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
Amendments to the Specification, Amendments to the Claims and Remarks submitted on 27 June 2025, in response to the Office Correspondence dated 31 March 2025, are acknowledged.
During a telephone conversation with the attorney of record, Anthony Venturino, on 21 March 2025, a provisional election was made with traverse to prosecute the invention of Group I, claims 1-15. Affirmation of this election was made by the Applicant in replying to the Office Correspondence dated 31 March 2025, wherein claims 16-20 were withdrawn from further consideration by the Applicant, as being drawn to a non-elected invention pursuant to 37 CFR 1.142(b). This restriction election to prosecute the invention of Group I, claims 1-15 is herein made final.
The listing of Claims filed 27 June 2025, have been examined. Claims 1-15 are pending. Claims 1, 10, 12 and 15 have been amended and are supported by the originally-filed disclosure. Claims 2-9, 11, 13 and 14 have been previously presented and claims 16-20 have been canceled. No new claims have been added.
Response to Amendment
The Specification has been amended to correct the typographical error of “Puddle” to “Paddle”. Claim 1 has been amended to clarify “closed state”. Claims 12 and 15 have been amended to correct informalities objected to by the Examiner. Thus, the Examiner considers the informalities noted to be resolved and the objections are withdrawn.
The Applicant argues in Remarks filed 27 June 2025, that the prior art does not teach or suggest the claimed "closed state" of heat treatment and that the presented unexpected results overcome the obviousness rejections. The Applicant has amended claim 1 to further limit a “closed state” and thus the rejections of claims 1-6 and 8-13 under 35 U.S.C. § 102(a)(1) as being anticipated by Yaginuma (US20090196934A1; publication date 06 August 2009) and the previous 35 USC § 103 rejections are withdrawn. However, the amendment necessitates new grounds of rejection of the claims under 35 U.S.C. § 103 for the reasons detailed below.
New Rejections
The following new rejections are made in light of the amended/newly cited limitations.
Claim Rejections - 35 USC § 103
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-AlA) 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 1-6 and 8-13 are rejected under 35 U.S.C. § 103 as being obvious by Yaginuma (US20090196934A1; publication date 06 August 2009) in view of Gendre (Gendre C, Genty M, Fayard B, Tfayli A, Boiret M, Lecoq O, Baron M, Chaminade P, Péan JM. Comparative static curing versus dynamic curing on tablet coating structures. Int J Pharm. 2013 Sep 10;453(2):448-53; e-publication date: 18 June 2013) and in further view of Zhong (CN102018658B; published: 12 March 2014) and Mapelli et al. (US9233105B2; published 12 January 2016), hereinafter referred to as Mapelli.
Regarding instant claim 1, Yaginuma describes a method for producing a granule comprising (1) a core particle active ingredient having an unpleasant taste as sulpyrine (paragraph [0085], [0095], [0119], and [0122]) having a bitter taste, along with various other unpleasant tasting active ingredients (paragraph [0034]); (2) core particle surface coating with ethylcellulose (paragraph [0041], [0043], and applied with spray [0087]); then (3) heat treatment as, “The granules thus obtained were spread widely over a tray and cured (heat treated to form a film) for 60 minutes in an oven of 80° C to obtain film-coated granules.” (paragraph [0087]) for producing bitter taste-masking film-coated granules.
Yaginuma does not explicitly teach the tray heat treated curing in a closed state wherein the trays are placed in a sealed chamber with restricted moisture flow with no gas or vapor venting (e.g., oven drying in a sealed container, fluidized bed drying with a close-loop air flow, autoclave, rotary dryer with sealed chambers, or microwave-assisted drying in closed vessels), such as used in the art for solvent retention in film coating or controlled slow drying.
Gendre teaches that the environmental conditions during curing (e.g., humidity) are critical variables that directly affect the quality and performance of a coated pharmaceutical product, specifically film formation and drug release (page 1, paragraph 2). Gendre compares "static curing" in a tray placed in a "vented oven" to "dynamic curing" in a fluidized bed. The teaching of Gendre is that controlling the curing environment is a known and necessary step for optimizing the coating process (page 2, paragraph 2). Gendre measures NIR spectral information to reveal variation in the absorbance of cured tablets attributed to water content of the coating layer in which dynamic curing conditions under 4 hours led to increased water content that were stated to directly correlate with dissolution results (page 4, paragraph 6- page 5 paragraph 2), thus indicating that water content in the coating after the curing process is a known factor influencing dissolution rates. Hence, it would be obvious for one of ordinary skill in the art to reduce tablet coating water content during the curing process by controlling/eliminating humidity through methods such as implementing a closed system to reduce early dissolution time and retain moisture within the particle for a more continuous ethylcellulose film, even when close states were not explicitly used under the conditions of the experiment. This is a logical and predictable outcome—trapping plasticizing moisture leads to better film formation, which in turn provides a better barrier and delays initial dissolution.
