`Date Filed: September 1, 2016
`
`Filed On Behalf Of:
`
`Alkermes Pharma Ireland Limited and
`Alkermes Controlled Therapeutics, Inc.
`
`By:
`Scott K. Reed
`sreed@fchs.com
`212-218-2100
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LUYE PHARMA GROUP LTD., LUYE PHARMA (USA) LTD., SHANDONG
`LUYE PHARMACEUTICAL CO., LTD., and NANJING LUYE
`PHARMACEUTICAL CO., LTD.,
`Petitioners,
`v.
`ALKERMES PHARMA IRELAND LTD, and ALKERMES CONTROLLED
`THERAPEUTICS, INC.,
`Patent Owners.
`____________
`
`Case IPR2016-01095
`Patent 6,667,061
`____________
`
`PATENT OWNERS’ PRELIMINARY RESPONSE PURSUANT TO
`37 C.F.R. § 42.107
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................1
`
`BACKGROUND OF THE INVENTION .....................................................5
`
`A.
`
`B.
`
`The Development of the ’061 Patent...................................................6
`
`The ’061 Prosecution History .............................................................7
`
`III.
`
`THE PERSON OF ORDINARY SKILL IN THE ART ................................9
`
`IV. CLAIM CONSTRUCTION........................................................................10
`
`A.
`
`B.
`
`“Suspension” and “Fluid Phase of Said Suspension” ........................10
`
`“Viscosity” .......................................................................................11
`
`V.
`
`VI.
`
`LEGAL STANDARDS ..............................................................................13
`
`PETITIONERS’ ALLEGED UNPATENTABILITY
`GROUNDS ARE FATALLY FLAWED ....................................................15
`
`A.
`
`IPR Should Not Be Instituted Based on Ground 1.............................15
`
`1.
`
`Goldenheim Does Not Disclose the Claimed
`Viscosity Limitation ...............................................................16
`
`a.
`
`b.
`
`Goldenheim’s Alleged Viscosity Disclosure
`Does Not Specify Temperature.....................................16
`
`Petitioners Also Failed to Relate
`Goldenheim’s Alleged Viscosity Disclosure
`to the Fluid Phase of a Suspension................................20
`
`2.
`
`Petitioners Improperly Picked and Chose from
`Unrelated Disclosures in Goldenheim.....................................22
`
`B.
`
`IPR Should Not Be Instituted Based on Ground 2.............................24
`
`1.
`
`Goldenheim in View of the Pharmacopeias Does
`Not Teach the Claimed Viscosity Limitation ..........................24
`
`- i -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`2.
`
`A POSA Would Not Have Combined Goldenheim,
`the Pharmacopeias and Ramstack With a
`Reasonable Expectation of Success.........................................25
`
`a.
`
`b.
`
`c.
`
`Petitioners Offer Only Conclusory and
`Vague Statements About Motivation to
`Combine and Likelihood of Success .............................27
`
`A POSA Would Not Have Combined
`Goldenheim, the Pharmacopeias and
`Ramstack ......................................................................29
`
`A POSA Would Not Have Had a
`Reasonable Expectation of Success in
`Combining Goldenheim, the Pharmacopeias
`and Ramstack................................................................33
`
`C.
`
`IPR Should Not Be Instituted Based on Ground 3.............................35
`
`1.
`
`2.
`
`Goldenheim in View of the Pharmacopeias Does
`Not Teach the Claimed Viscosity Limitation ..........................35
`
`A POSA Would Not Have Combined Goldenheim,
`the Pharmacopeias and Kino With a Reasonable
`Expectation of Success ...........................................................36
`
`a.
`
`b.
`
`c.
