Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined pursuant to the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
The Examiner acknowledges receipt of Applicants’ Response, filed 23 December 2025. Claims 1 - 3 are amended therein, claim 6 is canceled, and new claims 9 - 12 are added. Claim 8 remains withdrawn as being directed to a non-elected invention. Accordingly, claims 1 – 3, 7, and 9 - 12 are available for active consideration.
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statement (IDS) filed 24 December 2025, which ais now of record in the file.
REJECTIONS WITHDRAWN
Rejections Pursuant to 35 U.S.C. § 112
The rejections pursuant to 35 U.S.C. §§ 112(b) and (d) set forth in the Action of 1 October 2025 are hereby withdrawn in light of Applicants’ amendment of the claims.
Rejections Pursuant to 35 U.S.C. § 103
The rejections pursuant to 35 U.S.C. § 103 set forth in the Action of 1 October 2025 are hereby withdrawn in light of Applicants’ amendment of the claims, and in favor of the new grounds of rejection set forth below and, with respect to the obviousness rejection of claims 1 - 3 and 6 over Ogino ‘121 in view of Zhao (2016), in view of Applicants’ filing of the STATEMENT OF COMMON OWNERSHIP.
Obviousness-Type Double Patenting
The double patenting rejections set forth in the Action of 1 October 2025 are hereby withdrawn in light of the approval of Applicants’ Terminal Disclaimers.
NEW GROUNDS OF REJECTION
Rejections Pursuant to 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 that 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 absent any evidence to the contrary. Applicants are advised of the obligation pursuant to 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 1 – 3 and 9 - 12 are rejected pursuant to 35 U.S.C. § 103, as being obvious over US 2019/0000774 to Hamada, A. and M. Goto, published 3 January 2019 (“Hamada ‘774”), in view of Zhao (2016), and Gwak, H., et al., DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 30(2): 187 – 194 (2004) (“Gwak (2004)”).
The Invention As Claimed
Applicants claim a patch comprising a support, and an adhesive layer on the support, wherein the adhesive layer includes blonanserin, or a salt thereof, a thermoplastic elastomer, a higher fatty acid ester, an aliphatic dicarboxylic acid ester, and a fatty acid monoester of a polyhydric alcohol, wherein the components are distinct compounds, wherein the thermoplastic elastomer is a styrene-based block copolymer, and wherein a number of carbon atoms in an ester portion of the higher fatty acid ester is from 12 to 30, wherein a ratio of the higher fatty acid ester relative to 100 parts by mass of the thermoplastic elastomer is from 25 parts by mass to 300 parts by mass [1:4 – 3:1], wherein an amount of the higher fatty acid ester in the adhesive layer is more than 0% by mass to 75% by mass, wherein the aliphatic dicarboxylic acid ester is diisopropyl adipate, wherein the fatty acid monoester of polyhydric alcohol is propylene glycol monocaprylate, wherein the adhesive layer further includes an alcohol-based solvent, wherein an amount of blonanserin, or the salt thereof, in the adhesive layer is from 0.5% by mass to 30% by mass, wherein an amount of the thermoplastic elastomer in the adhesive layer is from 20% by mass to 70% by mass, wherein an amount of the higher fatty acid ester in the adhesive layer is from 10% by mass to 75% by mass, wherein an amount of diisopropyl adipate in the adhesive layer is from 0.2% by mass to 20% by mass, wherein an amount of propylene glycol monocaprylate in the adhesive layer is from 2% by mass to 30% by mass, and wherein an amount of the alcohol-based solvent in the adhesive layer is from 0.1 % by mass to 20% by mass, and wherein an amount of blonanserin or the salt thereof in the adhesive layer is from 1.5% by mass to 15% by mass, wherein an amount of the thermoplastic elastomer in the adhesive layer is from 30% by mass to 60% by mass, wherein an amount of the higher fatty acid ester in the adhesive layer is from 20% by mass to 65% by mass, wherein an amount of diisopropyl adipate in the adhesive layer is from 1.5% by mass to 3% by mass, wherein an amount of propylene glycol monocaprylate in the adhesive layer is from 5% by mass to 30% by mass, and wherein an amount of the alcohol-based solvent in the adhesive layer is from 0.5% by mass to 15% by mass.
