Ex Parte Nakamura et alDownload PDFPatent Trial and Appeal BoardDec 28, 201613808457 (P.T.A.B. Dec. 28, 2016) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/808,457 01/04/2013 Kazuhiro Nakamura Q200306 6793 23373 7590 12/30/2016 SUGHRUE MION, PLLC 2100 PENNSYLVANIA AVENUE, N.W. SUITE 800 WASHINGTON, DC 20037 EXAMINER ALLEY, GENEVIEVE S ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 12/30/2016 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): PPROCESSING@SUGHRUE.COM sughrue@sughrue.com USPTO@sughrue.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte KAZUHIRO NAKAMURA, TEPPEI OGAWA, and TOMOYA AKUTAGAWA1 Appeal 2015-006616 Application 13/808,457 Technology Center 1600 Before RICHARD M. LEBOVITZ, TAWEN CHANG, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. § 134(a) involving claims directed to formulations comprising coated fine particles. Claims 1, 3, and 4 are on appeal as rejected under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 We understand the Real Party in Interest to be Teijin Pharma Limited. App. Br. 2. Appeal 2015-006616 Application 13/808,457 STATEMENT OF THE CASE The appealed claims can be found in the Claims Appendix of the Appeal Brief. Claims 1 and 3 are the independent claims and read as follows: 1. An intraorally rapidly disintegrating tablet comprising a particle containing a 2-(3-cyano-4-isobutyloxyphenyl)-4- methyl-5-thiazolecarboxylic acid-containing core particle coated with a layer containing a methacrylic acid copolymer and further overcoated with a layer containing mannitol. 3. An intraorally rapidly disintegrating tablet obtained by compression molding of a particle comprising a 2-(3-cyano-4- isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid- containing core particle coated with a layer containing a methacrylic acid copolymer and further overcoated with a layer containing mannitol and a granule containing a disintegrant- containing particle coated with a disintegrant. App. Br. 14 (Claims App’x). The following rejection is on appeal: Claims 1,3, and 4 are rejected under 35 U.S.C. § 103 (a) over Akutagawa2 and Shimizu.3 Final Action 4. FINDINGS OF FACT We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions set out in the Final Action and 2 U.S. Patent Application Pub. No. 2009/0117182 A1 (published May 7, 2009) (hereinafter “Akutagawa”). 3 U.S. Patent No. 6,328,994 B1 (issued Dec. 11, 2001, to Toshihiro Shimizu et al.) (hereinafter “Shimizu”). 2 Appeal 2015-006616 Application 13/808,457 Answer. The findings of fact set forth below are provided only to highlight certain evidence of record. FF1. Akutagawa disclosed “an intraorally rapidly disintegrating tablet that can be formed using an ordinary apparatus, that has hardness with no practical problem and that disintegrates rapidly with good feeling in the oral cavity.” Akutagawa Abstract, 17, Table I (hardness being a measured objective); see also Final Action 4—8 (discussing Akutagawa). FF2. Further, Akutagawa disclosed its “intraorally rapidly disintegrating tablet [was] produced by compression molding of a granule coated with a disintegrant, in which the granule contains a disintegrant also inside thereof and a drug except ambroxol hydrochloride.” Akutagawa Abstract; see also Final Action 4—8 (discussing Akutagawa). FF3. Akutagawa further disclosed that its “active ingredient[]” could be “febuxostat,” “which is the equivalent trade name for the IUPAC name, 2-(3-cyano-4-5 isobutyloxyphenyl)-4-methyl-5- thiazolecarboxylic acid,” recited by claims 1 and 3. Akutagawa H 10, 38; and Final Action 4 (identifying the compound). FF4. Akutagawa disclosed that “[t]he drug used in the tablet of the present invention may be coated with a film-coating agent, an excipient, a binder, a lubricant, or the like depending on its properties, and a plasticizer may be added.” Akutagawa 112; see also Final Action 4—8 (discussing Akutagawa). 3 Appeal 2015-006616 Application 13/808,457 FF5. Akutagawa disclosed that “[t]he disintegrant used in the tablet of the present invention is not particularly limited, as far as it is a disintegrant used for pharmaceutical preparations,” and “can include crospovidone.” Akutagawa Tflf 13, 38; see also Final Action 4—8 (discussing Akutagawa). FF6. Akutagawa disclosed that “[a]ny excipient used for pharmaceutical preparations can be used without limitation, but examples of excipients used in the tablet of [its] invention can include sugars such as . . . [particularly preferred] mannitol,” and that “[t]he excipient used in [its] invention is contained in the inside of a granule constituting a tablet and/or in a coating of a disintegrant and/or in the outside of a granule coated with a disintegrant.” Akutagawa ^fl[ 25— 27, 38; see also Final Action 4—8 (discussing Akutagawa). FF7. Akutagawa disclosed producing its tablet “by compression molding the granule thus coated together with one or more kinds of pharmaceutically acceptable additives.” Akutagawa H 31 38; see also Final Action 4—8 (discussing Akutagawa). FF8. Akutagawa