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 .
Applicant filed a communication dated 10/18/2024 in which claims 1-50 are pending in the application. Preliminary amendment dated 4/22/2025 in which claims 2-20 have been amended and claims 21-50 have been canceled. Thus, the claims 1-20 are pending in the application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/22/2025 and 11/13/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner (see attached PTO-1449).
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 an abstract idea to calculate a risk probability for a cardiac event for a subject without significantly more.
Claim 1 is directed to a method, which is one of the statutory categories of invention (Step 1: YES).
The claim 1 recites a series of steps, e.g., detecting methylation in at least one of a plurality of sites in nucleic acids in a cell-free DNA (cfDNA) sample from a subject; generating a plurality of methylation calls for each of the plurality of sites; determining one or more metrics from the methylation calls; and processing the one or more metrics to calculate a risk probability for a cardiac event for the subject. These limitations describe the abstract idea to calculate a risk probability for a cardiac event for a subject which corresponds to a certain method of organizing human activity and hence are abstract in nature. The claim does not recite any additional elements. Thus, the claim 1 recites an abstract idea (Step 2A, Prong 1: YES).
This judicial exception is not integrated into a practical application because the claim does not recite any additional elements. Thus, the claim 1 is directed to an abstract idea (Step 2A-Prong 2: NO).
The claim 1 does not include additional elements that amount to add significantly more (Step 2B: NO). Thus, the claim 1 is not patent eligible.
Dependent claims 2-20 further define the abstract idea that is present in the independent claim 1, thus correspond to a Certain Methods of Organizing Human Activity and hence are abstract in nature. Dependent claims do not include any additional elements that integrate the abstract idea into a practical application or are sufficient to amount to significantly more than the judicial exception when considered both individually and as an ordered combination. Therefore, the claims 2-20 are directed to an abstract idea. Thus, the claims 1-20 are not patent eligible.
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.
Claims 1-4, 11-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Lambert, WO2024/112893 in view of Kim et al., US Patent Application No. 2021/0389309.
Regarding claim 1, Lambert discloses a method comprising:
detecting methylation in at least one of a plurality of sites in nucleic acids in a cell-free DNA (cfDNA) sample from a subject ([0004]-[0005], [0007], [0023]);
generating a plurality of methylation calls for each of the plurality of sites ([0237]);
determining one or more metrics from the methylation calls ([0138], [0237]); and
processing the one or more metrics to calculate a risk probability for a cardiac event for the subject ([0037], estimation of circulating tumor; [0073] recurrence risk; [0138], predicting a risk factor).
Lambert does not disclose
a cardiac event.
However, Kim discloses
a cardiac event (abstract).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert to include the above-noted disclosure of Kim. The motivation for combining these references would have been to determine the probability of a cardiac event.
Regarding claim 2, Lambert discloses wherein the at least one of the plurality of sites comprises one or more genes selected from the group consisting of: SIX2, KBTBD8, TAFA4, EVC, NCA, SNCA-AS, ARAP4, NT5E, XPO1, XPO1, TMEM181, NRG1, DYDC2, CACUL1,00RF888, FAM, FAM222A, MIR9-3HG, BCKDK, MAPK7, AlG, CACNA1, MXRA7, ADCYAP1, EPOR, MAST1, DKKL1, PCSK2, CGB7, EMB, TGFBI, COX6B1, ZNF347, and DKKL1 ([0018], XP01).
Regarding claim 3, Lambert discloses wherein the at least one of the plurality of sites comprises one or more genes selected from the group consisting of: SIX2, KBTBD8, TAFA4, EVC, NCA, SNCA-AS, CGB7, EMB, TGFBI, COX6B1, ZNF347, and DKKL1 ([0018], ZNF217, ZNF703).
Regarding claim 4, Kim discloses wherein the cardiac event comprises one or more of: stroke, transient ischemic attack (TIA), myocardial infarction (MI), angina, transient ischemic attack (TIA), stroke, and acute coronary syndrome ([0003]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert to include the above-noted disclosure of Kim. The motivation for combining these references would have been to determine the probability of a cardiac event.
