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 .
Status of the Claims
Claims 1-3, 5-23, and 25 are pending and under current examination. Claims 4 and 24 are cancelled.
Withdrawn Claim Objections and Rejections
All objections pertaining to claim 12 are withdrawn in view of the amendments to the claims filed 4/7/2026.
All rejections pertaining to claims 4 and 24 are moot because the claims are cancelled in the amendments to the claims filed 4/7/2026.
All rejections under 35 U.S.C. 112(b) are withdrawn in view of the amendments to the claims filed 4/7/2026.
All rejections under 35 U.S.C. 102 are withdrawn in view of the amendments to the claims filed 4/7/2026.
All rejections not reiterated have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s amendments to the claims filed 4/7/2026 have necessitated the new grounds of rejection.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-3, 6-15, and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Emgenbroich (WO2019/072998, publication date: 4/18/2019, cited in the IDS filed 9/26/2024, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 1, Emgenbroich teaches a transdermal therapeutic system for the transdermal administration of guanfacine comprising a backing layer and a guanfacine-containing layer [0104]. The guanfacine-containing layer may include a preservative such as benzoic acid, sorbic acid, levulinic acid, and anisic acid [0250]. Emgenbroich also teaches that when guanfacine is mentioned to be used in a particular form in the manufacture of the transdermal treatment system, this does not exclude interactions between this form of guanfacine and other ingredients of the guanfacine containing layer [0034]. Even if guanfacine is included in its free base form, it may be present in the final TTS in protonated or partially protonated form or in the form of an acid addition salt [0029]. The instant specification defines co-salt to mean that the guanfacine is present in a pre-mixture together with at least one mono-carboxylic acid, such that a e.g. proton transfer or the formation of hydrogen bonds is possible and preferably at least partly a guanfacine salt of the monocarboxylic acid is formed. In other words, the guanfacine may at least partly be present in protonated form ([0031] of the instant specification). Therefore, the Examiner considers the mixture of guanfacine and preservative taught by Emgenbroich to read on the “co-salt of guanfacine and a mono-carboxylic acid” limitation of the instant claim.
Regarding claim 2, Emgenbroich teaches that the guanfacine-containing layer comprises guanfacine and at least one polymer [0119]. The guanfacine-containing layer may include a preservative such as benzoic acid, sorbic acid, levulinic acid, and anisic acid [0250].
Regarding claim 3, Emgenbroich teaches that the guanfacine-containing layer may include sorbic acid [0250].
Regarding claim 6, Emgenbroich teaches that the matrix layer may be self-adhesive [0043].
Regarding claims 7 and 8, Emgenbroich teaches that the at least one polymer is selected from the group consisting of silicone polymers, acrylate polymers, and silicone acrylic hybrid polymers [0014].
Regarding claim 9, Emgenbroich teaches that the silicone polymers are obtainable by polycondensation of silanol endblocked polydimethylsiloxane with a silicate resin [0129].
Regarding claim 10, Emgenbroich teaches pressure sensitive adhesives suitable for inclusion as the polymer in the transdermal therapeutic system such as Duro-Tak 387-2287, a copolymer based on vinyl acetate, 2-ethylhexyl-acrylate, 2-hydroxyethyl-acrylate, and glycidyl-methacrylate), and Duro-Tak 87-4098, a copolymer based on 2-ethylhexyl-acrylate and vinyl acetate [0234].
Regarding claim 11, Emgenbroich teaches that the silicone acrylic hybrid polymer typically comprises the reaction product of a silicone-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality, an ethlenically unsaturated monomer, and an initiator [0131].
