues until at least day 8 (i.e., several days after pluripotency markers disappear), after which an HDAC inhibitor may be added. Therefore, applicant argues that Hajjar expressly teaches that undifferentiated pluripotent stem cells are absent from the cell population at the time the HDAC inhibitor is applied. See remark p. 5 1-2nd ¶.
In response to applicant's argument on the maturation of cardiomyocytes, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Therefore, applicant's arguments have been fully considered but they are not persuasive. In here, Hajjar discloses a method for producing cardiomyocyte cell population (abstract) comprising a step of bringing a histone deacetylase inhibitor into contact with a cell population containing cardiomyocytes and cells other than cardiomyocytes (e.g., endothelial and smooth muscle ([0011], [0017], claim 15, of Hajjar) and the cell population being obtained by culturing induced pluripotent stem cells in a medium for cardiomyocyte differentiation ([0011], [0013] of Hajjar). Hajjar further teaches that at least 70 ventricular cardiomyocytes (hPSC-VCM) are obtained from each non-terminally differentiated human pluripotent stem cell ([0013], claim 6 of Hajjar). Therefore, POSITA would have reasonably expected that the cell population comprise cardiomyocytes and undifferentiated pluripotent stem cells.
Regarding the rejection under 35 U.S.C. §103, the Applicant argues that the claimed method employs an HDAC inhibitor to selectively eliminate undifferentiated pluripotent stem cells from a mixed cell population, thereby purifying the cardiomyocytes. This is neither taught nor suggested by Hajjar, the method of which excludes undifferentiated pluripotent stem cells from HDAC treatment. See remark p. 6 4th ¶.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e selectively eliminate undifferentiated pluripotent stem cells from a mixed cell population) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that the Ping disclosure discusses conversion of somatic cells to cardiomyocytes, in which characterizes the method as including "culturing somatic cells" optionally in the presence of a HDAC inhibitor. See remark p. 7 2nd ¶.
In response to applicant's argument, MPEP 2145 remarks that 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In here, Ping provides a method for directly and efficiently inducing mesenchymal stem cells from somatic cells in a short period of time without artificial gene transfer, further comprising the step of differentiating the MSCs that can be used for treatment and other purposes ([0007]-[0009] of Ping). Furthermore, Ping teaches to autonomously beating cardiomyocytes emerge by culturing the somatic cells under HDAC for 8 to 20 days ([0040] of Ping). Therefore, POSITA would have been motivated at the time of filing to include HDAC inhibitor FK228 in the medium as taught by Ping because it will produce cTnT-positive cardiomyocytes (example 4, [0072] of Ping), cardiomyocytes can be separated by using a property characteristic thereof, or a marker specific thereto (paragraph [0048] of Ping), therefore, pure cardiomyocyte cells population can be used to treating heart diseases such as heart failure ([0055] of Ping). Accordingly, POSITA would have had a reasonable expectation of success in combining the teachings of Hajjar and Ping because each of these teachings both successfully generated cardiomyocyte.
Conclusion
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.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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