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 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.
Applicant's response, filed on 12/12/2025, is fully considered.
Rejections under 35 U.S.C. 112(b) are newly applied, resulting in this Non-Final Office Action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of claims
Claims 31-38 and 40-51 are pending.
Claims 31, 35-38, 40 and 50-51 are amended.
Claims 1-30 and 39 are canceled.
Claims 31 and 50-51 are independent claims.
Claims 31-38 and 40-51 are examined below.
Priority
As detailed on the 12/01/2021 filing receipt, this application claims priority to as early as 02/18/2020.
Drawings
The drawings filed 11/16/2021 are accepted.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/15/2025, 12/12/2025 and 02/03/2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of the list of references cited from each IDS is included with this Office Action.
Withdrawn Rejections/Objections
The rejection of claims 31-51 under 35 U.S.C. §101, in the Office action mailed 08/21/2025 is withdrawn in view of the amendments filed 12/12/2025.
The rejection of claims 31-51 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10-11, 13-14, 17-20, 22-30, 38-39, 42, 45-48, 50-56, 64-65, 68, 71-74, and 76-82 of U.S. Patent No. 11211147 (App. No. 17179267), in the Office action mailed 08/21/2025 is withdrawn in view of the Terminal Disclaimer filed 12/12/2025.
Claim Rejections - 35 USC § 112 (Newly Applied)
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 ma11er 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 ma11er which the applicant regards as his invention.
Claims 31-38 and 40-51 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 ma11er 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.
Independent claims 31 and 50-51 recite:
In Step C) “determining a plurality of segment-level coverage values by: forming, using the at least 500 bin-level coverage values, a plurality of segments by grouping respective subsets of adjacent bins in the plurality of bins based on a similarity between the respective bin-level coverage values of the subset of adjacent bins…”
In Step D) “determining the circulating tumor fraction for the test subject to be a first circulating tumor fraction based on agreement between corresponding values … in a plurality of integer copy states, that is consistent with the segment-level coverage value.”
The recitation of “based on a similarity,” “based on agreement” and “that is consistent” renders the claims indefinite. The phrases are of relative or vague degree or form of association and the metes and bounds of the claim are not clearly defined. The identified phrases are not defined by the claim. The specification also 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.
Claim 35 recites “…determining, for each respective circulating tumor fraction in the plurality of simulated circulating tumor fractions, a corresponding agreement and selecting the first circulating tumor fraction from among the plurality of circulating tumor fractions on the basis that the first circulating tumor fraction has the best agreement in the plurality of circulating tumor fractions.”
Claim 40 recites “wherein the agreement is based on an aggregate of a respective difference…”
The term “agreement” and the phrase “best agreement” renders the claim indefinite as identified in claims 35 and 40. The identified term or phrase are of relative or vague degree or form of association and the metes and bounds of the claim are not clearly defined. The identified phrases are not defined by the claim. The specification also 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.
Dependent claims are rejected for depending on rejected claims.
Regarding 35 USC 101
Claims 31-38 and 40-51 are patent-eligible under 35 U.S.C. 101 because independent claims 31 and 50-51 do not recite mathematical concepts or the mental process grouping of abstract ideas under Step 2A, 1st prong of the 101 analysis. The independent claims recite the step of determining a plurality of at least 500 bin-level coverage values using the plurality of at least 10,000 nucleic acid sequences, each respective bin-level coverage value in the plurality of bin-level coverage values corresponding to a respective bin in a plurality of at least 500 bins that require a level of complexity that is impractical to perform in the human mind, and consequently do not recite a mental process grouping of abstract ideas.
Regarding 35 USC 103—No Art Rejections Applied
The closest prior art is Valouev (United States Patent Application Publication No. US 2021/0102262, as cited on 11/16/2024 IDS Document). Valouev teaches methods of analyzing targeted sequence reads to determine copy number variations. Valouev does not teach analysis of sequence reads comprising sequences of cell-free DNA fragments corresponding to probe sequences used to enrich cell-free DNA fragments and sequence reads comprising sequences of cell-free DNA fragments that do not correspond to probe sequences used to enrich cell-free DNA fragments and simulated circulating tumor fraction in claims 31, 50 and 51. It is not clear that any combinable art of record would have rendered the claims obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KETTIP KRIANGCHAIVECH whose telephone number is (571)272-1735. The examiner can normally be reached 8:30am-5:00pm EDT.
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/K.K./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686