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 .
Formal Matters
Receipt of Applicant’s response, dated 11/03/2025, is acknowledged.
Claims 1-15 are pending.
Claims 1-13 are amended.
Claims 14-15 remain withdrawn from consideration as being drawn to a nonelected invention.
Claims 1-13 are under consideration in the instant Office action to the extent of the elected species, i.e., the hydrophobic polymer is hypromellose acetate succinate, the hydrophobic pharmaceutically active ingredient is ketoprofen, the hydrophobic solvent is methyl acetate, the hydrophilic polymer is polyvinyl alcohol, the at least one excipient being added is an antioxidant and is added to solution a).
OBJECTIONS/REJECTIONS WITHDRAWN
Specification
The objections to the specification and the abstract set forth in the Office action dated 07/01/2025 are hereby withdrawn in light of Applicant’s amendments to the specification.
Claim Objections
The objections to claims 1-13 set forth in the Office action dated 07/01/2025 are hereby withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112(b)
The indefiniteness rejections of claims 11 and 13 set forth in the Office action dated 07/01/2025 are hereby withdrawn in light of Applicant’s amendments to the claims.
REJECTIONS MAINTAINED
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 and 8-13 are rejected under 35 U.S.C. 103 as being unpatentable over Obeid et al (US 2018/0360736 A1, published 12/20/2018, cited in Notice of References Cited dated 07/01/2025) in view of Baek et al (KR 2003/0054221 A, published 07/02/2003, cited in Notice of References Cited dated 07/01/2025), Li et al (WO 2012/167878 A1, published 12/13/2012, cited in Notice of References Cited dated 07/01/2025), and Bilal et al (US 2016/0220480 A1, published 08/04/2016, cited in Notice of References Cited dated 07/01/2025).
Obeid et al teach a process for producing an oral film dosage form comprising mucoadhesive particles for buccal cavity delivery (e.g., Abstract, [0090]-[0091]).
Obeid et al teach that the process comprises the steps of:
Producing an inner phase solution comprising a polymer and active agent in an organic solvent system (e.g., ethyl acetate, isobutyl acetate);
Producing an outer phase solution for which the organic solvent system of the inner phase is partially miscible or non-miscible with (e.g., water) comprising a dispersed stabilizing agent (e.g., polyvinyl alcohol) (e.g., [0083]);
Emulsifying the inner and outer phase solutions resulting in mucoadhesive particles with a size range between 100 nm and 100 m depending on the desired particle morphology and size (e.g., [0083], [0085]);
Dispersing the mucoadhesive particles and additional ingredients using conventional mixing techniques (e.g., [0090]-[0091]);
Casting and drying the mixture of the mucoadhesive particles and additional ingredients forming a film (e.g., [0090]-[0091]).
Obeid et al teach that the active agent may be an anti-inflammatory agent (e.g., [0035]). Obeid et al teach that the active agent can be incorporated into the film generally from 0.1 to 80% by total weight of the film (e.g., [0038]), and specifically 0.5 to 20% by total weight of the film by the aforementioned process (e.g., [0086]).
Obeid et al teach that the mucoadhesive materials used to prepare the mucoadhesive particles include cellulose derivative polymers (e.g., [0041]). Obeid et al teach that the mucoadhesive particles may comprise an antioxidant (e.g., [0009]).
Obeid et al do not teach hypromellose acetate succinate as a suitable cellulose derivative polymer in the preparation of the mucoadhesive particles, nor do they teach the amount of polymer for the preparation of the mucoadhesive particles. Although Obeid et al teach that the active agent may be an anti-inflammatory, they do not teach ketoprofen as a suitable anti-inflammatory agent. Although Obeid et al teach ethyl acetate and isobutyl acetate as suitable organic solvent systems of the inner phase, they do not teach methyl acetate as a suitable organic solvent system of the inner phase.
These deficiencies are made up for in the teachings of Baek et al, Li et al, and Bilal et al.
Baek et al teach a laminated film composition for the oral cavity (e.g., Par. 1 of “Background-Art” on Page 1 of English translation). Baek et al teach that a film-forming polymer should be used from 10 to 75% by weight based on the film layer and can include hydroxypropyl methylcellulose acetate succinate (i.e., abbreviated as HPMCAS and synonymous with hypromellose acetate succinate) (e.g., Par. 2 on Page 4 of English translation). More specifically, Baek et al teach that cellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and cellulose acetate phthalate (CAP) were found to have good film forming ability but slow dissolution rate in the oral cavity (e.g., Par. 7 of Experimental Example 1 on Page 7 of English translation).
