This office action is intended to supersede the previous office action to correct the finality of office action by adding paragraph 21 below.
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 .
Application Status
The Amendments and Remarks filed 18 June 2026 have been entered. Claims 1-16 and 29-33 have been cancelled. Claims 17 and 46 is amended. Claims 17-28 and 34-46 are pending. Claims 25-27 remain withdrawn as being drawn to a nonelected invention. Claims 17-24, 28 and 34-46 are being examined on the merits.
Any objection or rejection not reiterated herein has been overcome by applicant’s claim amendments.
Priority
This application is a 371 PCT of JP2019/023599 filed 06/14/2019. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. JP2018-115025, filed on 06/15/2018. 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.
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 17-24, 28 and 34-46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature/natural phenomenon and a mental process without significantly more. This rejection is maintained and modified to address applicant’s claim amendments. Claim 17 recites a method of measuring the expression level and/or the promoter activity of at least one gene selected from the group consisting of ESRG, SFRP2 and CNMD in cells, comprising measuring the expression level and/or the promoter activity of said at least one gene in cells in a population with differentiated and undifferentiated cells, wherein the detection of a decrease in the expression of said at least one gene is an indication of a reduction of residual undifferentiated cells in the population, and the method excludes measuring the expression level and/or the promoter activity of NANOG. Claim 44 teaches a method of detecting undifferentiated cells at a detection sensitivity of 0.1% or less, comprising measuring the expression level and/or the promoter activity of at least one gene selected from the group consisting of ESRG and CNMD in a differentiated cell population, wherein the differentiated cell population comprises hepatic endoderm cells, differentiated mesodermal cells, or ectodermal cells. Claim 45 recites a method of measuring the expression level and/or the promoter activity of ESRG gene in cells, comprising measuring the expression level and/or the promoter activity of ESRG gene in cells in a population with differentiated and undifferentiated cells, wherein the detection of a decrease in the expression of ESRG gene is an indication of a reduction of residual undifferentiated cells in the population.
The claims recite at least one step or act and therefore falls within the statutory category of a process. The claims are directed to the judicial exception of a law of nature/natural phenomenon and abstract idea. This judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not include additional elements, when combined separately and in combination, that are sufficient to be markedly different than the judicial exception.
Subject Matter Eligibility Test for Products and Processes
Step 1 – Is the Claim to a Process, Machine, Manufacture, or Composition of Matter? YES
Claims 17, 44 and 46 are directed to a method measuring the expression level and/or the promoter activity of or a method of detecting undifferentiated cells comprising measuring the expression level and/or the promoter activity of at least one gene selected from the group consisting of ESRG, SFRP2 and CNMD in differentiated cell populations. The claim is a process, which is a statutory category.
Step 2A, Prong One – Does the Claim Recite a judicial exception? YES
The claims recite ‘measuring the expression level and/or the promoter activity of a gene selected from the group consisting of ESRG, SFRP2 and CNMD…in a population with differentiated and undifferentiated cells wherein the detection of a decrease in the expression of said at least one gene is an indication of a reduction of residual undifferentiated cells in the population”; and “a method of detecting undifferentiated cells”. Shi (Shi et al. Biochemical and Biophysical Research Communications 460 (2015) 130e135; previously cited) teaches that ESRG expresses abundantly in undifferentiated human embryonic stem cell hESC (pg. 131, col. 1, para 1]. Benvenisty (US 2013/0309769 A1; previously cited) teaches that SFRP2 and LECT1 (also known as CNMD) are expressed in hESC [0036]. For a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products used in the process. However, in the limited situation where a process claim reciting a nature-based product is drafted in such a way that there is no difference in substance from a product claim, the claim is subject to the markedly different analysis for the recited nature-based product. MPEP 2106.04(c)(I)(C). The reduction of the expression of ESRG, SFRP2 and/or CNMD in differentiated cells versus undifferentiated cells is a natural phenomenon and identifying its presence in a differentiated cell population is merely claiming the natural phenomena itself (see Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374). Therefore, the claims recite the judicial exception of a law of nature/natural phenomenon.
Claims 17 and 46 also recites wherein the detection of a decrease in the expression one of the genes is an indication of a reduction of residual undifferentiated cells in the population. This limitation recites the judicial exception of an abstract idea because it applies a detecting a decrease is a mental process can is performed in the human mind based on the measured expression levels.