Further, Zhong explicitly teaches the use of an airtight baking oven for healing [curing] (page 12, paragraph 2; page 13, paragraph 2; page 18, line 2) in controlled release preparations with improved performance using ethylcellulose polymers (page 6, paragraph 5), in particular relating to a zero-order release-controlled release.
In addition, Mapelli discloses a taste-masked, immediate-release microcapsules with ethylcellulose (EC) coatings (Abstract). Data show ≥90–97% drug released by 15 minutes in various media while early-time release is suppressed for taste masking with rapid overall release (Drawings, Figures 9-14). These disclosures map to an unpleasant-tasting API core, ethyl cellulose coating, and performance consistent with “taste masked” and “immediate release maintained.”
Hence, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to control humidity by using a closed system for heat curing instead of an open system, in order to provide a coated particle with a maintained release rate. The combination of references in the field teaches thermal curing of ethylcellulose coatings as a standard post-coat step to coalesce particles and stabilize release, sometimes utilizing humidity-control and closed/sealed environments to tune release. Together, the prior art references and Zhong’s explicit use of an airtight oven for curing teach both why and how to cure coated particulates under a closed, sealed conditions (i.e., “no gases and liquids enter/exit the container”). A person of ordinary skill in the art would expect that better film formation would yield better taste-masking performance. Therefore, these results are merely the natural and expected consequence of the claimed process and do not rise to the level of "unexpectedness" required to overcome a prima facie case of obviousness.
Regarding instant claim 2, Yaginuma teaches a coating “(1) comprising 30% by mass or greater of crystalline cellulose.” (paragraph [0016]), thus teaching the additional limitation of instant claim 2.
Regarding instant claims 3-6 and 8-10, Yaginuma also teaches the use of excipients including binders and disintegrants (paragraphs [0051] and [0062]), wherein, “In the layering method, granules are produced by coating spherical seed cores with a drug-containing coating layer. Specific examples of it include a method of simultaneously supplying drug powders and an aqueous solution of a binder and coating the spherical seed cores therewith; a method of supplying a suspension of drug particles and coating the spherical seed cores therewith; and a method of supplying an aqueous solution of a drug and coating the spherical seed cores therewith.” (paragraph [0004]), wherein “In the present invention, spherical elementary granules can be subjected to film coating in order to control a dissolution rate (sustained release, enteric release, timed release, pulse release, bitter-taste masking), moisture prevention or coloring of the drug.” (paragraph [0036]) and “A film coating liquid is sprayed to the spherical elementary granules. It may be supplied by a method suited for each of apparatuses such as top spray, bottom spray, side spray, and tangential spray. After completion of spraying, the resulting film-coated granules can be dried as are or after controlling the air flow rate or temperature as needed, without taking out the granules from the apparatus. The film coating liquid includes, for example, a solution that obtained by dissolving a solid film coating agent in an organic solvent, a dispersion liquid that obtained by dispersing both a film coating agent in fine powder form and a plasticizer in water, or a latex type film coating agent in which a plasticizer is added as needed.” (paragraphs [0039]-[0040]), thus teaching the additional limitations of instant claims 3-6 and 8-10.
Regarding instant claims 11 and 12, Yaginuma also teaches, “A coating amount of the drug-containing layer is determined based on the formulation design such as single dosage or size of the preparation. For example, it is generally from about 0.5 to 200% by mass relative to the spherical seed cores.” (paragraph [0067]) with an example including, “…until the coating amount for the spherical seed cores became 6.0% by mass…” (paragraph [0095]), thus the instant claim 11 and 12 ranges of coating on the surface of the core particles of 5-9 wt% or 5-7 wt%, relative to the core particle, respectively, are encompassed within the range taught by Yaginuma.
Regarding instant claim 13, Yaginuma teaches, “The granules thus obtained were spread widely over a tray and cured (heat treated to form a film) for 60 minutes in an oven of 80° C to obtain film-coated granules.” (paragraph [0087]), encompassed within the instant claim range of 70 to 100°C for 15 to 180 minutes.
