Ex Parte Kolter et alDownload PDFPatent Trial and Appeal BoardAug 26, 201613246324 (P.T.A.B. Aug. 26, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/246,324 09/27/2011 Karl Kolter 48394 7590 08/30/2016 SERVILLA WHITNEY LLC 33 WOOD A VE SOUTH SUITE 830 !SELIN, NJ 08830 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. PF71398 SE/GD 5477 EXAMINER COHEN, MICHAEL P ART UNIT PAPER NUMBER 1612 NOTIFICATION DATE DELIVERY MODE 08/30/2016 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): docket@dsiplaw.com jescobar@dsiplaw.com lmurphy@dsiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte KARL KOLTER and MAXIMILIAN ANGEL 1 Appeal2014-005479 Application 13/246,324 Technology Center 1600 Before DONALD E. ADAMS, FRANCISCO C. PRATS, and TIMOTHY G. MAJORS, Administrative Patent Judges. MAJORS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to coatings for dosage forms, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We AFFIRM. STATEMENT OF THE CASE Appellants disclose "protective coatings for pharmaceutical dosage forms containing acidic active ingredients, particularly film coatings based on a cationic polymer which is obtained by means of free-radical emulsion 1 Appellants identify the Real Party in Interest as BASF SE (App. Br. 3.) Appeal2014-005479 Application 13/246,324 polymerization of a monomer mixture comprising N,N- diethylaminoethylmethacrylate." (Spec. 1, 11. 9-12.) Claims 1-21 are on appeal. Claim 1 is illustrative: 1. A dosage form provided with protective coatings, in which a core comprising at least one acidic active ingredient is provided with at least one inner and one outer coating layer, where the outer layer comprises, as component A, a cationic polymer which is an emulsion polymer ofN,N- diethylaminoethyl methacrylate and further monomers. (App. Br. 16 (Claims App'x).) The claims stand rejected as follows: Claims 1-15 and 19-21under35 U.S.C. § 103(a) as unpatentable over Sastry et al. (US 2009/0197958 Al, publ. Aug. 6, 2009) ("Sastry") in view of Petereit et al. (US 2004/0249035 Al, publ. Dec. 9, 2004) ("Petereit '035"). Claims 16-18 under 35 U.S.C. § 103(a) as unpatentable over Sastry, Petereit '035, and further in view of Petereit et al. (WO 2006/010394, publ. Feb. 2, 2006) (CA 2570277 dated Dec. 13, 2006 used for translation) ("Petereit '394").2 ISSUE Does the preponderance of the evidence relied upon by the Examiner support a conclusion of obviousness? 2 This prior art reference is abbreviated "WO" by the Examiner in the record. (See, e.g., Ans. 6.) 2 Appeal2014-005479 Application 13/246,324 FACTUAL FINDINGS (FF) FF 1. The Examiner's findings of fact and statement of the rejections of claims 1-15 and 19-21 may be found at pages 3-9 of the Final Rejection dated February 22, 2013. (See also, Ans. 2---6, 7-10.) The Examiner's findings of fact and statement of the rejections of claims 16-18 may be found at pages 9-11 of the Final Rejection dated February 22, 2013. (See also, Ans. 6-7, 10-11.) We adopt the Examiner's findings and provide the following for emphasis. FF 2. Sastry teaches "[s]ustained release particulate oral dosage forms of (R)-baclofen prodrugs." (Sastry Abstract.) Sastry teaches an "[i]nert core [e.g., particulate form] can be coated with a formulation comprising a (R)-baclofen prodrug." (Id. at i-f 106; see also, id. at i-fi-1 105, 107.) FF 3. Sastry further teaches [O]ne or more additional coatings can be applied to particles having a coating of (R)-baclofen prodrug. The purpose of the one or more additional coatings can be for physical protection, and/or to facilitate further processing of the particles. These sealant or barrier coatings are not intended to modify or affect the release of a (R)-baclofen prodrug from the oral dosage form in the gastrointestinal tract. (Id. at i-f 109.) Materials that may be used in these "one or more additional [sealant or barrier] coatings" include hydroxypropyl methylcellulose and polyvinyl alcohol, among others. (Id.) FF 4. Sastry further teaches that "one or more additional coatings that impart desired release properties can be applied to a core having a coating of a (R)-baclofen prodrug. Such particles are referred to herein as controlled- 3 Appeal2014-005479 Application 13/246,324 release particles." (Id. at i-f 110.) Sastry discloses that "[a] controlled-release coating modifies or controls the release of a (R)-baclofen prodrug from a controlled-release particle in the gastrointestinal tract." (Id.) Sastry discloses "[ e ]xamples of coating materials for effecting controlled or modified release include ... methyl methacrylate copolymers, ... and methacrylic resins commercially available under the tradename Eudrag[i]t™" among others. (Id. at i-f 111.) Sastry discloses that "more than one controlled release coatings can be used to modify the release properties of a (R)-baclofen pro drug from a particle." (Id.) FF 5. Sastry further teaches that "a controlled-release coating can provide pH-dependent release of a (R)-baclofen prodrug from a particle having