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 .
Response to Amendment
The amendments received 03/02/2026 have been entered. Claims 16-19, 23-24, 26-27, and 29-30 are pending. Any objection or rejection previously set forth in the Office Action mailed 10/09/2025 not maintained herein has been overcome and is withdrawn.
Claim Objections
Claims 17-19 are objected to because of the following informalities: "the combination the beta blocker" should read "the combination of the beta blocker". Appropriate correction is required.
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.
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) 16-19, 23-24, 26-27, 29-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hawken et al. (Headache; 2001; previously cited by Examiner) in view of Peroutka et al. (US 2006/0142288 A1; 2006; IDS).
Hawken et al. discloses a method of treating severe migraine pain due to electroconvulsive therapy (ECT), comprising administering to a patient a pharmaceutical combination of 500 mg naproxen and 20 mg propranolol (p. 93, col. 1). The patient was administered 2.6 doses per day on ECT treatment days and 1.4 doses per day on non-ECT treatment days (p. 93, col. 2).
Hawken et al. does not disclose administering the propranolol with a non-selective NSAID that is flurbiprofen, diclofenac, or meloxicam. Hawken et al. does not disclose administering the naproxen with metoprolol. Hawken et al. does not disclose that the beta blocker and non-selective NSAID are in a single oral unit dose. However, these limitations are obvious over Peroutka et al.
Peroutka et al. discloses the combination of COX-3 inhibitors with beta-adrenergic receptor antagonists for the treatment of headache pain, including migraine (Abstract). Peroutka et al. points to particularly preferred combinations including “naproxen and metoprolol; naproxen and propranolol; meloxicam and metoprolol; meloxicam and propranolol” (p. 3, par. [0027]). Peroutka et al. additionally discloses the flurbiprofen and diclofenac are NSAIDs with known COX-3 inhibitory activity (p. 2, par. [0012]). Peroutka et al. discloses that the compositions may be combined in a form suitable for oral use with excipients and formulated such that the agents require administration once or twice a day (p. 3, par. [0027]; p. 4, par. [0032]).
It would have been prima facie obvious to i) substitute naproxen with meloxicam, flurbiprofen, or diclofenac, or ii) substitute propranolol with metoprolol. One would have been motivated to do so, with reasonable expectation of success, as these agents are known to be equivalent in function to each other as NSAIDs that function as COX-3 inhibitors and beta blockers, respectively. Moreover, Peroutka et al. suggests that these agents can be combined to treat or prevent headache pain, in particular migraine pain, as is similarly treated by Hawken et al. Therefore, one of ordinary skill in the art would be apprised that substitution of one agent for another would yield predictable results.
It would have been prima facie obvious for one of ordinary skill in the art to combine the beta blocker and non-selective NSAID into a single oral unit dose. One would have been motivated to do so, with reasonable expectation of success, in order to make administration more convenient and less frequent, as suggested by Peroutka et al. Moreover, it would be within the purview of one of ordinary skill in the art to add additional excipients as needed in order to facilitate oral administration.
Examiner additionally clarifies that in claim 27, the limitation “when the beta blocker is propranolol…” has been interpreted to mean that the amount of beta blocker only needs to be “in the range of 3 to 15 mg” when the beta blocker is propranolol in combination with flurbiprofen, diclofenac, or meloxicam (or, as in claim 26, naproxen).
Response to Arguments
Applicant's arguments filed 03/02/2026 have been fully considered but they are not persuasive.
Regarding the rejection of claims 16-19, 23-24, 26-30 under 35 U.S.C. 103 over Hawken et al. in view of Peroutka et al., Applicant argues that Hawken et al. fails to disclose or suggest the amounts of propranolol recited in claims 16 and 26, or the other claimed combinations. Applicant additionally argues that Peroutka et al. fails to remedy the deficiencies of Hawken et al. by also failing to disclose or suggest the amounts of propranolol recited in claims 16 and 26 or the specific combinations or amounts recited in the dependent claims. See Remarks p. 7-8. This is not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Moreover, regarding Applicant’s argument that the references do not teach the claimed amounts, Examiner acknowledges that while claim 16 requires a particular amount of propranolol (3 to 15 mg) when in combination with naproxen, claim 16 does not require this amount of propranolol when in combination with any other NSAID. Moreover, when the beta blocker is metoprolol, no amounts are required for either the beta blocker or the NSAID. Similarly, claim 26 only requires that the amount of beta blocker be from 1 to 20 mg unless the combination is propranolol and naproxen, wherein the amount of propranolol is 3 to 15 mg. Hawken et al. teaches a dose of 20 mg propranolol, which is within the scope of claim 26 (and claims 17-19 which depend from claim 16) when propranolol is administered with any of the claimed NSAIDs other than naproxen. Furthermore, regarding claims 27 and 30, claim 27 only requires a narrower range of beta blocker (3 to 15 mg) when the beta blocker is propranolol, but no amount of metoprolol is required. Claim 30 requires an amount of naproxen between 200 to 600 mg, which is taught by Hawken et al., but does not limit the amount of metoprolol if the two are combined.
Applicant has additionally provided no arguments about obviousness to substitute naproxen with another NSAID when considering Hawken et al. and Peroutka et al. in combination, as set forth in the above 103 rejection. Applicant has presented no arguments regarding obviousness to substitute propranolol with metoprolol when considering Hawken et al. and Peroutka et al. in combination, as set forth in the above 103 rejection. See Examiner’s comments above regarding attacking references individually. The rejection is maintained.
Examiner suggests amending the claims such that both the amounts of the beta blockers and the amounts of the NSAIDs are further limited in the independent claims. Applicant is welcome to contact Examiner to discuss any proposed amendments or to request clarification.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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/M.E.B./Examiner, Art Unit 1624 03/26/2026
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624