COATED FAMOTIDINE PARTICLE

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 . Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04 August 2026 has been entered. Formal Matters Applicant’s claim amendments and arguments in the reply filed on 04 August 2026 are acknowledged and have been fully considered due to the entered request for continued examination. Claims 1-3, 5-14, 16, 18, and 20-22 are pending. Claims 1-3, 5-7, 16, and 20-22 are under consideration in the instant office action. Claims 8-14 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Claims 4, 15, 17, and 19 are canceled. Applicant’s claim amendments and arguments necessitated a new rejection. Withdrawn Objections/Rejections Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn. New Rejections-Necessitated by Amendments 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. Claims 1–3, 5, 16, and 20–22 are rejected under 35 U.S.C. 103 as being unpatentable over Roche et al. (US 5,460,825, newly cited) in view of Oshlack et al. (US 6,077,533, newly cited). Note: The claims are examined with respect to the elected species only wherein lactose as the first and second filler; hydroxypropylmethylcellulose as the first and second binder; and amorphous silicon dioxide as the flowing agent. Applicant Claims Applicant claims a coated famotidine particle comprising at least one core and a coating layer, wherein: the core comprises 5–20% w/w famotidine, 70–93% w/w first filler, and 2–10% w/w first binder; the coating contains <5% w/w famotidine and comprises a second filler and a second binder; the coating comprises >90% w/w second filler and <5% w/w second binder (coat basis); fillers are selected from lactose, MCC, starch, dextrose, mannitol, sorbitol, xylitol, maltitol, and combinations; binders are selected from HPMC, HPC, MC, PVP, NaCMC, EC, PVA-povidone copolymer, pregelatinized starch, and combinations; and the coating accounts for 10–30% w/w of the particle. Determination of the Scope and Content of the Prior Art (MPEP §2141.01) Roche teaches chewable tablets made from coated rotogranules of famotidine. The rotogranules are formed from medicament (famotidine), binder (HPMC), and carrier (lactose), then coated. col. 1, ll. 6–20; abstract. Preferred rotogranulation: about 2 to 85% famotidine, about 4 to 10% HPMC, and about 10 to 94% lactose, by weight of the rotogranulation. col. 3, ll. 15–25. Example I: 5.2 kg famotidine + 2.4 kg HPMC E5 + 32.4 kg lactose. That is approximately 13.0% famotidine, 6.0% HPMC, and 81.0% lactose in the core — inside claim 1’s 5–20/ 2–10 / 70–93 windows, and the elected species. col. 4, ll. 20–35. Example IX coated rotogranules: famotidine 10 mg, HPMC (granulation) 4.62 mg, lactose 62.31 mg, cellulose acetate 6.65 mg, HPC (coating) 2.85 mg; total coated granule 86.43 mg. Coat solids are 9.5 mg ≈ 11% of coated-particle weight, which sits inside 10–30%. col. 5 table. Roche teaches the coat is for taste masking and that the granules are compressed with tableting excipients. Flow/tableting of coated granules is an express purpose. col. 2–3. Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012) Roche does not teach a coating layer that is >90% lactose (or other claimed filler) and <5% binder on a coat-weight basis. Roche’s working coat is a CA/HPC polymer film. These deficiencies are cured by the teachings of Oshlack. Oshlack teaches powder-layered lactose coat, 10–100% weight gain, HPMC binder.Oshlack teaches powder-layering a homogeneous powder onto inert beads (0.1–2.5 mm) using an aqueous binder spray until the beads achieve a weight gain of at least about 10% to about 100%. abstract; claim 12; col. 2. The powdered material consists essentially of hydrous lactose impalpable. claim 12; col. 3–4. Binders include hydroxypropylmethylcellulose, PVP, HPC, CMC, methylcellulose, and starch. col. 6, ll. 15–30. Aqueous binder solutions are preferred. col. 6. The process: spray binder onto the substrate to make a tacky surface, then powder-layer the lactose (or lactose/drug) powder. claim 12 steps (b)–(c). In that unit operation the solids deposited as the layer are predominantly the powder (lactose); the binder is applied as a dilute solution and remains a minor fraction of the dry coat. That is the definition of powder layering as distinguished from polymer film coating. Oshlack further coats the powder-layered beads with a hydrophilic material, expressly including HPMC. claims 10–11. Particle diameters of the starting beads are 0.1 mm to 2.5 mm (100–2500 µm). claim 12. Roche has the elected famotidine/lactose/HPMC core at claimed percentages and a coat at ~11% of particle weight, but the coat is CA/HPC rather than >90% lactose / <5% HPMC. Oshlack has powder layering of lactose with an HPMC (or other claimed) binder spray to 10–100% weight gain, which necessarily produces a layer that is filler-rich and binder-poor. Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-2143) It would have been obvious before the effective filing date to replace Roche’s CA/HPC film with Oshlack’s lactose powder layer applied with a dilute aqueous HPMC spray, at a weight gain in the overlapping 10–30% range.One of ordinary skill in the art making Roche’s famotidine/lactose/HPMC granules for taste masking and later tableting would have looked to known alternative coats. Oshlack teaches powder layering of the same filler Roche already uses in the core (impalpable lactose) with the same binder Roche already uses (HPMC), specifically to build a multiparticulate layer at 10–100% weight gain. One of ordinary skill in the art would have been motivated to do so because same materials already on the Roche bill of materials; powder layering is a standard way to put a high-filler, low-binder shell on granules for flow, bulk, and isolation of a bitter API (Roche’s purpose); and 10–30% is inside Oshlack’s 10–100% and already exemplified by Roche’s ~11% coat level. One of ordinary skill in the art would have had areasonable expectation of success because both references granulate/layer oral solids with lactose and cellulosic binders in fluid-bed/rotor equipment. Once the layer is built by feeding lactose powder while spraying dilute HPMC, the dry coat is necessarily mostly lactose. Selecting binder spray solids so that dried HPMC is <5% of the coat (and lactose >90%) is ordinary optimization of a result-effective variable (tack vs. coat purity) with no evidence of criticality. In re Aller, 220 F.2d 454, 456 (CCPA 1955); In re Wertheim, 541 F.2d 257 (CCPA 1976). Residual famotidine in that coat of <5% follows from layering a drug-free lactose powder onto the core, which is Oshlack’s inert-powder embodiment and Roche’s isolation goal. Regarding claim 2 Roche Example I and the preferred description use lactose and HPMC as both carrier and binder. Oshlack layers lactose with HPMC binder. Elected species is taught. Regarding claim 3 Roche and Oshlack teach pharmaceutical granules/beads. Colloidal silica / silicon dioxide is a conventional glidant in this exact art (Roche tableting; Oshlack processing aids). Adding a flowing agent selected from silica, colloidal silica, fumed silica, or aluminometasilicate to the Roche core is obvious. KSR, 550 U.S. 398 (2007) (known element for its known function). Regarding claim 5 Roche Example I core is ~13% FAM of the granule. After a 10–30% lactose coat, FAM on a coated-particle basis is about 10–12% (13% × 0.70 to 0.90), inside 10–15%. Binders 3–10%, fillers 75–90%, and glidant 0.1–1% on a coated-particle basis are the same Roche/Oshlack materials in overlapping amounts. Coat FAM <5% is the drug-free powder layer. Regarding claim 16 Roche’s coated famotidine granules are for oral treatment of GI conditions (H2 antagonist). The “for use” clause does not distinguish the particle. Roche Example I (~13% FAM in core before coat; ~10–12% after 10–30% coat; ~6% HPMC in core plus minor coat binder; lactose majority) sits inside 12–14% FAM in core, 5–6.5% binders, 80–83% fillers, and 0.5–0.7% glidant as routine optimization of the same recipe. Regarding claim 21 Roche is famotidine for gastric acid-related disorders. Heartburn, GERD, dyspepsia, and gastritis are the labeled uses of famotidine and do not patentably distinguish the particle. Regarding claim 22 Oshlack and Roche permit processing aids in the powder. Limiting flowing agent in the coat to <2% w/w is consistent with a lactose powder layer that is >90% filler. Silica at 0–2% of a layering powder is conventional. Furthermore, in the case where the claimed ranges for the amounts, concentrations of active agent and other ingredients “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 and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985). Furthermore, generally differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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). 