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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/05/2025 has been entered.
Status of the Claims
Claim 7 has been cancelled in a previous communication. Claim 9 has been cancelled. New claims 11-13 have been added.
Claims 1-6, 8, and 10-13 are pending and currently under examination.
All rejections not reiterated have been withdrawn.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statements (IDS) filed on 07/14/2025 is attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 1-6, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Jain et al. (US20180185298A1, Published 07/05/2018; as cited in the IDS filed 11/04/2022), as evidenced by Sozio et al. (Neuropsychiatr Dis Treat. 2012;8:361-368).
Applicant’s Invention
Applicant’s claims are drawn to a patch preparation comprising a support and an adhesive layer on at least one surface of the support, wherein the adhesive layer comprises a drug, levulinic acid, and propylene glycol fatty acid ester, and wherein the levulinic acid and the propylene glycol fatty acid ester are present in a mass ratio (levulinic acid : propylene glycol ester fatty acid) of 1:0.1 to 1:20, and the drug is a basic drug having at least one basic group selected from the group consisting of an alcoholic hydroxy group, a sulfanyl group, a phenolic hydroxy group, -NH2, -NRH, and NRR’, wherein R and R’ are each independently an optionally substituted alkyl group or an optionally substituted aryl group, provided that the drug excludes tandospirone and a pharmaceutically acceptable salt thereof.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1-3, Jain teaches a composition for preparing a patch for transdermal delivery of donepezil, wherein the composition comprises an adhesive matrix (i.e., adhesive layer) comprising at least about 5-50 wt % donepezil free base form (i.e., drug) (paragraph [0012]), at least one lipophilic permeation enhancer that is an acid such as levulinic acid (paragraph [0013]). Jain also teaches that the composition further comprises a second permeation enhancer such as propylene glycol monolaurate (paragraph [0015]). Jain further teaches a backing layer (i.e., support) provides a structural element for holding or supporting the adhesive layer (paragraph [0063]), wherein the adhesive layer adheres to the backing layer (paragraph [0066]). Jain also teaches the adhesive layer comprises about 1-20 wt % of the at least one acid lipophilic permeation enhancer such as levulinic acid (paragraph [0022]). Jain continues to teach the penetrating or permeating enhancer is included in an amount between about 1-10% relative to the weight of the adhesive matrix (paragraph [0057]). Jain further teaches Donepezil is an acetylcholinesterase inhibitor with the chemical structure 2,3-Dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one:
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(paragraph [0003]). The examiner points out that the instant specification teaches that -NRR’ is a tertiary amino group (paragraph [0026]). Therefore, Donepezil taught by Jain has a at least one basic group selected from -NRR’ as the cyclic amine present in the structure is also a tertiary amino group wherein the nitrogen is bonded to three different carbon atoms, two within the piperidine ring and a third attached to the benzyl group, as indicated in the -NRR group.
Regarding claims 4-5, Jain teaches compositions herein may include one or more permeation enhancer, wherein for use in the adhesive matrix include methyl laurate (i.e., other fatty acid ester) (paragraph [0057]).
Regarding claim 6, Jain teaches the penetrating or permeating enhancer is included in an amount between about 1-10% relative to the weight of the adhesive matrix (paragraph [0057]).
Regarding claim 8, Jain teaches the composition comprises an adhesive matrix (i.e., adhesive layer) comprising an adhesive polymer (i.e., adhesive base), wherein the adhesive polymer is selected from acrylic polymer (paragraph [0016]).
Regarding claim 10, Sozio teaches donepezil is considered to be physiochemically well-suited for transdermal delivery having a log P (i.e., logPow) value of 3.08 to 4.11.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Jain does not disclose a single embodiment or example where every limitation recited in the instant claims is taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art at the time of filing because Jain teaches all of the claimed elements. It would have been prima facie obvious to one of ordinary skill at the time of filing to make a patch preparation comprising a support and an adhesive layer on at least one surface of the support, wherein the adhesive layer comprises a drug, levulinic acid, and propylene glycol fatty acid ester, and wherein the levulinic acid and the propylene glycol fatty acid ester are present in a mass ratio (levulinic acid : propylene glycol ester fatty acid) of 1:0.1 to 1:20, provided that the drug excludes tandospirone and a pharmaceutically acceptable salt thereof because Jain teaches and contemplates all the elements required to make the composition.
