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’s election without traverse of BSTUI restriction enzyme as a species in the reply filed on 5/9/2023 is acknowledged.
Claims 3-7,11,13-17,19,20,22,23-29,32,35-38,40 are pending. Claims 20 and 22 are withdrawn as being drawn to a nonelected species.
Claims 1-2,8-10,12,18,21,30-31,33-34,39,41-44 have been cancelled.
The following rejections for claims 3-7,11,13-17,19 ,23-29,32,35-38,40 newly applied based upon the IDS filed 12/02/2025.
This action is NONFINAL.
Withdrawn Rejections
The 35 USC 103 rejections made in the previous office action are withdrawn based upon amendments to the claims.
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) 3-7,11,13-17,19 ,23-29,32,35, 36-38,40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Belhocine et al (US Patent Application Publication 20190361010 effective filing date 2/12/2018) in view of Jeddeloh et al. (WO 2005042704 May 12, 2005 cited on IDS).
With regard to claim 3, Belhocine et al teaches partitioned into subsets based upon methylation information (para 889). Belhocine teaches digesting with a methylation sensitive restriction enzyme, capturing and sequencing (para 889). Belhocine et al teaches first and second partitioned sets that have epigenetic target regions versus variable regions and wherein one is methylated and not methylated (para 252-259 and 1425-1435). The reference does not specifically teach physically partitioning the first set. The instant specification teaches that partition can be done with MBD and the methyminer methylated DNA enrichment kit (para 205). Although does not teach “thereby removing incorrectly partitioned molecules”, this would be the intended result of digesting.
With regard to claim 4, Belhocine et al teaches captaining using target specific probes for partition regions (para 854).
With regard to claim 5, Belhocine et al detecting of methylation status of the partitioned set (para 889).
With regard to claim 6, Belhocine et al teaches first and second partitioned sets that have epigenetic target regions versus variable regions and wherein one is methylated and not methylated (para 252-259 and 1425-1435).
With regard to claim 7, Belhocine et al et al. teaches using capturing sequencings to capture portions of the sets with adaptors (para 389-390).
With regard to claims 11, Belhocine et al teaches detection of cancer based upon epigenetic differences (para 437).
With regard to claim 13, Belhocine et al teaches partitioned sets and comparison of methylated to unmethylated and digestion of with a methylation sensitive restriction enzyme (para 735-737).
With regard to claim 14, Belhocine et al teaches that the adaptors can include a tag (para 179).
With regard to claim 15-16, Belhocine et al teaches partitioned into subsets based upon methylation information (para 889). Belhocine teaches digesting with a methylation sensitive restriction enzyme, capturing and sequencing (para 889). Belhocine teaches digestion at recognition sites and amplifying portions of the nucleic acid after digestion. Belhocine et al teaches first and second partitioned sets that have epigenetic target regions versus variable regions and wherein one is methylated and not methylated (para 252-259 and 1425-1435).
With regard to claims 17, 19, 23, Belhocine et al teaches methylation restriction enzymes that can including one or more of a combination that is at least 3 enzymes that include BstUI (para 748).
With regard to claims 24-25, Belhocine et al teaches 5-methocytosine or 5 hydroxymethylcytosine and an adaptor that is used before and after enzyme digestion (para 130-131 and 165).
With regard to claim 26-27, Belhocine et al teaches partitioned sets and comparison of methylated to unmethylated and digestion of with a methylation sensitive restriction enzyme with a protected adaptor (para 130-131, 165, 735-737).
With regard to claim 28, Belhocine et al teaches that the adaptors can include a tag (para 179).
With regard to claim 29, Belhocine et al teaches that the tags can be barcodes (para 175).
With regard to claims 32, Belhocine et al teaches 5-methocytosine or 5 hydroxymethylcytosine and an adaptor that is used before and after enzyme digestion (para 130-131 and 165).
With regard to claim 35, Belhocine et al teaches that the sample can be cfDNA (para 182 and 956).
With regard to claims 37-38, Belhocine et al teaches the partition based upon differential binding affinity (para 584). Further Belhocine et al teaches a methyl binding domain protein as it teaches MHC peptide complexes as a binding agent (para 599).
With regard to claim 40, Belhocine et al teach teaches detection of one or more genomic regions that have different methylation regions for cancer (para 437-440 and 737-740).
With regard to claim 3, Jeddeloh et al. teaches methods of detecting the presence of methylation by dividing the population of nucleic acids into at least 2 portion, and adding methylation restriction enzymes (p. 2-3). Jeddeloh et al. teaches that samples can be divided into different combinations of restriction digests and compared to one another (para 75). Further Jeddeloh et al.suggests multiple populations including different amounts and types of enzymes employed and proportions of cells that comprise methylated and unmethylated (p. 16-18). As such Jeddeloh et al. teaches different modifications of populations with restrictions enzymes after separation into groups.
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effected filing date to use a physical partition method known in the prior art (Jeddeloh et al.) to separate the methylation and unmethylated regions of a sample as taught by Jeddeloh et al.. It would be obvious to one of ordinary skill in the art at the time of filing to divide the nucleic acid population into two portions and contact there portion with methylation enzyme restriction enzymes and determine the present of methylation and unmethylated fragments in the populations. Absence secondary considerations it would be obvious to digest the partition sets with different sets of methylated and unmethylated molecules with restriction enzymes to digest. The digestion would remove incorrectly partitioned molecules in the partitioned samples.
Claim(s) 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Belhocine et al (US Patent Application Publication 20190361010 effective filing date 2/12/2018) and Jeddeloh et al. (WO 2005042704 May 12, 2005 cited on IDS) as applied to Claims 3-7,11,13-17,19 ,23-29,32,35, 36-38,40 and in view of Kennedy et al. (US Patent Application Publication 2020/0248272 August 6, 202
Belhocine et al teaches partitioned into subsets based upon methylation information (para 889). Belhocine teaches digesting with a methylation sensitive restriction enzyme, capturing and sequencing (para 889). Belhocine et al teaches first and second partitioned sets that have epigenetic target regions versus variable regions and wherein one is methylated and not methylated (para 252-259 and 1425-1435). The reference does not specifically teach physically partitioning the first set. The instant specification teaches that partition can be done with MBD and the methyminer methylated DNA enrichment kit (para 205). Belhocine et al teaches that the sample can be cfDNA (para 182 and 956). Jeddeloh et al. teaches digestion after separation and that the separation can encompass multiple different combinations of methylated and unmethylated.
However Belhocine et al. and Jeddeloh et al. does not teach the amount of cfDNA used in the assay.
.
With regard to claim 36, Kennedy et al. teaches methylation detection of cfDNA that includes 500ng of same for the assay (para 22).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effected filing date to modify a physical partition method known in the prior art of Belhocine and Jeddeloh to separate the methylation and unmethylated regions of a sample of cfDNA that is 500ng as taught by Kennedy et al. The ordinary artisan would be motivated as Kennedy et al. teaches methods of methylation detection in cfDNA and the amount of sample which can be used in methylation assays.
Conclusion
No claims are allowed.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682