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 15 January 2026 are acknowledged and have been fully considered. Claims 1-14, 16, 18, and 20-21 are pending. Claims 1-7, 16, and 20-21 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 Claims 8-14 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species, there being no allowable generic or linking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 15, 17, and 19 are canceled. Applicant’s claim amendments and arguments did not overcome the rejections under 35 USC 103 for reasons set forth in the previous office action and herein below.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
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.
Claims 1-3, 5, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Tidmarsh et al. (WO 2007/012019) in view of Jordan (US Patent. No. 5,630,871) and Stevens et al. (US Patent No. 5,599,577).
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 as recited in the amended claims.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Tidmarsh et al. teach a method for administration of ibuprofen to a subject in need of ibuprofen treatment is provided, in which an oral dosage form comprising a therapeutically effective amount of ibuprofen and a therapeutically effective amount of famotidine, in admixture, is administered three times per day (see abstract). The terms "solid oral dosage form," "oral dosage form," "unit dose form," "dosage form for oral administration," and the like are used interchangably, and refer to a pharmaceutical composition in the form of a tablet, capsule, caplet, gelcap, geltab, pill and the like. b.7 An "excipient," as used herein, is any component of an oral dosage form that is not an API. Excipients include binders, lubricants, diluents, disintegrants, coatings, glidants, and other components. Excipients are known in the art (see HANDBOOK OF PHARMACEUTICAL EXCIPIENTS, FIFTH EDITION, edited by Rowe et al., McGraw Hill). Some excipients serve multiple functions or are so-called high functionality excipients. For example, talc may act as a lubricant, and an anti-adherent, and a glidant. See Pifferi et al., 2005, "Quality and functionality of excipients" Farmaco. 54:1-14; and Zeleznik and Renak, Business Briefing: Pharmagenerics 2004 (see pages 11-12). Unit dose forms of the invention comprise ibuprofen (or other NSAID) in admixture with famotidine and at least one excipient. The unit dose form may be a tablet, caplet, gelcap, or other form. In some embodiments the dosage form includes a core comprising the ibuprofen and famotidine, which core is surrounded by an over coating which may be added to improve appearance, taste, swallowability, or other characteristics of the dosage form. It is preferred that the solid formulation of the present invention is durable to usual external manipulation yet able dissolve at the acceptable rate (see page 27). The term "over-coating," "over-coating layer," or "over-coat" refer to the outer most coating or coatings of a unit dose form such as a tablet or caplet, which may be added to improve appearance, taste, swallowability, or other characteristics of the tablet, caplet, capsule, gelcap, etc. The over coating layer does not contain an API. Suitable over-coatings are soluble in, or rapidly disintegrate in water, and, for purposes of this invention, are not enteric coatings. An exemplary over-coating material is Opadry II available from Colorcon, Inc., Westpoint PA. Materials for making over-coating layer are well known in the art and include, for example and not limitation, materials are described in Pat. No. 4,543,370 (Colorcon), incorporated herein by reference. In one embodiment the over coating comprises a non-toxic edible polymer, edible pigment particles, an edible polymer plasticizer, and a surfactant. A preferred material, "Opadry II" is available from Colorcon (West Point PA USA) and comprises HPMC (which is hydroxypropylmethylcellulose), titanium dioxide, plasticizer and other