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
Applicant’s claim amendments and arguments in the reply filed on 20 May 2026 are acknowledged and have been fully considered. Claims 1-3, 7-12, and 16-19 are pending. Claims 1-3, 7-8, and 18-19 are under consideration in the instant office action. Claim 9-12 and 16-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claims. Claims 4-6 and 13-15 are canceled. Applicant amended claim 1 to recite “A film-coated granule comprising: a core particle having a core substance, a molten component layer arranged on a surface of the core substance, and an active ingredient-containing layer arranged on a surface of the molten component layer; and a film arranged on a surface of the core particle, wherein the core substance is selected from a group consisting of amberlite IRP-64, ion exchange resin, kaolin, carmellose calcium, hydrous silicon dioxide, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, diatomaceous earth, synthetic aluminum silicate, aluminum oxide, aluminum hydroxide, absorbent cotton, magnesium carbonate, precipitated calcium carbonate, dextrin, silicon dioxide, composite potassium aluminum silicate grains, bentonite, polyethylene fiber, magnesium aluminometasilicate. medicinal charcoal, calcium silicate, cellulose acetate, anhydrous calcium hydrogen phosphate, microcrystalline cellulose, mannitol, sucrose, starch, lactose hydrate, and ammonioalkyl methacrylate copolymer, the molten component layer consists of a first melt component, the first melt component is selected from a group consisting of glycerin monostearate, macrogol, lauromacrogol and stearic acid, the active ingredient-containing layer consists of an active ingredient, and a second melt component or a first polymer, the film includes a porous substance, a plasticizer and a second polymer, and wherein the plasticizer is absorbed on a surface of the porous substance in the film and/or in the interior of pores of the porous substance in the film.” Applicant also amended claims 8-9 and 18. Applicant’s claim amendments and arguments necessitated a new ground of rejections under 35 USC 103 as set forth below.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 21 April 2026 is noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
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 1-3, 7-8, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Li (US20090022807) in view of SENDA et al. (JP 2020176107, newly cited, machine English translation provided), FujiSilTM Techincal Data Sheet (final version on July 17, 2019, and uploaded on May, 2020), and BUKOVEC et al. (WO 2012131005).
Note: The claims are examined with respect to the elected species of hydrated silicon dioxide as a specific core particle; stearic acid as a specific melt component; light anhydrous silicic acid as a specific porous substance; triethyl citrate as a specific plasticizer; aminoalkyl methacrylate copolymer E as a specific polymer; and sitagliptin phosphate as a specific active ingredient.
Applicants’ claims
Applicant claims “A film-coated granule comprising: a core particle having a core substance, a molten component layer arranged on a surface of the core substance, and an active ingredient-containing layer arranged on a surface of the molten component layer; and a film arranged on a surface of the core particle, wherein the core substance is selected from a group consisting of amberlite IRP-64, ion exchange resin, kaolin, carmellose calcium, hydrous silicon dioxide, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, diatomaceous earth, synthetic aluminum silicate, aluminum oxide, aluminum hydroxide, absorbent cotton, magnesium carbonate, precipitated calcium carbonate, dextrin, silicon dioxide, composite potassium aluminum silicate grains, bentonite, polyethylene fiber, magnesium aluminometasilicate. medicinal charcoal, calcium silicate, cellulose acetate, anhydrous calcium hydrogen phosphate, microcrystalline cellulose, mannitol, sucrose, starch, lactose hydrate, and ammonioalkyl methacrylate copolymer, the molten component layer consists of a first melt component, the first melt component is selected from a group consisting of glycerin monostearate, macrogol, lauromacrogol and stearic acid, the active ingredient-containing layer consists of an active ingredient, and a second melt component or a first polymer, the film includes a porous substance, a plasticizer and a second polymer, and wherein the plasticizer is absorbed on a surface of the porous substance in the film and/or in the interior of pores of the porous substance in the film.” Dependent claims thereof limitations further defining the different components of the claim.