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 .
Status of the Claims
Claims 1-18 and 156-164 are under examination.
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 1-18 and 156-164 are rejected under 35 U.S.C. 103 as being unpatentable over Dor et al. (WO 2015/159292 A2) in view of Chiu et al. (US 2016/0017419 A1).
Regarding claim 1, Dor et al. teach a method that includes receiving a plurality of sequencing reads (page 2, line 28-page 3, line 11) for a cfDNA obtained sample from the subject (page 2, line 28-page 3, line 11), wherein each sequencing read comprises methylation sequencing data (page 2, line 28-page 3, line 11) obtained from a nucleic acid sequence (page 2, line 28-page 3, line 11); determining a methylation pattern for a sequencing read in the plurality of sequencing reads (page 2, line 28-page 3, line 11) wherein the methylation pattern comprises a genomic region corresponding to the nucleic acid sequence and methylation status of one or more motifs in the genomic region (page 2, line 28-page 3, line 11); comparing the methylation pattern with each of the one or more pre-established methylation signatures to compute one or more likelihood scores (page 47, lines 3-31) wherein each of the one or more pre-established methylation signatures correlates with a cancer (page 47, lines 3-31) and wherein each pre-established methylation signature comprises at least one pre-determined signature region and pre-determined methylation rate associated therewith (page 47, lines 3-31; pages 61, example 5); characterizing the cfDNA sample as containing cfDNAs derived from the cancer tissue, based at least in part on at least one of the one or more likelihood scores thereby identifying the subject as having cancer (page 47, line 3- page 48, line 5; page 61, example 5).
While Dor et al. teach monitoring a treatment (page 14, lines 1-3), Dor et al. do not teach administering a treatment.
Regarding claim 1, Chiu et al. teach a method of identifying the disease state of a tissue (abstract) and treating with surgery, radiotherapy or chemotherapy based on the diagnosis (paragraph [0363]).
Regarding claim 2, Dor et al. disclose performing (b), (c), and (d) for each sequencing read in the plurality of sequencing reads (page 47, lines 3-8; each of the sequences are analyzed).
Regarding claim 3, Dor et al. teach establishing the one or more pre-established methylation signatures based on existing methylation sequencing data (page 16, lines 6-10).
Regarding claim 4, Chiu et al. teach determining a level of the cfDNAs derived from the cancer tissue based at least in part on a number of sequencing reads derived from the cancer tissue in the plurality of sequencing reads (paragraphs [0056], [0211]-[0214], [0225]-[0227]).
Regarding claim 5, Dor et al. disclose wherein the existing methylation sequencing data is selected from tissue-specific sequencing data (page 16, lines 19-21).
Regarding claim 6, Dor et al. disclose where the cfDNA sample is obtained from a plasma sample or blood sample from the subject (page 29, lines 1-3).
Regarding claim 7, Dor et al. disclose where the cancer tissue comprises a member selected from pancreas cancer tissue (page 46, lines 18-32).
Regarding claim 8, Dor et al. disclose where the cancer tissue comprises a member selected from pancreas cancer tissue (page 46, lines 18-32).
Regarding claim 9, Chiu et al. teach where the methylation status and pre-determined methylations status are determined at bin level (paragraph [0056]).
Regarding claim 10, Dor et al. teach where the methylation status and pre-determined methylations status are determined at CpG site level (page 7, lines 12-13; page 40, lines 1-2).
Regarding claim 11, Dor et al. teach where the motifs comprises a CpG site (page 40, lines 1-2).
Regarding claim 12, Dor et al. teach comparing the level of the cfDNAs derived from the cancer tissue to a first reference level derived from a reference subject with cancer (page 47, lines 13-31).
Regarding claim 13, Dor et al. teach comparing the level of the cfDNAs derived from the cancer tissue to a second reference level derived from a reference subject without cancer (page 47, lines 13-31).