disclosed as Example 1, a tablet formulation containing, inter alia, D-mannitol, crospovidone, and Febuxostat, having the disintegrant coated over a granule, formed by compression molding, and Akutagawa further indicated “[t]he results show that the tablets of the present invention satisfy all the evaluation items for hardness, compression moldability (friability) and disintegrating property. In addition, it has been shown that all these effects can be 4 Appeal 2015-006616 Application 13/808,457 achieved regardless of the type of drug.” Akutagawa Tflf 38, 42; see also Final Action 4—8 (discussing Akutagawa). FF9. Akutagawa disclosed that “coating [a granule] with a disintegrant is [] required” because uncoated comparison examples were “inferior” to coated examples in “disintegrating property and compression moldability . . . and sufficient hardness.” Akutagawa Tflf 60-65; see also Final Action 4—8 (discussing Akutagawa). FF10. Shimizu disclosed “[a]n orally disintegrable tablet,. . . which comprises (i) fine granules . . . coated by an enteric coating layer, . . . [which] has superior disintegrability or dissolution in the oral cavity[, . . .] will not impart roughness in mouth, [and] can be administered easily without discomfort at the administration.” Shimizu Abstract; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). FF11. Shimizu disclosed that, “[f]or many reasons, such as, masking a bitter taste, or providing enteric abilities or release abilities, it is desirable to prepare the solid pharmaceutical preparations as granules (or fine granules) [] ... in which the active ingredient of the drug is enteric coated.” Shimizu 2:22—28; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). FF12. Shimizu also disclosed such an enteric coating is needed “to develop a fine granule while maintaining enteric dissolution, a disintegrability and dissolution and suitable strength, and to develop an orally disintegrable preparation [i.e., tablet]. . . showing superior oral disintegrability and dissolution and having suitable strength 5 Appeal 2015-006616 Application 13/808,457 (hardness) so that it will not be damaged through production processes or handling.” Shimizu 2:56—3:3; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). FF13. Shimizu’s disclosure is directed to “acid-labile” drugs; however, Akutagawa disclosed the advantages of its coated-granule invention would be achieved “regardless of the type of drug.” Shimizu Abstract; cf. FF8, supra. FF14. Shimizu disclosed an “‘enteric coating layer’ which coats the ‘composition’” and preferably includes “methacrylate copolymer.” Shimizu 9:9—29, claims 17 and 18; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). FF15. Shimizu disclosed its tablets include “‘additives’ [which] include, for example, a water-soluble sugar alcohol,. . . [which] “includes, for example, . . . [preferably] mannitol,” “in order to obtain sufficient strength of the preparation and sufficient disintegration or dissolution in the oral cavity.” Shimizu 9:36—10:6; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). FF16. Shimizu disclosed “the composition coated with an enteric coating layer may be further coated by a water-soluble sugar alcohol, preferably mannitol” and “[i]n such a case, the strength of the orally disintegrable tablet comprising fine granules is improved.” Shimizu 16:23—27, 17:3—18, claim 5; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). 6 Appeal 2015-006616 Application 13/808,457 FF17. Shimizu disclosed its tablets include “‘disintegrants’ inlcud[ing] “crospovidone.” Shimizu 12:6—7; see also Final Action 5—7 and Ans. 2—5 (discussing Shimizu). FF18. Shimizu disclosed an objective of its invention was “[t]he strength of the ‘orally disintegrable tablet’ of the present invention (measurement with a tablet hardness tester),” so that the “preparation [] is superior in dissolution while retaining suitable strength,” and “because the orally disintegrable tablet of the present invention has a suitable strength such that it will not be substantially damaged through production processes or circulation processes, it is superior in stability for long-term storage and easy of use at the administration.” Shimizu 12:48—50, 15:12—13, 37:26—31; see also Final Action 5—7 and Ans. 2— 5 (discussing Shimizu). DISCUSSION We find the Examiner has established a prima facie case that the claims would have been obvious over the cited prior art combination. Appellants have not presented persuasive arguments or evidence that the Examiner’s determination was incorrect. We address Appellants’ arguments below. Appellants argue one of ordinary skill in the art would not have combined the teachings of Shimizu and Akutagawa because “Shimizu teaches away from coating particles to increase the storage stability in terms of improved retention of disintegration and dissolution properties and because the active ingredients in the two references are different.” App. Br. 6. This argument is not persuasive. 