`
`Petitioners Offer Only Conclusory and
`Vague Statements About Motivation to
`Combine and Likelihood of Success .............................36
`
`A POSA Would Not Have Combined
`Goldenheim, the Pharmacopeias and Kino....................39
`
`A POSA Would Not Have Had a
`Reasonable Expectation of Success in
`Combining Goldenheim, the Pharmacopeias
`and Kino .......................................................................41
`
`VII. PETITIONERS FAIL TO REBUT THE OBJECTIVE
`EVIDENCE OF NONOBVIOUSNESS......................................................42
`
`VIII. CONCLUSION ..........................................................................................44
`- ii -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`TABLE OF AUTHORITIES
`
`Cases
`Apple, Inc. v. Int'l Trade Comm'n,
`725 F.3d 1356 (Fed. Cir. 2013).................................................................. 43
`
`Aristocrat Techs. Australia Pty Ltd. v. Int’l Game Tech.,
`709 F.3d 1348 (Fed. Cir. 2013).................................................................. 11
`
`Continental Can Co. U.S.A. v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991).......................................................13, 17, 18
`
`Cook Biotech Inc. v. Acell, Inc.,
`460 F.3d 1365 (Fed. Cir. 2006).................................................................. 28
`
`Crocs v. U.S. Int’l Trade Comm’n,
`598 F.3d 1294 (Fed. Cir. 2010).............................................................34, 42
`
`In re GPAC Inc.,
`57 F.3d 1573 (Fed. Cir. 1995).................................................................... 44
`
`In re Montgomery,
`677 F.3d 1375 (Fed. Cir. 2012).............................................................13, 18
`
`In re Soni,
`554 F. 3d 746 (Fed. Cir. 1995)................................................................... 14
`
`King Pharms., Inc. v. Eon Labs., Inc.,
`616 F.3d 1267 (Fed. Cir. 2010).................................................................. 13
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007)........................................................................13, 14, 26
`
`Leo Pharm. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013 ..............................................................37, 39
`
`Mformation Techs., Inc. v. Research in Motion Ltd.,
`764 F.3d 1392 (Fed. Cir. 2014).................................................................. 11
`
`Net MoneyIN, Inc. v. VeriSign, Inc.,
`545 F.3d 1359 (Fed. Cir. 2008)...............................................................4, 22
`
`- iii -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005).................................................................. 12
`
`Procter & Gamble Co. v. Teva Pharms. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009)...............................................................14, 26
`
`Transocean Offshore Deepwater Drilling, Inc. v. Maersk
`Drilling USA, Inc.,
`699 F.3d 1340 (Fed. Cir. 2012).................................................................. 43
`
`Zenon Envtl., Inc. v. U.S. Filter Corp.,
`506 F.3d 1370 (Fed. Cir. 2012).................................................................. 28
`
`Statutes
`35 U.S.C. § 102 ..............................................................................................13, 15
`
`35 U.S.C. § 103 ..............................................................................................13, 15
`
`35 U.S.C. § 314(a) ............................................................................................... 13
`
`37 C.F.R. § 42.65(a) ............................................................................................ 37
`
`P.T.A.B.
`Conopco v. Procter & Gamble,
`IPR No. 2013-00510, Paper 9 (P.T.A.B. Feb. 12, 2014)............................. 26
`
`E.I. du Pont de Nemours & Co. v. Monsanto Tech. LLC,
`IPR No. 2014-00333, Paper 14 (P.T.A.B. July 11, 2014)........................... 26
`
`Fontaine Engineered Prods., Inc. v. Raildecks, Inc.,
`IPR No. 2013-00361, Paper 8 (P.T.A.B. Dec. 13, 2013) .................19, 21, 27
`
`Johns Manville Corp. v. Knauf Insulation, Inc.,
`IPR No. 2015-01633, Paper 10 (P.T.A.B. Jan. 4, 2016) ........................37, 39
`
`Merial Ltd. v. Virbac,
`IPR No. 2014-01279, Paper 13 (P.T.A.B. Jan. 22, 2015) ........................... 42
`
`Oxford Nanopore Techs. Ltd. v. Univ. of Wash.,
`IPR No. 2014-00512, Paper 12 (P.T.A.B. Sept. 15, 2014) ...................passim
`
`- iv -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`Phigenix, Inc. v. Immunogen, Inc.,
`IPR No. 2014-00676, Paper 39 (P.T.A.B. Oct. 27, 2015)........................... 44
`
`Praxair Distr. Inc. v. INO Therapeutics, Inc.,
`IPR No. 2015-00522, 2015-00524, 2015-00525, 2015-
`00526 Paper 12 (P.T.A.B. July 29, 2015)................................................2, 42
`
`Zetec, Inc. v. Westinghouse Elec. Co., LLC,
`IPR No. 2014-00384, Paper 10 (P.T.A.B. July. 23, 2014).....................19, 21
`
`- v -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`Alkermes Pharma Ireland Limited and Alkermes Controlled Therapeutics,
`
`Inc. (collectively “Patent Owners”) respectfully submit this Preliminary Response
`
`to the Petition of Luye Pharma Group Limited, Luye Pharma (USA) Limited,
`
`Shandong Luye Pharmaceutical Company, Limited and Nanjing Luye
`
`Pharmaceutical Co., Limited (collectively “Petitioners”) seeking inter partes
`
`review (“IPR”) of U.S. Patent No. 6,667,061 (“the ’061 patent”).1
`
`I.
