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 .
Information Disclosure Statement
The IDS received on May 22, 2024 and September 19, 2025 are acceptable are being considered by the Examiner.
Drawings
The drawings received on May 22, 2024 are acceptable.
Claim Rejections - 35 USC § 112
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 37, 39, and 45 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.
Claim 37 is indefinite for reciting the phrase, “list of cancer susceptibility gene comprises a list of gene loci for which variant sequences have a probability of greater than a second predetermined threshold of being germline in origin if identified during tumor sample sequence”. This makes no sense. No interpretation could be made for this claim.
Claim 39 is indefinite based on its dependency on claim 37. No further interpretation could be made for this claim.
Claim 45 recites the phrase, “reported as potential germline variants”. There is an insufficient antecedent basis for this phrase. For the purpose of prosecution, the phrase has been construed to mean, “potential pathogenic germline variants”.
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 1, 30, 31, 35, 37, 39, 41, 42, 44, 45, 46, 48-51, 55, and 98 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception in the form of an abstract idea without significantly more. The claims recite the judicial exceptions in the form of data collection and manipulation of data which do not result in a meaningful application of the manipulated. This judicial exception is not integrated into a practical application because additional steps required to harvest the data do not add a meaningful limitation to the method as they are insignificant extra-solution activity.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claims 1, 30, 31, 35, 37, 39, 41, 42, 44, 45, 46, 48-51, 55, and 98 satisfy the present inquiry as being drawn to a method.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Independent claim 1 which is representative of the invention recites the steps of:
providing a plurality of nucleic acid molecules from a sample;
ligating adapters thereto;
amplifying the ligated nucleic acid molecules;
capturing the amplified nucleic acid molecules;
sequencing the captured amplified nucleic acid molecules;
receiving, at one or more processors, the sequence read data for the plurality of sequence reads;
identifying, using the one or more processors, variant sequence data for one or more gene loci within the sequence read data;
filtering, using the one or more processors, the variant sequence data to identify variant sequences in a gene locus from a list of gene loci compsiring clinically-actionable germline variant;
filtering, using one or more processors, the variant sequences located in a gene locus on the list to identify variant sequences that are potentially germline pathogenic based on a sequence comparison to known clinically-actionable germline variants for the gene locus;
filtering, using the one or more processors, the potentially pathogenic germline variant sequences to identify variant sequences that have an allelic frequency greater than a first predetermined threshold; and
based on a determination that the allele frequence is greater than the first predetermined threshold, identifying the variant sequence as a clinically-actionable potential germline pathogen variant.
Data collection & manipulations:
Claim 1 Prong-1 inquiry under step 2A determines whether the claim(s) recites an abstract idea, a law of nature, or a natural phenomenon. Under this analysis, the claim recites the steps that are required to obtain the data necessary to perform the data manipulation. However, the recited steps are generic in nature and widely applied in the art of sequencing, and thus their recitation amounts to insignificant extra-solution activity, which the court has deemed not a meaningful limitation to the judicial exception that manipulates the data (i.e., sequence reads) that have been obtained with no meaningful application of the resulting data that have been produced through comparisons and series of filtering steps.
The claimed method therefore, tantamount to collection of data, analyzing the data by way of data comparison comparing the data to another data (of a database), and filtering process.
The Federal Circuit has explained that the courts “continue to ‘treat[] analyzing information … by mathematical algorithms, without more, as essentially mental processes within the abstract-idea category.’” (Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1146-7 (Fed. Cir. 2016). Cf. Diamond v. Diehr, 450 U.S. 175, 191 (1981) (“A mathematical formula as such is not accorded the protection of our patent laws.”). Therefore, the claim recites collection of data, and its manipulation using mathematical relationship, which is deemed abstract in nature therefore, patent ineligible as being directed to judicial exception.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
Claim 1 recites the additional elements in the form of a series of steps in producing the sequencing reads, which, as discussed above, are performed to obtain the data necessary for the data manipulation. However, the recited steps are generic in nature and widely applied in the art of sequencing, and thus their recitation amounts to insignificant extra-solution activity, which the court has deemed not a meaningful limitation to the judicial exception that manipulates the data (i.e., sequence reads) that have been obtained with no meaningful application of the resulting data that have been produced through comparisons and series of filtering steps.