Step 2A, Prong Two – Does the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
The additional elements recited in the claims merely require measuring naturally occurring gene expression using conventional laboratory techniques in differentiated cell populations. The limitation of “a detection sensitivity of the undifferentiated cells in the differentiated cells is 0.1 % or less” merely specifies the sensitivity with which the natural correlation is observed. Additionally, claims 18-24, 28, 33-43 and 45 limits the undifferentiated/differentiated cell populations, the expression level of the gene , and the markers being expressed. Accordingly, the claims merely observe and evaluate naturally occurring biological information and therefore do not integrate the judicial exception into a practical application.
Step 2B – Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claim as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05
In the instant case, the claims does not recite any additional elements that amount to significantly more or markedly different than the judicial exception. Additionally, claims 18-24, 28, 33-43 and 45 limits the undifferentiated/differentiated cell populations, the expression level of the gene , and the markers being expressed which also does not recite any additional elements that amount to significantly more or markedly different than the judicial exception.
Response to Arguments
Applicant’s arguments, see page 5, filed 06/18/2026, with respect to the rejection(s) of under 35 USC§ 101 have been fully considered and are found not persuasive.
Applicants argue that the claims are analogous to Subject Matter Eligibility Example 29 because the claims are directed to a process of measuring gene expression rather than to the naturally occurring gene themselves. Eligibility Example 29 concerns a method of detecting the presence of JUL-1 protein in a plasma sample using a specific immunoassay. The claim is directed to performing a laboratory detection assay on a patient sample to determine whether JUL-1 is present. Although JUL-1 is a naturally occurring protein, the claim as a whole is focused on carrying out a concrete laboratory detection process using plasma sample, rather than merely recognizing a naturally occurring relationship. The claimed advance of the instant claims resides in the discovery that expression of these endogenous genes correlated with the presence or absence of residual undifferentiated cells. Thus, unlike, Example 29, the claims are focus on the natural correlation itself. The instant claims do not employ the natural relationship in a manner that improves an existing technique or applies the natural relation in a technological process. Rather the claims merely measure the expression of naturally occurring marker genes and evaluate the resulting information to determine whether residual undifferentiated cells are present. The claims therefore remain focused on observing and evaluating the naturally occurring relationship itself.
Applicant further argues that the claims need not undergo a markedly different characteristics analysis because the claim are directed to a process. The Examiner agrees that the claims are process claims and therefore the markedly different characteristics analysis to nature-based products is not controlling here. Nevertheless, process claims directed to observing a natural law remain subject to the Mayo/Alice framework. The rejection is therefore based upon the recited law of nature and mental process, not upon the presence of a nature-based product per se.
Applicant further argue that ESRG, SFRP2 and CNMD unexpectedly achieve detection sensitivity of 0.1%. This argument has been fully considered but is not persuasive. Evidence of unexpected biological performances may be relevant to nonobviousness under 35 U.S.C. 103. However, unexpected results do not demonstration that the claims integrate the judicial exception into a practical application of recite significantly more than the judicial exception itself. The amended limitation requiring detection sensitivity of 0.1% or less merely narrows the degree of observation of the naturally occurring correlation and does not add any technological improvement or additional inventive concept. This limitation, for example, does not transform the measurement, require a specific novel assay, or require any treatment step.
According, Applicant’s amendments and arguments do not overcome the rejection under 35 U.S.C. 101.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: The closest prior art is Benvenisty (US 2013/0309769 Al, previously cited) and is discussed on pages 4-6 in the office action dated 02 January 2025. Benvenisty teaches all the limitations of the independent claims except wherein the method excludes measuring the expression level and/or the promoter activity of NANOG. Although Benvenisty does not teach that measuring NANOG is required, and the addition of Shi (Shi et al. Biochemical and Biophysical Research Communications 460 (2015) 130e135; previously cited) and KR Publication (KR20120114084, as cited on the Information Disclosure Statement dated 10/14/2022; previously cited) provides the missing elements from Benvenisty; applicants have provided unexpected results demonstrating that the undifferentiation markers have a high detection sensitivity. Applicants has provided unexpected results that demonstrates that ESRG, CNMD, and SFRP2 all have a detection sensitivity of 0.1 % in compared to other known markers for undifferentiated cells [see Benvenisty at 0036, 0059 and 0231; Shi at pg. 130, col. 2, para 2 and 131, col. 1, para 1]. Therefore, applicant's arguments of unexpected results rebuts the prima facie case set forth.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/TIFFANY NICOLE GROOMS/ Examiner, Art Unit 1637
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