The Teachings of the Cited Art
Hamada ‘774 discloses a transdermal absorption preparation comprising a drug-containing adhesive layer formed on a support, the adhesive layer comprising a thermoplastic elastomer and a higher fatty acid ester (see Abstract), wherein the content of the higher fatty acid ester in the drug-containing adhesive layer is more than 50 parts by weight and not more than 500 parts by weight per 100 parts by weight of the thermoplastic elastomer (see ¶[0021]; see also TABLE 1), wherein the thermoplastic elastomer is a styrene-isoprene-styrene block copolymer (see ¶[0025]), wherein the content of the thermoplastic elastomer in the drug-containing adhesive layer of the transdermal absorption preparation of the present invention is from 0.1 to 50% wgt (see ¶[0067]), wherein the higher fatty acid ester comprises myristic acid esters such as octyldodecyl myristate (see ¶[0058]), at, for example, 63% wgt (see TABLE 1, ¶[0090]), wherein the adhesive layer comprises an ester solvent (see ¶[0077]), such as diisopropyl adipate (see ¶[0079]), present, in exemplified embodiments, at 1.3 and 1.4% wgt (see TABLE 2), and an alcohol solvent at 12% wgt (see ¶[0101], TABLE 2). The reference does not disclose blonanserin at 0.5 to 30% wgt in the drug-containing adhesive layer, or a drug adhesive layer comprising propylene glycol monocaprylate at 2 – 30% wgt. The teachings of Zhao (2016) and Gwak (2004) remedy those deficiencies.
Zhao (2016) discloses the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin, prepared with a pressure-sensitive adhesive (PSA), the patch containing 5% (w/w) of blonanserin, and different concentrations of IPM (see Abstract), wherein an adhesive layer was prepared by dissolving IPM, blonanserin, and DURO-TAK 87-2287 in ethyl acetate, agitated thoroughly with a mechanical stirrer to obtain a homogeneous solution, evaporating the ethyl acetate solvent from the mixture, and coating the blonanserin-loaded adhesive onto a release liner (see p. 624, 2nd col., 2nd para.), and the adhesive layer was then laminated onto a polyester backing film (see p. 624, 2nd col., 4th para.).
Gwak (2004) discloses investigations into the effects of vehicles and penetration enhancers on the in vitro permeation of a pharmaceutically active agent (ondansetron hydrochloride) across dorsal hairless mouse skins, wherein the combination of propylene glycol monocaprylate (PGMC) and ethanol (80:20) increased the permeation flux six-fold compared to
PGMC alone (see Abstract; see also, Table 1, p. 189), wherein in vitro permeation tests of the active across hairless mouse skin were performed with solutions of pure solvent/vehicle at saturation or below saturation concentrations of the active (see p. 189, 1st col., pars. 2-3), and wherein when the hydrophilic vehicle (ethanol) was added to the hydrophobic vehicle (PGMC) at 20% concentration, a significantly enhanced flux (25.9±2.78 µg/cm2/h) was observed, compared to PGMC alone (4.04±0.31 µg/cm2/h) (see p. 191, 2nd col., 1st para.).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare a transdermal absorption preparation comprising a drug-containing adhesive layer formed on a support, the adhesive layer comprising a styrene-isoprene-styrene block copolymer
and a higher fatty acid ester, such as octyldodecyl myristate, at more than 50 parts by weight and not more than 500 parts by weight per 100 parts by weight of the thermoplastic elastomer, wherein the content of the thermoplastic elastomer in the drug-containing adhesive layer is from 0.1 to 50% wgt, wherein the adhesive layer comprises an ester solvent, such as diisopropyl adipate, present, in exemplified embodiments, at 1.3 and 1.4% wgt, and an alcohol solvent at 12% wgt, as taught by Hamada ‘774, wherein the drug in the drug-containing adhesive layer is blonanserin, as taught by Zhao (2016), and wherein the adhesive layer further comprises propylene glycol monocaprylate (PGMC), as taught by Gwak (2004). One of skill in the art would be motivated to do so, with a reasonable expectation of success in so doing, by the express teachings of Zhao (2016) as to the effective performance of patches comprising blonanserin (see Abstract, Table 5), and by the teachings of Gwak (2004) as to the enhancement of permeation with PGMC, and particularly with PGMC and ethanol (at 80:20).
With respect to those claims reciting quantitative ranges for the content of various components in the transdermal dosage forms, the Examiner notes that the cited references do not expressly disclose loadings for components that are exactly congruent with the claimed ranges. However, it is the Examiner’s position that the cited art teaches a range of loadings of these components that significantly overlap with the claimed loadings and, as such, would render the claimed invention obvious. See MPEP § 2144.05. “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 re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).”
