Endo Pharmaceutical Inc.v.Depomed, Inc.Download PDFPatent Trial and Appeal BoardSep 29, 201410045823 (P.T.A.B. Sep. 29, 2014) Copy Citation Trials@uspto.gov Paper 12 571-272-7822 Entered: September 29, 2014 UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ ENDO PHARMACEUTICALS INC., Petitioner, v. DEPOMED, INC., Patent Owner. ____________ Case IPR2014-00655 Patent 6,635,280 B2 ____________ Before ERICA A. FRANKLIN, GRACE KARAFFA OBERMANN, and TINA E. HULSE, Administrative Patent Judges. HULSE, Administrative Patent Judge. DECISION Denying Institution of Inter Partes Review 37 C.F.R. § 42.108 IPR2014-00655 Patent 6,635,280 B2 2 INTRODUCTION I. Petitioner Endo Pharmaceuticals Inc. filed a Corrected Petition requesting an inter partes review of claims 1, 2, 8, 9, 13–15, 43, 45, and 46 of U.S. Patent No. 6,635,280 B2 (Ex. 1001, “the ’280 patent”). Paper 5 (“Pet.”). Patent Owner Depomed, Inc. filed a Preliminary Response to the Petition. Paper 11 (“Prelim. Resp.”). We have jurisdiction under 35 U.S.C. § 314, which provides that an inter partes review may not be instituted “unless . . . there is a reasonable likelihood that the petitioner would prevail with respect to at least 1 of the claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering the Petition and Preliminary Response, we determine that Petitioner has not shown a reasonable likelihood that it would prevail in showing the unpatentability of any challenged claim. Accordingly, the Petition is denied. A. Related Proceedings Petitioner and Patent Owner identify various district court actions involving the ’280 patent, including an action involving the parties titled Depomed, Inc. v. Endo Pharmaceuticals Inc., L.P., No. 3:13-02467 (D.N.J.). Pet. 1; Paper 8 at 2–3. Petitioner also has filed five related petitions for inter partes review, one involving the ’280 patent (IPR2014-00656); two involving U.S. Patent No. 6,340,475 B2 (“the ’475 patent”), which is the parent of the ’280 patent (IPR2014-00653 and IPR2014-00654); and two involving U.S. Patent No. 6,723,340 B2 (IPR2014-00651 and IPR2014-00652). Previously, the Board instituted inter partes review proceedings involving the ’280 patent (IPR2014-00377), and the ’475 patent (IPR2014- IPR2014-00655 Patent 6,635,280 B2 3 00378 and IPR2014-00379), which were initiated by Petitioner Purdue Pharma LP. B. The ’280 Patent (Ex. 1001) The ’280 patent relates to drugs formulated as unit oral dosage forms by incorporating them into polymeric matrices comprised of hydrophilic polymers that swell upon imbibition of water to a size large enough to promote gastric retention of the drug during the fed mode. Ex. 1001, Abstract. Drugs administered by conventional tablets generally become available to body fluids at a high rate initially, followed by a rapid decline. Id. at 1:31–33. To address this delivery pattern, controlled drug delivery systems were introduced in the 1970’s. Id. at 1:35–37. Many of the controlled delivery systems utilize hydrophilic, polymeric matrices that provide controlled release of sparingly soluble drugs. Id. at 1:44–46. For soluble drugs, however, such matrices do not provide adequate control of drug release. Id. at 1:46–50. The claimed invention allows drugs that are highly soluble in water to be administered orally in a way that will prolong their delivery time to spread their release rate more evenly throughout the duration of the fed mode. Id. at 5:32–36. This more even release rate reduces the problem of transient overdosing, and controls the dosage to safer and more effective levels over an extended period of time. Id. at 5:36–41. Moreover, particles exceeding about one cm in size are larger than the pylorus and are retained in the stomach for approximately four to six hours. Id. at 11:66–12:3. The Specification states that these benefits are due to using a polymeric matrix that is water-swellable rather than just hydrophilic, that has an erosion rate substantially slower than its swelling rate, and that releases the drug IPR2014-00655 Patent 6,635,280 B2 4 primarily by diffusion. Id. at 5:57–62. Preferred polymeric matrices include water-swellable polymers such as hydroxypropylmethylcellulose (“HPMC”) and poly(ethylene) oxide (“PEO”). Id. at 7:54–8:51. C. Illustrative Claim Claims 1 and 43 of the ’280 patent are independent claims. Claims 8–15, 45, and 46 