Ex Parte Castan et alDownload PDFPatent Trial and Appeal BoardOct 5, 201712905387 (P.T.A.B. Oct. 5, 2017) 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. 12/905,387 10/15/2010 Catherine Castan 022290.0195PTUS (01529) 7881 127044 7590 10/10/2017 Porzio, Bromberg & Newman P.C. 1200 New Hampshire Ave., NW Suite 710 Washington, DC 20036 EXAMINER FALKOWITZ, ANNA R ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 10/10/2017 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): ipdocketing @ pbnlaw. com pbn_docketing@cardinal-ip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CATHERINE CASTAN and ANNE-SOPHIE DAVIAUD-VENET1 Appeal 2016-008209 Application 12/905,387 Technology Center 1600 Before ERIC B. GRIMES, ULRIKE W. JENKS, and DAVID COTTA, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35U.S.C. § 134 involving claims to a solid oral form of a pharmaceutical, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. STATEMENT OF THE CASE The Specification discloses a solid oral pharmaceutical form containing at least one viscosifying agent and an active ingredient formulated in the 1 Appellants identify the Real Party in Interest as FLAMEL IRELAND LIMITED. (Appeal Br. 1.) Appeal 2016-008209 Application 12/905,387 state of microparticles, the latter being resistant to crushing, in order to avoid misuse and suitable for obtaining a specific modified release profile comprising several release phases at least one of which depends on the pH. (Spec. 1:3-7.) Claims 1, 3—5, 8—11, 13, 14, 16—19, 21—31, and 33 are on appeal. Claim 1 is the only independent claim and reads as follows (emphasis added): 1. Solid oral pharmaceutical form comprising: at least microparticles comprising an active ingredient; and at least one viscosifying agent in a form isolated from said microparticles of active ingredient, wherein: said microparticles of active ingredient are modified release microparticles, said microparticles of active ingredient are resistant to crushing, said microparticles of active ingredient possess an average diameter ranging from 100 to 600 pm, and are formed by a core containing at least said active ingredient and coated with at least one coating layer, said coating layer comprises: - 25 to 70 % by weight relative to the total weight of said coating of at least one polymer A which is insoluble in water, wherein the polymer A is chosen from ethylcellulose, cellulose acetate butyrate, cellulose acetate, ammonio (meth)acrylate copolymers, poly(meth)acrylic acid esters, and mixtures thereof, - 30 to 75 % by weight relative to the total weight of said coating of at least one polymer B which is insoluble in water below pH 5 and soluble in water above pH 7, wherein said polymer B is chosen from methacrylic acid and methyl methacrylate copolymers, methacrylic acid and ethyl acrylate copolymers, cellulose acetate phthalate (CAP), cellulose acetate succinate (CAS), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose phthalate (hypromellose phthalate) (HPMCP), hydroxypropylmethylcellulose acetate succinate (hypromellose acetate succinate) (HPMCAS), 2 Appeal 2016-008209 Application 12/905,387 carboxymethylethylcellulose, shellac gum, polyvinyl acetate phthalate (PVAP), and mixtures thereof, and - 0 to 25 % by weight relative to the total weight of said coating of at least one plasticizer, said polymers A and B are in a polymers B / polymers A weight ratio between 0.4 and 2, and said coating layer represents at least 35 % by weight, relative to the total weight of said microparticle, said modified release of active ingredient from said modified release microparticles is characterized in vitro by : - in acid aqueous medium with a pH of less than 4.0, a latency period of 1 to 12 hours, followed by the start of the release of the active ingredient; - after increasing the pH to pH greater than 7.0, an acceleration of the release of the active ingredient. DISCUSSION The Examiner has rejected all of the claims on appeal under 35 U.S.C. § 103(a) as obvious based on Legrand,2 Guimberteau,3 and Morelia.4 (Non- Final Action5 4.) The Examiner finds that “Legrand discloses a microparticulate system for controlled release” that meets most of the limitations of claim 1, including microparticles “coated with a film 2 Legrand et al., US 2005/0037077 Al, published Feb. 17, 2005. 3 Guimberteau et al., WO 2007/054378 Al, published May 18, 2007. The Examiner relies on a partial translation of PCT/EP2006/062627 as an English-language equivalent of Guimberteau. (Non-Final Action 4.) Appellants do not dispute that the relied-upon application is an accurate partial translation of Guimberteau. 4 Morelia et al., EP 0 609 961 Al, published Aug. 10, 1994. 5 Office Action mailed Aug. 25, 2015. 