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 .
Status of Claims
This office action is responsive to the amendment filed 18 March 2026.
Claim 13 is canceled.
Claims 18 and 19 are added.
Claims 1, 2, 7, 8, 10, and 12 are amended.
Claims 1-12 and 14-17 are presently pending in this application.
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.
Claims 1-11 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Tokumoto et al. (US Patent Publication No. 20110288485 A1), hereinafter Tokumoto, in view of Pruitt et al. (US Patent Publication No. 20050063913 A1), hereinafter Pruitt, in further view of Hashimoto et al. (US Patent Publication No. 20160107189 A1).
Regarding claim 1, Tokumoto discloses a microneedle array (Tokumoto: Fig. 2, microneedle device 1) having microneedles (Fig. 2, microneedles 3) coated with a composition (Fig. 2, coating 5 is a liquid composition; para. 0042) comprising: a pharmaceutical particle (physiologically active ingredients; para. 0039 and 0042), 2% to 20% by weight of a binding agent (coating carrier is 10-65% by weight; para. 0041), and 60% by weight or more of water (The composition comprises water. If the coating agent is 10-65% by weight and the active ingredient is 10-30% by weight, then water is 5-80% by weight; para. 0039 and 0042).
Tokumoto does not expressly disclose the poorly water-soluble or water-insoluble particle with a mean particle size of 1 um or less.
Pruitt teaches a poorly water-soluble or water-insoluble particle (Pruitt: metaxalone is poorly soluble; para. 0181) with a mean particle size of 1 um or less (average particle size of less than 200 nm; para. 0081).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the poorly water-soluble or water-insoluble particle of Tokumoto such that the poorly water-soluble or water-insoluble particle has a mean particle size of 1 um or less as taught by Pruitt in order to provide nanoparticles of anti-inflammatory agents, allowing for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036, 0040, and 0112).
Tokumoto in view of Pruitt does not expressly disclose a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less.
Hashimoto teaches a coefficient of variation (CV) in an amount of a particle (variation coefficient of a drug coating microneedles; para. 0050) loaded on the microneedles is 10% or less (10% or less; para. 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the array of Tokumoto in view of Pruitt such that a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less as taught by Hashimoto in order to suppress variations in drug amount coating the microneedles and to allow stable production in aseptic environment (Hashimoto; para. 0050).
Regarding claim 2, Tokumoto in view of Pruitt and Hashimoto discloses the array above, wherein the binding agent (Tokumoto: coating carrier) comprises one or more selected from the group consisting of a saccharide or a derivative thereof (coating carrier consists of sucrose; para. 0040).
Regarding claim 3, Tokumoto in view of Pruitt and Hashimoto discloses the array above, the saccharide or a derivative thereof (Tokumoto: para. 0040) comprises sucrose (para. 0040).
Regarding claims 4-6, Tokumoto in view of Pruitt and Hashimoto discloses the array above.
Tokumoto does not expressly disclose that the poorly water-soluble or water-insoluble particle has a mean particle size of 700 nm or less and 50 nm or more.
Pruitt teaches poorly water-soluble or water-insoluble particle (Pruitt: metaxalone is poorly soluble; para. 0181) has a mean particle size of 700 nm or less and 50 nm or more (average particle size of less than 200 nm; para. 0081).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the poorly water-soluble or water-insoluble particle of Tokumoto such that the poorly water-soluble or water-insoluble particle has a mean particle size of 700 nm or less and 50 nm or more as taught by Pruitt in order to allow for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036 and 0040).
Regarding claim 7, Tokumoto in view of Pruitt and Hashimoto discloses the array above.
Tokumoto does not expressly disclose the poorly water-soluble or water-insoluble particle comprises at least one drug selected from indomethacin, diclofenac, flurbiprofen, etodolac, fentanyl, lidocaine, apomorphine, donepezil, buprenorphine, naproxen, meloxicam, estradiol, progesterone, Metaxalone, cyclosporine, celecoxib, cilostazol, ciprofloxacin, and a salt thereof.
Pruitt teaches a poorly water-soluble or water-insoluble particle is Metaxalone (Pruitt: metaxalone is poorly soluble; para. 0181).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the composition of Tokumoto such that the poorly water-soluble or water-insoluble particle is a drug selected from indomethacin, diclofenac, flurbiprofen, etodolac, fentanyl, lidocaine, apomorphine, donepezil, buprenorphine, naproxen, meloxicam, estradiol, progesterone, Metaxalone, cyclosporine, celecoxib, cilostazol, ciprofloxacin, or a salt thereof as taught by Pruitt in order to provide nanoparticles of anti-inflammatory agents, allowing for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036, 0040, and 0112).
