DETAILED CORRESPONDENCE
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed February 19, 2026. Currently, claims 1-6 are pending. Claim 3 has been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
The Improper Markush group rejection has been withdrawn in view of the amendment of the claims to the elected gene.
The 102 rejections over Fukagawa and Uehara have been withdrawn in view of the 102(b)(2)(C) statement of common-ownership at the time of the effective filing date on February 19, 2026.
Election/Restrictions
Applicant's election of SLC31A1 the paper filed October 8, 2025 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.
Priority
This application is a 371 of PCT/JP2021/025988, filed July 9, 2021 and claims priority to JAPAN 2020-119040, filed July 10, 2020.
It is noted that a translation of the foreign document has not been received.
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 1-2, 4-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 1-2, 4-6 are directed to “a method for detecting severity of atopic dermatitis in a sample” by measuring an expression level of elected SLC31A1, comparing the expression with a reference level and determining the severity of atopic dermatitis.
The claims are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “detecting severity of atopic dermatitis” and “comparing a measurement value with a reference value) and a law of nature/natural phenomenon (i.e. the natural correlation between the expression level of SLC31A1 and atopic dermatitis in sample).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 1 involves the patent-ineligible concept of an abstract process. Claim 1 requires performing the step of “detecting severity of atopic dermatitis”. Neither the specification nor the claims set forth a limiting definition for "detecting" and the claims do not set forth how “detecting” is accomplished. As broadly recited the detecting step may be accomplished mentally by thinking about a subject’s expression and assessing severity of atopic dermatitis. Thus, the determining step constitutes an abstract process idea.
Claim 1 further recites a comparison between the expression level and a reference control that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)).
A correlation that preexists in the human is an unpatentable phenomenon. The association between expression levels such as SLC31A1 and severity of atopic dermatitis is a law of nature/natural phenomenon. The "detecting" tells users of the process to predict severity of atopic dermatitis in the sample, amounts to no more than an "instruction to apply the natural law". This detecting preamble recitation is no more than a mental step. Even if the preamble requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The preamble does not require the process user to do anything in light of the correlation. The detecting fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites measuring an expression level of the elected SLC31A1, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Accordingly, the claims are directed to judicial exceptions.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The measuring expression by sequencing or amplification method is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the expression of biomarkers of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining the expression level of elected SLC31A1 was well known in the art at the time the invention was made. The prior art teaches that expression analysis using commercially available biochips and arrays that comprise the claimed genes. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any expression analysis assay to determine the expression. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the claims have been amended to require the measuring step to use nucleic acid amplification or sequencing and thus does not recite mental processes. This argument has been reviewed but not persuasive. Step 6 of Claim 1 explicitly recites “comparing” which the courts have said is a mental process. The claim also requires “determining the severity of atopic dermatitis”. The determining may also be performed mentally. Thus, the claim recites judicial exceptions of abstract ideas. The mere fact a claim recites steps in addition to a judicial exception does not render the claim patent eligible (see Example 29 of the 101 Guidelines).
The response asserts the claim recites additional elements that integrate the judicial exception into a practical application. The response argues that “determining the severity of atopic dermatitis by measuring expression level of SLC31A1 “ is a practical application. This argument has been reviewed but is not persuasive. The comparing and the determining severity of atopic dermatitis are not practical applications, they are judicial exceptions.
In the present claims, there is no improvement being made to the technologies of measuring the expression of SLC31A1 (the only non-JE that is in the claim). Rather, the applicant has identified a new natural phenomena, the relationship between the SLC31A1 expression and severity of atopic dermatitis, and applied routine and conventional technologies to perform data gathering steps required for application of the judicial exception. See e.g. MPEP 2106.05(g) relating to Insignificant extra-solution activity. While Applicants may have made a useful discovery of the natural correlation, there is no integration of the judicial exception into a system or process resulting in the improvement of the relevant technology. Rather, routine and conventional technologies to perform necessary data gathering for the general application of the judicial exceptions have been applied. The only “improvement” that appears to have been made is the discovery of the Judicial exception itself, which the MPEP makes clear cannot be the basis of an eligible inventive concept.
