DETAILED ACTION
Applicant's response, filed 3 February 2026, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
Election/Restrictions
Newly submitted claim 17 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: A process of making and a product made by the process can be shown to be distinct inventions if either or both of the following can be shown: (A) that the process as claimed is not an obvious process of making the product and the process as claimed can be used to make another materially different product; or (B) that the product as claimed can be made by another materially different process. A product defined by the process by which it can be made is still a product claim (In re Bridgeford, 357 F.2d 679, 149 USPQ 55 (CCPA 1966)) and can be restricted from the process if the examiner can demonstrate that the product as claimed can be made by another materially different process; defining the product in terms of a process by which it is made is nothing more than a permissible technique that applicant may use to define the invention. In the instant case, an aerosol or particulate matter can be made by numerous methods aside from that of claim 1 and as such, the claims are distinct.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 17 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Status
Applicant’s previous election without traverse of Group I, claims 1-9 is acknowledged.
It is noted that Claims 10-16 were 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 17 September 2025.
Claims 1-9 and 11-17 are currently pending.
Claims 1-9 are examined herein.
Claims 11-17 are withdrawn.
Claim 10 has been cancelled.
Specification
Note: All references to the Specification herein pertain to the PG publication: US20210403984.
Claim Objections
Claims 1 and 8 are objected to because of the following informalities:
Claim 1, step (7), recites, “determining that the heated tobacco product sample having 0.8 or less of PRE has low or absence of risk of chronic obstructive pulmonary disease (COPD) associated with the inhalation of the heated tobacco product sample”, wherein the recitation of PRE is assumed to be a typographical error in which PRE should read PRF. Correction is requested.
Claim 8, recite, “the airway epithelial cells is exposed to” which is grammatically incorrect and correction to “the airway epithelial cells are exposed to is requested.
Claim Rejections - 35 USC § 112(b)-Indefiniteness
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.
Claims 1-9 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1, as amended, recites, “(1) obtaining a sample solution containing an aerosol or particulate matter in the aerosol generated from a heated tobacco product sample (2) exposing airway epithelial cells to the sample solution; (3) extracting mRNA from the sample solution…” wherein the claim is not clear with respect to the extraction of the mRNA from the sample solution, as it is not specifically recited that the “sample solution” is that of the epithelial cells as exposed to said sample solution of step (1) and, as such the claim would appear to read only on extracting mRNA from an aerosol solution, which fails to make sense in the instant context. It is assumed for examination purposes that the extraction of mRNA is from the airway epithelial cells that have been exposed to the sample solution of step (1). Clarification through clearer claim language is requested. Claims 2-9 fail to remedy the above issues and are also rejected as such.
Further with respect to the above recitation in claim 1, it is not clear that any “gene expression” analysis takes place after extraction of mRNA rendering the “gene expression” analysis in step (4) indefinite as to from where said gene expressions are obtained/derived. Clarification is requested.
Claim 1 recites, “(4) obtaining probability PSMK, which is probability of being determined as a smoker, on the basis of data on the expression of 11 or more genes including at least the following 11 genes: TXNIP, EFNA1, ADM, SLC7A11, IGFBP3, WNT5A, HILPDA, EGLN3, CXCR4, AREG, and FBXO32 among the following 15 genes in the airway epithelial cells exposed to the sample solution: TXNIP, EFNA1, CYP1B1, ADM, AREG, DUSP6, SLC7A11, IGFBP3, WNT5A, CXCR4, PHLDA1, HILPDA, ZBED2, EGLN3, and FBXO32, with use of an intercept and coefficients calculated in advance by logistic regression analysis by using public data obtained from public databases, the probability PSMK being defined by the following formula…”, wherein the recitation of “with use of an intercept and coefficients calculated in advance by logistic regression analysis by using public data obtained from public databases” is indefinite with respect to calculation in advance by logistic regression by using public data obtained from public databases. It is not clear as to what occurs using the public data from public databases in the context of the claim. One interpretation is that the intercept and coefficients are obtained from public data in some database and then used for active determination of a probability. Another is that the logistic regression analysis is also performed prior and exists in a public database. The further recitation of Cns/smk as representing ratio of non-smokers’ intercept to smokers’ intercept obtained by the logistic regression is not clarifying as it is not clear whether this is actively done using the public database or the data in the database or the like. Further indefinite is the then recitation of gene expression data and a value after normalization of microarray data…or quantitative value of gene expression obtained by qPCR, there is no recitation of previous performance of either microarray analysis or qPCR or from where said data are derived. Claims 2-9 fail to remedy the above issues and are also rejected as such.
