Andreas Hugerth et al.Download PDFPatent Trials and Appeals BoardOct 1, 20212021000798 (P.T.A.B. Oct. 1, 2021) 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. 13/355,768 01/23/2012 Andreas Hugerth MAB5014USNP 9608 27777 7590 10/01/2021 JOSEPH F. SHIRTZ JOHNSON & JOHNSON ONE JOHNSON & JOHNSON PLAZA NEW BRUNSWICK, NJ 08933-7003 EXAMINER YOUNG, MICAH PAUL ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 10/01/2021 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): jnjuspatent@its.jnj.com lhowd@its.jnj.com pair_jnj@firsttofile.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte ANDREAS HUGERTH, KATARINA LINDELL, FREDERIK NICKLASSON, and KRISTINA THYRESSON1 ____________ Appeal 2021-000798 Application 13/355,768 Technology Center 1600 ____________ Before CAROLYN D. THOMAS, JEFFREY N. FREDMAN, and JOHN G. NEW, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies McNeil AB as the real party-in- interest. App. Br. 2. Appeal 2021-000798 Application 13/355,768 2 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1–2, 4–5, 7, 18–20, 22–27, and 30–35. Specifically, claims 1, 2, 4, 5, 7, 18–20, and 22–25 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Hansson (US 2004/0191322 A1, September 30, 2004) (“Hansson”), Adusumilli et al. (US 2004/0037879 A1, February 26, 2004) (“Adusumilli”), Parikh et al. (EP 1 219 291 A1, July 3, 2002) (“Parikh”), Sue et al. (WO 01/49270 A2, July 12, 2001) (“Sue”). Claims 1, 5, 7, 22–24, and 31–352 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Hansson, Adusumilli, Parikh, Sue, and Mezzache et al. (2003/0124184 A1, July 3, 2003) (“Mezzache”). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellant’s claimed invention is directed to a solid pharmaceutical dosage form for the release of nicotine in the oral cavity. Spec. Abstr. 2 Claims 26, 27, and 30 are also listed as rejected in the Final Office Action Summary (PTOL-326 (Rev. 11-13). However, neither Examiner nor Appellant otherwise addresses these claims in the Final Office Action, Answer, or Appeal Brief, respectively. Absent any argument on appeal by Appellant with respect to claims 26, 27, and 30, we summarily affirm the Examiner’s rejection of these claims. See 37 CFR § 41.37(c)(1)(iv) (“[A]ny arguments or authorities not included in the appeal brief will be refused consideration by the Board for purposes of the present appeal”). Appeal 2021-000798 Application 13/355,768 3 REPRESENTATIVE CLAIM Independent claim 1 is representative of the claims on appeal and recites: 1. A solid pharmaceutical dosage form comprising a core encapsulated by at least one film coating, wherein said dosage form is a lozenge and wherein: (i) the core comprises nicotine, a sweetener, a flavoring agent, and a buffer, wherein said nicotine is in the form of a nicotine cation exchanger and said buffer is selected from the group consisting of sodium bicarbonate and sodium carbonate; and (ii) the film coating comprises at least one film-forming polymer, a plasticizer and/or a surfactant, a sweetener and at least one flavoring agent, wherein said film-forming polymer is selected from the group consisting of hydroxy propyl methyl cellulose (HPMC) and polyvinyl alcohol, said plasticizer is selected from the group consisting or polyethylene glycol or triacetin, said surfactant is polyoxyethylene sorbitan monooleate, and said sweetener is selected from the group consisting of sucralose and aspartame, and wherein the at least one film coating is devoid of nicotine and devoid of buffer and wherein said core has a weight from about 50 mg to about 2000 mg and wherein said at least one film coating has a thickness from about 10 to about 500 microns and a weight of from about 1% to about 15% of the weight of the core and wherein the at least one film coating reduces an organoleptically disturbing sensation induced by said nicotine in the oral cavity until said dosage form is substantially dissolved as compared to an organoleptically disturbing sensation induced by nicotine in the oral cavity for an uncoated lozenge containing the same amount of nicotine, sweetener and flavoring agent as said solid pharmaceutical dosage form. Appeal 2021-000798 Application 13/355,768 4 App. Br. 10. ISSUES AND ANALYSIS We agree with, and adopt, the Examiner’s findings, reasoning, and conclusion that the claims are obvious over the teachings and suggestions of the combined cited prior art. We address Appellant’s arguments below. A. Claims 1, 2, 4, 5, 7, 18–20, and 22–25 The Examiner’s