With regards to claim 1, wherein a content ratio of the levulinic acid and the propylene glycol fatty acid ester is 1:0.1 to 1:20 in mass ratio, it would have been obvious to one of ordinary skill in the art to vary the amounts of levulinic acid and the propylene glycol fatty acid ester depending on the desired result. One would have understood in view of the adhesive layer comprises about 1-20 wt % of the at least one acid lipophilic permeation enhancer such as levulinic acid (paragraph [0022]) and the penetrating or permeating enhancer is included in an amount between about 1-10% relative to the weight of the adhesive matrix (paragraph [0057]). Therefore, it would have been obvious to one of ordinary skill in the art to optimize the amounts of levulinic acid and the propylene glycol fatty acid ester to obtain the desired ratio because Jain teaches amounts of levulinic acid and the propylene glycol fatty acid ester. Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Claims 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Jain et al. (US20180185298A1, Published 07/05/2018; as cited in the IDS filed 11/04/2022), as evidenced by Sozio et al. (Neuropsychiatr Dis Treat. 2012;8:361-368) in view of Ikesue et al. (EP1547595B1, Published 10/08/2014).
Applicant’s Invention
Jain and Sozio render obvious all the limitations of claim 1. Applicants claim 11 further adds the limitation wherein the acrylic polymer is a polymer obtained by copolymerizing a monomer mixture containing a N-vinylcyclic amide and an alkyl (meth)acrylate monomer. Claim 12 further adds the limitation wherein the alkyl (meth)acrylate monomer is an alkyl (meth)acrylate monomer whose alkyl group is a linear alkyl group or branched chain alkyl group having a carbon number of 4 to 13. Claim 13 further adds the limitation wherein the content of the N-vinylcyclic amide in the acrylic polymer is 15 to 65 mass%.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 11-13, Jain teaches in some embodiments, the at least one adhesive polymer is selected from an acrylic polymer, wherein the acrylic polymer can be selected from a cross-linked polyvinylpyrrolidone (paragraph [0016]). Jain also teaches that the acrylic polymer can be copolymers of a monomer or monomers selected from methacrylic acid esters (paragraph [0045]). Jain further teaches the adhesive matrix comprises at least about 25-80 wt % of polymers relative to the weight of the adhesive matrix (paragraph [0044]).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Jain does not teach wherein the acrylic polymer is obtained by copolymerizing a monomer mixture containing a N-vinylcyclic amide and an alkyl (meth)acrylate monomer; wherein the alkyl (meth)acrylate monomer is an alkyl (meth)acrylate monomer whose alkyl group is a linear alkyl group or branched chain alkyl group having a carbon number of 4 to 13; wherein the content of the N-vinylcyclic amide in the acrylic polymer is 15 to 65 mass%. However, these deficiencies are cured by Ikesue et al.
In the analogous art of patches for transdermal administration, Ikesue teaches a patch for transdermal administration comprising a backing and an adhesive layer comprising an adhesive base agent and a drug (paragraph [0001]). Ikesue also teaches the adhesive layer comprises an adhesive base agent in addition to the drug. Here, as the adhesive base agent according to the present invention, rubber polymer and acrylic polymer can be mentioned (paragraph [0019]), wherein As acrylic polymer, polymers employing alkyl (meth)acrylate esters in which carbon number in the alkyl group is 4 or more and, preferably, 15 or less, are preferable. Specific examples of such alkyl (meth)acrylate ester include alkyl (meth)acrylate esters having a linear alkyl group, a branched alkyl group such as butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and tridecyl (paragraph [0021]). Ikesue further teaches Further, a copolymerizable monomer may be copolymerized in the aforementioned alkyl (meth)acrylate ester, such as vinyl-series monomers such as N-vinyl-2-pyrrolidone, methylvinyl pyrrolidone, vinyl piperidone (i.e., N-vinylcyclic amide), wherein one kind of or two kinds or more in combination of these may be copolymerized These copolymerizable monomers can be used for the purpose of adjusting cohesion force of the adhesive layer or enhancing solubility of the drug. The copolymerization amount may be arbitrarily set within a range of 2-40 % by weight in accordance with purposes (paragraph [0022]).
