Ex Parte Awamura et alDownload PDFPatent Trial and Appeal BoardDec 27, 201613060707 (P.T.A.B. Dec. 27, 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. 13/060,707 02/25/2011 Tsutomu Awamura 376177US99X PCT 1426 22850 7590 12/29/2016 OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P. 1940 DUKE STREET ALEXANDRIA, VA 22314 EXAMINER BROWE, DAVID ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 12/29/2016 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): patentdocket @ oblon. com oblonpat @ oblon. com ahudgens@oblon.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte TSUTOMU AWAMURA, HISANOBU NISHIKAWA, and TOSHIO INAGI1 Appeal 2014-009825 Application 13/060,707 Technology Center 1600 Before ERIC B. GRIMES, FRANCISCO C. PRATS, and KRISTI L. R. SAWERT, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134(a) involves claims to a therapeutic film that contains the drug loperamide hydrochloride and a terpene, such as menthol. The Examiner rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE The object of Appellants’ invention “is to provide a film preparation in which a bitter taste of loperamide hydrochloride is masked.” Spec. 1 6. 1 Appellants state that “real party in interest in this appeal is KOWA CO. LTD and KYUKYU PHARMACEUTICAL CO, LTD by virtue of assignment recorded at Reel/Frame 025888/0029.” App. Br. 2. Appeal 2014-009825 Application 13/060,707 Appellants “surprisingly found that a bitter taste of loperamide hydrochloride could be noticeably masked by producing a film preparation in which coating layers containing specific ingredients were laminated on both sides of a drug-containing layer containing loperamide hydrochloride and specific ingredients.” Id. at 17. Claim 16, the only independent claim on appeal, and claim 23 illustrate the appealed subject matter and read as follows (App. Br. 17, 18): Claim 16: A film preparation comprising a drug- containing intermediate layer laminated on both sides with coating layers; wherein the drug-containing intermediate layer comprises loperamide hydrochloride, a terpene, and a film-forming agent; and wherein the coating layer comprises a film-forming agent and a plasticizing agent, but does not contain a terpene. Claim 23: The film preparation of claim 16, wherein the at least one terpene comprises menthol. The sole rejection before us for review is the Examiner’s rejection of claims 16, 19-23, and 26—35 under 35 U.S.C. § 103(a) for obviousness over Yasuda2 and Fukushima.3 Ans. 2-4. OBVIOUSNESS The Examiner’s Position The Examiner cited Yasuda as describing three-layered therapeutic film compositions that include, in the middle layer, a drug such as 2 US 2005/0147653 A1 (published Jul. 7, 2005). 3 JP 05-117149 (published May 14, 1993). 2 Appeal 2014-009825 Application 13/060,707 loperamide hydrochloride, and menthol. Ans. 2—3. The Examiner found that Yasuda differs from the rejected claims in that, “while disclosing loperamide hydrochloride as an active agent, and that the active agent is present at 0.1— 40 wt%, [Yasuda] nevertheless do[es] not explicitly disclose that loperamide hydrochloride is present specifically at 1—5 wt%.” Id. at 3. To address that deficiency the Examiner cited Fukushima as disclosing “a composition for oral administration comprising 0.1—5 wt% loperamide or a salt thereof, and further comprising hydroxypropylcellulose and a film-forming coating, wherein the composition can be orally administered with no bitter taste and is pharmaceutically useful for the treatment of diarrhea.” Id. Based on the references’ teachings, the Examiner concluded that an ordinary artisan would have considered it obvious to combine the disclosures in Yasuda and Fukushima “to devise Appellant’s presently claimed film.” Id. The Examiner reasoned that, in view of Fukushima’s disclosure, an ordinary artisan would have been “motivated to incorporate specifically 0.1—5 wt% loperamide hydrochloride in the intermediate layer of the Yasuda et al. film preparation, with the reasonable expectation of success that the resulting film preparation can be orally administered for the rapid treatment of diarrhea.” Id. at 4. The Examiner further noted that Yasuda’s Example 26, like Appellants’ claims, describes a three-layered therapeutic film composition with a drug-containing middle layer “laminated on both sides with support (i.e. ‘coating’) layers. Yasuda expressly discloses that this film preparation contains menthol, and that the menthol is present only in the drug-containing intermediate layer, but not in either one of the two support (i.e. ‘coating’) 3 Appeal 2014-009825 Application 13/060,707 layers.” Id. at 5. The Examiner noted, moreover, that “Yasuda consistently teaches, in each and every one of their examples in which menthol is expressly employed, that menthol is present only in the drug-containing layer, but not in a support (i.e. coating) layer (see [Ejxamples 24, 25, and 26).” Id. Based on these teachings, the Examiner reasoned as follows: Although in [Ejxample 26 the drug in the intermediate layer is chlorpheniramine maleate, it would be just as obvious ... to employ any one of the other drugs expressly listed in [|] 0089, including loperamide hydrochloride, as the drug in the intermediate layer of the film preparation of Example 26, which drugs are essentially all “equivalent” substitutes for one another in the Yasuda film preparation. Id. at 6. Analysis As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden ... of presenting a prima facie case of unpatentability. . . . After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. Appellants’ arguments do not persuade us that a preponderance of the evidence fails to support the Examiner’s conclusion that the rejected claims would have been obvious to an ordinary artisan. Claim 16, the sole independent claim on appeal, recites a three layered film composition that includes, in the middle layer, a film-forming agent, loperamide hydrochloride, and a terpene, which may be menthol. App. Br. 17; see also id. at 18 (claim 23 reciting menthol as the terpene). 4 Appeal 2014-009825 Application 13/060,707 Claim 16 specifies that the outer coating layers contain a film-forming agent and a plasticizing agent, but do not contain a terpene. App. Br. 17. As required by claim 16, Yasuda discloses three-layered film compositions that have a middle drug-containing layer, sandwiched between two coating layers. Yasuda 1 85 (describing film preparation having a “three-layer structure in which a support layer is provided on one side or both sides of the drug layer”); see also id. at 1114 (describing film preparations “In the Case of Laminate (Three Layers) of Drug Layer and Support Layers on Both Sides Thereof’). Yasuda discloses that the drug layer “contains the drug and an edible polymer, and a saccharide, a plasticizer and the like if necessary. The support layer contains an edible polymer, and a saccharide, a plasticizer and the like if necessary.” Id. at | 85. Yasuda discloses that, in addition to those ingredients, “the use of various flavors, colorants such as titanium oxide and various dyes is, of course, permissible.” Id. at | 87. To that end, we note that Yasuda discloses including sweeteners and flavors in the drug-containing layers, but not the supporting layers, of its multi-layer compositions. Id. at || 112—115. Yasuda discloses that drugs suitable in its formulations include drugs “which exert[] no adverse effect on the digestive organs and the like.” Id. at | 88. Among such drugs, Yasuda lists “antidiarrheal drugs such as loperamide hydrochloride . . . .” Id. at | 89. As the Examiner found, Example 26 of Yasuda discloses a three layered film composition in which the middle drug-containing layer contains chlorpheniramine maleate, and also contains menthol. Id. at 1130. As the 5 Appeal 2014-009825 Application 13/060,707 Examiner found, the outer coating layers in the composition of Example 26 do not contain menthol, as recited in Appellants’ claim 16. Id. Given Yasuda’s teaching that loperamide hydrochloride is suitable as the drug in the middle drug-containing layer of its three-layered film composition, we agree with the Examiner that an ordinary artisan had a good reason for, and a reasonable expectation of success in, incorporating loperamide hydrochloride as the drug in the middle layer of its three-layered film compositions, as required by claim 16. Moreover, given Yasuda’s teaching that it was useful to include menthol in the middle drug-containing layer, but not the coating layers, of its three-layer compositions, we also agree with the Examiner that an ordinary artisan had a good reason for, and a reasonable expectation of success in, including menthol in the middle drug- containing layer, but not the coating layers, of a film composition that contained loperamide hydrochloride in its middle layer, as recited in Appellants’ claim 16. Accordingly, we further agree with the Examiner that the composition of Appellants’ claim 16 would have been prima facie obvious to an ordinary artisan. Appellants’ arguments do not persuade us to the contrary. Because, as noted, Yasuda teaches that both loperamide hydrochloride and menthol are desirably included only in the middle layer of its three layered film compositions, Appellants do not persuade us (App. Br. 13—14; Reply Br. 3—7), that