depend from claim 1, either directly or indirectly. Claim 1 is illustrative and is reproduced below: 1. A controlled-release oral drug dosage form for releasing a drug whose solubility in water is greater than one part by weight of said drug in ten parts by weight of water, said dosage form comprising one or more polymers forming a solid polymeric matrix with said drug incorporated therein at a weight ratio of drug to polymer of from 15:85 to 80:20, said dosage form being one that when swollen in a dimensionally unrestricted manner as a result of imbibition of water is of a size exceeding the pyloric diameter in the fed mode to promote retention in the stomach during said fed mode, that releases said drug into gastric fluid by the dissolution and diffusion of said drug out of said matrix by said gastric fluid, that upon immersion in gastric fluid retains at least about 40% of said drug one hour after such immersion and releases substantially all of said drug after such immersion, and that remains substantially intact until substantially all of said drug is released. Claim 43, the only other independent claim challenged in the Petition, is directed to a method of orally administering to a subject a therapeutic drug in a dosage form comprising a solid polymeric matrix that, inter alia, “releases said drug into gastric fluid by the dissolving of said drug by said gastric fluid and either erosion of said matrix or diffusion of said dissolved drug out of said matrix,” and “releases substantially all of said drug within about ten hours after [] immersion” IPR2014-00655 Patent 6,635,280 B2 5 in gastric fluid, thereby extending the release rate of the drug with time during the fed mode. D. The Prior Art Relied Upon Petitioner relies upon the following prior art references: Shell US 5,007,790, issued Apr. 16, 1991 (“the Shell ’790 patent”) Ex. 1005 Edgren US 4,871,548, issued Oct. 3, 1989 (“the ’548 patent”) Ex. 1006 Shell WO 93/18755, published Sept. 30, 1993 (“the Shell 1993 publication”) Ex. 1007 Baveja Zero-Order Release Hydrophilic Matrix Tablets of β-adrenergic Blockers, 39 INT’L J. OF PHARM. 39–45 (1987). Ex. 1008 Colombo Drug Release Modulation by Physical Restrictions of Matrix Swelling, 63 INT’L J. OF PHARM. 43–48 (1990). Ex. 1009 Wong US 6,120,803, issued Sept. 19, 2000 (“the ’803 patent”) Ex. 1010 E. The Asserted Grounds of Unpatentability Petitioner challenges the patentability of claims 1, 2, 8, 9, 13–15, 43, 45, and 46 of the ’280 patent on the following grounds: Reference Basis Claims Challenged ’548 patent § 102(b) 1, 2, 8, 9, 13–15, 43, 45, and 46 Shell 1993 publication § 102(b) 1, 2, 13–15, 43, 45, and 46 Shell ’790 patent § 102(b) 1, 2, 8, 9, 13–15, 43, 45, and 46 Baveja § 102(b) 1, 8, 9, 13–15, 45, and 46 Colombo § 102(b) 1, 2, 13–15, 45, and 46 IPR2014-00655 Patent 6,635,280 B2 6 Reference Basis Claims Challenged ’803 patent § 102(e) 43 ANALYSIS II. A. Claim Construction In an inter partes review, the Board interprets claim terms in an unexpired patent according to the broadest reasonable construction in light of the specification of the patent in which they appear. 37 C.F.R. § 42.100(b). Under that standard, and absent any special definitions, we give claim terms their ordinary and customary meaning, as would be understood by one of ordinary skill in the art at the time of the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any special definitions for claim terms must be set forth with reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). 1. Previously Construed Terms The Board previously construed the terms of the ’280 patent set forth in the table below in the Decision instituting inter partes review in IPR2014- 00377 (Ex. 2003): Claim Term Claim(s) Construction “gastric fluid” 1, 43 “both the fluid in the stomach and simulated or artificial fluids recognized by those skilled in the art as a suitable model for the fluid of the human stomach” (Ex. 2003, at 6) IPR2014-00655 Patent 6,635,280 B2 7 Claim Term Claim(s) Construction “releases substantially all of said drug after such immersion” 1 “at least 80% of the drug has been released” (Ex. 2003, at 7) “releases substantially all of said drug within about ten hours after such immersion” 43 “at least 80% of the drug has been released after ten hours of immersion in gastric fluid” (Ex. 2003, at 7) “substantially intact” 1 “substantially retains its size and shape without deterioration due to becoming solubilized in the gastric fluid or due to breakage into fragments or small particles” (Ex. 2003, at 7–8) Based on the information presented at this stage of the proceeding, we again determine that these constructions are the broadest reasonable constructions consistent with the Specification, and, on that basis, we adopt them for the purposes of this Decision. In addition to the terms that we construed previously, we construe the following terms proposed by the parties. 