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 26 January 2026. Claim 1 is amended therein. Claims 1 – 9, 19, 20, and 22 remain withdrawn as being directed to a non-elected invention. Accordingly, claims 10 - 18, 21, and 23 - 26 remain available for active consideration.
Claim Objections Withdrawn
The objection to claim 1 set forth in the Action of 17 November 2025 is hereby withdrawn in light of Applicants’ amendment of the claim.
REJECTIONS MAINTAINED
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.
The rejection of claims 10 – 18, 21, and 23 - 26 pursuant to 35 U.S.C. § 103, as being obvious over US 2014/0052081 A1 to Yang, K.-H., et al., published 2 February 2014 (Yang ‘081), in view of WO 2012/084969 A1 to Nink, J., et al., published 28 June 2012, identified on the Information Disclosure Statement (IDS) filed 1 March 2023, cite no. 187 (FOR) (“Nink WO ‘969”), and US 2010/0178307 A1 to Wen J. and Y. Stowell, identified on the IDS filed 12 October 2023, cite no. 24 (USPAT) (“Wen ‘307”), is hereby maintained.
The Invention As Claimed
Applicants claim a method for the manufacture of an adhesive matrix, comprising solubilizing a copolymer of n-vinyl-2-pyrrolidone and vinyl acetate in toluene, solubilizing a combination of polyisobutylene and polybutene in a second solvent, such as toluene, mixing the solubilized copolymer of n-vinyl-2-pyrrolidone and vinyl acetate and the solubilized combination of polyisobutylene and polybutene to form a homogeneous solution, adding to the homogeneous solution an acrylic acid/vinyl acetate copolymer solubilized in a third solvent, such as ethyl acetate, to form an adhesive solution, adding donepezil, and forming an adhesive matrix from the adhesive solution with the active agent that comprises between about 35 - 80% wgt of an acrylic acid-vinyl acetate adhesive, between about 0.01 - 30% wgt mixture of polyisobutylene and polybutene, between about 10 - 25% wgt of the n-vinyl-2-pyrrolidone/vinyl acetate copolymer, and between about 5 - 50% donepezil, wherein the copolymer of n-vinyl-2-pyrrolidone and vinyl acetate is a 60:40 copolymer, wherein the acrylic acid/vinyl acetate copolymer does not include methacrylic acid/vinyl acetate copolymers, wherein forming an adhesive matrix comprises applying the adhesive solution with the active agent onto a substrate and drying at a temperature of from 50 - 100° C, and wherein the adhesive matrix comprises 15 - 25% wgt donepezil, 50 - 60% wgt acrylate acid/vinyl acetate adhesive, 7 - 15% wgt polyisobutylene and polybutene mixture, and 10 - 20% wgt polyvinylpyrrolidone-vinyl acetate copolymer.
The Teachings of the Cited Art
Yang ‘081 discloses a donepezil transdermal patch comprising a backing layer and a pressure sensitive adhesive matrix layer, wherein the pressure sensitive adhesive matrix layer comprises donepezil free base and an acrylic pressure sensitive adhesive agent, such as a copolymer of 2-ethylhexyl acrylate and vinyl acetate, or a copolymer of 2-ethylhexyl acrylate, vinyl acetate, and hydroxyl-containing monomers, (see Abstract), wherein the donepezil is present in the adhesive layer in an amount of from about 1% to about 15% (see ¶[0022]), wherein the 2-ethylhexyl acrylate and vinyl acetate copolymer is present in an amount of about 25 to about 35% wgt (see ¶[0019]), or about 50% to about 99% (see ¶[0026]), and wherein the donepezil transdermal patch of the present invention is prepared by a method comprising the steps of dissolving a composition comprising donepezil free base and an acrylic pressure sensitive adhesive agent in a solvent such as toluene or ethyl acetate, coating the solution on a release liner or a backing layer, removing the solvent by drying, and then binding the laminate coated with the solution to a backing layer or a release liner (see ¶[0036]). The reference does not disclose preparing an adhesive matrix by solubilizing a 60:40 copolymer of n-vinyl-2-pyrrolidone and vinyl acetate at a loading of 10 – 25% wgt in toluene, or solubilizing a mixture of polyisobutylene and polybutene at a loading of 0.01 – 30% wgt in toluene, or a second solvent, or drying the adhesive matrix comprising donepezil at a temperature between 50 and 100° C. The teachings of Nink WO ‘969 and Wen ‘307 remedy those deficiencies.