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 have the acrylic polymer is obtained by copolymerizing a monomer mixture containing a N-vinylcyclic amide and an alkyl (meth)acrylate monomer as Jain’s acrylic polymer in the adhesive polymer of the patch for transdermal delivery. Jain teaches the at least one adhesive polymer is selected from an acrylic polymer wherein the acrylic polymer can be selected from a cross-linked polyvinylpyrrolidone (paragraph [0016]) and that the acrylic polymer can be copolymers of a monomer or monomers selected from methacrylic acid esters (paragraph [0045]). One would have understood in view of Ikesue that the adhesive layer comprises an adhesive base agent such as acrylic polymer (paragraph [0019]), wherein as acrylic polymer, polymers employing alkyl (meth)acrylate esters in which carbon number in the alkyl group is 4 or more and, preferably, 15 or less, are preferable. Ikesue further teaches a copolymerizable monomer may be copolymerized in the aforementioned alkyl (meth)acrylate ester, such as vinyl-series monomers such as N-vinyl-2-pyrrolidone, methylvinyl pyrrolidone, vinyl piperidone (i.e., N-vinylcyclic amide), wherein one kind of or two kinds or more in combination of these may be copolymerized. It would have been obvious to one of ordinary skill in the art to have the acrylic polymer is obtained by copolymerizing a monomer mixture containing a N-vinylcyclic amide and an alkyl (meth)acrylate monomer as Jain’s acrylic polymer in the adhesive polymer of the patch for transdermal delivery because Jain teaches that the adhesive layer is an acrylic polymer which can be made from a cross-linked polyvinylpyrrolidone (paragraph [0016]) and that the acrylic polymer can be copolymers of a monomer or monomers selected from methacrylic acid esters (paragraph [0045]), and Ikesue teaches an adhesive layer which comprises an adhesive base agent such as acrylic polymer (paragraph [0019]), wherein as acrylic polymer, polymers employing alkyl (meth)acrylate esters in which carbon number in the alkyl group is 4 or more and, preferably, 15 or less, are preferable. Ikesue further teaches a copolymerizable monomer may be copolymerized in the aforementioned alkyl (meth)acrylate ester, such as vinyl-series monomers such as N-vinyl-2-pyrrolidone, methylvinyl pyrrolidone, vinyl piperidone (i.e., N-vinylcyclic amide), wherein one kind of or two kinds or more in combination of these may be copolymerized. Therefore, an acrylic polymer obtained by copolymerizing a monomer mixture containing a N-vinylcyclic amide and an alkyl (meth)acrylate monomer was known to serve the same purpose as an acrylic polymer in an adhesive layer. See MPEP 2144.06(II).
With regards to claim 13, wherein the content of the N-vinylcyclic amide in the acrylic polymer is 15 to 65 mass %, it would have been obvious to one of ordinary skill in the art to optimize the amount of the N-vinylcyclic amide in the acrylic polymer. Ikesue teaches these copolymerizable monomers can be used for the purpose of adjusting cohesion force of the adhesive layer or enhancing solubility of the drug. The copolymerization amount may be arbitrarily set within a range of 2-40 % by weight in accordance with purposes (paragraph [0022]). Therefore, it would have been obvious optimize the amount of the N-vinylcyclic amide in the acrylic polymer to obtain the desired amount because Ikesue teaches that the copolymerizable monomers can be used for the purpose of adjusting cohesion force of the adhesive layer and can be in the amount of 2-40% by weight, therefore, optimizing the amounts of the monomers can be done by routine experimentation for the desired results of cohesion force of the adhesive layer. Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07). See MPEP 2144.05.
Response to Arguments
Applicant's arguments filed 08/05/2025 have been fully considered but they are not persuasive.
On pages 5-6 of Applicants remarks, Applicants argue that Jain does not disclose or reasonably suggest an adhesive layer comprising a basic drug having at least one basic group selected from the group consisting of an alcoholic hydroxy group, a sulfanyl group, a phenolic hydroxy group, -NH2, -NRH, and NRR’, wherein R and R’ are each independently an optionally substituted alkyl group or an optionally substituted aryl group. Rather Jain discloses a patch for transdermal delivery of donepezil which is not a basic drug having at least one basic group selected from the group consisting of an alcoholic hydroxy group, a sulfanyl group, a phenolic hydroxy group, -NH2, -NRH, and NRR’, wherein R and R’ are each independently an optionally substituted alkyl group or an optionally substituted aryl group. Instead donepezil is a drug having a cyclic amine, a ketone, and methyl ether functional groups, none of which are within the scope of the basic group as defined in the pending claims.
This argument is not persuasive. The Examiner points out as Applicants have cited that donepezil has a cyclic amine, a ketone, and methyl ether functional groups, the Examiner interprets the cyclic amine to read on -NRR’ a tertiary amine, therefore donepezil reads on Applicants basic drug having at least one basic group.
