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 .
DETAILED ACTION
Claim status
Claims 1-20 are pending
Claims 18-20 are withdrawn
Claims 1-17 are under examination
Election/Restrictions
Applicant’s election of the following invention in the reply filed on 3/11/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-17, drawn to a method of making cardiomyocytes from EPSCs.
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Information Disclosure Statement
No information disclosure statement (IDS) has been submitted.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 16 is objected to because of the following informalities: instant claim uses the term “1640”, which should be amended to “RPMI 1640”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1, 5-9, and 15-17 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.
Claim 1 recites the method for preparing a cardiomyocyte, wherein the cardiomyocyte “is prepared from” an EPSC. However, instant claim recites no active steps in the claimed method. MPEP 2173.05 states that attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b). For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parteErlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).
Claims 5 and 6 recite the limitation that the method comprises a “rapid transition and transformation” of the cells. A claim may be rendered indefinite by reference to term of degree (see MPEP 2173.05(b), I). Specifically, when a term of degree is used in the claim, the examiner should determine whether the specification provides some standard for measuring that degree. Hearing Components, Inc. v. Shure Inc., 600 F.3d 1357, 1367, 94 USPQ2d 1385, 1391 (Fed. Cir. 2010); Enzo Biochem, Inc., v. Applera Corp., 599 F.3d 1325, 1332, 94 USPQ2d 1321, 1326 (Fed. Cir. 2010); Seattle Box Co., Inc. v. Indus. Crating & Packing, Inc., 731 F.2d 818, 826, 221 USPQ 568, 574 (Fed. Cir. 1984). In instant case, the specification does not provide some standard for measuring that degree (i.e., what constitutes a rapid transition and transformation). Dependent claims 7-9 are included in the basis of the rejection because they do not clarify what is a rapid transition and transformation.
Claim 5 contains the trademark/trade names “mTeSR”, “KnockOut”, and “B27”. Claim 6 contains the trademark/trade name “B27”. Claim 16 contains the trademark/trade name “B27”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe types of media and, accordingly, the identification/description is indefinite. Because this reagent was developed by the manufacturer at the time of the applicant’s invention under the trade names “mTeSR”, “KnockOut”, and “B27” and as a result is proprietary, which means what constitutes as these media can change, and these changes do not need to be disclosed by these companies to the public. Accordingly, the identification of the trade name is indefinite.
Claims 15 and 17 recite the limitation that the searching “preferably”. A claim may be rendered indefinite by reference to subjective term (see MPEP 2173.05(b), IV). Specifically, the term “preferably” is a subjective term which renders the claim indefinite. The term "preferably" is not defined by the claim(s), the specification does not provide a standard for some standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Appropriate correction is required.
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 1-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claim(s) 1-4 is/are directed to preparing a cardiomyocyte based on a natural process. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they are not substantially more.
Briefly summarized here, the guidance for patent subject matter eligibility cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to Step 1, Claims 1-4, are drawn to a process, a method for preparing a cardiomyocyte.
In regard to Step 2A prong one, this part of the eligibility analysis evaluates whether the claim recites a judicial exception. Claims 1 recites that the cardiomyocyte is prepared from an extended pluripotent stem cell (EPSC). Claim 2 similarly states the method comprises induced differentiation of the EPSC. Under its broadest reasonable interpretation consistent with the specification, the plain and ordinary meaning of this limitation requires an EPSC, which is a totipotent stem cell capable of giving rise to both embryonic and extra-embryonic tissues (e.g., placenta), such as the zygote and early blastomeres, and allowing them to form a complete organism. As this step simply requires the development of an embryo, the limitation falls into the “natural phenomena” grouping of judicial exception (see MPEP 2106.04(b)). Thus, the claim(s) are directed to the judicial exception of (a mathematical concept-type abstract idea, a mental process-type abstract idea, and a law of nature) (Step 2A, Prong One: YES).
In regard to Step 2A, prong two: this part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. In the present situation, Claims 1 and 2 recited no additional steps, and although Claims 3 and 4 recite the method step of inducing differentiation into cardiomyocytes through small molecule-based phased regulation of a Wnt signaling pathway, these molecules are recited with such a high degree of generality that they encompass naturally occurring Wnt signaling pathway molecules secreted during embryonic development. Thus, even when considering the elements in combination, the claim(s) as a whole do not meaningfully integrate the recited exception into a practical application (Step 2A, prong two: No).
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
As stated supra, additional elements such small molecule-based phased regulation of a Wnt signaling pathway were considered include naturally occurring molecules present in embryonic development in Step 2A, prong two. Consequently, for the reasons discussed above, the additional elements individually or in combination with the judicial exception do not provide an inventive concept; so, the claim as a whole does not amount to significantly more than the judicial exception. (Step 2B: NO).
