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 .
In view of the appeal brief filed on 0717/2026, PROSECUTION IS HEREBY REOPENED. New grounds of rejection are set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/GARY BENZION/ Supervisory Patent Examiner, Art Unit 1681
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claim(s) recite(s) “quantifying deletions resulting from imperfect DNA repair with mixture modeling to produce a quantified deletion distribution” (claim 1) and “decomposing” (claims 1, 7, 8, 10), which are mathematical calculations (MPEP 2106.04(a)(2)(I)(C)); “mapping”, “identifying”, “determining a distribution” (claim 1), “determining a clonal profile” (claims 2, 3), “determining a correlation between the quantified deletion distribution and one or more clonal substitutions” (claims 4, 5), “selecting high-complexity regions” and “filtering systematic effects” (claim 6) amount to organizing and manipulating information (MPEP 2106.04(a)(2)(I)(A), Example iv: “organizing information and manipulating information through mathematical correlations”). “Receiving” (claim 1) or “obtaining” (claim 12) data amounts to mere data gathering which corresponds to extra-solution activity (MPEP 2106.05(g)). Determining a correlation between a mutational signature or biomarker and cancer (claims 13, 14) is another judicial exception, that being a natural correlation between such mutations/biomarkers and cancer (MPEP 2106.04(b)(I), Example v: “a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk”). Claim 16 merely links the judicial exception to a field of use (MPEP 2106.05(h)). Claims 17-19 recite another judicial exception, which is the natural correlation between the quantified deletion distribution and the responsiveness of cancer to a given treatment (MPEP 2106.04(b)(I), Example xi: “the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone”). The claims begin with data, manipulate the data using statistical and mathematical algorithms, and end with a subset of categorized data (MPEP 2106.04(a)(2)(I)(A), Example iv: Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). The patentee in Digitech claimed methods of generating first and second data by taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form. The court explained that such claims were directed to an abstract idea because they described a process of organizing information through mathematical correlations, like Flook's method of calculating using a mathematical formula. 758 F.3d at 1350, 111 USPQ2d at 1721.). Claim 20 merely recites generic computer hardware for carrying out the method (MPEP 2106.05(f): “…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.”).
This judicial exception is not integrated into a practical application because the process ends with a quantified deletion distribution, but it does not do anything with that distribution in the physical world. The claim consists entirely of computational and informational steps. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because obtaining samples, sequencing, and mapping sequencing reads to the genome were well-known, routine and conventional; see Zhao (US 2016/0224724, para 0396). Similarly, filtering out low-complexity regions (i.e. limiting analysis to “high-complexity” regions) when detecting copy-number variations (CNVs, which encompasses “deletions”, as well as duplications, aneuploidy, etc.) was well-known, routine and conventional; see Trost (The American Journal of Human Genetics 102:142-155, 2018) page 144, left column, 1st and 2nd full paragraphs: “Both array- and sequencing-based methods of CNV detection can be confounded by repetitive and low-complexity regions (RLCRs).” “For generating filtered sets of CNVs, a given CNV was removed if ≥70% of the CNV overlapped with RLCRs.” Measuring sequence complexity using entropy was also well-known, routine and conventional; see Monge & Crespo (2014) entire article. Determining a deletion distribution was also routine and conventional; see Liu (Journal of Pathology 243:176-192; 2017) fig. 3. Using decomposition to analyze insertions and deletions was also routine and conventional; see Jarjour (US 2019/0184035; para 0583). Using mixture modeling to analyze deletions was also routine and conventional; see Cooper (Nature Genetics 40(10):1199-1203 (2008)) abstract.
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 1-20 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 term “relatively high-complexity” in claim 1 is a relative term which renders the claim indefinite. The term “relatively high-complexity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The specification notes that "Reads with low complexity sequences may contain stretches of homopolymer nucleotides or simple sequence repeats." (paragraph 0070) However, this does not constitute a limiting definition by which one of ordinary skill in the art may distinguish between “high-complexity sequence context” and “non-high-complexity sequence context”. The specification also states (paragraph 0114):
"Subsequent tests are for low complexity genomic context of a deletion. For example, low complexity analysis may be performed by calculating entropy of kmer distributions for kmers of length 1-5, within the range of ~60bp to the left and to the right (~120bp total). In other cases, different parameters may be used in the filter, i.e. different functions than entropy, different sizes of sequence regions, and different size of kmers. If a sequencing read is determined to have a repetitive environment, the read is discarded at 172. If a read passes the filter by not having a repetitive environment, the read is retained at 128 for further filtering and processing."
This discussion does not provide any sort of numerical value (of entropy of kmer distributions, e.g.) that determine whether a sequence context is “high-complexity”. The term “repetitive environment” is also not helpful, since “repetitiveness” is also somewhat relative. For example, one might argue that GATCGATC is a repetitive sequence, while others might argue that repetitiveness requires 4 iterations: GATCGATCGATCGATC. Similarly, some might argue that a repeat must be exactly matching: GAATTCGAATTC. Others might argue that some mismatches would still constitute “repetitiveness”: GAATTCGAAATC. Some might argue that a simple mononucleotide sequence constitutes “repetitive”: AAAAAAAAA. Others might argue that repetitiveness excludes such sequence and requires at least a dinucleotide repeating unit: ACACACAC.
Because the term “relatively high-complexity” is not defined and different people could come to different conclusions regarding what is and is not “relatively high-complexity” sequence context, the claim is vague and indefinite. Claims 2-20 depend ultimately from claim 1 and are rejected for the same reason.
Response to Arguments
Applicant's arguments filed 07/17/2026 (in the appeal brief) have been fully considered but they are not persuasive. Applicant’s arguments do not establish any quantitative demarcation between what is “high complexity” and what is “low complexity”. In addition, the fact that “complexity” is measured using entropy does not establish the boundary between what is “high complexity” and what is “low complexity” any more than measuring distance in kilometers establishes what is a “long distance” and what is a “short distance”. Applicant’s arguments do not shed any light on whether or not one infringes the claim for any given degree of “complexity”. The claim language is entirely up to interpretation and does not provide any clear boundary regarding infringement.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/ Primary Examiner, Art Unit 1681
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