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 1-9 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The instant rejection reflects the framework as outlined in the MPEP at 2106.04:
Framework with which to Evaluate Subject Matter Eligibility:
(1) Are the claims directed to a process, machine, manufacture or composition of matter;
(2A) Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
(2B) If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1 Analysis: Are claims directed to process, machine, manufacture/composition of matter
With respect to step (1): yes, the claims are directed to an in vitro method for evaluating the risk of chronic obstructive pulmonary disease associated with inhalation.
Step 2A, Prong 1 Analysis: Do claims recite abstract idea
With respect to step (2A)(1), yes, the claims recite abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the (2A)(1) evaluation, the claims are found herein to recite abstract ideas that fall into the grouping of mathematical concepts (in particular mathematical relationships and formulas) and mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
The claim steps to abstract ideas are as follows:
Independent claim
Claim 1:
obtaining probability PSMK on the basis of data…with use of an intercept and coefficients calculated in advance by logistic regression analysis by using public data obtained from public databases, the probability being defined by the following formula; [
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wherein CNNS/SMK represents ratio…, βi represents the coefficient for each gene, ai represents gene expression data and represents a value after normalization…x represents any integer of 11 to 15
obtaining probability PCOPD… on the basis of data…with use of an intercept and coefficients calculated in advance by logistic regression analysis by using the public data obtained from the public databases…defined by the following formula;
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wherein CSMK/COPD represents ratio of smokers’ intercept to COPD patients’ intercept… γi represents the coefficient for each gene, bi represents gene expression data and represents a value after normalization of microarray data by GC-RMA or a quantitative value of gene expression obtained by the qPCR method, and y represents any integer of 4 to 10
determining the potential risk factor (PRF) of chronic obstructive pulmonary disease (COPD) associated with inhalation of the heated tobacco product sample from the probability PsMK and the probability PCOPD , PRF being defined by the following formula:
PRF=psmk x pcopd/1 – (psmk x pcopd ) ; and
(7) determining that the heated tobacco product sample having 0.8 or less PRE [PRF] has low or absence of risk of COPD…
wherein said claim steps recite mathematical formulas, mathematical calculations, and mental activity and therefore are directed to abstract ideas.
Dependent claims
Claim 2: the probability PSMK is calculated by the logistic regression analysis on the basis of data which is a step further defining that the operations are performed using logistical regression (math).
Claim 3: the probability PCOPD is calculated on the basis of data…with use of coefficients calculated in advance by logistic regression analysis using the public data… which is a step further defining that the operations are performed using logistical regression (math).
Claim 9: wherein the PRFs of the two types of heated tobacco products are compared to each other, wherein steps of “comparison” are those that are directed to mental operations wherein one can “compare” one result to another.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined herein to each cover performance either in the mind (comparison step) and performance by mathematical operation (calculations using mathematical formula as recited in the claims). There are no specifics as to the methodology involved other than mere calculation and thus, under the BRI, said operations are abstract mathematical processes. These recitations are similar to the concepts of collecting information, analyzing it and providing certain results from the collection and analysis (Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations (Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in (Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind with pen and paper, and can include mathematical concepts.
Further, see MPEP § 2106.04(a)(2), subsection III. The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation (see, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674: noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand."); Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1139, 120 USPQ2d 1473, 1474 (Fed. Cir. 2016): holding that claims to a mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper").
Step 2A, Prong 2 Analysis: Integration to a Practical Application
Because the claims do recite judicial exceptions, direction under (2A)(2) provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application (MPEP 2106.04(d). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the abstract idea is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract idea, the claim is said to fail to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
With respect to the instant recitations, the claims do not include any additional elements beyond the calculation steps. It is noted that under the Broadest Reasonable Interpretation of the claims herein, the data steps, such as on the basis of data on the expression of 11 or more genes…data on the expression of 4 or more genes including at least the following 4 genes… are not actively performed in the claim due to lack of clarity of steps (1)-(3) as now amended and thus the steps are directed purely to the “data” input for said calculation recitations and do not limit the claims (see 112b above). Dependent claims do not remedy this interpretation, as they further limit the types of data only.