`
`INTRODUCTION
`
`The ’061 patent “relates to injectable suspensions having improved
`
`injectability, and to methods for the preparation of such injectable suspensions.”
`
`(Exh. 1001 at 1:11-14.) Long-acting injectable dosage forms offer a number of
`
`advantages over oral medications, including improved patient compliance, reduced
`
`risk of overdose and more consistent bioavailability. Such benefits are especially
`
`important in treating diseases, such as schizophrenia, which have a lifelong course
`
`and are progressive in nature.
`
`However, injectable suspensions are among the “most difficult dosage forms
`
`to develop.” (Id. at 1:24-25; Exh. 1014 at 285; Exh. 1020 at 212; Exh. 2001 at
`
`173.) For instance, in order to be effective and pharmaceutically acceptable, a
`
`1 Petitioners have also filed another petition for IPR (IPR No. 2016-01096 (“the
`
`1096 petition”)) challenging claims 1-13 and 17-23 of the ’061 patent.
`
`- 1 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`suspension must achieve a certain level of injectability. (Exh. 1001 at 1:39-43.)
`
`“Injectability includes factors such as pressure or force required for injection,
`
`evenness of flow, aspiration qualities, and freedom from clogging.” (Id. at 1:62-
`
`64; Exh. 1014 at 299.) Injectability failures often manifest themselves in the form
`
`of a clog at the tip of the needle, and occur immediately or shortly after injection
`
`has been initiated. (Exh. 1001 at 4:52-55.) In view of this problem, conventional
`
`wisdom has been to keep viscosity of injectable suspensions low in order to make
`
`suspensions easier to inject. (Id. at 2:27-31, 2:37-40, 4:60-62; Exh. 1014 at 287,
`
`299.) This is particularly true for compositions containing microparticle
`
`preparations, where the “higher concentration of solids, as well as the larger solid
`
`particle size, make it more difficult to successfully inject” such suspensions. (Exh.
`
`1001 at 2:41-53.)
`
`The invention of the ’061 patent provides “injectable compositions . . . [that]
`
`overcome injectability problems, particularly injectability failures that occur upon
`
`injection into muscle or subcutaneous tissue.” (Id. at 4:47-50.) Surprisingly, the
`
`present invention addresses the problem by increasing viscosity of the fluid phase,
`
`contrary to conventional wisdom. This unexpected outcome was addressed in
`
`detail during prosecution, including through the submission of declaration
`
`evidence—making the Petitioners’ silence on the issue of unexpected results even
`
`more glaring. Praxair Distr. Inc. v. INO Therapeutics, Inc., IPR Nos. 2015-00522,
`
`- 2 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`2015-00524, 2015-00525, 2015-00526, Paper 12 at 16-17 (P.T.A.B. July 29, 2015)
`
`(denying institution where petitioner failed to address arguments made during
`
`prosecution, which the Examiner found persuasive).
`
`Moreover, despite the importance of the claimed viscosity range described in
`
`the specification and highlighted during prosecution, Petitioners fail to identify any
`
`piece of prior art that teaches the viscosity limitation. Specifically, the claims
`
`require a viscosity range of the fluid phase of a suspension at a particular
`
`temperature, while the primary reference—Goldenheim—offers only a viscosity of
`
`the “final reconstituted product” and also fails to indicate any particular
`
`temperature requirement. (Exh. 1004 at 35:10-12.) This problem is exacerbated
`
`by the fact that other references cited by Petitioners explain that viscosity was
`
`known to be measured at numerous different temperatures, with the different
`
`temperatures having a significant impact on the stated viscosity and that the
`
`particular temperature used for the viscosity measurement was often dependent on
`
`the equipment being used. These deficiencies are fatal to each of Petitioners’
`
`grounds. Oxford Nanopore Techs. Ltd. v. Univ. of Wash., IPR No. 2014-00512,
`
`Paper 12 at 15 (P.T.A.B. Sept. 15, 2014) (denying institution where petition failed
`
`to explain why the prior art possessed a claimed structural attribute).
