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 11 November 2025. In that Response, Applicants amended claims 1 and 10, canceled claims 5, 6, 8, 11, 13 – 15, 17, 18, 20, and 21, and added new claims 23 – 34. Consistent with the election of species (see below), claims 1, 2, 7, 12, 22, 27, 28, 33 and 34 are available for active consideration.
Elected Invention
As set forth in the Action of 17 June 2025, Applicants elected the species, octreotide acetate, from the genus of active ingredient. In the Response filed 11 November 2025, Applicants amended claim 10 to delete the limitation directed to octreotide acetate as the active ingredient, leaving leuprorelin as the only active ingredient recited in the claim. In light of the species election, claim 10 is directed to a non-elected invention and is, consequently, withdrawn from further consideration.
Furthermore, new claims 23 – 26 are directed to transdermal patches comprising active ingredients having molecular weights of 10,000, or greater. The molecular weight of the elected species of active ingredient, octreotide acetate, is 1139.24 (see specification, at ¶[0139]). Consequently, claims 23 – 26 are directed to a non-elected invention, and are hereby withdrawn from consideration. Likewise, claims 29 – 32 and 35 – 37, dependent from claims 23 – 26, are
also withdrawn from further consideration as being directed to a non-elected invention. See 37 CFR § 1.142(b).
REJECTIONS WITHDRAWN
Rejections Pursuant to 35 U.S.C. § 103
The Obviousness rejections set forth in the Action of 28 January 2025 are hereby withdrawn in light of Applicants’ amendments to the claims, and in favor of the new grounds of rejection set forth below.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. § 103
The following is a quotation of pre-AIA 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office Action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(s) absent any evidence to the contrary. Applicant is 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, 2, 7, 12, 22, 33, and 34 are rejected pursuant to 35 U.S.C. § 103, as being obvious over JP 2014-172840 A to Miyazaki, K. and W. Toru, published 22 September 2014, identified on the Information Disclosure Statement (ids) FILED 15 April 2022, cite no. 5 (FOR) (“Miyazaki JP ‘840”), in view of US 2018/0185273 A1 to Akamine, T., et al., published 5 July 2018, identified on the Information Disclosure Statement (IDS) filed 15 April 2022, cite no. 4 (USPATAPP) (“Akamine ‘273”).
The Invention As Claimed
Applicants claim a transdermal absorption-type patch, comprising a support material, and an adhesive layer laminated on the support material, wherein the adhesive layer comprises a solid composite material comprising octreotide acetate as an active ingredient, enclosed by a surfactant with an HLB value of 5 or less, an oil phase, and an adhesive agent containing alkyl (meth)acrylate having an alkyl group with 6 to 14 carbon atoms in an ester portion, wherein the content of the acrylic elastomer is 30% to 70% by mass, based on a total mass of the acrylic elastomer and the oil phase, and the composite material is in the form of a solid-in-oil type particle dispersed in the oil phase, wherein the content of the acrylic elastomer is 40% to 50% by mass based on the total mass of the acrylic elastomer and the oil phase, wherein the acrylic elastomer includes 2-ethylhexyl (meth)acrylate, and wherein the adhesive layer further comprises another additive.