Regarding claim 12, Emgenbroich teaches that the silicon-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality comprises the condensation reaction product of a silicone resin, a silicone polymer, and a silicon-containing capping agent which provides said acrylate or methacrylate functionality [0048]. The silicon-containing capping agent is of the general formula XYR’bSiZ3-b, wherein X is a monovalent radical of the general formula AE, where E is -O- or -NH- and A is an acryl group or a methacryl group, Y is a divalent alkylene radical having from 1 to 6 carbon atoms, R’ is a methyl or phenyl radical, Z is a monovalent hydrolysable organic radical or halogen, and b is 0 or 1 [0185]. The silicone resin and silicone polymer are reacted to form a pressure-sensitive adhesive, wherein the silicon-containing capping agent is introduced prior to, during or after the silicone resin and silicone polymer are reacted [0185]. The silicon-containing capping agent reacts with the pressure-sensitive adhesive after the silicone resin and silicone polymer have been condensation reacted to form the pressure-sensitive adhesive or the silicon-containing capping agent reacts in-situ with the silicone resin and silicone polymer [0185].
Regarding claim 13, Emgenbroich teaches that the ethylenically unsaturated monomer may be selected from aliphatic acrylates, aliphatic methacrylates, cycloaliphatic acrylates, cycloaliphatic methacrylates, and combinations thereof. The alkyl radicals of these compounds can include up to 20 carbon atoms [0196].
Regarding claim 14, Emgenbroich teaches that the transdermal therapeutic system comprises guanfacine in an amount of from 1 to 100mg/TTS, preferably from 8 to 72 mg/TTS [0123].
Regarding claim 15, Emgenbroich teaches that the guanfacine-containing layer comprises guanfacine in an amount of from 1 to 20% by weight, preferably from 3 to 16% by weight, based on the total weight of the guanfacine-containing layer [0125].
Regarding claim 17, Emgenbroich teaches that the at least one polymer is present in an amount of from 20 to 99%, preferably from 30 to 97%, and most preferably from 35 to 92% by weight based on the total weight of the guanfacine-containing layer [0015].
Regarding claim 18, Emgenbroich teaches that the transdermal therapeutic system contains at least one additive selected from the group consisting of dispersing agents, permeation enhancers, and solubilizers [0011].
Regarding claim 19, Emgenbroich teaches that the area weight of the guanfacine-containing layer ranges from 40 to 250 g/m2, preferably from 50 to 180 g/m2 [0157] and the area of release ranges from 1 to 100 cm2, preferably from 2.5 to 50 cm2 [0113].
Regarding claim 20, Emgenbroich teaches a method of treating a human patient wherein the transdermal treatment system is applied to the skin of a patient [0263].
Regarding claim 21, Emgenbroich teaches a method of treating a human patient wherein the transdermal treatment system is suitable for use in a method of treating hypertension or attention deficit hyperactivity disorder (ADHD) and/or as adjunctive therapy to stimulant medication [0262].
Regarding claim 22, Emgenbroich teaches that the transdermal treatment system is applied to the skin of the patient for at least 24 hours, preferably at least 72 hours, and more preferably about 84 hours [0263].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 1-3, 6-15, and 17-22, Emgenbroich doesn’t teach a single embodiment or example meeting all limitation of the invention of claims 1-3, 6-15, and 17-22.
Finding of a Prima Facia Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 1-3, 6-15, and 17-22, within the broader scope of Emgenbroich all of the limitations of the invention of claims 1-3, 6-15, and 17-22 are met. It would have been prima facie obvious for one having ordinary skill in the art to choose the limitations in the instant claims from those disclosed by Emgenbroich and arrive at this conclusion because such was contemplated by Emgenbroich.
Claims 5, 16, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Emgenbroich (WO2019/072998, publication date: 4/18/2019, cited in the IDS filed 9/26/2024, of record), as applied to claims 1-3, 6-15, and 17-22 above, and further in view of Wauer (WO2019/175096, publication date: 9/19/2019, cited in the IDS filed 9/26/2024, of record).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Emgenbroich renders obvious the relevant limitations of claim 1 above.
Regarding claim 5, Emgenbroich teaches that when guanfacine is mentioned to be used in a particular form in the manufacture of the transdermal treatment system, this does not exclude interactions between this form of guanfacine and other ingredients of the guanfacine containing layer. If guanfacine is included in the transdermal treatment system in its free-base form, it may be present in the final transdermal treatment system in the form of an acid addition salt [0034]. Emgenbroich also teaches that the additives present in the transdermal treatment system are suitable for improving the release properties of the transdermal treatment system by allowing homogenous dispersion of the guanfacine within the transdermal therapeutic system [0019].