3 Appeal 2016-008209 Application 12/905,387 comprising hydrophilic polymer A and compound B (Abstract). Polymer A of the prior art comprises mixtures of EUDRAGIT ® L and cellulose acetate ([0098] - [0100]).” (Id. at 5.) The Examiner finds that Guimberteau and Morelia teach the limitations that are missing from Legrand (id. at 5—6) and concludes that the combined teachings of the cited references would have made the invention of claim 1 obvious to a person of ordinary skill in the art (id. at 8). Appellants argue, among other things, that they have provided two declarations under 37 C.F.R. § 1.132 to show that the disclosure of “cellulose acetate” in Legrand is an obvious error. (Appeal Br. 11.) Appellants argue that the declaratory evidence shows that “[o]ne of ordinary skill in the art would recognize the obvious error and simply substitute the correct compounds and/or disregard the listing of ‘cellulose acetate’.” (Id., citing In re Yale, 434 F.2d 666, 668-669 (CCPA 1970).) We agree with Appellants that the rejection on appeal is not supported by a preponderance of the evidence of record. “An examiner bears the initial burden of presenting a prima facie case of obviousness.” In re Huai- Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011). “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.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). The Examiner cites Legrand’s disclosure of a controlled release system comprising microparticles of an active agent coated with a mixture of 4 Appeal 2016-008209 Application 12/905,387 “polymer A” and “compound B.” (See Legrand, abstract.) The Examiner points to Legrand’s statement that [according to one preferred characteristic of the invention, the hydrophilic polymer A is selected from: (meth)acrylic acid/alkyl (e.g. methyl) (meth-)acrylate copolymers (EUDRAGIT® S or L) and mixtures thereof; cellulose derivatives, preferably cellulose acetate and/or phthalate, hydroxypropyl methyl cellulose phthalate and hydroxypropyl methyl cellulose acetate and/or succinate; and mixtures thereof. (Id. 97—100, emphasis added.) The Examiner finds that, based on this passage, Legrand discloses that its polymer A can consist of a mixture of EUDRAGIT® L (a methacrylic acid and methyl methacrylate copolymer) and cellulose acetate, thus meeting the requirements of both the polymer A and polymer B recited in claim 1. (Non-Final Action 5.) Appellants, however, argue that they have “submitted two declarations showing that one of ordinary skill in the art at the time of the invention would have immediately recognized that the listing of ‘cellulose acetate’ in paragraph [0099] of Legrand was an error.” (Appeal Br. 13.) Specifically, Appellants cite the Castan Declaration6 and the Guillard Declaration.7 (Id.) 6 Declaration under 37 C.F.R. § 1.132 of Catherine Castan, submitted Aug. 10, 2015. 7 Declaration under 37 C.F.R. § 1.132 of Herve Guillard, submitted Dec. 1, 2014. 5 Appeal 2016-008209 Application 12/905,387 Dr. Castan is one of the inventors of both the instant application and the Legrand reference, and declares that “we (i.e., the inventors in Legrand) intended polymer A to be cellulose acetate derivatives carrying groups that are ionized at neutral pH and which are insoluble in acidic media at pH below 5 and soluble in neutral media.” (Castan Decl. 1 8.) Dr. Castan also declares that Legrand’s “wording . . . may have led to a misunderstanding that ‘cellulose acetate’ . . . could be an example of a polymer A in Legrand. This potential reading of paragraph 0099 in Legrand is incorrect, however, based on the chemistry required for polymer A in Legrand.” (Id. 19.) Dr. Castan notes that “[t]his rationale is clearly set forth in the previously submitted Declaration of GUILLARD.” (Id.) Dr. Guillard declares that, as a skilled artisan, he “understand^] that film coatings are divided into different groups, depending on dissolution, permeability and disintegration performance. This is well explained, for instance, in the technical book ‘Coated Dosage Forms' at Chapter 4, from page 65 to page 70 (See Exhibit 1).” (Guillard Decl. 19.) Dr. Guillard declares that Legrand’s “hydrophilic polymer A carrying groups that are ionized at neutral pH” (Legrand 190) fall into the category of “‘polymers with free carboxylic groups (that) are insoluble in acid media and that dissolve by salt formation above pH 5-6.’” (Guillard Decl. 110, quoting Exh. I,8 p. 66.) 8 Bauer et al., Coated Pharmaceutical Dosage Forms: Fundamentals, Manufacturing Techniques, Biopharmaceutical Aspects, Test Methods and Raw Materials 65-71 (CRC Press, Boca Raton 1998). 