Li et al teach an edible oral film strip dosage form comprising ketoprofen as the acidic active pharmaceutical ingredient (e.g., Abstract, claim 12). Li et al teach that ketoprofen is one of the most potent NSAIDs and well known for treating symptoms associated with chronic arthritis, osteoarthritis, acute tendonitis, bursitis, headaches, migraines, chronic neuropathic pains, shingles, premenstrual symptoms, sports injuries and like (e.g., Par. 2 of Background of the Invention).
Bilal et al teach a film oral dosage form useful for buccal or sublingual administration of an active agent including at least one film forming polymer, at least one plasticizer, at least one active agent, and a residual organic solvent (e.g., Abstract). Bilal et al exemplify esters that can be used as the organic solvent as butyl acetate, ethyl acetate, ethyl formate, isobutyl acetate, isopropyl acetate, propyl acetate, and methyl acetate (e.g., [0028]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use cellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), or cellulose acetate phthalate (CAP) as the polymer from 10 to 75% by weight in the process for producing an oral film dosage form of Obeid et al. One of ordinary skill in the art would have been motivated to do so in order to provide an oral film dosage form comprising a good film forming polymer with slow release in the oral cavity. There would have been a reasonable expectation of success because Obeid et al teach that cellulose derivative polymers are suitable for use as the polymer in the process for producing an oral film dosage form.
It would have also been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate ketoprofen as the anti-inflammatory agent in the process for producing an oral film dosage form of Obeid et al because ketoprofen is one of the most potent NSAIDs and is well known for treating symptoms associated with chronic arthritis, osteoarthritis, acute tendonitis, bursitis, headaches, migraines, chronic neuropathic pains, shingles, premenstrual symptoms, sports injuries and like according to Li et al. There would have been a reasonable expectation of success because Obeid et al teach that anti-inflammatory agents are suitable for use as the active agent in the process for producing an oral film dosage form and Li et al teach ketoprofen in an oral film.
It would have also been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use methyl acetate as the organic solvent system in the process for producing an oral film dosage form of Obeid et al. One of ordinary skill in the art would have been motivated to do so because ethyl acetate and methyl acetate are interchangeable organic solvents used in a film oral dosage form according to Bilal et al. There would have been a reasonable expectation of success because Obeid et al teach other alkyl acetates, i.e., ethyl acetate and isobutyl acetate, as suitable for use as the organic solvent system in the process for producing an oral film dosage form.
The modified process for producing an oral film dosage form of Obeid et al in view of Baek et al, Li et al, and Bilal et al wherein the polymer is cellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), or cellulose acetate phthalate (CAP) from 10 to 75 wt%, the active agent is ketoprofen, the inner phase organic solvent system is methyl acetate, the outer phase solvent system is water, and the stabilizing agent is polyvinyl alcohol renders obvious the process for producing an oral thin film of instant claims 1-6 and 8-13. The mucoadhesive particles of the oral film dosage form having a size range between 100 nm and 100 m renders obvious the oral thin film comprising microparticles as required by instant claim 1.
Regarding instant claim 5, because the hypromellose acetate succinate in the modified process of Obeid et al is the same compound as the hypromellose acetate succinate in the process of the instant claims, the hypromellose acetate succinate in the modified process of Obeid et al necessarily has a logP value of greater than about 1. Regarding instant claim 12, because the ketoprofen in the modified process of Obeid et al is the same compound as the ketoprofen in the process of the instant claims, the ketoprofen in the modified process of Obeid et al necessarily has a logP value of greater than about 1. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present (In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
The polymer being cellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), or cellulose acetate phthalate (CAP) from 10 to 75 wt% by total weight of the film renders obvious instant claim 8 requiring hypromellose acetate succinate as the elected species of the hydrophobic polymer be added from 1 to 70 wt% in relation to the total weight of the dried oral thin film. The active agent being ketoprofen from 0.1 to 80% by total weight of the film renders obvious instant claim 9 requiring ketoprofen as the elected species of hydrophobic pharmaceutically active ingredient be added from 0.01 to 20 wt% in relation to the total weight of the dried oral thin film. A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003)).
Regarding instant claim 10, Obeid et al are silent regarding whether an emulsifier and/or pH regulator are added in the process. Thus, a skilled artisan would have understood that an emulsifier and/or pH regulator were not added in the process of Obeid et al. See AC Technologies S.A. v. Amazon.com, Inc., 912 F.3d 1358, 1367 (Fed. Cir. 2019) (“[A] reference need not state a feature’s absence in order to disclose a negative limitation.”); Sud-Chemie, Inc. v. Multisorb Techs., Inc., 554 F.3d 1001, 1004–05 (Fed. Cir. 2009) (affirming finding that reference disclosed “uncoated” film where it did not describe the film as coated and did not suggest necessity of coatings).