Claim 7 is rejected under 35 U.S.C. § 103 as being unpatentable over Yaginuma (US20090196934A1; publication date 06 August 2009) in view of Gendre (Gendre C, Genty M, Fayard B, Tfayli A, Boiret M, Lecoq O, Baron M, Chaminade P, Péan JM. Comparative static curing versus dynamic curing on tablet coating structures. Int J Pharm. 2013 Sep 10;453(2):448-53; e-publication date: 18 June 2013) and in further view of Zhong (CN102018658B; published: 12 March 2014), Mapelli et al. (US9233105B2; published 12 January 2016), hereinafter referred to as Mapelli, and Kamada (US5384130A; publication date: 24 January 1995).
Regarding instant claim 7, the teachings of Yaginuma, Gendre, Zhong, and Mapelli in regards to instant claim 1 are discussed above. Yaginuma also teaches “The spherical elementary granules obtained by the above process can be used as granules, capsules, tablets or the like after subjected to particle size regulation and sustained release film coating, enteric film coating, or bitterness masking film coating if necessary.” (paragraph [0075]) and “After drying, coarse particles having a size of 710 μm or greater and fine powders having a size of 300 μm or less were screened out to obtain spherical seed cores A.” (paragraph [0084]), suggesting some sort of sieving of the particles to obtain a decided particle size. In addition, Yaginuma teaches “In the layering method, granules are produced by coating spherical seed cores with a drug-containing coating layer. Specific examples of it include a method of simultaneously supplying drug powders and an aqueous solution of a binder and coating the spherical seed cores therewith” (paragraph [0004]), with the use of a “drug powders” potentially utilizing some sort of grinding. However, Yaginuma does not explicitly detail grinding or sieving of the particles.
Kamada teaches “The microcrystalline cellulose used in the present invention is … a product obtained by mechanical treatment such as grinding of the above-mentioned chemically treated product …Preferably, the microcrystalline cellulose has a water absorption capacity of 1.0 to 2.8 ml/g, and no more than 80% of its fractions is retained on a 200 mesh-sieve.”(page 4, column 4, lines 20-35), disclosing grinding a granulated product and sieving the particles to obtain a decided particle size.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to grind and sieve a granulated unpleasant tasting active ingredient with a preparation agent to obtain a desired particle size for coating, as it was known in the art to be used with microcrystalline cellulose for the same purpose at the time of the invention.
Claim 14 is rejected under 35 U.S.C. § 103 as being unpatentable over Yaginuma (US20090196934A1; publication date 06 August 2009) in view of Gendre (Gendre C, Genty M, Fayard B, Tfayli A, Boiret M, Lecoq O, Baron M, Chaminade P, Péan JM. Comparative static curing versus dynamic curing on tablet coating structures. Int J Pharm. 2013 Sep 10;453(2):448-53; e-publication date: 18 June 2013) and in further view of Zhong (CN102018658B; published: 12 March 2014), Mapelli et al. (US9233105B2; published 12 January 2016), hereinafter referred to as Mapelli, and Takeda (JP2007031292A; publication date: 8 February 2007).
Regarding instant claim 14, the teachings of Yaginuma, Gendre, Zhong, and Mapelli in regards to instant claim 1 are discussed above. Yaginuma teaches use of active ingredients that include “…vitamin preparations, such as retinol acetate, …” (paragraph [0034]), but does not explicitly disclose the use of the unpleasant tasting active ingredient as zinc acetate.
Takeda teaches zinc acetate is known to have an unpleasant taste and that masking the unpleasant taste is a desirable problem to be solved (Abstract, Claim 2).
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to use the instant invention, aimed at masking unpleasant tasting active ingredients, with unpleasant tasting zinc acetate as the active ingredient, given it was known at the time of the invention to be an unpleasant tasting active ingredient and, as such, was the subject of other taste masking inventions.
Claim 15 is rejected under 35 U.S.C. § 103 as being unpatentable over Yaginuma (US20090196934A1; publication date 06 August 2009) in view of Gendre (Gendre C, Genty M, Fayard B, Tfayli A, Boiret M, Lecoq O, Baron M, Chaminade P, Péan JM. Comparative static curing versus dynamic curing on tablet coating structures. Int J Pharm. 2013 Sep 10;453(2):448-53; e-publication date: 18 June 2013) and in further view of Zhong (CN102018658B; published: 12 March 2014), Mapelli et al. (US9233105B2; published 12 January 2016), hereinafter referred to as Mapelli, and Fujihara (US9907794B2; publication date: 06 March 2018).
Regarding instant claim 15, the teachings of Yaginuma, Gendre, Zhong, and Mapelli in regards to instant claim 1 are discussed above. Yaginuma teaches the method of producing the granule but does not teach dissolution rate is 80% or less at a test time of 5 minutes, and 85% or more at a test time of 15 minutes using the specified instant claim method.
