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 .
Detailed Action
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8 October 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. See attached copy of PTO-1449.
Status of Application
2. Applicants’ arguments/remarks filed 2 January 2026 are acknowledged. Claims 1-3 and 6-24 are currently pending. Claims 4-5 have been cancelled. Claims 1-3, 6-8, 15, and 20-23 are amended. Claims 1-3 and 6-24 are examined on the merits within.
Withdrawn Objections
3. Applicants’ arguments, filed 2 January 2026, with respect to the claim objections have been fully considered and are persuasive. The objections of claims 1-3, 15, and 20-23 have been withdrawn. The 35 U.S.C. 112(b) Rejections have been withdrawn in view of the claim amendments.
Modified Rejections
Claim Rejections – 35 U.S.C. 103
4. 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.
5. Claim(s) 1-3, 6-13 and 16-24 is/are again rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (WO2016/154503) in view of Wang et al. (Pharm Res 2014).
Zhao et al. teach soft gel capsules and liquid fills. See abstract. Active ingredients include nalbuphine. See page 5. The soft capsule shell comprises 20-60% polymers, 30-70% plasticizer, 0-2% polymer modifiers, 0-50% sweeteners, 10-40% solvents and 0.1-10% excipients. See Table 1. Polymers include gelatin such as 10-40% gelatin 150 Bloom and 1-20% Gelatin 100 Bloom combined with 10-50% glycerol and 1-30% maltitol. See Table 2. The soft capsule shell comprises one or more plasticizers including glycerol, maltitol, sorbitol, and combinations thereof. See page 31. Polymer modifiers include citric acid. See page 3. The formulation may comprise antimicrobial preservatives including methylparaben or propylparaben. See page 39. The solvent is water. See page 39. The composition comprises flavoring agents such as citric acid or sodium citrate. See page 3. The composition comprises teeth whitening agents. See page 49. Emulsifying and solubilizing agents include sorbitan. See pages 39-40.
Zhao et al. do not teach polysorbate 20 or PEG 400.
Wang et al. teach nalbuphine in combination with Tween 20 and PEG 400. See abstract. The Tween-PEG significantly enhanced the analgesic effects of orally administered nalbuphine. See abstract. 50, 100 or 200 mg/kg nalbuphine were administered with 4 mg/kg Tween-PEG. See page 1679. Tween 20 and PEG 400 are suitable for manufacturing soft oral capsules. See page 1684. Nalbuphine is used to treat pain. See page 1677.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to use the combination of nalbuphine, tween 20 and/or PEG 400 as the fill material in the soft shell capsule of Zhao et al. because Zhao et al. teaches that nalbuphine is an active used in the soft shell capsule and Wang et al. teach addition of Tween 20 and/or PEG400 significantly enhanced the analgesic effects of orally administered nalbuphine. It would have been well within the purview of the skilled artisan to modify the amounts of each ingredient in both the fill material and shell material to the achieve the desired capsule properties and therapeutic effect. It would have been well within the purview of the skilled artisan to use routine lab procedures of mixing, sieving, granulating, drying and filling, as well as controlling parameters such as pressure and temperature, to prepare the oral soft capsule.
6. Claim(s) 14-15 is/are again rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (WO2016/154503) in view of Wang et al. (Pharm Res 2014) as applied to claims 1-3, 6-13 and 16-24 above and further in view of Oliver et al. (U.S. Patent Application No. 2009/0074708).
Zhao et al. and Wang et al. do not teach isorhamnetin.
Oliver et al. teach UGT2B inhibitors are capable of increasing the bioavailability of a drug, wherein the inhibitor is selected from the group consisting of isorhamnetin, PEG400, TWEEN 20 and combinations thereof. See abstract. This invention provides a method to improve the oral bioavailability of morphine-like analgesic agents, where said method orally coadministers morphine-like analgesic agents with Uridine diphosphate (UDP)-glucuronosyltransferases 2B (UGT2B) inhibitor and where the morphine-like agents are a combination of the following: morphine, naloxone, nalorphine, oxymorphone, hydromorphone, dihydromorphone, codeine, naltrexone, nalbuphine and buprenorphine. See paragraph [0063]. Isorhamnetin has an at least 30% inhibition rate on nalbuphine. See paragraph [0099]. 4 mg/kg caillarisin (inhibitor) is used in the examples. See paragraph [0112].
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to add isorhamnetin to the formulation made obvious by Zhao et al. and Wang et al. to increase the oral bioavailability of the formulation because Oliver et al. teach this resultant effect of isorhamnetin on analgesic agents including nalbuphine. It would have been well within the purview of the skilled artisan to modify the amount of isorhamnetin to achieve the desired analgesic effect.
Response to Arguments
Applicants’ arguments filed 2 January 2026 have been fully considered but they are not persuasive.
7. Applicants argued, “Zhao does not teach a sorbitol component in a percentage of not less than 4% but less than 18% in the capsule shell. In the present invention, a sorbitol component contained in the capsule shell is not used as a plasticizer as taught by Zhao. The sorbitol component in the capsule shell provides an unexpectedly good shelf life.”
In response to applicants’ arguments, Zhao specifically states that sorbitol is used in the soft capsule shell. The term plasticizer is a function of the ingredient. The ingredient does not need to be added for the same reason, although the function will inherently result by its addition. Zhao teaches “In one embodiment, the plasticizer comprises one or more of glycerol, sorbitol, mannitol, maltitol (Lycasin® ), xylitol (Xylisorb® ), or combinations thereof. In one aspect, the plasticizer comprises glycerol, sorbitol, or combinations thereof.” See page 31. Table 6 uses maltitol in an amount of 16.1%. Since the plasticizers are interchangeable, it would have been well within the purview of the skilled artisan to substitute one plasticizer for another, in the same amount taught, which reads on the instant claims. Applicants argued that the presence of sorbitol in the shell provides unexpectedly good shelf life. Since this component is already present in the prior art of Zhao, it should function in the same manner, devoid of evidence to the contrary.
Thus this rejection is maintained.
Conclusion
8. Applicants’ 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.
Correspondence
9. No claims are allowed at this time.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Wax can be reached at 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JESSICA WORSHAM/Primary Examiner, Art Unit 1615