components (see pages 13-14). In one embodiment the oral dosage form is a tablet. In one embodiment the formulation contains 76-78% ibuprofen; 1.5-2.5% famotidine; 9-11% microcrystalline cellulose; 0.5-1.5% pregelatinized starch, 0.2-1% hydroxypropyl cellulose, 1-3% low substituted hydroxypropyl cellulose, 0.2-1% silicon dioxide, 2-4% silicified microcrystalline cellulose; 0.5-2.5% croscarmellose sodium, and 0.5-2.9 % magnesium stearate (see pages 7-8). A "binder" is an excipient that imparts cohesive qualities to components of a pharmaceutical composition. Commonly used binders include, for example, starch; sugars, such as, sucrose, glucose, dextrose, and lactose; cellulose derivatives such as powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose (SMCC), hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose); and mixtures of these and similar ingredients (see page 12). In one preferred embodiment, the solid tablet carrier contains at least one, and preferably at least two, of the following components: microcrystalline cellulose, croscarmellose sodium, lactose, magnesium stearate, hydroxypropyl cellulose, starch and talc. For example, the unit dose form may contain one or more of the following excipients: 5-15% microcrystalline cellulose, 0.5-5% croscarmellose sodium, 10-85% lactose, 0.5-5% magnesium stearate, 2-6% hydroxypropyl cellulose, 3-15% pregelatinized starch (e.g. Starch 1500) , and/or 1-10% talc. In one embodiment the unit dose form comprises all of the all of the above excipients. It is most preferred, in this embodiment, that the tablet formulation comprises a therapeutically effective amount of ibuprofen or its pharmaceutically acceptable salts, in combination with famotidine with pharmaceutically acceptable excipients in a pharmacokinetically effective ratio. In one embodiment the excipients include microcrystalline cellulose 5-15% by weight, croscarmellose sodium 0.5-5% by weight, lactose 10-85% by weight, magnesium stearate 0.5-5% by weight, hydroxypropyl cellulose 2-6% by weight, pregelatinized starch 3-15% by weight and talc 1-10% by weight (see page 27).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.012)
Tidmarsh et al. do not specifically teach the inclusion of lactose in the coating layer. These deficiencies are cured by the teachings of Jordan.
Jordan teaches a dry film coating composition for use in coating pharmaceuticals, food, confectionery forms, agricultural seeds, and the like, comprises a cellulosic polymer, and lactose (see abstract). A dry film coating composition for forming a coating suspension for film coating pharmaceuticals, food, confectionery forms, and agricultural seeds, comprising a cellulosic polymer, and lactose, the cellulosic polymer being from 11% to 56% by weight of the composition, the lactose being from 11% to 56% by weight of the composition (see claim 1). A preferred formula for the present inventive dry film coating composition is:
______________________________________
COMPONENT % w/w
______________________________________
CELLULOSIC POLYMER 26.80
LACTOSE 40.20
PLASTICIZER 8.00
PIGMENT 25.00
______________________________________
The following examples of the invention all disclose formulations which may be mixed into water to form an aqueous coating suspension effective to coat pharmaceutical tablets, food and confectionery pieces, and agricultural seeds. Seeds are advantageously coated to meet various needs, such as color coating for identification purposes, adhesion of various additives, (e.g., pest control agents and inocula), prevention of handling damage, and facilitating the use of mechanical planting equipment. The coated forms include medicinal tablets, vitamin tablets, aspirin tablets, capsules, chewing gum balls, candy pieces, breakfast cereals, and agricultural seeds (see column 2).
Furthermore, Tidmarsh et al. and Jordan do not specifically teach the amount of famotidine as recited in claims 1 and 5. These deficiencies are cured by the teachings of Stevens et al.
