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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/14/2026 has been entered.
Status of the Claims
Claims 1-10, 15-18 and 23-26 were canceled in a previous communication. Claims 12, 20, and 28 have been cancelled.
Claims 11, 13-14, 19, 21-22, 27 and 29-31 are pending and currently under examination.
All rejections not reiterated have been withdrawn.
Claim Rejections - 35 USC § 103
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.
Claims 11, 13-14, 19, 21-22, 27 and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (Asian Journal of Pharmaceutical Sciences, Volume 10, Issue 5, 2015, Pages 405-414) in view of Mahboubian et al. (Iran J Pharm Res. 2010 Fall;9(4):369-78).
Applicant’s Invention
The applicant’s claims are drawn to a method for preparing a microsphere, comprising: dissolving donepezil and a biodegradable polymer in an organic solvent to prepare a dispersed phase; dissolving a salt and a water-soluble polymer in water to prepare a continuous phase; mixing and stirring the dispersed phase and the continuous phase to form an emulsion; removing the organic solvent; and drying, wherein the salt is sodium chloride (NaCl) or potassium chloride (KCl), and wherein the water-soluble polymer is polyvinyl alcohol.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 11, 14, 19, 22, 27, and 30-31, Guo teaches developing a PLGA microsphere-based donepezil (DP) formulation which was expected to sustain release of donepezil for one week with high encapsulation efficiency; wherein the DP microspheres are administered via subcutaneous injection (abstract). Guo also teaches DP-loaded PLGA microspheres were prepared by a conventional O/W emulsion-solvent evaporation method. Briefly, 5 mg DP and 20 mg of PLGA (i.e., biodegradable polymer) were dissolved in 200 µl of dichloromethane (DCM) (i.e., organic solvent), then injected into 4 ml aqueous phase containing certain concentration of PVA (i.e., water-soluble polymer) as emulsifier and homogenized with a high speed dispersion homogenizer (i.e., mixed) under 1500 rpm for 4 min to form an O/W emulsion. The emulsion was subsequently transferred to a larger volume of distilled water or PVA solution to dilute the emulsion and avoid the aggregation of particles. After the emulsion was stirred for 4 h at room temperature to evaporate the solvent, the microspheres were collected by centrifugation under 252 g (1500 rpm) for 3 min (800-centrifuge, Jintan Ronghua instrument manufacture Co., Ltd. China), washed three times with redistilled water and then lyophilized (i.e., drying step), stored at −20 °C (2.3. Preparation of donepezil loaded PLGA microspheres section).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Guo does not teach dissolving a salt wherein the salt is sodium chloride or potassium chloride (instant claims 11, 13, 21, and 29). However this deficiency is cured by Mahboubian et al.
Mahboubian teaches that the present study describes the formulation of a sustained release microparticulate drug delivery system containing triptoreline acetate, using poly (D,L lactide-co-glycolide) (PLGA) (abstract). Mahboubian also teaches Triptoreline acetate-loaded microspheres were prepared by a double emulsion-solvent evaporation technique. Briefly, 500 mg PLGA was dissolved in 5 mL dichloromethane (oil phase). An aqueous solution containing different amounts of triptoreline acetate was prepared separately (inner aqueous phase or W1).
The first aqueous phase (w1) was emulsified into the oil phase (containing PLGA), using a high-speed homogenizer (T18 basic, IKA, Germany) at different speeds and time durations. Afterwards, the primary emulsion was added to 250 mL of 0.5% w/v poly-vinyl alcohol solution, while stirring with a mechanical mixer at different rates to form the w1/o/w2 double emulsion. Mixing was continued for 8 h at room temperature, until complete evaporation of dichloromethane. The resulted microparticles were collected by filtration, washed with water and dried overnight at room temperature. In some formulations, 2% w/v poloxamer 407, 1% or 10% v/v Span 20 were added to the first (w1/o) emulsion. In some formulations, 5% w/v sodium chloride was added to the external water phase (w2) in the presence or absence of emulsifier (Preparation of microspheres section).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to dissolve sodium chloride in water to prepare a continuous phase in Guo’s PLGA microsphere-based donepezil (DP) formulation. The artisan of ordinary skill would have been motivated to do so because Mahboubian teaches that the addition of NaCl resulted in a smoother surface with a lower porosity. The presence of pores on the surface of microspheres, in the absence of NaCl, could be attributed to the migration of w2 towards w1 due to the lower osmotic pressure of w2 (Results and discussion section, first paragraph). Mahboubian further teaches that the results indicated that the drug encapsulation efficiency and the cumulative drug release rates were affected by the presence of NaCl in the outer water phase, inner water phase volume, type and concentration of co-encapsulated surfactant. Ultimately, spherical PLGA microparticles with encapsulation efficiencies higher than 90% and prolonged triptoreline release over 45 days were obtained (In conclusion paragraph). The skilled artisan would have had a reasonable expectation of success because Guo teaches a PLGA microsphere formulation for sustained release injections formulated using PLGA, dichloromethane, water, and polyvinyl alcohol in an emulsion and Mahboubian also teaches a PLGA microsphere formulation for sustained release injections formulated using PLGA, dichloromethane, water, and polyvinyl alcohol in an emulsion.
Response to Arguments
Applicant’s arguments, filed 01/14/2026, with respect to the rejection(s) of claim(s) under 35 USC § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Guo et al. (Asian Journal of Pharmaceutical Sciences, Volume 10, Issue 5, 2015, Pages 405-414) in view of Mahboubian et al. (Iran J Pharm Res. 2010 Fall;9(4):369-78).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614