findings and conclusions The Examiner finds that Hansson teaches a solid pharmaceutical dosage form comprising a core coating with a film coating, in which the dosage is in the form of a lozenge and comprises nicotine, and the coating does not comprise a buffer. Final Act. 3 (citing Hansson Abstr., claim 29, ¶ 96). The Examiner finds that Hansson teaches that buffers can be used and include sodium bicarbonate or carbonate. Id. (citing Hansson ¶ 45). The Examiner finds that the core of the dosage form taught by Hansson comprises zinc salts or complexes, can comprise a cation exchange resin, and has a weight of about 1250 mg. Final Act, 3 (citing Hansson ¶¶ 27, 96, 60). The Examiner finds that nicotine is present in Hansson’s composition as a base, solvate, or complex. Id. (citing Hansson ¶ 27, claim 7). The Examiner also finds that Hansson teaches that the film coating further comprises one or more sweeteners like aspartame in the coating, and can also include sweeteners such as sugar alcohols and polyethylene glycol, and that the film-forming polymer is hydroxypropyl methylcellulose or methylcellulose. Id. (citing Hansson ¶¶ 96–97, 43, claim 41). The Appeal 2021-000798 Application 13/355,768 5 Examiner further notes that Hansson teaches a nicotine lozenge with a film coating that is not buffered and does not comprise nicotine. Id. The Examiner finds that, although Hansson teaches a coating material on its dosage form, it teaches different concentrations for the coating and is, furthermore, silent with respect to the dissolution of the coating. Final Act. 3. However, the Examiner finds that the coating of a nicotine core with an immediate release coating was known in the art, as taught by Adusumilli. Id. The Examiner finds that Adusumilli teaches a dosage form that can be in the form of a lozenge, tablet or capsule, and the core comprises nicotine, which can be present in its compositions in various forms including salts and complexes. Final Act. 3 (citing Adusumilli ¶¶ 5, 32). The Examiner finds that Adusumilli teaches a solid pharmaceutical dosage form comprising a core encapsulated by at least one coating, and that at least one coating comprises a film-forming polymer, hydroxypropyl methylcellulose, and is devoid of both nicotine and buffering agents. Id. (citing Adusumilli Abstr., Table 3). The Examiner notes that the coating of Adusumilli is about 2.3% of the weight of the core, weighing about 232 mg. Id. (citing Adusumilli Table 3, Table 1). The Examiner finds that Adusumilli teaches that the coating dissolves immediately, with nicotine being released within the first minute of administration. Id. (citing Adusumilli Fig. 2). The Examiner concludes that it would have been obvious to a person of ordinary skill in the art to combine this coating to the formulation of Hansson in order to impart an immediate release effect to the formulation. Final Act. 4. Appeal 2021-000798 Application 13/355,768 6 The Examiner acknowledges that although Hansson discloses a coated nicotine formulation, it is silent with respect to specific components cited in the claims presently on appeal before us. Final Act. 4. However, the Examiner finds, inclusion of plasticizers, surfactants and other components ancillary to a coated solid dosage form were well known in the art, as taught by Parikh. Id. The Examiner finds that Parikh teaches a taste-masked solid dosage form with a core and at a coating, the latter of which comprises film-forming polymers, and which has a thickness of about 40 microns when two coatings are applied. Final Act. 4 (citing Parikh Abstr., ¶¶ 25, 30). The Examiner finds that Parikh teaches that the coating comprises film-forming polymers, such as hydroxypropyl methylcellulose, a surfactant, and a plasticizer. Id. (citing Parikh ¶¶ 24–28). The Examiner finds that the surfactant taught by Parikh cam include polyoxyethylene sorbitan monooleate, and that the plasticizer include polyethylene glycol. Id. (citing Parikh ¶¶ 22, 28). The Examiner finds that Parikh further teaches that the coating may further comprise flavoring agents. Id. (citing Parikh ¶ 35, Examples). The Examiner finds that Parikh teaches that the total weight of the taste-masked coating is from 3–20% of the weight of the core. Id. (citing Parikh ¶ 32). The Examiner concludes that it would also have been obvious to combine these components with the coating materials of Hansson so as to improve the flavor of the formulation. Final Act. 4. The Examiner acknowledge that Parikh teaches