Regarding claim 16, Emgenbroich teaches that the guanfacine-containing layer comprises guanfacine in an amount of from 1 to 20% by weight, preferably from 3 to 16% by weight, based on the total weight of the guanfacine-containing layer [0125]. Emgenbroich also teaches that the additives, including preservatives, may be present in the guanfacine containing layer in an amount of from 0.001 to 15% by weight [0238].
Regarding claims 23 and 25, Emgenbroich teaches that the transdermal therapeutic system may be manufactured by first combining guanfacine, at least one polymer, and at least one additive to obtain a coating composition, coating the coating composition onto a backing layer, and drying the coating composition to form the guanfacine-containing layer [0272].
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 4, 5, 23, and 25 Emgenbroich does not teach that the guanfacine and the monocarboxylic acid are present in the form of a pre-mixture. However, this deficiency is cured by Wauer.
Wauer discloses a method of manufacture of a transdermal therapeutic system comprising the steps of providing a buprenorphine-containing coating composition comprising buprenorphine and carboxylic acid such as levulinic acid [0252]. The buprenorphine base and the carboxylic acid are suspended in ethanol and subsequently combined with the polymer adhesive to provide the coating composition [0254]. Wauer also teaches that the buprenorphine base is preferably dissolved in the carboxylic acid to form a buprenorphine carboxylic acid solution which forms dispersed deposits in the polymer matrix [0028]. In an exemplary manufacturing procedure, levulinic acid and buprenorphine base are weighed and added to a mixing vessel with ethanol and stirred for at least 1 hour until a buprenorphine base-containing solution is formed [0265]. The instant specification defines the “slurry method” to comprise a process of weighing in guanfacine free base and a monocarboxylic acid in equimolar amounts. Solvent is added and the mixture is stirred with a magnetic stirring bar at room temperature [0086 of instant specification]. The Examiner therefore interprets the pre-mix manufacturing procedure recited by Wauer to read on the “slurry method” of the instant claims 5 and 25.
Regarding claim 16, Emgenbroich does not teach that the guanfacine and mono-carboxylic acid are present in equimolar amounts. However, this deficiency is cured by Wauer.
Wauer teaches a method of manufacture of a transdermal therapeutic system comprising the steps of providing a buprenorphine-containing coating composition comprising buprenorphine and carboxylic acid such as levulinic acid [0252]. The buprenorphine base is preferably dissolved in the carboxylic acid to form a buprenorphine carboxylic acid solution which forms dispersed deposits in the polymer matrix [0028].
Finding of a Prima Facia Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 4, 5, 23, and 25, it would have been prima facie obvious to one of ordinary skill in the art of filing to include the guanfacine and carboxylic acid of Emgenbroich as a pre-mixture obtainable by a slurry method. One would have understood in view of Wauer that a drug in the form of a free base may be dissolved in a carboxylic acid using a slurry method prior to the addition of a polymer adhesive when manufacturing a transdermal treatment system. It would have been obvious to pre-mix the guanfacine and carboxylic acid of Emgenbroich before addition of the polymer adhesive. One of ordinary skill in the art of filing would have been motivated to mix the guanfacine and carboxylic acid in order to form dispersed deposits of the drug in the polymer matrix. The artisan of ordinary skill in the art would have had reasonable expectation of success because Emgenbroich teaches that the additives present in the transdermal treatment system are suitable for improving the release properties of the transdermal treatment system by allowing homogenous dispersion of the guanfacine within the transdermal therapeutic system [0019].
Regarding claim 16, the molar ratio of guanfacine and monocarboxylic acid is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal ratio in order to best achieve the desired results as such would provide advantageous dispersion effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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 the instant case, Wauer teaches that a drug in the form of a free base dissolved in a carboxylic acid allows for improved dispersion properties of the drug in a transdermal drug delivery system [0028]. The Examiner considers it prima facie obvious to optimize the molar ratio of guanfacine and mono-carboxylic acid, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amount of mono-carboxylic acid relative to the amount of guanfacine would have a direct effect on the dissolution and dispersion of the free base form of the drug and therefore be an optimizable variable.