`
`Petitioners’ anticipation-based ground (Ground 1) also fails because
`
`Goldenheim does not disclose all of the limitations as set forth in the claims of the
`
`- 3 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`’061 patent. See, e.g., Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371
`
`(Fed. Cir. 2008).
`
`In addition, for Petitioners’ obviousness-based grounds (Grounds 2 and 3),
`
`Petitioners fail to explain why or how a person of ordinary skill in the art
`
`(“POSA”) would have combined the alleged teachings of the prior art references
`
`relied upon by Petitioners in Grounds 2 and 3 in the manner recited by the claims
`
`with a reasonable expectation of successfully improving suspension injectability.
`
`For instance, Petitioners offer only vague and nonspecific arguments as to why a
`
`POSA looking at Goldenheim would have turned to the monographs for
`
`carboxymethyl cellulose (“CMC”) from the U.S. or European Pharmacopeias.
`
`Likewise, Petitioners argue that “[a] POSA would look to combine . . . sustained
`
`release microparticles, to improve the injectability of the suspension” (Petition at
`
`48), without showing that a POSA would have reasonably expected any of the
`
`changes to lead to such an improvement. Indeed, a POSA would not have made
`
`such selective and nonsensical combinations. Moreover, given the conventional
`
`wisdom of the time, a POSA would not reasonably have expected to improve
`
`injectability by increasing viscosity. These failures are fatal to Petitioners’
`
`obviousness-based grounds. See, e.g., Oxford Nanopore Techs., Paper 12 at 17
`
`(denying institution where petition did “not discuss, with any specificity, the
`
`- 4 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`teachings . . . that would have prompted an ordinary artisan to use” one prior art
`
`element in another prior art’s system).
`
`For at least these reasons, institution of IPR should be denied.
`
`II.
`
`BACKGROUND OF THE INVENTION
`
`The ’061 patent relates to injectable suspensions having improved
`
`injectability. (Exh. 1001 at 1:12-15.) A central concept of the patent is that the
`
`fluid phase of the suspension has a viscosity greater than about 20 centipoise (cp)
`
`and less than about 600 cp (when measured at 20°C) in order to achieve improved
`
`injectability.
`
`Claim 1, the sole independent claim of the ’061 patent, recites:
`
`1. A composition suitable for injection through a needle into a host,
`comprising:
`microparticles comprising a polymeric binder; and
`
`an injection vehicle, wherein said microparticles are
`suspended in said injection vehicle at a
`concentration of greater than about 30 mg/ml to
`form a suspension, wherein a fluid phase of said
`suspension has a viscosity greater than about 20 cp
`and less than about 600 cp at 20º C., wherein the
`viscosity of said fluid phase of said suspension
`provides injectability of the composition through a
`needle ranging in diameter from 18-22 gauge.
`
`- 5 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`A.
