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 16 October 2025 are acknowledged and have been fully considered. Claims 4-8, 11, 16, and 19 are pending. Claims 11, 16, and 19 are under consideration in the instant office action. Claims 4-8 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking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 1-3, 9-10, 12-15, and 17-18 are canceled. Applicant’s claim amendments necessitated a new ground of rejections under 35 USC 112 as set forth below. Accordingly, this office action is made Final.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11, 16, and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “wherein the discontinuity layer is a laminar space” renders the claim indefinite because the phrase ‘laminar space” is unclear and lacks a precise meaning to one of ordinary skill in the art. The specification discloses on paragraph 0057 “Further, in one embodiment, the drug-containing particle of the present embodiment has a discontinuity layer between the raw material particle and the coating layer. The “discontinuity layer” here refers to a laminar space existing between the raw material particle being at the center of the particle and the coating layer enclosing the raw material particle, which can be observed with, for example, an electron microscope or an optical microscope.” This disclosure in the original specification does not provide a clear definition of ‘laminar space,” and the term “laminar” as conventionally known is commonly associated with fluid dynamics (e.g., smooth, parallel-layered flow without turbulence), which does not readily apply to static structural element like a discontinuity layer in a particle composition. It is uncertain whether “laminar space” refers to a space with a specific shape (e.g., flat or sheet-like), a layered space with particular dimensions or properties, a space allowing for laminar fluid movement within the particle, or something else entirely. Without clarification, one of ordinary skill in the art cannot determine the metes and bounds of the claim, such as how to identify or measure a “laminar space” versus a nonlaminar one, or what structural features distinguish it from a generic space. For examination purposes, the phrase ‘laminar space” is interpreted as any space between the core and the coating layer. Dependent claims 16 and 19 do not clarify the issue. Hence, claims 16 and 19 are incorporated in the rejection for carrying the indefinite phrase.
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.
Note: The claims are examined with respect to the elected species only wherein crystalline cellulose as the raw material particle, hydroxypropyl cellulose as the elected polymer for coating and levofloxacin as the drug type.
Claim(s) 11, 16, and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over Pathak et al. (WO 2009/121178, previously cited) in view of Rudnic et al. (US Patent No. 6,667,057, previously cited) and Vladyka et al. (US Patent No. 6,858,725, previously cited).
Note: The claims are examined with respect to the elected species only wherein crystalline cellulose as the raw material particle, hydroxypropyl cellulose as the elected polymer for coating and levofloxacin as the drug type.
Applicants’ claims
Applicant claims in claim 11 “A composition comprising a plurality of drug-containing particles, wherein: each drug-containing particle comprises: a raw material particle comprising a pharmaceutically acceptable additive, wherein the raw material particle does not comprise a drug; a coating layer comprising a drug; and a discontinuity layer between the raw material particle and the coating layer, wherein the discontinuity layer is a laminar space; and the plurality of drug-containing particles have a particle-size distribution span of not more than 1.0 and a compressibility of not more than 14%.”
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Pathak et al. teach a controlled-release bead containing a pharmaceutically active ingredient, the controlled-release bead comprising:
(a) a core made of a substantially water-insoluble inert material;
(b) a first layer disposed over the core, the first layer comprising a substantially water-soluble polymer;
(c) a second layer disposed over the first layer, the second layer containing the pharmaceutically active ingredient and a polymer; and
(d) a third layer disposed over the second layer, the third layer comprising a controlling release polymeric system (see claim 1). The controlled-release bead according to claim 1 or 2, wherein the core is made of materials selected from the group consisting of: microcrystalline cellulose and starch (see claim 3). The controlled-release bead according to any one of claims 1 to 3, wherein the core has a diameter ranging from about 0.05 to about 2 mm (see claim 4). The controlled-release bead according to any one of claims 1 to 4, wherein the amount of water-soluble polymer in the first layer is in the range from about 2% to about 30% by weight of the controlled-release bead (see claim 5). The controlled-release bead according to any one of claims 1 to 5, wherein the second layer constitutes from about 0.1% to about 30% by weight of the controlled release bead (see claim 6). The controlled-release bead according to any one of claims 1 to 10, wherein the water-soluble polymer of the first layer is selected from the group consisting of: cellulose ethers, povidone, and copovidone. Pathak et al. teach in Example 1 A bead according to a preferred embodiment of the present invention containing tolterodine L-tartrate as the pharmaceutical active ingredient has the following components: Core - MCC spheres (manufactured by Celphere®) comprising about 70% w/w of the final bead. These MCC spheres are used as substrate on which further coatings can be applied. First layer - comprises a water soluble polymer and consists about 5% w/w of the final bead. Since MCC is known to adsorb drug on its surface, it is important to provide a seal coat (which is equivalent to the discontinuity layer in claim 11) on the MCC spheres which also provides a uniform surface to undergo further processing (coating). This is achieved by providing a water soluble coat using hydroxypropylcellulose (HPC) as the film forming polymer (the examiner notes that both the MCC and the HPC layer do not contain drug).The examiner takes the position as per the detailed explanation provided in the 35 USC 112 rejection above the phrase, for examination purposes, the phrase ‘laminar space” is interpreted as any space between the core and the coating layer. Therefore, with the broadest reasonable interpretation (BRI) of the phrase, the seal coat which exists between the raw material particle (microcrystalline cellulose) and the coating layer comprising a drug entails or reads on laminar space.