The teaching that the mucoadhesive particles may comprise an antioxidant renders obvious the process further comprising the addition of an antioxidant as the elected species of at least one excipient required by instant claim 11.
Regarding instant claim 13, because the mixture of the inner and outer phase solutions in the modified process of Obeid et al is the same as the mixture of c2) in instant claim 1, the mixture of the inner and outer phase solutions in the modified process of Obeid et al necessarily can be spread and dried so that the dried emulsion has a basis weight of about 20 to about 250 g/m2.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Obeid et al (as cited above) in view of Baek et al (as cited above), Li et al (as cited above), and Bilal et al (as cited above) as applied to claims 1-6 and 8-13 above, and further in view of Mueller et al (WO 2009/138170 A2, published 11/19/2009, cited in Notice of References Cited dated 07/01/2025).
The modified process for producing an oral film dosage form of Obeid et al in view of Baek et al, Li et al, and Bilal et al has been discussed supra.
None of Obeid et al, Baek et al, Li et al, and Bilal et al teach the amount of polyvinyl alcohol, or more broadly the amount of stabilizing agent, to be used in the outer phase solution in the process for producing an oral film dosage form.
This deficiency is made up for in the teaching of Mueller et al.
Mueller et al teach water-soluble, solid, film-shaped preparations comprising polyvinyl alcohols (e.g., Abstract). Mueller et al teach that polyvinyl alcohols are film-forming polymers that function as a stabilizer for films with an oily component for oral administration (e.g., Par. 6-7 on Page 3 of English translation). Mueller et al provide a range of 5 to 70 wt% of polyvinyl alcohol in the film-form preparations (e.g., Page 5 of English translation).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use polyvinyl alcohol as the stabilizing agent from 5 to 70 wt% in the modified process for producing an oral film dosage form of Obeid et al. One of ordinary skill in the art would have been motivated to do so because Mueller et al provide this range of polyvinyl alcohol as having stabilizing and good emulsifying power in film-form preparations for oral administration. There would have been a reasonable expectation of success because Obeid et al teach that polyvinyl alcohol is suitable for use as the stabilizing agent in the process for producing an oral film dosage form and do not teach any constraints on suitable amounts.
The modified process for producing an oral film dosage form of Obeid et al in view of Baek et al, Li et al, Bilal et al, and Mueller et al wherein the stabilizing agent is polyvinyl alcohol from 5 to 70 wt% by total weight of the film renders obvious instant claim 7 requiring polyvinyl alcohol as the elected species of hydrophilic polymer be added from 30 to 99 wt% in relation to the total weight of the dried oral thin film. A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003)).
Response to Applicant’s Arguments
Applicant’s arguments filed on 11/03/2025 have been considered.
Applicant argues that the process of the instant invention involves the formation of an oral thin film directly following the preparation of an emulsion, wherein microparticles are not produced separately in advance and incorporated into a polymer matrix, whereas the process taught by Obeid et al involves the particles being isolated in a first process step and then incorporated subsequently into a hydrophilic polymer matrix in a second process step. Applicant argues that the mucoadhesive materials comprising the mucoadhesive particles are hydrophilic polymers, such as poly(ethylene oxide), and not hydrophobic polymers, and therefore Obeid et al do not teach or suggest hydrophobic polymers for the formation of oral thin films. Applicant argues that the emulsification techniques of Obeid et al are fundamentally different from that of instant claim 1 and the emulsions of Obeid et al appear to be based on oil droplets in a polymer matrix and not on microparticles based on a hydrophobic polymer, a hydrophobic active ingredient, and a hydrophobic solvent as in the present application.