The Teachings of the Cited Art
Miyazaki JP ‘8401 discloses a patch that uses solid-in-oil (S/O) type fine particles in which
a hydrophilic drug is coated with a surfactant, and contains an adhesive composition which is combined with an acrylic polymer as an adhesive layer (see ¶[0009]), wherein the S/O type fine particles have a configuration in which a hydrophilic drug is coated with a surfactant, and the hydrophilic portion of the surfactant associates with the hydrophilic drug and coats the surroundings (see ¶[0015]), wherein the molecular weight of the hydrophilic drug in the present invention is preferably 10,000, or less (see ¶[0019]), wherein the surfactant can be used without any particular limitation as long as it is acceptable in pharmaceutical preparations, including nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants (see ¶[0020]), wherein the surfactant has an HLB value of 6, or less (see ¶[0022]), wherein the S/O-type fine particles may contain a stabilizer, such as hydrophilic proteins that are coated with a surfactant together with the hydrophilic drug, thereby improving the stability of the S/O particles, and preventing leakage of the hydrophilic drug outside the S/O type fine particles (A) in the patch (see ¶[0025]), wherein the particles are prepared by adding an organic solvent solution containing a surfactant and, if necessary, a stabilizer, to an aqueous solution containing a hydrophilic drug and, if necessary, a stabilizer, and mixed by high speed stirring using a homogenizer to prepare a water-in-oil (W/O) type emulsion, which is then dried by freeze-drying, or the like, to produce solid W/O type microparticles (see ¶[0030]), wherein the S/O type microparticles are preferably dispersed in oils and fats before being mixed with other components of the pressure-sensitive adhesive composition (see ¶[0031]), wherein a preferred long-chain fatty acid ester for the oil phase is isopropyl myristate (see ¶[0032]), wherein, when the S/O type microparticles are dispersed in fats and oils, the mass ratio of fats and oils to the S/O type microparticles is 0.1 to 5 (see ¶[0033]), wherein the acrylic polymer of the adhesive contains a constitutional unit represented by general formula (1), as depicted on p. 9, has excellent compatibility with the S/O-type microparticles, and is excellent in releasing a solid from S/O type microparticles (id.), wherein the acrylic polymer may be a copolymer of a monomer composition containing an alkyl (meth)acrylate ester having 6 to 14 carbon atoms in the alkyl group of the ester moiety and a monomer having a plurality of polymerizable unsaturated groups, such as 2-ethylhexyl(meth)acrylate (see ¶[0041]), wherein the pressure-sensitive adhesive composition, when the amount of the S/O type fine particles is A parts by mass, and the amount of the acrylic polymer is B parts by mass, the mass ratio A/B is from 1/99 to 60/40 (see ¶[0042]), wherein the adhesive composition contains a transdermal absorption enhancer at 0.1% to 60% by mass (see ¶[0055]), wherein the patch has an adhesive layer and a support substrate on one side of the adhesive layer (id.), wherein the substrate is an acrylic resin (see ¶[0062]), wherein the patch has a release sheet on at least one side of the adhesive layer, and functions to protect the adhesive surface of the adhesive layer during storage of the (unused) patch (see ¶[0062]), wherein, in an exemplified embodiment, a solution of 2.065 parts by mass of sucrose oleate as a surfactant was dissolved in 80 parts by mass of cyclohexane, and added to an aqueous solution of 0.085 parts by mass of a hydrophilic drug dissolved in 40 parts by mass of ultrapure water, and the mixture was stirred at high speed at 24,000 rpm for 5 minutes with a homogenizer to prepare a W/O type emulsion which was then freeze-dried for 2 days to obtain S/O-type fine particles (see ¶[0069]), wherein the content of the active in the microparticles was 4.0% mass (see ¶[0070]), wherein a monomer composition containing 95 mol% of lauryl acrylate and 5 mol% of 2-hydroxyethyl acrylate was solution polymerized using a radical polymerization initiator to obtain a solution of acrylic polymer with solids content at 34% mass (id.), and wherein 2.15 parts by mass of the S/O particles were added to 0.43 parts by mass of isopropyl myristate to prepare a dispersion, and 2.58 parts by mass of the dispersion and 0.026 parts by mass of a crosslinking agent were added to 6.3 parts by mass of a solution of the acrylic polymer, and the mixture was stirred to prepare the adhesive layer, followed by application of the adhesive mixture to a release liner, which was then heated and dried to yield a layer comprising 45.2% mass of the S/O particles comprising 1.8% mass active, and 9% mass of the oil phase, and a supporting substrate was laminated onto the adhesive layer to form the patch (see ¶[0071]). The reference does not disclose a patch wherein the hydrophilic active ingredient is octreotide acetate, or a patch with an adhesive layer that further comprises another additive. These deficiencies are remedied by the teachings of Akamine ‘273.