Second layer - a pharmaceutically acceptable active ingredient, in this case, tolterodine L-tartrate, combined with a polymer, such as for example HPC. The second layer comprises about 12.2 % w/w of the final bead. The w/w ratio of active ingredient to polymer is about 1:5. The purpose of this second layer is to act as a drug supply. The examiner equates this as the coating comprising active agent).
Third layer - combination of ethylcellulose and HPC. The third layer comprises about 13% w/w of the final bead. The w/w ratio of ethylcellulose to HPC is about 90:10 . The purpose of this third layer is to achieve drug release rate control.
A wide variety of pharmaceutically active ingredients may be used in conjunction with the present invention. While the active ingredient usually is a low or medium dose drug, also high-dose drugs may be contemplated for use in the present invention. An exemplary class of compounds which may be used as active ingredients in the present invention include any active ingredient listed in the Compendium of Pharmaceuticals and specialties ("CPS"), in particular tolterodine, their pharmaceutically acceptable salts with physiologically acceptable acids and, when the compounds can be in the form of optical isomers, the racemic mixture and the individual enantiomers. It is of course to be understood herein that any salt, ester, analog, and prodrugs of a pharmaceutically acceptable active ingredient may be used in accordance with the present invention.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Pathak et al. do not specifically teach the elected active levofloxacin as called in claim 11. This deficiency is cured by the teachings of Rudnic et al.
Rudnic et al. teach an antibiotic product, in particular levofloxacin, is comprised of at least three dosages forms, each of which has a different release profile, with the Cmax for the antibiotic product being reached in less than about twelve hours. In one embodiment, there is an immediate release dosage form, as well as two or more delayed release dosage forms, with each of the dosage forms having a different release profile, wherein each reaches a Cmax at different times (see abstract). This invention relates to an antibiotic product, as well as the use and formulation thereof. The invention further relates to a levofloxacin antibiotic product, including derivatives thereof such as salts, esters, metabolites, etc. A wide variety of antibiotics have been used, and will be used, in order to combat bacterial infection. In general, such antibiotics can be administered by a repeated dosing of immediate release dosage forms, which results in poor compliance or as a controlled release formulation (slow release) at higher administered doses. The present invention is directed to providing for an improved antibiotic product. In accordance with one aspect of the present invention, there is provided an antibiotic pharmaceutical product which is comprised of at least two, preferably at least three, antibiotic dosage forms. Such dosage forms are formulated so that each of the dosage forms has a different release profile.
Pathak et al. and Rudnic et al. are silent with regard to the plurality of drug -containing particles having a particle-size distribution span of not more than 1.0 and a compressibility of not more than 14%. These deficiencies are cured by the teachings of Vladyka et al. and the prima facie arguments set forth below.
Vladyka et al. teach granulation of microcrystalline cellulose with a granulating fluid consisting of water and a water-miscible, volatile, polar organic solvent yields porous granules which are comprised of particles that are larger than the ungranulated microcrystalline cellulose. This granulated microcrystalline cellulose is capable of cushioning controlled release particles and barrier coated particles from the compression forces used in tableting, thereby maintaining the physical integrity of the components of the tablet (see abstract). Vladyka et al. teach in claim 1 a method for preparing porous microcrystalline cellulose granules comprising the following steps:
(a) granulating microcrystalline cellulose with a granulating fluid comprising water and a water-miscible, volatile, polar organic solvent to provide a granulated microcrystalline cellulose;
(b) drying the granulated microcrystalline cellulose at a controlled rate with no heat input at ambient temperature for a time sufficient to remove at least substantially all of the polar organic solvent from the granulated microcrystalline cellulose without removing at least a substantial portion of the water from the granulated microcrystalline cellulose, and without extruding or spheronizing the granulated microcrystalline cellulose from granulation step (a); and
(c) subsequent to step (b), removing at least a substantial portion of the water from the granulated microcrystalline cellulose.
