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 August 11, 2025. Currently, claims 1-3, 5-9 are pending. Claim 6 has been withdrawn as drawn to non-elected subject matter.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Any objections and rejections not reiterated below are hereby withdrawn.
The Improper Markush group rejection has been withdrawn in view of the amendment of the claims to the elected gene.
Election/Restrictions
Applicant's election of TMPRSS11E the paper filed August 11, 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/JP2021/017112, filed April 28, 2021 and claims priority to four JAPAN foreign applications with the earlier priority date of May 1, 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 1-3, 5, 7-9 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.
Claims 1-5, 7-9 are directed to “a method for detecting adult atopic dermatitis in a sample” by determining expression level of elected TMPRSS11E. Claims 1 and 5 are specifically directed to a comparing step.
The claims are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “detecting adult 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 TMPRSS11E and adult 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 adult 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 adult atopic dermatitis. Thus, the determining step constitutes an abstract process idea.
Claims 1 and 5 further recites a comparison between the expression level and a reference control or a discriminant 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 TMPRSS11E and adult atopic dermatitis is a law of nature/natural phenomenon. The "determining" tells users of the process to predict adult atopic dermatitis in the sample, amounts to no more than an "instruction to apply the natural law". This detecting preamble recitation and the detecting step 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 TMPRSS11E, 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 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 TMPRSS11E 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 b 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 “detecting adult atopic dermatitis in an adult“ is a practical application. This argument has been reviewed but is not persuasive. The comparing and the detecting adult atopic dermatitis in an adult 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 TMPRSS11E (the only non-JE that is in the claim). Rather, the applicant has identified a new natural phenomena, the relationship between the TMPRSS11E expression and detecting adult atopic dermatitis in an adult, 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.
Claim Rejections - 35 USC § 112
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 1-3, 5, 7-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-3, 5, 7-9 are indefinite because it is unclear how comparing the expression level with a reference expression level of TMPRSS11E determines the presence or absence of the adult atopic dermatitis. It is unclear how a comparison determines presence or absence of a phenotype. The claim nor the specification teach when adult atopic dermatitis is present or absent. Clarification is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
Dup rem
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rodriguez-Cerdeira et al. (The Open Biochemistry Journal, Vol. 8, pages 21-34, 2014).
The only active method step in the instant claims is measuring an expression level of TMPRSS11E in a biological sample collected from an adult test sample.
Rodriguez-Cerdeira teaches determining expression levels of TMPRSS11E. Rodriguez-Cerdeira teaches TMPRSS11E is down-regulated in normal keratinocyte differentiation (page 26, col. 1). Table 2 provides TMPRSS11E expression is correlated with normal keratinocyte differentiation (page 26).
Response to Arguments
The response traverses the rejection. The response asserts Rodriguez-Cerdeira does not teach or suggest comparing expression level of TMPRSS11E with a reference level to determine the presence or absence of adult atopic dermatitis. This argument has been considered but is not convincing because the claim requires measuring an expression level of TMPRSS11E and comparing the expression with a reference expression level. The claim then provides that determines the presence or absence of adult atopic dermatitis. The “thereby determining” is a recitation of inherent property. The claim does not require any active step of determining the presence of adult atopic dermatitis. Rodriguez-Cerdeira teaches TMPRSS11E is “down-regulated” which inherently teaches a comparison was performed to determine TMPRSS11E was expressed less than a reference. Rodriguez-Cerdeira teaches this determined the absence of adult atopic dermatitis. Thus for the reasons above and those already of record, the rejection is maintained.
Claim(s) 1-2, 7-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Suarez-Farinas et al. (J. of Allergy and Clinical Immunology, Vol. 127, No. 4, pages 954-964, April 2011).
Suarez-Farinas teaches expression analysis of nonlesional atopic dermatitis skin and normal skin. Suarez-Farinas teaches skin biopsy specimens were collected from moderate-to-severe AD and 10 healthy volunteers. Suarez-Farinas teaches using the Affymetrix human U133A plus 2 arrays for analysis of mRNA. The U133A plus2 array comprises probes for analysis of TMPRSS11E. Thus, analysis of the U133Aplus2 array analysis inherently comprises measuring an expression level of TMPRSS11E as well as the genes listed in Claims 7-9.
Response to Arguments
The response traverses the rejection. The response asserts while Suarez-Farinas studied expression levels of TMPRSS11E and numerous other genes in skin samples, Suarez-Farinas teaches TMPRSS11E among differentially expressed genes in comparative genomic profiling. This argument has been considered but is not convincing because the claim is directed to a method that permits that analysis of expression levels in large collections. The claim is directed to a method “comprising” measuring expression level of TMPRSS11E. The transitional claim language “comprising” is open to analysis of additional genes. Thus, the analysis of TMPRSS11E along with other genes is not excluded from the instant claim.
The response argues the method of Suarez-Farinas is not used to determine the presence or absence of adult atopic dermatitis. This argument has been reviewed but not convincing. Suarez-Farinas teaches expression analysis of nonlesional atopic dermatitis skin and normal skin. Suarez-Farinas teaches skin biopsy specimens were collected from moderate-to-severe AD and 10 healthy volunteers. Suarez-Farinas does detect adult atopic dermatitis based upon the compassion of the genes.
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.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
March 11, 2026