2. “when swollen in a dimensionally unrestricted manner” The term “when swollen in a dimensionally unrestricted manner” appears in independent claims 1 and 43. Petitioner contends that this term is indefinite, but proposes that the Board adopt the construction previously adopted by several district courts, including the court in Depomed, Inc. v. Lupin Pharmaceuticals, Inc. Pet. 10–11 (citing Exs. 1012-1014). That is, Petitioner contends that this limitation should be construed to mean “[t]he dosage form, which comprises a polymeric matrix, increases in size due to the ingress of water.” See Ex. 1012, at 12. Patent Owner contends that this IPR2014-00655 Patent 6,635,280 B2 8 term is not indefinite and should be construed according to its plain and ordinary meaning. Prelim. Resp. 20. When construing claims, we interpret claims “with an eye toward giving effect to all terms in the claim.” Bicon Inc. v. Straumann Co., 441 F.3d 945, 950 (Fed. Cir. 2006). Thus, we decline to adopt Petitioner’s construction because it reads out the “dimensionally unrestricted manner” limitation. See Stumbo v. Eastman Outdoors, Inc., 508 F.3d 1358, 1362 (Fed. Cir. 2007) (denouncing claim constructions that render limitations superfluous). Claim 1 recites that the “dosage form compris[es] one or more polymers forming a solid polymeric matrix . . ., said dosage form being one that when swollen in a dimensionally unrestricted manner as a result of imbibition of water is of a size exceeding the pyloric diameter.” Ex. 1001, 17:48–53. Moreover, the ’280 patent Specification states that the water- swellable polymer forming the matrix “swells in a dimensionally unrestricted manner upon imbibition of water.” Ex. 1001, 7:56–57. Consistent with this disclosure, the Lupin district court explained: “It is not the swelling itself that is unrestricted, but the swelling of the dimensions of the dosage form—that is, length, the width, or other dimension of the dosage form—based on the swelling characteristics of the selected polymer.” Ex. 1012, at 10. On this record, given the claim language and the Specification, we construe “when swollen in a dimensionally unrestricted manner” to mean that the dosage form “has increased in size in such a way that is not restricted in any dimension.” IPR2014-00655 Patent 6,635,280 B2 9 3. “releases said drug . . . by the dissolution and diffusion of said drug out of said matrix” / “releases said drug . . . by the dissolving of said drug . . . and either erosion of said matrix or diffusion of said dissolved drug out of said matrix” The term “releases said drug . . . by the dissolution and diffusion of said drug out of said matrix” (i.e., the “dissolution and diffusion” limitation) appears in independent claim 1. And the term “releases said drug . . . by the dissolving of said drug . . . and either erosion of said matrix or diffusion of said dissolved drug out of said matrix” (i.e., the “erosion or diffusion” limitation) appears in independent claim 43. Patent Owner contends that the “dissolution and diffusion” limitation should be construed according to the district court’s construction as “rapid dissolution of the drug, followed by slow diffusion of the drug out of the water-swollen matrix, such that the drug is released at a rate primarily controlled by the rate of diffusion.” Prelim. Resp. 14 (emphasis omitted). Patent Owner further contends that the “erosion or diffusion” limitation should be construed as “releases said drug into gastric fluid by either (a) rapid dissolution of the drug followed by slow rate-controlling diffusion of the drug out of said matrix or (b) rapid dissolution of the drug and rate-controlling erosion of said matrix.” Id. at 15–16. Petitioner does not propose a construction for either limitation. Patent