different concentrations for its components, but points out that Parikh expressly teaches the general conditions of the claims on appeal. Id. The Examiner reasons that the prior art teaches a solid dosage form with a core and a coating that encapsulates the core where the Appeal 2021-000798 Application 13/355,768 7 core comprising nicotine and coating comprises film-forming polymers and components that reduce organoleptic disturbances. Id. According to the Examiner, when the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranged by routine experimentation. Id. (citing In re Aller, 220 F.2d 454, 456 (C.C.P.A. 1955). The Examiner reasons that the combined teachings of the cited prior art provide for a solid pharmaceutical dosage form, in the form of a lozenge, with at least one coating, in which the core comprises nicotine, and the coating comprising polymers, plasticizer, surfactant and sweetener. Final Act. 4. The Examiner notes, however, that the prior art cited previously is silent with respect to the limitation reciting the reduction of organoleptically-disturbing sensations associated with nicotine, in comparison to an uncoated dosage form. Id. However, the Examiner finds, the use of such film coatings, comprising similar components, are well known in the art to shield the user from the negative effects of bitter- or ill- tasting drugs cores, especially those of plant or organic extracts. Id. at 4–5. The Examiner finds that such film coatings are taught by Sue. Id. at 5. The Examiner finds that Sue teaches a solid dosage form with an odor and taste masking coating applied to the core. Final Act. 5 (citing Sue Abstr.). The Examiner finds that the coating taught by Sue is specifically designated to effectively mask the unpleasant odor and taste of plant extract in the core of the dosage form. Id. (citing Sue, 3). The Examiner finds that the coating taught by comprises hydroxypropyl methylcellulose, polyethylene glycol and sweeteners. Id. (citing Sue, 6). Appeal 2021-000798 Application 13/355,768 8 The Examiner concludes that it would have been obvious to a person of ordinary skill in the art that combining the coating of Sue with the teachings of the prior art cited supra would have been useful in providing a masking effect for the negative organoleptically-disturbing sensation induced by nicotine. Final Act. 5. The Examiner reasons that this is because the coating does not comprise nicotine and the coating is effective for masking the taste and smell of the core ingredient and, additionally, comprises sweetening agents that would further mask the taste, as taught by Sue. Id. Issue 1 Appellant argues that the Examiner erred by finding that the combined cited prior art teaches or suggests a film coating that: reduces an organoleptically disturbing sensation induced by said nicotine in the oral cavity until said dosage form is substantially dissolved as compared to an organoleptically disturbing sensation induced by nicotine in the oral cavity for an uncoated lozenge containing the same amount of nicotine, sweetener and flavoring agent as said solid pharmaceutical dosage form, as recited in claim 1. App. Br. 5. Analysis Appellant argues that a person of ordinary skill in the art would not have any motivation or suggestion to consider or combine the references cited, other than via hindsight analysis. App. Br. 5. Appellant first contends that the teachings of Hansson are deficient because: (1) Hansson does not teach the addition of a flavoring agent or surfactant in a film coating; (2) although the coating disclosed in Hansson Appeal 2021-000798 Application 13/355,768 9 acts to delay the release of nicotine (citing Hansson ¶¶ 42–43), Hansson does not teach a coating for a lozenge that acts to reduce the organoleptically disturbing sensation induced by nicotine even after such coating has dissolved; (3) Hansson does not teach a coating with a thickness from (a) about 10 to about 500 microns, (b) a weight from about 1% to about 15% of the weight of the core, or (c) that dissolves or disintegrates in less than one minute from the moment of administration. App. Br. 5–6 (citing Final Act. 5). Appellant contends that Adusumilli does not cure the alleged deficiencies of Hansson. Final Act. 6. According to Appellant, Adusumilli does not teach the addition of a plasticizer and/or a surfactant, a sweetener, and a flavoring agent in a film coating. Id. Further, argues Appellant, Adusumilli neither teaches nor suggests a coating used for taste