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 .
Status of Claims
Applicant’s amendment filed 09/23/2023 is acknowledged. Claims 1, 4, and 8 have been amended. Claims 11 have been added. Claims 3, 7, and 9-10 have been cancelled. Claims 1-2, 4-6, 8, and 11 are pending in the instant application and the subject of this non-final office action.
Regarding the Table of primer sequences provided by Applicants on April 29, 2026, it is noted that the primer sets from the instant application do not include sequence identifiers. Inclusion of the sequence identifiers for any of the primer sets listed in the instant application is requested. However, lack of sequence identifiers for the instant primer sets did not preclude examination of the application.
Claim Objections
Claims 1, 4, and 8 objected to because of the following informalities:
Claim 1 recites “amplified by following primer pairs”. There appears to be a missing word/typo.
Claim 1, 4, and 8 lack a conjunction in the list of primer pair sequences and the phrase “the primer pairs have sequences” should be “the primer pairs having sequences”.
Claims 4 and 8 recite “a primer combination of SSR molecular marker for Procapra prezwalksii”. The term “marker” should be plural. See also 112(b) below. The claims also recites “any one or more of primer pairs”; the “of” should be removed.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-2, 4-6, 8, and 11 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.
The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Regarding claims 1, 4, and 8, the claims recite “the primer pairs have sequences set forth in in SEQ ID NO: 1-2 ... SEQ ID NO: 51-52”. This phrase, combined with the respective recitations of “one or more of PR-6 ... and PR-97” (claim 1) and “any one or more of primer pairs” (claims 4 and 8) appears to be acting as a Markush group.
The phrase lacks a conjunction and therefore it is not clear whether they are actually closed. Applicant may also consider more traditional Markush language to improve clarity (e.g., “a primer combination comprising one or more primer pairs having sequences selected from SEQ ID NO: 1-2, ... and SEQ ID NO: 51-52”).
Claims 2, 5-6, and 11 are indefinite for depending on claims 1, 4, and 8, respectively, and not rectifying the deficiency.
Regarding claims 4, 8, and 11, the claims recite the “primer combination of SSR molecular marker for Procapra przewalksii”. It is not clear whether this limitation is intended to be combination of primers capable of, for example, amplifying SSR molecular markers; a combination of SSR molecular markers with primers; or something else.
Claims 5-6 are indefinite for depending on claim 4 and not rectifying the deficiency.
Regarding claims 8 and 11, the claim recites “a method ... comprising using a primer combination” without any active, positive steps delimiting how this use is actually practiced and is therefore indefinite. See MPEP 2173.05(q).
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 8 and 11 are rejected under 35 U.S.C. 101 because the claimed invention the claimed invention is directed to nonstatutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter.
Claims 8 and 11 are method claims. However, there are no actual method steps recited in either claim, beyond the intended use. Therefore, claims 8 and 11 are deemed not to fall within at least one of the four categories of patent eligible subject matter
Claims 1-2, 4-6, 8, and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) without significantly more. The claim(s) recite(s) natural product(s)/natural phenomena/abstract idea(s). This judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Note: The paragraph numbers herein are referring to the version comprising the “Reference to Sequence Listing” dated 09/29/2023.
The following three inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter?
Yes. Claims 1-2 are directed to a composition of matter, claims 4-6 are directed to a product (manufacture).
Claims 8 and 11 purport to be directed to a process/method but fail to recite steps beyond the “use”; see MPEP 2173.05(q).
Step 2A, prong 1. Does the claim recite a law of nature, a natural phenomenon, or an abstract idea (recognized judicial exceptions)?
Yes.
Regarding claims 1-2, the claims recite molecular markers in P. przewalksii. The disclosure recites that these are “simple sequence repeats” (e.g., para [0007-9]), i.e., microsatellites (para [0004]), found within the genome (para [0074]). Therefore, they are natural products. See 2106.04(b)(II).
As the claim is directed to a product (of nature), the process of “are sequentially amplified by the following primer pairs...” is interpreted as a product-by-process limitation to set the structural boundaries of the claimed marker, i.e., the DNA.
There are no claimed features to differentiate these segments of the genome from the natural counterpart of the corresponding segments of the genome. See MPEP 2106.04(c)(II)(A). The courts have found that the incidental changes resulting from isolation of DNA is not sufficient to make the isolated sequence markedly different, either as gene sequence or as a primer. See MPEP 2106.04(c)(III)(C)(2). Claim 2 requires further requires that the molecular markers comprise a given set of markers, but the sequences themselves are interpreted to remain directed to those of the natural counterpart. Accordingly, it remains a product of nature.