`
`The Development of the ’061 Patent
`
`The invention of the ’061 patent overcomes injectability problems,
`
`particularly injectability failures that occur upon injection into muscle or
`
`subcutaneous tissues. (Exh. 1001 at 4:47-50.) The ’061 patent describes a series
`
`of tests directed at evaluating injectability. (Id. at Examples 1-4.) These tests
`
`revealed that “injectability is improved, and in vivo injectability failures
`
`significantly and unexpectedly reduced, by increasing the viscosity of the fluid
`
`phase of an injectable suspension.” (Id. at 4:47-60, Examples 2-4.) This is in
`
`direct contrast to “conventional teachings that an increase in the viscosity hinders
`
`injectability.” (Id. at 4:60-62; see also Exh. 1014 at 33 (“Increases in the following
`
`characteristics tend to reduce syringeability or make material transfer through the
`
`needle more difficult: The viscosity of the vehicle . . . Probably the most important
`
`of these factors is viscosity.”), 287 (“However, most parenteral suspensions are
`
`usually dilute and have practical limitations for viscosity because of syringeability
`
`and injectability constraints.”), 297 (“However, the high viscosity and poor
`
`syringeability of such systems limit their use in parenteral suspensions.”), 299
`
`(“Increase in the viscosity, density, particle size, and concentration of solids in
`
`- 6 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`suspension hinders the syringeability of suspension.”).)2 This discovery was all the
`
`more unexpected because it “contradicted” the in vitro studies conducted by the
`
`inventors. (Exh. 1001 at Example 1.) Their in vivo injectability studies, by
`
`contrast, showed “a dramatic improvement in injectability with increased injection
`
`vehicle viscosity.” (Id.; see also Examples 2-3.)
`
`The inventors’ work further revealed that (1) “[v]iscosities of at least about
`
`20 cp are necessary for successful and medically acceptable injectability rates” but
`
`that viscosities of up to about 600 cp could be used in the invention (id. at
`
`Examples 3-4, 10:64-65) and (2) the inclusion of density enhancing agents results
`
`in fewer injectability failures (id. at Examples 3-4).
`
`B.
`
`The ’061 Prosecution History
`
`U.S. Pat. Appl. No. 09/577,875 (“the ’875 application”) was filed on May
`
`25, 2000, and issued as U.S. Patent No. 6,495,164 on December 17, 2002. The
`
`’875 application is the parent to U.S. Pat. Appl. No. 10/259,949 (“the ’949
`
`application”), which was filed on September 30, 2002, as a continuation of the
`
`2 Petitioners’ declarant, Dr. Patrick DeLuca, relies on Exh. 1014 (see, e.g., Exh.
`
`1002 at ¶¶ 18-22) but fails to address that Exh. 1014 specifically teaches away
`
`from the invention by disclosing that increasing viscosity tends to decrease
`
`syringeability.
`
`- 7 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`’875 application and issued as the ’061 patent on December 23, 2003. (Exh.
`
`1001.)
`
`During prosecution, the Examiner considered prior art including the Kino
`
`reference relied upon by Petitioners. (See, e.g., Exh. 1001 at References Cited;
`
`Exh. 1016 at 3-4; Exh. 1017 at 2-4; Exh. 1018.) Despite Petitioners’ claims
`
`otherwise (Petition at 35), the Examiner also considered Ramstack during
`
`prosecution. It, as well as its U.S. counterpart (U.S. Patent No. 5,650,173), are
`
`clearly cited on the face of the patent. (Exh. 1001 at References Cited.)
`
`Initially, the Examiner rejected the claims of the ’949 application,
`
`concluding that “absent unexpected results regarding the criticality of the viscosity,
`
`Kino discloses all the limitations of the instant claims.” (Exh. 1016 at 4.) The
`
`Examiner explained that “Kino discloses a sustained release microsphere
`
`preparation, which is produced by including a hydrophobic antipsychotic drug”
`
`and that the drug may be risperidone, a leading treatment for schizophrenia, which
`
`is injected intramuscularly. (Id. at 3-4.) In response, the applicants argued that
`
`“none of the cited documents or other documents of record discloses or suggests
`
`the relationship between increased viscosity and improved injectability.” (Exh.
`
`1017 at 2.) This argument was further supported by the Declaration of Mark A.
`
`Tracy, Ph.D., which was originally filed during prosecution of the parent ’875
`
`application. (Exh. 1018 at ¶ 3.) Consistent with the teachings in the art at the time,
`
`- 8 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`Dr. Tracy also established that, assuming measurement at 20ºC, the viscosity of the
`
`compositions disclosed in Kino fell far below the claimed range. (Id. at ¶¶ 4-5.) In
`
`Examples 1, 3 and 4 of Kino, the viscosity would be approximately 1 cp, if
`
`measured at 20ºC, and in Example 2 the viscosity would be less than 7 cp, if
`
`measured at 20ºC. (Id.) Kino thus taught a low viscosity for injections of
`
`antipsychotic drugs, including risperidone.