Yasuda fails to teach or suggest the combination of those two ingredients only in the middle layer of a three-layered film composition, as recited in Appellants’ claim 16. We acknowledge Yasuda’s broad disclosure that drugs suitable in its compositions are those “which exert[] no adverse effect on the digestive 6 Appeal 2014-009825 Application 13/060,707 organs and the like.” Yasuda 1 88. Loperamide hydrochloride, however, is one of only about 45 drugs expressly named by Yasuda as being suitable in its compositions. Id. at| 89. Thus, although Yasuda’s disclosure might encompass more drugs than those expressly named, we are not persuaded that the Examiner erred in finding that it would have been obvious to select loperamide hydrochloride from the list of drugs expressly named in Yasuda. Nor are we persuaded that MPEP § 2144.08 mandates that the Examiner erred in that regard, particularly given Yasuda’s express naming of Appellants’ claimed drug as suitable in its formulations. See Reply Br. 4—5, 7. Although, as noted above, Yasuda discloses the suitability of including flavors in its compositions (Yasuda 1 87), Yasuda does not appear to state expressly the purpose of including menthol in its formulations, as Appellants contend. Reply Br. 6. Nonetheless, given Yasuda’s disclosure of including menthol in the middle drug-containing layer of its three-layer compositions, but not the outer coating layers (Yasuda 1130 (Example 26)), we are not persuaded that the Examiner erred in finding that it would have been obvious to include menthol only in the middle layer, as required by Appellants’ claim 16. See also id. at || 112—115 (consistent with Example 26, generic disclosure of flavorings and sweeteners in drug-containing layer, but not support layers, of multi-layer compositions). That Yasuda’s suggestion for incorporating menthol in the middle layer, but not the outer layers, of a loperamide-containing three-layer composition, might not have been expressly for Appellants’ purpose of masking the bitter taste of loperamide hydrochloride, does not demonstrate the Yasuda failed to suggest a three-layered film having that configuration. 7 Appeal 2014-009825 Application 13/060,707 See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007) (“In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103.”). In sum, for the reasons discussed above, Appellants’ arguments do not persuade us that the evidence of record fails to support the Examiner’s prima facie case of obviousness as to claim 16. Appellants also do not persuade us, for the reasons discussed below, that the secondary evidence of nonobviousness is sufficient to outweigh the evidence of prima facie obviousness. “[Wjhen an applicant demonstrates substantially improved results . . . and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). In the present case, as noted above, Appellants assert that they have unexpectedly found that a terpene may be used to mask the bitter taste of loperamide hydrochloride in multi-layer film compositions. Spec, 7—8. Appellants support that assertion with comparative experimental evidence, the results being shown in Table 1 from the Specification, reproduced below: 8 Appeal 2014-009825 Application 13/060,707 (Table 11 Example 1 Corapa r a tive Example i Comparat. iva Example 2 u HypKore 11 oss' 7.2 6.7 6.7 >+ si* Macrogol 400 0,8 0, S 0.8 £ g Titanium oxide 1 I I Powdered hydrogenated maltose starch syrup 1 1 1 o 1-Menthol - 0.5 0 , s Loperamide hyd rochIor1de 0.5 0,5 0 . S 73 * Powdered hydrogena t ed maltose starch syrup 4.75 4.75 4.75 '7 & & % Hy dr oxypr opyl c e 1 Xu 1 os a1 7.05 7,55 7 C3 !> 8 3U £ Hacrogo1 4 00 1,2 1.2. 1.2 .a Saccharin sodium 1 1 1 1-Menthol 0 . $ •• 0.5 Flavoring agent G . 0 25 ■D ,.025 0.025 Total score 11 points/ 12 points S points/ 12 point® g points/ 12 points 1) Hyprosnellose: TC-5R {Shin- Etisu. Chemical. Co. , Ltd,) 2) Hydroxypropylcelluioae: HPC-SSL {Mppors Soda. Co,, Ltd.) Spec. 143. Table 1 shows the results of a taste evaluation by six panelists of Example 1 (three-layered film composition encompassed by Appellants’ claims with loperamide hydrochloride and menthol in the middle layer, and no menthol in the outer coating layers), Comparative Example 1 (three layered film composition with loperamide hydrochloride in the middle layer, and menthol only in the outer coating layers), and Comparative Example 2 (three-layered film composition with loperamide hydrochloride in the middle layer, and menthol in both the middle layer and the outer coating layers). The Specification explains that the panelists gave each formulation either 2 points (“a bitter taste is virtually unnoticeable”), 1 point (“a bitter 9 Appeal 2014-009825 Application 13/060,707 taste is slightly noticeable”), or zero points (“a bitter taste is noticeable and the taste is bad”). Spec. 142. As seen in Table 1, the formulation encompassed by independent claim 16 achieved a score of 11 points out of a possible 12, despite containing menthol only in the middle drug-containing layer, whereas Comparative Example 2, which contained menthol in both the inner and coating layers, achieved a score of only 6 points out of a possible 12. Id. at|43. The Examiner does not identify, nor do we discern, any persuasive evidence suggesting that the superior result for the claimed preparation would have been expected. The Examiner rejects Appellants’ data as being an “improper comparison,” apparently because the closest prior art embodiment is Yasuda’s Example 26, discussed above. Ans. 7. We do not find the Examiner’s position persuasive. Given the absence of any evidence of record that the chlorpheniramine maleate in Yasuda’s Example 26 has a bitter taste, with the same degree of bitterness as loperamide hydrochloride, we are not persuaded that a side-by-side comparison to Example 26 would be sufficient to show whether embodiments encompassed by Appellants’ claims possess unexpected properties. The Examiner also seems to contend that an appropriate comparison would be between a claimed embodiment and Yasuda’s Example 26 modified to contain loperamide hydrochloride instead of chlorpheniramine, that is, a comparison of a claimed embodiment to the composition suggested by the prior art. See id. at 7—9. Our reviewing court’s predecessor has squarely rejected that proposition, however. See In re Chapman, 357 F.2d 418, 422 (CCPA 1966) (when evaluating evidence of unexpected results, it 10 Appeal 2014-009825 Application 13/060,707 is improper to require applicant to compare claimed invention to product suggested by prior art because doing so “would amount to requiring comparison of the results of the invention with the results of the invention”). As to Appellants’ evidence of unexpected results, however, our reviewing court has explained that “[ejvidence of secondary considerations must be reasonably commensurate with the scope of the claims. . . . This does not mean that an applicant is required to test every embodiment within the scope of his or her claims.” In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011). Rather, “[i]f an applicant demonstrates that an embodiment has an unexpected result and provides an adequate basis to support the conclusion that other embodiments falling within the claim will behave in the same manner, this will generally establish that the evidence is commensurate with scope of the claims.” Id. As discussed above, Appellants identify in Table 1 a single composition (Example 1) that exhibits significantly improved properties which, on this record, have not been shown to be expected. That composition, however, is limited to a single specific concentration of loperamide hydrochloride, which appears to be 0.5 % by weight of either the drug-containing layer or the entire composition. See Spec. 143 (Table 1). Appellants’ claim 16, in contrast, does not limit the concentration of loperamide hydrochloride to any particular range, and Appellants’ claims 19 and 20 encompasses concentrations of that ingredient many times the concentration of the inventive composition shown in Table 1. See App. Br. 17. Because loperamide hydrochloride was known in the art to have a bitter taste (see Fukushima 14), and because Appellants have not identified an adequate basis to support a conclusion that the same result shown in Table 1 11 Appeal 2014-009825 Application 13/060,707 would occur even when the bitter-tasting loperamide was increased to the significantly higher concentrations encompassed by the claims, we find that Appellants’ showing in Table 1 is not commensurate in scope with the claimed subject matter. Similarly, Appellants’ showing in Table 1 is limited to menthol (Spec. 143 (Table 1)), whereas all claims except claim 23 encompass any terpene. See App. Br. 17—20. Because Appellants have not identified an adequate basis to support a conclusion that the same result shown in Table 1 would occur when using terpenes other than menthol, we find, for this additional reason, that Appellants’ showing in Table 1 is not commensurate in scope with the claimed subject matter. As to claim 23, which recites menthol, we note that it, nonetheless, does not limit the loperamide concentration, as discussed above. In sum, for the reasons discussed, Appellants do not persuade us that the Examiner erred in finding that the cited references suggest the composition recited in independent claim 16. For the reasons discussed, Appellants also do not persuade us that the evidence of unexpected results is sufficient to outweigh the Examiner’s evidence of prima facie obviousness. We, therefore, affirm the Examiner’s rejection of claim 16 under § 103(a) over Yasuda and Fukushima. Claim 35 was not argued separately. See Reply Br. 10—12 (claim 35 not included in separately argued claims subject to new ground of rejection in Examiner’s Answer). Claim 35, therefore, falls with claim 16. 