Response to Arguments
Applicant's arguments filed 4/7/2026 have been fully considered but they are not persuasive.
On page 11, Applicant argues that Emgenbroich does not teach or reasonable suggest a co-salt of guanfacine and a mono-carboxylic acid. This is not found persuasive. In response, please refer to MPEP 2123(I), which states: “a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments”. Please also refer to MPEP 2141.03(I) regarding the factors to consider when determining level of ordinary skill: "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. In the instant case, Emgenbroich teaches that when guanfacine is mentioned to be used in a particular form in the manufacture of the transdermal treatment system, this does not exclude interactions between this form of guanfacine and other ingredients of the guanfacine containing layer. If guanfacine is included in the transdermal treatment system in its free-base form, it may be present in the final transdermal treatment system in the form of an acid addition salt [0034]. The instant specification defines co-salt to mean that the guanfacine is present in a pre-mixture together with at least one mono-carboxylic acid, such that a e.g. proton transfer or the formation of hydrogen bonds is possible and preferably at least partly a guanfacine salt of the monocarboxylic acid is formed. In other words, the guanfacine may at least partly be present in protonated form ([0031] of the instant specification). One of ordinary skill in the art would have reasonably concluded that the teachings of Emgenbroich read on an acid addition salt of guanfacine and the other ingredients of the guanfacine-containing layer, which may include a mono-carboxylic acid. Therefore, the argument is not persuasive and the rejection is maintained.
On pages 11 and 13, Applicant argues that the co-salt of guanfacine and the mono-carboxylic acid provides improved properties that a skilled artisan would not have expected based on the disclosure of Emgenbroich. This is not found persuasive. In response, 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.
Differences in results are in fact unexpected and unobvious: The evidence of unexpected properties amounts to higher permeated amounts of guanfacine due to a guanfacine and mono-carboxylic acid co-salt. However, Miwa (U.S. Patent No. 9,974,858, issue date: 5/22/2018) teaches that sorbic acid exhibits an excellent accelerating effect for percutaneous absorption of basic medicament (col. 1 lines 56-60). One of ordinary skill in the art would have therefore recognized that the pairing of guanfacine free base and sorbic acid would improve the permeation of guanfacine. Therefore, the differences are not unexpected and unobvious.
Differences are of both practical and statistical significance: The evidence of unexpected properties amounts to increased transdermal permeability of guanfacine with corresponding statistical analysis, therefore the differences are of practical and statistical significance.
Evidence of unexpected properties must be in commensurate scope with the claims: The claims embrace a transdermal therapeutic system comprising any concentration of guanfacine, mono-carboxylic acid, and polymer. In order to be in commensurate scope with the claims, the evidence of unexpected results must demonstrate increased permeability at every concentration of guanfacine, mono-carboxylic acid, and polymer. However, the evidence of unexpected results demonstrate increased permeability at a single concentration of guanfacine, sorbic acid, and polymer. Therefore, the evidence of unexpected results is not in commensurate scope with the claims.
Thus, the Applicant’s argument is not persuasive and the rejection is maintained.
On page 13, Applicant argues that the combination of Emgenbroich with Wauer does not teach or suggest the process for manufacturing the active layer. This is not found persuasive. In response, please refer to MPEP 2141.03(I) regarding the factors to consider when determining level of ordinary skill: "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. As described in the obviousness rejection above, one of ordinary skill in the art would have understood in view of Wauer that a drug in the form of a free base may be dissolved in a carboxylic acid using a slurry method prior to the addition of a polymer adhesive when manufacturing a transdermal treatment system. It would have been obvious to pre-mix the guanfacine and carboxylic acid of Emgenbroich before addition of the polymer adhesive. One of ordinary skill in the art of filing would have been motivated to mix the guanfacine and carboxylic acid in order to form dispersed deposits of the drug in the polymer matrix. The artisan of ordinary skill in the art would have had reasonable expectation of success because Emgenbroich teaches that the additives present in the transdermal treatment system are suitable for improving the release properties of the transdermal treatment system by allowing homogenous dispersion of the guanfacine within the transdermal therapeutic system [0019]. Therefore, the argument is not persuasive and the rejection in maintained.