The method of claim 1 further comprising the step of adding to the granulated microcrystalline cellulose about 1 to about 30% by weight of a hydrocolloid, based on the weight of the granulated microcrystalline cellulose (see claim 7). The method of claim 7 wherein in the adding step the hydrocolloid is coated onto the surface of the microcrystalline cellulose granules (claim 10). The method of claim 7 wherein the hydrocolloid comprises one or more hydrocolloids selected from the group consisting of: methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, gelatin, water soluble cellulose acetate, polyvinyl pyrrolidone, starches, alginates, alginic acid, locust bean seed extract, guar seed extract, carrageenan, gum tragacanth, gum arabic and gum karoya (claim 11). The method of claim 11 wherein the hydrocolloid is selected from the group consisting of polyvinyl pyrrolidone, methylcellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose (see claim 12).
Vladyka et al. teach if a spray drying operation is employed, aggregates of the individual MCC-containing crystallites are formed. The spray-dried, unattrited material is sold commercially as a powder in grades having different average particle sizes ranging from about 20 microns to 190 microns. Typical of commercially available MCC are the materials sold by FMC Corporation as Avicel® PH grades (column 2, lines 41-47). Porous, granulated microcrystalline cellulose made by the process of claim 7 having a loose bulk density of from about 0.2 g/cc to about 0.4 g/cc, and a mean particle size of from about 250 microns to about 1500 microns (claim 14). As produced in this process, the particle size of the MCC granules can be distributed over a wide range, typically including particles smaller than about 100 microns to particles larger than 2000 microns. More preferably, the MCC granules have particle sizes distributed over a range of about 150 to 1500 microns and even more preferably 250-1250 microns. Generally, the MCC granules will have particle sizes which form a substantially Gaussian particle size distribution containing particles having sizes varying over a relatively wide range. Thus, the MCC granules preferably will have a mean particle size of 200-1500 microns, more preferably the mean particle size is from 250-1000 microns and most preferably the mean particle size is from 400-900 microns. The MCC granules are of irregular shape and a wide particle size distribution which promotes packing in tablets made with the MCC granules. Since the irregular shape of the MCC granules, as well as their wide particle size distribution are advantageous for the present invention, further processing of the MCC granules by, for example, extrusion or spheronization is generally undesirable and thus should be avoided (column 5, lines 30-52). The examiner notes that the hydrocolloid HPC coated microcrystalline cellulose (MCC) particles do not contain drug in the core (MCC particles) or on the coating HPC layer.
A tablet which comprises from about 5% to about 80% by weight of granulated microcrystalline cellulose as claimed in claim 16; from about 5% to about 80% by weight of one or more of controlled release particles and barrier coated materials which contain an active ingredient; and from 0% to about 20% by weight of other excipients, based on the total weight of the tablet (claim 26). Friability and hardness correlate rather closely with the compression force employed to produce the tablets. Tablets in which MCC granules are a component that have a hardness near or above 4 Kiloponds (Kp) usually have friability below about 3%; and more preferably, below about 2%. The selection of compression forces during tableting is a variable that one skilled in the art of tableting can manipulate to form satisfactory tablets that have the desired sustained release properties, hardness, and friability (column 7, lines 42-50).