masking of organoleptically disturbing sensations induced by nicotine. Id. Appellant also asserts that the dosage form disclosed in Adusumilli is not a lozenge, but is rather a controlled-release oral dosage form that may provide an immediate release of nicotine in the oral cavity followed by further release of nicotine once the dosage form reaches the gastrointestinal tract. Id. (citing Adusumilli ¶¶ 14–15). Appellant argues that there would have been no motivation or suggestion for a person of ordinary skill in the art to combine the teachings of Hansson and Adusumilli. Id. Rather, argues Appellant, a person of ordinary skill in the art would not have looked to Adusumilli for suggestions on how to develop a taste masking coating for a nicotine-containing lozenge as the reference does not relate to a lozenge or to taste masking. Id. Appeal 2021-000798 Application 13/355,768 10 Similarly, argues Appellant, the Examiner relies upon Parikh as teaching “[t]he inclusion of plasticizers, surfactants and other ancillary components to a coated solid dosage form are well known in the art.” Final Act. 6 (citing Final Act. 4). However, Appellant argues, Parikh teaches “texture masked particles” that “advantageously exhibit sufficient elasticity without the need for added plasticizers to maintain integrity during tableting and prevent release of the drug into the mouth during chewing.” Id. (citing Parikh ¶¶ 7–8). Appellant contends that Parikh does not teach a lozenge which remains in the oral cavity over a period of time-releasing drug, does not disclose coatings for a lozenge and does not disclose nicotine as an active ingredient and, therefore, does not teach a taste-masking coating for a nicotine-containing lozenge. Id. Appellant acknowledges that Parikh teaches a texture-masking coating and a taste-masking coating. Final Act. 6 (citing Parikh ¶¶ 12–21, 22–31). However, Appellant argues, neither coating contains all of the limitations of claim 1, nor does Parikh teach a coating that reduces an organoleptically-disturbing sensation induced by nicotine in the oral cavity during administration of a lozenge. Id. By way of example, Appellant contends that Parikh does not teach the addition of a flavoring agent to a film coating. Id. at 6–7. Appellant acknowledges that Parikh states that flavors may be added to the chewable tablet, but does not disclose flavors as ingredients in a film coating. Id. at 7 (citing Parikh ¶ 35, Example 2 (listing a coating with no flavor (or polyoxyethylene sorbitan monooleate the surfactant required by claim 1 of the invention) present. Id. Appellant next notes that the Examiner points to Sue as teaching that “the use of … film coatings, comprising similar components are well known Appeal 2021-000798 Application 13/355,768 11 to shield the user from the negative effects of bitter or ill tasting drug cores.” App. Br. 7 (citing Final Act. 5). Appellant contends however, that Sue does not disclose a lozenge that dissolves in the mouth, but instead discloses a tablet with multiple coatings that can be immediately swallowed. Id. According to Appellant, Sue discloses a tablet that contains valerian extract, which is well known to have a pungent and noxious odor and multiple coatings are required to mask its smell. Id. (citing Sue, Background; also citing Declaration of Katarina Lindell (the “Lindell Declaration”)). Appellant further contends that Sue does not teach a coating with all of the elements required by claim 1. App. Br. 7. Appellant asserts that Sue does not disclose the sweeteners required by claim 1 (sucralose or aspartame) nor does Sue disclose the use of artificial sweeteners in a coating at all. Id. (citing Sue 6). Appellant contends that a skilled artisan would not look to Sue for suggestions on how to develop a taste masking coating for a nicotine-containing lozenge, because the reference does not relate to a lozenge or to taste masking. Id. (citing Lindell Decl.). We are not persuaded by Appellant’s arguments. As an initial matter, all of the references cited by the Examiner are related to oral dosage forms; Hansson and Adusumilli are expressly directed to forms with nicotine as the active agent, and Sue teaches valerian as an active agent, but also teaches “masking or reducing the detectable presence of certain characteristic odor or odors, taste or tastes of pharmaceutical preparations.” See Hansson, Abstr., Adusumilli, Abstr., Sue, Abstr. Parikh likewise teaches that “[c]ertain drug particles have a bitter