The MPEP identifies cases that may not be sufficient to show an improvement in technology and cites Cleveland Clinic Foundation v. True Health Diagnostics, LLC (Fed Cir. 2017), CAFC Appeal No. 16-1766, which is a precedential decision. The claims in the Cleveland Clinic case are quite similar to the instant claims. The CAFC confirmed that the correlation of a marker (MPO) to a disease is nothing more than a recognition of a natural phenomenon and that the steps for measuring the marker were nothing more than what was already known in the art. Further, they found that applicants did not purport to invent a new statistical method, either. With regard to use of data to infer a threshold (or other comparative) value, the Court found: Rather, the claims here instruct that MPO levels be detected or determined using any of these known techniques. The claims of the testing patents also contain a “comparing” step where MPO levels are compared to statistically derived control or predetermined values. Here too, Cleveland Clinic does not purport to derive new statistical methods to arrive at the predetermined or control levels of MPO that would indicate a patient’s risk of cardiovascular disease. Known statistical models and data analysis can be employed, as described, for example, in the specification. The specification teaches the ranking using Wilcoxon signed-rank test is used for data analysis (page 8). This is not new or inventive. Likewise, while Cleveland Clinic argues that its discovery of the relationship between MPO and cardiovascular health was groundbreaking, “even such valuable contributions can fall short of statutory patentable subject matter, as it does here.” Id. at 1380.
The response argues that the claims as a whole add significantly more because they include a specific, non-routine combination of elements. The response argues biomarker assessment does not routinely use SSL, a lipid fraction collected non-invasively from the skin surface. This argument has been reviewed but is not persuasive because the art teaches collection of nucleic acid for detection was well understood, routine and conventional at the time the invention was made. For example, PBI (Pressure BioSciences, Shetage) teaches collecting DNA from sebum samples. The limitations in addition to the judicial exceptions are routine and well understood data collection methods. Thus, for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-2, 4-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of measuring an expression level of SLC31A1, does not reasonably provide enablement for detecting severity of atopic dermatitis in a test subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and breadth of claims
Claims 1-2, 4-6 are drawn to detecting severity of atopic dermatitis in a test subject by measuring an expression level of SLC31A1.
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The unpredictability of the art and the state of the prior art
The art teaches the degree of progression (severity) of atopic dermatitis is classified into, for example, no symptoms, minor, mild (low grade), moderate (intermediate grade) and severe (high grade) (see Fukagawa et al. US 2023/0235399, July 27, 2023, para 65).
Guidance in the Specification.
The specification provides no evidence that the skilled artisan can detect severity of atopic dermatitis in a test subject by measuring an expression level of SLC31A1, for example. The specification provides SLC31A1 was decreased in healthy vs moderate patients (see Table 2-2). The specification teaches that no difference may be detected in healthy vs mild or mild vs moderate test subject.
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The guidance provided by the specification amounts to an invitation for the skilled artisan to try and follow the disclosed instructions to make and use the claimed invention.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to determine whether a test subject has no symptoms, minor, mild (low grade), moderate (intermediate grade) and severe (high grade) atopic dermatitis based solely on measuring expression level of SLC31A1, for example. The specification does not provide any comparison of expression levels of SLC31A1 in patients with no symptoms, minor or severe atopic dermatitis and provides that mild and healthy can not be distinguished, nor can mild vs moderate. Therefore, detecting severity would be unpredictable and undue and would require further experimentation to detect severity of atopic dermatitis in a test subject. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of a working example and the negative teachings in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
The response traverses the rejection. The response asserts the specification demonstrates the claimed method in practice with consistent p-values below 0.1 across group comparisons. This argument has been considered but is not convincing because the art teaches statistically significant associations occur when the p-value is less than 0.05. As provided by Thisted, “it has become scientific convention to say that p-values exceeding 0.05 (one in twenty) just aren’t strong enough to be the sole evidence that two treatments being studied really differ in their effect. Thus, the p-values in the specification of 0.09 and 0.067 are not strong enough to demonstrate statistically significance.
The response argues the claims do not require “perfect discrimination between every possible adjacent severity category 100% of the time”. This argument has been reviewed but it not persuasive. The enablement rejection requires the invention may be practiced without undue or unpredictable experimentation. The art, as discussed above, has conventionally found that p-values exceeding 0.05 are not evidence of an effect. Here, the p-values are greater than 0.05 and thus, it is unpredictable whether there is an association or not. Thisted considered “with a p-value of 0.52, it would be incorrect to conclude that aspirin and placebo are equally effective. Rather, we would have to conclude that aspirin's effectiveness remains unproven.” Analogously, here, it would be incorrect to conclude that expression of SLC31A1 and severity of atopic dermatitis is associated with the p-values of 0.067 and 0.09. Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
JP-2020-74769, May 2020 teaches analyzing the expression level of RNA prepared from SSL from a group of atopic dermatitis and subjects without atopic dermatitis. The genes listed do not include SLC31A1.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
March 11, 2026