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 before the effective filing date of the instant application to modify the teachings of Pathak et al. by using its formulation for the delivery of levofloxacin because Rudnic et al. teach an antibiotic product, in particular levofloxacin, is comprised of at least three dosages forms, each of which has a different release profile, with the Cmax for the antibiotic product being reached in less than about twelve hours. In one embodiment, there is an immediate release dosage form, as well as two or more delayed release dosage forms, with each of the dosage forms having a different release profile, wherein each reaches a Cmax at different times (see abstract). This invention relates to an antibiotic product, as well as the use and formulation thereof. The invention further relates to a levofloxacin antibiotic product, including derivatives thereof such as salts, esters, metabolites, etc. A wide variety of antibiotics have been used, and will be used, in order to combat bacterial infection. In general, such antibiotics can be administered by a repeated dosing of immediate release dosage forms, which results in poor compliance or as a controlled release formulation (slow release) at higher administered doses. The present invention is directed to providing for an improved antibiotic product. In accordance with one aspect of the present invention, there is provided an antibiotic pharmaceutical product which is comprised of at least two, preferably at least three, antibiotic dosage forms. Such dosage forms are formulated so that each of the dosage forms has a different release profile. One of ordinary skill in the art would have been motivated to do so first Rudnic et al. teach a wide variety of antibiotics have been used, and will be used, in order to combat bacterial infection. In general, such antibiotics can be administered by a repeated dosing of immediate release dosage forms, which results in poor compliance or as a controlled release formulation (slow release) at higher administered doses. The present invention is directed to providing for an improved antibiotic product. In accordance with one aspect of the present invention, there is provided an antibiotic pharmaceutical product which is comprised of at least two, preferably at least three, antibiotic dosage forms. Such dosage forms are formulated so that each of the dosage forms has a different release profile. Additionally, Pathak et al. clearly also teach a wide variety of pharmaceutically active ingredients may be used in conjunction with the present invention. While the active ingredient usually is a low or medium dose drug, also high-dose drugs may be contemplated for use in the present invention. An exemplary class of compounds which may be used as active ingredients in the present invention include any active ingredient listed in the Compendium of Pharmaceuticals and specialties ("CPS") which the examiner notes that levofloxacin is one of the actives, in particular tolterodine, their pharmaceutically acceptable salts with physiologically acceptable acids and, when the compounds can be in the form of optical isomers, the racemic mixture and the individual enantiomers. It is of course to be understood herein that any salt, ester, analog, and prodrugs of a pharmaceutically acceptable active ingredient may be used in accordance with the present invention. 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). One of ordinary skill in the art would have had a reasonable chance of success by combining the teachings of Pathak et al. and Rudnic et al. because both references teach formulations that can solve the problems of compliance and dosing. Furthermore, in the case where the amount of ingredients, concentrations, 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). 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). With regard to the limitation reciting “A plurality of core particles for powder coating by a wet method” in claim 1, the claim is written in a product-by-process manner. The examiner indicates that "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). See also Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim").
With regard to the limitation reciting the plurality of drug-containing particles having a particle size distribution span of not more not 1.0, the examiner notes that the combination of Pathak et al. and Rudnic et al. teach the same microcrystalline cellulose particles with overlapping mean particle size and overlapping particle size distributions as described in Applicant’s original disclosure (paragraph 0018 and paragraph 0035). Additionally. Pathak et al. teach the MCC being coated with HPC and adding a drug containing layer. Since the combination teachings of Pathak et al. and Rudnic et al. meet the claimed structure, the plurality of drug-containing particles having a particle size distribution span of not more not 1.0 would necessarily be the same or substantially identical. With regard to compressibility, Vladyka et al. teach a tablet which comprises from about 5% to about 80% by weight of granulated microcrystalline cellulose as claimed in claim 16; from about 5% to about 80% by weight of one or more of controlled release particles and barrier coated materials which contain an active ingredient; and from 0% to about 20% by weight of other excipients, based on the total weight of the tablet (claim 26). Friability and hardness correlate rather closely with the compression force employed to produce the tablets. Tablets in which MCC granules are a component that have a hardness near or above 4 Kiloponds (Kp) usually have friability below about 3%; and more preferably, below about 2%. One of ordinary skill in the art would have been motivated to utilize a compressibility of not more than 14% because Vladyka et al. teach that the selection of compression forces during tableting is a variable that one skilled in the art of tableting can manipulate to form satisfactory tablets that have the desired sustained release properties, hardness, and friability (column 7, lines 42-50). Vladyka et al. further teach generally, the mixing time will depend, to some extent on the type of granulating apparatus employed. Over-mixing and over-wetting are generally undesirable since this may, in some cases, result in an increased density of the dried granulate and, concomitantly, a reduction in the effectiveness of cushioning property of the MCC granules (see column 3, lines 66-67 and column 4, lines 1-11). One of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Pathak et al., Rudnic et al. and Vladyka et al. because Pathak et al. and Vladyka et al. teach compositions containing MCC core coated with HPC as in the instant invention where active agents of such as levofloxacin of Rudnic et al. can be delivered.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been prima facie obvious before the effective filing date of the instant application 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 application, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 16 October 2025 have been fully considered but they are not persuasive.
Applicant argues none of the cited references, either alone or in combination, teaches or suggests each and every limitation of the present claim 11. In particular, none of the references teaches or reasonably suggests that the discontinuity space is a laminar space. Pathak prepares a solution of HPC and sprays it onto the MCC core using a fluid bed coater to form a seal coat as the first layer. The seal coat described in Pathak is an actual layer coated over the MCC core. Therefore, the drug-containing particle of the present application is clearly different from the controlled-release beads of Pathak. The beads in Pathak do not have a laminar space between the surface of the MCC core and the active ingredient layer.