Owner urges the Board to adopt a construction that limits the claims such that the rate of drug release is “primarily controlled by the rate of diffusion” in claim 1 or by “rate-controlling” diffusion or erosion in claim 43. Prelim. Resp. 14–16. The claim language, however, does not support limiting the construction in this manner. Nothing in claim 1 or claim 43 requires the drug release to be “primarily” by diffusion or erosion. Although the Specification states that beneficial effects are achieved “by using a IPR2014-00655 Patent 6,635,280 B2 10 formulation in which the drug is dispersed in a polymeric matrix . . . that releases the drug primarily by diffusion” (Ex. 1001, 5:58–62), we decline to import limitations from the Specification when applying the broadest reasonable construction. This is particularly true in light of claim 43, which allows for drug release by erosion or diffusion. Ex. 1001, 25:51–54 (reciting the “erosion or diffusion” limitation). Accordingly, we construe the claims according to their plain and ordinary meaning and decline to import any requirement that the drug release occur “primarily” by diffusion in claim 1, or by “rate-controlling” erosion or diffusion in claim 43. 4. All Remaining Terms We determine that, for purposes of this Decision, none of the other terms proposed by the parties requires express construction at this time. B. Anticipation by the ’548 Patent (Ex. 1006) 1. The ’548 Patent The ’548 patent relates to a controlled-release dosage form comprising a drug and at least two different cellulose ethers. Ex. 1006, 1:12–16. According to the ’548 patent specification, “[an] object of the present invention is to provide a dosage form of delivering a drug in the gastrointestinal tract that substantially avoids a premature disintegration.” Id. at 3:1–4. The ’548 patent specification also states that the disclosed invention “delivers a drug at a rate of dosage form release that corresponds to the rate of change of the integrity of the dosage form over a prolonged period of at least eight hours.” Id. at 3:4–7. Moreover, the dosage form uses cellulose ethers, which swell extensively when hydrated and lessen direct drug contact with mucosal tissues. Id. at 11:23–26. The drug delivery matrix is suitable for gastric IPR2014-00655 Patent 6,635,280 B2 11 retention over the releasing lifetime of the dosage system. Id. at 10:65–68. Furthermore, “when all the drug is released, the system bioerodes into innocuous particles and dissolved polymers that pass from the gastrointestinal tract.” Id. at 10:68–11:3. 2. Analysis Petitioner contends that the ’548 patent anticipates claims 1, 2, 8, 9, 13–15, 43, 45, and 46 of the ’280 patent. Pet. 13–19. Patent Owner disagrees. Prelim. Resp. 25–30. As support for its anticipation claim, Petitioner relies on several different embodiments disclosed in the ’548 patent. For example, regarding independent claim 1, as disclosure of a “drug whose solubility in water is greater than one part by weight of said drug in ten parts by weight of water,” Petitioner cites the ’548 patent’s disclosure of potassium chloride. Pet. 14. But for the disclosure of “retain[ing] at least about 40% of said drug one hour after such immersion” and “releases substantially all of said drug after such immersion,” Petitioner relies on Example 3 and Figure 6 of the ’548 patent. Id. at 15. Example 3 and Figure 6, however, describe an embodiment that uses ibuprofen, not potassium chloride. Ex. 1006, 9:4–15. Similarly, for independent claim 43, Petitioner cites aspirin as teaching a “drug [that] has at least one ionized group in the pH range of 5 through 8” (id. at 37), and again cites the ibuprofen embodiment in Example 3 and Figure 6 as teaching a matrix that “retains at least about 40% of said drug one hour after such immersion in gastric fluid” (id. at 38–39). Although Petitioner also generally states that “drugs in salt form described in the ’548 patent would have at least one ionized group in the pH range 5 through 8,” Petitioner fails to cite sufficient support for this statement in IPR2014-00655 Patent 6,635,280 B2 12 either the ’548 patent specification or from its witness, Dr. Clive Wilson. Id. at 37. Thus, Petitioner has not shown that ibuprofen is a drug that has at least one ionized group in the pH range of 5 through 8. We, therefore, do