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 1-23 are pending. Claims 11-23 are being examined on the merits. Claims 1-10 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 11-23) in the reply filed on October 20, 2025 is acknowledged.
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 20, 2025.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The Information Disclosure Statement submitted June 1, 2023 has been considered.
Claim Objections
Claims 17 and 21 are objected to because of the following informalities:
In each of claims 17 and 21, a period should be added at the end of the claim.
Appropriate correction is required.
Claim Interpretation
The specification recites that an “adulterant” is an “unwanted substance[]” that “can be added to the processed botanical material accidently, negligently, or intentionally” (para. 83). The specification also recites that a “non-target” species is an “adulterant” (para. 85). Thus, the terms “adulterant” and “non-target species” are interpreted as having the same meaning.
Claim 23 recites, in part, “a sequence as set forth in SEQ ID NO: 31 or 33” and “a sequence as set forth in SEQ ID NO: 32 and 34”. Both the sequence listing and the specification indicate that SEQ ID NOs: 31 through 34 comprise nucleotides with phosphorothioate linkage modifications (Example 3, p. 40). Thus, the phrase “a sequence as set forth in SEQ ID NO: [31/32/33/34]” is being interpreted as requiring both the corresponding recited linear nucleotide sequence and the phosphorothioate modifications. This is in contrast to instant SEQ ID NOs: 29 and 30 which have the same linear nucleotide sequences as SEQ ID NOs. 31 and 33, and 32 and 34, respectively, but do not comprise the phosphorothioate modifications.
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 11-13 and 17-21 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 11-13 and 17-21 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 11-13 and 17-21 recite a judicial exception. Specifically, the inner and outer primers are a product of nature (i.e., a natural phenomenon). The claims require primer pairs that each specifically bind to a particular botanical species. It is not clear that these primers exist in nature, but these oligonucleotides, are, nevertheless, judicial exceptions because they are derived from naturally occurring nucleic acids (e.g., see GenBank Accession Nos. JZ705370.1 and EF590501.1, cited below in the “Prior Art” section) 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.
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 11-13 and 17-21 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 11-13 and 19-21, do not require any components other than the judicial exception. Further, in claims 17-18, the elements in the claim other than the judicial exception (i.e., a DNA polymerase) constitute 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 11-13 and 17-21 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because claims 11-13 and 19-21 need not have any components other than the recited primers, and claims 17-18 merely include additional reagents all of which encompass naturally occurring products, which are routine and conventional elements. In addition, the combination of various reagents, including oligonucleotide primers, DNA polymerases and samples was routinely taught in the art prior to the effective filing date of the claimed invention (e.g., see Kim, cited below in the prior art rejections). Therefore, the additional elements in claims 17-18 are not non-routine or unconventional.
In view of the foregoing, claims 11-13 and 17-21 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
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.
Claims 11-13 and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim1 (Molecular Identification of Allium ochotense and Allium microdictyon using multiplex-PCR based on single nucleotide polymorphisms, Horticulture, Environment, and Biotechnology, 59(6), 1-10, 2018).
Regarding independent claim 11 and dependent claims 12-13, Kim teaches …
A multiplex PCR system for identifying processed botanical material, wherein the processed botanical material comprises a target species and/or a closely related non-target species/adulterant, said system comprises: an inner forward primer and an inner reverse primer, wherein a 3' terminus of the inner forward primer comprises a sequence that is complementary to a sequence specific to the target species, and wherein a 3' terminus of the inner reverse primer comprises a sequence that is complementary to a sequence specific to the non-target species/adulterant, or vice versa; and an outer primer pair consisting of an outer forward primer and an outer reverse primer. Further, the sequences specific to the target and non-target species/adulterant differ by a single base (i.e., an SNP) (Table 3; Fig. 2; Sections 2.1, 3.2).
Regarding dependent claims 19-20, Kim additionally teaches that the botanical material is processed (section 2.1) and that the botanical material is a market ginseng root material, specifically P. ginseng (p. 9, left col., para. 1).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Molecular Identification of Allium ochotense and Allium microdictyon using multiplex-PCR based on single nucleotide polymorphisms, Horticulture, Environment, and Biotechnology, 59(6), 1-10, 2018) as applied to claim 1 above, and further in view of Heissl, et al. (2017. High-Throughout Genotyping with TaqMan Allelic Discrimination and Allele-Specific Genotyping Assays. In: White, S., Cantsilieris, S. (eds.) Genotyping. Methods in Molecular Biology, vol. 1492. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6442-0_3).
Regarding dependent claims 14-16, Heissl teaches that the inner forward primer and/or
the inner reverse primer(s) have 3’ end phosphorothioate bond modifications, optionally 4 consecutive modifications. (p. 48, para. 1).
Regarding dependent claims 17-18, Heissl teaches a DNA polymerase that lacks 3’ to 5’ exonuclease activity, and specifically Taq DNA polymerase (p. 44, para. 8).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Kim system to incorporate the phosphorothioate bond modifications of Heissl. Kim teaches the need for high specificity assays to distinguish between template with single nucleotide mismatches. Heissl teaches that introducing phosphorothioate bounds into the primer backbone increases primer specificity. The ordinary artisan would have been motivated to incorporate the Heissl modifications into the Kim system with the expectation that doing so would result in a highly specific multiplex PCR system. In addition, the selection of a known material based on its suitability for its intended purpose supports a prima facie obviousness determination. MPEP 2144.07. The ordinary artisan would have had an expectation of success as the design and optimization of primers is well-known in the art.
