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 .
This action is in response to papers filed 4/17/2026.
Applicant’s election without traverse of Group I in the reply filed on 2/26/2024 is acknowledged.
Claims 3-11,15-16,100-108 are pending. Claims 1-2,12-14,17-99 have been cancelled.
The following rejections are newly applied (35 USC 112b and 35 USC 101 and 35 USC 103)
This action is NONFINAL.
Withdrawn Rejections
The obviousness double patenting rejection made in the previous office action is withdrawn based upon the terminal disclaimer filed 4/17/2026.
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 3-11,15-16,100-108 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.
Claims 3-11,15-16,100-108 are indefinite over step c of claim 3 and step b of claim 16. The claims require mapping the set of sequencing reads of the at least two sample to a reference to determine a plurality of epigenetic rates for DNA methylation. It is not clear what epigenetic rate for DNA methylation is intending to encompass. The claim further states that the plurality of epigenetic rates comprise a plurality of methylation rates. The specification recites “methylation rate” in paragraph 22 which states “at least one epigenetic rate comprises methaytlion rate”. The examiner is interpreting the term as “the proportion of a specific nucleobase in a genome that is chemically modified by the addition of a methyl group”. Therefore the claim mapping set is interpreted as measuring a plurality of DNA methylation rates for a plurality of genomic regions. The claim further states that the genomic regions comprise differently methylated regions that are perturbed by the cancer the can has or is suspected of haring. As such the limitation appears to require differently methylated regions perturbed by cancer, however, the subject is not required to have cancer and as such it is not clear how these regions comprise differently methylated regions perturbed by cancer in the subject “suspected of having”.
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.
After review of the claims the following 35 USC 101 is provided based upon the breadth of the claims such that the claims do not require an integration of the judicial exceptions. In particular the claims require mapping but does not require a particular integration.
Claims 1-11, 15-16, 100-108 76 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental step without significantly more. The claim(s) recite(s) the abstract idea or mental steps of mapping. This judicial exception is not integrated into a practical application because there are no steps which depend from or otherwise integrate the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because if there are no steps which depend from or otherwise integrate the judicial exception.
Claim analysis
The instant claims are directing towards obtaining samples from two different time points, proceeding the polynucleotides by partitioning, and mapping. The step of mapping is considered mental steps or abstract ideas.
Dependent claims 4-5, 100-108 limit the sample types. Dependent claims 6-7 modify the classifying the subject which is considered an additional abstract idea. Depending claims 8-9, 10-11, 15-16 limit to an identifying step of analyzing sequencing reads which could be interpreted as additional abstract idea.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract idea or mental step.
Claim 3 recites mapping the set of sequencing reads to determine a plurality of epigenetic rates for DNA methylation. Claim 16 recites mapping the set of sequence reads from at least two sets of sequencing reads.
This is an abstract idea or mental step. (UNIVERSITY OF UTAH RESEARCH v. AMBRY GENETICS CORPORATION).
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as there are no additional steps which depend from or otherwise integrate the judicial exception..
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No
The claims further recite steps of obtaining samples from the subject from at least two different time points. This step can encompass any known method of obtaining and as such the step encompasses conventional techniques that are well known and routine to obtain nucleic acids from a naturally occurring sample (see pages 20-21 of specification). The second step is processing partitioning samples based upon methylation and sequencing to produce reads. Zhao (Cellular Reprogramming 2014 Vol 16 p. 175-184) teaches steps of partitioning based upon methylation and sequencing those reads (see p. 177).
Thus the claim does not provide additional steps which are significantly more.
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.
Claim(s) 3,5-6,8-11,15-16,100-108 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (Cellular Reprogramming (2014) volume 16, pages 175-184) in view of DeCarvalho et al. (WO 2019/084659 May 9, 2019).
With regards to claim 3, and 16 Zhao teaches obtaining samples however, Zhao does not teach obtaining g samples from two different time pointes from a subject having cancer. Zhao et al. teaches partitioning based upon methylation. Zhao et al. teaches the a addition of spiked DNA with cytosine, 5mC and 5hmC to samples, separating and enrich the sample into subsets by use of antibodies and dynabeads (methylated DNA immunoprecipitation (176-177). Zhao teaches partition as Zhao et al. teaches the method of MeDIP-seq (p 178-179). Zhao teaches Zhao teaches sequencing, reads and alignment and data analysis (177, 1st column-2nd column).
With regard to claim 108, Zhao et al. teaches methods of partitioning portions of the polynucleotides. The claim limitation asserts a further partition based upon one or more additional epigenetic features, which can include methylation or histone modification. Zhao teaches partition in 5C, 5mC, and 5hmC (figure 1) and as such would encompass multiple epigenetic features.
With regard to claim 3, and 16 DeCarvalho et al. teaches that one can use MeDIP (p 30). DeCarvalho et al. teaches that measurements were obtained at different time points to determine methylation patterns (rates) (example 2 pages 38-39). DeCarvalho et al. teaches mapping these cancer types and classifying based upon trained mapping (p 36).
With regard to claim 5, DeCarvalho et al teaches using cfDNA profiling (p. 39).
With regard claim 6, DeCarvalho et al. teaches that threshold for methylation can be adjusted (p.7 figure 6). Therefore DeCarvalho et al. suggests that the thresholds can be adjusted such that different regions can be compared.
With regard to claims 8-9, DeCarvalho et al. teaches sequencing read analysis of somatic mutations that can encompass SNPs (figure 1).
With regard to claim 10, DeCarvalho et al teaches a method of classifying based upon the presence or absence of ctDNA determination of IDH mutational status (p 32, 37, 39).
With regard to claims 11 and 15, DeCarvalho et al. the method determination likelihood of cancer based upon the combined regions of a sample and methylation enrichment and class probabilities based upon the combination of data (p. 7 and 32).
With regard to claims 100-101, DeCarvalho et al. teaches time points of starting therapy and surgery (p 38 example 2).
With regard to claims 102-103, DeCarvalho et al. teaches measurement prior to a therapy, including surgery (p. 38 example 2).
With regard to claim 104-106, DeCarvalho et al. teaches times can encompass 235 days (p. 38 Example 2).
With regard to Claim 107, although DeCarvalho et al. does not teach a year, it would be obvious to one of ordinary skill in the art to further measure samples after therapy for a number of years after treatment to determine changes in methylation after treatment and reemission.
Therefore it would have been prima facie obvious before the effective filing date of the claims to add the time period sampling of cancer patients as taught by DeCarvalho to the method of Zhao. The artisan would be motivated to measure methylation changes (rates) in subjects to make determination of methylation changes in cancer patients at different times. The artisan would have a reasonable expectation of success as the artisan is using known methodology and mapping techniques to a known population (cancer patients).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached on 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682
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