Nink WO ‘969 discloses transdermal therapeutic systems (TTS’s) comprising an adhesive composition that comprises a pressure-sensitive adhesive (PSA), such as a polyisobutylene, a copolymer of vinyl pyrrolidone and vinyl acetate as a permeation enhancer, and an active ingredient effective for the treatment of dopamine-related disorders such as Parkinson's Disease (see Abstract), wherein the active ingredient is rotigotine (see p. 1, l1. 14 - 17), wherein the TTS comprises a backing layer and a release liner (see p. 4, ll. 30 – 34), wherein the active ingredient is present in the drug containing adhesive composition in an amount of 1 to 30% by weight (see p. 7, ll. 15 – 16), wherein the amount of PSA in the adhesive composition preferably ranges from 40 to 98% by weight (see p. 8, ll. 4 – 5), wherein a preferred tackifier for PIB is a polybutene (see p. 12, l. 2), wherein the polyisobutylene adhesive can be a mixture of two, three, or more, different polyisobutylenes (see p. 11, ll. 20 – 21), wherein the adhesive compositions comprise a copolymer of vinyl pyrrolidone and vinyl acetate, such as sold commercially as KOLLIDON® VA 64 (with 6 parts vinyl pyrrolidone and 4 parts vinyl acetate), present in amounts of from 1 – 30% wgt (see p. 13, ll. 1 – 22), wherein the copolymer of vinyl pyrrolidone and vinyl acetate distinctly increases the skin permeation rate of the active ingredient after application of a TTS containing the adhesive composition (see p. 14, ll. 5 – 7), wherein the TTS’s are manufactured by processes comprising mixing the PSA with the active ingredient and a copolymer of vinylpyrrolidone and vinyl acetate in a solvent such as toluene to form a first solution, preparing a second solution comprising the adhesive polymer, and mixing the two solutions (see p. 25, ll. 16 – 34), wherein the resulting mixture is coated on a release liner and dried to remove the solvent, forming the drug-adhesive layer (see p. 26, ll. 4 – 8), wherein, in some embodiments, the release liner is first coated with one or more adhesive layers being free of active ingredient, followed by coating the backing layer or release liner (i.e,. the one not coated with the drug-free adhesive layer) with one or more adhesive layers containing the active ingredient, wherein the coated layers of the backing/release liner layers are combined by lamination (see p. 26, ll. 11 – 15).
Wen ‘307 discloses methods for administering an anti-dementia active agent, such as donepezil, in a transdermal system to a subject suffering from Alzheimer’s disease (see Abstract; see also ¶¶[0001] – [0002]; cf. claim 1), wherein the system comprises an active agent layer comprising the active agent in an amount ranging from about 0.5 – 50% wgt (see ¶[0020]; cf. claim 21), wherein the transdermal system may include additional layers, such as one or more of a backing layer, an adhesive layer, an intermediate layer, a release liner, etc. (see ¶[0019]; cf. claim 5), wherein the active agent is donepezil, present as the free base form or the salt form (see ¶[0021]; cf. claim 1), wherein the active agent layer may comprise a number of additional components such as stability enhancers and/or flux modulators, plasticizers (carboxylic acid esters), percutaneous absorption enhancers (carboxylic acid esters), an active agent stabilizer (polyhydric alcohol), a physicochemical stabilizer (acrylic polymer), and an aminated polymer (see ¶[0025]), wherein the carboxylic acid esters can comprise esters of a polyvalent carboxylic acid and a monohydroxy alcohol, and esters of a fatty acid and a polyhydric alcohol, and combinations thereof (see ¶[0027]), wherein the active agent layer may also comprise polyhydric alcohols, such as glycerin [glycerol] (see ¶[0031]), wherein the active agent layer further comprises an acrylic polymer (see ¶[0032]), wherein the system further comprises a substrate layer, such as a pressure sensitive adhesive (PSA) layer (see ¶[0035]; cf. claim 5), wherein the PSA layer includes one or more components in common with the active agent reservoir layer, such as the acrylic polymer and the carboxylic acid esters (see ¶[0041]), wherein the transdermal systems may be configured to provide for a skin permeation rate sufficient to administer a target dosage of the active agent to a subject over a period of time at levels of 15 mg/day, or greater (see ¶[0055]; cf. claim 3), wherein the adhesive mass solution obtained by mixing the constituent materials of the active agent layer and coating the resulting mixture on a release liner, followed by drying the adhesive coating at 70 - 80° C, to obtain the active agent layer, on which a backing layer is laminated (see ¶[0056]), and wherein the transdermal systems may be applied to the skin for an amount of time sufficient to deliver a target dose of the active agent to a subject over a period of time ranging from 1 to 14 days, or for seven days (see ¶[0064]; cf. claim 4).