37 C.F.R. § 41.37(c)(l)(iv). Claim 19 recites “[t]he film preparation of claim 16, wherein the drug- containing intermediate layer contains 1% to 5% by weight loperamide hydrochloride; or wherein the entire film preparation contains 0.1% to 15% 12 Appeal 2014-009825 Application 13/060,707 by weight loperamide hydrochloride.” App. Br. 17. Yasuda discloses that suitable concentrations of the drug in its film compositions, which as discussed above may be loperamide hydrochloride, range from 0.01 to 40% by weight. Yasuda 190. Given the significant overlap between the claimed concentration range and the suitable drug concentration range taught in Yasuda, Appellants do not persuade us that Yasuda fails to suggest the range of loperamide recited in claim 19. We, therefore, affirm the Examiner’s rejection of claim 19 as well. Because it was argued in the same claim grouping as claim 19 (see Reply Br. 10—11), claim 20 falls with claim 19. 37 C.F.R. §41.37(c)(l)(iv). Claim 23 recites “[t]he film preparation of claim 16, wherein the at least one terpene comprises menthol.” App. Br. 18. As discussed above, Yasuda discloses incorporating menthol into the middle layer, but not the coating layers of its three-layered film compositions. Yasuda 1130 (Example 26). Appellants, therefore, do not persuade us that Yasuda fails to suggest using the particular terpene recited in claim 23 in its compositions, in the manner recited in claim 23. We, therefore, affirm the Examiner’s rejection of claim 23 as well. Because they were argued in the same claim grouping as claim 23 (see Reply Br. 11), claims 21 and 22 fall with claim 23. 37 C.F.R. §41.37(c)(l)(iv). Claim 26 recites “[t]he film preparation of claim 16, wherein the film- forming agent of the drug containing intermediate layer or a coating layer comprises at least one selected from the group consisting of hypromellose (hydroxypropylmethylcellulose).” App. Br. 18. Yasuda discloses that the “edible polymer” in both the drug-containing and support layers of its film compositions may be “hydroxypropylmethyl cellulose (HPMC).” Yasuda 1 13 Appeal 2014-009825 Application 13/060,707 87. Appellants, therefore, do not persuade us that Yasuda fails to suggest using HPMC in its three-layered compositions. We, therefore, affirm the Examiner’s rejection of claim 26 as well. Because they were argued in the same claim grouping as claim 26 (see Reply Br. 11), claims 27—30 fall with claim 26. 37 C.F.R. § 41.37(c)(l)(iv). Claim 31 recites “[t]he film preparation of claim 16, wherein the plasticizer is at least one selected from the group consisting of glycerin, propylene glycol and macrogol 400.” App. Br. 19. Appellants’ Specification explains that macrogol 400 is polyethylene glycol 400 (PEG 400). Spec 120. Yasuda discloses the use of both glycerin and PEG 400 as plasticizers in the support layer of its compositions. Yasuda Tflf 85, 87. Appellants, therefore, do not persuade us that Yasuda fails to suggest using the plasticizers of claim 31 in its three-layered compositions. We, therefore, affirm the Examiner’s rejection of claim 31 as well. Because it was argued in the same claim grouping as claim 31 (see Reply Br. 11), claim 32 falls with claim 31. 37 C.F.R. § 41.37(c)(l)(iv). Claim 33 recites “[t]he film preparation of claim 16 that is 30 to 300 pm thick.” App. Br. 19. As to its film compositions, Yasuda discloses that the “whole thickness is suitably from 30 to 300 pm.” Yasuda ^ 90. Appellants, therefore, do not persuade us that Yasuda fails to suggest three layered compositions with a thickness recited in claim 33. We, therefore, affirm the Examiner’s rejection of claim 33 as well. Because it was argued in the same claim grouping as claim 33 (see Reply Br. 11), claim 34 falls with claim 33. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY 14 Appeal 2014-009825 Application 13/060,707 For the reasons discussed, we affirm the Examiner’s rejection of claims 16, 19—23, and 26—35 under 35 U.S.C. § 103(a) for obviousness over Yasuda and Fukushima. TIME PERIOD 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 15 Copy with citationCopy as parenthetical citation