Akamine ‘273 discloses a core-shell structure that has high skin permeability and that contains a hydrophilic drug having a molecular weight of 400 or more, a shell portion containing a surfactant, with a core portion that is a solid, and the surfactant has an alkyl group, or an alkenyl group, having 10 to 20 carbon atoms (see Abstract), wherein the hydrophilic drug is regarded to be difficult to permeate through skin among hydrophilic drugs (see ¶[0008]), wherein the hydrophilic drug is coated, partially or wholly, by the surfactant contained in the shell portion (see ¶[0024]), wherein, when the core-shell structure is dispersed in a base phase as an oil phase, an S/O (Solid in Oil) type external preparation is formed (see ¶[0029]), wherein the hydrophilic drug is octreotide acetate (see ¶[0033]; see also Ex. 5, ¶[0124]), wherein the core portion contains an additional component, such as a transdermal absorption promoter (see ¶[0036]), such as higher alcohols, N-acyl sarcosine and a salt thereof, higher monocarboxylic acids, higher monocarboxylic acid esters, aromatic monoterpene fatty acid esters, divalent carboxylic acids having 2 to 10 carbon atoms and salts thereof, polyoxyethylene alkyl ether phosphates and salts thereof, lactic acid, lactic acid esters and citric acid, and the like (see ¶[0039]), wherein the method for drying the W/O emulsion containing the active ingredient in the aqueous phase is not limited as long as the solvents (the aqueous solvent and the oil solvent) contained in the emulsion can be removed, such as freeze drying and drying under reduced pressure (see ¶[0076]), wherein, if the base phase is an oil phase, an S/O (Solid in Oil) type external preparation is formed by dispersing the core-shell structure in the oil phase of the base phase (see ¶[0084]), wherein the additional component can include an adhesive (see ¶[0106]), wherein the external preparation can be in the form of a patch (see ¶[0107]), wherein the external preparation is prepared by uniformly applying a solution comprising components of the preparation on a release liner and a support is laminated on the layer to obtain a transdermal absorption type formulation (see ¶[0112]), and wherein the formulation further comprises an adhesive layer (see ¶[0114]).
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 patch that uses solid-in-oil (S/O) type fine particles in which a hydrophilic drug is coated with a surfactant, and contains an adhesive composition comprising an acrylic polymer as an adhesive layer, wherein the molecular weight of the hydrophilic drug in the present invention is preferably 10,000, or less, wherein the surfactant can be nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants , wherein the S/O-type fine particles may contain a stabilizer, such as hydrophilic proteins that are coated with a surfactant together with the hydrophilic drug, thereby improving the stability of the S/O particles, and preventing leakage of the hydrophilic drug outside the S/O type fine particles in the patch, wherein the S/O type microparticles are preferably dispersed in oils and fats before being mixed with other components of the pressure-sensitive adhesive composition, wherein a preferred long-chain fatty acid ester for the oil phase is isopropyl myristate, wherein, when the S/O type microparticles are dispersed in fats and oils, the mass ratio of fats and oils to the S/O type microparticles is 0.1 to 5, wherein the acrylic polymer of the adhesive contains an alkyl (meth)acrylate ester having 6 to 14 carbon atoms in the alkyl group of the ester moiety and a monomer having a plurality of polymerizable unsaturated groups, such as 2-ethylhexyl(meth)acrylate, wherein the pressure-sensitive adhesive composition, when the amount of the S/O type fine particles is A parts by mass, and the amount of the acrylic polymer is B parts by mass, the mass ratio A/B is from 1/99 to 60/40, wherein the adhesive composition contains a transdermal absorption enhancer at 0.1% to 60% by mass, wherein the patch has an adhesive layer and a support substrate on one side of the adhesive layer, wherein the patch has a release sheet on at least one side of the adhesive layer, and functions to protect the adhesive surface of the adhesive layer during storage of the (unused) patch, and wherein 2.15 parts by mass of the S/O particles were added to 0.43 parts by mass of isopropyl myristate to prepare a dispersion, and 2.58 parts by mass of the dispersion and 0.026 parts by mass of a crosslinking agent were added to 6.3 parts by mass of a solution of the acrylic polymer, and the mixture was stirred to prepare the adhesive layer, followed by application of the adhesive mixture to a release liner, which was then heated and dried to yield a layer comprising 45.2% mass of the S/O particles comprising 1.8% mass active, and 9% mass of the oil phase, and a supporting substrate was laminated onto the adhesive layer to form the patch, as taught by Miyazaki JP ‘840, wherein the hydrophilic drug is octreotide acetate, as taught by Akamine ‘273. 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 Akamine ‘273 to the effect that octreotide acetate is a hydrophilic drug that is regarded to be difficult to permeate through skin (see ¶[0008]), and that it can be delivered from a transdermal patch construct at effective rates of permeation (see Table 1: Example 5).