Regarding claims 4-6, the claims recite a kit comprising one or more primer pairs with given sequences. As above, the evidence of record indicates that the primers bind to the P. przewalksii genome upstream and downstream of the microsatellites (para [0074]) and the courts have found that the isolation of DNA is not sufficient to render it markedly different from the natural sequence. Therefore, they are natural products.
Claims 5 and 6 recite “further comprising a genome extraction reagent and a PCR reaction reagent” (claim 5) or “further comprising a reagent for capillary electrophoresis” (claim 6).
Marmol (Mármol P, et al. An innovative DNA extraction method: Water versus commercial buffers. Forensic Science International: Genetics Supplement Series. 2019 Dec;7(1):282–4) teaches water as a genome extraction reagent.
AAT Bioquest (What is the function of MgCl2 in PCR? [Internet]. AAT Bioquest; 2020 [cited 2026 May 11]. Available from: https://www.aatbio.com/resources/faq-frequently-asked-questions/What-is-the-function-of-MgCl2-in-PCR) teaches MgCl2 as a PCR reaction reagent.
Stellwagen (Stellwagen E, Stellwagen NC. Probing the electrostatic shielding of DNA with capillary electrophoresis. Biophys J. 2003 Mar;84(3):1855-66) teaches that NaCl is a reagent for capillary electrophoresis of DNA (entire document, e.g., Abstract).
The counterparts of each would water, MgCl2, and NaCl. Accordingly, under the broadest reasonably interpretation of either claim, the claim require only elements that encompass natural products and there is no indication that each are mixed.
Regarding claims 8 and 11, for the sake of compact prosecution, insofar as the claims may be interpreted to recite a method for detection of population genetic diversity ... comprising using a primer combination ... comprising ... one or more ... primer pairs, under the best possible interpretation.
The relationship between the presence or absence of microsatellite alleles detectable by “use” of one or more of the primer pairs and the population genetic diversity is a natural phenomenon. See MPEP 2106.04(b)(I).
Additionally, such a “use”, which does not require any physical steps, also encompasses abstract ideas including mental processes (including those that may be accomplished using pen and paper), e.g., “in silico” PCR and counting of the number of repeats within the microsatellite between the aligned sequences of the primer pair.
Step 2A, prong 2. Is the judicial exception(s) integrated into a practical application?
In claim 1, the limitation directed to sequential amplification is not a practical application at least because the claim is directed to a product and therefore serves only to limit the structures of the structures of the product. As above, the requirement that claim 2 comprise a set of markers fails to integrate the claim because it requires no more than the sequence of each of the individual markers and isolation is not significant transformation.
For claims 4-6, the claims require no more than elements present in the appropriate natural counterpart, under the markedly different characteristics analysis directed by MPEP 2106.04(c), and therefore encompass only natural products. Further, there is no requirement that the products be transformed or otherwise integrated into a human-made product (e.g., that one of the primers have a fluorescent label; see para [0089]).
For claims 8 and 11, under the best possible interpretation as a “method” for the sake of compact prosecution, the claims require only use of one or more primer pairs having given sequences. No physical steps are required. As described above, such limitations may encompass the abstract idea of, for example, “in silico PCR”/sequence alignment and counting the number of repeats.
Therefore, none of the claims are integrated into a practical application.
Step 2B. Does the claim amount to significantly more?
No, MPEP 2106.05(I) recites that the inventive concept cannot be furnished by the unpatentable judicial exception itself. As the claims require no more than judicial exceptions themselves, they fail to receive significantly more than the judicial exception.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 8, and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Metz (Metz S, et al. FullSSR: Microsatellite Finder and Primer Designer. Adv Bioinformatics. 2016;2016:6040124. Epub 2016 Jun 6.) in view of NCBI (Procapra Przewalskii Genome Assembly PLG [Internet]. U.S. National Library of Medicine; 2019 [cited 2026 May 14]. Available from: https://www.ncbi.nlm.nih.gov/datasets/genome/GCA_006410515.1/); Duo (Duo, H., et al. Genetic diversity of Przewalskis Gazelle using noninvasive DNA and its implications for conservation. African Journal of Biotechnology. 2015 Apr 1;14(13):1107–13); and Mburu (Mburu, D. and Hanotte, O. A practical approach to microsatellite genotyping with special reference to livestock population genetics [Internet]. Nairobi, Kenya: ILRI; 2005 [cited 2026 May 15]. Available from: https://www.iaea.org/sites/default/files/21/06/nafa-aph-manual-dna-manual.pdf), as evidenced by UCSC (PLG Jun. 2019 Przewalski’s gazelle (PLG-pushi 2019) (GCA_006410515.1) [Internet]. UCSC; 2026 [cited 2026 May 14]. Available from: https://genome.ucsc.edu/h/GCA_006410515.1).
