DETAILED ACTION
The Office Action is in response to the Applicant's reply filed October 1, 2025 to the non-final rejection made on July 1, 2025.
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 10/1/25 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 “Nothing in Durrant teaches or suggests that any particular compound of formula (1), such as Compound 1, should be administered in any particular dose within the disclosed range.” Applicant states “the claimed dose range correspond to tiny fractions of the broader dose ranges disclosed in Durrant. Accordingly, the broad ranges disclosed in Durrant do not establish a prima facie case of obviousness for the claimed dosing regimens. See, e.g., MPEP 2144.05(D, 2144.05(D)(D). Further, the specific dosing schedule is not taught by the prior art.
The Examiner points out the rejections were not made on an anticipatory but an obviousness type rejection. Specifically, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. “An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In rePayne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In rePapesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In reDillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c). Furthermore, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In reWertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In reWoodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of “about 1-5%” while the claim was limited to “more than 5%.” The court held that “about 1-5%” allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of “50 to 100 Angstroms” considered prima facie obvious in view of prior art reference teaching that “for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms].” The court stated that “by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.”). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941). Additionally, the Examiner’s contention is that absent evidence of unexpected and surprising results, choosing a compound and/or a dosage amount with structural similarity and/or properties taught by the prior art is obvious. Durrant clearly teaches 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]
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. The rejection is maintained. Applicant argues Aurora et al. and Butreddy do not teach the dosing regimen.
In response, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify the dosage, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USP 233.
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 1-3, 7-8, 11-16, 18-20, 23 and 34 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 NPRS score scale as recited in claims 7, and 18-19.
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 9-10, 21-22 and 31-33, are rejected under 35 U.S.C. 103 as obvious over Durrant (WO2021113627), as applied to claims 1-3, 7-8, 11-16, 18-20, 23 and 34 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
The arguments are not persuasive and the rejection is made FINAL.
Applicant's 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 extension fee 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
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
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