not find Petitioner’s arguments sufficient. Petitioner has not shown that ibuprofen is a drug whose solubility is greater than one part by weight of drug in ten parts by weight of water or that ibuprofen has at least one ionized group in the pH range of 5 through 8. Nor has Petitioner shown that a dosage form with potassium chloride or aspirin achieves the drug release limitations above. In light of these deficiencies, Petitioner has not shown sufficiently that the ’548 patent anticipates the claimed invention. Petitioner cannot combine parts of separate embodiments disclosed in the ’548 patent to piece together the claimed invention. As our reviewing court’s predecessor stated, for anticipation, the prior art reference “must clearly and unequivocally disclose the claimed compound or direct those skilled in the art to the compound without any need for picking, choosing, and combining various disclosures not directly related to each other by the teachings of the cited reference.” In re Arkley, 455 F.2d 586, 587 (CCPA 1972); see also Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008) (holding that “unless a reference discloses within the four corners of the document not only all of the limitations claimed but also all of the limitations arranged or combined in the same way as recited in the claim, it cannot be said to prove prior invention of the thing claimed, and, thus, cannot anticipate under 35 U.S.C. § 102”). IPR2014-00655 Patent 6,635,280 B2 13 Accordingly, we determine that Petitioner has not established a reasonable likelihood that it would prevail in showing that the ’548 patent anticipates claims 1, 2, 8, 9, 13–15, 43, 45, and 46 of the ’280 patent. C. Anticipation by the Shell 1993 Publication (Ex. 1007) 1. Shell 1993 Publication The Shell 1993 publication discloses a sustained-release oral drug dosage form that releases a solution of a drug into the stomach and that comprises a tablet or capsule of a plurality of particles of a solid-state drug dispersed in alkyl cellulose. Ex. 1007, 2:13–17. The alkyl cellulose “swells unrestricted dimensionally via imbibition of gastric fluid to increase the size of the particles . . . with consequent increase in gastric retention time of the particles.” Id. at 2:17–21. The dosage form also “permits dissolution of the dispersed drug by imbibed gastric fluid while the drug is within the particle and release of the resulting solution” and “maintains its physical integrity over at least a substantial portion of the time period during which the drug is released into the stomach and then dissolves.” Id. at 2:23–31. 2. Analysis Petitioner contends that the Shell 1993 publication anticipates claims 1, 2, 13–15, 45, and 46 of the ’280 patent. Pet. 17–19. Patent Owner opposes Petitioner’s contention. Prelim. Resp. 30–33. Like its argument with respect to the ’548 patent, Petitioner relies on several different embodiments of the Shell 1993 publication to arrive at a teaching of the claimed invention. For example, Petitioner relies on potassium chloride as teaching the water solubility limitation (Pet. 17), but relies on the drug release studies of dosage forms using aspirin as teaching the requisite drug release limitations (id. at 18–19). For the same reasons IPR2014-00655 Patent 6,635,280 B2 14 stated above, we reject Petitioner’s argument. Petitioner cannot establish anticipation by picking and choosing from the elements of different embodiments within the Shell 1993 publication. Arkley, 455 F.2d at 587; Net MoneyIN, 545 F.3d at 1371. Accordingly, we determine that Petitioner has not established a reasonable likelihood that it would prevail in showing that the Shell 1993 publication anticipates claims 1, 2, 13–15, 45, and 46 of the ’280 patent. D. Anticipation by the Shell ’790 Patent (Ex. 1005) 1. Shell ’790 Patent The Shell ’790 patent discloses a sustained-release oral dosage form that “is retained well in the stomach and releases drug as a solution into the stomach.” Ex. 1005, 1:6-9. The dosage form comprises a plurality of solid particles composed of a solid-state drug dispersed within a hydrophilic, water-swellable polymer that swells in gastric fluid to increase the particle size to a level that promotes retention in the stomach over the time period. Id. at 1:54–61. The dosage form also “permits slow dissolution of the dispersed drug by gastric fluid and release of the resulting solution from the particles.” Id. at 1:61–63. Finally, the dosage form “maintains its physical integrity over at least a substantial portion of the time period and thereafter rapidly dissolves.” Id. at 1:65–67. 