a coating of a (R)-baclofen prodrug in the gastrointestinal tract." (Id. at i-f 112.) According to Sastry, materials for use in such pH-dependent coating materials include, for example, "methacrylic acid ester copolymers." (Id.) Sastry teaches "[i]n certain embodiments, a pH-dependent coating can be a copolymer synthesized from diethylaminoethyl methacrylate and other neutral methacrylic esters, also known as methacrylic acid copolymers or polymer methacrylates, commercially available as Eudragit™ (Rohm Pharma)." (Id.) Sastry identifies several exemplary Eudragit™ polymers, such as Eudragit™ E, Eudragit™ L, and Eudragit™ S. (Id.; see also, id. at i-f 147 (describing other "useful pH-independent release polymers" that may be used or combined with other methacrylic acid copolymers, for example, to achieve a desired release property).) FF 6. Petereit '035 teaches methods of producing coatings for oral dosage forms. (Petereit '035 Abstract.) Petereit teaches the content of 4 Appeal2014-005479 Application 13/246,324 monomers having tertiary amino groups in a copolymer coating (id. at i-f 21) and the preparation of methacrylate copolymers by free-radical emulsion polymerization (id. at i-f 23). Petereit '035 further teaches representative thicknesses for a polymer layer in dosage forms, such as "between 1 and 100 µm, [and] preferably between 10 and 50 µm." (Id. at i-f 70.) FF 7. Petereit '394 teaches multi-layer dosage forms having a core, and inner and outer coatings. (Petereit '394 Abstract.) Petereit '394 teaches the inner layer includes a copolymer comprising polymerized vinylic monomers, and an outer copolymer layer comprising polymerized C1- to C4- alkyl esters of acrylic or of methacrylic acid, as well as methacrylate monomers. (Id. at 4, 11. 1-19.) Petereit '394 further teaches the inner layer may comprise polyvinyl acetate stabilized with polyvinylpyrollidone (Kollicoat® SR 30D), polyvinyl alcohol, as well as cellulose derivatives. (Id. at 7, 11. 12-19; id. at 8, 11. 1-14.) Petereit '394 also discloses the thickness of the inner coating layer "may be for example in the range of 10- 100, preferably from 20 to 40 µm." (Id. at 8, 11. 36-38.) Principles of Law "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'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). 5 Appeal2014-005479 Application 13/246,324 ANALYSIS Rejection Over The Combination Of Sastry And Petereit '035 Claim 1 The Examiner concludes it would have been obvious based on Sastry to design a dosage form having (R)-baclofen prodrug as the acidic active ingredient, and to coat that active ingredient with an inner sealant or barrier layer of a material such as polyvinyl alcohol, and an outer-controlled release layer, including a copolymer comprised of a methacrylic acid ester such as N,N-diethylaminoethyl methacrylate and other monomers. (Ans. 2--4, 8-10; FF 1-5.) Because the Examiner finds that Sastry does not specify that the outer layer is the product of emulsion polymerization, the Examiner turns to Petereit '035. (Ans. 4.) 3 The Examiner finds that Petereit '035 teaches the formation of copolymers for coatings through free-radical emulsion polymerization, and the Examiner concludes it would have been obvious to apply this known technique to synthesize the outer copolymer layer. (Id. at 4--5; FF 6.) The Examiner thus concludes that the skilled artisan would have predictably designed a modified dosage form within the scope of claim 1. (FF 1.) Appellants raise multiple counterarguments. Appellants argue Sastry does not teach "two discrete coating layers in the order claimed." (App. Br. 6; see also, Reply Br. 3--4.) More specifically, Appellants argue the layers in Sastry, are provided as "alternatives," not layers that would be used "at 3 The Examiner also relies on Petereit '035 for teaching elements for certain of the dependent claims (e.g., the thickness of the coating layer in claims 19-21 ). (Ans. 4.) 6 Appeal2014-005479 Application 13/246,324 the same time." (App. Br. 9.) Moreover, even if Sastry disclosed multiple layers, Appellants contend Sastry provides "absolutely no indication of the relative order for two such coatings." (Id. at 10.) Appellants also argue that, although Sastry identifies "diethylaminoethyl methacrylate" as one of the example materials useful for synthesizing a pH-dependent controlled-release layer, that identification is incorrect. (Id. at 8.) In fact, according to Appellants, Sastry should have identified "dimethylaminoethyl methacrylate," which is evident from the product sheets for Eudragit™ polymers. (Id. at 8-9.) Appellants thus argue the prior art and claim 1 are different, and that the Examiner has not provided sufficient reasoning to modify the dosage forms described in the art to arrive at the claimed subject matter. (Id. at 11-12.) Notwithstanding Appellants' arguments to the contrary, we agree with the Examiner that claim 1 would have been obvious over the combination of Sastry and Petereit '035. Appellants' argument that Sastry does