Regarding claim 8, Tokumoto in view of Pruitt and Hashimoto discloses the array above.
Tokumoto does not expressly disclose the wherein the poorly water-soluble or water-insoluble particle is pre-milled particle.
Pruitt teaches a poorly water-soluble or water-insoluble particle (Pruitt: metaxalone is poorly soluble; para. 0181) is pre-milled particle (metaxalone is milled; para. 0181).
It would have been obvious to one of ordinary skill in the art before the effective filing date to mill the poorly water-soluble or water-insoluble particle of Tokumoto as taught by Pruitt in order to reduce the particle size to the desired average particle size allowing for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036, 0040, and 0112).
Regarding claim 9, Tokumoto in view of Pruitt and Hashimoto discloses the array above.
Tokumoto does not expressly disclose the amount of the poorly water-soluble or water-insoluble particle is 60% or more relative to the total amount of the composition excluding water.
Pruitt teaches an amount of a poorly water-soluble or water-insoluble particle (Pruitt: metaxalone is poorly soluble; para. 0181) is 60% or more relative to the total amount of the composition excluding water (Claim 43, metaxalone can comprise 0.5-90% by weight of the dry ingredients).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the composition of Tokumoto such that the amount of the poorly water-soluble or water-insoluble particle is 60% or more relative to the total amount of the composition excluding water in order to provide nanoparticles of anti-inflammatory agents at an optimal amount of depending on factors such as melting point, surface tension, etc. (Pruitt: para. 0174).
Regarding claim 10, Tokumoto discloses a method of manufacturing a microneedle array (Tokumoto: 1), which comprises: preparing a pharmaceutical compound (physiologically active ingredients; para. 0039 and 0042), preparing a composition (5) comprising the pharmaceutical compound (physiologically active ingredients; para. 0039 and 0042), 60% by weight or more of water (The composition comprises water. If the coating agent is 10-65% by weight and the active ingredient is 10-30% by weight, then water is 5-80% by weight; para. 0039 and 0042) and 2% to 20% by weight of a binding agent (coating carrier is 10-65% by weight; para. 0041), and coating the composition on microneedles (Fig. 2, coating 5 is coated on the microneedles 3).
Tokumoto does not expressly disclose milling the poorly water-soluble or water-insoluble compound until the mean particle size of the compound is 1 um or less.
Pruitt teaches milling (Pruitt: metaxalone is milled; para. 0181) a poorly water-soluble or water-insoluble compound (metaxalone is poorly soluble; para. 0181) until the mean particle size of the compound is 1 um or less (average particle size of less than 200 nm; para. 0081).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Tokumoto such that it including milling the poorly water-soluble or water-insoluble compound until the mean particle size of the compound is 1 um or less as taught by Pruitt in order to provide nanoparticles of anti-inflammatory agents, allowing for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036, 0040, and 0112).
Tokumoto in view of Pruitt does not expressly disclose a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less.
Hashimoto teaches a coefficient of variation (CV) in an amount of a particle (variation coefficient of a drug coating microneedles; para. 0050) loaded on the microneedles is 10% or less (10% or less; para. 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the array of Tokumoto in view of Pruitt such that a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less as taught by Hashimoto in order to suppress variations in drug amount coating the microneedles and to allow stable production in aseptic environment (Hashimoto; para. 0050).
Regarding claim 11, Tokumoto in view of Pruitt and Hashimoto discloses the method above,
Tokumoto does not expressly disclose the milling of the poorly water-soluble or water-insoluble compound is wet milling with a bead mill.
Pruitt teaches milling (metaxalone is milled; para. 0181) of a poorly water-soluble or water-insoluble compound (metaxalone is poorly soluble; para. 0181) is wet milling with a bead mill (wet milling with a DYNO Mill KDL, which is a bead mill; para. 0201).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Tokumoto such that the milling of the poorly water-soluble or water-insoluble compound is wet milling with a bead mill as taught by Pruitt in order to reduce the particle size to the desired average particle size (Pruitt: para. 0181).