For the reasons set forth above, the claims are not considered to recite something significantly different than a judicial exception and thereby are not directed to patent eligible subject matter.
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 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gao et al. (Nature Cell Bio, 2019, 21:687-699)
In regard to claims 1-4, Gao teaches a method for preparing an embryo (which comprises cardiomyocytes), wherein the cardiomyocytes are from ESPCS (p.700, Methods, In vivo chimera assay). Specifically, 26-28 day porcine embryos demonstrated and EPSCs transferred to the developing embryo contributed to multiple embryonic organs such as alpha-SMA positive tissues which include developing cardiomyocytes (p. 668,col 2, 2nd para., Fig. 2g, Supplemental Fig. 3). In regard to the method comprising small molecule-based phased regulation of a Wnt signaling pathway, these molecules are recited with such a high degree of generality that they encompass naturally occurring Wnt signaling pathway molecules secreted during embryonic development.
Accordingly, Gao anticipates instant claims.
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 1-5, 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., (US 11,028,369, filed 8/12/2016, patented 6/08/2021, prior art of record), in view of Lian et al., (PNAS, 2012, 109(27)E1848-E1857).
Deng teaches methods of making EPSCs, and suggests their differentiation into somatic cells that can be used to replace damaged organs such as the heart and myocytes thereof (col 20, last two para.). Thus, Deng reasonably suggests differentiating EPSCs into cardiomyocytes.
However, Deng is silent to a method of differentiating EPSCs into cardiomyocytes.
In regard to claims 1-5, Lian teaches method of differentiating stem cells into cardiomyocytes comprising the steps of culturing pluripotent cells in mTeSR1 for 5d (pre-conditioning at day -5); followed by inducing the pluripotent cells to differentiate into cardiomyocytes through a small molecule-based phased regulation comprising the steps of adding 12 mM of a small molecule CH compound such as CHIR99021 on day 0, and adding the Wnt signaling inhibitor IWP2 at 5 mM on day 3 (p.E1856, Methods, see Fig 6B, excerpt below).
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In regard to claims 7-9, Lian teaches the pluripotent stem cells were allowed to achieve confluence before being treating with the CH RPMI/B27-insulin at day 0 (p. E1856, Methods, 4th para.,).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have practice the method of preparing cardiomyocytes from ESPCs as suggested by Deng, and choose the method of differentiation as taught by Lain with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Lian because this method can achieve over 80% cTNT+ cardiomyocytes (see Fig. 6A).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 10, and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., (US 11,028,369), in view of Lian et al., (PNAS, 2012, 109(27)E1848-E1857), as applied to claim 4, in further view of Miyagawa et al. (WO 2019/163802, filed 2/20/2019, published 8/29/2019)
As stated supra, Deng in view of Lian make obvious a method of preparing cardiomyocytes comprising a small molecule phase induction of cardiac differentiation in a RPMI/B27 minus insulin media with a CH compound such as CHIR99021 at 12 mM and an IWP molecule such as IWP2 at 5 mM.
However, Lian is silent to combining the inhibitor of WNT production (IWP) with an inhibitor of WNT regulation (IWR).
In regard to claim 10, Miyagawa teach a muti-step method of differentiating pluripotent stem cell to cardiomyocytes comprising a media comprising both a IWP2 at 10 mM molecule and an IWR1 molecule at 4 mM (p. 23, Example 1, [0067].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a multi-step method of differentiating ESPCs to cardiomyocytes comprising a small molecule based media comprising IWP as suggested by Deng and Lian, and combine an IWR1 molecule as taught by Miyagawa with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so as taught by Miyagawa because it is prima facie obvious to combine two agents each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to claims 13-14, as stated supra, Miyagawa teaches the small molecule phase induction of cardiac differentiation uses IWR1 at 4 mM. In regard to claim 14, MPEP 2144.05(I) states that a prima facie case of obviousness exists where the claimed amounts do not overlap with the prior art but are merely close. In instant case, the concentrations of 8 and 7.5 are so close that prima facie one skilled in the art would have expected them to have the same properties.
In regard to claim 15, as stated supra, Lian teaches the small molecule phase induction of cardiac differentiation uses IWP2 at 5 mM. Thus, the ordinary skilled artisan would have been motivated to do so since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
In regard to claim 16, as stated supra, Lian teaches the small molecule phase induction of cardiac differentiation is in a RPMI/B27 minus insulin.
In regard to claim 17, as stated supra, Lian teaches the small molecule phase induction of cardiac differentiation is from day 0 to day 5 (i.e., about 5 days).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., (US 11,028,369), in view of Yeo et al., (Sci Rep. 2016, 6, 31068).
