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 .
Claim Status
Currently, claims 12-16, 21-23 are pending in the instant application. Claims 1-11, 17-20 have been canceled. Claim 23 has been added and claims 13, 15-16, and 22 are withdrawn. This action is written in response to applicant' s correspondence submitted 02/24/2026. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Claims 12, 14, 21, and 23 are under examination with respect to cg08559711, cg14014955, cg16997642 and rs1436175 and rs4436578.
Withdrawn Objections/Rejections
The object to claim 14 is withdrawn in view of the amendment to the claims.
The rejection of claims 8, 12, 14 and 21 35 U.S.C. 112(b) is withdrawn in view of the amendment to the claims.
The rejection of claims 1-3, 5-6, 8, 12, 14, 21 are rejected under 35 U.S.C. 101 is withdrawn in view of the amendment to the claims.
The rejection of claims 1-2, and 8 under 35 U.S.C. 102(a)(1) as being anticipated by Montalvo-Ortiz (Scientific Reports, 2019, 9:4660, cited on IDS) is withdrawn in view of the amendment to the claims.
Maintained Rejections
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 12, 14, 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Montalvo-Ortiz (Scientific Reports, 2019, 9:4660, cited on IDS) in view of Langerveld (WO2020/247490) and Zhang (Psychopharmacology, 2021, 238: 3511-3518). This rejection was previously presented and has been rewritten to address amendment to the claims.
Montalvo-Ortiz teaches 140 opioid dependence samples and 80 opioid exposed control samples (see material and methods). Montalov-Ortiz teaches obtaining genomic DNA and determining methylation status using Illumina Infinium Human MethylationEPIC bead array (see genomic DNA extraction, Bisulfite Modification, Methylation array, pg. 2). The Illumina Methylation EPIC bead array comprises probes for determining methylation status including positions cg08559711, cg14014955, and cg16997642 and comprises probes for determining a specific panel of SNPs. Because Montalvo-Ortiz teaches determining methylation status and genomic analysis using MethylationEPIC bead array, the method of Montalvo-Ortiz will include determining methylation at position cg08559711, cg14014955, and cg16997642 and panel of SNPs, therefore will comprising conducting a molecular assay on a DNA sample to detect a specific panel of SNPs and specific panel of methylated sites associated with OUD. Montalvo-Ortiz does not teach detecting SNP markers rs1436175 or rs4436578. Montalvo-Ortiz does not teach use of non-opioid therapies in patients with high risk OUD.
However it was known in the art that rs1436175 and rs4436578 are variants that are associated with opioid dependence and the presence of the SNPs are associated with OUD.
Langerveld teaches a method of assessing risk of opioid addiction by determining the presence of alleles in biological samples, comparing the risk value to reference values and administering a medical assisted treatment based on the risk score (see para 7). Langerveld teaches determining the allele of rs1436171 (see para 15) (table 1) and rs4436578 (table 1). Langerveld teaches tapering off the opioid and the use of non-opioid therapies in patients with high risk of OUD (see para 44).
Zhang teaches analysis of SNPs and methylation of CpG sites determined in patients with heroin use disorder compared to healthy control (see objectives) Zhang teaches SNP and methylation in genes are attractive candidates for variations of disease susceptibility and phenotypic traits (see pg. 3512, 1st column). Zhang teaches several associations between genotypes of SNPs and CpG methylations in DRD2 gene (see pg. 3514, 2nd column and pg. 3516, 1st column). Zhang teaches genome-wide screening could be performed to gain a comprehensive view of the role of CpG and SNPs in opioid use disorder (see pg. 3516, 1st column).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the method of determining risk of OUD by analysis of methylation as taught by Montalvo-Ortiz to include additional markers including SNP analysis to allow for a comprehensive view of genetics in opioid use disorder as taught by Zhang and include known SNPs associated with opioid use disorder including rs1436175 and rs4436578 as taught by Langerveld including altering pain treatment to include non-opioid therapy as taught by Langerveld to allow for a more robust method of identify risk and treatment of OUD. The ordinary artisan would have been motivated to improve the method of determining risk of OUD by methylation analysis as taught by Montalvo-Ortiz with the teaching of Zhang to include analysis of both methylation and SNP detection to allow for a more robust association of OUD and Langerveld because Langerveld teaches SNP analysis for risk of OUD and further teaches treatment of pain in patients with risk of OUD by treating with non-opioid therapy. The ordinary artisan would have had a reasonable expectation of success that the use of SNP detection including rs1436175 and rs4436578 and treatment with non-opioid therapy to high risk subjects with OUD as taught by Lagervald could be used in the method of Montalvo-Ortiz because Zhang teaches SNP and methylation in genes are attractive candidates for variations of disease susceptibility and phenotypic traits and genome-wide screening could be performed to gain a comprehensive view of the role of CpG and SNPs in opioid use disorder.