or otherwise unpleasant taste. In order to make palatable chewable tablets from these, their taste must be masked for example by dispersing or coating the particles with a coating Appeal 2021-000798 Application 13/355,768 12 composition.” Parikh ¶ 3. Consequently, all of the references are directed to analogous art, i.e., directed to oral dosage forms with active agents that produce an organoleptically-disturbing sensation. A person of ordinary skill in the art of oral dosage forms could be expected to be familiar with all of the teachings of these references. See Standard Oil Co. v. American Cyanamid Co., 774 F.2d 448, 454 (Fed. Cir. 1985) (holding that a person of ordinary skill in the art is “presumed to be aware of all the pertinent prior art”). Appellant’s arguments are not persuasive because Appellant’s contentions do not accurately reflect the Examiner’s findings of fact and legal conclusion of obviousness. The Examiner acknowledges that, as Appellant argues, Hansson does not teach or suggest the addition of a flavoring agent or surfactant in a film coating, a coating for a lozenge that acts to reduce the organoleptically disturbing sensation induced by nicotine even after such coating has dissolved, or a coating with a thickness from (a) about 10 to about 500 microns, (b) a weight from about 1 % to about 15% of the weight of the core, or (c) that dissolves or disintegrates in less than one minute from the moment of administration. The Examiner relies upon the additional references as teaching these limitations. Specifically, the Examiner relies upon Adusumilli as teaching “coating of a nicotine core with an immediate release coating.” See Final Act. 3. Adusumilli teaches “[that] [o]ne preferred transmucosal delivery system is a lozenge for buccal delivery, comprising nicotine dispersed in an adsorbent or absorbent excipient and a nonnutritive sweetener, preferably made by direct compression.” Adusumilli ¶ 5. Adusumilli further teaches that the nicotine core can be contained within a controlled release Appeal 2021-000798 Application 13/355,768 13 formulation made using a dry coating process. See Adusumilli ¶ 27 (teaching that “[c]ellulosic materials and polymers, including alkylcelluloses provide hydrophobic materials suitable for forming the oral release layer or for coating the beads….); see also Fig. 3. Adusumilli also teaches that the coating can comprise hydroxypropyl methylcellulose. Adusumilli, Table 3. Furthermore, we agree with the Examiner that Adusumilli teaches emodiments in which coating is about 2.3% of the weight of the core (Table 3) and has a mass of about 232 mg (Table 1), both of which fall squarely within the ranges recited in claim 1. The Examiner turns to Parikh as teaching that the inclusion of plasticizers, surfactants and other ancillary components to a coated solid dosage form were known in the art at the time of invention. See Final Act. 4. Parikh teaches: [T]exture masked particles are comprised of a core containing an active ingredient, an optional first coating layer comprised of a taste masking agent that substantially covers the core; and a second coating layer, which optionally may substantially cover the first coating layer or the core, comprised of a film forming polymer and a[n] anti-grit-agent. Parikh Abstr. Parikh further teaches that: The first layer coating is then overcoated with a texture masking coating layer comprised of a water soluble and/or water swellable film forming polymer and an anti-grit agent. Examples of suitable film forming polymers include, but are not limited to, all pharmaceutically suitable water soluble cellulosic polymers that nonexclusively include hydroxypropyl methylcellulose (“HPMC”),….” Parikh ¶ 26. Furthermore, Parikh teaches that: Appeal 2021-000798 Application 13/355,768 14 The thickness of the texture masking overcoating on the coated core is typically from about 1 to about 20 microns, e.g., from about 2 to about 15 microns or from about 4 microns to about 9 microns. The texture masking overcoating is present in an amount, based upon the weight of the taste masked particle, from about 2 percent to about 40 percent, e.g. from about 3 percent to about 20 percent or about 5 percent to about 10 percent. Parikh ¶ 30. Parikh thus teaches ranges of coating thickness and relative weight that overlap with the ranges recited in claim 1. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (holding that “[i]n cases involving overlapping ranges, we and our predecessor court have consistently held that even a slight overlap in range establishes a prima facie case of obviousness.) Although Parikh teaches that, in its formulations “[t]he overcoated particles of the invention advantageously exhibit sufficient elasticity without the need for added plasticizers to maintain integrity during tableting and prevent release of the drug into the mouth during chewing” (Parikh ¶ 12), Adusumilli teaches that: The oral release layer comprises a film formed of one or more water soluble polymers, one or more plasticizers, a source of nicotine and, of course, small amounts of the solvent, e.g. water, used in processing. Water soluble polymers found useful in the present invention are hydrophilic polymers and polysaccharides, and alkylcellulose polymers. Adusumilli ¶ 25. Hansson also teaches that plasticizers were well known in the art. See Hansson, ¶ 78. Finally, the Examiner relies upon Sue as teaching a coating “specifically designated to effectively mask the unpleasant odor and taste of plant extract in the core of the dosage form” and that the coating comprises hydroxypropyl methylcellulose, polyethylene glycol and sweeteners. Sue, 3, Appeal 2021-000798 Application 13/355,768 15 6. Moreover, both Hansson and Parikh teach the use of aspartame as a sweetener, as recited in claim 1. See Hansson ¶ 96, Parikh ¶ 35. “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Furthermore, “If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” Id. at 417. The combined teachings of the prior art cited by the Examiner teems with such predictable variations of the elements recited in claim 1. We agree with the Examiner that the combination of the familiar elements recited in claim 1 would have been prima facie obvious to a person of ordinary skill in the art at the time of invention. However, Appellant argues that its allegedly unexpected results overcome the Examiner’s prima facie conclusion of obviousness. Accordingly, we next turn to Appellant’s contention in that respect. Issue 2 Appellant argues that the unexpected results disclosed by the Specification overcome the Examiner’s prima facie conclusion of obviousness. App. Br. 7–8. Analysis Appellant contends that it has unexpectedly discovered that a coating with at least one-film forming polymer, a plasticizer and/or a surfactant, a sweetener and at least one flavoring agent unexpectedly reduced the rate of tingling/burning sensation associated with a nicotine containing lozenge. Appeal 2021-000798 Application 13/355,768 16 App. Br. 8 (citing Lindell Decl.). Appellant points to Example 11 of the Specification, which: [C]ompared two nicotine lozenge 4 mg formulations; lozenge A, uncoated, with all of flavoring agents and sweeteners in the tablet core, lozenge B with an additional film coating. The additional film coating for lozenge B carried a portion of flavoring agents and sweeteners, while corresponding amount was withdrawn from the lozenge core. Thus the total amount of flavoring agents and sweeteners was the same in both lozenges. The lozenge cores for both A and B had the same composition except for the amounts of flavoring and sweetening agents. Spec. 28. Applicant contends that the study of Example 11 unexpectedly found that 75% of participants gave the lowest score (almost no burning/tingling) on a five-grade scale after 30 seconds of testing for formulation B while only 44% of participants gave the lowest score for formulation A. App. Br. 8. Appellant asserts that this unexpected effect of adding the coating was persistent even after the lozenge had completely dissolved as 63% of participants gave the lowest score for formulation B while only 44% gave the lowest score for formulation A. Id. According to Appellant, such an unexpected finding is not taught, nor suggested, by Hansson, especially with a dosage form where the coating is only from about 1 % to about 15% of the weight of the core. Id. We are not persuaded. “To be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Circ. 2014). Example 11 expressly compares “two Appeal 2021-000798 Application 13/355,768 17 nicotine lozenge 4 mg formulations; lozenge A, uncoated, with all of flavoring agents and sweeteners in the tablet core, lozenge B with an additional film coating.” Spec. 28. Hansson, the closest prior art, expressly teaches (as do the other references) oral formulations with a core and a coating. See, e.g., Hansson ¶¶ 42, 96–97. Consequently, to be probative of unexpected results, Appellant must demonstrate