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Li teaches a drug composition comprising a coated bead is used in the manufacture of immediate release and/or controlled release drug compositions. In a specific embodiment, the bead includes an inert core of a water-soluble or water-swellable material, which has been coated with a seal layer formed from a non-polymeric hydrophobic material. The immediate and/or controlled release beads may be used to form tablets or capsules. A method of making the beads by sequential deposition of multiple layers on the inert cores is also described (see abstract) Li teaches a controlled release drug composition comprising a bead, said bead comprising: an inert core; a seal layer positioned on said core layer, said seal layer containing a non-polymeric hydrophobic material; a layer containing at least one active ingredient positioned on said seal layer; and a layer of at least one release-controlling polymer positioned on said layer containing at least one active ingredient (see claim 1). The controlled release drug composition of claim 1, wherein the non-polymeric hydrophobic material is selected from the group consisting of a fatty alcohol, a fatty carboxylic acid, a fatty carboxylic acid ester, a hydrogenated oil, a triglyceride fat, a wax, and mixtures thereof (see claim 2). The controlled release drug composition of claim 1, wherein the non-polymeric hydrophobic material is selected from the group consisting of a C12-C20 fatty alcohol, a C12-C20 fatty carboxylic acid, an ester of a C12-C20 fatty carboxylic acid, a hydrogenated vegetable oil, a triglyceride fat, and mixtures thereof (see claim 3). The controlled release drug composition of claim 1, wherein the non-polymeric hydrophobic material is selected from the group consisting of stearyl alcohol, cetyl alcohol, stearic acid, an ester of stearic acid with a lower alcohol or polyol, an ester of cetyl alcohol, hydrogenated castor oil, and mixtures thereof (see claim 4). The controlled release drug composition of claim 1, wherein the inert core is water-soluble or water-swellable (see claim 5). The controlled release drug composition of claim 5, wherein the inert core comprises an inert material selected from the group consisting of starch, dextrose, sucrose, lactose, maltose, and microcrystalline cellulose (see claim 6). The controlled release drug composition of claim 1, wherein the release-controlling polymer includes ethylcellulose, hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, an ammonio methacrylate copolymer, a methacrylic acid copolymer, or a mixture thereof (see claim 16). The controlled release drug composition of claim 1, wherein the release-controlling polymer includes ethylcellulose, optionally in combination with at least one water soluble or water mobile pore forming agent (see claim 17). The controlled release drug composition of claim 17, wherein the water soluble or water mobile pore forming agent is hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose, carboxymethylcellulose, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, cellulose acetate trimellitate, polymethacrylates, an ammonium salt of a copolymer of methacrylic acid and methacrylic acid alkyl ester, sucrose, lactose, maltose, mannitol, maltodextrin, NaCl, or a mixture thereof (see claim 18). The controlled release drug composition of claim 1, wherein the release-controlling polymer includes an enteric polymer (see claim 19). The controlled release drug composition of claim 19, wherein the enteric polymer is cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, cellulose acetate trimellitate, polymethacrylates, or an ammonium salt of a copolymer of methacrylic acid and methacrylic acid alkyl ester (see claim 20). Li teaches in example 1 an exemplary capsule containing 4 mg/unit acid-stabilized tolterodine L-tartrate as active ingredient comprises a plurality of beads. Each bead includes as an inert core, a sugar sphere, 20-25 mesh (20/25). As a first seal layer, stearyl alcohol is deposited on the sugar sphere. Next, a layer containing Tolterodine L-tartrate, tartaric acid, and an Opadry II Clear dispersion containing hydroxypropylmethylcellulose (HPMC) is deposited on the seal layer. Finally, a third layer of Surelease® and Opadry Clear is deposited on the Tolterodine L-tartrate layer as a release-controlling layer. The ratio of Surelease® solids:Opadry Clear is 80:20. Surelease® is an aqueous film-coating dispersion, about 25% solids, consisting primarily of ethylcellulose plasticized with fractionated coconut oil, and is manufactured by Colorcon, Inc, USA.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Li does not specifically teach the incorporation of light anhydrous silicic acid as the porous substance, aminoalkyl methacrylate copolymer as the first polymer, and triethyl citrate as plasticizer in the film. These deficiencies are cured by the teachings of SENDA et al.
