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 .
This action is in response to the papers filed May 26, 2026.
Claims 1-23 are pending in the application.
Applicant’s election without traverse of Group I (Claims 1-7, 12-13, and 15-19) in the reply filed on 05/26/2026 is acknowledged.
Claims 8-11, 14 and 20-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 05/26/2026.
Therefore, claims 1-7, 12-13, and 15-19 are examined on the merits. Claims 1, 2, 6, 7, 15, 16 and 19 are independent claims.
Priority
The present application is a CIP of national stage filing of International Application No. PCT/JP2021/038071 filed October 14 2021.
Applicant’s claim for the benefit of a prior-filed Japanese application JP2020-173581 filed October 14, 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is October 14, 2020.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 2 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof, and vice versa.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 15-19 are rejected under 35 U.S.C. 101 because the claimed invention is
directed to a judicial exception (i.e. product of nature) without significantly more.
Claim 15 recites “myocardial stem/progenitor cells obtained by culturing cardiomyocytes in the presence of ROCK inhibitor.”
Myocardial stem/progenitor cells are a product of nature.
Claim 16 recites “an exosome or secretome derived from cardiomyocytes cultured in the presence of a ROCK inhibitor.”
Exosomes and secretomes are products of nature.
Claim 19 recites “a fibrosis suppressor or defiberizing agent, comprising ROCK inhibitor, cardiomyocytes cultured in the presence of a ROCK inhibitor, or the exosome and secretome according to claim 16 as an active ingredient.”
Exosomes and secretomes are products of nature.
A three part inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101 for process claims that involve laws of nature. See Subject Matter Eligibility Guidance.
This inquiry comprises answering:
Step 1: Is the claimed invention directed to one of the four statutory patent-eligible
subject matter categories: process, machine, manufacture, or composition of matter?
Step 2A:
Prong one: Does the claim recite or involve one or more judicial exceptions? Judicial exceptions include abstract ideas, laws of nature/natural principles, natural phenomena, and natural products; and
Prong two: Whether the additional elements integrate the exception into a practical application? Does the additional element apply, rely or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Step 2B: Does the claim as a whole recite something significantly different than the
judicial exception(s)?
In the instant application,
With respect to step 1, the claimed invention is directed to a product.
With respect to step 2A prong one, the claimed invention recites myocardial progenitor cells, exosomes and secretomes which are products of nature.
With respect to prong two of the analysis, the claimed invention further recites a
pharmaceutical composition for suppressing fibrosis wherein the cardiac progenitor cells or exosome and secretome are an active ingredient. This is not an integration of a practical application as there are no administration steps. Furthermore, there are no additional elements listed, merely an intended use for the cells, exosome or secretome and the potential to utilize as an active ingredient. The other dependent claims such as 17 and 18 broadly claim miRNA which does not distinguish the cells from its natural counterpart. Therefore, additional limitations do not impose a meaningful limitation on the judicial exception.
With respect to prong 2B, claims 15-19 do not include additional elements that are
sufficient to amount to significantly more than the judicial exception as there are no additional
elements.
Therefore, claims 15-19 are rejected as being directed to a judicial reception.
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 applicant regards as his invention.
Claims 3-5 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.
Claims 3 and 4 are rejected for reciting the term “and/or.” It is unclear what the metes and bounds of this term, as “and” could be interpreted in claim 3 to include only the culture time period, or the culture time and expression of markers, or, “or” would imply that the findings are in the alternative. The same rationale applies to the markers of claim 4.
Appropriate correction is required.
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 1-2, 7, 12-13, and 15-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao (Cardiovascular Research (2019)115,343–356) as evidenced by Xuan (Hindawi, Stem Cells International, Volume 2019, Article ID 3726392)
Regarding claims 1, 2, and 12, Zhao teaches a method of culturing cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) with a ROCK inhibitor such as Y27623 (i.e. (1 R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl)cyclohexanecarboxamide) (Abstract, Methods and Results; p. 344).