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 an adhesive matrix for a donepezil transdermal patch agent comprising a backing layer and a pressure sensitive adhesive matrix layer, wherein the pressure sensitive adhesive matrix layer comprises donepezil free base and an acrylic pressure sensitive adhesive agent, such as a copolymer of 2-ethylhexyl acrylate and vinyl acetate, wherein the donepezil is present in the adhesive layer in an amount of from about 1% to about 15%, wherein the 2-ethylhexyl acrylate and vinyl acetate copolymer is present in an amount of about 25 to about 35% wgt, or about 50% to about 99%, wherein the donepezil transdermal patch of the present invention is prepared by a method comprising the steps of dissolving a composition comprising donepezil free base and an acrylic pressure sensitive adhesive agent in a solvent such as toluene or ethyl acetate, coating the solution on a release liner or a backing layer, removing the solvent by drying, and then binding the laminate coated with the solution to a backing layer or a release liner, as taught by Yang ‘081, wherein the adhesive matrix further comprises a pressure-sensitive adhesive (PSA), such as a polyisobutylene, a copolymer of vinyl pyrrolidone and vinyl acetate as a permeation enhancer, and an active ingredient effective for the treatment of dopamine-related disorders, wherein the amount of PSA in the adhesive composition preferably ranges from 40 to 98% by weight, wherein the adhesive matrix further comprises a polybutene as a tackifier for polyisobutylene, wherein the copolymer of vinyl pyrrolidone and vinyl acetate is KOLLIDON® VA 64 (with 6 parts vinyl pyrrolidone and 4 parts vinyl acetate), present in amounts of from 1 – 30% wgt, wherein transdermal therapeutic systems (TTS’s) comprising the adhesive matrix are manufactured by processes comprising mixing the PSA with the active ingredient and a copolymer of vinylpyrrolidone and vinyl acetate in a solvent such as toluene to form a first solution, preparing a second solution comprising the adhesive polymer, and mixing the two solutions, wherein the resulting mixture is coated on a release liner and dried to remove the solvent, forming the drug-adhesive layer, as taught by Nink WO ‘969, and wherein the adhesive mass solution is obtained by mixing the constituent materials of the active agent layer and coating the resulting mixture on a release liner, followed by drying the adhesive coating at 70 - 80° C, to obtain the active agent layer, on which a backing layer is laminated, as taught by Wen ‘307. One of skill in the art would be motivated to do so, with a reasonable expectation of success in so doing, by the teachings of Nink WO ‘969 to the effect that wherein the copolymer of vinyl pyrrolidone and vinyl acetate distinctly increases the skin permeation rate of the active ingredient after application of a TTS containing the adhesive composition (see p. 14, ll. 5 – 7).
With respect to those claims reciting quantitative limitations directed to the relative mass loadings of the components of the adhesive matrix (see claims 10, 25), the Examiner notes that the cited references disclose relative loadings that are not 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).”