Response to Arguments
The response traverses the rejection on pages 8-9 of the remarks mailed 02/24/2026. The response asserts Montalvo-Ortiz fails to provide any guidance for selecting any particular site for analyzing methylation including the specific sets of markers disclosed in the current claims. The response further asserts that Montalvo-Ortiz does not teach an assay that investigates methylation patterns in conjunction with SNP markers and Zhang does not provide guidance for selecting the claimed combination of markers. This response has been reviewed but not found persuasive. The claims are not limited to only the elected combination of markers. The claims encompasses detecting methylation state of two or more DNA sites and detecting the presence of one or more SNPs, while the claims recite the elected combination the claims do not exclude additional sites from being detecting. As such the teaching of Montalvo-Ortiz analyzes methylated state of the elected methylation sites and identifies subjects at risk of OUD. It is noted the claims do not require detecting any specific methylation level as such the use of the array in Montalvo-Ortiz encompasses analysis of the elected methylation levels. Zhang provides the motivation to include analysis of SNP and methylation sites to detect opioid risk dependence.
The response asserts that Langerveld does not teach the specific combination of rs1436171 and rs4436578 for OUD risk. The response asserts that the table of Langerveld discloses 180 SNPs and is devoid of any suggestion of using the specification combination of rs1436171 and rs4436578 for OUD risk. The response further asserts the laundry list of SNPs markers fails to provide guidance for conducting as assay utilizing SNP markers in combination with the cg08559711, cg14014955, and cg16997642. This response has been reviewed but not found persuasive. Langerveld was not cited to teach the combination of SNPs with cg08559711, cg14014955, and cg16997642. Langerveld was cited to teach rs1436171 and rs4436578 for OUD risk. While table 1 discloses 180 SNPs, the claims do not exclude additional SNPs in the analysis of identifying OUD risk. Even arguendo the claims were limited to the only two SNPs, Langerveld teaches a finite number of identified predictable SNPs that are associated with OUD risk. One of ordinary skill in the art would have pursued the known potential solutions with a reasonable expectation of success, one of ordinary skill in the art would have looked for additional markers that correlated to OUD risk and would have been able to narrow the number of associated markers, as taught by Langerveld with the knowledge of Zhang that analysis of SNPs and methylation of CpG sites gain a comprehensive view of the role in opioid use disorder and teach associations in the DRD2 gene.
The response asserts that the Office errs by adopting an unsupported obvious to try rationale and the Examiner fails to provide any object reasoning for why one of ordinary skill would have specifically selected the claimed combination of methylation markers and SNPs for analysis of OUD risk. This response has been reviewed but not found persuasive. The claims are limited to only the 3 elected CpG sites and the 2 elected SNPs sites. Additionally the claims are not limited to specific methylation levels or specific alleles detected at the SNP sites, the claims read on measuring any level and any allele, which would include wild type alleles. While the claims are not limited to only detecting the elected combination, the examiner did address the reasoning for why one of ordinary skill would have selected the claimed combination o methylation markers and SNPs for analysis of OUD risk. The rejection addressed that it would have been obvious to improve the method of determining risk of OUD risk as taught by Montalvo-Ortiz to include additional markers including SNP markers to allow for a comprehensive view of genetics in OUD as taught by Zhang and include known SNPs associated with OUD as taught by Langerveld to allow for a more robust method of identifying risk and treatment of OUD. For these reasons and reasons of record this rejection is maintained and applied to newly added claim 23.
Conclusion
No claims are allowable
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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