Stevens et al. teach a method of making solid oral dosage form for the treatment of gastrointestinal disorders comprising a therapeutically effective amount of a pharmaceutical suitable for the treatment of gastric disorders selected from the group consisting of cimetidine, ranitidine, famotidine, diphenoxylate, loperamide, loperamide-N-oxide, pharmaceutically acceptable salts thereof and combinations thereof; and a therapeutically effective amount of simethicone wherein the pharmaceutical and simethicone are separated by a barrier. The barrier is formed by coating with a polymer impermeable to simethicone (see abstract). Stevens et al. teach coated famotidine particles with a core granulated using lactose as major diluent and binders, with famotidine at approximately 5-20% (based on 5-40 mg dosage in granules) and coatings free of famotidine using HPMC. Other suitable excipients can be found in the Handbook of Pharmaceutical Excipients, published by the American Pharmaceutical Association which is incorporated herein by reference. The following formulation provides weight percentages (based on the total tablet being 100 weight percent) of the various components of a chewable multilayered tablet:
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that
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 Tidmarsh et al. by incorporating lactose in the coating layer in addition to the polymer HPMC because Jordan et al. a dry film coating composition for use in coating pharmaceuticals, food, confectionery forms, agricultural seeds, and the like, comprises a cellulosic polymer, and lactose (see abstract). A dry film coating composition for forming a coating suspension for film coating pharmaceuticals, food, confectionery forms, and agricultural seeds, comprising a cellulosic polymer, and lactose, the cellulosic polymer being from 11% to 56% by weight of the composition, the lactose being from 11% to 56% by weight of the composition (see claim 1). A preferred formula for the present inventive dry film coating composition is:
______________________________________
COMPONENT % w/w
______________________________________
CELLULOSIC POLYMER 26.80
LACTOSE 40.20
PLASTICIZER 8.00
PIGMENT 25.00
______________________________________
One of ordinary skill in the art would have been motivated to do so because Jordan et al. teach that the following examples of the invention all disclose formulations which may be mixed into water to form an aqueous coating suspension effective to coat pharmaceutical tablets, food and confectionery pieces, and agricultural seeds. Seeds are advantageously coated to meet various needs, such as color coating for identification purposes, adhesion of various additives, (e.g., pest control agents and inocula), prevention of handling damage, and facilitating the use of mechanical planting equipment. The coated forms include medicinal tablets, vitamin tablets, aspirin tablets, capsules, chewing gum balls, candy pieces, breakfast cereals, and agricultural seeds (see column 2). 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). It is within the purview of the skilled artisan to optimize result effective parameters such as amounts and concentrations of active and inactive ingredients. The skilled artisan would have had a reasonable expectation of success in combining the teachings of Tidmarsh et al. and Jordan et al. because both references teach pharmaceutical formulations with coating layers.
It would have been prima facie obvious before the effective filing date of the instant application to modify the teachings of Tidmarsh et al. and Jordan by including famotidine in amounts as recited in claims 1 and 5 because Stevens et al. teach a method of making solid oral dosage form for the treatment of gastrointestinal disorders comprising a therapeutically effective amount of a pharmaceutical suitable for the treatment of gastric disorders selected from the group consisting of cimetidine, ranitidine, famotidine, diphenoxylate, loperamide, loperamide-N-oxide, pharmaceutically acceptable salts thereof and combinations thereof; and a therapeutically effective amount of simethicone wherein the pharmaceutical and simethicone are separated by a barrier. The barrier is formed by coating with a polymer impermeable to simethicone (see abstract). One of ordinary skill in the art would have been motivated to do so because Stevens et al. teach coated famotidine particles with a core granulated using lactose as major diluent and binders, with famotidine at approximately 5-20% (based on 5-40 mg dosage in granules) and coatings free of famotidine using HPMC. Other suitable excipients can be found in the Handbook of Pharmaceutical Excipients, published by the American Pharmaceutical Association which is incorporated herein by reference. The following formulation provides weight percentages (based on the total tablet being 100 weight percent) of the various components of a chewable multilayered tablet:
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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). It is within the purview of the skilled artisan to optimize result effective parameters such as amounts and concentrations of active and inactive ingredients. The skilled artisan would have had a reasonable expectation of success in combining the teachings of Tidmarsh et al., Jordan et al., and Stevens et al. because all of the references teach pharmaceutical formulations with coating layers.
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) 4 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tidmarsh et al. (WO 2007/012019) in view of Jordan (US Patent. No. 5,630,871) and Stevens et al. (US Patent No. 5,599,577) as applied to claims 1-3, 5, and 16 above, and further in view of Rubino (US 2008/0254115).
Note: The claims are examined with respect to the elected species only wherein microcrystalline cellulose as the specific biocompatible excipient; at least one of lactose, croscarmellose sodium and/or stearic acid as the specific one of more pharmaceutically acceptable additives, binders, or fillers.