SENDA et al. teach in the abstract a coated tablet which suppresses practically sufficient moisture absorption while containing a component having extremely strong hygroscopicity. SOLUTION: There is provided a coated tablet comprising an uncoated tablet containing a hygroscopic component and a coating layer containing an aminoalkyl methacrylate copolymer E and/or a polyvinylalcohol-acrylic acid-methyl metacrylate copolymer. There is provided a coated tablet comprising an uncoated tablet containing a hygroscopic component and two coating layers selected from the group consisting of a coating layer containing an aminoalkyl methacrylate copolymer E, a coating layer containing a polyvinylalcohol-acrylic acid-methyl methacrylate copolymer, a coating layer containing a polyvinyl alcohol-polyethylene glycol-graft copolymer, a coating layer containing hypromellose and a coating layer containing ethylcellulose and methylcellulose. SENDA et al. teach in the additives section the first to third coated tablets of the present invention can contain any additives usually used in medicines and foods as long as the effects of the invention are not impaired. Additives include fluidizers, disintegrants, excipients, binders, lubricants, brighteners, bases, emulsifiers or solubilizers, preservatives, colorants, flavoring agents, sweeteners, fragrances, etc. Examples include plasticizing agents (plasticizing agents can be contained in the coating layer). Additives may be used alone or in combination of two or more The fluidizing agent can be added to either the uncoated tablet or the coating layer. The fluidizing agent means a substance that can be used as a fluidizing agent in the field of formulation, and is not particularly limited as long as it is a substance that can be used as a fluidizing agent. For example, silicic acid compounds, talc, titanium oxide, stearic acid, stearate (magnesium stearate, calcium stearate, aluminum stearate, zinc stearate, etc.), stearate ester (sodium stearyl fumarate, glycerin monostearate, etc.) (Glycerin palmitostearate, etc.), sodium lauryl sulfate, glycerin fatty acid ester, sucrose fatty acid ester, sodium potassium tartrate, carnauba wax, L-leucine, hardened oil and the like. The silicic acid compound in the present invention is not particularly limited as long as the above-mentioned effect of the present invention is produced, and examples thereof include known silicic acid compounds published in the Japanese Pharmacopoeia, Pharmaceutical Additive Standards, Quasi-drug Raw Material Standards, and the like. Be done. Among them, light anhydrous silicic acid, calcium silicate, magnesium aluminomerate, magnesium silicate, synthetic aluminum silicate, hydrous silicon dioxide and metasilicic acid from the viewpoint of further suppressing related substances of levocarnitine (free form). Magnesium aluminate is preferable, and light anhydrous silicic acid and calcium silicate are more preferable (see description). Examples of the plasticizer include polyethylene glycol, propylene glycol, glycerin, glycerin fatty acid ester such as triacetin (glycerin triacetic acid), liquid paraffin, sorbitan monolaurate, monostearate, triethyl citrate, tributyl citrate, diethyl phthalate. , Dibutyl phthalate, diethyl sebacate, dibutyl sebacate, poroxamer, polyoxyethylene hydrogenated castor oil and the like.
Li does not specifically teach hydrated silicon dioxide as the core substance. These deficiencies are cured by the teachings of FujiSilTM Techincal Data Sheet.
FujiSilTM Techincal Data Sheet teaches FujiSilTM is a spray-dried granular amorphous Silica, designed as a superior inert carrier for pharmaceutical applications. FujiSilTM has a unique internal structure and remarkable flow properties giving high internal porosity and superior compressibility properties. The unique internal granular structure of FujiSilTM imparts superior flowability and compressibility during the tableting process. This results in improved tablet strength as illustrated in the following two charts representing key aspects of tablet strength. The key features are minimum reactivity with actives, very high porosity, high oil adsorption capacity (up to 3.3ml/g), solid dispersions, superior tabletability, and unique structure and processing improves both the flowability and compressibility. Typical applications include transform liquids to solid dosage forms, solid dispersions, improved processability and stability, solubility enhancement for BCS class II & IV drugs, granules suitable for coating, taste masking, controlled /delayed release, and moisture protection properties. FujiSilTM Techincal Data Sheet further teaches that the general name of silicon dioxide is Silicon Dioxide (USP/NF), Silica, colloidal hydrated (EP), and Hydrous silicon dioxide (JPE) (se whole document).