Regarding claims 1, 8, and 11, Metz teaches a bioinformatic tool for microsatellite (SSR) detection and primer design using genomic data (entire document, e.g., Abstract), including partial genome sequences (Abstract; pg. 2, col 2, 3.2. Data Entry), which can detect all SSRs within a group of sequences and design primers for each SSR detected (pg. 1, col 2, para 1), including 4-mer SSRs (see Tables 1 and 2).
Metz teaches using techniques inclusive of those of RepeatMasker (pg. 2, col 1, lines 5-7; pg. 2, col 1, para 1; see also citation 11) and including only “perfect” microsatellites (pg. 2, col 1, para 3).
Metz teaches the ability to modify primer design parameters (pg. 2, 2.2., Primer Design; Fig. 1).
Metz fails to teach SSRs for Procapra przewalksii.
NCBI teaches the scaffold-level [i.e., partial] genome assembly GCA_006410515.1. NCBI teaches perfect microsatellite repeats within at least PR-6 and PR-8, as evidenced by UCSC. While NCBI does not explicitly teach the annotations, such sequence is inherently present as evidenced by UCSC.
Duo teaches that Procapra przewalksii is the most endangered antelope species in the world and has been listed as Critically Endangered (pg. 1107, Introduction, para 1). Duo teaches that determination of phylogeographic structure and information on distribution of genetic variation within and among populations is important for identification of evolutionary significant units and management units for declining or endangered species, which can enable targeting of conservation efforts towards genetically distinct populations (pg. 1108, col 1, lines 6-13). Duo teaches microsatellites are currently one of the markers of choice for molecular characterization of animal genetic diversity and conservation genetics (pg. 1108, col 1, lines 23-25).
Mburu teaches designing primers using software (pg. 16, iii) including sequencing data (pg. 17, iv, a) but that no computer program can accurately predict the success or failure of a primer, so the artisan should avoid obvious problems in designing the best primers possible but if there are a few options, it is advisable to try a few candidate primers (pg. 19, d, para 3). Mburu teaches that the test of a good primer is only in its use and relaxing criteria according to the number that survive parameters in the design stage (pg. 20, f).
Mburu teaches optimal primer design characteristic parameters for use with a computer (pg. 18, c).
Mburu is concerned with molecular characterization of small ruminant genetic resources in Asia (Title page) and population genetics/genetic variation (pg. 5).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the bioinformatic tool of Metz to the Procapra przewalksii partial genome sequence of NCBI, motivated by the desire to improve the determination of the phylogeographic structure and information of the distribution of genetic variation within/among population of the gazelle using a marker of choice in the field of conservation genetics, as taught by Duo. The ordinary artisan would have reasonably expected the bioinformatic tool of Metz to identify the corresponding biomarkers of at least PR-6 and PR-8, given the perfect microsatellite sequence of the RepeatMasker-identified SSRs evidenced by UCSC within at least these loci and the identification of all such SSRs within the sequences it is applied to.
The precise binding coordinates of primer SEQ ID NOs within a genome represent a matter of routine optimization. See MPEP 2133.05(II). Both Metz and Mburu teaches setting parameters for primer design and Mburu teaches testing multiple viable primers to determine which works the best in practice. Accordingly, it would have been obvious to the ordinary artisan before the EFD of the invention, given the routine optimization of primers in the art, to select the respective pairs of primers set forth in the claims for the SSRs based on the one or more routinely optimize parameters in amplifications (e.g., Tm, GC, amplicon length, etc.), as taught by Metz and/or Mburu.
Having developed the SSR molecular markers bounded by optimized primer pair sequences in the design step (instant claim 1), it would have been obvious to the ordinary artisan before the EFD of the claimed invention to have utilized such primers in a method of detecting population diversity of P. przewalksii (instant claims 8 and 11, under an interpretation where being in a kit is a matter of nomenclature), motivated by the desire to monitor the most endangered gazelle species in order to target conservation efforts, as taught by Duo. The amplicons produced also represent the natural product of claim 1.