Double Patenting
Applicant’s amendments to the claims filed 4/7/2026 have necessitated the new grounds of rejection.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 6-15, and 17-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,576,874 in view of Emgenbroich (WO2019/072998, publication date: 4/18/2019, cited in the IDS filed 9/26/2024, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Inter alia, the claims of the ‘874 patent embrace a transdermal therapeutic system for the transdermal administration of guanfacine comprising a guanfacine-containing layer and a backing layer. The guanfacine-containing layer comprises at least one silicone polymer and at least two additives selected from the group consisting of dispersing agents, permeation enhancers, and solubilizers. The permeation enhancer may include oleic acid and levulinic acid. The Examiner considers the oleic acid and levulinic acid to read on the mono-carboxylic acid limitation of the instant claims. The guanfacine-containing layer is self-adhesive. The silicone polymer is obtainable by polycondensation of silanol endblocked polydimethyl siloxane with a silicate resin. Guanfacine is present in the guanfacine-containing layer structure from 1 to 75mg/TTS and from 1 to 20% by weight based on the total weight of the guanfacine-containing layer. The polymer is present in the guanfacine-containing layer from 35 to 70% by weight, based on the total weight of the guanfacine-containing layer. The guanfacine-containing layer may also contain at least two dispersing agents, permeation enhancers, and solubilizers. The area-weight of the guanfacine-container layer ranges from 40 to 250 g/m2 and an area of release ranging from 1 to 100 cm2. The claims of the ‘874 patent also embrace a method of treating hypertension or ADHD in a human patient comprising administering the transdermal therapeutic system to the skin of the patient. The transdermal therapeutic system is applied for at least 24, 72 or about 84 hours.
The claims of the ‘874 patent do not embrace a co-salt of guanfacine and a mono-carboxylic acid, sorbic acid or any of the limitations pertaining to the acrylic, silicone-acrylic hybrid, and silicone polymers embraced by the instant claims 10-12. However, this deficiency is cured by Emgenbroich. Emgenbroich teaches a transdermal therapeutic system for the transdermal administration of guanfacine comprising a backing layer and a guanfacine-containing layer [0104]. The guanfacine-containing layer may include a preservative such as benzoic acid, sorbic acid, levulinic acid, and anisic acid [0250]. Emgenbroich teaches that the at least one polymer is selected from the group consisting of silicone polymers, acrylate polymers, and silicone acrylic hybrid polymers [0014]. The pressure sensitive adhesives suitable for inclusion as the polymer in the transdermal therapeutic system such as Duro-Tak 387-2287, a copolymer based on vinyl acetate, 2-ethylhexyl-acrylate, 2-hydroxyethyl-acrylate, and glycidyl-methacrylate), and Duro-Tak 87-4098, a copolymer based on 2-ethylhexyl-acrylate and vinyl acetate [0234]. Emgenbroich teaches that the silicone acrylic hybrid polymer typically comprises the reaction product of a silicone-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality, an ethlenically unsaturated monomer, and an initiator [0131]. The silicon-containing pressure-sensitive adhesive composition comprising acrylate or methacrylate functionality comprises the condensation reaction product of a silicone resin, a silicone polymer, and a silicon-containing capping agent which provides said acrylate or methacrylate functionality [0048]. The silicon-containing capping agent is of the general formula XYR’bSiZ3-b, wherein X is a monovalent radical of the general formula AE, where E is -O- or -NH- and A is an acryl group or a methacryl group, Y is a divalent alkylene radical having from 1 to 6 carbon atoms, R’ is a methyl or phenyl radical, Z is a monovalent hydrolysable organic radical or halogen, and b is 0 or 1 [0185]. The silicone resin and silicone polymer are reacted to form a pressure-sensitive adhesive, wherein the silicon-containing capping agent is introduced prior to, during or after the silicone resin and silicone polymer are reacted [0185]. The silicon-containing capping agent reacts with the pressure-sensitive adhesive after the silicone resin and silicone polymer have been condensation reacted to form the pressure-sensitive adhesive or the silicon-containing capping agent reacts in-situ with the silicone resin and silicone polymer [0185]. Emgenbroich also teaches that the