Li does not specifically teach sitagliptin phosphate as active agent. These deficiencies are cured by the teachings of BUKOVEC et al.
BUKOVEC et al. teach stable pharmaceutical compositions comprising amorphous sitagliptin and processes for their preparation. Pharmaceutical compositions are prepared from a solution comprising sitagliptin and a crystallization inhibitor (see abstract). A pharmaceutical composition comprising amorphous sitagliptin, wherein the amorphous sitagliptin has been prepared from a solution comprising sitagliptin and a crystallization inhibitor (see claim 1). The pharmaceutical composition according to claim 1, 2, or 3, wherein the sitagliptin is a sitagliptin salt (see claim 2). The pharmaceutical composition according to claim 4, wherein the sitagliptin salt is selected from the group consisting of hydrochloride salt, hydrobromide , sulfate, citrate, phosphate, tartrate, lactate, fumarate, maleate and/or mandelate (see claim 3). The glidant can be selected from the group consisting of but not limited to colloidal silicon dioxide, talc, stearic acid, palmitic acid, polyethylene glycol, carnauba wax and/or mixtures thereof (see page 11). The composition is optionally film coated. Film coating can be used to provide improved surface smoothness and color, increased chemical and physical stability of the active agent due to reduced permeability for gases such as oxygen and/or water vapor, less disintegration of the solid composition in acidic medium resulting in decreased gastrointestinal side effects, and easier swallowing of tablet. The film coating comprises coating materials generally known in the art. Suitable coating materials include polymers such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, ethylcellulose, povidone and copovidone, graft copolymers of polyethyleneglycol and polyvinyl alcohol (Kollicoat IR) , shellac, polymers of methacrylic acid or methacrylic acid esters, methacrylic acid-methyl acrylate copolymers, polyvinyl alcohol, plasticizers such as propylene glycol, polyethylene glycol, glycerol triacetate, triethyl citrate, antitacking agents such as talc, glycerol monostearate, magnesium stearate and colorants or pigments such as titanium dioxide or iron oxide (see pages 13-14).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art at the time the present invention was filed to modify the teachings of Li by incorporating aminoalkyl methacrylate copolymer, light anhydrous silicic acid, hydrous silica dioxide, and triethyl citrate in the film layer because SENDA et al. teach in the abstract a coated tablet which suppresses practically sufficient moisture absorption while containing a component having extremely strong hygroscopicity. SOLUTION: There is provided a coated tablet comprising an uncoated tablet containing a hygroscopic component and a coating layer containing an aminoalkyl methacrylate copolymer E and/or a polyvinylalcohol-acrylic acid-methyl metacrylate copolymer. There is provided a coated tablet comprising an uncoated tablet containing a hygroscopic component and two coating layers selected from the group consisting of a coating layer containing an aminoalkyl methacrylate copolymer E, a coating layer containing a polyvinylalcohol-acrylic acid-methyl methacrylate copolymer, a coating layer containing a polyvinyl alcohol-polyethylene glycol-graft copolymer, a coating layer containing hypromellose and a coating layer containing ethylcellulose and methylcellulose. SENDA et al. teach in the additives section the first to third coated tablets of the present invention can contain any additives usually used in medicines and foods as long as the effects of the invention are not impaired. Additives include fluidizers, disintegrants, excipients, binders, lubricants, brighteners, bases, emulsifiers or solubilizers, preservatives, colorants, flavoring agents, sweeteners, fragrances, etc. Examples include plasticizing agents (plasticizing agents can be contained in the coating layer). Additives may be used alone or in combination of two or more The fluidizing agent can be added to either the uncoated tablet or the coating layer. The fluidizing agent means a substance that can be used as a fluidizing agent in the field of formulation, and is not particularly limited as long as it is a substance that can be used as a fluidizing agent. For example, silicic acid compounds, talc, titanium oxide, stearic acid, stearate (magnesium stearate, calcium stearate, aluminum stearate, zinc stearate, etc.), stearate ester (sodium stearyl fumarate, glycerin