With respect to claim 16, which recites a limitation directed to the acrylate adhesive being an acrylic acid/vinyl acetate copolymer that “is one without a cross-linker agent,” the Examiner notes that the primary reference, Yang ‘081, does not affirmatively address whether the acrylate copolymer has been cross-linked. It is the Examiner’s position, however, that the reference’s failure to affirmatively disclose crosslinking of the acrylate copolymer gives rise to a reasonable presumption that the copolymer is not cross-linked. In addition, the reference does not disclose an adhesive matrix further comprising a recognizable cross-linking agent, the absence of which acts to affirm the presumption that the 2-ethylhexyl acrylate and vinyl acetate copolymer is not cross-linked.
In addition, with respect to the quantitative limitation recited in claim 16 that is directed to the viscosity of the acrylic acid/vinyl acetate copolymer being “between about 2000 – 8000 mPa·sec”, the Examiner notes that the cited references do not expressly disclose an acrylic acid/vinyl acetate copolymer with a dynamic viscosity within that range. However, the Examiner notes that Yang ‘081 specifically discloses an acrylate pressure-sensitive adhesive in the form of a copolymer of 2-ethylhexyl acrylate and vinyl acetate, which copolymer, as addressed above, is not cross-linked. In light of the disclosure of that specific non-cross-linked acrylate adhesive copolymer, it is the Examiner’s position that the discloses acrylate copolymer would necessarily display a viscosity within the claimed range. See MPEP § 2182: “if the prior art reference teaches the identical structure or acts but is silent about performing the claimed function, a reasonable presumption is that the prior art structure inherently performs the same function,” citing In re Spada, 911 F.2d 705, 708, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
With respect to claim 17, which claim recites a limitation directed to a solvent in which polyvinylpyrrolidone homopolymer is insoluble, the Examiner notes that the cited references do not expressly teach the solubility characteristics of the disclosed solvent, toluene. However, claim 18 is directed specifically to toluene as the first solvent. Consequently, the Examiner presumes that the polyvinylpyrrolidone homopolymer is insoluble in toluene, thus reading on this limitation.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 10 – 18, 21 , and 23– 26 would have been obvious within the meaning of 35 USC § 103.
Response to Applicants’ Arguments
The Examiner has considered the Arguments presented by Applicants in the Response filed 26 January 2026 but does not find them persuasive. Applicants first argue that “Nink does not teach or suggest solubilizing a mixture of polyisobutylene and polybutene that comprises between about 0.01-30 wt% [of the] polyisobutylene and polybutene mixture [in the adhesive matrix].” Applicants go on to argue that “the minimum amount of polyisobutylene by weight in Nink is 40% by weight. This amount of polyisobutylene alone is well out of the range of found in the instant claims, which has a maximum of 30 wt% for a mixture of polyisobutylene and polybutene.” The Examiner respectfully disagrees, primarily on the basis that Applicants are misinterpreting the teachings of Nink WO ‘969.
In this regard, the Examiner notes, as cited in the above rejection, the disclosed adhesive compositions are prepared by adding the active and a copolymer of vinyl pyrrolidone and vinyl acetate to a suitable solvent to form a first solution, forming a second solution comprising the adhesive polymer (PIB) and a suitable solvent, and then adding the second solution to the first solution to form the adhesive matrix (see p. 25, ll. 30 – 34). Applicants argue that the polyisobutylene of the claimed invention is present at a maximum loading of 30% (see claim 1), compared to a loading of 40 – 98% as disclosed by Nink WO ‘969, thus falling outside the claimed range. However, Applicants err in not taking into account that the disclosed loading to which Applicants refer applies only to the second solution. Given that the reference further discloses that the copolymer of vinyl pyrrolidone and vinyl acetate (KOLLIDON® VA 64) can be present at up to 30% of the total composition (see p. 13, ll. 20 – 24), then the content of PIB in the final adhesive layer composition must necessarily be diluted well below the cited 40%, without even taking into consideration the mass contribution of the solvents in the solutions, thus reading on the limitation in question.
Consequently, based on the above discussion, Applicants’ arguments are not persuasive and claims 10 – 18, 21, and 23 – 26 stand rejected pursuant to 35 U.S.C. § 103.
NO CLAIM IS ALLOWED.
THIS ACTION IS MADE FINAL. Applicants are reminded of the extension of time policy as set forth in 37 CFR § 1.136(a).
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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 Response 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.
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