Fujihara teaches an active ingredient with a water-soluble excipient and a water-soluble polymeric binder in a rapid dissolution oral administration preparation, “wherein the tablet has a dissolution rate of 80% or more at 30 minutes as measured according to Japanese Pharmacopoeia, Dissolution test, Method 2, where the tablet is subjected to the Dissolution test using paddle rotation at a rotation rate of 50 rpm in 900 mL of a diluted McIlvaine buffer having a pH of 3.8 to 4.0.” (Claim 1)
Thus, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to use the method taught by Fujihara for an immediate release preparation to measure the dissolution rate of the granule preparation taught by Yaginuma and arrive at a 5-minute dissolution rate of 80% or less and a 15-minute dissolution rate of 85% or more through routine experimentation of parameters taught by the prior art.
Response to Arguments
In the Remarks submitted on 27 June 2025, in response to the Office Correspondence dated 31 March 2025, the Applicant argues that Yaginuma does not anticipate claim 1 because it "merely describes drying in an oven" and does not explicitly teach a "closed state" where "no gases and liquids enter the container and no gases and liquids exit the container." The Examiner agrees that the claim, as amended is no longer is anticipated by the prior as Yaginuma does not explicitly teach the use of a hermetically sealed system, however the claims are now rendered obvious by the prior art.
Yaginuma teaches "curing (heat treating) at 80°C for 60 minutes" in an oven (¶[0047]). A person of ordinary skill in the art would understand that a standard industrial or laboratory oven, by its very nature and function, constitutes a closed system during operation to maintain a stable, controlled temperature. While not hermetically sealed like a desiccator, an oven chamber is designed to significantly restrict the uncontrolled flow of gases and liquids to ensure thermal efficiency. The Applicant's argument that an oven is not a "container" is unpersuasive; an oven is a large, enclosed container for heat processing materials.
The amendment, narrows the claim further to limit the closed state, “wherein the closed state occurs in a container, wherein no gases and liquids enter the container and no gases and liquids exit the container, wherein the gases and liquids comprise water vapor and air flow”, which is not an explicit condition disclosed by Yaginuma. However, the combination of Yaginuma, Gendre, Zhong, and Mapelli renders the claimed invention obvious and the rejection of claims 1-15 under 35 U.S.C. § 103 is made, as described in detail above.
Thus, the data disclosed in the instant Specification Table 1 (¶[0064]), wherein the dissolution rate (%) at the 5-minute time point was suppressed (resulting in superior taste masking and maintaining equivalent dissolution/ immediate release at 15 minutes) in the granule heated under the closed condition more than in the granule heated under the open condition are expected, not unexpected. The Specification itself provides the reasoning: heating in a closed state retains moisture within the particle, which promotes the formation of a more effective, continuous ethylcellulose film (¶[0043]). This is a logical and predictable outcome—trapping plasticizing moisture leads to better film formation, which in turn provides a better barrier and delays initial dissolution. A person of ordinary skill in the art would expect that better film formation would yield better taste-masking performance. Therefore, these results are merely the natural and expected consequence of the claimed process and do not rise to the level of "unexpectedness" required to overcome a prima facie case of obviousness.
A person of ordinary skill in the art, seeking to optimize Yaginuma's process, would have been motivated to consider and control the environmental conditions of the curing step. The most straightforward and obvious way to control humidity and temperature during the curing process, and if a tighter control of moisture was desired, it would have been obvious to control venting/restrict flow within an oven to prevent ingress or egress of moisture or use closed state sealed containers to achieve moisture control. The combination of references provides motivation to use a controlled, closed environment for heat treatment to reduce rapid dissolution rates.
Support for a prima facie case of obviousness, based on facts gleaned from the prior art, including all of the limitations of newly amended claim 1, have been addressed above. Further, "The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference.... Rather, the test is what the combined teachings of those references would have suggested to those of ordinary skill in the art." (In re Keller, 642 F.2d 413, 425, 208 USPQ 871, 881 (CCPA 1981)). As such, the Applicant’s Remarks and arguments have been fully considered and are not persuasive. Claims 1-15 are rejected under 35 U.S.C. § 103, in light of the prior art.
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 (87 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L. SCOTLAND whose telephone number is (571) 272-2979. The examiner can normally be reached M-F 9:00 am to 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at: http:/Awww.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’ s supervisor, Robert A. Wax can be reached at (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https:/Awww.uspto.gov/patents/apply/patent- center for more information about Patent Center and https:/Awww.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at (866) 217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call (800) 786-9199 (IN USA OR CANADA) or (571) 272-1000.
/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615