monostearate, etc.) (Glycerin palmitostearate, etc.), sodium lauryl sulfate, glycerin fatty acid ester, sucrose fatty acid ester, sodium potassium tartrate, carnauba wax, L-leucine, hardened oil and the like. The silicic acid compound in the present invention is not particularly limited as long as the above-mentioned effect of the present invention is produced, and examples thereof include known silicic acid compounds published in the Japanese Pharmacopoeia, Pharmaceutical Additive Standards, Quasi-drug Raw Material Standards, and the like. Be done. Among them, light anhydrous silicic acid, calcium silicate, magnesium aluminomerate, magnesium silicate, synthetic aluminum silicate, hydrous silicon dioxide and metasilicic acid from the viewpoint of further suppressing related substances of levocarnitine (free form). Magnesium aluminate is preferable, and light anhydrous silicic acid and calcium silicate are more preferable (see description). Examples of the plasticizer include polyethylene glycol, propylene glycol, glycerin, glycerin fatty acid ester such as triacetin (glycerin triacetic acid), liquid paraffin, sorbitan monolaurate, monostearate, triethyl citrate, tributyl citrate, diethyl phthalate. , Dibutyl phthalate, diethyl sebacate, dibutyl sebacate, poroxamer, polyoxyethylene hydrogenated castor oil and the like (see description plasticizers section). One of ordinary skill in the art would have been motivated to substitute one plasticizer with another because the plasticizers are functionally equivalent. With regard to the aminoalkyl methacrylate copolymer E, light anhydrous silicic acid, and hydrous silica dioxide the selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.). With regard to the limitation reciting wherein the plasticizer is absorbed on a surface of the porous substance in the film and/or in the interior of pores of the porous substance in the film, it should be recognized that Li teach the inclusion of light anhydrous silicic acid and hydrous silica dioxide (Applicant’s porous substance) and also Li teach the inclusion of plasticizers) in the preparation of the film on the core particle. Therefore, the plasticizer will necessarily get absorbed on the surface of the porous substance or into the pores of the porous substance light anhydrous silicic acid on the film.
It would have been prima facie obvious to a person of ordinary skill in the art at the time the present invention was filed to modify the teachings of Li by utilizing hydrated silicon dioxide as the core material because FujiSilTM Techincal Data Sheet teaches FujiSilTM is a spray-dried granular amorphous Silica, designed as a superior inert carrier for pharmaceutical applications. One of ordinary skill in the art would have been motivated to do so because FujiSilTM Techincal Data Sheet teaches that FujiSilTM has a unique internal structure and remarkable flow properties giving high internal porosity and superior compressibility properties. The unique internal granular structure of FujiSilTM imparts superior flowability and compressibility during the tableting process. This results in improved tablet strength as illustrated in the following two charts representing key aspects of tablet strength. The key features are minimum reactivity with actives, very high porosity, high oil adsorption capacity (up to 3.3ml/g), solid dispersions, superior tabletability, and unique structure and processing improves both the flowability and compressibility. Typical applications include transform liquids to solid dosage forms, solid dispersions, improved processability and stability, solubility enhancement for BCS class II & IV drugs, granules suitable for coating, taste masking, controlled /delayed release, and moisture protection properties. FujiSilTM Techincal Data Sheet further teaches that the general name of silicon dioxide is Silicon Dioxide (USP/NF), Silica, colloidal hydrated (EP), and Hydrous silicon dioxide (JPE) (se whole document). Furthermore, in the case where the amount of ingredients, particle sizes, concentrations of ingredients, weight ratios etc., "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) Furthermore, differences in concentration or size will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here 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, 456, 105 USPQ 233,235 (CCPA 1955). An ordinary skill in the art would have had a reasonable chance of success in combining Li and FujiSilTM Techincal Data Sheet because both references teach pharmaceutical compositions utilizing inert core materials.
