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 the Application
Claims 2-3, 5-8, 10, 12, 16, 20-21, 25, 29-30, 52, 80 are pending and under examination
Claim(s) 27, 32, 72, and 77 are canceled.
The following Office Action is in response to Applicant's communication dated 06/29/2026.
Applicant’s election without traverse of Group I, which includes claims 2-3, 5-8, 10, 12, 16, 20-21, 25, 29-30, 52, 80 in the reply filed on 06/29/2026is acknowledged.
Claim(s) 27, 32, 72, and 77 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of calculating degree of relatedness from DNA profile, nucleic acid library; and method of identifying genetic relatives and generating family tree, there being no allowable generic or linking claim.
Claim Interpretation
Claim 29 step (3) is interpreted as comprising two distinct operations:
Ranking the reference DNA profiles
Primary Sort: Rank profiles having fewest relative first and most relatives last.
Tie-Breaker: For profiles with the same number of related entries, rank profiles with most ancestry-diverged ahead of others.
Iterative processing the ranked profiles to construct unrelated/related sample sets
Start with profile at the top of the list first
If the current profile has not been marked as related to a previously selected profile, add it to the unrelated sample set. Then mark all of its related profiles as belonging to related sample set.
If the current profile has been marked as belonging to the related sample set, skip to next profile.
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 2, 3, 5, 7, 8, 10, 12, 16, 20, 21, 25, 29, 30, 52, and 80 are rejected under 35 U.S.C. 101 because the claimed invention(s) is/are directed to one or more judicial exceptions (i.e., product of nature, a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claims 2 recites method for performing DNA-based kinship analysis, and is directed to one or more of a law of nature, a natural phenomenon, a product of nature, and an abstract idea. In the present claim, the steps of “calculating the degree of relationship of the DNA profile to one or more reference DNA profiles.” The step reasonably recites so-called “mathematical concepts” as per MPEP § 2106.04(a)(2)(I), since the broadest reasonable interpretation of these steps include explicit use of one or more computational algorithms in calculating the degree of relationship of the DNA profile one or more reference DNA profiles from sequencing data. Therefore, the claims recite one or more judicial exceptions as per Prong One of the revised Step 2A analysis from the 2019 Revised Patent Subject Matter Eligibility Guidance issued Jan. 7, 2019 in the Federal Register Vol. 84, No. 4. The same Guidance requires analysis of Prong Two, which is whether the claim recites additional elements that integrate the exception(s) into a practical application of that exception(s).
Note that MPEP 2106.04(II)(B) states:
In other claims, multiple abstract ideas, which may fall in the same or different groupings, or multiple laws of nature may be recited. In these cases, examiners should not parse the claim. For example, in a claim that includes a series of steps that recite mental steps as well as a mathematical calculation, an examiner should identify the claim as reciting both a mental process and a mathematical concept for Step 2A Prong One to make the analysis clear on the record. However, if possible, the examiner should consider the limitations together as a single abstract idea for Step 2A Prong Two and Step 2B (if necessary) rather than as a plurality of separate abstract ideas to be analyzed individually. (emphasis added)
In Step 2B, claim 2 must further be analyzed to identify additional elements to determine whether the claim, as a whole, amounts to significantly more than the judicial exception(s). For claim 2 the additional elements consist of:
providing a nucleic acid sample,
amplifying the nucleic acid sample with a plurality of primers that specifically hybridize to a plurality of target sequences collectively comprising a plurality of single nucleotide polymorphisms,
generating a nucleic acid library from the amplification products.,
sequencing the nucleic acid library generated from the amplification products,
determining the genotypes of the plurality of SNPs, thereby generating a DNA profile
These steps all constitute routine, convention, and well-understood activities known in the industry at the time of the invention, specified as a high level of generality, and therefore are not enough to qualify as “significantly more” when recited with the judicial exception(s) of the claim. This is equally true both when considering the steps individually and as an ordered combination. Specifically, the amplifying the nucleic acid sample with a plurality of primers that specifically hybridize to a plurality of target sequences collectively comprising a plurality of at least between at or about 5,000 to 50,000 single nucleotide polymorphisms (SNPs) was commonplace in high-throughput multiplex amplification technique as disclosed in Ryan et al. (US20120122701A1, EFD: December 22nd 2011), Wutke et al. (Methods Mol Biol. 2019;1963:141-147), Shapero et al. (Nucleic Acids Res. 32.22 (2004)), and Zhang et al. (Sci Rep 10, 5623 (2020)). The additional limitations can also be considered to be insignificant extra-solution activity (specifically data gathering steps), which, as per MPEP § 2106.05(g), as explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional.