not teach the claimed inner and outer layer is unpersuasive. The barrier or sealant layer disclosed in i-f 109 of Sastry is not an "alternative" to the controlled-release layer disclosed in paragraphs 110-112. (FF 3-5.) These layers provide a different function. Indeed, Sastry confirms the barrier or sealant layer is "not intended to modify or affect the release" of the active ingredient (FF 3), yet the purpose of the controlled-release layer is to do just that- modify or affect (i.e., prolong) the effect of the drug through sustained release. (FF 4--5.) Because the invention described in Sastry is related to sustained-release formulations, it would make little sense for the skilled artisan to use a barrier coating, 7 Appeal2014-005479 Application 13/246,324 which Sastry teaches is not intended to affect release of the drug in the gastrointestinal tract, and then not consider using the controlled-release coating to realize Sastry's objective. (See Sastry Abstract, i-fi-f l and 14.) At a minimum, Sastry suggests the barrier and controlled-release coatings should be used together, which is implied when these paragraphs appear immediately next to each other and teach that "one or more additional coatings can be applied" to the particles comprising the drug. (FF 2-5 (emphasis added). )4 Appellants' argument that the Examiner erred because Sastry does not teach the relative order of the layers is similarly unpersuasive. Instead, we agree with the Examiner that "[i]t is within the knowledge of the ordinary practitioner to determine the order of application [of] the coatings based on their individual functions." (Ans. 9.) The Examiner has bolstered that reasoning by noting that Sastry teaches "the specific coatings have a particular purpose, such as physical protection of the drug in the core." (Id.) We thus conclude, based on the preponderance of the evidence, that the skilled artisan would have predictably designed a dosage form with inner 4 Sastry also teaches one or more controlled-release coatings can be applied. (FF 3--4; Final Act. 8.) Sastry discloses that cellulosic polymers are suitable materials "for effecting controlled or modified release" and a controlled- release layer can further provide pH-dependent release by using a coating comprising, for example, "methacrylic acid ester copolymers." (Sastry i-fi-f 111-112). Sastry thus teaches and suggests a dosage form having multiple controlled-release layers, where the layers may be formed with the same types of materials as Appellants' invention. (See Spec. 8, 11. 22-26 (describing materials suitable for the inner layer); see also, Spec. 9-15 (describing suitable compounds for "Component A" of the outer layer).) 8 Appeal2014-005479 Application 13/246,324 and outer layers with each providing its respective function as set forth in Sastry (e.g., an inner layer protecting a drug core and an outer layer providing controlled pH-dependent release in the gastrointestinal tract). (FF 1-5.) We next tum to Appellants' argument that the identification of diethylaminoethyl methacrylate was a misstatement in Sastry. (App. Br. 8- 9; Reply Br. 4.) The evidence suggests Appellants are correct, and that in describing the composition of Eudragit, Sastry meant to identify dimethylaminoethyl methacrylate. (See Aug. 6, 2013 Pre-Appeal Brief Review Decision at 3 (stating "panel agrees that Manufacturer's data sheet controls for definition").) Like the Examiner, however, we note that Sastry is not alone in describing Eudragit™ as comprising diethylaminoethyl methacrylate. Other prior art has done likewise. 5 Even if Sastry' s identification of diethylaminoethyl methacrylate was a misstatement, the obviousness inquiry does not end. Eudragit™ and copolymers of dimethylaminoethyl methacrylate (assuming that is what Sastry intended) are identified as one preferred example for use in pH- dependent controlled-release layers. Of course, "in 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." Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (internal quotation marks omitted). 5 See Final Act. 8 (identifying other prior art references such as US 6, 197,331 at col. 11, 11. 3-5 ("Eudragit™ Eis a cationic copolymer based on diethylaminoethyl methacrylate and neutral methacrylic acid esters.")). 9 Appeal2014-005479 Application 13/246,324 Sastry also teaches generally that "methacrylic acid ester copolymers" and other materials may be used. (Sastry i-fi-f 111-112.) And the Examiner concluded that diethylaminoethyl methacrylate ("DEAEMA") would have been an obvious variant to use in a coating material given the close structural similarity to dimethylaminoethyl methacrylate ("DMAEMA"). (Final Act. 8-9; see also, Aug. 6, 2013 Pre-Appeal Brief Review Decision at 3 ("claims are still viewed as obvious based on close structural relationship").) Moreover, the Examiner cited Appellants' Specification, which acknowledges that DEAEMA was a known methacrylic acid ester in the prior art for forming coating compositions. (Final Act. 8; see also, Spec. 2, 11. 