It would have been prima facie obvious to a person of ordinary skill in the art at the time the present invention was filed to modify the teachings of Li by using the pharmaceutical composition of Li for the delivery of sitagliptin phosphate because BUKOVEC et al. teach stable pharmaceutical compositions comprising amorphous sitagliptin and processes for their preparation. Pharmaceutical compositions are prepared from a solution comprising sitagliptin and a crystallization inhibitor (see abstract). One of ordinary skill in the art would have been motivated to do so because first Li teach in general active agent which teaches that in various exemplary embodiments, the controlled release tablets contain at least one active ingredient in the controlled release beads, where the at least one active ingredient is a water-soluble drug (see paragraph 0043). It should be noticed that sitagliptin phosphate is soluble form of the drug. Second, BUKOVEC et al. teach a pharmaceutical composition comprising amorphous sitagliptin, wherein the amorphous sitagliptin has been prepared from a solution comprising sitagliptin and a crystallization inhibitor (see claim 1). The pharmaceutical composition according to claim 1, 2, or 3, wherein the sitagliptin is a sitagliptin salt (see claim 2). The pharmaceutical composition according to claim 4, wherein the sitagliptin salt is selected from the group consisting of hydrochloride salt, hydrobromide , sulfate, citrate, phosphate, tartrate, lactate, fumarate, maleate and/or mandelate (see claim 3). The glidant can be selected from the group consisting of but not limited to colloidal silicon dioxide, talc, stearic acid, palmitic acid, polyethylene glycol, carnauba wax and/or mixtures thereof (see page 11). An ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Li and BUKOVEC er al. because both references teach pharmaceutical composition containing a film coating for the delivery of actives.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 20 May 2026 have been fully considered but they are not persuasive.
Applicants argue Li describes that the exemplary bead 10 includes an inert core 1 made of a water-soluble or water-swellable material. In various exemplary embodiments, the core 1 is made of a low molecular weight sugar, such as maltose, lactose, dextrose, or sucrose and alternatively, the core 1 is made of a hydrophilic polysaccharide, such as starch, microcrystalline cellulose, carboxymethylcellulose, croscarmellose, hydroxyethylcellulose, or hydroxypropyl methylcellulose, and in various exemplary embodiments, the core 1 is made of a partially or completely water-soluble pharmaceutically acceptable inorganic salt, and in various exemplary embodiments, the core 1 is made of a water-swellable synthetic polymer, such as crosslinked acrylic or methacrylic acid polymers and copolymers or crospovidone. (See Li, paragraph [0022]). Li also describes that a coating 3 of a non-polymeric water-insoluble material is positioned on core 1. The non-polymeric water-insoluble material prevents water from entering into the core 1 and causing the core 1 to dissolve or swell. (See Li, paragraph [0023]). Li does not teach or suggest the feature of "the core substance is selected from a group consisting of amberlite IRP-64, ion exchange resin, kaolin, carmellose calcium, hydrous silicon dioxide, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, diatomaceous earth, synthetic aluminum silicate, aluminum oxide, aluminum hydroxide, absorbent cotton, magnesium carbonate, precipitated calcium carbonate, dextrin, silicon dioxide, composite potassium aluminum silicate grains, bentonite, polyethylene fiber, magnesium aluminometasilicate, medicinal charcoal, calcium silicate, cellulose acetate, anhydrous calcium hydrogen phosphate, microcrystalline cellulose mannitol, sucrose, starch, lactose hydrate, and ammonioalkyl methacrylate copolymer" recited in claim 1. In addition, the use of hydrated silicon dioxide as the core substance according to FujiSil asserted by the Office does not meet the disclosures of Li, namely an inert core 1 made of a water-soluble or water-swellable material. If hydrated silicon dioxide, which is not the inert core made of a water-soluble or water swellable material, is used as the core substance in Li, stearic acid is not required as the non-polymeric hydrophobic material as the seal layer positioned on said core layer, said seal layer containing a non-polymeric hydrophobic material, because the non-polymeric water-insoluble material prevents water from entering into the core 1 and causing the core 1 to dissolve or swell. Therefore, the use of hydrated silicon dioxide as the core substance in Li disrupts the bead and the controlled release drug composition of Li.