2. Analysis a. Claims 1, 2, 8, 9, 13–15, 45, and 46 Petitioner asserts that the Shell ’790 patent anticipates claims 1, 2, 8, 9, 13–15, 45, and 46 of the ’280 patent. Pet. 19–23, 31–36. Patent Owner disagrees. Prelim. Resp. 30–33. IPR2014-00655 Patent 6,635,280 B2 15 Claim 1 recites that the dosage form “upon immersion in gastric fluid retains at least about 40% of said drug one hour after such immersion.” Ex. 1001, 17:57–60. As disclosure of this limitation, Petitioner cites the Shell ’790 patent’s teaching that “the polymer [is] to remain insoluble for the desired time period, normally at least from about 4 hours to 8 hours up to 12 hours.” Pet. 21 (citing Ex. 1005, 3:7–10). But Petitioner does not explain why the disclosure that the polymer remains insoluble for a certain period of time discloses the limitation that at least about 40% of the drug is retained after one hour. Because Petitioner has not established a connection between the cited disclosure and the claim limitation, we determine that Petitioner has not established a reasonable likelihood that it would prevail in showing that the Shell ’790 patent anticipates claim 1 or any of its dependent claims 2, 8, 9, 13–15, 45, and 46. b. Claim 43 Petitioner asserts that the Shell ’790 patent anticipates claim 43 of the ’280 patent. Pet. 44-47. Patent Owner disagrees. Prelim. Resp. 32-33. Petitioner again relies on various elements selected from different embodiments of the Shell ’790 patent to arrive at a disclosure of the claimed invention. For example, Petitioner relies on aspirin as disclosing the limitation “where said drug has at least one ionized group in the pH range of 5 through 8.” Pet. 45. Petitioner then relies on drug release studies of dosage forms using potassium chloride as disclosing “releases substantially all of said drug within about ten hours after such immersion.” Id. at 46–47. For the same reasons stated above, we reject Petitioner’s argument. See Arkley, 455 F.2d at 587; Net MoneyIN, 545 F.3d at 1371. Thus, we IPR2014-00655 Patent 6,635,280 B2 16 determine that Petitioner has not established a reasonable likelihood that it would prevail in showing that the Shell ’790 patent anticipates claim 43. E. Anticipation by Baveja (Ex. 1008) 1. Baveja Baveja discloses a dosage form comprised of a swellable hydrophilic matrix that exhibits zero-order (i.e., constant) release of a drug. Ex. 1008, Summary. Baveja uses β-adrenergic blockers propranolol hydrochloride, alprenolol hydrochloride, and metoprolol tartrate as model drugs. Id. at 40. Baveja describes tablets with different ratios of HPMC, sodium carboxymethylcellulose (“Na CMC”), and drug, which are then subjected to an in vitro dissolution study. The in vitro dissolution study involves placing the tablets into a dissolution rate test apparatus with diluted HCl (pH 3.0) for three hours and then in 0.2 M phosphate buffer (pH 7.4) for another 9 hours. Id. The results of the dissolution studies for tablets formed from just HPMC and drug are shown in Figures 1–3. For example, Figure 2 is reproduced below: IPR2014-00655 Patent 6,635,280 B2 17 Figure 2 illustrates the cumulative percent of metoprolol tartrate released as a function of time from tablets containing metoprolol tartrate to HPMC in the ratios shown. Id. at 41. As explained by Baveja, the rate of release of the tablets made of drug and HPMC decreases with time, which may be due to “an increase in diffusional path length for the drug[,] which in turn may be due to slower erosion rate of the rubbery layer and faster advancement of swelling front into the glassy polymer.” Id. Baveja also describes tablets formed from HPMC, Na CMC, and drug in varying amounts that exhibit a nearly zero-order rate of release. Id., Summary. IPR2014-00655 Patent 6,635,280 B2 18 2. Analysis Petitioner contends that Baveja anticipates claims 1, 8, 9, 13–15, 45, and 46 of the ’280 patent. Pet. 23–28. Patent Owner disagrees, arguing, among other things, that the Board has determined already in IPR2014- 00377 that Baveja does not expressly or inherently disclose the “substantially