Applicant Claims
Applicant claims “A coated famotidine particle having at least a core and a coating layer, wherein the particle core comprises from 5% to 20% w/w of famotidine, from 70% to 98% w/w of a first filler and from 2% to 10% w/w of a first binder, and the coating layer is substantially free from famotidine and comprises a second filler and a second binder, wherein the first and second filler may be similar or different; and selected from the group consisting of lactose, microcrystalline cellulose, starch, dextrose, mannitol, sorbitol, xylitol, maltitol or combination thereof and wherein the first and second binder may be similar or different, and selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, polyvinylpyrrolidone, Sodium Carboxymethylcellulose, Ethyl cellulose, Polyvinyl alcohol-povidone copolymer, pregelatinized starch, or combination thereof.” 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 Tidmarsh et al., Jordan, and Stevens et al. 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)
Tidmarsh et al., Jordan, and Stevens et al. do not specifically teach the coating levels as recited in claim 4 and the particle size limitations recited as recited in claim 7. These deficiencies are cured by the teachings of Rubino.
Rubino teaches a novel pellets adapted for biologically active preparations and a novel process for preparing said pellets. The novel pellets are adapted for use in the delivery of a biologically active agent. The pellets have an inner zone comprising a plurality of micropellets which are bound together to form a pellet when the micropellets are dispersed in a matrix of an inert pharmaceutical excipient, a biologically active agent and optionally having an outer zone comprising a surface layer comprising a pharmaceutical excipient with or without a biologically active agent. The pellets will have an arcuate surface due to the manner in which they are formed (see abstract). As used herein the term "micropellet" means a shaped particle which may have an irregular shape, a spherical shape or a cubic shape having a aspect ratio (a ratio of the length of the pellet divided by the width found at an angle of 90° in respect to the length) which is less than about 1.4, more preferably less than about 1.3, even more preferably less than about 1.2, especially preferably less than about 1.1, and most preferably less than about 1.05 and an approximate average diameter of 50 to 500 microns, preferably 50 to 200 microns (paragraph 0005). Generally the micropellets according to the invention will have an average diameter of from 50 to 500 microns or preferably from 50 to 200 microns. The layer or layers on the pellets will preferably be from 1-10% of the total thickness of the pellet and more preferably from 1 to 5% of the thickness of the pellet. The pellets, of a specific composition, prepared according to the invention preferably have a narrow particle size distribution such that a maximum of 20% by weight of the pellets have a diameter deviating from the average diameter of all by more than 20%. Preferably, a maximum of 10% by weight of the pellets have a diameter deviating from the average diameter of all, by more than 20%. Further preferably, a maximum of 20% by weight of the pellets have a diameter deviating from the average diameter of all pellets by more than 10% by weight. An especially preferred micropellet product has a particle size distribution such that a maximum of 10% by weight of the pellets have a diameter deviating from the average diameter of all pellets by more than 10% by weight. All percents by weight are based on the total weight of the pellets (paragraph 0024). Generally the pellets according to the invention will have an average diameter of from 0.25 mm to 2.5 mm, and preferably from 0.70 mm to 1.5 mm. All percents by weight are based on the total weight of the pellets (paragraph 0025).