that its claimed composition demonstrates unexpected results when compared to the compositions taught by Hansson. Having failed to meet this burden, the results disclosed by Example 11 of Appellant’s Specification are not dispositive of unexpected results. B. Claims 1, 5, 7, 22–24, and 31–35 Appellant repeats by reference the arguments presented with respect to Issue A.1 supra, and contends that Mezzache also fails to disclose or suggest the claimed lozenge. App. Br. 9. Appellant argues further that Mezzache teaches away from a lozenge, as acknowledged by the Examiner, and teaches, rather, a “fast dissolving oral formulation where the film dissolves within 30 seconds.” Id. (citing Final Act. 6). Appellant notes that the Examiner further finds that Mezzache teaches that “‘the fast dissolving film of Mezaache provides almost immediate release of nicotine to the body upon administration.’” Id. This is in contrast, argues Appellant, to the requirements of claim 1, which requires that the film coating is “devoid of nicotine.” Id. Appellant asserts that, in the present invention, the nicotine resides in the core of the lozenge, which is not fast dissolving, but rather is slower-dissolving to allow the product to act as a lozenge. Id. Appeal 2021-000798 Application 13/355,768 18 The Examiner responds that the coatings used to surround the core comprising the active agent, as taught by Mezzache, do not comprise any active agents. Ans. 10 (citing Mezzache ¶¶ 96–126). The Examiner finds that the coatings of Mezzache comprise the same cellulose polymers, flavors, and plasticizer of the claims on appeal. Id. (citing Mezzache ¶ 80). The Examiner relies upon Hansson as teaching the compositional components of Appellant’s claims, and that Hansson also establishes the level of skill in the art regarding oral formulations, such as chewable tablets, lozenges, particles, etc. Id. The Examiner concludes that it would have been obvious to modify the speed of the release by combining the teachings of Hansson and Mezzache. Id. The Examiner notes that Appellant argues that the core of the instant claims is slow-releasing. Id. The Examiner finds that the core of Hansson is also slow releasing, and that a person of ordinary skill in the art would have understood that the core of Hansson could be modified by the similar film coating of Mezzache, as they have similar components and solve the same problem. Id. We are not persuaded by Appellant’ argument. The Examiner relies upon Mezzache as teaching the use of the recited cellulose polymer (hydroxypropyl methylcellulose, see Mezzache ¶ 99), flavoring agent (see Mezzache ¶¶ 112, 123, 135), and plasticizer (polyethylene glycol, see Mezzache ¶¶ 76, 77, 80) in the coatings of the active-agent containing core of the claims on appeal. Mezzache teaches that its compositions can contain nicotine as an active agent. Mezzache ¶ 63. More importantly, the Examiner relies upon Mezzache, in combination with the remaining cited references, and Appeal 2021-000798 Application 13/355,768 19 especially Hansson, as teaching elements of controlled-release coatings that are well understood in the art. Specifically, Mezzache teaches: One or both of the microspheres and the dosage units can be coated or encapsulated with at least one coating. Useful coating formulations contain polymeric ingredients as well as excipients conventionally employed in such coatings. The coatings are generally used for such purposes as taste-masking, controlling release and the like. Mezzache ¶ 97. We agree with the Examiner that a person of ordinary skill in the art would have understood that the controlled-release coatings of Mezzache, in combination with those taught by the other cited references, as a means controlling the release of the active agent, nicotine, situated in the lozenge core. We are consequently not persuaded by Appellant’s arguments. CONCLUSION The rejection of claims 1–2, 4–5, 7, 18–20, 22–27, and 30–35 as unpatentable under 35 U.S.C. § 103(a) is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136. AFFIRMED Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 2, 4, 5, 7, 18–20, 22–25 103(a) Hansson Adusumilli, Parikh, Sue 1, 2, 4, 5, 7, 18–20, 22– 25 Appeal 2021-000798 Application 13/355,768 20 Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 5, 7, 22– 24, 31–35 103(a) Hansson Adusumilli, Parikh, Sue, Mezzache 1, 5, 7, 22– 24, 30–35 Overall Outcome 1–2, 4–5, 7, 18–20, 22– 27, 30–35 Copy with citationCopy as parenthetical citation