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 .
Election/Restrictions
Applicant's election with traverse of Species 1A (claims 3) in the reply filed on 01/13/2026 is acknowledged. The traversal is on the ground(s) that species are not patentably distinct and relate to a single, overarching inventive concept, as the claims recite applying a ruleset to test sequences obtained from methylation-aware sequencing and is configured to remove test sequences determined to reflect a transcription error, and the variations amount guanine, adenine, thymine, and cytosine at identified sites represent natural permutations within a single analytical framework and do no impose an additional examination burden sufficient to justify a restriction requirement (Applicant’s Arguments, p 23, para 4- p 28, para 5. This is not found persuasive because, as currently recited, the instant claims recites species of individual and separate rules/rulesets (see Tables 4-6) that are not dependent on other rules recited in other claims, and would require a separate search as each species is not an obvious variant of the other.
The requirement is still deemed proper and is therefore made FINAL.
Claims 4-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/13/2026.
Claim Status
Claims 1-22, 35-35 and 67-68 are pending.
Claims 4-22 are withdrawn, pursuant to a restriction requirement.
Claim 1-3, 34-35 and 67-68 are under examination herein.
Claim 2 is objected to.
Claims 1-3, 34-35 and 67-68 are rejected.
Priority
The instant application claims priority from Provisional Application 63/080670, filed 09/18/2020. As such, the effective filing date assigned to each of claims 1-3, 34-35 and 67-68 is 09/18/2020.
Information Disclosure Statement
The Information Disclosure Statements filed 11/11/2022 and 06/28/2023 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. A signed copy of the IDS is included with this Office Action.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because:
reference characters "600"(fig 6A), "630" (fig 6B) and “1500” (fig 15) have been used to designate “contamination detection workflow”.
Reference character “602” (fig 6A) and “610” (instant specification) have both been used to designate the “clean up sequencing data” step.
Reference character “610” (fig 6A) and “612” (instant specification) have both been used to designate the “identify likely source of contamination” step.
reference character “3130” has been used to designate both “access filtering rule table” and “filter samples based on rules in rule table” steps in fig 31.
reference character “3530” has been used to designate both “filter samples based on blacklist” and “determine a contamination event” steps in fig 35.
Reference character “2800” and “3500” have both been used in the instant specification to designate the “”blacklist filtering workflow”.
they include the following reference character(s) not mentioned in the description: “602” (fig 6) and “A50” (fig 37).
they do not include the following reference sign(s) mentioned in the description: “612”, “3540”, and “3750”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 2 objected to because of the following informalities: “methylation aware sequencing” should be “methylation-aware sequencing” for consistency. Appropriate correction is required.
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 2-3 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 2, and those claims dependent thereon, are unclear with respect to “a corresponding alternate sequence read generated during the methylation aware sequencing”. The metes and bounds of claims 2 and 3 are rendered indefinite by the lack of clarity. Specifically, the claim 1, on which claims 2 and 3 depend, recites receiving a plurality of sequence read pairs comprising forward strand and reverse strand sequence reads obtained from methylation-aware sequencing and is silent on alternate reads generated during methylation aware sequencing.
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 1-3, 34-35 and 67-68 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claims 1, 34 and 67 recite generating a population of sequence read pairs from the plurality of sequence read pairs by filtering the plurality of sequence read pairs according to a filtering ruleset indicating methylation status of the plurality of sequence read pairs, wherein the filtering ruleset comprises a plurality of rules for filtering forward strand sequence reads of the plurality and reverse strand sequence reads of the plurality based on the methylation-aware sequencing and; determining a prior contamination probability for each SNP of the population of sequence read pairs based on a minor allele frequency for each SNP; applying a contamination model including at least one likelihood test to a sequence read pair of the population using the contamination probabilities for the SNPs in that sequence read pair, each likelihood test configured to produce a test contamination probability representing the likelihood that the sequence read pair indicates a contamination in the test sample; and identifying the contamination in the test sample when the test contamination probability is above a likelihood threshold.