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 Tidmarsh et al., Jordan, and Stevens et al. by preparing active including particles with particle sizes as recited in claim 7 and coating levels as recited in claim 4 because Rubino teaches a novel pellets adapted for biologically active preparations and a novel process for preparing said pellets. The novel pellets are adapted for use in the delivery of a biologically active agent. The pellets have an inner zone comprising a plurality of micropellets which are bound together to form a pellet when the micropellets are dispersed in a matrix of an inert pharmaceutical excipient, a biologically active agent and optionally having an outer zone comprising a surface layer comprising a pharmaceutical excipient with or without a biologically active agent. The pellets will have an arcuate surface due to the manner in which they are formed (see abstract). As used herein the term "micropellet" means a shaped particle which may have an irregular shape, a spherical shape or a cubic shape having a aspect ratio (a ratio of the length of the pellet divided by the width found at an angle of 90° in respect to the length) which is less than about 1.4, more preferably less than about 1.3, even more preferably less than about 1.2, especially preferably less than about 1.1, and most preferably less than about 1.05 and an approximate average diameter of 50 to 500 microns, preferably 50 to 200 microns (paragraph 0005). Generally the micropellets according to the invention will have an average diameter of from 50 to 500 microns or preferably from 50 to 200 microns. The layer or layers on the pellets will preferably be from 1-10% of the total thickness of the pellet and more preferably from 1 to 5% of the thickness of the pellet. The pellets, of a specific composition, prepared according to the invention preferably have a narrow particle size distribution such that a maximum of 20% by weight of the pellets have a diameter deviating from the average diameter of all by more than 20%. Preferably, a maximum of 10% by weight of the pellets have a diameter deviating from the average diameter of all, by more than 20%. Further preferably, a maximum of 20% by weight of the pellets have a diameter deviating from the average diameter of all pellets by more than 10% by weight. An especially preferred micropellet product has a particle size distribution such that a maximum of 10% by weight of the pellets have a diameter deviating from the average diameter of all pellets by more than 10% by weight. All percents by weight are based on the total weight of the pellets (paragraph 0024). Generally the pellets according to the invention will have an average diameter of from 0.25 mm to 2.5 mm, and preferably from 0.70 mm to 1.5 mm. All percents by weight are based on the total weight of the pellets (paragraph 0025). Accordingly, it is a primary object of the present invention to provide novel pellets which are useful for the delivery of biologically active agents (paragraph 0030). 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). 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. The skilled artisan would have had a reasonable expectation of success in combining the teachings of Tidmarsh et al., Jordan, Stevens et al., and Rubino because all of the references teach active containing particles coated with a layer.
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 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tidmarsh et al. (WO 2007/012019) in view of Jordan (US Patent. No. 5,630,871) and Stevens et al. (US Patent No. 5,599,577) as applied to claims 1-3, 5, and 16 above, and further in view of Roy (WO2013054352).
Note: The claims are examined with respect to the elected species only wherein microcrystalline cellulose as the specific biocompatible excipient; at least one of lactose, croscarmellose sodium and/or stearic acid as the specific one of more pharmaceutically acceptable additives, binders, or fillers.
Applicant Claims
Applicant claims “A coated famotidine particle having at least a core and a coating layer, wherein the particle core comprises from 5% to 20% w/w of famotidine, from 70% to 98% w/w of a first filler and from 2% to 10% w/w of a first binder, and the coating layer is substantially free from famotidine and comprises a second filler and a second binder, wherein the first and second filler may be similar or different; and selected from the group consisting of lactose, microcrystalline cellulose, starch, dextrose, mannitol, sorbitol, xylitol, maltitol or combination thereof and wherein the first and second binder may be similar or different, and selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, polyvinylpyrrolidone, Sodium Carboxymethylcellulose, Ethyl cellulose, Polyvinyl alcohol-povidone copolymer, pregelatinized starch, or combination thereof.” Dependent claims thereof recite further thickness of the coating layer.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
The teachings of Tidmarsh et al., Jordan, and Stevens et al. 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)
Tidmarsh et al., Jordan, and Stevens et al. do not specifically teach the thickness of the coating layer. These deficiencies are cured by the teachings of Roy et al.
Roy et al. teach a stable pharmaceutical composition in a single unit dosage form comprising: plurality of multiple unit particles (MUPS) comprising ibuprofen or salt thereof; and plurality of multiple unit particles (MUPS) comprising famotidine or salt thereof in direct physical contact with ibuprofen MUPS (see claim 6). The composition as claimed in claim6, wherein the multiple unit particles are coated with a barrier layer (see claim 7). The composition as claimed in claim 1 or 7, wherein the barrier layer comprises a polymer selected from hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and ethyl cellulose; methacrylic polymers, amino-alkylmethacrylate copolymers, polyvinyl acetate phthalate or polyvinyl alcohol (see claim 8). The composition as claimed in claim 1 or 7, wherein the barrier layer has a thickness ranging from 20 to 3,000 microns (see claim 9). The composition as claimed in claim 1 or 7, wherein the barrier layer has a thickness ranging from 25 to 250 microns (see claim 10).