7 Appeal 2015-006616 Application 13/808,457 The Examiner found that Akutagawa describes a disintegrating tablet comprising the recited compound as claimed, but not with recited layer of methacrylic acid copolymer and overcoating with a layer containing mannitol. Final Action 4—5. For the latter features, the Examiner cited the teachings in Shimizu, determining that it would have been obvious to have coated the tablet as described by Shimizu, such as masking bitter taste and providing enteric abilities. Id. at 5. There is no reason to believe such a combination would not be advantageous in the same ways each of the references are individually advantageous. Appellants have not provided persuasive evidence that the combination would not be reasonably successful, as the Examiner has determined. Akutagawa and Shimizu disclose the same general technology (rapidly disintegrating, coated oral tablets) using the same or similar components (e.g., crospividone and mannitol) and methods of production (e.g., granule coating and compression molding), for the same or similar objectives (e.g., rapid disintegration, good oral properties, sufficient hardness). FF1, FF2, FF4—FF13, FF15—FF18. Moreover, Akutagawa expressly disclosed its coatings (e.g., mannitol) worked with any drug, which refutes Appellants’ argument that the active ingredients of the two references are too different to expect to have successfully combined their disclosed coatings. FF8. Finally, Shimizu does not teach away from improving disintegration and dissolution properties while also improving hardness and storability; quite the opposite—it teaches these properties are all improved by its coatings. FF15, FF16. 8 Appeal 2015-006616 Application 13/808,457 The Examiner explained that the skilled artisan would be motivated to combine the cited references to include the advantages of the Shimizu coatings (e.g., taste masking, enteric protection) in the similarly coated Akutagawa tablet. Final Action 5. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose. . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980). Here, the purposes of the tablets of the references significantly overlap. Both Akutagawa and Shimizu disclose coating an orally dissolving tablet with mannitol to improve the tablet’s dissolution, strength, and hardness properties and, further, Shimizu disclosed providing an enteric coating under the mannitol coating to also provide proper dissolution, strength, and hardness properties. See FF8, FF9, FF12, F14, FF15, FF16, FF18. Appellants argue the Examiner failed to consider Shimizu as a whole and that “it is common technical knowledge that if a tablet has high hardness it is splinterless, and therefore the active ingredient in the tablet is less subject to dissolution.” App. Br. 6. Appellants contend this would keep the skilled artisan from considering Shimizu and that the reference teaches away from the claimed invention. Id. at 6—7. These arguments are not persuasive. Shimizu expressly indicates that it adds mannitol “in order to obtain sufficient strength of the preparation and sufficient disintegration or dissolution in the oral cavity,” and in using mannitol in a coating over its enteric coating, “the strength of the orally disintegrable tablet comprising 9 Appeal 2015-006616 Application 13/808,457 fine granules is improved.” FF16. Thus, as recognized by the Examiner (Final Action 5, Ans. 4—5), Shimizu teaches that its addition of a mannitol- containing-coating took advantages in both dissolution and hardness/strength (durability) into consideration. Moreover, Appellants provide no evidence to support their allegation regarding “common technical knowledge,” an allegation that is at odds with the disclosure of Shimizu as a whole. “An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). “Attorneys’ argument is no substitute for evidence.” Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989). Appellants argue that because Akutagawa’s febuxostat and Shimizu’s acid-labile active ingredients have different physical properties, Shimizu is not analogous art. App. Br. 7. This argument is not persuasive. Akutagawa expressly indicates that its mannitol coating and tableting technology’s advantages are “achieved regardless of the type of drug.” FF8. Further, beyond their conclusory statement, Appellants offer no evidence that any differences between the active ingredients disclosed by each reference would pose any actual difficulties in combining the references’ components. Again, mere attorney argument will not suffice here to rebut the strong prima facie case for obviousness. Johnston, 885 F.2d at 1581. Both cited publications are in the same field as the claimed invention, namely, pharmaceutical formulations. Appellants have not provided evidence that one of ordinary skill would not have considered each of 10 Appeal 2015-006616 Application 13/808,457 Akutagawa and Shimizu reasonably pertinent to the subject matter of the claim. In re Clay, 966 F.2d 656, 658-59 (Fed. Cir. 1992). “References are selected as being reasonably pertinent to the problem based on the judgment of a person having ordinary skill in the art.” In re Kahn, 441 F.3d 977, 986- 87 (Fed. Cir. 2006). Appellants argue they have shown the claimed invention provides unexpectedly superior properties, namely “superior storage stability in terms of dissolution or intraorally rapidly disintegrating properties, even when stored under high temperature/high humidity conditions.” App. Br. 9. This is not persuasive. “[B]y definition, any superior property must be unexpected to be considered evidence of non-obviousness.