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 .
Election/Restrictions
2. Applicant’s election of Species B, claims 14, 16, and 26 in the reply filed on March 10, 2026 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 § 818.01(a)).
Claim 13 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Status of the Claims
Claims 1-12 and 14-26 are under examination.
Claim 13 is withdrawn.
Information Disclosure Statement
3. An entry in the information disclosure statement filed November 1, 2022 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because it does not include a publication date. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Drawings
4. The drawings are objected to because Figs. 1-9 are executed in color and a petition to accept color drawings has not been filed. Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via EFS-Web or three sets of color drawings or color photographs, as appropriate, if not submitted via EFS-Web, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
5. The drawings are objected to because Figure 1 contains multiple nucleotide sequence listings of more than 10 nucleotides but does not provide the assigned sequence identifier number for the listed sequences, which is required by 37 C.F.R. 1.821(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
6. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 22-24 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 22-24 recites the limitation "the providing of the sample in step (b)" . However, there is not recitation of “the providing of the sample in step (b)” previously in the instant claim or in the claim for which it depends. It is unclear to what the limitation is referring. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
7. 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 1-12 and 14-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 1-12 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 2-12 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, providing training set data, treating a subset of genomic DNA fragments with bisulfite, and detecting methylation states for the CpG sites. 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, providing training set data, treating a subset of genomic DNA fragments with bisulfite, and detecting methylation states for the CpG sites. 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.
Examiner’s Note:
8. The closest prior art is Lo et al. (U.S. 2014/0080715 A1). Lo et al. teach a method of creating a methylation profile from CpG sites (paragraphs [0267], [0268], [0299] and [0308]-[0311]. The prior art does not teach utilizing individual CpG sites in the calculation of the aggregate methylation score for the combination of one-sided p-values for each CpG site.
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.
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/JERRY LIN/ Primary Examiner, Art Unit 1685
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