`
`By contrast, the claimed range requires a viscosity of greater than about
`
`20 cp and less than about 600 cp at 20ºC. The applicants also pointed to portions
`
`of the specification of the ’949 application, which establish the criticality of
`
`viscosity to improved injectability, and explained that such criticality was
`
`unexpected given the “conventional teachings that an increase in the viscosity
`
`hinders injectability and syringeability.” (Exh. 1017 at 3-4.)
`
`Upon consideration of these arguments and this evidence, the Examiner
`
`withdrew all rejections and allowed the instant claims. (Exh. 1019.)
`
`III. THE PERSON OF ORDINARY SKILL IN THE ART
`
`Patent Owners disagree with Petitioners’ proposed definition of a POSA and
`
`reserve the right to offer a correct definition. At this point, however, given the
`
`deficiencies in the petition, institution should be denied under any definition of a
`
`POSA.
`
`- 9 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`IV. CLAIM CONSTRUCTION
`
`Petitioners advance proposed constructions for a number of claim terms in
`
`the ’061 patent. Patent Owners reserve the right to fully respond to each of
`
`Petitioners’ proposed constructions. At this stage, however, Patent Owners focus
`
`on several highly erroneous constructions proposed by Petitioners, which may
`
`impact the Board’s institution analysis.
`
`A.
`
`“Suspension” and “Fluid Phase of Said Suspension”
`
`Petitioners contend that “suspension” means “a mixture of microparticles
`
`dispersed throughout an injection vehicle” (Petition at 19) while “fluid phase of
`
`said suspension” means “the reconstituted product in a two-phase product
`
`formulation” (id. at 20). While Petitioners’ proposed construction for
`
`“suspension” is reasonable in light of the patent claims and specification (see, e.g.,
`
`Exh. 1001 at 1:17-19, 5:8-13, 6:20-27, 11:55-13:61, claim 1), their proposed
`
`construction for “fluid phase of said suspension” is not.
`
`Petitioners have improperly limited their proposed construction of “fluid
`
`phase of said suspension” to only reconstituted suspensions. This limitation is
`
`clearly at odds with the patent specification, which makes clear that “injectable
`
`suspensions [of the invention] may be formulated as a ready-to-use injection or
`
`require a reconstitution step prior to use.” (Exh. 1001 at 1:30-32.)
`
`- 10 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`Therefore, consistent with the patent specification and claims, Patent
`
`Owners propose that “fluid phase of said suspension” be given its broadest
`
`reasonable construction, which includes ready-to-use injections and those that
`
`require a reconstitution step prior to use.
`
`B.
`
`“Viscosity”
`
`Petitioners also contend that “viscosity” should be construed to include the
`
`requirement that “[u]nless otherwise specified, viscosity is typically measured at
`
`20 or 25ºC.” (Petition at 22.) Petitioners’ proposed construction ignores that claim
`
`1 expressly specifies the particular temperature (20ºC) that corresponds to the
`
`claimed viscosity range. Thus, Petitioners’ proposed definition of viscosity
`
`improperly seeks to rewrite the claim language which expressly specifies the
`
`temperature at which viscosity should be measured. It is also contradicted by the
`
`teachings of Petitioners’ own cited references.
`
`There is no reason to construe the viscosity term of the ’061 patent to
`
`implicitly include a temperature at which viscosity is presumed to be measured
`
`when claim 1 expressly recites elsewhere that the claimed viscosity range
`
`corresponds to a measurement at 20ºC. See, e.g., Mformation Techs., Inc. v.
`
`Research in Motion Ltd., 764 F.3d 1392, 1399 (Fed. Cir. 2014) (favoring a
`
`construction that does not render another limitation “superfluous”); Aristocrat
`
`Techs. Australia Pty Ltd. v. Int’l Game Tech., 709 F.3d 1348, 1356-57 (Fed. Cir.
`
`- 11 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`2013) (declining to adopt proposed construction that would render another
`
`limitation “superfluous”); Phillips v. AWH Corp., 415 F.3d 1303, 1314 (Fed. Cir.
`
`2005) (finding claim term “baffles” does not inherently mean objects made of steel
`
`where claim also referred to “steel baffles”).