Regarding claim 11, Lambert discloses wherein determining one or more metrics from the methylation calls comprises determining counts of methylated molecules for the at least one of the plurality of sites ([0007], absolute number; [0029], a total number).
Regarding claim 12, Lambert discloses wherein the counts are peak counts ([0029], a total number serves as peak counts).
Regarding claim 13, Lambert discloses wherein processing the one or more metrics comprises selection on the basis of tumor fraction and/or methylated molecule counts ([0138], [0237]).
Regarding claim 14, Lambert discloses wherein processing the one or more metrics comprises application of a model ([0224], Bayesian mutation calling method serves as a model, [0225], [0235]).
Regarding claim 15, Lambert discloses wherein the model is a probabilistic model ([0224]-[0225], [0235]).
Regarding claim 16, Lambert discloses wherein processing the one or more metrics comprises determining probabilities based on the one or more metrics ([0137], [0221]).
Regarding claim 17, Lambert discloses wherein the probabilities based on the one or more metrics generates calculation of the risk probability for the cardiac event for the subject ([0137], will develop a disease (e.g., cancer), [0221]).
Kim discloses the cardiac event (abstract).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert to include the above-noted disclosure of Kim. The motivation for combining these references would have been to determine the probability of a cardiac event.
Regarding claim 18, Lambert discloses wherein the risk probability for the subject is an increased risk for a cardiac event ([0137], [0221]).
Kim discloses
a cardiac event (abstract).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert to include the above-noted disclosure of Kim. The motivation for combining these references would have been to determine the probability of a cardiac event.
Regarding claim 20, Lambert discloses wherein the another disease or condition in the subject is selected from one or more diseases or conditions from the group consisting of: cancer, coronary heart disease, heart attack, high blood pressure, diabetes, thyroid disease, viral hepatitis, HIV1, and viral infections ([0003], [0005], cancer).
Claims 5-10 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Lambert, WO2024/112893 in view of Kim et al., US Patent Application No. 2021/0389309 in view of Anastassiadis et al., US Patent Application No. 2023/0203510.
Regarding claim 5, Anastassiadis discloses wherein the cardiac event is associated with cardiomyopathy selected from the group consisting of: dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular dysplasia (Table 6).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Regarding claim 6, Anastassiadis wherein the cardiomyopathy comprises inherited cardiomyopathy (Table 6, hereditary).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Regarding claim 7, Anastassiadis wherein the cardiomyopathy comprises acquired cardiomyopathy (Table 6).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Regarding claim 8, Anastassiadis discloses wherein the cardiomyopathy is associated with an agent (Table 6).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Regarding claim 9, Anastassiadis discloses wherein the agent is a drug (Table 6).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Regarding claim 10, Anastassiadis discloses wherein the drug is Letrozole, Palbociclib, Capecitabine, Tamoxifen, Trastuzumab, T-DM1, Pertuzumab, Ado- trastuzumab emtansine, Neratinib, Lapatinib, Tucatinib, Margetuximab, and Trastuzumab deruxtecan (Table 6).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Regarding claim 19, Anastassiadis discloses wherein the cardiomyopathy (Table 6)
Lambert discloses is a comorbidity with another disease or condition in the subject ([0003], [0005], cancer).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Lambert and Kim to include the above-noted disclosure of Anastassiadis. The motivation for combining these references would have been to determine the cause of a cardiac event.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure are listed on the attached PTO-892.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJESH KHATTAR whose telephone number is (571)272-7981. The examiner can normally be reached M-F 8AM-5PM.
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, Shahid Merchant can be reached at 571-270-1360. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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RAJESH KHATTAR
Primary Examiner
Art Unit 3684
/RAJESH KHATTAR/Primary Examiner, Art Unit 3684