It would have been additionally obvious to further incorporate the Heissl Taq polymerase into the Kim system because Heissl teaches that Taq polymerase is useful for such a purpose. In addition, it would have been obvious to try the Taq polymerase in the Kim system because the ordinary artisan would have been motivated to customize the system as needed through routine optimization. The ordinary artisan would have had an expectation of success as the design and optimization of amplification assays is well-known in the art.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Molecular Identification of Allium ochotense and Allium microdictyon using multiplex-PCR based on single nucleotide polymorphisms, Horticulture, Environment, and Biotechnology, 59(6), 1-10, 2018) as applied to claim 1 above, and further in view of Lu (US Patent App. Pub. No. 2019/0032153).
Regarding dependent claims 20-21, Kim additionally teaches that the target species is P. ginseng (p. 9, left col., para. 1), while Lu teaches detecting Petroselinum crispum, P. quinquefolius, P. notoginseng, E. senticosus and Apium graveolens (para. 10). Lu also teaches authenticating processed botanical material, including to determine whether a non-target species/adulterant is present (paras. 8, 59). Kim does not specifically designate whether the various botanical materials are “target” or “non-target”, but the ordinary artisan would understand that it is an obvious matter of design choice whether a substance being detected is considered a target or a non-target. MPEP 2144 (VI)(C).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Kim system to incorporate the Lu botanical materials. Kim teaches that the system is useful for assaying a variety of substances, including botanical materials, including P. ginseng and related materials. Thus, it would have been obvious to try the various Lu materials in the Kim system, because Lu teaches the need to assay these materials, and Kim teaches a system which is useful for assaying similar substances. The ordinary artisan would have had an expectation of success as the design and optimization of amplification reactions is well-known in the art.
Prior Art
Regarding claims 22-23, the following art is relevant: GenBank Accession No. DQ500902.1 (Polianthes longiflora tRNA-Leu (trnL) gene, intron; chloroplast, 2006); GenBank Accession No. HQ917115.1 (Loranthus grewingkii voucher GUH-3998 tRNA-Leu (trnL) gene, partial sequence; trnL-trnF intergenic spacer, complete sequences; and tRNA-Phe (trnF) gene, partial sequence; chloroplast, 2011); GenBank Accession No. JZ705370.1 (KSU-FB-SSH-ST59 Vicia faba L. cDNA suppression subtractive hybridization library Vicia faba cDNA clone KSU-FB-SSH-ST59, mRNA sequences, 2014); GenBank Accession No. EF590501.1 (Angelica archangelica voucher NMNH 06-8344 ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast, 2016).
SEQ ID NO: 12 is identical to the reverse complement of GenBank Accession No. DQ500902.1 nucleotides 491-514.
SEQ ID NO: 13 has 96.6% homology to the reverse complement of GenBank Accession No. HQ917115.1 nucleotides 215-239.
SEQ ID NOs: 31 and 33 have the same nucleotide sequence as instant SEQ ID NO: 29, however, SEQ ID NOs: 31 and 33 comprise four or three, respectively, phosphorothioate linkage modifications. SEQ ID NO: 29 is identical to GenBank Accession No. JZ705370.1 nucleotides 45-65. However, the phosphorothioate linkages in SEQ ID NOs: 31 and 33 are not known in the art.
SEQ ID NOs: 32 and 34 have the same nucleotide sequence as instant SEQ ID NO: 30, however, SEQ ID NOs: 32 and 34 comprise four or three, respectively, phosphorothioate linkage modifications. SEQ ID NO: 30 is identical to the reverse complement of GenBank Accession No. EF590501.1 nucleotides 366-351. However, the phosphorothioate linkages in SEQ ID NOs: 32 and 34 are not known in the art.
Thus, there are individual sequences known in the art corresponding to, at least, SEQ ID NOs: 12 and 31-34, and a sequence with a high degree of homology to SEQ ID NO: 13. Generally primer design and optimization is known in the art, as is the modification or primers with phosphorothioate linkages, e.g., to increase specificity. However, the instant primer pairs of SEQ ID NOs: 12-13, and SEQ ID NOs: 31 or 33, and 32 or 34 are not taught in the art. In order to design such pairs, the ordinary artisan would have to know that the corresponding target and non-target sequences have a single nucleotide mismatch at a particular position, and then design the primer pair so that 3’ terminal end of one primer is complementary to one of the mismatched nucleotides, while the 3’ terminal end of the other primer is complementary to the other mismatched nucleotide. Since the art does not teach sequences or alignments showing such mismatches in the target and/or non-target species, there does not appear to be any motivation for ordinary artisan to design these particular primer pairs. Thus, the primer pairs recited in claims 22-23 are free of the art.
Allowable Subject Matter
Claims 22-23 are 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 11-23 are being examined. Claims 11-21 are rejected. Claims 17 and 21-23 are objected to. No claims are allowed.
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/Examiner, Art Unit 1681
1 Kim was cited in the Information Disclosure Statement submitted June 1, 2023.