On pages 7-9 of Applicants remarks, Applicants argue that as described at paragraph 0023, and as demonstrated by the Examples set forth in Tables 3, 6, and 7, of the present application, the patch preparation of the present invention simultaneously achieves good skin permeability of a drug and practical adhesive properties. Applicants also argue that Jain et al. does not disclose or reasonably suggest an adhesive layer comprising levulinic acid and propylene glycol fatty acid ester present in a mass ratio of 1:0.1 to 1:20, much less recognize the unexpected benefits. Applicants further argue that Jain et al. merely discloses levulinic acid among a large list of lipophilic permeation enhancers and merely discloses propylene glycol monolaurate among a large list of optional second permeation enhancers. Applicants continue to argue that Applicants have unexpectedly discovered that levulinic acid when used in combination with a propylene glycol fatty acid ester, significantly enhances the skin permeation amount of a drug as compared to lactic acid, when used in combination with the same propylene glycol fatty acid ester.
These arguments are not persuasive. The Examiner reiterates that insomuch as this may be an assertion of unexpected results, please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims. The Examiner points out that Applicants have not provided a side-by-side comparison to the closest prior art, which the examiner considers to be Jain’s invention. Jain’s Example 1 teaches an adhesive formulation comprising inter alia donepezil (i.e., basic drug), levulinic acid, and lauryl lactate (i.e., second permeation enhancer) (paragraph [0085]), therefore Jain is teaching a combination of two permeation enhancers. Jain teaches the composition further comprises at least a second permeation enhancer selected form inter alia propylene glycol monolurate and lauryl lactate, so it would have been obvious to one of ordinary skill in the art to substitute the lauryl lactate used in Jain’s Example 1 for propylene glycol monolurate because Jain teaches both for the purpose of being a second permeation enhancer. See MPEP 2144.06 (II). The Examiner continues to point out that a proper comparison would be to a composition taught in Jain comprising levulinic acid combined with the second permeation enhancers, as Jain teaches the adhesive matrix includes skin penetration enhancers and an acid permeation enhancer (levulinic acid), wherein the permeation enhancer forms a complex with the active agent thereby increasing the solubility of the active agent in the skin resulting in enhanced permeation of the active agent through the skin (paragraph [0072]). The only difference in the formulation of the instant invention and Jain is that the instant invention claims propylene glycol monolaurate as the second penetration enhancer, wherein the Jain uses a different second permeation enhancer (i.e., lauryl lactate), but the adhesive layer on a surface of a support comprising a basic drug and levulinic acid are taught in Jain. Therefore, the Applicants need to establish the difference between the closest prior art and their invention, as Jain teaches the claimed elements. The Examiner further points out that amounts of drug, additive 1 (i.e., levulinic acid and lactic acid), additive 2 (i.e., second permeation enhancer) in Applicants examples and comparative examples. The Examiner also points out that Applicants data in Tables 3, 6, and 7, Applicants only made formulations using fingolimod, agomelatine, and lidocaine, as the drugs in the formulations, whereas the claims read on any drug wherein the drug is a basic drug with a logPow of -1 to 7, therefore, the data is not commensurate in scope of the claims. For these reasons, Applicants have not met the burden to overcome an obviousness rejection with a persuasive showing of unexpected results.
With regards to the argument that Jain et al. merely discloses levulinic acid among a large list of lipophilic permeation enhancers and merely discloses propylene glycol monolaurate among a large list of optional second permeation enhancers, the Examiner points out that it would have been obvious to combine levulinic acid and propylene glycol monolurate because Jain teaches that they are both permeation enhancers. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06 (I). Also, the Examiner directs attention to Merck &Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Circ. 1989), which states with regards to its more than 1200 combinations: that the prior art “discloses a multitude of effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose taught by the prior art.” The Examiner also does not agree with Applicants characterization that Jain’s list of permeation enhancers is a long list, because one of ordinary skill in the art would have an M.D. or Ph.D. in formulation science and would have access to high-throughput screening tools, therefore, it would have been routine optimization to screen the permeation enhancers to arrive at the formulation.
On page 10 of Applicants remarks, Applicants argue that Applicants have unexpectedly discovered that the practical adhesive properties (e.g., cohesive strength and water-resistance adhesiveness) can also be affected by the kind of acrylic polymer constituting the adhesive layer. Jain and Sozio fails to disclose or reasonably suggest an acrylic polymer as defined by newly added claims 11-13.
This argument is not persuasive for the reasons set forth above in the 103 rejection. The examiner further points out that In response to applicant's argument that the practical adhesive properties (e.g., cohesive strength and water-resistance adhesiveness) can also be affected by the kind of acrylic polymer constituting the adhesive layer, the fact that the inventor has 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).
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 BOATENG Examiner, Art Unit 1617
/ALI SOROUSH/ Supervisory Patent Examiner, Art Unit 1614