The above assertions are not found persuasive because the examiner takes the position as per the detailed explanation provided in the 35 USC 112 rejection above the phrase “laminar space”, for examination purposes, is interpreted as any space between the core and the coating layer. Therefore, with the broadest reasonable interpretation (BRI) of the phrase, the seal coat which exists between the raw material particle (microcrystalline cellulose) and the coating layer comprising a drug entails or reads on laminar space absent evidence to the contrary.
Applicant argues that the microcrystalline cellulose granules generally do not include a drug, as shown at least in Example 1 and Example 5. Claim 11 recites that the drug containing particles have a span of less than 1.0 while claim 16 recites that the raw material particles have a span of less than 1.0. Vladyka fails to disclose either of these limitations. In particular, Vladyka teaches that the raw material granules are irregularly shaped and have a wide particle size distribution which promotes packing in tablets made with the MCC granules. See, e.g. col. 5, Ins. 37-51. Vladyka also teaches that the irregular shape and wide particle size distribution are advantageous for the invention. Id. Thus, Vladyka teaches away from the instant claims.
The above assertions are not found persuasive because 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). Pathak as described above clearly teach coating microcrystalline cellulose with hydroxypropyl cellulose where both of them do not comprise drug. Vladyka et al. is incorporated in the rejection to address the fact that Pathak et al. and Rudnic et al. being silent with regard to the plurality of drug -containing particles having a particle-size distribution span of not more than 1.0 and a compressibility of not more than 14%. With regard to the limitation reciting the plurality of drug-containing particles having a particle size distribution span of not more not 1.0, the examiner notes that the combination of Pathak et al. and Rudnic et al. teach the same microcrystalline cellulose particles with overlapping mean particle size and overlapping particle size distributions as described in Applicant’s original disclosure (paragraph 0018 and paragraph 0035). Additionally. Pathak et al. teach the MCC being coated with HPC and adding a drug containing layer. Since the combination teachings of Pathak et al. and Rudnic et al. meet the claimed structure, the plurality of drug-containing particles having a particle size distribution span of not more not 1.0 would necessarily be the same or substantially identical. With regard to compressibility, Vladyka et al. teach a tablet which comprises from about 5% to about 80% by weight of granulated microcrystalline cellulose as claimed in claim 16; from about 5% to about 80% by weight of one or more of controlled release particles and barrier coated materials which contain an active ingredient; and from 0% to about 20% by weight of other excipients, based on the total weight of the tablet (claim 26). Friability and hardness correlate rather closely with the compression force employed to produce the tablets. Tablets in which MCC granules are a component that have a hardness near or above 4 Kiloponds (Kp) usually have friability below about 3%; and more preferably, below about 2%. One of ordinary skill in the art would have been motivated to utilize a compressibility of not more than 14% because Vladyka et al. teach that the selection of compression forces during tableting is a variable that one skilled in the art of tableting can manipulate to form satisfactory tablets that have the desired sustained release properties, hardness, and friability (column 7, lines 42-50). Vladyka et al. further teach generally, the mixing time will depend, to some extent on the type of granulating apparatus employed. Over-mixing and over-wetting are generally undesirable since this may, in some cases, result in an increased density of the dried granulate and, concomitantly, a reduction in the effectiveness of cushioning property of the MCC granules (see column 3, lines 66-67 and column 4, lines 1-11). One of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Pathak et al., Rudnic et al. and Vladyka et al. because Pathak et al. and Vladyka et al. teach compositions containing MCC core coated with HPC as in the instant invention where active agents of such as levofloxacin of Rudnic et al. can be delivered.
Applicant then further argues the Office cites Kamada as teaching "spherical granules comprising [pharmacologically inactive spherical seed cores] coated with a powdery layer comprising active ingredients and having an outer layer of coating provided on the powdery layer." Office Action, page 4 (emphasis added). However as discussed during the telephonic interview of June 3, 2025, Kamada does not disclose or suggest a plurality of core particles each comprising "a raw material particle and a polymer coated on the raw material particle," wherein "the raw material particle and the polymer do not comprise a drug," and particularly wherein "the amount of the polymer coated on the raw material particle is 15 to 300 parts by mass based on 100 parts by mass of the raw material particle," as recited in independent claim 1, as amended.
The above assertions are not found persuasive because 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). Pathak as described above clearly teach coating microcrystalline cellulose with hydroxypropyl cellulose where both of them do not comprise drug. Furthermore, claim 1 is canceled and the amount of the polymer is no longer a limitation in claim 11. Kamada is not depended on to render claims 11, 16, and 19 obvious.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (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.
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.
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/TIGABU KASSA/
Primary Examiner, Art Unit 1619
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