The above argument regarding additional process steps being taught in the prior art has been fully considered by the Examiner but is not found persuasive because the process of the instant claims uses ‘comprising the steps of’ language, meaning that the process is inclusive, or open-ended, and therefore does not exclude the presence of additional, unrecited process steps. The above argument regarding Obeid et al teaching hydrophilic polymers, such as poly(ethylene oxide), as the mucoadhesive materials comprising the mucoadhesive particles and not hydrophobic polymers has been fully considered by the Examiner but is not found persuasive because although Obeid et al does include poly(ethylene oxide) as an example of a mucoadhesive material used to prepare the mucoadhesive particles, the mucoadhesive materials are not taught as being limited to strictly hydrophilic polymers, i.e., Obeid et al teach that mucoadhesive materials used to prepare the mucoadhesive particles include cellulose derivatives, wherein chitosan, which is a cellulose derivative having both hydrophilic and hydrophobic characteristics, is exemplified (See Par. [0041] of Obeid et al). The above arguments regarding the differences between the emulsification/emulsions taught by Obeid et al and that of instant claim 1 have been fully considered by the Examiner but are not found persuasive because instant claim 1 in limitations cI) and c2) recite “mixing…to obtain an emulsion” generically and therefore the teachings of Obeid et al render obvious these limitations. The Examiner suggests that Applicant amend claim 1 to be commensurate with the process of the instant invention in order to overcome the process taught by the prior art.
Applicant argues that Baek et al teach hydrophilic polymers such as cellulose derivatives for the preparation of water-soluble films and disclose these as film-forming agents. Applicant argues that Baek et al do not disclose or mention emulsions, microparticles, or the process according to instant claim 1 and do not mention or suggest whether such cellulose derivatives would be appropriate for the preparation of oral thin films comprising microparticles according to instant claim 1. Applicant argues that none of Baek et al, Li et al, and Bilal et al teach a skilled artisan to depart from the process of Obeid et al.
The above argument regarding cellulose derivatives (including hydromellose acetate succinate) being taught as a hydrophilic polymer film-forming agent by Baek et al has been fully considered by the Examiner but is not found persuasive because the instant claims are being examined to the extent of the elected species, i.e., the hydrophobic polymer is hypromellose acetate succinate, for which Obeid et al in view of Baek et al teach hypromellose acetate succinate as the polymer of the inner phase. The above argument regarding Baek et al not teaching all of the limitations of instant claim 1 has been fully considered by the Examiner but is not found persuasive because the rejection is based on the combined teachings of the prior art applied in the rejection, not the individual teaching of Baek et al. The above argument regarding none of Baek et al, Li et al, and Bilal et al teaching a skilled artisan to depart from the process of Obeid et al has been fully considered by the Examiner but is not found persuasive because there did exist motivation for a person of ordinary skill in the art to look to each of the teachings of Baek et al, Li et al, and Bilal et al from the teaching of Obeid et al, i.e., one of ordinary skill in the art would have been motivated to use cellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), or cellulose acetate phthalate (CAP) as the polymer from 10 to 75% by weight in the process for producing an oral film dosage form of Obeid et al in order to provide an oral film dosage form comprising a good film forming polymer with slow release in the oral cavity, to incorporate ketoprofen as the anti-inflammatory agent in the process for producing an oral film dosage form of Obeid et al because ketoprofen is one of the most potent NSAIDs and is well known for treating symptoms associated with chronic arthritis, osteoarthritis, acute tendonitis, bursitis, headaches, migraines, chronic neuropathic pains, shingles, premenstrual symptoms, sports injuries and like according to Li et al, and to use methyl acetate as the organic solvent system in the process for producing an oral film dosage form of Obeid et al because ethyl acetate and methyl acetate are interchangeable organic solvents used in a film oral dosage form according to Bilal et al (See the maintained rejection under 35 USC 103 for more details). Applicant is reminded that the art needs to provide a motivation and not the same motivation as Applicant or necessarily recognize the same problem/solution as Applicant. "In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls." KSR Int'l Co. v. Teleflex lnc., 550 U.S. 398,419 (2007). Instead, "any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed." Id. at 420. Further, Applicant is reminded that 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).
Applicant argues that Mueller et al provide no teaching or suggestion that would lead a skilled artisan to modify the process of Obeid et al in a manner suitable for achieving the present process for in-situ formation of the microparticle inclusive oral thin film.
The above argument has been fully considered by the Examiner but is not found persuasive because there did exist motivation for a person of ordinary skill in the art to look to the teaching of Mueller et al, i.e., one of ordinary skill in the art would have been motivated to use polyvinyl alcohol as the stabilizing agent from 5 to 70 wt% in the modified process for producing an oral film dosage form of Obeid et al because Mueller et al provide this range of polyvinyl alcohol as having stabilizing and good emulsifying power in film-form preparations for oral administration (See the maintained rejection under 35 USC 103 for more details). Applicant is reminded that the art needs to provide a motivation and not the same motivation as Applicant or necessarily recognize the same problem/solution as Applicant. "In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls." KSR Int'l Co. v. Teleflex lnc., 550 U.S. 398,419 (2007). Instead, "any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed." Id. at 420. Further, Applicant is reminded that 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).
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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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/K.E.O./Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619