Claim 3 merely further limits sequencing technique as massively parallel sequencing, which is routine, conventional, and well-understood . This limitation does not add significantly more to the judicial exception, and cannot transform the claims into patent eligible subject matter.
Claim 5 adds a step of generating a family tree, which merely present a way to organize the results of mathematical relationship calculation and constitute insignificant post-solution activity. See MPEP 2106.05 (g).
Claim 7 merely further limits nucleic acid sample comprises genomic DNA, which does not add significantly more to the judicial exception since this is commonplace sample to provide for analysis. See MPEP § 2106.05 (h) & (g).
Claim 8 further limits the nucleic acid sample comprises one or more enzyme inhibitors, which merely specify a characteristic of sample and does not recite any particular technological modification for the presence of said nucleic acid sample. See MPEP § 2106.05 (h) & (g).
Claims 10 and 12 further limits the nucleic acid sample as having low-quality with a defined degradation index (DI), which merely characterize the quality of sample and does not recite any particular technological modification to the amplification, library generation, sequencing, or relationship calculation steps. See MPEP § 2106.05 (h) & (g).
Claim 16, 20, 21, 25, 30, and 80 merely further limits sample characteristics, DNA quality, SNP type, SNP quantity, or number of reference profiles. These limitations restrict the source, amount, or content of the information processed but do not apply the mathematical concepts in a manner that can transform the claims into patent eligible subject matter.
Claim 29 further narrow the mathematical and statistical operations of claim 2 to include (1) performing a KING-Robust kinship estimation between all pairs of DNA profiles; calculate/obtain kinship coefficients; comparing the coefficients with numerical thresholds of > 0.01 and less than <-0.025; determining whether at least 5% of genotype data is missing; counting related and ancestry divergent profiles; ranking the profiles according to the calculated values; resolving ties base on these counts; and iteratively assigning profiles to related and unrelated sets. The calculating steps are judicial exception similar to the “calculating” in step (e) of claim 1, analyzed above; and steps of comparing DNA profiles are also a judicial exception (i.e. an abstract idea, being a mental process as detailed in MPEP § 2106.04(a)(2)(III)(A) and (C).
Claims 52 recites method for constructing a DNA profile, and is directed to one or more of a law of nature, a natural phenomenon, a product of nature, and an abstract idea. In the present claim, the steps of “determining the genotypes of the plurality of SNPs, thereby generating a DNA profile” recites so-called “Mental processes” as per MPEP § 2106.04(a)(2)(III), since the broadest reasonable interpretation of these steps encompasses evaluating sequencing information to identify genotype associated with each SNP. Such broadly recited determining step constitute observations, evaluations, or judgments that falls within mental process group. Therefore, the claims recite one or more judicial exceptions as per Prong One of the revised Step 2A analysis from the 2019 Revised Patent Subject Matter Eligibility Guidance issued Jan. 7, 2019 in the Federal Register Vol. 84, No. 4. The same Guidance requires analysis of Prong Two, which is whether the claim recites additional elements that integrate the exception(s) into a practical application of that exception(s).
In Step 2B, claim 52 must further be analyzed to identify additional elements to determine whether the claim, as a whole, amounts to significantly more than the judicial exception(s). For claim 2 the additional elements consist of:
providing a nucleic acid sample
amplifying the nucleic acid sample with a plurality of primers that specifically hybridize to a plurality of target sequences collectively comprising a plurality of single nucleotide polymorphisms,
sequencing the amplification products
These steps all constitute routine, convention, and well-understood activities known in the industry at the time of the invention, specified as a high level of generality, and therefore are not enough to qualify as “significantly more” when recited with the judicial exception(s) of the claim. This is equally true both when considering the steps individually and as an ordered combination. Specifically, the amplifying the nucleic acid sample with a plurality of primers that specifically hybridize to a plurality of target sequences collectively comprising a plurality of at least between at or about 5,000 to 50,000 single nucleotide polymorphisms (SNPs) was commonplace in high-throughput multiplex amplification technique as disclosed in Ryan et al. (US20120122701A1, EFD: December 22nd 2011), Wutke et al. (Methods Mol Biol. 2019;1963:141-147), Shapero et al. (Nucleic Acids Res. 32.22 (2004)), and Zhang et al. (Sci Rep 10, 5623 (2020)). The additional limitations can also be considered to be insignificant extra-solution activity (specifically data gathering steps), which, as per MPEP § 2106.05(g), as explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 2, 3, 6, 7, 10, 16, 20, 21, 25, 30, 52, and 80 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ryan et al. (US20120122701A1, EFD: December 22nd 2011).
