Ex Parte KimDownload PDFBoard of Patent Appeals and InterferencesApr 26, 201111207126 (B.P.A.I. Apr. 26, 2011) 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. 11/207,126 08/17/2005 Cherng-Ju Kim 110.010US1 8195 66981 7590 04/26/2011 HUGH MCTAVISH MCTAVISH PATENT FIRM 429 BIRCHWOOD COURTS BIRCHWOOD, MN 55110 EXAMINER ORWIG, KEVIN S ART UNIT PAPER NUMBER 1611 MAIL DATE DELIVERY MODE 04/26/2011 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte CHERNG-JU KIM __________ Appeal 2010-009244 Application 11/207,126 Technology Center 1600 __________ Before TONI R. SCHEINER, FRANCISCO C. PRATS, and JEFFREY N. FREDMAN, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims to a sustained release pharmaceutical composition. The Examiner rejected the claims for obviousness and new matter. We have jurisdiction under 35 U.S.C. § 6(b). We reverse the Examiner‟s rejections, but enter a new ground of rejection for obviousness under 37 C.F.R. § 41.50(b). Appeal 2010-009244 Application 11/207,126 2 STATEMENT OF THE CASE Claims 13-17, 19, 20, and 40-45 are on appeal (App. Br. 3). Claim 13, the only independent claim, is representative and reads as follows: 13. A pharmaceutical composition comprising: a sustained-release ionic complex containing (i) an ionic small molecule pharmaceutically active agent having a molecular weight of less than 2,000 and a solubility in water of at least 2 mg/ml, complexed with (ii) an oppositely charged ionic surfactant; in combination with a pharmaceutically acceptable diluent or carrier; wherein the pharmaceutical composition releases the ionic pharmaceutically active agent into solution with zero- order kinetics in an aqueous solution containing salt; wherein the sustained-release ionic complex is formed by a process comprising contacting the ionic small molecule pharmaceutically active agent with the oppositely charged ionic surfactant in aqueous solution to form the sustained-release ionic complex as a solid precipitate; and wherein the pharmaceutical composition releases the ionic pharmaceutically active agent into solution in aqueous solution containing salt more slowly than does an otherwise identical composition comprising, in place of the sustained- release ionic complex, a salt of the active agent with a small oppositely charged ion that is not a surfactant. The following rejections are before us for review: (1) Claims 13-17, 19, 20, and 40-45, under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement due to the introduction of new matter (Ans. 5-7); and Appeal 2010-009244 Application 11/207,126 3 (2) Claims 13-17, 19, 20, and 40-45, under 35 U.S.C. § 103(a) as obvious over Pillay 1 and Penkler 2 (Ans. 7-9). NEW MATTER The Examiner contends that the response filed September 15, 2009 entered new matter into the claims (Ans. 5). Specifically, the Examiner urges that the following recitation in claim 13 lacks adequate support in the Specification: wherein the pharmaceutical composition releases the ionic pharmaceutically active agent into solution in aqueous solution containing salt more slowly than does an otherwise identical composition comprising, in place of the sustained-release ionic complex, a salt of the active agent with a small oppositely charged ion that is not a surfactant. (Id.) The Examiner urges that the portions of the Specification cited by Appellant as supporting this language do not describe the “concept of an otherwise identical composition (as is currently claimed) which may include other elements in addition to the complex” (id.). Moreover, the Examiner urges, the Specification “only provides support for the sustained-release ionic complex releasing the drug more slowly than the corresponding conventional salt of the active agent, such as chloride or sodium,” whereas the language at issue “is not limited to conventional salts, but rather includes any small oppositely charged ion that 1 Viness Pillay and Reza Fassihi, Electrolyte-Induced Compositional Heterogeneity: A Novel Approach for Rate-Controlled Oral Drug Delivery, 88 J. PHARM. SCI. 1140-1148 (1999). 2 U.S. Patent No. 6,255,502 B1 (issued July 3, 2001). Appeal 2010-009244 Application 11/207,126 4 is not a surfactant. There is also nothing in . . . the specification that excludes a surfactant as the oppositely charged ion” (id. at 5-6). Appellant contends that there is no legal requirement for claims to have word-for-word support in the Specification (Reply Br. 17). Thus, Appellant urges, a reading of the relevant portions of the Specification shows that Appellant possessed an invention having the concepts in the language at issue (id. at 17-19). As stated in TurboCare Div. of Demag Delaval Turbomachinery Corp. v. General Elec. Co., 264 F.3d 1111, 1118 (Fed. Cir. 2001): The written description requirement and its corollary, the new matter prohibition of 35 U.S.C. § 132, both serve to ensure that the patent applicant was in full possession of the claimed subject matter on the application filing date. When the applicant adds a claim or otherwise amends his specification after the original filing date . . ., the new claims or other added material must find support in the original specification. The test for determining whether a specification is sufficient to support a particular claim “is whether the disclosure of the application relied upon „reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter.‟” Ralston Purina Co. v. Far- Mar-Co, Inc., 772 F.2d 1570, 1575 (Fed.Cir.1985) (quoting In re Kaslow, 707 F.2d 1366, 1375 (Fed.Cir.1983)). Thus, “[i]t is not necessary that the application describe the claim limitations exactly, but only so clearly that persons of ordinary skill in the art will recognize from the disclosure that appellants invented processes including those limitations.” In re Wertheim, 541 F.2d 257, 262 (CCPA 1976) (citation omitted); see also Purdue Pharma L.P. v. Faulding, Inc., 230 F.3d 1320, 1323 (Fed. Cir. 2000) (“In order to satisfy the written description Appeal 2010-009244 Application 11/207,126 5 requirement, the disclosure as originally filed does not have to provide in haec verba support for the claimed subject matter at issue.”). We agree with Appellant that an ordinary artisan viewing the Specification would have recognized that Appellant possessed the claimed invention. The language at issue requires the composition of claim 13 to release the ionic pharmaceutically active agent into an aqueous salt-containing solution more slowly than an otherwise identical composition that contains, in place of the sustained-release ionic complex, a salt of the active agent with a small oppositely charged ion that is not a surfactant. The Specification summarizes Appellant‟s invention as follows: The inventors have discovered that water-soluble ionic pharmaceutical agents form complexes with oppositely charged ionic surfactants, such as anionic bile surfactants. The complexes dissociate slowly to release the pharmaceutical agents in aqueous solutions containing salts. The release kinetics are close to zero order. The release kinetics can be made slower and even closer to pure zero order by formulating the complexes with sustained-release polymers or fillers, such as hyroxypropylmethylcellulose [sic]. Thus, complexes between ionic pharmaceutical agents and oppositely charged ionic surfactants are effective sustained-release formulations of the pharmaceutical agents. (Spec. 1.) The Specification then defines the sustained release ionic complexes of the invention: The term “sustained release ionic complex” refers to an ionic complex between a small molecule pharmaceutically active agent and an oppositely charged ionic surfactant that in aqueous solution releases the active agent into solution more slowly than it is released from the corresponding conventional Appeal 2010-009244 Application 11/207,126 6 salt of the active agent with a small oppositely charged ion such as chloride or sodium. (Id. at 4.) The Specification then provides an example in which 5% w/v solutions of the drug salt diltiazem-HCl and the bile salt surfactant sodium deoxycholate were combined to yield a diltiazem-deoxycholate complex that precipitated from the solution (id. at 12 (Example 1)). After the precipitate was separated from the solution, it was formed into tablets, and the drug release properties over time were assessed (id. (“At the first time point, all diltiazem from the diltiazem-HCl was released. Diltiazem from diltiazem- deoxycholate released slowly over a time period of over 1500 minutes with kinetics close to zero-order.”)). Example 1 also describes a comparison of the release properties of tablets containing hydroxypropylmethylcellulose (HPMC) and diltiazem-deoxycholate and otherwise identical tablets, except that the drug salt was diltiazem-HCl (id.). Thus, the Specification explains that Appellant‟s invention is directed to forming complexes of charged drug compounds with oppositely charged ionic surfactants, such as anionic bile surfactants (id. at 1). The Specification then explains that those complexes have a significantly slower drug release rate than conventional drug salts, such as sodium or chloride (id. at 4), and goes on to exemplify a drug release rate comparison between a composition containing a drug-bile salt complex, diltiazem-deoxycholate, and an identical composition that contains a drug-conventional salt complex, diltiazem-HCl, rather than the drug-bile salt complex (id. at 12). Given these disclosures, we are not persuaded that Appellant‟s Specification would have failed to convey to an ordinary artisan that Appeal 2010-009244 Application 11/207,126 7 Appellant possessed a composition having the properties recited in the language at issue in claim 13. We therefore reverse the Examiner‟s new matter rejection of claim 13 and its dependents. OBVIOUSNESS – PILLAY AND PENKLER The Examiner finds that “Pillay teaches each element of instant claim 13 except for an explicit teaching of precipitating the drug and surfactant together prior to their inclusion in the matrix” (Ans. 8). The Examiner reasons, however, that “the only active step required by the instant claims for forming a precipitate is contacting the ionic active agent with the ionic surfactant in aqueous solution,” and finds that “Pillay teaches this step . . . wherein the induced intragel pH and release characteristics were measured from tablets swollen in aqueous solution” (id.). Moreover, the