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007). And, “it is well settled that unexpected results must be established by factual evidence. ‘Mere argument or conclusory statements in the specification does not suffice.’” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (quoting In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)). The alleged surprising result of improved (long-term) storage stability would be expected in view of Shimizu (and Akutagawa). Ans. 4—5; FF8— FF10, FF12, FF15, FF16, FF18. A primary objective and advantage of the Shimizu technology, particularly the inclusion of a mannitol-containing- coating, is an improvement in long term storage and handling, which would certainly contemplate relevant storage conditions such as temperature and climate. Moreover, concerning the evidence in the Specification at 15 (Table 2) pointed to by Appellants, the Examiner reasonably questioned its 11 Appeal 2015-006616 Application 13/808,457 relevance because it showed that in each case the hardness values decreased over time whether the embodiments included a mannitol coating or not. See Advisory Action 4 (dated Apr. 29, 2014). Appellants have not established that the Examiner’s determination was incorrect. Furthermore, both coating components recited in the claim are described by Shimizu. FF14, FF15. The properties relied upon by Appellants therefore would be possessed by Shimizu. “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). Appellants argue the Examiner misunderstood the disclosure of Shimizu because the reference did not disclose mannitol as a coating, but rather as an excipient in the tablet. App. Br. 11. This is not persuasive. Appellants are not considering Shimizu as a whole. Shimizu expressly disclosed using mannitol in a coating over an enteric coating. FF16. This was the Examiner’s determination. Final Action 5 (citing, e.g., Shimizu claim 5 and col. 16). Appellants argue Shimizu is an improper reference because it did not solve the same problem as the claimed invention. App. Br. 12. This argument is not persuasive. “In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. . . . [A]ny need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed.” KSR Int’l Co. v. Teleflex 12 Appeal 2015-006616 Application 13/808,457 Inc., 550 U.S. 398, 419-20 (2007). However, Shimizu does expressly address the same or at least a very similar problem, i.e., hardness and related storability/handling or tablets, as addressed by the claimed invention and also solves it in the same or at least very similar ways, using multiple coatings of similar materials. FF10—FF18. Appellants argue Shimizu does not disclose tablet strength or storage stability or disintegrability being improved by the mannitol coating. Reply Br. 5—6. This argument is not persuasive, and is largely cumulative of Appellants’ previous arguments. Shimizu expressly disclosed that, when coating with mannitol, “the strength of the orally disintegrable tablet comprising fine granules is improved” and the “preparation [] is superior in dissolution while retaining suitable strength.” FF16, FF18. Unexpected results must be compared to the closest prior art. Baxter, 952 F.2d at 392. In this case, the showing in Table 2 is not to the closest prior art because Shimizu teaches a tablet with an overcoating of mannitol. Thus, a proper comparison would have been between a core particle coated with mannitol and an enteric coating described in Shimizu. See, e.g., col. 22,1. 36. Such a showing is necessary to establish that that improved disintegration property is a result of the claimed invention (i.e., a layer containing a methacrylic acid copolymer and further overcoated with a layer containing mannitol) and not just the mannitol coating itself—because the mannitol coating is a feature of the prior art, any benefit of which would be inherent. Tyco Healthcare Group LP v. Mutual Pharma Co., Inc., 642 F.3d 1370,1373 (Fed. Cir. 2011) (discovering new properties of known 13 Appeal 2015-006616 Application 13/808,457 compositions, even where unobvious, cannot impart patentability to the known composition). For at least the reasons above, we find Appellants’ arguments unpersuasive and affirm the Examiner’s obviousness rejection. SUMMARY The rejection of claims 1, 3, and 4 under 35 U.S.C. § 103(a) over Akutagawa and Shimizu is affirmed. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 14 Copy with citationCopy as parenthetical citation