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 Tidmarsh et al., Jordan, and Stevens et al. by preparing a coating layer with thickness values as recited in claim 6 because Roy et al. teach a stable pharmaceutical composition in a single unit dosage form comprising: plurality of multiple unit particles (MUPS) comprising ibuprofen or salt thereof; and plurality of multiple unit particles (MUPS) comprising famotidine or salt thereof in direct physical contact with ibuprofen MUPS (see claim 6). The composition as claimed in claim6, wherein the multiple unit particles are coated with a barrier layer (see claim 7). The composition as claimed in claim 1 or 7, wherein the barrier layer comprises a polymer selected from hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and ethyl cellulose; methacrylic polymers, amino-alkylmethacrylate copolymers, polyvinyl acetate phthalate or polyvinyl alcohol (see claim 8). The composition as claimed in claim 1 or 7, wherein the barrier layer has a thickness ranging from 20 to 3,000 microns (see claim 9). The composition as claimed in claim 1 or 7, wherein the barrier layer has a thickness ranging from 25 to 250 microns (see claim 10). One of ordinary skill in the art would have been motivated to do so because The thickness of the barrier and/or protective layer can vary over a wide range, but is generally in the range 20 to 3,000 microns, such as on the order of about 25 to 250 microns. Preferably the barrier layer retards the release of famotidine by less than 5 minutes, preferably less than 4 minutes and more preferably by less than 3 minutes (see page 7). Furthermore, in the case where the claimed ranges for the amounts, concentrations of active agent and other ingredients or thickness values 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). 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. The skilled artisan would have had a reasonable expectation of success in combining the teachings of Tidmarsh et al., Jordan, Stevens et al., and Roy because all of the references teach active containing particles coated with a layer.
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.
Response to Arguments
Applicant's arguments filed 15 January 2026 have been fully considered but they are not persuasive.
Applicant argues Tidmarsh provides general statements about coatings (see paragraph 6.14) but fails to provide any details about the formulation of any coating, composition or respective proportion of components. No example of coating is provided. Jordan teaches a coating with a maximum of 56% of lactose, compared to more than 90% in the present invention claim 1. Jordan teaches a coating with a minimum of 11% of HPMC, compared to less than 5% in the present invention claim 1. Jordan fails to teach a coating layer according to currently amended claim 1. Stevens is silent about a percentage of famotidine in a dosage form. Knowing the daily dosage of famotidine is not enough for a person skilled in the art to deduce a percentage of famotidine per coated famotidine particle.
The above assertions are not found persuasive because first the rejection is based on the combined teachings of the references. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). With regard to the amounts of ingredients and active absent a showing of criticality for those amounts it is within the purview of one of ordinary skill in the art to optimize the amounts. With regard to the lactose and HPMC Tidmarsh et al. teach a method for administration of ibuprofen to a subject in need of ibuprofen treatment is provided, in which an oral dosage form comprising a therapeutically effective amount of ibuprofen and a therapeutically effective amount of famotidine, in admixture, is administered three times per day (see abstract). The terms "solid oral dosage form," "oral dosage form," "unit dose form," "dosage form for oral administration," and the like are used interchangably, and refer to a pharmaceutical composition in the form of a tablet, capsule, caplet, gelcap, geltab, pill and the like. b.7 An "excipient," as used herein, is any component of an oral dosage form that is not an API. Excipients include binders, lubricants, diluents, disintegrants, coatings, glidants, and other components. Excipients are known in the art (see HANDBOOK OF PHARMACEUTICAL EXCIPIENTS, FIFTH EDITION, edited by Rowe et al., McGraw Hill). Some excipients serve multiple functions or are so-called high functionality excipients. For example, talc may act as a lubricant, and an anti-adherent, and a glidant. See Pifferi et al., 2005, "Quality and functionality of excipients" Farmaco. 