Regarding claim 17, Tokumoto discloses a microneedle array (Tokumoto: 1) having microneedles (3) incorporating a pharmaceutical particle (physiologically active ingredients; para. 0039 and 0042) and 2% to 20% by weight of a binding agent (coating carrier is 10-65% by weight; para. 0041).
Tokumoto does not expressly disclose the poorly water-soluble or water-insoluble particle with a mean particle size of 1 um or less.
Pruitt teaches a poorly water-soluble or water-insoluble particle (Pruitt: metaxalone is poorly soluble; para. 0181) with a mean particle size of 1 um or less (average particle size of less than 200 nm; para. 0081).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the poorly water-soluble or water-insoluble particle of Tokumoto such that he poorly water-soluble or water-insoluble particle has a mean particle size of 1 um or less as taught by Pruitt in order to provide nanoparticles of anti-inflammatory agents, allowing for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036, 0040, and 0112).
Regarding claim 19, Tokumoto in view of Pruitt and Hashimoto discloses the array above.
Tokumoto does not expressly disclose the poorly water-soluble or water insoluble particle comprises indomethacin.
Pruitt teaches a poorly water-soluble or water-insoluble particle that comprises indomethacin (the composition can be combined with NSAIDs such as indomethacin; para. 0118-0119).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the array of Tokumoto in view of Hashimoto such that the poorly water-soluble or water insoluble particle comprises indomethacin as taught by Pruitt in order to provide a formulation with greater benefits with acute musculoskeletal problems than just analgesic alone (Pruitt: para. 0191).
Claims 12 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ronnander et al. (US Patent Publication No. 20200206489 A1), hereinafter Ronnander, in view of Pruitt, in further view of Hashimoto.
Regarding claim 12, Ronnander discloses a method of manufacturing a microneedle array (Ronnander: preparation of a polymeric microneedle array; para. 0051), which comprises: pouring a composition comprising 60% by weight or more of water (water is the preferred solvent. The solution comprises 15-40 wt.% binder, less than 2 wt.% humectant, less than 2 wt.% surfactant, 1-15 wt.% compound. Therefore, the solution comprises 59-84 wt.% water; para. 0027 and 0051) and 2% to 20% by weight of a binding agent (water soluble polymer as a binder. Binder comprises 15-40% by weight; para. 0027 and 0044) into a mold with a concave portion forming the form of microneedles (liquid polymer solution is poured into negative molds; para. 0051), evaporating water to form a microneedle array (microneedle array is dried; para. 0051), and removing the formed microneedle array from the mold (microneedle array can be peeled from the mold after drying; para. 0051).
Ronnander does not expressly disclose that the composition comprises a poorly water-soluble or water-insoluble particle with a mean particle size of 1 um or less.
Pruitt teaches a composition (nanoparticulate composition; para. 0025) comprising a poorly water-soluble or water-insoluble particle (Pruitt: metaxalone and other NSAIDs such as diclofenac are poorly soluble; para. 0119 and 0181) with a mean particle size of 1 um or less (average particle size of less than 200 nm; para. 0081).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the poorly water-soluble or water-insoluble particle of Ronnander such that he poorly water-soluble or water-insoluble particle has a mean particle size of 1 um or less as taught by Pruitt in order to provide nanoparticles of anti-inflammatory agents, allowing for faster onset of action, smaller doses to obtain the same pharmacological effect, and increased dissolution (Pruitt: para. 0036, 0040, and 0112).
Ronnander in view of Pruitt does not expressly disclose a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less.
Hashimoto teaches a coefficient of variation (CV) in an amount of a particle (variation coefficient of a drug coating microneedles; para. 0050) loaded on the microneedles is 10% or less (10% or less; para. 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the array of Ronnander in view of Pruitt such that a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less as taught by Hashimoto in order to suppress variations in drug amount coating the microneedles and to allow stable production in aseptic environment (Hashimoto; para. 0050).
Regarding claim 14, Ronnander in view of Pruitt and Hashimoto discloses the method above.
Ronnander does not expressly disclose milling a poorly water-soluble or water-insoluble compound to obtain the poorly water-soluble or water-insoluble particle with a mean particle size of 1 um or less before pouring the composition into the mold.
