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 .
Priority
This application was filed on June 14, 2022, and is a 371 application of PCT/JP2020/001488 filed on January 17, 2020.
Claim Status
In the response filed on the 10th of June 2026, Applicant has amended claims 12 and 18, and cancelled claims 1-11, and 15.
Applicant has elected Group I, claims 12 and 18, drawn to a method for evaluating differentiation state of cells, and elected Species III (i.e. an evaluation that involves neuronal cells) filed on the 10th of Sept. 2025, and the without traverse is acknowledged.
Claims 13-14, 16-17, and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 September 10, 2025.
Currently, claims 12 and 18 are under examination.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The rejection of claims 12 and 18 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn due to Applicants amendments to the claims.
The rejection of claim 12 under 35 U.S.C. 102(a)(2) as being anticipated by Suzuki, et al. (US2019/0119650 A1, published April 25, 2019, cited IDS 6/14/2022, hereinafter as “Suzuki 2019”) is withdrawn due to Applicants amendments to the claims, reciting differentiating into neuronal cells.
The rejection of claim 12 under 35 U.S.C. 102(a)(1) as being anticipated by Suzuki, et al. (US2017/0052171 A1, published 2017, cited IDS 6/14/2022) is withdrawn due to Applicants amendments to the claims, reciting differentiating into neuronal cells.
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 12 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on June 10, 2026, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
The claims recite “a method for evaluating a differentiation state of cells during culturing for inducing undifferentiated pluripotent stem cells to differentiate into neuronal cells” (see claim 12, lines 1-3) and “wherein the desired cell are neuronal cells, and the progression of induced differentiation is determined using any of a-ketoglutaric acid (AKG), succinic acid (Sue), and fumaric acid (Furn) as the metabolites of the tricarboxylic acid cycle (TCA cycle)” (see claim 18). This judicial exception (i.e. mental process) is not integrated into a practical application because the claims are broadly drawn to a mental analysis (i.e. a method for evaluating a differentiation state of cells) and do not add a meaningful claim limitation that amount to implementing the mental process into a practical application. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the new claim limitation of “wherein the progression of induced differentiation is determined using glycine and threonine contained in the culture solution”(claim 12, lines 17-18) does not add meaningful limitations as it is merely a nominal or extra solution component of the claim and is nothing more than an attempt to generally link the abstract idea to a particular environment.
Per the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 7, 2019 (84 Fed. Reg. 50), if a claim recites a limitation that can practically be performed in the human mind, the limitation falls within the mental processes grouping, and the claim recites an abstract idea. Claims recite a mental process when they contain limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgments, and opinions.
The courts consider a mental process (thinking i.e. evaluating) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work' that are open to all.' " 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work' " (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978). (see MPEP § 2106.04(a)(2), subsection III).
Regarding claim 12, the method of “evaluating” is considered to embrace a mental process. See also MPEP 2106.04(a-b). Further, the claimed invention is drawn to method for evaluating a differentiation state of cells. The claims are broadly drawn such that they include an entirely mental analysis. For example, the claims require “determining a progression of induced differentiation from changes over time in the components of the culture solution and the measurement results; and determining the progression of induced differentiation using a ratio of amounts of change over time in two or more types of amino acids contained in the culture solution, a ratio of amounts of change over time in any two or more types of the metabolites of glycolysis, or a ratio of amounts of change over time in any two or more types of the metabolites of the tricarboxylic acid cycle (TCA cycle) as an index of progression of induced differentiation, wherein the progression of induced differentiation is determined using glycine and threonine contained in the culture solution”. The determining step encompasses an entirely mental process whereby determining occurs via consultation with a medical file or a database. Thus, there is no recitation of a machine or transformation with is explicit or inherent in the practice of the claimed method. Here the general concept of the claim is disembodied, and the mechanism by which the steps are implemented is imperceptible. In the present situation, the claims are not directed to patent-eligible subject matter since they are not tied to any particular machine or apparatus, and they do not require any particular article to be transformed into another state or thing. Nor do the claims directly apply a law of nature in a practical manner with meaningful execution steps or implement more than a concept by performing observable and verifiable steps. These factors weigh heavily against the patentability of the subject matter, and thus it is found that the claims are drawn to an abstract idea. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010).
Step 1-Statutory Category: According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories of invention (i.e. process, machine, manufacture, or composition of matter). Claim 12 is drawn to a method for evaluating function, status and/or activity a differentiation state of cells during culturing for inducing undifferentiated pluripotent stem cells to differentiate into desired cells. Thus, the process meets the requirements for step 1 of the analysis as it is drawn to a method.
Next the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019 PEG, “directed to" is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application", requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 210 6.05 for examples of integration of practical application).