Regarding claim 7, as the claim does not define the “recovering” active step, it is interpreted that the culture media of Zhao which is obtained through the method steps of claims 1 and 2 of culturing cardiomyocytes in the presence of a ROCK inhibitor meets the preparing a secretome or exosome as these components are in the culturing conditioned media.
Regarding claim 13, Zhao teaches the iPSCs which are differentiated to cardiomyocytes are human cells (p. 344, 1st column). Therefore, the cardiomyocytes are human cardiomyocytes.
Regarding claims 15 and 16, as Zhao teaches culturing cardiomyocytes in the presence of a ROCK inhibitor as discussed above, it is interpreted that the cells of Zhao read on the resulting myocardial stem/ progenitor cells and the media obtained comprises exosomes and secretomes derived from said culture.
Regarding claim 17 and 18, as evidenced by Xuan. Xuan teaches cardiac progenitor cells secreted extracellular vesicles (EV) comprise miRNAs such as miR-373 (abstract). Therefore, through Y-27632 culture of hiPSC-CM comprising exosomes and secretomes derived from said culture, inherently comprise miRNA which target genes such as miR-373, miR-367, miR-520, miR-548ah, and miR-548q (p. 2, 2nd column; Figure 3). Previous studies have reported that miR-373 targets the TGFB signaling pathway (p. 8, 1st column). Therefore, it is interpreted as miR-373 targets a gene involved in a TGFB1 signaling pathway.
Regarding claim 19, as there are no additional elements in the composition other than the cardiomyocytes cultured in the presence of the ROCK inhibitor as in the method of claim 1 or the exosome or secretome according to claim 16, it is interpreted that Zhao additionally reads on this claim limitations.
Therefore, the invention is anticipated by Zhao.
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.
Claims 2-6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (Cardiovascular Research (2019)115,343–356) in view of Dong (Eur J Pharmacol 746: 186-197, 2015)
Regarding claims 2-5, Zhao teaches a method of culturing cardiomyocytes with a ROCK inhibitor such as Y27623 (i.e. (1 R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl)cyclohexanecarboxamide) for 12 hours (Abstract, Methods and Results; p. 344). Moreover, Zhao teaches expression of phosphorylated myosin light chain 2 (i.e. MYL2 or MLC2) is reduced by the Y27623 treatment (p. 346 ; Figure 3; Supplemental Material). Therefore the maturation marker is reduced.
However, Zhao does not teach that the cardiomyocytes are cultured with a ROCK inhibitor for more than a month (claim 3) or that myocardial cell progenitor markers are higher as a result of said culture duration (Claim 5).
Dong teaches polydatin as a means of inhibiting ROCK activity via suppressing intracellular oxidative stress and compares polydatin to other ROCK inhibitors such as Y27623 (p. 187, 1st column). Moreover, Dong further teaches that polydatin has been utilized at durations of 1 and 3 months and that it has a potent antihypertrophic effect in vitro and in vivo and reduces the increase of intracellular reactive oxygen species levels (p. 191, 2nd paragraph; p. 195-196, bridging paragraph; p. 196, last full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to culture Zhao’s cardiomyocytes with a ROCK inhibitor for a duration longer than a month as taught by Ke and Dong with a reasonable expectation of success. An artisan would have been motivated to utilize the ROCK inhibitor of Zhao in the cell culture for more than a month as Dong teach that long term ROCK inhibitor usage for over a month results in beneficial effects such as reducing the increase of intracellular reactive oxygen species levels (p. 191, 2nd paragraph).
Moreover, as each and every limitation is taught by Zhao, the same method steps would yield the same predictable results of cardiomyocytes modulating expression of specific markers in response to ROCK inhibitors.
Regarding claim 6, Zhao teaches that Rock inhibitors are widely utilized to protect stem/progenitor cells (p. 344; 1st column). Therefore, it would have been obvious to one of ordinary skill in the art to utilize the ROCK inhibitor for Zhao for the maintenance culture of myocardial stem/ progenitor cells.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Conclusion
No claims are allowed.
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/ALEXANDRA F CONNORS/ Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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