intact” limitation of claim 1. Prelim. Resp. 33–35. We agree with Patent Owner, because Petitioner relies solely on the experiments run by Purdue’s witness, Kinam Park, Ph.D., as support for the “substantially intact” limitation. Prelim. Resp. 26–27. According to Petitioner, “Dr. Park’s test results confirm that the polymeric matrix used in the ’280 tablets remain substantially intact until all of the drug is released.” Pet. 24. As explained in our Decision to Institute in IPR2014-00377, however, Dr. Park never established that the dosage form that he prepared was actually the same as the dosage form that Baveja prepared. Purdue Pharma L.P. v. Depomed, Inc., Case IPR2014-00377, slip op. at 11 (PTAB July 10, 2014) (Paper 9). To establish this, Dr. Park could have, for example, subjected the alprenolol tablets that he prepared to the same dissolution study disclosed in Baveja to demonstrate that his tablets achieved the same results as those disclosed for Baveja’s formulation. Without such evidence, we cannot reasonably conclude that Dr. Park, in fact, tested the dosage form disclosed by Baveja. Ex. 2003, at 10–12; see also Purdue Pharma, IPR2014-00377 Order Denying Petitioner’s Request for Rehearing, IPR2014-00377 (Paper 17) at 3–4. Thus, for all the same reasons discussed in our Decision to Institute in IPR2014-00377, we determine that Petitioner has not established a IPR2014-00655 Patent 6,635,280 B2 19 reasonable likelihood that it would prevail in showing that Baveja anticipates claims 1, 8, 9, 13–15, 45, or 46 of the ’280 patent. F. Anticipation by Colombo (Ex. 1009) 1. Colombo Colombo relates to swellable matrix systems in the form of a tablet comprising a mixture of the drug diltiazem, HPMC, ethylcellulose, and mannitol. Ex. 1009, at 44. Colombo discloses three different matrices: Case 0, the plain matrix; Case 1, the matrix coated with cellulose acetate propionate (“CAP”) on one face; and Case 2, the matrix coated with CAP on both faces. Id. Colombo describes “[s]welling and release experiments” in which the matrices were swollen in deionized water, and the drug release measurements were obtained concomitantly with the matrix swelling observations. Id. Colombo describes and depicts the morphological changes in the matrices over time, observing that, in the uncoated system (Case 0), “[v]ery quickly (after 15 min) the swelling of the matrix moves both in axial and radial directions.” Id. Colombo also discloses the drug release profiles of the systems. Id. at 45. Figure 5 of Colombo is reproduced below: IPR2014-00655 Patent 6,635,280 B2 20 Figure 5 depicts the fraction of diltiazem released over time for the Case 0, Case 1, and Case 2 matrices. 2. Analysis Petitioner asserts that claims 1, 2, 13–15, 45, and 46 of the ’280 patent are anticipated by Colombo. Pet. 28–36. Patent Owner disagrees, noting that the Board determined already that Colombo does not disclose the “upon immersion in gastric fluid” limitation of claim 1. Prelim. Resp. 37–39. Claim 1 of the ’280 patent requires a drug dosage form that exhibits certain characteristics “upon immersion in gastric fluid.” Ex. 1001, 17:45– 61. Colombo, however, does not disclose immersion in gastric fluid. Colombo discloses immersion in deionized water for its swelling and release tests. Ex. 1009, at 44. Recognizing this difference, Petitioner’s witness Dr. Wilson states, “Although the experiments were conducted in water, a POSA would have understood that these matrices would have performed in substantially the same manner [if immersed] in gastric fluid.” Ex. 1011 IPR2014-00655 Patent 6,635,280 B2 21 ¶ 73. Dr. Wilson offers no objective support for that assertion. The statement, therefore, is of little probative value. See 37 C.F.R. § 42.65(a) (stating opinion testimony that does not disclose underlying facts or data “is entitled to little or no weight”); Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 294 (Fed. Cir. 1985) (stating a lack of objective support for expert opinion “may render the testimony of little probative value in a validity determination”). Further, we note that Dr. Wilson states that Colombo’s matrices would perform in “substantially the same manner in gastric fluid.” Ex. 1011 ¶ 73 (emphasis added). Dr. Wilson does not explain what “substantially the same” means in this context, or in what ways, if