6 Appeal 2016-008209 Application 12/905,387 Dr. Guillard declares that “cellulose acetate is a hydrophobic and insoluble cellulose polymer that does not contain any free carboxylic groups. Cellulose acetate solubility is pH-independent.” (Id. 115.) Dr. Guillard points to the Guillard Declaration’s Exhibits 59 and 610 as showing that the structural formula of cellulose acetate lacks any free carboxylic groups (id.) and to the Guillard Declaration’s Exhibit 2* 11 as “present[ing] cellulose acetate as an insoluble polymer.” (Id.) Dr. Guillard concludes that “[tjherefore, one of ordinary skill in the art would understand that cellulose acetate clearly does not correspond to the hydrophilic polymer A carrying groups that are ionized at neutral pH as required by Legrand.” (Id. 117.) The Examiner responds that “Appellants[’] attempt to only limit Legrand to cellulose acetate derivatives with ionized groups at a neutral pH, is not consistent with the text of Legrand.” (Ans. 6.) The Examiner states that “[t]he prior art has been interpreted in light of what it actually reads, in this case cellulose acetate.” (Id. at 7.) However, “the meaning of a prior art reference requires analysis of the understanding of an artisan of ordinary skill.” Finisar Corp. v. DirecTV Group, Inc., 523 F.3d 1323, 1336 (Fed. Cir. 2008). “[T]he test [for obviousness] is what the combined teachings of the references would have 9 Rowe et al., Handbook of Pharmaceutical Excipients 141-143 (Pharmaceutical Press, London 6th Edition) (2009). 10 Eastman Cellulose Esters for Pharmaceutical Drug Delivery 1- 13 (Eastman Chem. Co. 2006). 11 Qiu et al., Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice 484-485 (Academic Press, Burlington, MA 2009). 7 Appeal 2016-008209 Application 12/905,387 suggested to those of ordinary skill in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations omitted). In this case, Appellants have presented evidence—two declarations supported by documentary evidence—showing that a person of ordinary skill in the art would have known that Legrand’s recitation of “cellulose acetate and/or phthalate” as one possible polymer A constituent of its coating was an obvious error because cellulose acetate does not have the property that Legrand previously disclosed as necessary for its polymer A; namely, a hydrophilic polymer carrying groups that are ionized at neutral pH. Dr. Guillard declared that a skilled artisan would have recognized Legrand’s polymer A as a polymer with free carboxylic groups that are insoluble in acid media and that dissolve by salt formation above pH 5—6. (Guillard Decl. 110.) Dr. Guillard cited documentary evidence supporting this position. (Id.) Dr. Guillard also cited evidence to show that cellulose acetate does not have this property, because it is insoluble. (Id. 115.) The Examiner has not provided evidence to contradict Dr. Guillard’s declaration and supporting evidence. We agree with Appellants that a preponderance of the evidence of record shows that a person of ordinary skill in the art would have recognized the recitation of cellulose acetate for Legrand’s polymer A was an obvious error. In re Yale, 434 F.2d 666 (CCPA 1970), is therefore on point. In Yale, the claimed invention was the compound CF3CF2CHClBr and its use as an anesthetic. Id. The claims were rejected based on a reference (Clements) that recited the same compound. Id. at 667. The Appellant 8 Appeal 2016-008209 Application 12/905,387 argued, and presented supporting evidence, that the recitation of this compound in the reference was an obvious error and that a skilled artisan would have recognized that CF3CHClBr was intended. Id. The Yale court concluded that not only is the listing of CF3CF2CHClBr in Clements a typographical error but also this fact would be apparent to one of ordinary skill in the art when reading the Clements article. Since it is an obvious error, it cannot be said that one of ordinary skill in the art would do anything more than mentally disregard CF3CF2CHClBr as a misprint or mentally substitute CF3CHClBr in its place. Certainly he would not be led by the typographical error to use the erroneous compound as an anesthetic Id. at 668—669. Just as in Yale, the evidence here shows that Legrand’s error in listing cellulose acetate as polymer A would have been apparent to one of ordinary skill, because the properties desired for polymer A are not possessed by cellulose acetate. Thus, the skilled worker would either mentally disregard the listing of cellulose acetate as a misprint or mentally substitute the appropriate polymer (apparently cellulose acetate phthalate) in its place. In any case, the skilled worker would not have been led to use cellulose acetate in a mixture with EUDRAGIT® L as the polymer A component of Legrand’s coating. The Examiner has not pointed to any disclosure in Guimberteau or Morelia that makes up for the deficiency in Legrand. Thus, the Examiner has not shown that the cited references would have made obvious one of claim 1 ’s polymer A components with one of the polymer B components in a coating layer for microparticles in a pharmaceutical dosage form. We therefore reverse the rejection of claim 1, and dependent claims 3—5, 8—11, 9 Appeal 2016-008209 Application 12/905,387 13, 14, 16—19, 21—31, and 33, under 35 U.S.C. § 103(a) based on Legrand, Guimberteau, and Morelia. REVERSED 10 Copy with citationCopy as parenthetical citation