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 .
Election/Restrictions
Applicant’s election of:
(i) 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (RVX-208 or RVS000222) of examined claim 5 (Examiner notes that claim 4 has been canceled with the amendment, formula I removed from claim 1, and the elected compound is now recited by amended claim 1); (this compound is also known as apabetalone)
(ii) vildagliptin (amended claim 1, 27);
(iii) the patient population of examined claim 9 (human with type 2 diabetes and low HDL cholesterol and recent acute coronary syndrome (ACS)), has been included in amended claim 1, and claim 9 has been canceled;
(iv) Non-fatal myocardial infarction as the MACD event specie (claims 11, 14, 17-18);
(v) treating (claim 1);
(vi) simultaneously (claim 20);
in the reply filed on 10/13/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 13, 19, 21-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/13/2025.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 102
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 1, 5-6, 11, 14, 17-18, 20, 27 is/are rejected under 35 U.S.C. 102((a)(1)) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Ray et al. (“Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design and baseline characteristics of the BETonMace trial”; 2019 Aug; Am. Heart J.; 217:72-83; IDS reference); in view of Liu et al. (“Dipeptidyl peptidase 4 (DPP-4) inhibitors and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM): a systematic review and meta-analysis”; 2019; NMC Pharmacology and Toxicology; 20:15; pp 1-9; IDS reference).
Ray teaches patients with acute coronary syndrome in the preceding 7-90 days, with type 2 diabetes and low HDL cholesterol (<=40 mg/dL for men, <= 45 mg/dL for women), receiving intensive or maximum-tolerated therapy with atorvastatin or rosuvastatin were assigned in double-blind fashion to receive apabetalone (Applicant elected RVX-208) 100 mg orally twice daily or matching placebo. Baseline characteristic include myocardial infarction (Applicant elected non-fatal MI) as index ACS event (abstract; Design).
The baseline characteristics set forth in Table IV include, under diabetes medications, 157 patients taking DPP4 inhibitors.
Examiner notes that this teaching matches the required method for Applicant elected treating MACE, with the same elected compound apabetalone, on a statin therapy, having type 2 diabetes, and the required level of low HDL cholesterol, and having a recent ACS event.
Ray makes clear that a portion of the patents received DPP4 inhibitors, but only presents them as a class of compounds, without naming specific DPP4 inhibitors. The skilled artisan would construe that about half of the patients taking DPP4 inhibitors also received active apabetalone. The elected vildagliptin is not explicitly named.
While likely that some of these patients received applicant elected vildagliptin, the skilled artisan would have found it obvious to evaluate DPP4 inhibitors and the relation to cardiovascular events to evaluate suitable compounds. Among these references are Liu.
Liu teaches a systematic comparison of cardiovascular outcomes associated with DPP-4 inhibitors v. non-DPP4 inhibitor users, having T2DM; non-fatal myocardial infarction is among primary endpoints. Endpoint was not significantly different for DPP-4 group. The current analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes in these patient with T2DM indicating that those drugs might be safe to use in terms of cardiovascular events (abstract). Among drugs searched are vildagliptin (p. 2, right, top paragraph). Thus, selection of Applicant elected vildagliptin would have been an obvious DPP-4 inhibitor to include in the Ray trial for patients taking a DPP-4 inhibitor, rendering obvious the instant elected method.
Examiner notes that combination of DPP-4 inhibitors and apabetalone has a significantly reduced rate of incidence of Applicant elected non-fatal MI (compare Figure 7 with Figure 8; see also Figure 9. However, the evidence is presented for only a class of DPP-4 inhibitors. This class of compounds is clearly taught by Ray.
The Examiner did not identify disclosure of superiority of vildagliptin over the class of DPP-4 inhibitors or over other specific DPP-4 inhibitors. Therefore, there is not unexpected result of the elected combination.
Regarding the elected simultaneously dosing (claim 20) this would have been one obvious choice for dosing the combinations of the apabetalone and vildagliptin, as a technique for dosing both of these active compounds.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIMOTHY P THOMAS whose telephone number is (571)272-8994. The examiner can normally be reached M-Th 6:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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TIMOTHY P. THOMAS
Primary Examiner
Art Unit 1614
/TIMOTHY P THOMAS/Primary Examiner, Art Unit 1614