ethylenically unsaturated monomer may be selected from aliphatic acrylates, aliphatic methacrylates, cycloaliphatic acrylates, cycloaliphatic methacrylates, and combinations thereof. The alkyl radicals of these compounds can include up to 20 carbon atoms [0196]. Emgenbroich also teaches that when guanfacine is mentioned to be used in a particular form in the manufacture of the transdermal treatment system, this does not exclude interactions between this form of guanfacine and other ingredients of the guanfacine containing layer [0034]. Even if guanfacine is included in its free base form, it may be present in the final TTS in protonated or partially protonated form or in the form of an acid addition salt [0029]. The instant specification defines co-salt to mean that the guanfacine is present in a pre-mixture together with at least one mono-carboxylic acid, such that a e.g. proton transfer or the formation of hydrogen bonds is possible and preferably at least partly a guanfacine salt of the monocarboxylic acid is formed. In other words, the guanfacine may at least partly be present in protonated form ([0031] of the instant specification). Therefore, the Examiner considers the mixture of guanfacine and preservative taught by Emgenbroich to read on the “co-salt of guanfacine and a mono-carboxylic acid” limitation of the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art of filing that the mixture of oleic acid or levulinic acid and guanfacine present in the transdermal therapeutic system embraced by the claims of the ‘874 patent. One would have understood in view of Emgenbroich that the guanfacine present in a transdermal therapeutic system is suitable to interact with the other ingredients present in the guanfacine layer to form an acid addition salt [0029]. It would have been obvious that the oleic acid or levulinic acid embraced by the ‘874 patent may also form a co-salt with the guanfacine present in the transdermal therapeutic system. The artisan of ordinary skill in the art of filing would have had reasonable expectation of success because Emgenbroich teaches that guanfacine may interact with the other ingredients present in the guanfacine layer to form an acid addition salt [0029]. See MPEP 2144.07.
The idea for combining compounds each of which is known to be useful for the same purpose, in order to form a composition which is to be used for the same purpose, flows logically from their having been used individually in the prior art. See In re Kerkhoven 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). As shown by the recited teachings, the instant claims define nothing more than the concomitant use of conventional polymers used in guanfacine-containing layers of transdermal therapeutic systems. It would follow that the recited claims define prima facie obvious subject matter. See MPEP 2144.06.
It would have been prima facie obvious to one of ordinary skill in the art of filing to include sorbic acid in the transdermal therapeutic system embraced by the claims of the ‘874 patent. One of ordinary skill in the art of filing would have understood in view of Emgenbroich that sorbic acid is suitable for inclusion in a transdermal therapeutic system as a preservative. It would have been obvious to include a preservative in the composition embraced by the claims of the ‘874 patent. One of ordinary skill in the art of filing would have been motivated to include a preservative in order to prolong the stability of the transdermal therapeutic system. The artisan of ordinary skill would have had reasonable expectation of success because Emgenbroich teaches that sorbic acid is suitable for inclusion in a transdermal therapeutic system nearly identical to the system embraced by the claims of the ‘874 patent.
Claims 5, 16, 23, and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,576,874 in view of Emgenbroich (WO2019/072998, publication date: 4/18/2019, cited in the IDS filed 9/26/2024, of record), as applied to claims 1-3, 6-15, and 17-22 above, and further in view of Wauer (WO2019/175096, publication date: 9/19/2019, cited in the IDS filed 9/26/2024, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Inter alia, the claims of the ‘874 patent embrace the relevant limitations above. The claims of the ‘874 patent also embraces guanfacine present from 1 to 20% by weight and from 0.5 to 10% by weight of at least two additives. The claims of the ‘874 patent do not embrace a pre-mixture, dry-milling or slurry method, or a process of manufacturing an active pharmaceutical containing layer. However, this deficiency is cured by Emgenbroich and Wauer.
