Office Action 2: Notice of Allowance (2025-01-02)

CLAIMS:
We claim:

1\. A method for predicting post-traumatic stress disorder (PTSD) in a subject comprising the steps of:
a. measuring the DNA methylation level of a CpG located on the minus strand of chromosome 17, at position 57187729, from DNA isolated from a sample collected from the subject;
b. identifying the genotype at the single nucleotide polymorphism (SNP), rs7208505, from DNA isolated from a sample collected from the subject; and
c. predicting PTSD in the subject using a linear model that utilizes the DNA methylation level, genotype at rs7280505, age and sex.

2\. The method of claim 1, wherein the linear model further utilizes a stress/anxiety metric.

3\. The method of claim 2, wherein the stress/anxiety metric comprises the results from a stress/anxiety questionnaire.

4\. The method of claim 2, wherein the stress/anxiety metric comprises salivary cortisol measurement from the subject.

5\. The method of claim 2, wherein the stress/anxiety metric comprises a biomarker of salivary cortisol measured from the subject.

6\. The method of claim 1, wherein the sample is a blood, serum, or saliva sample.

7\. A method for predicting PTSD in a subject comprising the steps of:
a. measuring the DNA methylation level of a CpG located on the minus strand of chromosome 17, at position 57187729, from DNA isolated from a sample collected from the
subject;
b. identifying the genotype at the single nucleotide polymorphism (SNP), rs7208505, from DNA isolated from a sample collected from the subject; and
c. predicting PTSD in the subject using a linear model that utilizes the DNA methylation level, genotype at rs7280505, age, sex and a stress/anxiety metric.
8\. The method of claim 7, wherein the stress/anxiety metric comprises the results from a stress/anxiety questionnaire.

9\. The method of claim 7, wherein the stress/anxiety metric comprises salivary cortisol measurement from the subject.

10\. The method of claim 7, wherein the stress/anxiety metric comprises a biomarker of salivary cortisol measured from the subject.

11\. The method of claim 7, wherein the sample is a blood, serum, or saliva sample.

12\. A method for predicting PTSD comprising the steps of:
a. measuring DNA methylation level at a CpG dinucleotide located in the 3'
untranslated region (UTR) of SKA2 from DNA isolated from a sample collected from the subject;
b. identifying the genotype at the SNP rs7208505, from DNA isolated from a sample collected from the subject; and
c. predicting PTSD in the subject using a linear model that incorporates the
measured DNA methylation level and genotype.

13\. The method of claim 12, wherein the CpG dinucleotide in the 3' UTR of SKA2 is located on the minus strand of chromosome 17, at position 57187729.

14\. The method of claim 12, wherein the linear model further utilizes age and sex as additive covariates.

15\. The method of claim 12, wherein the linear model further utilizes a stress/anxiety metric.

16\. The method of claim 15, wherein the stress/anxiety metric comprises the results from a stress/anxiety questionnaire.

17\. The method of claim 15, wherein the stress/anxiety metric comprises salivary cortisol measured from the subject or a biomarker thereof.
18\. The method of claim 12, wherein the sample is a blood, serum, or saliva sample.

19\. The method of claim 12, wherein the sample is a blood, serum, or saliva sample taken before a stressor and then again after a stressor

20\. The method of claim 12, wherein the difference in DNA methylation at SKA2 is modeled with rs7208505 as an additive covariate to predict PTSD risk. 65 66 67 5 10 15 20 25 30 35

OFFICE 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 .
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance:
The claims are directed to measuring DNA methylation level of the CpG dinucleotide located on the minus strand of chromosome 17, at position 57187729 (cg13889295) and the genotype at the same position (rs7208505) and using a linear model to predict PTSD in the subject and administering a PTSD treatment to a subject predicted to have PTSD.  The claims have been amended to require a particular treatment for PTSD.
The specification teaches predicting PTSD in patients using the CpG dinucleotide located on the minus strand of chromosome 17, at position 57187729 (cg13889295) and the genotype at the same position (rs7208505)(para 102).  Figure 1 illustrates the area under the curve for the analysis is 0.78.
The Double Patenting rejection over Patent 10,280,464 has been withdrawn in view of the terminal disclaimer filed on November 20, 2024.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion

APPLICANT REBUTTAL: REMARKS
Claims 21-29 are pending. Claims 1-20 were canceled previously without prejudice. In this Reply and Amendment, claims 22 and 29 are canceled without prejudice. Applicant reserves the right to file a continuing application directed to the canceled subject matter.
Claims 21 and 28 are amended. Support for amended claims 21 and 28, can be found throughout the specification including, but not limited to, the original claims and page 11, lines 15-21. No new matter is added.
Accordingly, claims 21 and 23-29 are currently under consideration.
Rejection Under 35 U.S.C. 101
Claims 21-29 were rejected as being directed to a judicial exception without significantly more. Applicant respectfully traverses.
Nevertheless, without acquiescing to the rationale of the rejection and in an effort to
expedite prosecution, Applicant has amended claim 21 to incorporate the limitations of claim 29 (now canceled). Amended claim 21 provides specific PTSD treatments. Applicant submits that amended claim 21 addresses the rejection. Claim 22 is canceled without prejudice. Claims 23- 29 depend from amended claim 21.
Accordingly, Applicant respectfully requests reconsideration and withdrawal of the present rejection.
Rejection Under 35 U.S.C. 112(a)
Claims 21-29 were rejected for lack of enablement. Applicant respectfully traverses.
Nevertheless, without acquiescing to the rationale of the rejection, and in an effort to expedite prosecution, Applicant has amended claim 21 to recite a specific CpG dinucleotide located on the minus strand of chromosome 17, at position 57187729. Applicant submits that amended claim 21 addresses the rejection. Claim 22 is canceled without prejudice. Claims 23- 29 depend from amended claim 221. Applicant respectfully requests reconsideration and withdrawal of the present rejection.
Rejection Under 35 U.S.C. 112(b)
Claims 21-29 were rejected as being indefinite. Applicant has amended claim 21 to
delete the phrase "and diagnosed as such", which addresses the rejection. Claim 22 is canceled without prejudice. Claims 23-29 depend from currently amended claim 21. Claim 28 is
amended to refer to a difference in methylation level "relative to a control", which addresses the rejection. Applicant respectfully requests reconsideration and withdrawal of the present rejection.
Double Patentin
g
Claims 21-29 were rejected on the ground of non-statutory double patenting as being
unpatentable over claims 1-5 and 7-13 of U.S. Patent No. 10,280,464, in view of Khan, Arifulla (WO 2011/11927, September 29, 2011). In addition, claims 21-29 were rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,072,828, in view of Helton et al. (WO 2009/062134, May 14, 2009). Without acquiescing to the rational of the rejection, and in an attempt to expedite prosecution, Applicant files herewith a terminal disclaimer.
Conclusion