Ex Parte MayerDownload PDFPatent Trials and Appeals BoardMay 1, 201911992823 - (D) (P.T.A.B. May. 1, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 11/992,823 03/26/2008 20462 7590 05/03/2019 GlaxoSmithKline Global Patents UP4110 1250 South Collegeville Road Collegeville, PA 19426 FIRST NAMED INVENTOR Friedrich Karl Mayer 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 ATTORNEY DOCKET NO. CONFIRMATION NO. CN34537 2978 EXAMINER CHONG,YONGSOO ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 05/03/2019 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): US_cipkop@gsk.com laura.m.mccullen@gsk.com eofficeaction@appcoll.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte FRIEDRICH KARL MA YER1 Appeal2018-006674 Application 11/992,823 Technology Center 1600 Before RYAN H. FLAX, RACHEL H. TOWNSEND, and CYNTHIA M. HARDMAN, Administrative Patent Judges. HARDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims directed to a method of treatment of a dermatophyte skin infection using a single dose of a film-forming composition that is maintained on the skin for at least 48 hours. The Examiner rejected the claims as obvious over the prior art. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. 1 Appellant identifies the real party in interest as "Novartis Consumer Health SA." (Br. 3.) Herein, we reference the Specification filed Mar. 26, 2008 ("Spec."); Final Office Action mailed Oct. 25, 2017 ("Final Action"); Appeal Brief filed Jan. 31, 2018 ("Br."); and Examiner's Answer mailed Apr. 12, 2018 ("Answer"). Appeal2018-006674 Application 11/992,823 STATEMENT OF THE CASE The Specification states that topical pharmaceutical compositions designed to treat dermatophyte infections exist, but "fully complying with the regimen to a successful treatment is difficult and premature terminations of the treatment are common." Spec. 1. Accordingly, the present invention is directed to "a topical liquid antifungal composition containing an antifungal agent, a film-forming agent and a solvent," which provides "a single-dose application composition for treating dermyotophyte [sic] infections, making the treatment simple." Id. at 2. Claims 5, 8, 9, and 17-46 are on appeal. Claim 5 is illustrative and reads as follows: 5. A one dose method of treatment of a dermatophyte skin infection selected from tinea pedis, tinea corporis, tinea cruris and tinea capitis, said method comprising topically applying to the infected skin a single dose of a film-forming composition capable of adhering to the skin for a period of at least 48 hours, and maintaining said composition on the skin for at least 48 hours, said composition comprising upon application a) an antifungal agent terbinafine or a salt thereof, b) a hydrophilic film-forming agent comprising a hydroxyalkyl cellulose, and c) a hydrophobic film-forming polymer selected from the group consisting of octylacrylamide, octylacylamide acrylate copolymer; octylpropenamide acrylate copolymer, in a solvent selected from an aqueous solvent, organic solvent, or a mixture thereof, whereby said single dose application of said composition results in sufficient absorption of the antifungal agent by the stratum comeum to provide effective treatment of the dermatophyte skin infection, said effective treatment consisting 2 Appeal2018-006674 Application 11/992,823 of a mycological cure rate of at least 50% at six weeks following application of said single dose. Br. 23 (Claims Appendix). The claims stand rejected as follows: Claims 5, 8, 9, 17-20, 23-42, and 46 are rejected under 35 U.S.C. § 103(a) as obvious over Chaudhuri,2 Canter,3 and Sawaya.4 Final Act. 3. Claims 21-22 and 43-45 are rejected under 35 U.S.C. § 103(a) as obvious over Chaudhuri, Canter, Sawaya, and Edgren. 5 Id. at 6. The issue with respect to these rejections is whether the Examiner has established a prima facie case of obviousness by the preponderance of the evidence. DISCUSSION The Examiner determined that claims 5, 8, 9, 17-20, 23-42, and 46 would have been obvious over Chaudhuri, Canter, and Sawaya, and that claims 21, 22, and 43-45 would have been obvious over the same combination of references plus Edgren. The Examiner found that Chaudhuri teaches topical formulations for the treatment of nail fungal diseases, which comprise about 1-10% of an antifungal compound (butenafine ), about 0.1- 3% of a film-forming agent (polyvinyl acetate or vinylpyrrolidone/vinylacetate copolymer), about 0.5-15% of a gelling agent (hydroxypropylcellulose ), and 30-70% by weight of a solvent. Final Act. 3. 2 Chaudhuri et al., US Patent 6,143,794, issued Nov. 7, 2000. 3 Canter et al., US Patent 6,060,547, issued May 9, 2000. 4 Sawaya, US Patent 5,519,059, issued May 21, 1996. 5 Edgren et al., US Patent 5,006,346, issued Apr. 9, 1991. 