Response to Amendment
The amendment filed 14 July 2026 is acknowledged. The amendment focused claim 1 to specific sets of primers. The current status of the claims is as follows: claims 1 and 7-11 are pending; claims 7-11 have been withdrawn; claims 2-6, and 12 have been cancelled.
In regards to the office action mailed 22 April 2026, after thorough review and consideration of Applicant’s amendments and arguments, any objections or rejections not reiterated or amended below have been withdrawn as being obviated by the claim amendments.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (including a product of nature) without significantly more.
The claim is directed to two examination reagents. The first is a set of primers. The second is multiple sets of primers. In both instances, the primers were designed to analyze the degree of methylation at specific claimed CpG sites. Primers that are nothing more than fragments of naturally occurring nucleic acids lack markedly different characteristics from their natural counterparts (see MPEP 2106.04(C).II.C.2; Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244). Furthermore, the ability to serve as a starting material for amplification is innate to DNA itself, and was not created or altered by the patentee (University of Utah Research Foundation V. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014).
Although the claim places the primers into sets, this does not structurally modify the primers themselves into something that would amount to more than the product of nature and is simply creating sets of naturally occurring sequences. Therefore, this judicial exception is not integrated into a practical application because merely placing products of nature together in a set does nothing more than attempt to generally link the products of nature to a technological environment. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements limit what the reagents are analyzing, leaving the products of nature themselves unchanged. As no additional limitations exist which would modify the products of nature in a meaningful way, claim 1 does not contain eligible subject matter.
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 –
(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.
Claim 1 is rejected under 35 U.S.C. 102(a)1 as being anticipated by Illumina 1 (Illumina. HumanMethylation450v1.2 Manifest File (CSV Format). 2013 May 23.) as evidenced by Illumina 2 (Illumina. Infinium® HumanMethylation450 BeadChip. 2012 March 09: p1-4; previously cited.) and Illumina 3 (Illumina. Infinium® HD Assay Methylation Protocol Guide. 2015 November: p1-244.).
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A pairwise comparison was conducted between the claimed CpG sites and the CpG sites interrogated by the Illumina Infinium® HumanMethylation450 BeadChip. As a result, all of the claimed CpG sites were determined to be interrogated by the HumanMethylation450 BeadChip. Five exemplary entries from the BeadChip probe manifest which matched with five of the claimed CpG sites are shown below with irrelevant columns hidden for ease of viewing. A table has been appended to this office action which lists each of the claimed CpG sites in relation to their matching BeadChip probe.
This BeadChip provides quantitative methylation measurement at the single-CpG-site level for normal and formalin-fixed paraffin-embedded samples using both Infinium I and Infinium II assays, which differ in the number of beads used [Illumina 2, p1C1, Fig. 3]. According to Illumina 3, these assays involve hybridizing the fragmented DNA samples to the BeadChip oligonucleotides. This captured DNA serves as the template for single-base extension of the BeadChip oligonucleotides which incorporates a detectably labeled nucleotide and determines the methylation level of the query CpG sites [Illumina 3, p8, Figure 9]. Therefore, the BeadChip oligonucleotides anticipate the primers of the instant application as they prime an extension reaction for each of the claimed CpG sites. While the instant application orders the CpG sites into sets, the claim does not require that these sets are physically or temporally separate from each other and does not exclude the presence of primers for additional CpG sites.
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Response to Arguments
Argument regarding 35 U.S.C § 101 rejection:
Applicant’s argument, see p11, filed 14 July 2026, that the amended claim overcomes this rejection due to the inclusion of language which limits the examination reagents to specifically designed primer sets is not persuasive. As discussed in the rejection above, placing primers into sets does not structurally modify the primers themselves into something that would amount to more than the product of nature. Simply grouping naturally occurring sequences into sets does not amount to more than the sum of the individual nature-based products.
Arguments regarding 35 U.S.C. § 102(a)(1) rejection:
Applicant’s arguments, see p11, filed 14 July 2026, with respect to the rejections of claim 1 under Nunes et al. and Illumina (hereinafter “Illumina 2”) as evidenced by Xia have been fully considered and are persuasive as none of the cited art anticipates the claimed primer sets. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Illumina 1 as evidenced by Illumina 2 and Illumina 3 as described above.
Conclusion
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 Kara N Kovach whose telephone number is (571)272-8134. The examiner can normally be reached Monday - Friday, 9am - 3pm.
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/K.N.K./Examiner, Art Unit 1681
/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
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