any, Colombo’s matrices may respond differently when immersed in gastric fluid. See id. Accordingly, Petitioner has not established that Colombo’s matrices would necessarily perform in the same manner upon immersion in gastric fluid as they do in deionized water. “To establish inherency, the extrinsic evidence ‘must make clear that the missing descriptive matter is necessarily present in the thing described in the reference . . . .’” In re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999) (citation omitted). Inherency is not proven “by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient.” Id. (quotation omitted). Because Petitioner has not shown that Colombo inherently teaches the “upon immersion in gastric fluid” limitation of claim 1, we determine that Petitioner has not established a reasonable likelihood that it would prevail in showing that claims 1, 2, 13–15, 45, and 46 of the ’280 patent are anticipated by Colombo. IPR2014-00655 Patent 6,635,280 B2 22 G. Anticipation by the ’803 Patent (Ex. 1010) 1. The ’803 Patent The ’803 patent relates to a drug dosage form adapted for retention in the stomach to deliver a drug over a sustained period of time. Ex. 1010, 1:10–14. The dosage form includes a drug and a polymer matrix formed of a swellable, water-soluble polymer that expands when contacted with fluids in the stomach, and a rigid or semi-rigid band of insoluble material in which swelling of the water-soluble polymer is constrained. Id. at 5:12–18. Figures 1B and 2 are reproduced side-by-side below: Figure 1B depicts one embodiment of the dosage form with insoluble band 15 circumscribing a portion of the polymer matrix in a form before placement in the stomach, and Figure 2 depicts the dosage form of Figure 1B in its initially swollen state after having expanded in the stomach. Id. at 7:42–45. IPR2014-00655 Patent 6,635,280 B2 23 Similarly, Figures 4A and 4B are reproduced side-by-side below: Figure 4A depicts a different embodiment of the dosage form with two bands of insoluble material in a form before placement in the stomach, and Figure 4B depicts the dosage form of Figure 4A in its swollen state. Id. at 11:60–12:4. The insoluble band prevents that portion of the polymer matrix that it surrounds from imbibing fluid, thus “substantially limiting any swelling of polymer matrix 11 at that location.” Id. at 11:47–48. The insoluble band also “facilitates the dosage form remaining in the stomach of a subject over a prolonged period of time.” Id. at 5:19–21. 2. Analysis Petitioner contends that claim 43 of the ’280 patent is anticipated by the ’803 patent. Pet. 48–51. Patent Owner opposes Petitioner’s challenge. Prelim. Resp. 39–41. Petitioner asserts that the ’803 patent discloses the limitation that the dosage form is “swollen in a dimensionally unrestricted manner as a result of imbibition of gastric fluid.” Pet. 49–50. Petitioner, however, has not shown sufficiently that the ’803 patent teaches this limitation. As discussed above, we have construed this limitation to mean that the dosage form “has increased in size in such a way that is not restricted in IPR2014-00655 Patent 6,635,280 B2 24 any dimension.” As is clear from the specification and the accompanying figures of the ’803 patent, the insoluble bands prevent the dosage form from swelling in such a way that is not restricted in any manner. Indeed, the Specification states that the band “substantially limit[s] any swelling of polymer matrix 11 at that location.” Ex. 1010, 11:47–48. Because Petitioner has not shown sufficiently that the ’803 patent teaches the “swollen in a dimensionally unrestricted manner,” we determine that Petitioner has not established a reasonable likelihood that it would prevail in showing that claim 43 of the ’280 patent is anticipated by the ’803 patent. CONCLUSION III. We conclude that Petitioner has not demonstrated a reasonable likelihood that it would prevail in showing that any claims of the ’280 patent are unpatentable based upon any of the asserted anticipation grounds. ORDER IV. In consideration of the foregoing, it is hereby ordered that the Petition is denied. IPR2014-00655 Patent 6,635,280 B2 25 FOR PETITIONER: Bruce Haas Endo-ipr@fchs.com Henry Rend Endo-ipr@fchs.com Stephen Yam syam@fchs.com FOR PATENT OWNER: Arlene L. 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