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 before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary. Claim(s) 6 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Roche et al. (US 5,460,825, newly cited) in view of Oshlack et al. (US 6,077,533, newly cited) as applied to claims 1–3, 5, 16, and 20–22 above, and further in view of Rubino (US 2008/0254115, previously cited) and Roy (WO 2013/054352, previously cited). Applicant Claims Applicant claims a coated famotidine particle comprising at least one core and a coating layer, wherein: the core comprises 5–20% w/w famotidine, 70–93% w/w first filler, and 2–10% w/w first binder; the coating contains <5% w/w famotidine and comprises a second filler and a second binder; the coating comprises >90% w/w second filler and <5% w/w second binder (coat basis); fillers are selected from lactose, MCC, starch, dextrose, mannitol, sorbitol, xylitol, maltitol, and combinations; binders are selected from HPMC, HPC, MC, PVP, NaCMC, EC, PVA-povidone copolymer, pregelatinized starch, and combinations; and the coating accounts for 10–30% w/w of the particle. Dependent claims thereof recite further thickness and particle size features. Determination of the Scope and Content of the Prior Art (MPEP §2141.01) The teachings of Roche and Oshlack are described in detail above and are incorporated herein by reference. Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012) Roche and Oslack do not specifically teach coat thickness in microns Claim 6 (coat thickness 50–300 µm) and the particle size as recited in claim 7. These deficiencies are cured by the teachings of Roy and Rubino. Roy teaches famotidine multiparticulates with a barrier layer of HPMC, HPC, or ethylcellulose having thickness 20 to 3,000 µm, preferably 25 to 250 µm. claims 8–10; p. 7. 50–300 µm overlaps 25–250 µm. One of ordinary skill in the art applying Oshlack’s 10–30% lactose/HPMC powder layer to Roche granules would land in that thickness band for particles a few hundred microns across. One of ordinary skill in the art would have been motivated to do so because Roy uses the same polymer family on famotidine particles to isolate the API. Regarding claim 7 Oshlack beads start at 0.1–2.5 mm (100–2500 µm). claim 12. Rubino teaches micropellets of average diameter 50 to 500 µm, preferably 50–200 µm, and finished pellets 0.25–2.5 mm, with a narrow PSD, paragraphs 0005, 0024–0025. 200–500 µm is inside both ranges. Selecting a cut in that window for flow and content uniformity of coated famotidine granules is routine. Roche already screens rotogranules before coating. Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-2143) It would have been prima facie obvious before the effective filing date of the instant application to modify the teachings of Roy and Oshlack to meet the limitations of claims 6 and 7 because Roy teaches famotidine multiparticulates with a barrier layer of HPMC, HPC, or ethylcellulose having thickness 20 to 3,000 µm, preferably 25 to 250 µm. claims 8–10; p. 7. 50–300 µm overlaps 25–250 µm. One of ordinary skill in the art applying Oshlack’s 10–30% lactose/HPMC powder layer to Roche granules would land in that thickness band for particles a few hundred microns across. One of ordinary skill in the art would have been motivated to do so because Roy uses the same polymer family on famotidine particles to isolate the API. Regarding claim 7 Oshlack beads start at 0.1–2.5 mm (100–2500 µm). claim 12. Rubino teaches micropellets of average diameter 50 to 500 µm, preferably 50–200 µm, and finished pellets 0.25–2.5 mm, with a narrow PSD, paragraphs 0005, 0024–0025. 200–500 µm is inside both ranges. Selecting a cut in that window for flow and content uniformity of coated famotidine granules is routine. Roche already screens rotogranules before coating. Furthermore, in the case where the claimed ranges for the amounts, concentrations of active agent and other ingredients, particle sizes “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 and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985). Furthermore, generally differences in concentration or particle size will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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). It is within the purview of the skilled artisan to optimize result effective parameters such as amounts and concentrations of active and inactive ingredients such as croscarmellose sodium. 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 before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIGABU KASSA whose telephone number is (571)270-5867. The examiner can normally be reached on 8 AM-5 PM. 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://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /TIGABU KASSA/Primary Examiner, Art Unit 1619