Step 2A Judicial Exception-Prong 1 (claim is directed to a judicial exception): Prong 2A asks whether the claim recites an abstract idea, law of nature, or natural phenomenon (product of nature).
Regarding claim 12, recites a judicial exception in the step of “a method for evaluating a differentiation state of cells during culturing for inducing undifferentiated pluripotent stem cells to differentiate into neuronal cells,” which requires a mental step. Further, claim 12 recites measuring an amount to determine a procession of change over time, which reads on an abstract idea involving mental processes, because a simple determining step of comparing ratios obtained can be performed mentally.
Regarding claim 18, dependent on claim 12, recites “wherein the desired cell are neuronal cells, and the progression of induced differentiation is determined using any of a-ketoglutaric acid (AKG), succinic acid (Sue), and fumaric acid (Furn) as the metabolites of the tricarboxylic acid cycle (TCA cycle)”. Claim 18 just describes the cell type and the assay substance. Therefore, claim 18 does not remedy the deficiency of claim 12. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Furthermore, there is nothing about claims 12, and 18 that include additional elements that are sufficient to amount to significantly more than the judicial exception since the invention as claimed does not introduce or recite any step of compositions that is beyond that which is well understood, routine and conventional.
Step 2A Judicial Exception-Prong 2 (Judicial exception is integrated into a practical application): The phrase, "integration of a practical application", requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful Iimitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application). Under step 2A prong two, this judicial exception is not integrated into a practical application because the additional claim limitations outside the abstract idea only present generic computing components and insignificant extra-solution activity for performing the abstract idea. Thus, Prong 2 asks whether a claim recites additional elements that integrate the judicial exception into a practical application.
Regarding claim 12, there is no significant additional step after the claim recites “a method for evaluating a differentiation state of cells during culturing for inducing undifferentiated pluripotent stem cells to differentiate into neuronal cells”, for requiring a practical application (e.g. applying a treatment, or action step). The amended claim indicates a measuring and determining step, which provides an insignificant extra-solution activity (i.e. mere data gathering/output, see MPEP § 2106.05(g)). When viewed in combination or as a whole, the recited additional elements do no more than more data gathering; see MPEP § 2106.05(g) Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012). Thus, claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Further, the claims does not require any particular application of the measurements. Thus, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 18, dependent on claim 12, recites “wherein the desired cell are neuronal cells, and the progression of induced differentiation is determined using any of a-ketoglutaric acid (AKG), succinic acid (Sue), and fumaric acid (Furn) as the metabolites of the tricarboxylic acid cycle (TCA cycle)”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Thus, claims 12 and 18 meet the requirements of step 2A as being directed to a judicial exception.
Step 2B Significantly More: The "significantly more" analysis includes determining whether a claim is patent eligible if the claims recite structures or functions that transform the abstract idea in a manner that make the claim markedly different from the judicial exception. Further, the Examiner must consider whether each claim limitation individually or as an ordered combination amounts to significantly more than the abstract idea.
Regarding claim 12, the claim does not add significantly more than the judicial exception. The claim recites “determining a progression of induced differentiation from changes over time in the components of the culture solution and the measurement results; and determining the progression of induced differentiation using a ratio of amounts of change over time in two or more types of amino acids contained in the culture solution, a ratio of amounts of change over time in any two or more types of the metabolites of glycolysis, or a ratio of amounts of change over time in any two or more types of the metabolites of the tricarboxylic acid cycle (TCA cycle) as an index of progression of induced differentiation, wherein the progression of induced differentiation is determined using glycine and threonine contained in the culture solution (lines 9-18).” Therefore, claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional limitations are considered directed towards generic mental components carrying out the mental process. See MPEP 2106.04(d) referencing MPEP 2106.05(h). Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional physical steps or elements claimed. Therefore, claim 12 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 18, dependent on claim 12, recites “wherein the desired cell are neuronal cells, and the progression of induced differentiation is determined using any of a-ketoglutaric acid (AKG), succinic acid (Sue), and fumaric acid (Furn) as the metabolites of the tricarboxylic acid cycle (TCA cycle)”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 18 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions (see MPEP 2106.04(a)(2)(III)). It is well established that data gathering steps required to use the method do not add a meaningful limitation to the method as they are insignificant activity (see also MPEP 2106.05(g)).
In conclusion, claims 12 and 18 recite abstract ideas which are not considered to disclose eligible subject matter under 35 U.S.C. 101, and therefore are deemed not patent eligible.