Step 2B Analysis: Do Claims Provide an Inventive Concept
The claims are lastly evaluated using the (2B) analysis, wherein it is determined that because the claims recite abstract ideas, and do not integrate that abstract ideas into a practical application, the claims also lack a specific inventive concept. Applicant is reminded that the judicial exception alone cannot provide the inventive concept or the practical application and that the identification of whether the additional elements amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements of data gathering described above do not rise to the level of significantly more than the judicial exception. As directed in the Berkheimer memorandum of 19 April 2018 and set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, steps directed the “data” in the claims are merely directed to types of “data”, as indicated above and thus the claims contain only abstract ideas without any additional element herein as it is unclear that any actual steps of gene expression analysis by isolation of the particular genes listed is performed (112b). With respect to steps as now indicated to obtaining sample solutions of aerosol…, exposing epithelial airway cells to the sample, and extracting mRNA, said operations are well-known and conventional practices in the art for assessment of gene expression. The prior art to Aufderheide et al. (BioMed Research International Volume 2013, Article ID 734137, 15 pages; cited previously) discloses the CULTEX Radial Flow System for culture of airway epithelial cells. Said reference provides methodology for exposure of epithelial cells to mimic an inhalation cycle in vitro. Further, prior art to Banerjee et al. (Applied In Vitro Toxicology (2017) Volume 3, Number 1:15 pages; cited previously) discloses comparisons of transcriptomic perturbations in MucilAir™, a commercially available lung epithelial tissue, after short repeated exposure to cigarette smoke (3R4F) and e-cigarette (Vype ePen) aerosols. Deep RNA sequencing and secreted inflammatory cytokine profiling postexposure was utilized for analysis of gene expression. In addition, the prior art to Ishikawa et al. (Toxicology in Vitro 54 (2019): 251–262; cited previously) discloses the use of three-dimensional organotypic human bronchial tissue cultures and metabolomics, transcriptomics, and proteomics to investigate changes in biological processes affected by repeated whole-cigarette smoke exposure.
The dependent claims have been analyzed with respect to step 2B and none of these claims provide a specific inventive concept, as they all fail to rise to the level of significantly more than the identified judicial exception.
For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Applicant’s Arguments
1. Applicant states that “claim 1 is amended to recite (1) obtaining a sample solution containing an aerosol or particulate matter in the aerosol generated from a heated tobacco product sample; (2) exposing airway epithelial cells to the sample solution; and (3) extracting mRNA from the sample solution. Thus, it is further clarified that the claimed method is not a mere abstract idea upon entry of the current amendments to the claims”.
Applicant includes that “further, claim 1 is amended to recite ‘(7) determining that the heated tobacco product sample having 0.8 or less of PRE has low or absence of risk of chronic obstructive pulmonary disease (COPD) associated with the inhalation of the heated tobacco product sample’ (based on claim 8) to further clarify the practical application of the "PRF" value”.
It is respectfully submitted that this is not persuasive. First, due to the lack of clarity in claim 1 with respect to the origin of the “gene expression” of the listed genes and actual use of said genes for the analysis thereafter, the arguments are not persuasive because it is not clear that, beyond performing extraction of mRNA, that the particular genes as listed are those that are actually isolated by any particular means. Further, performing steps to “get data” that include obtaining a sample solution and exposing airway cells to sample solutions to isolate (assumingly from said cells) mRNA, is a process known in the art for assessing gene expression data for inhalation protocols. For example the art, as discussed above discloses such measures. It is noted that no particular isolation of the cited genes is performed nor are any probes or primers or any particular array, for example, recited such that said specific genes are isolated for analysis.
With respect to determining that the heated tobacco product sample having 0.8 or less of PRE has low or absence of risk of chronic obstructive pulmonary disease (COPD) associated with the inhalation of the heated tobacco product sample as a practical application, it is noted that said step is, itself directed to an abstract steps whereby “determining” is a mental operation that can be performed by analysis of data using pen and paper or with the aid of a computer. It is further noted that the practical application and/or improvement must be realized in the claim by steps that are "in addition" to the recite judicial exception and cannot be provided by the exception itself, as is instantly argued. Applicant will refer to the (MPEP 2104, II., A., 2.): wherein, it is stated, "judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC V. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. V. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B. If there are no additional elements in the claim, then it cannot be eligible."
As such, the claims remain ineligible under 35 USC 101.
Conclusion
No claims are allowed.
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 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.
E-mail Communications Authorization
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/Lori A. Clow/Primary Examiner, Art Unit 1687