With respect to claim 1, which claim recites a limitation directed to the patch of the invention comprising an acrylic elastomer at 30 – 70% wgt, the Examiner notes that the cited references do not expressly disclose an adhesive polymer content within the claimed ranges. However, Miyazaki JP ‘840 discloses patch dosage forms comprising an acrylic adhesive polymer (2-ethylhexyl(meth)acrylate), and that, when the amount of the S/O-type fine particles is A parts by mass, and the amount of the acrylic polymer is B parts by mass, the mass ratio A/B is from 1/99 to 60/40 (see ¶[0042]). It is the Examiner’s position that this ratio would encompass, or significantly overlap, the claimed range. Consequently, the disclosure renders the invention as claimed 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 22, which claim recites limitations directed to pharmacokinetic parameters of the patch formulation of the invention compared to octreotide acetate compositions administered by injection, the Examiner notes that the cited references do not expressly disclose such parameters. However, it is the Examiner’s position that due to substantial identify between the invention as claimed and formulations according to the cited references (same active, same acrylic adhesive, same loadings, etc.), the prior art formulations would necessarily display pharmacokinetic parameters reading on the limitation in question.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 1, 2, 7, 12, 22, 33, 34 would have been obvious within the meaning of 35 USC § 103.
Claims 27 and 28 are rejected pursuant to 35 U.S.C. § 103, as being obvious over Miyazaki JP ‘840, in view of Akamine ‘273, as applied in the above rejection of claims 1, 2, 7, 12, 22, 33, and 34, and further in view of Stefano ‘116.
The Invention As Claimed
Applicants claim a transdermal patch comprising a support material, and an adhesive layer laminated on the support material, wherein the adhesive layer comprises a solid composite material comprising octreotide acetate as an active ingredient, enclosed by a surfactant with an HLB value of 5 or less, an oil phase, and an adhesive agent containing alkyl (meth)acrylate having an alkyl group with 6 to 14 carbon atoms in an ester portion, wherein the patch further comprises a promoter layer disposed between the support material and the adhesive layer, the promoter layer containing a transdermal absorption promoter.
The Teachings of the Cited Art
The teachings of Miyazaki JP ‘840 and Akamine ‘273 are relied upon as applied in the above rejection of claims 1, 2, 7, 12, 22, 33, 34. The references do not disclose a transdermal patch comprising a promoter layer disposed between the support material and the adhesive layer, the promoter layer containing a transdermal absorption promoter. These deficiencies are addressed by the teachings of Stefano ‘116.
