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
Request for Continued Examination
A Request for Continued Examination pursuant to 37 CFR § 1.114, including the fee set forth in 37 CFR § 1.17(e), was filed in this application after final rejection. Because this application is eligible for continued examination pursuant to 37 CFR § 1.114, and Applicants have timely paid the fee set forth in 37 CFR § 1.17(e), the finality of the previous Office Action has been withdrawn pursuant to 37 CFR § 1.114. Applicant's submission filed on 15 May 2013 has been entered.
Status of the Claims
Applicants filed claims 1 - 26 with the instant application according to 37 CFR § 1.114, on 14 May 2026. In an Amendment entered with the Request for Continued Examination, Applicants amended claim 10. Claims 1 – 9, 19, 20, and 23 – 26 remain withdrawn as being directed to a non-elected invention. Consequently, claims 10 – 18, 21, and 23 - 26 are available for consideration.
REJECTIONS WITHDRAWN
Rejections Pursuant to 35 U.S.C. § 103
The obviousness rejection set forth in the Action of 12 March 2026 is hereby withdrawn in light of Applicants’ amendment of the claims, and in favor of the new grounds of rejection set forth below.
NEW GROUNDS OF REJECTION
Rejections Pursuant to 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 25 is rejected pursuant to 35 U.S.C. § 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The claim recites limitations directed to relative mass loadings of components of the adhesive matrix prepared according to the method of the invention. The claim recites a dependency from claim 10, which claims also recites relative mass loadings of components of the adhesive matrix. However, claim 10 further recites that the mass loadings are relative to “the total weight of the adhesive matrix.” Claim 25 is indefinite in that one of ordinary skill in the art would be uncertain as to whether the relative loadings recited in claim 25 are different from those recited in claim 10, or the same.
Appropriate correction or cancelation is required.
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 Examiner directs Applicants’ attention to the fact that the instant rejection applies the same references as applied in previous rejections of the claims pursuant to 35 U.S.C. § 103. However, the teachings of these references are applied in a manner different from how those teachings were applied in a prior rejection, necessitated by Applicants’ amendment of the claims, thus constituting a new basis of rejection.
Claims 10 – 18, 21, and 23 - 26 are rejected 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”).
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, based on the total weight of the adhesive matrix, wherein the acrylic acid/vinyl acetate copolymer does not include methacrylic acid/vinyl acetate copolymers, wherein the acrylic acid/vinyl acetate copolymer is one without a cross-linker agent, and has a viscosity between about 2000 - 8000 mPa·s when measured at 25° C, 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 (see Abstract), present in the adhesive layer in an amount of from about 1% to about 15% (see ¶[0022]), and an acrylic pressure sensitive adhesive agent, such as a copolymer of 2-ethylhexyl acrylate and vinyl acetate, present in an amount of a 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 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 polyisobutylene, or mixtures thereof, and a copolymer of vinyl pyrrolidone and vinyl acetate, and an active ingredient effective for the treatment of dopamine-related disorders such as Parkinson's Disease (see Abstract), such as 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 total amount of PSA in the adhesive composition ranges from 40 to 98% by weight (see p. 8, ll. 4 – 5), wherein the polyisobutylene is used in amounts of 1 to 15% wgt, based on the total weight of the drug containing adhesive composition (see p. 11, ll. 5 – 9), wherein the polyisobutylene comprises polybutene as a preferred tackifier (see p. 12, ll. 1 - 2), wherein the copolymer of vinyl pyrrolidone and vinyl acetate, is a commercially available 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 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 mixture of polyisobutylene and polybutene, and a copolymer of vinyl pyrrolidone and vinyl acetate (KOLLIDON® VA 64, with 6 parts vinyl pyrrolidone and 4 parts vinyl acetate), present in amounts of from 1 – 30% wgt, wherein the total amount of PSA in the adhesive composition ranges from 40 to 98% by weight, 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 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), and that polyisobutylene comprising polybutene as a tackifier, is an effective PSA for transdermal systems used for treating systems of Alzheimer’s disease.
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 disclosed acrylate copolymer would necessarily display a viscosity within the claimed range. See MPEP § 2112: “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 14 May 2026 but does not find them persuasive, to the extent still relevant in light of the new grounds of rejection set forth above. Applicants’ initial arguments are focused on a limitation recited in claim 1 directed to the relative mass loading of the mixture of polyisobutylene and polybutene being “between about 0.01-30 wt%.” Applicants contrast this limitation to a reading of the disclosure of Nink WO ‘969 that allegedly discloses the mixture of polyisobutylene and polybutene in a range from 40 – 98% by weight . . . based upon the total weight of the [adhesive] composition.” Although Applicants correctly quote the disclosure of the reference, they have apparently failed to take into account that the disclosed quantitative range is for the PSA (pressure sensitive adhesive), and not specifically for the polyisobutylene/polybutene mixture. In so arguing, Applicants ignore that the disclosed compositions comprise a high molecular weight polymer, such as polyisobutylene, “used in amounts of 1 to 15% wgt, based on the total weight of the drug containing adhesive composition (see p. 11, ll. 5 – 9),” and that the polyisobutylene (PIB) comprises polybutene as a tackifier for the PIB (see p. 12, ll. 1 - 2). In looking more closely at the reference, it is the Examiner’s position that the quantitative PSA loading cited by Applicants is reasonably read to be directed to the total PSA “[t]he amount of the PSA in the adhesive composition,” and not just to PIB. Given that the reference discloses not only PIB/PB, but also other components that one of ordinary skill in the relevant art would recognize as PSA’s, such as copolymers of vinyl pyrrolidone and vinyl acetate (see Abstract), it becomes apparent that the PIB/PB mixture does not constitute up to 98% wgt.
Applicants also argue that the reference discloses that the “minimum amount of tackifier as taught by Nink is 10% by weight.” However, that teachings is not directed specifically to polybutene. Furthermore, the reference explicitly states that the polyisobutylene comprises polybutene as a tackifier, thus leading to an interpretation that is logically and grammatically reasonable that the stated loadings of polyisobutylene refer to the mixture of polyisobutylene comprising polybutene.
Further with respect to claim 10, Applicants amended the claim in the Response filed 14 May 2026 to recite that the relative mass loadings of the components are “based on the total weight of the adhesive matrix.” However, Applicants did not amend claim 25, which claim also recites relative mass loadings of the components, to be consistent with amended claim 10. This, then, raises the question as to whether claim 25 is directed to a different base for calculation of relative loading ranges than that used for claim 10. Applicants have argued, with respect to distinguishing over the cited art on the basis of relative loadings as now modified by the limitation, “based on the total weight of the adhesive matrix,” that the new limitation to claim 10 somehow impacts the calculation of those loadings, without necessarily describing precisely how, leaving the skilled practitioner in the dark.
Consequently, based on the discussion above, 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.
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 am - 5:30 pm.
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/DANIEL F COUGHLIN/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/ Supervisory Patent Examiner, Art Unit 1619
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