4--12, 27-31.) Appellants nevertheless argue that DMAEMA and DEAEMA are not "obvious homologs." (App. Br. 10-11.) In support, Appellants provide product sheets, which Appellants contend show DMAEMA is water soluble while DEAEMA is not. (Id.) Because "solubility is an important property for pharmaceutical dosage forms," Appellants argue, "one skilled in the art would not have attempted to interchange one monomer for the other." (Id. at 11; see also, Reply Br. 4.) We are not persuaded. Although the solubility of DEAEMA and DMAEMA may be different, Appellants have not shown by objective, fact- based evidence why that is important in the context of the pending claims. See In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997) (argument by counsel cannot take the place of evidence). The Examiner, on the other hand and citing Sastry, finds that what is important is the pH-dependent solubility imparted by the overall copolymer, which can be tailored as desired. (Ans. 10 Appeal2014-005479 Application 13/246,324 9-10.) Appellants have not provided persuasive evidence that solubility differences of individual monomers would render DEAEMA unsuitable for use in forming a layer for the (R)-baclofen prodrugs disclosed in Sastry. Nor have Appellants provided persuasive evidence that water solubility of individual monomers in "component A" is critical relative to coating the generic "acidic active ingredient" recited in claim 1. In re Lindner, 457 F .2d 506, 508 (CCP A 1972) ("It is well established that the objective evidence of nonobviousness must be commensurate in scope with the claims."). In sum, Appellants' arguments do not persuade us the Examiner erred in concluding the skilled artisan would have predictably used DEAEMA as an "obvious variant" in a copolymer coating composition. (Ans. 9-10.) Finally, we have considered the "comparative example" cited by Appellants, but that does not change our conclusion that claim 1 would have been obvious. (App. Br. 12-13.) Appellants point to Example 1 in the present application, which Appellants argue "shows that the presence of the inner layer enhances the stability of the dosage form because such a dosage form prevents a bitter taste in the mouth" and "did not adversely affect the release properties of the drug." (Id. at 12.) We are not, however, persuaded that this result is unexpected over the dosage form taught and suggested in Sastry. Sastry teaches a sealant/barrier coating for a drug having substantially the same ingredients as the inner layer in Example 1 (e.g., polyvinyl alcohol, talc). (Compare Spec. 30, with Sastry i-f 109.) And, as noted above, Sastry teaches this layer is "not intended to modify or affect the release" of the drug. (FF 3.) The results reported in Appellants' Specification are thus consistent with what the skilled artisan would have 11 Appeal2014-005479 Application 13/246,324 expected based on Sastry. In re Skoner, 517 F.2d 947, 950 (CCPA 1975) ("Expected beneficial results are evidence of obviousness of a claimed invention."). For the above reasons, we are not persuaded by Appellants' contention that the combination of Sastry and Petereit '035 fails to make obvious Appellants' claimed invention. (App. Br. 6-12; Reply Br. 3--4; cf FF 1---6.) Rejection Over The Combination Of Sastry, Petereit '035, And Petereit '394 Based on the combination of Sastry, Petereit '035, and Petereit '394, the Examiner concludes it would have been obvious to design a dosage form with the compounds taught and suggested in Sastry and Petereit '035 as discussed above, but having a thickness for the inner coating layer as taught in Petereit '394 and as recited in claims 16-18. (Ans. 6-7.) Appellants argue Petereit '394 "does not remedy the deficiencies of Sastry and Petereit ['035]" and further note that the inner and outer layers of Petereit '394 are anionic. (App. Br. 14; Reply Br. 5.) Having found no deficiencies in Sastry or Petereit '035, Appellants' argument is not persuasive. Also, Appellants' contention that the layers in Petereit '394 are anionic is immaterial because: (i) claims 16-18 (and claim 1 from which claims 16-18 depend) do not require the inner layer be anionic, cationic, etc.; and (ii) the Examiner relies on Sastry for teaching the outer cationic layer. In sum, we are unpersuaded that Sastry, Petereit '035, and Petereit '394 fail to make obvious claims 16-18. (FF 1-7.) 12 Appeal2014-005479 Application 13/246,324 CONCLUSION OF LAW The preponderance of evidence relied upon by the Examiner supports a conclusion of obviousness. The rejection of claim 1under35 U.S.C. §103(a) based on the combination of Sastry and Petereit '035 is affirmed. Appellants did not separately argue claims 2-15 and 19-21 and these claims thus fall with claim 1. The rejection of claims 16-18 under 35 U.S.C. §103(a) based on the combination of Sastry, Petereit '035, and Petereit '394 is also 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 13 Copy with citationCopy as parenthetical citation