`
`Petitioners’ construction seems to be an attempt to circumvent the prior art
`
`that teaches that temperatures for viscosity measurements can range from 20ºC to
`
`121ºC. (See, e.g., Exh. 1006 at 1840.) Furthermore, Petitioners’ construction
`
`seems to be an attempt to use claim construction to overcome the failure of the
`
`asserted prior art to actually specify a temperature that corresponds to the alleged
`
`viscosity disclosure.
`
`Moreover, Petitioners’ construction attempts to include a temperature option
`
`higher than the one required by the claims. Such an attempt is improper in view of
`
`Petitioners’ own evidence, which states that “[t]he specifying of temperature is
`
`important because viscosity changes with temperature” and even “small
`
`temperature changes may lead to marked changes in viscosity.” (Exh. 1006 at
`
`1840.)
`
`Patent Owners propose that “viscosity” be given its broadest reasonable
`
`construction, consistent with the specification’s teaching that “viscosity describes
`
`the resistance that a liquid system offers to flow when it is subjected to an applied
`
`shear stress.” (Exh. 1001 at 2:14-15.)
`
`- 12 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`V.
`
`LEGAL STANDARDS
`
`To institute an IPR, Petitioners must show a reasonable likelihood of
`
`prevailing on unpatentability. See 35 U.S.C. § 314(a).
`
`For a claim to be unpatentable under 35 U.S.C. § 102, a single prior art
`
`reference must disclose each and every limitation of the claimed invention. King
`
`Pharms., Inc. v. Eon Labs., Inc., 616 F.3d 1267, 1275 (Fed. Cir. 2010). A prior art
`
`reference may anticipate without disclosing a feature of the claimed invention if
`
`that missing characteristic is necessarily present, or inherent, in the single
`
`anticipating reference. Continental Can Co. U.S.A. v. Monsanto Co., 948 F.2d
`
`1264, 1268 (Fed. Cir. 1991). “Inherency, however, may not be established by
`
`probabilities or possibilities. The mere fact that a certain thing may result from a
`
`given set of circumstances is not sufficient.” Id. at 1269. “The keystone of the
`
`inherency doctrine is inevitability . . . Absent inevitability, inherency does not
`
`follow even from a very high likelihood that a prior art method will result in the
`
`claimed invention.” In re Montgomery, 677 F.3d 1375, 1384 (Fed. Cir. 2012).
`
`For a claim to be unpatentable under 35 U.S.C. § 103, the differences
`
`between the claimed subject matter and the prior art must be such that the subject
`
`matter as a whole would have been obvious at the time the invention was made to a
`
`POSA in the art to which the subject matter pertains. KSR Int’l Co. v. Teleflex Inc.,
`
`550 U.S. 398, 406 (2007). “[A] patent composed of several elements is not proved
`
`- 13 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`obvious merely by demonstrating that each of its elements was, independently,
`
`known in the prior art.” Id. at 418. A party that petitions the Board for a
`
`determination of obviousness must show that “a skilled artisan would have been
`
`motivated to combine the teachings of the prior art references to achieve the
`
`claimed invention, and that the skilled artisan would have had a reasonable
`
`expectation of success in doing so.” Procter & Gamble Co. v. Teva Pharms. USA,
`
`Inc., 566 F.3d 989, 994 (Fed. Cir. 2009). Furthermore, a showing of obviousness
`
`may be overcome with objective evidence of secondary considerations such as
`
`unexpected results. See, e.g., In re Soni, 554 F.3d 746, 751 (Fed. Cir. 1995)
`
`(“[W]hen an applicant demonstrates substantially improved results . . . and states
`
`that the results were unexpected, this should suffice to establish unexpected results
`
`in the absence of evidence to the contrary.”) (emphasis in original); see also
`
`Procter & Gamble Co., 566 F.3d at 994 (“If a patent challenger makes a prima
`
`facie showing of obviousness, the owner may rebut based on ‘unexpected results’
`
`by demonstrating ‘that the claimed invention exhibits some superior property or
`
`advantage that a person of ordinary skill in the relevant art would have found
`
`surprising or unexpected.’”).