Claims 30, 31, 35, 37, 39, 41, 42, 44-46, 48-51, and 98 recite additional elements in the form of: (i) the data which are being compared against in a database, however, these process are also considered judicial exception in that they are part of the data manipulation with no meaningful application of the resulting data; (ii) producing a report of the result and diagnosing a condition (iii) which are also deemed insignificant solution activity that does not amount to a meaningful application of the produced data as diagnosing is no more than a mental conclusion of the produced data outcome without a meaningful application of the outcome. While claim 55 recites a selection of anti-cancer therapy is made, but the claim only results in the selection of a therapy and not application of the therapy to the subject and therefore is lack a meaningful application as discussed above. Claim 98 is directed to a method as discussed for claim 1, without the series of steps which were necessary to harvest the data. Claim 98, therefore, simply relies on the receiving of data and manipulation of the collected data. However, as discussed above for claim 1, the data reception and their manipulation does not result in a meaningful application and thus lacks patent eligibility as discussed for claim 1.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
Presently, the additional elements which are provided in the claims, such as the means of collecting the data in the form of ligating adapters to nucleic acid sequences, amplifying the ligated nucleic acid sequences, amplifying the sequences, and purifying (or capturing) the amplified sequences for sequencing fail to further add more than the judicial exception because they are recited in a highly generic way as well as being routine and conventional means of providing sequencing data.
Therefore, these elements are not deemed significantly more than inclusion of that are commonly used, routine and conventional.
Therefore, the present claims lack patent eligibility.
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.
(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.
Claims 68, 98, 1, 30, 31, 35, 41, 42, 44, 45, 48, 50-52, 55, and 56 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Finkle et al. (US 2021/0257055 A1, published August 19, 2021, priority February 2020).
The preamble of the claims above are ordered based on the formatting of the rejection for better context.
With regard to claim 98, Finkle et al. teach a method for reporting clinically-actionable potential germline variants comprising the steps of:
receiving, at one or more processors, variant sequence data for one or more gene loci in a sample from a subject (“the raw sequence reads resulting from the sequencing reaction are output from the sequencer … file is passed directly to a bioinformatic pipeline (e.g., variant analysis 206)”, section [0239]; also Fig. 2A, step 206);
filtering, using one or more processors, the variant sequence data to identify variant sequences located in a gene locus from a list of gene loci comprising clinically-actionable germline variants (“variants in the germline of the subject are identified, e.g., using a germline variant identification module”, section [0158]; “genomic variant analysis algorithms 163 evaluate various genomic features 131 by querying database, e.g., a look-up-table (‘LUT’) of actionable genomic alterations”, section [0166]);
filtering, using one or more processors, the variant sequences located in a gene locus on the list to identify variant sequences that are potentially germline based on a sequence comparison to known clinically-actionable germline variants for the gene locus (“the genomic alteration interpretation algorithms 161 include one or more pathogenic variant analysis algorithms 162, which evaluate various genomic features to identify the presence of an oncogenic pathogen associated with the patient’s cancer and/or targeted therapies associated with an oncogenic pathogen infection in the cancer … one or more pathogenic variant analysis algorithms 162 evaluates whether the presence of an oncogenic pathogen in a subject is associated with an actionable therapy for the infection. In some embodiment, system 100 queries a database, e.g., a look-up-table (‘LUT’), of actionable oncogenic pathogen infections”, section [0168]);
filtering, using the one or more processors, the potentially germline pathogenic variant sequences to identify variant sequences that have an allele frequency greater than a first predetermined threshold (“determining, for each respective germline variant in the plurality of germline variants, a corresponding germline variant allele frequency for the liquid biopsy sample”, section [0375]); and
based on a determination that a particular potentially pathogenic germline variant sequence has an allelic frequency above the first predetermined threshold, reporting the potentially pathogenic germline variant sequence as a clinically-actionable potential germline pathogenic variant (“variants are … classified as either germline or somatic, e.g., based on sequencing data, population data, or a combination thereof … variants are classified as germline variants, when they are represented in the population above a threshold level1”, section [0264]).
With regard to claim 68, Finkle et al. teach a processor and a memory that is configured to perform the tasks discussed above (“a computer system having one or more processors, and memory strong one or more programs for execution”, section [0025]).