More specifically with respect to claims 11 and 12 reciting limitations directed to the loadings of propylene glycol monocaprylate (PGMC), the Examiner first notes that Gwak (2004) discloses results for in vitro permeation testing of an active ingredient across hairless mouse skin from solutions comprising various solvents/vehicles and permeation enhancers for use in transdermal dosage forms. As such, the reference does not disclose specific embodiments of such drug delivery devices and, hence, no specific loadings in the devices. However, the results disclosed in the reference provide clear motivation to one of ordinary skill in the art to use PGMC in such devices due to its demonstrated ability to enhance skin permeation. It is the Examiner’s position that determining the amount of PGMC in the transdermal devices amounts to nothing more than optimization of a result-effective variable, the exercise of which is well with the expertise of one of ordinary skill in the appropriate art. Consequently, in the absence of evidence as to the criticality of such parameter, this limitation cannot support patentability. See MPEP § 2144.05 II. A.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 1 – 3 and 9 - 12 would have been obvious within the meaning of 35 USC § 103.
Claim 7 is rejected pursuant to 35 U.S.C. § 103, as being obvious over Hamada ‘774, in view of Zhao (2016), as applied in the above rejection of claims 1 – 3 and 9 - 12, and further in view of Loftsson, T., et al., Die Pharmazie, 52(6): 463 – 465 (1997) [Abstract] (“Loftsson (1997)”).
The Invention As Claimed
The invention with respect to claim 1 is described above. In addition, Applicants claim a patch further including glycerin monoether.
The Teachings of the Cited Art
The disclosures of Hamada ‘774, Zhang (2016), and Gwak (2004) are relied upon as applied in the above rejection of claims 1 – 3 and 9 - 12. The references do not disclose a blonanserin patch comprising a glycerin monoether. The teachings of Loftsson (1997) remedy that deficiency.
Loftsson (1997) discloses that glycerol monoether, extracted from the liver oil of deep-sea shark, although somewhat less effective as skin penetration enhancer than oleic acid and other potent fatty acid penetration enhancers, was still a very effective enhancer in a hairless mouse skin model (see Abstract).
Application of the Cited Art to the Claims
It would have been prima facie obvious before the filing date of the claimed invention to prepare a drug-in-adhesive transdermal patch comprising blonanserin as an active ingredient, isopropyl myristate (IPM) as a penetration enhancer, and styrene-isoprene-styrene as a thermoplastic elastomer, according to the teachings of Zhao (2016) and Ogino ‘121, and wherein the patch further comprises glycerin monoether, as taught by Loftsson (1997). One of skill in the art would be motivated to do so, with a reasonable expectation of success in so doing, by the express teachings of Loftsson (1997) as to the excellent transdermal penetration properties of glycerin monoether.
In this regard, the Examiner further notes that it is generally obvious to add known ingredients to known compositions with the expectation of obtaining their known function. See, e.g., In re Linder, 457 F.2d 506, 507 (CCPA 1972).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claim 7 would have been obvious within the meaning of 35 USC § 103.
Response to Applicants’ Arguments
The Examiner has considered the arguments that Applicants have presented in the Response filed 23 December 2025, but does not find them persuasive, to the extent still relevant in light of the new grounds of rejection set forth above.
With respect to their invention, Applicants first state that “[t]he specification of the present application indicates that in Examples 2, 3, and 5 to 8, which contain both diisopropyl adipate ((iv) an aliphatic dicarboxylic acid ester) and propylene glycol monocaprylate ((v) a fatty acid monoester of polyhydric alcohol), the results for cohesive forth were superior,” and further argue that “[n]one of Hamada '774, Zhao (2016), or Loftsson (1997) describe or suggest the use of at least (v) the fatty acid monoester of polyhydric alcohol and the above effect of suppressing the decrease in cohesive force.” However, the above rejection cites to Hamada ‘774 for its disclosure of the use of diisopropyl adipate (see ¶[0079]), present, in exemplified embodiments, at 1.3 and 1.4% wgt (see TABLE 2). In addition, the current rejection now cites to the teachings of Gwak (2004) as to the enhanced in vitro permeation of numerous active ingredients achieved with PGMC. Thus, the current rejection cites prior at that teaches these specific components.
Although Applicants state that the inclusion of these components is responsible for “suppressing the decrease in cohesive force,” the fact that Applicants have recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In this regard, Applicants are reminded that the invention as claimed is directed to a composition of matter, and that, as a consequence, the reasons for combining the teachings of cited references, are not necessarily controlling to the patentability of the compositions, as claimed. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).
Consequently, based on the above discussion, Applicants’ arguments are unpersuasive and claims 1 – 3, 7, and 9 – 12 stand rejected pursuant to 35 U.S.C. § 103.
NO CLAIM IS ALLOWED.
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.
CONCLUSION
Any inquiry concerning this communication or any other communications from the Examiner should be directed to Daniel F. Coughlin whose telephone number is (571)270-3748. The Examiner can normally be reached on M - F 8:30 a.m. - 5:00 p.m.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, David Blanchard, can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/DANIEL F COUGHLIN/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/ Supervisory Patent Examiner, Art Unit 1619