3 Appeal2018-006674 Application 11/992,823 The Examiner further found that Chaudhuri also teaches other antifungal agents, including terbinafine. Id. at 3-4. The Examiner acknowledged that Chaudhuri does not disclose the film-forming agent octylacrylamide acrylate copolymer (available under the tradename DERMACRYL). Id. at 4. The Examiner cited Canter, which teaches that DERMACRYL is a well-known film-forming polymer. Id. The Examiner stated that a person of ordinary skill in the art would have been motivated to substitute the film-forming agent in Chaudhuri with Canter's DERMACRYL "because of the functional equivalency of both being well- known film-forming polymers," and because "Canter et al. teaches that Dermacryl is water soluble and thus provides the additional benefit of ease in formulation." Id. at 5. Regarding the claim limitation "maintaining said composition on the skin for at least 48 hours," the Examiner stated that "none of the cited prior art teaches removing the composition after a certain period of time after application," and that "[i]t would have been obvious to maintain such composition on the skin so as to permit sufficient time for the active agents to be effective." Id. at 6. We adopt the Examiner's findings of fact and rationale on obviousness as set forth in the Final Action and Answer. We address Appellant's arguments below. Findings of Fact The following findings of fact highlight certain evidence. FF 1. Chaudhuri states: "[T]he invention relates to a stable topical formulation useful for the treatment of a nail fungal disease, comprising an 4 Appeal2018-006674 Application 11/992,823 antifungal agent and one or more pharmaceutically acceptable excipients sufficient to form a gel capable of delivering the antifungal through the nail barrier." Chaudhuri 2:11-16. Chaudhuri further states: "The antifungal compound useful in this invention is one that is effective when applied topically to treat the fungal infection." Id. at 4:61-63. Chaudhuri further states that "[t]he antifungal agents of particular utility in this invention have a structure represented by Formula (I)," and that butenafine, one of the agents that falls within the scope of Formula I, is of "particular interest." Id. at 5:22-30. FF2. Chaudhuri discloses that the composition comprises a therapeutically effective amount of an antifungal compound, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient to provide a mixture having a consistency sufficient to adhere to the surface of a nail so that the antifungal is delivered through the nail plate. Generally the composition is a liquid or semisolid, such as a cream, ointment, lotion, or gel (preferably a gel) having a solvent in which the antifungal compound, or its salt, is dissolved. Thus, the composition will contain at least the antifungal compound, a solvent for the compound, and a gelling agent. Id. at 4:40-51. The composition may also include a film-forming agent. Id. at 4:52-59. FF3. With respect to preferred gelling agents, Chaudhuri states: "Preferably the gelling agent is chosen from methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl- cellulose, carboxymethylcellulose and carbomer." Id. at 6:42-45. 5 Appeal2018-006674 Application 11/992,823 FF4. Chaudhuri states: "The gel composition of this invention is characterized by its ability to adhere to the nail being treated." Id. at 6:46- 47. It further states: To further aid in retaining the gel composition of this invention on the surface of the nail, the composition may optionally include a film-forming agent in an amount sufficient to form a film on the surface of the gel exposed to air. Representative optional film forming agents include povidone (l-ethyenyl-2- pyrrolidone polymers, e.g., PVP K-90)[,] polyvinyl alcohol, polyvinyl acetate, polyvinylethyl ether, polyviny[l]stearyl ether, vinylpyrrolidone[/] vinylacetate copolymers, nitrocellulose and the like. Id. at 7:59-67. FF5. Chaudhuri states: Once the composition is on the nail it is retained there for an appropriate length of time that will depend on the concentration of the active ingredient in the composition and the individual patients' requirements. The composition may be kept on for a shorter period of time if a higher concentration of the active ingredient is employed and is kept on for a longer period of time if a lower concentration is used. Id. at 10:43-49. FF6. Chaudhuri states: Preferably, the composition will be maintained in contact with the nail for a period of time during which the patient is sleeping or inactive to avoid contact that might remove the composition from the nail. Thus, this will generally be up to about 24 hours, and usually about 4 to about 12 hours. Preferably a composition is kept on the nail for about 6 to 10 hours, more preferably about 8 hours. While it is conceivable that a regimen could be established wherein the composition is maintained in contact with the nail over an extended period of time, that is continuously, for example, for a week to a month, such a regimen would be somewhat difficult for a patient to adhere to. 6 Appeal2018-006674 Application 11/992,823 Id. at 10:50-61. FF7. With respect to film-forming polymers (see heading at col. 6, line 30), Canter states: "Examples of preferred polymers that have acceptable Tg [glass transition temperature], skin adhering properties and viscosity include ... Dermacryl acrylic resins (available from National Starch), polyvinylpyrrolidinones (PVP), including LUVISKOL Kl 7, K30 and K90 (available from BASF), water soluble copolymers of PVP, including PVP/VA S-630 and W-735 .... " Canter 7:4-20. Analysis Appellant argues that the present invention is directed to "a novel composition of polymers" and the active ingredient terbinafine, as well as a novel method of use, i.e., "a one time only treatment of a skin infection." Br. 13. We find, however, that there is no patentable distinction between prior art antifungal compositions and the features of the claimed composition, nor any patentable distinction relating to the claimed method of using the compositions. In other words, we find that Appellant's claims are directed to the combination of known pharmaceutical ingredients used for their known purposes, and that the composition is used in a known manner, to achieve predictable results. The Supreme Court has stated that "[t]he 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). "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 7 Appeal2018-006674 Application 11/992,823 objective reach of the claim. If the claim extends to what is obvious, it is invalid [or unpatentable] under§ 103." Id. at 419. The pharmaceutical components required by Appellant's independent claims are: the antifungal agent terbinafine; a hydrophilic film-forming agent that comprises hydroxyalkyl cellulose; a hydrophobic film-forming polymer (which can be octylacrylamide acrylate copolymer, i.e. DERMACRYL); and a solvent or mixture of solvents. Br. 23-26 (Claims Appendix). Chaudhuri teaches a composition having very similar components, i.e.: an antifungal agent, identifying terbinafine as such an agent (FFl, FF2); a gelling agent such as hydroxypropylcellulose (FF2, FF3); an optional film-forming agent (FF2, FF4); and a solvent (FF2). See also Final Act. 3-4. The main difference between the components of Chaudhuri's composition and the components of the claimed composition is the identity of the film-forming agent. While Chaudhuri identifies a number of representative film-forming agents (see FF4), it does not specifically identify the claimed hydrophobic film-forming agents, such as octylacrylamide acrylate copolymer (DERMACRYL). Final Act. 4. The Examiner found that a person of ordinary skill in the art would have been motivated to substitute Chaudhuri' s polyvinyl acetate or vinylpyrrolidone/vinylacetate copolymer (taught as suitable film-forming agents in Chaudhuri, see FF4), with Canter's DERMACRYL "because of the functional equivalency of both being well-known film-forming polymers," and because "Canter et al. teaches that Dermacryl is water soluble and thus provides the additional benefit of ease in formulation." Final Act. 5. In response, Appellant argues that DERMACRYL was "not 8 Appeal2018-006674 Application 11/992,823 chosen for use by Canter." Br. 18 (emphasis in original). This argument is not persuasive, because Canter in fact identifies DERMACRYL acrylic resins as preferred polymers. FF7. "[A] reference is not limited to the disclosure of specific working examples." In re Mills, 4 70 F .2d 649, 651 (CCP A 1972). "Patents [ and publications] are part of the literature of the art and are relevant for all they contain." In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991). Appellant makes several arguments directed to distinguishing Chaudhuri's compositions from those in the claims. First, Appellant argues that Chaudhuri is directed to formulations comprising butenafine, not terbinafine. Br. 14. This reads Chaudhuri too narrowly. The reference is not limited to butenafine compositions. Rather, Chaudhuri discloses use of antifungals in its formulations more generally, with butenafine merely being one such preferred antifungal agent. See, e.g., FF 1; see also Chaudhuri at 8:58-9:25 (Tables Band Care directed to any antifungal agent). As noted by the Examiner, Chaudhuri teaches that terbinafine, like butenafine, was a well-known antifungal agent. Final Act. 3-4, citing Chaudhuri at 1: 13-18; Ans. 3. Except when discussing preferred embodiments, Chaudhuri refers to its active components as "an antifungal agent," "an antifungal compound," or "the antifungal," generally. As such, we agree with the Examiner that the use of the antifungal terbinafine is suggested by Chaudhuri. "The question is whether there is something in the prior art as a whole to suggest the desirability, and thus the obviousness, of making the combination, not whether there is something in the prior art as a whole to suggest that the combination is the most desirable combination available." In re Fulton, 9 Appeal2018-006674 Application 11/992,823 391 F.3d 1195, 1200 (Fed. Cir. 2004) (citation and emphases omitted). We agree with the Examiner that Appellant has not provided persuasive evidence that any