Emgenbroich teaches that when guanfacine is mentioned to be used in a particular form in the manufacture of the transdermal treatment system, this does not exclude interactions between this form of guanfacine and other ingredients of the guanfacine containing layer. If guanfacine is included in the transdermal treatment system in its free-base form, it may be present in the final transdermal treatment system in the form of an acid addition salt [0034]. Emgenbroich also teaches that the additives present in the transdermal treatment system are suitable for improving the release properties of the transdermal treatment system by allowing homogenous dispersion of the guanfacine within the transdermal therapeutic system [0019]. Emgenbroich also teaches that the transdermal therapeutic system may be manufactured by first combining guanfacine, at least one polymer, and at least one additive to obtain a coating composition, coating the coating composition onto a backing layer, and drying the coating composition to form the guanfacine-containing layer [0272]. Wauer discloses a method of manufacture of a transdermal therapeutic system comprising the steps of providing a buprenorphine-containing coating composition comprising buprenorphine and carboxylic acid such as levulinic acid [0252]. The buprenorphine base and the carboxylic acid are suspended in ethanol and subsequently combined with the polymer adhesive to provide the coating composition [0254]. Wauer also teaches that the buprenorphine base is preferably dissolved in the carboxylic acid to form a buprenorphine carboxylic acid solution which forms dispersed deposits in the polymer matrix [0028]. In an exemplary manufacturing procedure, levulinic acid and buprenorphine base are weighed and added to a mixing vessel with ethanol and stirred for at least 1 hour until a buprenorphine base-containing solution is formed [0265]. The instant specification defines the “slurry method” to comprise a process of weighing in guanfacine free base and a monocarboxylic acid in equimolar amounts. Solvent is added and the mixture is stirred with a magnetic stirring bar at room temperature [0086 of instant specification]. The Examiner therefore interprets the pre-mix manufacturing procedure recited by Wauer to read on the “slurry method” of the instant claims 5 and 25.
It would have been prima facie obvious to one of ordinary skill in the art of filing to include the guanfacine and carboxylic acid of the claims of the ‘874 patent as a pre-mixture obtainable by a slurry method. One would have understood in view of Wauer that a drug in the form of a free base may be dissolved in a carboxylic acid using a slurry method prior to the addition of a polymer adhesive when manufacturing a transdermal treatment system. It would have been obvious to pre-mix the guanfacine and carboxylic acid of the claims of the ‘874 patent before addition of the polymer adhesive. One of ordinary skill in the art of filing would have been motivated to mix the guanfacine and carboxylic acid in order to form dispersed deposits of the drug in the polymer matrix. The artisan of ordinary skill in the art would have had reasonable expectation of success because Emgenbroich teaches that the additives present in the transdermal treatment system are suitable for improving the release properties of the transdermal treatment system by allowing homogenous dispersion of the guanfacine within the transdermal therapeutic system [0019].
The molar ratio of guanfacine and monocarboxylic acid is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal ratio in order to best achieve the desired results as such would provide advantageous dispersion effect. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. 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 the instant case, Wauer teaches that a drug in the form of a free base dissolved in a carboxylic acid allows for improved dispersion properties of the drug in a transdermal drug delivery system [0028]. The Examiner considers it prima facie obvious to optimize the molar ratio of guanfacine and mono-carboxylic acid, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amount of mono-carboxylic acid relative to the amount of guanfacine would have a direct effect on the dissolution and dispersion of the free base form of the drug and therefore be an optimizable variable.
Response to Arguments
Applicant's arguments filed 4/7/2026 have been fully considered but they are not persuasive. Applicants’ request for the double patenting rejection of record to be held in abeyance is acknowledged. However, this request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an objection or requirements as to form (see MPEP 37 CFR 1.111(b) and 714.02). Accordingly, the rejection will be maintained until a terminal disclaimer is filed or claims are amended to obviate the rejection.
Conclusion
No claims are 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.
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ELIZABETH ANNE MEYERSExaminer, Art Unit 1617
/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617
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