With regard to claims 1 and 50, in conjunction with the above discussion of claim 98, Finkel et al. additionally teach a method of generating a sequencing read data from a sample comprising the steps of:
providing a plurality of nucleic acid molecules obtained from a sample from a subject (“[n]ucleic acid sequencing of one or more samples collected from the subject is performed” section [0207]; also “[w]et lab processing 204 then includes preparing a nucleic acid library from the isolated nucleic acids (e.g., DNA);
ligating one or more adapters onto one or more nucleic acid molecules from the plurality of nucleic acid molecules (“during library preparation, adapters … are ligated onto the nucleic acid molecules”, section [0208]);
amplifying the one or more ligated nucleic acid molecules from the plurality of nucleic acid molecules (“DNA libraries are amplified and purified using commercial reagents”, section [0210]);
capturing amplified nucleic acid molecules from the amplified nucleic acid molecules (“DNA libraries are amplified and purified using commercial reagents”, section [0210]; also “nucleic acid sequence analysis (e.g., extraction, library prep, capture+hybridize, pooling, and sequencing”, section [0194]); and
sequencing, by a sequencer, the captured nucleic acid molecules to obtain a plurality of sequence reads that represent the captured nucleic acid molecules (“[n]ucleic acid sequencing of one or more samples collected from the subject is performed”, section [0233]; also “[s]equence reads are then generated (312) from the sequencing library or pool of sequencing libraries”, section [0202]).
With regard to claims 30 and 31, the resulting variant as clinically-actionable potential pathogenic variant is reported (“methods described herein include generating a clinical report 139-3 (e.g., a patient report)”, section [0424]; also “report includes information related to the specific characteristics of the patient’s cancer, e.g., detected genetic variants …”, section [0425]).
With regard to claim 35, the gene loci is retrieved from a database (“a predicted functional effect and/or clinical interpretation for one or more identified variants is curated by using information from variant databases”, section [0426]).
With regard to claim 41, passenger mutation information is also determined (“mutation that is present in both the cancer genome of the subject and the germline of the subject is not informative for precision oncology, e.g., when the mutation is so-called ‘passenger mutation,’ which does not contribute to the initiation and/or development of the cancer”, section [0079]).
With regard to claim 42, the known clinically-actionable germline variants for the gene locus comprises variant sequences that have been observed previously as being germline in origin and are listed as either pathogenic or likely pathogenic in a public or a private gnomic database (“one or more pathogenic variant analysis algorithms 162 evaluates whether the presence of an oncogenic pathogen in a subject is associated with an actionable therapy for the infection. In some embodiment, system 100 queries a database, e.g., a look-up-table (‘LUT’), of actionable oncogenic pathogen infections”, section [0168]).
With regard to claim 44, a threshold is determined based on allelic frequency (“variants are classified as germline variants, and/or non-actionable variants, when they are represented in the population above a threshold level, e.g., as determined using a population database such as ExAC or gnomAD … variants that are represented at least 1% … at least 10% or more of the alleles in a population are annotated as germline and/or non-actionable …”, section [0264]).
With regard to claims 45 and 48, predetermined threshold is set to at least 85% (“threshold metric value associated with 25% … 75, or more …”, section [0278]).
With regard to claims 51, 52, 55, and 56, cancer diagnosis is made and treatment is applied (“method … improving upon conventional methods … for cancer diagnosis, … and treatment”, section [0067]).
Therefore, Finkle anticipate the invention as claimed.
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.
Claims 46 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Finkle et al. (US 2021/0257055 A1, published August 19, 2021).
The teachings of Finkle et al. have already been discussed above.
While Finkle et al. teach the collection of data derived from samples other than tissue samples, such as liquid biopsy sample (“liquid biopsies offer several advantages over conventional solid tissue biopsy analysis”, section [0013]), the artisans do not explicitly teach that different threshold should be employed (claim 46), or that the list of gene loci queried comprises a founder (or ancestor) mutation (claim 49).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to take the teachings of Finkle et al. with the practice which are conventional in the art, thereby arriving at the invention as determining a threshold for different types of samples observed would have involved common sense as mutations are present in different frequencies in different types of samples, and querying the germline mutation data which backs to ancestry mutation would have provided a better data set from which to filter when arriving at a potential germline clinically-actionable variant.
The invention as claimed is deemed prima facie obvious therefore.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 June 27, 2026
/YJK/
1 As a variant allele frequency is used to determine the germline variants, this necessarily includes actionable pathogenic germline variants and that clinically actionable variants have a frequency above a certain threshold since variants that are below a frequency threshold are rare and lack sufficient evidence of clinical relevance.
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