difference in "solubility and other physical parameters" between Chaudhuri' s disclosed, known antifungal agents would have given one of ordinary skill in the art reason not to use terbinafine in the Chaudhuri formulation. "[J]ust because better alternatives exist in the prior art does not mean that an inferior combination is inapt for obviousness purposes." In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012). Appellant asserts that the claimed compositions are liquid, whereas Chaudhuri "discusses compositions which are a liquid or a semi-solid." Br. 15. We are not persuaded that this patentably distinguishes the claimed compositions from those in Chaudhuri. Rather, we agree with the Examiner that the term "liquid" is not recited in Appellant's claims (Final Act. 8-9; Ans. 4-5), and in any event, Appellant acknowledges that Chaudhuri discloses liquid compositions. Br. 15; see also FF2. Appellant also asserts that Chaudhuri does not require a film-former (it is only optional), and that in general, the total amount of film-forming polymers used in Appellant's claims will exceed that taught by Chaudhuri. Br. 15. We are not persuaded by these arguments. First, Chaudhuri not only teaches the use of film formers, but exemplifies and claims compositions comprising film formers. Final Act. 8; Ans. 5; Chaudhuri claim 1. Second, not all of Appellant's claims require specific amounts of film-formers. But, even where the claims do recite such amounts, the recited amounts overlap with the amounts taught by Chaudhuri. See Chaudhuri 7:67-8:4 (teaching that the "optional film forming agent will be present in an amount of from 10 Appeal2018-006674 Application 11/992,823 0% by wt. to about 5% by wt."); Br. 15 (acknowledging that the amount of film-forming polymer taught in Chaudhuri ("about Oto about 5% w/w") overlaps with Appellant's preferred range of 0.05 to 30% for each of the film-forming polymers); Ans. 5. The disclosure of an overlapping range such as here is sufficient to establish a prima facie case of obviousness. In re Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003). Thus, "the burden [ shifted] to the applicant to show that his invention would not have been obvious" (id. at 1330), such as (1) by establishing "the existence of unexpected properties in the range claimed" or (2) by showing "that the art in any material respect taught away" from the claimed invention. In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997) (citation omitted). Appellant has done neither. We are also not persuaded by Appellant's argument that "Chaudhuri does not even contemplate nor disclose use of a mixture of film formers." Br. 15. In addition to the optional film-forming agent, Chaudhuri teaches use of a gelling agent such as hydroxypropylcellulose (FF2, FF3), which the Specification indicates is a suitable hydrophilic film-forming agent. Spec. at 4. Accordingly, Chaudhuri's gelling agent in combination with its film- forming agent constitutes a mixture of film-forming agents, as contemplated by Appellant's disclosure. Appellant also argues that Canter has several shortcomings, including that it does not contemplate inclusion of a pharmaceutically acceptable active agent, and that it fails to teach that "use of a Dermacryl product without a second hydrophobic film forming polymer would produce an effective treatment for a dermatophyte skin infection." Br. 18-19 ( emphasis 11 Appeal2018-006674 Application 11/992,823 in original). We are not persuaded by these arguments because they fail to account for the teachings of Chaudhuri and Sawaya, which together teach treatment of a dermatophyte skin infection using a composition comprising a film-forming agent. "[O]ne cannot show non-obviousness by attacking references individually where, as here, the rejections are based on combinations of references." In re Keller, 642 F.2d 413,426 (CCPA 1981) ( citation omitted). In a similar vein, Appellant argues that Chaudhuri is directed to nail infections, whereas the instant claims are directed to skin infections. Br. 14. This argument ignores Sawaya, which teaches that the same fungus discussed in Chaudhuri is well-known to infect both nails and skin. Final Act. 5-6. And although Appellant argues that differences are required between nail and skin formulations to achieve the desired end effect (Br. 15), Appellant has not identified any such difference that is pertinent here. Indeed, Appellant did not dispute the Examiner's finding that "[s]ince Chaudhuri teaches a composition designed to penetrate the less permeable barrier of the nail, one of ordinary skill in the art would expect better penetration for the skin layer with the same composition." Ans. 4. Appellant also makes several arguments regarding differences between the claimed method of use and the methods taught in Chaudhuri. Specifically, Appellant argues that Chaudhuri teaches "on and off daily usage," whereas the claims teach a "one dose method" and maintaining the composition on the skin for at