DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ arguments and amendments, filed July 8, 2026, have been fully considered and they are persuasive in-part. The following rejections are reiterated. They constitute the complete set of rejections presently being applied to the instant application.
Status of the Claims
Claims 11-12 and 14-26 are under examination.
Claim 13 is withdrawn.
Claim Rejections - 35 USC § 101
2. 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 11-12 and 14-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 11-12 and 14-26 are directed to method [describe method]. As described in Alice Corp. Pty. Ltd. V. CLS Bank Int’l, 573 U.S._, 134 S. Cr. 2347, 110 U.S.P.Q.2d 1976 (2014), a two-step analysis is required in considering the patent eligibility of the claimed subject matter. The first step requires determining if the claimed subject matter is directed to a judicial exception. The instant claims require the steps of providing a mean methylation level and standard deviation of methylation level for each CpG site in the baseline genomic DNA, determining, for each CpG site, the methylation difference between the first genomic DNA and the baseline genomic DNA, thereby, providing a normalized methylation difference for each CpG site, converting the normalized methylation difference for each CpG site into a one-sided p-value, and determining an aggregate methylation score for the combination of one-sided p-values for each CpG site for the first genomic DNA. These steps are mental steps that can be practically carried practically in the human mind or with pen and paper. Furthermore, the steps of providing a mean methylation level and standard deviation of methylation level for each CpG site in the baseline genomic DNA, determining the methylation difference between the first genomic DNA and baseline genomic DNA to provide a normalized methylation difference, converting the normalized methylation difference into a one-sided p-value and determining an aggregate methylation score recite a textual equivalent to a mathematical calculation or recite the mathematical formula for carrying out the mathematical calculation. These steps are drawn to a mathematical algorithm. The courts have found mathematical algorithms to be drawn to the judicial exception of an abstract idea (In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)). Dependent claims 12 and 14-26 recite additional mental steps, mathematical steps, or the source of data. Thus, the instant claims are drawn to a judicial exception.
This judicial exception is not integrated into a practical application. The instant claims do not recite an element that reflects an improvement in the functioning of a computer or other technology, an element that applies the judicial exception to effect a particular treatment, an element that implements the judicial exception with a particular machine, or an element that effects a transformation of a particular article to a different state or thing. The instant claims recite the steps of providing test data, providing methylation states and providing training set data. However, each of these steps are extra solution data gathering steps. Extra solution steps do not provide a practical application for the judicial exception. The instant claims do not integrate the judicial exception into a practical application.
The second part of the analysis requires determining if the claims include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant claims recite the additional elements of providing test data, providing methylation states, and providing training set data. These limitations equate to well-understood, routine and conventional activity as evidenced by the instant specification, Bock et al. (Nature Reviews Genetics 2012, Vol. 13, pgs. 705-719; 14 December 2017) and Schwarzenbach et al. (Nature Reviews Cancer 2011, vol. 11, pgs. 426-437). The instant specification at pg. 23, line 22 to pg. 29, line 13 and pg. 125, line 29 to pg. 127, line 16 discloses that the methylation of sites can be measured using any of a variety of techniques used in the art and includes the use of commercially available products and methods in order to carry out these steps. Bock et al. discloses that there are three commonly used assay for methylation-specific DNA analysis that includes bisulphite sequencing, bisulphite microarrays for preselected regions and enrichment-based methods (pg. 706, col. 1, para. 2 to col. 2, para. 1; Fig. 1; Box 1). Schwarzenbach et al. discloses a review of the use of cell-free nucleic acids for evaluating the methylation status in mixed samples including tumor circulating cell-free DNA (pg. 426, col. 2, para. 1 to pg. 428, col. 1, para. 2; pg. 431, col. 1, para. 1 to col. 2, para. 1; Table 1). Reciting such well-understood, routine, and conventional data gathering steps do not transform a judicial exception into patent eligible subject matter. In addition, the recitation of the specific types of data or the source of data, to be used in the judicial exception, does not transform the abstract idea into a non-abstract idea. (See buySAFE, Inc. v Google, Inc. 765 F.3d 1350, 112 U.S.P.Q.2d 1093 (Fed.Cir.2014)). Furthermore, the elements taken as a combination are also well-understood, routine, and conventional, since the elements are merely specifying the types of data for a data gathering step. Thus, the instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Response to Arguments
3. Applicants have responded to this rejection by stating that the instant claims do not recite a mathematical concept because the mathematical relationships, formulas or calculations are not explicitly recited. The instant claims recite determining the methylation difference. Determining a difference between data points is a mathematical calculation. Alternatively, determining the difference between data may be viewed as a mental step. The instant claims recite converting the methylation difference for each CpG site into a one-sided p-value. Determining the one-sided p-value of data is a mathematical or statistical calculation. In addition , the instant claims recite a step of determining the aggregate methylation score for the combination of one-sided p-values. However, aggregating scores is a mathematical calculation. Alternatively, determining an aggregate score may be interpreted as a mental step. While each of these steps do not recite a formula, each of these steps recite an explicit mathematical concept (e.g. finding the difference, determining one sided p-values, and aggregating data). Furthermore, although applicants have amended claims 15-18 to remove the mathematical formulas, instant claims 15-18 recite calculating the mean, the difference, the standard deviation, the aggregate, and one-sided p-value which are mathematical concepts. Thus, the instant claims remain drawn to the abstract idea of a mathematical concept which is a judicial exception.
The instant claims are distinguishable from Example 38 of the of the PEG Training Examples. Example 38 does not recite a mathematical concept, relationship, or formula. In contrast, the instant claims recite calculating the mean, the difference, the standard deviation, the aggregate, and one-sided p-value which are explicit mathematical concepts. Thus, the instant claims are drawn to a judicial exception.
This rejection is maintained.
Withdrawn Rejections
4. Applicant’s arguments and amendments, filed July 9, 2026, with respect to the rejections made under 35 U.S.C. §112 have been fully considered and are persuasive. The amendment are sufficient to overcome the rejection made under 35 U.S.C. §112. This rejection is withdrawn. Furthermore, the objection to the drawings is withdrawn.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JERRY LIN whose telephone number is (571)272-2561. The examiner can normally be reached T-F 7am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JERRY LIN/Primary Examiner, Art Unit 1685
