DETAILED ACTION
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 .
Claims 99-118 are pending and are being examined on the merits.
Specification
The disclosure is objected to because of the following informalities: The “Cross-References to Related Applications” paragraph on p. 1 of the Specification should be updated to reflect that US Patent App. No. 17/409,132 has issued into US Patent No. 12,049,671.
Appropriate correction is required.
Information Disclosure Statement
The Information Disclosure Statements submitted October 14, 2025, November 18, 2025, December 29, 2025 and August 6, 2026 have each been considered. The Information Disclosure Statement submitted September 29, 2025 has also been considered, except for NPL Nos. 8 and 10, which were not submitted.
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 99-107 and 109-118 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Eligibility is considered in light of MPEP 2106 III, which incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 17, 2019 (84 Fed. Reg. 50) and is clarified in the October 2019 Update.
As can be seen in the MPEP 2106 III Figure, eligibility analysis requires one to address the following questions: (i) Step 1 – Is the claim directed to one of the four statutory categories (i.e., process, machine, manufacture or composition of matter); (ii) Step 2A – Is the claim directed to a judicial exception (i.e., a natural phenomenon, law of nature or abstract idea); and (iii) Step 2B – does the claim recite additional elements that amount to significantly more than the judicial exception. In addition, as can be seen in the MPEP 2106.04 II Figure, Step 2A is a two-prong inquiry, with Prong One asking whether the claims recite a judicial exception (i.e., an abstract idea, natural phenomenon or law of nature) and Prong Two asking whether the claims recite additional elements that integrate the judicial exception into a practical application.
In this case, as to Step 1, claims 99-107 and 109-118 are directed to one of the four statutory categories since they are drawn to a composition of matter.
The analysis cannot be streamlined, so the claims are considered with respect to Step 2A.
With respect to Prong One of Step 2A, claims 99-107 and 109-118 recite a judicial exception. Specifically, the marker and reference oligonucleotides in claim 110 are a product of nature (i.e., a natural phenomenon). The complexes in claim 99 comprising a target region of a methylation marker DNA or of B3GALT6 DNA and a corresponding oligonucleotide specifically hybridized to the target region or the B3GALT6 DNA, respectively, are also products of nature. Further, regarding the marker and reference oligonucleotides, it is not clear that these oligonucleotides exist in nature, but these oligonucleotides, are, nevertheless, judicial exceptions because they are derived from naturally occurring genomic nucleic acids and possess no structural or functional differences relative to their naturally occurring counterpart. For example, the oligonucleotides are not required to include a label or non-naturally occurring nucleotides, nor do they have functions not possessed by naturally occurring nucleic acids. As well, MPEP 2164.04(b)(i) identifies isolated nucleic acids having no structural or functional differences from naturally occurring nucleic acids as an example of a patent-ineligible natural product. Similarly, the complexes which comprise a target region of a methylation marker DNA and a corresponding oligonucleotide specifically hybridized to the target region encompass double-stranded genomic DNA, and thus, are also judicial exceptions.
In addition, as discussed in MPEP 2016.04(b)(II), “[P]roduct of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” See Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244. In this case, the claimed oligonucleotides have no functional differences relative to their naturally occurring counterparts since both the claimed and naturally occurring molecules hybridize to complementary nucleic acids.
In view of the foregoing, claims 99-107 and 109-118 clearly recite a judicial exception. With respect to Prong Two of Step 2A, the claims do not recite additional elements that integrate the judicial exceptions into a practical application for the following reason. In particular, claims 99-107, 110-111 and 116, do not require any components other than the judicial exceptions. Further, in claims 109, 112-115 and 117-118, the elements in the claim other than the judicial exception (i.e., oligonucleotides, enzymes, various reagents) constitute insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g). In addition, to the extent that “kit” in the claim 110 preamble is construed to require something additional, such as assembling the various oligonucleotides into container(s), this also constitutes insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g).
Thus, the answer to step 2A is “Yes, the claims are directed to a judicial exception,” and the analysis moves to Step 2B, which asks if the additional elements in the claim amount to significantly more than the judicial exception.
In this case, claims 99-107 and 109-118 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because claims 99-107, 110-111 and 116 need not have any components other than the recited DNA/oligonucleotides, and claims 109, 112-115 and 117-118 merely include additional reagents all of which are routine and conventional elements. In addition, the combination of oligonucleotide primers with DNA samples and PCR reagents was routinely taught in the art prior to the effective filing date of the claimed invention, as well assembling nucleotides into kits (e.g., see Ahlquist 2; cited below in the prior art section: paras. 7-8, 13-14, 16-17, 89-99, 105, 120, 124-125, 151-201). Therefore, the additional elements in claims 109, 112-115 and 117-118 are not non-routine or unconventional.
In view of the foregoing, claims 99-107 and 109-118 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
Prior Art
Claims 99-118 are free of the art. The closest prior art is Ahlquist (WO 2015/153283 A1) and Ahlquist (US Patent App. Pub. No. 2016/0168643; hereinafter, “Ahlquist 2”). Ahlquist and Ahlquist 2 each teach compositions and methods comprising methylation marker primers and various reagents for amplifying methylated marker DNAs. Ahlquist additionally teaches the PDGFD and the VAV3 biomarkers, while Ahlquist 2 teaches the SFMBT2 and VAV3 biomarkers. However, neither Ahlquist not Ahlquist 2 teach or suggest that the compositions or reaction mixtures additionally comprise B3GALT6 DNA, or corresponding target-specific oligonucleotides. While B3GALT6 is generally known in the art, there does not appear to be any reason to modify the compositions and methods of Ahlquist or Ahlquist 2 to incorporate B3GALT6 DNA or corresponding oligonucleotides.
Allowable Subject Matter
Claim 108 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 99-118 are being examined. Claims 99-107 and 109-118 are rejected. Claim 108 is objected to, but is otherwise directed to allowable subject matter.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
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