least 48 hours. Br. 16-17. Appellant further argues that the instant claims require administration of an effective amount of the composition to produce the claimed "mycological cure rate," and that 12 Appeal2018-006674 Application 11/992,823 "[o]ne has no way of knowing that a one-time only application of the formulations of Chaudhuri will produce in use an effective amount of the formation being present on the skin (not the nail) at least 48 hours after application." Id. at 17. We are not persuaded by Appellant's arguments, which again read Chaudhuri too narrowly. We must consider the prior art for all that it teaches and suggests; both preferred and non-preferred embodiments must be considered. See, e.g., Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976) ("[I]n a section 103 inquiry, 'the fact that a specific [embodiment] is taught to be preferred is not controlling, since all disclosures of the prior art, including unpreferred embodiments, must be considered."'). While Chaudhuri teaches a preference for an "on and off daily usage" for compliance reasons, it also contemplates an array of regimens where the composition is maintained in contact with the nail for longer periods, e.g., "for a week to a month." FF6. Moreover, the prior art indicates that the cure rate depends on the amount of the antifungal agent used and the length of time the composition is maintained on the patient. Specifically, Chaudhuri indicates that it was within the skill in the art to select an appropriate length of time over which to retain the composition on the patient, in view of the concentration of active ingredient used. FF5. For the reasons discussed above, we conclude that the Examiner has established a primafacie case that claims 5, 8, 9, 17-20, 23-42, and 46 would have been obvious over the combination of Chaudhuri, Canter, and 13 Appeal2018-006674 Application 11/992,823 Sawaya. Appellant has not persuaded us that the Examiner erred. Therefore, for the reasons above, we affirm this rejection. Appellant presents separate arguments relating to the Examiner's rejection of dependent claims 21, 22, and 43-45 based on the combination of Chaudhuri, Canter, Sawaya, and Edgren. Br. 19-21. These dependent claims additionally recite a plasticizer, which claim 22 specifically defines as a medium chain triglyceride. Id. at 25, 27-28 (Claims Appendix). The Examiner stated that "[a] person of ordinary skill in the art would have been motivated to add plasticizers because it will facilitate processing, increase flexibility, and toughness of the film forming polymer of the anti- fungal composition, thereby maintaining the integrity of the active agent over the intended delivery site." Final Act. 7. Appellant responds that Edgren is in a "non-analogous art area ( oral tablets versus topical compositions)," and that the choice of polymers "for oral use in producing a delayed absorption of the active are different from those chosen for use herein." Br. 21. Appellant also asserts that, although Edgren discusses plasticizers, "[t]here is no direction given to the skilled artisan to pick and choose amongst this long list a triglyceride as a preferred plasticizer, nor in particular a medium chain triglyceride as claimed in claim 22." Id. Edgren discloses the use of plasticizers to facilitate processing and to increase flexibility and toughness of drug coatings. Edgren at 5:26-32. Although Edgren discloses applying the coatings to a variety of dosage forms and devices (id. at 4:43-55), it is for the purpose of coating a drug formulation or device. Thus, even accepting that "plasticizers are generally known in the art to facilitate processing, increase flexibility, and toughness" 14 Appeal2018-006674 Application 11/992,823 (Final Act. 10) in coatings, still missing from the Examiner's analysis is an identification of any teaching that plasticizers (including medium chain triglycerides, as more-specifically recited in claim 22) are useful or desirable in the context of a liquid, semisolid, or gel drug formulation (FF2) where such a gel includes "a film-forming agent in an amount sufficient to form a film on the surface of the gel exposed to air" (FF4) after it has been topically applied. Accordingly, we find insufficient evidence in the record to support a conclusion that a skilled artisan would have been motivated to modify the formulations disclosed in Chaudhuri to add an Edgren plasticizer, with a reasonable expectation of success. Therefore, we reverse the rejection of claims 21, 22, and 43-45 based on the combination of Chaudhuri, Canter, Sawaya, and Edgren. SUMMARY We affirm the rejection of claims 5, 8, 9, 17-20, 23-42, and 46 under 35 U.S.C. § 103(a) as obvious over Chaudhuri, Canter, and Sawaya. We reverse the rejection of claims 21, 22 and 43-45 under 35 U.S.C. § 103(a) as obvious over Chaudhuri, Canter, Sawaya, and Edgren. 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. § l .136(a)(l )(iv). AFFIRMED-IN-PART 15 Copy with citationCopy as parenthetical citation