Pruitt teaches milling a poorly water-soluble or water-insoluble compound (Pruitt: metaxalone is milled; para. 0181) to obtain the poorly water-soluble or water-insoluble particle (metaxalone is poorly soluble; para. 0181) with a mean particle size of 1 um or less (average particle size of less than 200 nm; para. 0081) before preparing the composition (para. 0179).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Ronnander such that it including milling the poorly water-soluble or water-insoluble compound until the mean particle size of the compound is 1 um or less as taught by Pruitt in order to reduce the particle size to the desired average particle size (Pruitt: para. 0181).
Regarding claim 15, Ronnander in view of Pruitt and Hashimoto discloses the method above.
Ronnander does not expressly disclose the milling of the poorly water-soluble or water-insoluble compound is wet milling with at least one mill selected from the group of a jet mill, a bead mill and a planetary mill.
Pruitt teaches milling (metaxalone is milled; para. 0181) of a poorly water-soluble or water-insoluble compound (metaxalone is poorly soluble; para. 0181) is wet milling with a bead mill (wet milling with a DYNO Mill KDL, which is a bead mill; para. 0201).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Pruitt such that the milling of the poorly water-soluble or water-insoluble compound is wet milling with a bead mill as taught by Pruitt in order to reduce the particle size to the desired average particle size (Pruitt: para. 0181).
Regarding claim 16, Ronnander in view of Pruitt and Hashimoto discloses the method above, wherein a microneedle array is manufactured by the method above (Ronnander: preparation of a polymeric microneedle array; para. 0051).
Claims 1 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Tokumoto, in view of Pathak et al. (US Patent No. 10624865), hereinafter Pathak, in further view of Hashimoto.
Regarding claim 1, Tokumoto discloses a microneedle array (Tokumoto: Fig. 2, microneedle device 1) having microneedles (Fig. 2, microneedles 3) coated with a composition (Fig. 2, coating 5 is a liquid composition; para. 0042) comprising: a pharmaceutical particle (physiologically active ingredients; para. 0039 and 0042), 2% to 20% by weight of a binding agent (coating carrier is 10-65% by weight; para. 0041), and 60% by weight or more of water (The composition comprises water. If the coating agent is 10-65% by weight and the active ingredient is 10-30% by weight, then water is 5-80% by weight; para. 0039 and 0042).
Tokumoto does not expressly disclose the poorly water-soluble or water-insoluble particle with a mean particle size of 1 um or less.
Pathak teaches a poorly water-soluble or water-insoluble particle (Pathak: drug is insoluble; col 49, ln 36-38) with a mean particle size of 1 um or less (particle size of 0.1um to 500 um; col 49, ln 36-38).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the poorly water-soluble or water-insoluble particle of Tokumoto such that the poorly water-soluble or water-insoluble particle has a mean particle size of 1 um or less as taught by Pruitt in order to provide a drug solution that can disperse and precipitate drug crystals/solids, allow for slow dissolution (col 6, ln 29-38).
Tokumoto in view of Pathak does not expressly disclose a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less.
Hashimoto teaches a coefficient of variation (CV) in an amount of a particle (variation coefficient of a drug coating microneedles; para. 0050) loaded on the microneedles is 10% or less (10% or less; para. 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the array of Tokumoto in view of Pathak such that a coefficient of variation (CV) in the amount of the particle loaded on the microneedles is 10% or less as taught by Hashimoto in order to suppress variations in drug amount coating the microneedles and to allow stable production in aseptic environment (Hashimoto; para. 0050).
Regarding claim 18, Tokumoto in view of Pathak and Hashimoto discloses the array above.
Tokumoto does not expressly disclose the poorly water-soluble or water insoluble particle excludes metaxalone.
Pathak teaches poorly water-soluble or water insoluble particle (col 49, ln 36-48) that does not include metaxalone.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the array of Tokumoto such that the poorly water-soluble or water insoluble particle excludes metaxalone as taught by Pathak in order to have a desired therapeutic effect (col 12, ln 42-60).
Response to Arguments
Applicant’s arguments, see pages 6-7, filed 18 March 2026, with respect to the rejections of claims 1-12 and 14-17 under 35 USC 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Takumoto in view of Pruitt or Pathak for claims 1-11 and 17 and Ronnander in view of Pruitt, in further view of Hashimoto cited above, for claims 12 and 14-16.
Conclusion
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 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.
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/LEI GONZALEZ/ Examiner, Art Unit 3783
/SCOTT J MEDWAY/ Primary Examiner, Art Unit 3783
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