Ex Parte Kolter et alDownload PDFPatent Trial and Appeal BoardAug 1, 201613122827 (P.T.A.B. Aug. 1, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/122,827 04/06/2011 Karl Kolter 48394 7590 08/03/2016 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. PF61286 2997 EXAMINER PALLAY,MICHAELB ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 08/03/2016 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 ANGELIKA MASCHKE 1 Appeal2014-008771 Application 13/122,827 Technology Center 1600 Before FRANCISCO C. PRATS, JACQUELINE W. BONILLA, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a process for producing oral dosage forms with controlled active ingredient release, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm-in-part. STATEMENT OF THE CASE Processes for making controlled release pharmaceutical formulations employing a matrix "in which the active ingredient is embedded in a base from which it slowly diffuses ... on contact with gastric or intestinal juices" are known, and include direct tableting and wet granulation. (Spec. 1: 10- 1 Appellants identify the Real Party in Interest as BASF SE. (Appeal Br. 4.) Appeal2014-008771 Application 13/122,827 17.) The Specification discloses that "[t]he matrix formers frequently employed [in these formulations] are erodable substances or gel formers such as hydroxypropyl methylcellulose or xanthan, which control the release on contact with aqueous media." (Spec. 1:18-20.) According to the Specification, however, these processes and formulations result in variability in the dosage forms produced with respect to release and mechanical stability. (Spec. 1: 21-27.) The claimed invention seeks to avoid the foregoing problems. (Spec. 2:9-20.) Claims 1-3, 5-16, 18, and 19 are on appeal. Claim 1 is representative and reads as follows: 1. A process for producing solid oral dosage forms with controlled active ingredient release, comprising a mixture of a) at least one active ingredient, and b) a preformulated mixture of polyvinyl acetate and polyvinylpyrrolidone, wherein the mixture is obtained by joint processing of components a) and b) in an extruder at temperatures between 80° and 180°C; wherein said preformulated mixture is obtained by dissolving polyvinylpyrrolidone in a fine-particle aqueous dispersion of polyvinyl acetate with a particle size of the polyvinyl acetate particles of from 100 to 300 nm, and subsequently spray drying; and wherein extrusion takes place under a pressure of from 2 to 25 MPa. (Appeal Br. 22.) 2 Appeal2014-008771 Application 13/122,827 The following three grounds of rejection by the Examiner are before us on review: 1. Claims 1-3, 5-10, 12, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, 2 Woo, 3 and Kolter. 4 2. Claims 1-3, 5-13, 15, 16, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, Kolter, Kolter '852,5 and Llinas. 6 3. Claims 1-3, 5-10, 12, 14, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, Kolter, and McGinity.7 DISCUSSION Obviousness Rejections 1 and 3 The Examiner's obviousness rejection over Anonymous, Woo, and Kolter with or without McGinity relies on the following assertions regarding Anonymous: (1) that it teaches extruding a polymer matrix and a pharmaceutical, (Final Action 5, 13), and (2) although it specifically identifies using as the matrix material the polyvinylpyrrolidone ("PVP")/polyvinyl acetate ("PV A") copolymer, KOLLIDON V A64, it also 2 Placement of additives into a fluid stream, Research Disclosure 468113, 623-639, Apr. 2003, Questal, ("Anonymous"). 3 Woo et al., US 2007/0196500 Al, published Aug. 23, 2007. 4 Kolter et al., Kollicoat SR30D A new sustained release excipient, 3 BASF ExAct, Nov. 1999, ("Kolter"). 5 Kolter et al., US 2001/0038852 Al, published Nov. 8, 2001 ("Kolter '852). 6 Llinas et al., Diclofenac Solubility: Independent Determination of the Intrinsic Solubility of Three Crystal Forms, 50 (5) J. Med. Chem., 979-983, Feb. 14, 2007. 7 McGinity et al., 2001/0006677 Al, published Jul. 5, 2001. 3 Appeal2014-008771 Application 13/122,827 teaches "virtually any suitable extrudable material" is "useful as the matrix" (Final Action 5-6), including homopolymers like polyvinylpyrrolidone and cellulose, (Ans. 4). According to the Examiner, while Anonymous does not specifically teach the claimed preformulated mixture, Woo teaches that such homopolymer mixtures were known in the art, e.g., Kollidon SR® and Kollicoat SR 30D®, and Kolter describes that Kollicoat SR 30D® has a mean particle size of 160 nm. (Final Action 6-7.) The Examiner finds that using the mixture of homopolymers described in Woo in Anonymous would be obvious "given that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose." (Ans. 4; Final Action 7.) According to the Examiner, the motivation "to combine the prior art teachings is to confer sustained release capability of the active ingredient for an extended period of time regardless of pH of the aqueous medium as suggested by Woo et al., to provide stability to the dispersion as suggested by Kolter et al., and to provide the mixture in the preferable form of a powder as suggested by Woo et al." (Ans. 5.) The Examiner further finds that because Anonymous "specifically teaches [the] use of PVP homopolymer" and the "use of PV A in a copolymer," and "suggests use of polymers in general," as well as providing "an exemplary extrusion process carried out at 180 °C," there would be an 4 Appeal2014-008771 Application 13/122,827 expectation of success in substituting the mixture of homopolymers of Woo in the Anonymous process. (Ans. 6.)8 Appellants contend the Examiner has failed to establish a prima facie case of obviousness with respect to claim 1. According to Appellants, Anonymous does not teach or suggest using a mixture of two homopolymers as the matrix and one of ordinary skill in the art would not look to Woo' s disclosure of mixtures of homopolymers of PV A and PVP in controlled release formulations prepared by wet granulation to substitute for the disclosed matrix materials used to make controlled release formulations by the hot melt extrusion process of Anonymous. (Appeal Br. 12-17; Reply Br. 2.) We agree with Appellants that the Examiner has failed to provide the evidence necessary to support a prima facie case of obviousness of claim 1 over Anonymous, Woo, and Kolter with or without McGinity. We note that "[ o ]bviousness requires more than a mere showing that the prior art includes separate references covering each separate limitation in a claim under examination." Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011) (citing KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).) "Rather, obviousness requires the additional showing that a person of ordinary skill at the time of the invention would have selected and 8 McGinity is relied upon for its disclosure of a hot-melt extrusion process to make a controlled release film to address limitations of dependent claims. (Final Action 13.) 5 Appeal2014-008771 Application 13/122,827 combined those prior art elements in the normal course of research and development to yield the claimed invention." Id. "[A] combination is [ unpatentable as] obvious to try if a person of ordinary skill has 'a good reason to pursue the known options.'" Id. (quoting KSR, 550 U.S. at 421). On the other hand, "[w]hen a field is 'unreduced by direction of the prior art,' and when prior art gives 'no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful,' an invention is not [unpatentable as] obvious to try." Id. We agree with Appellants that the Examiner has not advanced a "rational reason why one skilled in the art faced with the teachings of Anonymous would tum to the teachings of Woo for a suggestion of ingredients to modify a dosage form, regardless of what Woo says regarding Kollidon® SR." (Appeal Br. 15.) Neither Woo, nor Kolter teach or suggest that a mixture of PVP and PVA homopolymers would be suitable in melt- extrusion processes of forming sustained release tablets. Woo teaches a wet granulation process that involves formulating the active pharmaceutical into a granule by mixing the active with the mixture of homopolymers and "subjecting the mixture to wet grinding, compression molding, and pheronizing to obtain a wet granule." (Appeal Br. 14; Woo i-fi-130, 32.) The one process in which the use of heat is described, i.e., hot-spray coating of a homopolymer mixture on a formed granule, involves temperatures of at most 40 °C. (Woo i-f4 l.) Kolter discloses a process of coating theophylline pellets with a film, where the coating is cured at 60°C. (Kolter 3.) The 6 Appeal2014-008771 Application 13/122,827 claimed process requires extrusion take place at temperatures between 80° and 180°C. In light of the foregoing, we conclude that the Examiner's rejection does not provide a sufficient reason to pursue the homopolymer mixture disclosed in Woo and Kolter over the matrix materials disclosed in Anonymous. Moreover, we do not discern any such reason based on the teachings of Anonymous, Woo, and Kolter with or without McGinity. Accordingly, we agree with Appellants that the Examiner has not shown that one of ordinary skill in the art would have considered claim 1 prima facie obvious over Anonymous, Woo, and Kolter or Anonymous, Woo, Kolter and McGinity. In light of the foregoing, we reverse the Examiner's rejection of claims 1-3, 5-10, 12, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, and Kolter as well as the rejection of claims 1-3, 5-10, 12, 14, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, Kolter, and McGinity. Obviousness Rejection 2 Appellants also contend that "[t]he Examiner failed to establishprima facie obviousness due to the fact Kolter '852 as evidenced by Llinas does not remedy the deficiencies of the combination of Anonymous, Woo, and Kolter." (Appeal Br. 18). In particular, Appellants contend that Kolter '852 ... does not make-up for the deficiencies in the combination of Anonymous, Woo, and Kolter, providing no basis to provide a preformulated mixture of two homopolymers for use during extrusion at a temperature of between 80°C and 180°C and a pressure of from 2 to 25 MP a. (Appeal Br. 19.) We disagree with Appellants. 7 Appeal2014-008771 Application 13/122,827 As the Examiner noted, Kolter et al. '852 discloses producing, by melt extrusion, tablets with delayed release of active ingredient, where the tablet formulation can be made with a mixture of PVA and PVP homopolymers combined with the active ingredient. (Final Action 11 (citing Kolter '852 abstract, i-f 68).) The mixture of homopolymers that Kolter '852 specifically mentions is Kollidon® SR. (See, e.g., Kolter '852 (Example 3).) That is one of the "[ s ]uitable preformulated mixtures of polyvinyl acetate and polyvinylpyrrolidone" noted in Appellants Specification. (Spec. 4:6-8.) Thus, Kolter '852, cited by the Examiner, provides a reason to pursue the use of the claimed preformulated mixture of PV A and PVP in a tablet formulation that is to be made using melt extrusion, KSR, 550 U.S. at 421, and the teachings of Anonymous, Woo, Kolter, Kolter '852, and Llinas, "taken as a whole, would have made obvious the ... invention [of claim 1]," In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). Accordingly, we agree with the Examiner's conclusion that claim 1 is unpatentable under 35 U.S.C. § 103(a) over Anonymous, Woo, Kolter, Kolter '852, and Llinas. Claims 2-3, 5-13, 15, 16, 18, and 19 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY We reverse the Examiner's rejection of Claims 1-3, 5-10, 12, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, and Kolter. We also reverse the Examiner's rejection of claims 1-3, 5-10, 12, 14, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, Kolter, and McGinity. We affirm the Examiner's rejection of claims 8 Appeal2014-008771 Application 13/122,827 1-3, 5-13, 15, 16, 18, and 19 under 35 U.S.C. § 103(a) as unpatentable over Anonymous, Woo, Kolter, Kolter '852, and Llinas. 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-IN-PART 9 Copy with citationCopy as parenthetical citation