Regarding claim 2, 6, and 52, Ryan discloses method for performing DNA-based kinship analysis, comprising: providing a nucleic acid sample, (e.g. methods for determining the paternity comprises obtain sample (blood or saliva) [¶0258]
amplifying the nucleic acid sample with a plurality of primers that specifically hybridize to a plurality of target sequences collectively comprising a plurality of at least between at or about 5,000 to 50,000 single nucleotide polymorphisms (SNPs), thereby generating amplification products, wherein the amplification is carried out in one or more multiplex PCR reactions, generating a nucleic acid library from the amplification products., (e.g. Ryan uses 9,600 target specific tagged primer pairs to amplify specific target SNPs loci on chromosomes 1, 2, 13, 18, 21, X and Y, thereby generating multiplex amplification products [¶0258-0263])
sequencing the nucleic acid library generated from the amplification products, determining the genotypes of the plurality of SNPs, thereby generating a DNA profile, and calculating the degree of relationship of the DNA profile to one or more reference DNA profiles. (e.g. sequencing data was analyzed using informatics methods disclosed herein and each of a set of ten unrelated males from a reference set were determined to not be the biological father of each of the gestating fetuses. [¶0264]. In an embodiment, the paternity determination involves detecting the presence or absence of phenotype or genotype [¶0174] and generating a report comprising the established paternity of the fetus [¶0019]).
Regarding claim 3, Ryan discloses the sequencing is conducted using massively parallel sequencing (MPS) (e.g. genetic data of the target individual and/or of the related individual can be transformed from a molecular state to an electronic state by measuring the appropriate genetic material using tools and or techniques taken from a group including, but not limited to: ILLUMINA GENOME ANALYZER, or LIFE TECHNOLGIES' SOLID SYSTEM [¶0133]; or method may be used along with next-generation sequencing [¶0161])
Regarding claim 7, Ryan discloses the nucleic acid sample comprises genomic DNA (e.g. methods may be used for analysis of genomic DNA. [¶0169])
Regarding claim 10, Ryan discloses the nucleic acid sample comprises low-quality nucleic acid molecules and/or low quantity nucleic acid molecules. (e.g. The methods described herein are particularly advantageous when used on samples where a small amount of DNA is available [¶0047] or highly fragmented DNA [¶0048])
Regarding claim 16, Ryan discloses the nucleic acid sample is a forensic sample and/or is derived from saliva, blood, semen, hair, teeth, or bone. (e.g. The genetic measurements used as part of these methods could be made on any sample comprising DNA or RNA, for example but not limited to: blood, plasma, body fluids, urine, hair, tears, saliva, tissue, skin, fingernails, blastomeres, embryos, amniotic fluid, chorionic villus samples, feces, bile, lymph, cervical mucus, semen, or other cells or materials comprising nucleic acids. [¶0048])
Regarding claim 20 and 21, Ryan discloses the nucleic acid sample comprises between or between about 50 pg and 100 ng or between about 100pg and 5ng of genomic DNA of genomic DNA. (e.g. a small or limited quantity of DNA may refer to an amount between 100 pg and 1 ng [¶0149] ).
Regarding claim 25, Ryan discloses the plurality of SNPs comprises SNPs selected from one or more of the groups consisting of kiSNPs, aiSNPs, iiSNPs, piSNPs, xSNPs, and ySNPs. (e.g. 9,600 sequence specific primer pairs were used in the single-well reactions; the primers were designed to target SNPs found on chromosomes 1, 2, 13, 18, 21, X and Y [¶0262]).
Regarding claim 30, Ryan discloses the one or more reference DNA profiles comprises at or about or at least or at least about 3,000, 4,000, 5,000, 10,000, 20,000, 30,000, 40,000, 50,000, 75,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000, 250,000, 275,000,300,000,400,000, 500,000, 600,000, 700,000, 800,000, 900,000, 1,000,000, 1,250,000, 1,500,000, 1,750,000, 2,000,000, 3,000,000, 4,000,000, 5,000,000, or 10,000,000 reference DNA profiles. (e.g. Population frequencies are calculated from a large population data set, for example, more than 500 individuals, more than 1,000 individuals, more than 5,000 individuals or more than 20,000 individuals [¶0193]).
Regarding claim 80, Ryan discloses the plurality of SNPs comprises between about 9,000 to 13,000 SNPs. . (e.g. 9,600 9,600 sequence specific primer pairs were used in the single-well reactions; the primers were designed to target SNPs found on chromosomes 1, 2, 13, 18, 21, X and Y [¶0262]).
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.
Ryan et al. and Barber et al.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al. (US20120122701A1, EFD: December 22nd 2011) in view of Barber et al. (US9390225B2, EFD: March 15th 2014)
Regarding claim 5, Ryan does not disclose generating a family tree.