There would have been a strong expectation of success as all are directed to microsatellite tools and methods and/or sequences of the organism and/or optimization techniques applicable to Bovidae.
Claim(s) 4-6 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Metz (Metz S, et al. FullSSR: Microsatellite Finder and Primer Designer. Adv Bioinformatics. 2016;2016:6040124. Epub 2016 Jun 6.) in view of NCBI (Procapra Przewalskii Genome Assembly PLG [Internet]. U.S. National Library of Medicine; 2019 [cited 2026 May 14]. Available from: https://www.ncbi.nlm.nih.gov/datasets/genome/GCA_006410515.1/); Duo (Duo, H., et al. Genetic diversity of Przewalskis Gazelle using noninvasive DNA and its implications for conservation. African Journal of Biotechnology. 2015 Apr 1;14(13):1107–13); and Mburu (Mburu, D. and Hanotte, O. A practical approach to microsatellite genotyping with special reference to livestock population genetics [Internet]. Nairobi, Kenya: ILRI; 2005 [cited 2026 May 15]. Available from: https://www.iaea.org/sites/default/files/21/06/nafa-aph-manual-dna-manual.pdf), as evidenced by UCSC (PLG Jun. 2019 Przewalski’s gazelle (PLG-pushi 2019) (GCA_006410515.1) [Internet]. UCSC; 2026 [cited 2026 May 14]. Available from: https://genome.ucsc.edu/h/GCA_006410515.1) as applied to claims 1 and 8 above, and further in view of Nielsen (US 2015/0136604 A1; published 05/21/2015).
Regarding claims 4-6 and 11, as described and cited above in at least claims 1 and 8, the combination of Metz, NCBI, Duo, and Mburu, as evidenced by UCSC, suggest the primers combinations corresponding to at least PR-6 and/or PR-8 [i.e., SEQ ID NO: 1-2 and/or SEQ ID NO: 5-6, respectively].
However, they fail to explicitly teach that the primer is in a kit, that the kit would further comprise a genome extract reagent and a PCR reaction reagent, or that the kit would further comprise a reagent for capillary electrophoresis.
Nielsen teaches a kit for STR [SSR/microsatellite] analysis that can include reagents for DNA extraction for a sample (e.g., lysis buffer), reagents for performing STR amplification (e.g., primers, polymerase), and reagents for electrophoresis (e.g., electrophoresis buffer) (para [0355]). Nielsen teaches that the one or more buffers may be for capillary electrophoresis (para [0220]).
Nielsen teaches that such embodiments of kits can include all consumable reagents necessary for every step in analysis run performed by an analytical instrument for which the kit is configured (para [0355]), and that the integrated sample-to-answer system of the disclosure (Abstract) may comprise a capillary plate/capillary electrophoresis assembly (Fig. 2; para [0014] and [0240-304]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have assembled a kit comprising the set(s) of primers for the assay (instant claim 4), a polymerase [a PCR reaction reagent], a lysis buffer [a genome extraction reagent] (instant claim 5) , a capillary electrophoresis buffer (instant claim 6), motivated by the desire to include all consumable reagents necessary for every step in an analysis run performed by a corresponding instrument, such as that of Nielsen, as taught by Nielsen, in order to improve convenience. There would have been a strong expectation of success as Nielsen is also directed to STR analysis and the artisan would be capable of selecting appropriate reagents in view of the art.
Under an interpretation of the method where the kit provides a structural difference to the primers, it would also be obvious to the ordinary artisan before the effective filing date to utilize the same primers from within such a kit (instant claim 11), motivated by the desire to improve the convenience of the method by making use of a kit that includes all consumable reagents necessary for every step of the analysis, as suggested by Nielsen. The expectation for success is the same as above.
Conclusion
No claims are allowed.
No art was identified suggesting the combination of markers of claim 2. While all are present in the sequenced genome, at least the repeats PR-22 and PR-25 are imperfect repeats and would not have been suggested by the tool of Metz.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Emma R Hoppe whose telephone number is (703)756-5550. The examiner can normally be reached Mon - Fri 11:00 am - 7:00 pm.
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/EMMA R HOPPE/Examiner, Art Unit 1683
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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