Response to Traversal:
Applicant argues that the human mind cannot practically implement measuring an amount of any of the metabolites of glycolysis or any of the metabolites of the tricarboxylic acid cycle (TCA cycle), as measurement results (Remarks, page 6-7). Applicant asserts that the human mind cannot measure an amount of any of the metabolites of glycolysis or any of the metabolites of the tricarboxylic acid cycle (TCA cycle) from a culture solution and cannot use the measurement results” (Remarks, page 7).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants arguments, the claims does not recite how the measurements are “practically implement” in the method. Thus, it is unclear how applicant is interpreting the measuring step in the claims. It is noted that the claims do not provide any information as to how the measurement is performed or how the determining step is to be performed in the method and to what application is being applied to produce the measurements. As discussed above, the independent claim has been amended to indicate a measuring and determining step, which provides an insignificant extra-solution activity (i.e. mere data gathering/output, see MPEP § 2106.05(g)). When viewed in combination or as a whole, the recited additional elements do no more than more data gathering; see MPEP § 2106.05(g) Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012). Thus, claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application.
In response to applicants’ argument that the human mind “cannot use the measurement results.” Applicant is reminded that 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). In the instant case, it is unclear what measurement Applicant is referring to that the human mind cannot measure and cannot use, since there is not claim limitations directed to an application that uses of the measurements. As discussed above, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the new claim limitation of “wherein the progression of induced differentiation is determined using glycine and threonine contained in the culture solution”(claim 12, lines 17-18) does not add meaningful limitations as it is merely a nominal or extra solution component of the claim and is nothing more than an attempt to generally link the abstract idea to a particular environment.
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 12 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Suzuki, et al. (WO2017/068727A1, published 2017, hereinafter as “Suzuki”; previously presented), in view of Shibuya, et al. (US2015/0192568 A1, published 2015; previously presented), Folmes, et al. (Cell metabolism 14.2 (2011): 264-271, published 2011; previously presented), Takashi Suzuki, et al.,(Shimadzu Review: 123-131,published 2014, hereinafter as “Suzuki 2014” ; previously presented), and Winkle, et al., (Frontiers in Cell and Developmental Biology 7: 300, published 2019; previously presented).
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on June 10, 2026, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding Claim 12 and 18, Suzuki discloses a method for evaluating a differentiation state of cells during culturing for inducing undifferentiated pluripotent stem cells to differentiate into desired cells (see e.g. abstract, claims and results, wherein a ratio of amounts (i.e. test cells/control cells) of change over time (i.e. Day 3 -Day 6)(see e.g. fig. 4, and Results section) in two or more types of amino acids (e.g. alanine and cystine) contained in the culture solution (see e.g. see results section and Table 11-12) as an index of progression of induced differentiation. Further Suzuki discloses the method of evaluating involved measuring biomarkers and that the abundance of the indicator substance in the culture supernatant used in the cell differentiation state evaluation method according to the present invention may be determined using any method, and representative methods include liquid chromatography analysis and mass spectrometry (see e.g. pages 3-4), corresponding to the claim limitation of measuring an amount of metabolites as measurement results contained in a culture solution. Further, Suzuki discloses differentiation state was evaluated based on the abundance of compounds (i.e. ratio) (see e.g. tables and data analysis section), which were determined based on the change of their index value (see e.g. page 4), which was the difference between the retention index set in the DB (a numerical value relative to the retention time)(see e.g. whole document), corresponding to the claim limitation of determining the progression of induced differentiation using a ratio of amounts of change over time in two or more types of metabolites as an index of progression of induced differentiation.
As stated supra, Suzuki does not explicitly state the desired cells are neuronal cells, measuring and determining metabolites are from glycolysis or the tricarboxylic acid cycle (TCA cycle), wherein the progression of induced differentiation is determined using glycine and threonine contained in the culture solution.
However, the prior art of Shibuya discloses a method for determine the degree of differentiation of stem cells using an analytical step of analyzing metabolites of the TCA cycle in the culture solution (see e.g. abstract, claim 1), and discloses that pluripotent stem cells in the method may grow to become nerves in the brain called neural stem cells (see e.g. page 3-4). Further, the prior art of Folmes discloses that the pluripotent stem cell transition requires glycolysis for pluripotency and to facilitate nuclear reprogramming (see e.g. page 264-267).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to have modified the evaluation method, as taught by Suzuki, to incorporate a measuring and determining step wherein the desired cells are neuronal cells or the metabolites are from glycolysis or the tricarboxylic acid cycle (TCA cycle), as taught by Shibuya and Folms, with a reasonable expectation of success because one of ordinary skill in the art would know that metabolites of the TCA cycle can determine the degree of differentiation (see Shibuya, see abstract). Further, Folms discloses that glycolysis is required for nuclear reprogramming (see e.g. page 264-267). A person of ordinary skill in the art would have had predictable results with a reasonable expectation of success of incorporating neuronal cells, the measuring and determining steps of metabolites that are from glycolysis, or the tricarboxylic acid cycle (TCA cycle) as taught by Shibuya and Folms, because a person of ordinary skill in the art would utilize metabolites for understanding differentiation and pluripotency. Therefore, a person of ordinary skill in the art would have combined the cell types (i.e. stem cells) and metabolites (i.e. from glycolysis or TCA cycle), which would have led to predictable results with a reasonable expectation of success. Moreover, an artisan of ordinary skill in the art of (i.e. stem cell differentiation) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007). Thus, it would have been obvious to combine prior art elements according to known methods to yield predictable results.