The above assertions are not found persuasive because Li is not required to teach hydrous silicon dioxide as the core. The rejection does not rest on Li alone teaching every recited limitation. Under 35 USC 03 the question is whether a person of ordinary skill in the art starting from Li’s architecture would have found it obvious to use hydrous silicon dioxide as the inert core and to apply the remaining layers and film components taught by Senda, FujiSil, and Bukovec. The rejection is based on the combination teachings of references. Li’s water soluble or water swellable language describes preferred cores not a closed genus that excludes silica. The art routinely uses silica, silicon dioxide and microcrystalline cellulose particles as inert cores for layered beads. FujiSil is sold and described for exactly that use: spray dried granular amorphous silica meeting JPE “hydrous silicon dioxide” used as an inert core to create smaller taste masking granules than conventional carriers. Substituting FujiSIl (or an equivalent hydrous silicon dioxide granule) for Li’s sugar sphere is substitution of one known inert core for another, with a predictable result: spherical, flowable, coatable particle on to which Li’s melt seal, drug layer and outer film can be applied. Regarding the stearic acid argument, first a feature that is optional or redundant for one purpose is not a teaching away from using it. Li’s seal layer is taught as a hydrophobic, nonpolymeric barrier. Even if prevention of core dissolution is less critical on an insoluble silica core, the same layer still functions as a moisture/water barrier protecting the drug layer from the core and from processing moisture; a compatible surface for subsequent layering; and a melt processable intermediate that Applicant’s own specification uses for the same structural reason. Obviousness does not require that every motivation stated in the primary reference remain the only motivation after substitution. Second, the combination is not inoperative. A water insoluble silica core plus a stearic acid melt layer plus a sitagliptin containing layer plus an outer polymer film is conventional stacked bead construction. Nothing in Li teaches that the seal layer must not be used unless the core is water soluble. Li does not criticize silica cores, does not state that hydrophobic seals are incompatible with insoluble cores, and does not limit the invention to sugar spheres only. Third, Applicant’s own disclosure undercuts the disruption argument. The specification describes core particles comprising a core substance and an active ingredient containing layer on the molten component layer and expressly contemplates hydrous silicon dioxide as the core substance and stearic acid as the first melt component. Applicant therefore practiced and claimed the very arrangement they now say would disrupt Li. That is strong evidence that one of ordinary skill in the art would have viewed a stearic acid melt coat on a hydrous silicon dioxide core as operable and desirable not destructive. The remaining claimed limitations are supplied by the other secondary references as described in detail above.
Applicants argue the layer containing Tolterodine L-tartrate deposited on the seal layer of Li does not meet "the active ingredient-containing layer consists of an active ingredient, and a second melt component or a first polymer" of claim 1 because tartaric acid is contained with Tolterodine L-tartrate in the layer of Li.
The above assertions are not found persuasive because the claim recites “a second melt component or a first polymer. Li’s binder (HPMC/Opadry II clear, HPC, PVP, PEG) is a first polymer in the drug layer. Even is Applicant focuses on the melt component alternative , the polymer alternative is independently met by Li. Applicant’s tartaric acid argument does not touch that branch of the limitation. Additionally, no evidence that tartaric acid is required for sitagliptin phosphate layering or that its omission is unexpected.
Applicants argue Senda merely describes a file to coat an uncoated tablet but does not teach or suggest "a film arranged on a surface of the core particle" included in the "film-coated granule" as recited in claim 1. Bukovec was not applied in a manner that attempted to make up for the above-identified deficiencies.
The above assertions are not persuasive because Applicants tablet versus granule distinction attacks Senda in isolation and ignores Li. Li already teaches a film arranged on the surface of the core particles as described above. Senda is relied on for what the film is made of and how it is formed, not for inventing the idea of coating a particle.
Conclusion
No claims are allowed.
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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/TIGABU KASSA/
Primary Examiner, Art Unit 1619
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