Examiner reasons, “precipitation of bile acid/basic drug complexes was recognized in the art, and doing so would actually complement Pillay‟s method and is no more than an obvious variation thereof” (id.). The Examiner cites Penkler to support this assertion, and based on the two references‟ teachings concludes that an ordinary artisan would have considered it obvious to “form a complex of a cationic drug (e.g. diltiazem) and anionic bile acid surfactant (e.g. deoxycholate) for use in Pillay‟s dosage forms” (id. at 8-9). Appellant argues, among other things, that Penkler is directed to compositions for transmucosal or transdermal absorption, whereas “Pillay concerns tablets and formulations for oral delivery. These dissolve in the stomach or intestine, a route that Penkler indicates is not applicable to the Penkler invention” (Reply Br. 7). Thus, Appellant argues, since “the motivation to combine cited by the Examiner does not make sense in the Appeal 2010-009244 Application 11/207,126 8 context of both references, there is no prima facie case of obviousness” (id. at 8). “In proceedings before the Patent and Trademark Office, the Examiner bears the burden of establishing a prima facie case of obviousness based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992). In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), the Supreme Court emphasized “an expansive and flexible approach” to the obviousness question, but also reaffirmed the importance of determining “whether there was an apparent reason to combine the known elements in the fashion claimed by the patent at issue.” Id. at 418 (emphasis added). Ultimately, therefore, “[i]n determining whether obviousness is established by combining the teachings of the prior art, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations omitted). We agree with Appellant that the Examiner has not made a prima facie case of obviousness based on the asserted combination of references. Pillay describes the results of a study that investigated techniques for improving the sustained release properties of orally administered tablets (see Pillay 1141 (“The aim of this work was to provide and expand on a means to design, formulate, and develop a novel oral monolithic, controlled-release tablet dosage form for drugs of various solubility that may be tailored to provide zero- order or quasi-steady-state drug release over a 24-h period.”)). Pillay found that including certain “electrolytes,” such as sodium bicarbonate, in tablets containing hydrophilic polymer and a model drug, Appeal 2010-009244 Application 11/207,126 9 diltiazem, “enabled control of diltiazem hydrochloride release in a zero- order manner in different pH environments over a 24-h period” (id. at 1140 (abstract)). Pillay discloses that sodium deoxycholate was among the electrolytes tested (id. at 1143-44). In contrast, Penkler is directed to preparing a pharmaceutical composition which contains “an acid addition salt of a basic drug and a fatty acid or bile acid. The acid addition salts thus formed exhibit enhanced transmucosal and transdermal penetration of the basic drug” (Penkler, abstract). Thus, Penkler discloses: The compositions of this invention may be utilized in delivering the pharmaceutically active agent to the following target areas: (1) the sublingual surface or floor of mouth, (2) the buccal cavity, (3) the gums, (4) the nasal passages, (5) the rectum or colon, (6) the vagina, (7) the ocular cavity or cul-de-sac of the eye, and (8) the skin. The preferred pharmaceutical forms are sublingual tablets, nasal sprays, buccal tablets, suppositories (rectal and vaginal), transdermal patches and topical gels. (Id. at col. 13, ll. 3-12.) We agree with Appellant that the Examiner has not adequately explained why an ordinary artisan would have been prompted to include Penkler‟s drug-bile acid addition salt in Pillay‟s oral dosage forms. Specifically, while the Examiner asserts that an ordinary artisan would have viewed the permeation-enhancing properties of Penkler‟s compositions as useful in Pillay‟s oral dosage forms (Ans. 9), as Appellant points out, Penkler‟s orally administered formulations are intended to be absorbed quickly through the oral mucosae (see e.g., Penkler, col. 1, ll. 27-29 (“The mucosal route of drug delivery is a useful alternative to parenteral delivery Appeal 2010-009244 Application 11/207,126 10 where rapid therapeutic effect is desired.”)), which is the opposite objective of Pillay‟s oral dosage forms having sustained drug release for 24 hours. Thus, because the teachings advanced by the Examiner as supporting the references‟ combination appear to be at odds in their ultimate objectives, we are not persuaded that an ordinary artisan would have been prompted to combine the references in the manner advanced by the Examiner to arrive at the combination of ingredients recited in claim 13. We therefore reverse the Examiner‟s obviousness rejection of that claim, and its dependents, as obvious over Pillay and Penkler. NEW GROUND OF REJECTION Under the provisions of 37 C.F.R. § 41.50(b), we enter the following new ground of rejection: Claim 13 is rejected under 35 U.S.C. § 103(a) as obvious over Penkler. Claim 