Regarding claim 12 and 18, as stated supra, Suzuki does not explicitly state wherein the metabolites are glycine, threonine, succinic acid (Suc) or fumaric acid (Fum).
However, the prior art of Suzuki 2014 discloses a metabolome analysis for undifferentiated and differentiated pluripotent stem cells (see e.g. page 6-8), and discloses glycine, threonine, succinic acid (Suc), and fumaric acid (Fum)(see e.g. table 1, page 1-5) in the culture solution.
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods as taught by Suzuki to incorporate the metabolites as taught by Suzuki 2014 because Suzuki 2014 discloses that the analysis method involving metabolites that are involved in glycolysis and citric acid cycle can distinguish between undifferentiated and differentiated states of pluripotent stem cells (see e.g. page 7). Thus, a person of ordinary skill in the art would have a predictable and reasonable expectation of success. Further, the prior art of Winkle discloses that threonine is converted to glycine and acetyl Co-A, and glycine is metabolized specifically to regulate trimethylation of lysine (H3K4me3), which is needed to regulate and maintain stem cell proliferation and pluripotency (see e.g. page 1). Therefore, through the scientific nexus it would have been obvious for one of ordinary skill in the art to analyze the metabolites of glycine and threonine. Further, Winkle discloses that understanding of this regulation (i.e. stem cells that require these one-carbon units to produce H3K4me3 and remain undifferentiated) is essential for treatment of human diseases and disorder (see e.g. page 5). Moreover, an artisan of ordinary skill in the art of (i.e. stem cell differentiation) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant asserts that the specification’s teaches glycine, and threonine can serve as indicator components for neural cell differentiation (e.g. Specification Examples, Figs. 18, 19, 20, and 26)(Remarks, page 8-9). Further, Applicant asserts that “In the case of neuronal cells, as shown in FIG. 26, the index value (glycine/threonine) takes a positive value in differentiation induction, whereas the index value takes a negative value in undifferentiation, thereby allowing for discrimination between them”(Paras. [0113] - [0114] of the pre-grant publication, with reference to Example 5, Fig. 26)(Remarks, page 9-10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
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. the index value of glycine and threonine can serve as indicator components for neural cell differentiation having a positive and negative value) 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). In the instant case, the claims do not recite how the index value is obtained (i.e. machine, assay or method). It is noted that the specification recite “Although the method of PTL1 (i.e. PTL 1: WO 16/052558) is a noninvasive method, it is desired to further improve the accuracy of the evaluation index of the differentiation state”(see e.g. para. 12 and 16). Therefore, it is unclear how this assertion compares to or overcomes the closest prior art.
Applicant argues that the prior art of “Shibuya discloses an analytical step of analyzing at least one type of a metabolite of the pentose phosphate pathway and/or the TCA cycle in the culture solution. (Claim 1 of the publication of Shibuya). The Office also relies on Folmes for disclosing that the pluripotent stem cell transition requires glycolysis for pluripotency” (Remarks, page 10)
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, the prior art of Shibuya is not cited for disclosing an analytical step of analyzing, the prior art of Suzuki is cited for teaching the evaluation method. As discussed above, the prior art of Shinuya is cited for teaching the specific TCA metabolites. As discussed above, the prior art of Fomes is not cited for disclosing the pluripotent stem cell transition requires glycolysis for pluripotency, as the prior art of Suzuki and Shinuya are cited for disclosing pluripotent stem cell differentiation. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Applicant asserts that the prior art of Suzuki 2014 or Winkle do not cure the deficiencies in Suzuki, Shibuya or Folmes, whether considered individually or in combination. (Remarks, page 11).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As discussed above, prior art of Suzuki 2014 discloses a metabolome analysis for undifferentiated and differentiated pluripotent stem cells (see e.g. page 6-8), and discloses glycine, threonine, succinic acid (Suc), and fumaric acid (Fum)(see e.g. table 1, page 1-5) in the culture solution. Further, the prior art of Winkle discloses that threonine is converted to glycine and acetyl Co-A, and glycine is metabolized specifically to regulate trimethylation of lysine (H3K4me3), which is needed to regulate and maintain stem cell proliferation and pluripotency (see e.g. page 1). Therefore, through the scientific nexus it would have been obvious for one of ordinary skill in the art to analyze the metabolites of glycine and threonine. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claim is allowed.
Applicants’ 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 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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/JOSEPHINE GONZALES/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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