54:1-14; and Zeleznik and Renak, Business Briefing: Pharmagenerics 2004 (see pages 11-12). Unit dose forms of the invention comprise ibuprofen (or other NSAID) in admixture with famotidine and at least one excipient. The unit dose form may be a tablet, caplet, gelcap, or other form. In some embodiments the dosage form includes a core comprising the ibuprofen and famotidine, which core is surrounded by an over coating which may be added to improve appearance, taste, swallowability, or other characteristics of the dosage form. It is preferred that the solid formulation of the present invention is durable to usual external manipulation yet able dissolve at the acceptable rate (see page 27). The term "over-coating," "over-coating layer," or "over-coat" refer to the outer most coating or coatings of a unit dose form such as a tablet or caplet, which may be added to improve appearance, taste, swallowability, or other characteristics of the tablet, caplet, capsule, gelcap, etc. The over coating layer does not contain an API. Suitable over-coatings are soluble in, or rapidly disintegrate in water, and, for purposes of this invention, are not enteric coatings. An exemplary over-coating material is Opadry II available from Colorcon, Inc., Westpoint PA. Materials for making over-coating layer are well known in the art and include, for example and not limitation, materials are described in Pat. No. 4,543,370 (Colorcon), incorporated herein by reference. In one embodiment the over coating comprises a non-toxic edible polymer, edible pigment particles, an edible polymer plasticizer, and a surfactant. A preferred material, "Opadry II" is available from Colorcon (West Point PA USA) and comprises HPMC (which is hydroxypropylmethylcellulose), titanium dioxide, plasticizer and other components (see pages 13-14). In one embodiment the oral dosage form is a tablet. In one embodiment the formulation contains 76-78% ibuprofen; 1.5-2.5% famotidine; 9-11% microcrystalline cellulose; 0.5-1.5% pregelatinized starch, 0.2-1% hydroxypropyl cellulose, 1-3% low substituted hydroxypropyl cellulose, 0.2-1% silicon dioxide, 2-4% silicified microcrystalline cellulose; 0.5-2.5% croscarmellose sodium, and 0.5-2.9 % magnesium stearate (see pages 7-8). A "binder" is an excipient that imparts cohesive qualities to components of a pharmaceutical composition. Commonly used binders include, for example, starch; sugars, such as, sucrose, glucose, dextrose, and lactose; cellulose derivatives such as powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose (SMCC), hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose); and mixtures of these and similar ingredients (see page 12). In one preferred embodiment, the solid tablet carrier contains at least one, and preferably at least two, of the following components: microcrystalline cellulose, croscarmellose sodium, lactose, magnesium stearate, hydroxypropyl cellulose, starch and talc. For example, the unit dose form may contain one or more of the following excipients: 5-15% microcrystalline cellulose, 0.5-5% croscarmellose sodium, 10-85% lactose, 0.5-5% magnesium stearate, 2-6% hydroxypropyl cellulose, 3-15% pregelatinized starch (e.g. Starch 1500) , and/or 1-10% talc. In one embodiment the unit dose form comprises all of the all of the above excipients. It is most preferred, in this embodiment, that the tablet formulation comprises a therapeutically effective amount of ibuprofen or its pharmaceutically acceptable salts, in combination with famotidine with pharmaceutically acceptable excipients in a pharmacokinetically effective ratio. In one embodiment the excipients include microcrystalline cellulose 5-15% by weight, croscarmellose sodium 0.5-5% by weight, lactose 10-85% by weight, magnesium stearate 0.5-5% by weight, hydroxypropyl cellulose 2-6% by weight, pregelatinized starch 3-15% by weight and talc 1-10% by weight (see page 27). The amounts either overlap in scope or they are close enough to be optimized to the claimed amounts. 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). It is within the purview of the skilled artisan to optimize result effective parameters such as amounts and concentrations of active and inactive ingredients.
Conclusion
No claim is 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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