Stefano ‘116 discloses a device for the transdermal delivery of a pharmacologically active substance that has first and second superimposed mutually contacting adhesive layers, wherein an active substance is in both adhesive layers (see Abstract), wherein the superposition of the two adhesive layers of different thickness, composition and interaction with the active substance gives as a result a device of particular useful characteristics, which may not be predictable from the individual behavior (performance) of each layer and are not predictable from the resulting behavior of the combination of these adhesives in a single layer (see ¶[0042]), wherein the first layer comprises a pressure sensitive adhesive and, in use, is brought into contact with the skin, the active substance being dissolved in both layers (see ¶[0043]), wherein the device has a first layer made of a pressure-sensitive adhesive and a second layer made of a pressure-sensitive adhesive, or a mixture of pressure-sensitive adhesives, in which one or more active substances are dissolved, where each layer presents a different adhesive composition (see ¶[0044]), wherein the two-layered device of the present invention, the first layer is designed to be in close contact with the skin of the patient and is the one that delivers the necessary dose of active substance to obtain the desired pharmacological action, while the second layer is effective to replenish the loss of active substance from the first layer when the device is in contact with the skin, thus achieving a highly constant efflux rate during the period of use (see ¶[0045]), wherein the device for the transdermal administration of an active pharmaceutical ingredient such as, for example, fentanyl, wherein, initially, the device comprises between about 2 and about 4% of the active in the layer to be in contact with the skin, and between about 4 and about 10% of the active in the second layer (see ¶[0053]), wherein the thickness of the first layer that will be in contact with the skin should be thicker than the second layer (see ¶[0066]), wherein an important component of the present invention is a permeation enhancer (see ¶[0069]), wherein the devices comprise a backing layer (see ¶[0072]), and a release liner (see ¶[0073]), wherein each of the layers comprise an adhesive and the active drug, with or without a permeation enhancer (see ¶[0092]), and wherein the devices are prepared with the permeation enhancer present in the first layer (closest to the backing layer), and the second layer (closest to the skin) is prepared without a permeation enhancer (see EXAMPLE 9).
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 patch that uses solid-in-oil (S/O) type fine particles in which a hydrophilic drug is coated with a surfactant, and contains an adhesive composition comprising an acrylic polymer as an adhesive layer, as taught by Miyazaki JP ‘840 and Akamine ‘273, wherein the patch is a two-layer patch, wherein the layer closest to the backing layer comprises an active and a permeation enhancer, and the layer closer to the skin comprises an active, but does not comprise a permeation enhancer, as taught by Stefano ‘116, the layer closer to the backing layer (comprising a permeation enhancer) serving in effect as the promoter layer. One of ordinary skill in the at would be motivated to do so, with a reasonable expectation of success in so doing by the express teachings of Stefano ‘116 to the effect that the two-layer configuration provides for the second layer to replenish the loss of active substance from the first layer when the device is in contact with the skin.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by claims 27 and 28 would have been obvious within the meaning of 35 USC § 103.
Response to Applicants’ Arguments
The Examiner has considered the arguments submitted by Applicants in their Response of 11 November 2025, but does not find them persuasive, to the extent still relevant in light of the new grounds of rejection set forth above. Applicants first argue that “neither of the cited references provides any suggestion or motivation for obtaining a formulation with these highly desirable sustained-release and safety characteristics by specifically limiting the HLB value to 5 or less. The Examiner respectfully disagrees on the basis that the primary reference, Miyazaki JP '840 specifically discloses the use of surfactants with an HLB of “six or less” (see ¶[0022]). Although the reference does not expressly address the “highly desirable sustained-release and safety characteristics” attributed by Applicants to the use of surfactants with HLB values in this range, 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).
Applicants also argue that “claims 23-26 are distinguished by limiting the hydrophilic protein encapsulated in the solid composite material to one having a molecular weight greater than 10,000. This limitation directs the claims toward the most challenging high-molecular-weight therapeutics.” However, as addressed above, claims 23 – 26 are withdrawn from consideration due to the fact that they are directed to a non-elected invention (one with an active ingredient with a molecular weight of 10,000), because of the species election of octreotide acetate, with a molecular weight of 1139.24.
Consequently, based on the above discussion, Applicants’ arguments are unpersuasive, and claims 1, 2, 7, 12, 22, 27, 28, 33 and 34 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
1 Citations to the reference are to the English language machine translation, previously provided.