Barber discloses generating a family networks/tree using combinations of DNA analysis and genealogical information. [Abstract]
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to generate a family networks after acquired genealogical information using Ryan’s genetic measurements to organize, represent, and communicate the identify biological relationships in a conventional genealogical format. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143).
Ryan et al. and Jäger et al.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al. (US20120122701A1, EFD: December 22nd 2011) in view of Jäger et al.( Forens. Sci. Int. Genet. 28 (2017): 52-70, disclosed in IDS).
Regarding claim 8, Ryan does not disclose nucleic acid sample comprises one or more enzyme inhibitors.
Jäger discloses multiplex amplification and sequencing of forensic genetic markers using samples containing known PCR inhibitor including hematin, humic acid, indigo dye, tannic acid and urban dust, each of which were independently spiked directly into PCR reaction [Abstract and “PCR inhibition studies” sections].
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to apply Ryan’s targeted multiplex SNP sequencing method to PCR inhibitor containing samples because biological samples often contain polymerase enzyme inhibitors and testing methods that able to tolerate such inhibitors allow robust, reliable, and reproducible performance on samples [Jäger’s Abstract]. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143).
Ryan et al. and Carrasco et al.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al. (US20120122701A1, EFD: December 22nd 2011) in view of Carrasco et al.( Int J Legal Med 134, 79–91 (2020)).
Regarding claim 12, Ryan does not disclose the low-quality nucleic acid molecules have a degradation index (DI) of at or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35,40,45,50,55,60,65, 70, 75,80,85,90,95, 100,105,110,115,120,125,130,135,140,145, 150,155,160,165,170,175,180,185,190, 195,or200.
Carrasco discloses characterizing degraded DNA using degradation index (DI) calculated from relative concentrations of short DNA and long DNA targets and performing SNP target amplification, sequencing preparation, massively parallel sequencing, and genotype determination on samples with DI of 460 [Abstract].
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to characterize Ryan’s fragmented DNA samples using degradation index in order to achieve informative nuclear DNA results from challenging, low-level, and/or degraded samples [“Conclusions and future directions” section]. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143).
Ryan et al., Conomos et al., Staples et al., and Laurie et al.
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ryan et al. (US20120122701A1, EFD: December 22nd 2011) in view of Conomos et al. (Genet Epidemiol. 2015 May ; 39(4): 276–293, disclosed in IDS), Staples et al.(Genet Epidemiol. 2013;37(2):136-141), and Laurie et al. (Genetic epidemiology 34.6 (2010): 591-602).
Regarding claim 29, Ryan does not disclose the large cohort method.
Conomos teaches KING-robust, method developed for relatedness inference in samples from populations with discrete substructure using SNP genotype data, and it is a consistent estimator of the kinship coefficient for a pair of outbred individuals from the same subpopulation [page 5]. Conomos further discloses PC-AiR method, which identifies pairs as related based on a selected positive kinship threshold, identifying ancestry divergent pairs using threshold of −0.025, and partitions the sample set into ancestry representative divergence subset and kinship subset [page 7]. Conomos also teaches excluding individuals having high levels of missing genotype data from the analysis as a result of standard quality control [page 8].
Laurie suggested filtering out any sample-chromosome combination with a missing call rate greater than 5%, since such chromosomes may contain undetected aberrations, as part of routine Genome-wide association studies (GWAS) quality control [pages 2-6].
Staples discloses selecting an unrelated subset from a relationship graph using user specified relatedness threshold and selection criteria, include prioritizing individuals with least ties and applying weighting parameters when select among candidate individuals.
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to apply KING-robust estimator and PC-AiR partitioning method to accurately compute/analyze relationships in large cohort containing known or cryptic relatives [Conomos’s abstract]. It would further have been obvious to apply Stable’s least to most related selection procedure to maximize the number of unrelated individuals retained for further analysis, and prevent needless loss of resources [Stable’s Abstract]. When profiles have equal number if relatives, it would have been obvious to use Conomos’ ancestry divergent count as Staple’s secondary weighting criterion to rank profiles having more ancestry divergent pairing first to consistently prioritize more unique profile and maintain Staple’s least related first selection strategy. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143).
It would also have been obvious to remove profiles having at least 5% missing genotype as suggested by Laurie and Conomos to ensure reliable pair relativeness analysis. Additionally, Conomos teaches a relative kinship coefficient of 0.025, wherein pairs with a kinship coefficient above this value are typically flagged as related [page 16]. Selecting 0.01 would constitute routine adjustment of known parameter to identify more distant relatives. See MPEP § 2144.05 (II) "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KHAI QUYNH TIEN PHAM/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
Prosecution Insights