Regarding claim 14, Dor et al. teach a method that includes determining the second reference level at least in part by receiving a second plurality of sequencing reads (page 2, line 28-page 3, line 11) for a cfDNA obtained sample from the reference subject without cancer (page 2, line 28-page 3, line 11), wherein each of the second sequencing reads comprises second methylation sequencing data (page 2, line 28-page 3, line 11) obtained from a second nucleic acid sequence (page 2, line 28-page 3, line 11); determining a second methylation pattern for a sequencing read in the second plurality of sequencing reads (page 2, line 28-page 3, line 11) wherein the second methylation pattern comprises a second genomic region corresponding to the second nucleic acid sequence and methylation status of one or more motifs in the second genomic region (page 2, line 28-page 3, line 11); comparing the second methylation pattern with each of the one or more pre-established methylation signatures to compute one or more second likelihood scores (page 47, lines 3-31); characterizing the second cfDNA sample as containing cfDNAs derived from the cancer tissue, based at least in part on at least one of the one or more second likelihood scores (page 47, line 3- page 48, line 5; page 61, example 5), repeating the determining, comparing and characterizing for each sequencing read in the second plurality of sequencing reads (page 47, lines 3-8)
However, Dor et al. does not disclose determining a level of cfDNA derived from the cancer tissue in the reference subject without cancer based in part on a number of sequencing reads derived from the cancer tissue in the second plurality of sequencing reads.
Regarding claim 14, Chiu et al. teach determining a level of cfDNA derived from the cancer tissue in the reference subject without cancer based in part on a number of sequencing reads derived from the cancer tissue in the second plurality of sequencing reads (paragraphs [0056], [0211]-[0214], [0225]-[0227]).
Regarding claim 156, Dor et al. teach where each of the plurality of sequencing reads comprises methylation sequencing data obtained from a consecutive nucleic acid sequence of 50 or more nucleic acids (page 2, line 28-pae 3, line 11).
Regarding claim 157, Dor et al. teach characterizing the cfDNA sample as containing cfDNAs derived from the cancer tissue, based at least in part on whether the at least one of the one or more likelihood scores exceeds a threshold value (page 47, lines 3-31).
Regarding claim 158, Dor et al. disclose where the cfDNA sample is obtained from a plasma sample from the subject (page 29, lines 1-3).
Regarding claim 159, Dor et al. disclose where the cfDNA sample is obtained from a blood sample from the subject (page 29, lines 1-3).
Regarding claim 160, Dor et al. disclose where the cancer tissue is liver cancer tissue (page 46, lines 18-32).
Regarding claim 161, Dor et al. disclose where the cancer tissue is lung cancer tissue (page 46, lines 18-32).
Regarding claim 162, Chiu et al. disclose where the cancer tissue is kidney cancer tissue (paragraphs [0167] and [0383]).
Regarding claim 163, Dor et al. disclose where the cancer tissue is colon cancer tissue (page 11, lines 16-18).
Regarding claim 164, Chiu et al. disclose where the cancer tissue is breast cancer tissue (paragraphs [0053] and [0060]).
It would have been obvious for one of ordinary skill in the art, at the time of filing, to combine the references of Chiu et al. and Dor et al. Dor et al. teach a method of determining the source of cfDNA for diagnosing disease as well as monitoring therapeutic regimens (page 1, lines 5-9). Similarly, Chiu et al. disclose a method for diagnosing the disease state for a tissue by determining the contributions of various tissue types (abstract). One of ordinary skill in the art would have been motivated to incorporate the teachings of Chiu et al. to determine the disease state after diagnosing a patient through Dor et al.’s method. In addition, one of ordinary skill in the art would have had a reasonable expectation of success since the methods could be performed consecutively or in parallel using the same samples.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JERRY LIN whose telephone number is (571)272-2561. The examiner can normally be reached T-F 7am-5pm.
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/JERRY LIN/Primary Examiner, Art Unit 1685