`
`- 14 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`VI. PETITIONERS’ ALLEGED UNPATENTABILITY GROUNDS ARE
`FATALLY FLAWED
`Petitioners advance three grounds in their attempt to render claims of the
`
`’061 patent unpatentable. In Ground 1, Petitioners argue that claims 1-3, 6-9, 12-
`
`13, 17-19, and 22-23 are inherently anticipated by Goldenheim under
`
`35 U.S.C. § 102. In Ground 2, Petitioners argue that claims 1-3, 6-9, 12-13, and
`
`17-23 are obvious under 35 U.S.C. § 103 over Goldenheim again, in view of
`
`Ramstack, the U.S. Pharmacopeia, and the European Pharmacopoeia. In Ground 3,
`
`Petitioners argue that claims 1-13 and 17-23 are obvious over Goldenheim again,
`
`in view of Kino, the U.S. Pharmacopeia, and the European Pharmacopeias.
`
`(Petition at 4.) As detailed below, Petitioners have failed to show there is a
`
`reasonable likelihood they will prevail in rendering unpatentable even one claim of
`
`the ’061 patent based on any of their asserted grounds.
`
`A.
`
`IPR Should Not Be Instituted Based on Ground 1
`
`IPR based on Ground 1 should not be instituted for, at least, the following
`
`reasons:
`
` Goldenheim does not disclose the claimed viscosity limitation.
`
` Petitioners improperly, and without explanation, picked and chose
`
`from unrelated disclosures in Goldenheim in a failed attempt to
`
`demonstrate the limitations in the claims of the ’061 patent.
`
`- 15 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`1.
`
`Goldenheim Does Not Disclose the Claimed Viscosity
`Limitation
`
`Claim 1, the only independent claim of the ’061 patent, specifically requires
`
`that the “fluid phase of said suspension has a viscosity greater than about 20 cp and
`
`less than about 600 cp at 20º C . . .” (Exh. 1001 at claim 1.) However, as
`
`Petitioners acknowledge, “Goldenheim does not expressly describe how viscosity
`
`is measured or at what temperature . . .” (Petition at 45; see also, id. at 35-6.)
`
`Additionally, Petitioners have not shown that a POSA would have understood
`
`Goldenheim’s alleged viscosity disclosure to apply to the fluid phase of a
`
`suspension as claimed in the ’061 patent.
`
`a.
`
`Goldenheim’s Alleged Viscosity Disclosure Does Not
`Specify Temperature
`
`As Petitioners’ own reference, the U.S. Pharmacopeia, provides when
`
`measuring viscosity, “[t]he specifying of temperature is important because
`
`viscosity changes with temperature” and even “small temperature changes may
`
`lead to marked changes in viscosity.” (Exh. 1006 at 1840; see also, Exh. 1014 at
`
`301 (“The viscosity of CMC systems is dependent upon temperature . . .”).)
`
`Indeed, the claims of the ’061 patent require a particular viscosity at 20°C.
`
`Petitioners rely on a viscosity measurement in Goldenheim that “may be, e.g.,
`
`about 35 cp.” But Goldenheim fails to specify the temperature corresponding to
`
`the “about 35 cp” viscosity measurement. Petitioners acknowledge this deficiency.
`
`- 16 -
`
`
`
`Case IPR2016-1095
`U.S. Patent 6,667,061
`
`(Petition at 35-36, 45.) Nevertheless, in Ground 1, advancing an inherent
`
`anticipation theory, Petitioners argue that “a POSA would understand that viscosity
`
`is typically measured at 20 or 25ºC” and point to the CMC monographs from the
`
`U.S. and European Pharmacopeias to confirm that alleged knowledge.3 (Petition at
`
`23 (emphasis added); see also Exh. 1002 at ¶ 56.) Similarly, in describing the
`
`CMC monographs, Petitioners’ expert, Dr. Patrick DeLuca, states that the “US
`
`Pharmacopoeia teaches that viscosity is typically measured at about 25ºC” and that
`
`the “European Pharmacopoeia teaches that viscosity is typically measured at about
`
`20ºC” (Exh. 1002 at ¶ 56 (emphasis added).)
`
`“Typically measured” is not good enough under controlling law. To succeed
`
`based on inherent anticipation, it is not enough to establish that the “about 35 cp”
`
`viscosity in