13 recites a pharmaceutical composition. Claim 13 specifies two components that must be present in the composition: (1) a sustained-release ionic complex that contains (i) an ionic pharmaceutically active agent having a molecular weight of less than 2,000 and a solubility in water of at least 2 mg/ml, complexed with (ii) an oppositely charged ionic surfactant; and (2) a pharmaceutically acceptable diluent or carrier. As the Specification explains, diltiazem, the elected species 3 of pharmaceutical agent, is a cationic drug compound that has the properties required by claim 13 (Spec. 9). As the Specification also explains, a number 3 See Response to Election/Restriction entered June 9, 2008, at page 2. Appeal 2010-009244 Application 11/207,126 11 of anionic bile salt surfactants, including the elected species deoxycholate, 4 as well as glycodeoxycholate, are suitable for complexation with cationic drugs (see id. at 5-7). Claim 13 requires the sustained release ionic complex to be formed by contacting the ionic pharmaceutically active agent with the oppositely charged ionic surfactant in aqueous solution to form the complex as a solid precipitate. Claim 13 also requires the composition to release the ionic pharmaceutically active agent into an aqueous salt-containing solution with zero-order kinetics. Claim 13 further requires the composition to release the ionic pharmaceutically active agent into an aqueous salt-containing solution more slowly than an otherwise identical composition that contains, in place of the sustained-release ionic complex, a salt of the active agent with a small oppositely charged ion that is not a surfactant. As seen in Appellant‟s Example 1, these functional properties are attained by forming the precipitated complex between an ionic drug, such as diltiazem, and a bile acid, such as deoxycholate (id. at 12-13; see also Specification, generally). Like claim 13, Penkler describes a “pharmaceutical composition [which] contains an acid addition salt of a basic drug and a fatty acid or bile acid. The acid addition salts thus formed exhibit enhanced transmucosal and transdermal penetration of the basic drug” (Penkler, abstract). 4 See Response to Election/Restriction entered June 9, 2008, at page 2. Appeal 2010-009244 Application 11/207,126 12 As required by claim 13, Penkler‟s compositions can contain a variety of pharmaceutical excipients, including those consistent with orally administered sustained release compositions: The acid addition salt present in part or completely as a cyclodextrin inclusion complex may be formulated together with conventional pharmaceutical excipients into sustained release buccal tablets or patches with uni-directional release according to methods known in the art. Preferred excipients for sustained release buccal tablets or patches are muco-adhesive polymers such as cross-linked polyacrylic acids (carbomers, polycarbophils). (Id. at col. 12, ll. 9-15 (emphasis added).) As also required by claim 13, Penkler‟s drug-bile acid addition salt is a complex that is produced by mixing solutions of the drug and bile acid to form a precipitate: [T]he sodium salt of the fatty acid or bile acid is dissolved in water at elevated temperature. A solution of the commercially available salt of the drug (e.g hydrochloride, sulphate, succinate, phosphate, etc) is added slowly with stirring at elevated temperature. The resulting solution is cooled to room temperature and the addition salt precipitate collected on a filter, washed with cold water and dried in vacuo. (Id. at col. 11, ll. 29-36.) Thus, Example 7 of Penkler describes the preparation of a drug-bile acid addition complex by combining solutions of the drug salt loperamide-HCl and sodium deoxycholate to form a precipitate (id. at col. 15, ll. 1-16). While Penkler does not exemplify the elected species of drug (diltiazem) or surfactant (deoxycholate), 5 Penkler discloses that diltiazem is 5 See Response to Election/Restriction entered June 9, 2008, at page 2. Appeal 2010-009244 Application 11/207,126 13 among the drugs suitable for formulation according to its teachings (id. at col. 8, ll. 54-55), and that deoxycholate is among suitable bile acids (id. at col. 10, l. 66, through col. 11, l. 2). Thus, in view of the teachings of Penkler discussed above, we find that an ordinary artisan would have been prompted to prepare a composition containing (1) a sustained release pharmaceutical excipient and (2) a drug-bile acid addition complex produced by combining solutions of diltiazem and deoxycholate to form the precipitated complex, as required by claim 13. With respect to the functional properties required by claim 13, as noted above, Appellant‟s Specification discloses that the claimed zero-order and slower release kinetics are achieved by forming the same drug-bile acid precipitated complex as Penkler, in essentially the same fashion as taught in Penkler. Thus, as stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (citations omitted): Where . . . the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . . . Whether the rejection is based on „inherency‟ under 35 U.S.C. § 102, on „prima facie obviousness‟ under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO‟s