Deng teaches methods of making EPSCs, and suggests their differentiation into somatic cells that can be used to replace damaged organs such as the heart and myocytes thereof (col 20, last two para.). Thus, Deng reasonably suggests differentiating EPSCs into cardiomyocytes.
However, Deng is silent to a method of differentiating EPSCs into cardiomyocytes.
In regard to claims 1-5, Yeo teaches method of differentiating stem cells into cardiomyocytes comprising the steps of culturing pluripotent cells in mTeSR1 for 5d (pre-conditioning at day -5); followed by inducing the pluripotent cells to differentiate into cardiomyocytes through a small molecule-based phased regulation comprising the steps of adding 8 mM of a small molecule CH compound such as CHIR99021 on day 0, and adding the Wnt signaling inhibitor IWR-1 at 5 mM on day 3 (p.9, Methods, 3rd para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have practice the method of preparing cardiomyocytes from ESPCs as suggested by Deng, and choose the method of differentiation as taught by Yeo with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Yeo because this method can achieve over 93% cTNT+ cardiomyocytes (p. 6, Results, 1st para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., (US 11,028,369), in view of Yeo et al., (Sci Rep.2016, 6, 31068), as applied to claim 4, in further view of Ludwig et al. (Nat Biotech, 2006, 2:185-187) and Yao et al. (PNAS, 2006, 103(18)6907-6912).
As stated supra, Deng in view of Yeo make obvious a method of preparing cardiomyocytes comprising a preconditions phase of culturing the stem cells in TeSR1 media.
However, Yeo is silent to the components of the mTeSR1 media.
Nevertheless, Ludwig discloses that TeSR1 media is composed of a DMEM/F12 base + bFGF + TGFbeta (p. 185, Introduction, 3rd para.).
However, Yeo is silent to further including B27 in the media comprising DMEM/F12 base + bFGF + TGFbeta.
Yao teaches a media for the culturing of stem cells comprising DMEM/F12 based “N2-CDM” media with a B27 supplement with insulin (p. 6911-6912, Monolayer culture of hESCs in the N2/B27-CDM provides a defined platform for directed differentiation studies, Materials and Methods).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of preconditioning ESPCs in a DMEM/F12 +bFGF + TGFbeta (i.e., TeSR1) media as suggested by Deng and Yao as evidence by Ludwig, and combine B27 as taught by Yeo with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so as taught by Yeo because the B27 supplemented media basic platform for further development of
more efficient and defined culture conditions for hESCs, as well as characterization of hESC self-renewal and directed differentiation (p. 6911, Discussion, last para.).
In regard to claim 6, as stated supra, Yao teaches the B27 comprises insulin, and Yeo teaches the preconditioning is for 5 days.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 10-14, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al., (US 11,028,369), in view of Yeo et al., (Sci Rep.2016, 6, 31068), as applied to claim 4, in further view of Miyagawa et al. (WO 2019/163802, filed 2/20/2019, published 8/29/2019)
As stated supra, Deng in view of Yeo make obvious a method of preparing cardiomyocytes comprising a small molecule phase induction of cardiac differentiation is in a RPMI/B27 minus insulin with a CH compound such as CHIR99021 at 8 mM and an IWR molecule such as IWR1 at 5 mM .
However, Yeo is silent to combining the inhibitor of WNT regulation (IWR) with an inhibitor of WNT production (IWP).
In regard to claim 10, Miyagawa teach a multi-step method of differentiating pluripotent stem cell to cardiomyocytes comprising a media comprising both a IWP2 at 10 mM molecule and an IWR1 molecule at 4 mM (p. 23, Example 1, [0067]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a multi-step method of differentiating ESPCs to cardiomyocytes comprising a small molecule based media comprising IWR as suggested by Deng and Yeo and combine an IWP2 molecule as taught by Miyagawa with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so as taught by Miyagawa because it is prima facie obvious to combine two agents each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
In regard to claims 11-12, as stated supra, Yeo teaches the CHIR is 8 mM. Furthermore, in regard to claim 12, MPEP 2144.05(I) states that a prima facie case of obviousness exists where the claimed amounts do not overlap with the prior art but are merely close. In instant case, the concentrations of 8 and 7.5 are so close that prima facie one skilled in the art would have expected them to have the same properties.
In regard to claims 13-14, as stated supra, Yeo teaches the small molecule phase induction of cardiac differentiation uses IWR1 at 5 mM. Thus, the ordinary skilled artisan would have been motivated to do so since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
In regard to claim 16, as stated supra, Yeo teaches the small molecule phase induction of cardiac differentiation is in a RPMI/B27 minus insulin.
In regard to claim 17, as stated supra, Yeo teaches the small molecule phase induction of cardiac differentiation is from day 0 to day 5 (i.e., about 5 days).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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