DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 19, 2026 has been entered.
Claims 12-16, 20-23, 31-33 and 36 are currently pending and are examined on the merits herein.
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 .
Priority
This Application filed on 12/06/2024 has PRO 63/626,017 filed on 01/28/2024, PRO 63/625,906 filed on 01/26/2024, PRO 63/609,206 filed on 12/12/2023, and PRO 63/607,389 filed on 12/07/2023.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 3/19/26, 8/7/26, 9/15/26 is in compliance with the provisions of S7 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
Response to Arguments
Applicant’s arguments over the 35 U.S.C. 103(a) rejection of claims 1-3, 7-8, 11-16, 18-20, and 23 over Durrant (WO2021113627) is not persuasive. The rejection is maintained. Applicant argues “the p-value of 0.025 for the high dose cohort means that there is only a ~2.5 % chance that the difference in mean SPID48 between the high dose cohort and placebo is attributable to random variation in the data.” “By contrast, subjects receiving the unclaimed mid and low doses did not show a statistically significant improvement in mean SPID48 compared to placebo. Again, this conclusion is evident from the p-values reported for the mid dose (p = 0.3859) and low dose (p = 0.5379) cohorts, which are well above the threshold required for statistical significance (p < 0.05) and thus suggest a 38% and 54% chance, respectively, of observing such data under random variation.” Applicant makes similar arguments regarding the Bunionectomy Study and Abdominoplasty Study.
The Examiner requested clarification on the argument that the regimen is statistically significant improvement in pain reduction presented on 03/19/2026. Applicant provided supplemental arguments on 08/07/2026. The supplemental arguments have been considered. However, the Examiner points out that the effect of pain relief is known. The question is not whether the higher dose regimen is more effective in treating pain relief than a mid or low dose regimen, but if the results of pain relief are surprising and unexpected over the teachings of the prior art, especially because the reference teaches a dosage level of about 100 mg/kg. Applicant has not provided that data. The Examiner suggests a comparison of the claimed dosing regimens and the dosing of the closest art of record. In this case, where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)
Applicant’s arguments over the 35 U.S.C. 103(a) rejection of claims 9-10, 21-22 and 31-33, over Durrant (WO2021113627), as applied to claims and further in view of Aurora et al. (US20100204292A1) and Butreddy (Hydroxypropyl methylcellulose acetate succinate as an exceptional polymer for amorphous solid dispersion formulations: A review from bench to clinic. Eur J Pharm Biopharm. 2022 Aug;177:289-307. doi: 10.1016/j.ejpb.2022.07.010. Epub 2022 Jul 21. PMID: 35872180.) is not persuasive. Applicant' s argument over claims 9-10, 21-22 and 31-33 rejections depends on the validity of the previous arguments which were not found persuasive. The rejection is maintained.
The rejections are as below:
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.
Claims 12-16, 20, 23 and 36 are rejected under 35 U.S.C. 103 as obvious over Durrant (WO2021113627).
Durrant teaches a method of treating or lessening the severity in a subject of chronic pain, gut pain, neuropathic pain which comprises diabetic neuropathy, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postsurgical pain (e.g., bunionectomy pain, herniorrhaphy pain or abdominoplasty pain),visceral pain, multiple sclerosis, etc comprising administering to the subject an effective amount of the compound
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(see claims 42 and 100). The compound, salts, and compositions of the invention may be administered orally or parenterally at dosage levels of about 0.001 mg/kg to about 100 mg/kg, or about 0.01 mg/kg to about 50 mg/kg, of subject body weight per day, one or more times a day, effective to obtain the desired therapeutic effect [00446]. Solid dosage forms, the active compound or salt is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. Various carriers used in formulating pharmaceutically acceptable compositions and known techniques for the preparation thereof such as cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate. Some examples of materials which can serve as pharmaceutically acceptable carriers include, but are not limited to, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, etc. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. [00452] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art.
The prior art does not describe the dosing regimen of subsequent 40-60 mg every 12 hours.
It would have been obvious to one of ordinary skill in the art at the time of filing to improve the NPRS score as recited in the claims. The motivation to improve the NPRS score is because Durrant teaches the treating or lessening the severity in a subject of postsurgical pain (e.g., bunionectomy pain) with the compound
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(see claims 42 and 100). Therefore, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
Claims 21-22 and 31-33, are rejected under 35 U.S.C. 103 as obvious over Durrant (WO2021113627), as applied to claims 12-16, 20, 23 and 36 and further in view of Aurora et al. (US20100204292A1) and Butreddy (Hydroxypropyl methylcellulose acetate succinate as an exceptional polymer for amorphous solid dispersion formulations: A review from bench to clinic. Eur J Pharm Biopharm. 2022 Aug;177:289-307. doi: 10.1016/j.ejpb.2022.07.010. Epub 2022 Jul 21. PMID: 35872180.).
Durrant is as discussed above.
Durrant fails to teach an intra and extragranular formulation, ie. the HPMCAS, microcrystalline cellulose, or croscarmellose sodium.
Butreddy teaches HPMCAS has been widely utilized as a solubility enhancer and precipitation inhibitor or stabilizer to achieve supersaturation and inhibit crystallization of drugs in the gastrointestinal tract. The characteristics of HPMCAS ASDs such as less hygroscopic, strong drug-polymer hydrophobic interactions, high solubilization efficiency, greater potential to generate, maintain drug supersaturation and crystallization inhibition outperform other polymeric carriers in ASD development. Furthermore, combining HPMCAS with other polymers or surfactants as ternary ASDs could be a viable approach for enhancing oral absorption of poorly soluble drugs.
Aurora et al. teaches a pharmaceutical composition comprising i) an intra-granular fraction containing a pharmaceutically acceptable active component and a first excipient and ii) an extra-granular fraction containing a second excipient. Examples include, actives in combination with the intragranular fraction further containing croscarmellose sodium, colloidal silicon dioxide, microcrystalline cellulose, an extra-granular fraction element comprising microcrystalline cellulose, croscarmellose sodium,
It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate an intra and extragranular formulation, ie. the HPMCAS, microcrystalline cellulose, or croscarmellose sodium. The motivation to incorporate an intra and extragranular formulation, ie. the HPMCAS, microcrystalline cellulose, or croscarmellose sodium is because Butreddy teaches HPMCAS has been widely utilized as a solubility enhancer and precipitation inhibitor or stabilizer to achieve supersaturation and inhibit crystallization of drugs in the gastrointestinal tract. The characteristics of HPMCAS ASDs such as less hygroscopic, strong drug-polymer hydrophobic interactions, high solubilization efficiency, greater potential to generate, maintain drug supersaturation and crystallization inhibition outperform other polymeric carriers in ASD development. Furthermore, combining HPMCAS with other polymers or surfactants as ternary ASDs could be a viable approach for enhancing oral absorption of poorly soluble drugs and from the teaching of Aurora that an intra-granular fraction containing a pharmaceutically acceptable active component and a first excipient and ii) an extra-granular fraction containing a second excipient composition is substantially surfactant-free and exhibits a rapid-dissolution profile . Therefore, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
Conclusion
No claims allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAYLA SOROUSH whose telephone number is (571)272-5008. The examiner can normally be reached Monday thru Friday; 8:30 AM to 5:00 PM EST.
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/LAYLA SOROUSH/Primary Examiner, Art Unit 1622