These recitations equate to steps of collecting information, analyzing data and making observations, evaluations and judgements that can be carried out in the human mind. Specifically, generating sequence read pairs by filtering the reads based on a ruleset comprising a plurality of rules, determining a prior contamination probability based on a minor allele frequency for each SNP, and applying a contamination model, and identifying the contamination int the test sample can be practically performing the human mind as claimed and are similar to the concepts of collecting and comparing known information in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011) and collecting information, analyzing it, and reporting certain results of the collection and analysis in Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016) that the courts have identified as concepts that can be practically performed in the human mind. Therefore, each of the above recited limitations fall under the “Mental Processes” grouping of abstract ideas. Furthermore, the steps of determining a prior contamination probability based on a minor allele frequency for each SNP, and applying a contamination model with a likelihood test that can produce a test contamination probability equate to organizing information and manipulating information through mathematical correlations and reciting a mathematical equation, similar to the concepts of taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form in Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). Therefore, these limitations fall under the “mathematical concepts” grouping of abstract ideas. Claims 2-3, 35 and 68 further qualify the judicial exceptions. As such, claims 1-3, 34-35 and 67-68 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology, applies or uses the recited judicial exception to affect a particular treatment for a condition, implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, effects a transformation or reduction of a particular article to a different state or thing or applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. Rather, the instant claims recite additional elements that amount to mere data gathering and mere instructions to implement the abstract idea in a generic computing environment. Specifically, the claims recite the following additional elements:
Claims 1, 34 and 67 recite receiving a plurality of sequence read pairs comprising a plurality of forward strand sequence reads and a plurality of reverse strand sequence reads, wherein: each of the plurality of sequence read pairs are obtained from methylation-aware sequencing, each of the plurality of sequence read pairs comprise at least one single nucleotide polymorphism (SNP);one or more of the sequence reads pairs comprises a site modification that occurred during the methylation-aware sequencing.
Claim 34 and 67 further recite anon-transitory computer-readable storage medium/ one or more memories storing computer program instructions and processor(s).
Claims 2 and 3 do not recite elements in addition to the recited judicial exceptions. Claims 1, 34 and 67 recites further limitations of how data is obtained and the type of data. These limitations equate to mere data gathering activity to obtain the data necessary for the mental evaluations and judgements (see MPEP 2106.05(g)). There is no indication that any of these additional elements provide a practical application of the recited judicial exception outside of the judicial exception itself. Claims 34 and 67 merely recites using a generic computing systems and computer program products to carry out instructions to implement an abstract idea on a computer. The computer system and computer program product as claimed fails to recite details of how a solution to a problem is accomplished and only recites the idea of a solution or outcome. There are no limitations that indicate that the claimed steps require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. Furthermore, the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). As such, claims 1-3, 34-35 and 67-68 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). Further analyzing the additional elements under step 2B, the additional elements as described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims under the 2B analysis, the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Furthermore, the instant specification discloses in para 00115 that sequencing data may be acquired from the enriched DNA sequences by known means in the art, and commercial systems exist for acquiring such data. Therefore, the additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception, and the claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1-3, 34-35 and 67-68 are not patent eligible under 35 U.S.C. 101.
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.
Claims 1-3, 34-35 and 67-68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sakarya and Lamping (US20180373832A1; 11/11/2022 IDS US Patent Document #1; hereafter referred to as Sakarya).
With respect to claims 1, 34 and 67, Sakarya discloses that to detect cross-contamination, test sequences including at least one single nucleotide polymorphism (SNP) are prepared using genome sequencing techniques and that some of the test sequences can be filtered to improve accuracy and precision (abstract).
Sakarya further discloses receiving sequencing data, including from bisulfite sequencing, and that bisulfite conversion can modify some of the nucleobases in a sequence and lead to false positive calls for contamination detection, such as bisulfate conversion can cause a T to C conversion in an SNP which leads to a higher chance of detecting contamination (incorrectly) (claim 1; para 0194).
Sakarya also discloses filtering the received sequences based on bisulfate conversion, considering both forward and reverse strands (as heterozygous and homozygous alleles are determined), based on rules (para 0095; para 0194-0196).
Sakarya further discloses that prior contamination probability for each test sequence is determined based on a minor allele frequency, and a contamination model including a likelihood test is applied to a test sequence (abstract; para 0081-0086).
Sakarya also discloses the likelihood test obtains a current contamination probability representing the likelihood that the test sample is contaminated”, thereby identifying a contaminated sample (abstract; para 004-005; para 0130).
Sakarya further discloses the methods can be computer implemented (para 0199-200).
With respect to claims 2, 35 and 68, Sakarya discloses filtering based on bisulfate conversion and that sequence read is comprised of a read pair denoted as R1 and R2 and nucleotide base pairs of the first read R1 and second read R2 may be aligned consistently (e.g., in opposite orientations) with nucleotide bases of the reference genome, and alignment position information derived from the read pair R1 and R2 may include a beginning position in the reference genome that corresponds to an end of a first read (e.g., R1) and an end position in the reference genome that corresponds to an end of a second read (e.g., R2), and so, the beginning position and end position in the reference genome represent the likely location within the reference genome to which the nucleic acid fragment corresponds (para 0064). Therefore, Sakarya discloses determining the nucleotide bases at a SNP site on the forward and reverse strands of a read, and a reference (i.e. alternate) (para 0064; section XII)
With respect to claim 3, Sakarya discloses the contamination detection workflow can filter the received sequences and include only SNPs with A to T and T to A SNP, suggesting that all other SNPs are removed and therefore, a read with SNP with a cytosine in the forward or reverse strand would be discarded (para 0194).
Conclusion
No claims allowed.
Inquires
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/N.D./ Examiner, Art Unit 1686
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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