inability to manufacture products or to obtain and compare prior art products. In sum, for the reasons discussed, we find that an ordinary artisan would have been prompted by Penkler to combine the ingredients required by claim 13, in the manner required by the claim. As following Penkler‟s Appeal 2010-009244 Application 11/207,126 14 teachings would result in a composition having the required functional properties, we conclude that claim 13 would have been prima facie obvious to an ordinary artisan. We have carefully considered Appellant‟s arguments as they pertain to this new ground of rejection, but are not persuaded that the new rejection is unsupported by the evidence of record. We acknowledge that it is improper to base an obviousness rejection on an unknown inherent property present in the prior art. See In re Rijckaert, 9 F.3d 1531, 1534 (Fed. Cir. 1993) (“„That which may be inherent is not necessarily known. Obviousness cannot be predicated on what is unknown.‟ Such a retrospective view of inherency is not a substitute for some teaching or suggestion supporting an obviousness rejection.”) (quoting In re Spormann, 363 F.2d 444, 448 (CCPA 1966)). In the instant case, however, the rationale for combining the claimed components, including the preparation of a drug-bile acid precipitate/complex comes from Penkler‟s explicit teachings, and is not derived from any knowledge unavailable to an ordinary artisan. We acknowledge Penkler‟s disclosure that its drug-bile acid complexes can be used in compositions that deliver the complexed drug quickly (see e.g., Penkler, col. 1, ll. 27-29 (“The mucosal route of drug delivery is a useful alternative to parenteral delivery where rapid therapeutic effect is desired.”); see also id. at col. 11, ll. 52-56). However, as noted above, Penkler also discloses that its drug-bile acid complexes are useful in orally administered dosage forms that provide sustained release: Appeal 2010-009244 Application 11/207,126 15 The acid addition salt present in part or completely as a cyclodextrin inclusion complex may be formulated together with conventional pharmaceutical excipients into sustained release buccal tablets or patches with uni-directional release according to methods known in the art. Preferred excipients for sustained release buccal tablets or patches are muco-adhesive polymers such as cross-linked polyacrylic acids (carbomers, polycarbophils). (Id. at col. 12, ll. 9-15 (emphasis added); see also id. at col. 1, ll. 29-30 (“The transermal [sic, transdermal] route is advantageous for sustained release of active agents.”)) Thus, we are not persuaded that an ordinary artisan following Penkler‟s teachings lacked a reasonable expectation in producing a composition having claim 13‟s functional properties, nor are we persuaded that the claimed properties of zero-order kinetics and slower release compared to conventional salts would have been considered unexpected when viewed alongside the relevant teachings in Penkler, absent evidence to the contrary. Moreover, the fact that Appellant‟s purpose in formulating the claimed composition -- producing a composition with zero-order kinetics -- might have been different than Penkler‟s purpose does not demonstrate that claim 13 would have been unobvious to an ordinary artisan viewing Penkler‟s teachings. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (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 objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103.”). Appeal 2010-009244 Application 11/207,126 16 In sum, for the reasons discussed, we conclude that claim 13 would have been obvious to an ordinary artisan in view of Penkler. While we have only included claim 13 in this rejection, should prosecution resume in this case, the Examiner should consider whether any of its dependent claims should be subject to this rejection. SUMMARY We reverse the Examiner‟s new matter rejection of claims 13-17, 19, 20, and 40-45, under 35 U.S.C. § 112, first paragraph. We also reverse the Examiner‟s obviousness rejection of claims 13-17, 19, 20, and 40-45 over Pillay and Penkler. We enter a new ground of rejection of claim 13 under 35 U.S.C. § 103(a) as being obvious over Penkler. TIME PERIOD FOR RESPONSE This decision contains a new ground of rejection pursuant to 37 C.F.R. § 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960 (August 12, 2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37 C.F.R. § 41.50(b) provides “[a] new ground of rejection pursuant to this paragraph shall not be considered final for judicial review. 37 C.F.R. § 41.50(b) also provides that the appellant, WITHIN TWO MONTHS FROM THE DATE OF THE DECISION, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: (1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new evidence relating to the claims so rejected, or both, and have the matter Appeal 2010-009244 Application 11/207,126 17 reconsidered by the examiner, in which event the proceeding will be remanded to the examiner . . . . (2) Request rehearing. Request that the proceeding be reheard under § 41.52 by the Board upon the same record . . . . REVERSED, 37 C.F.R. § 41.50(b) alw Copy with citationCopy as parenthetical citation