`
`
`Filed on behalf of: Amgen Inc.
`
`
`
`
`
` Paper No. ___
`Date: February 2, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`COMPLEX INNOVATIONS LLC,
`Petitioner
`
`v.
`
`AMGEN INC.,
`Patent Owner
`_____________
`
`Case IPR2016-00085
`U.S. Patent No. 7,829,595 B2
`_____________
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`UNDER 37 C.F.R. §42.107
`
`
`
`
`
`
`
`
`
`
`
`
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`

`

`
`
`
`
`I.
`
`II.
`
`TABLE OF CONTENTS
`
`Introduction ...................................................................................................... 1
`
`Background ...................................................................................................... 4
`
`A.
`
`The ’595 Patent ..................................................................................... 4
`
`III. Level of Ordinary Skill in the Art ................................................................... 8
`
`IV. Claim Construction .......................................................................................... 9
`
`V.
`
`Law .................................................................................................................. 9
`
`A.
`
`B.
`
`C.
`
`Evidence ................................................................................................ 9
`
`Burden of Proof ................................................................................... 10
`
`Obviousness ......................................................................................... 10
`
`VI. References Relied Upon ................................................................................ 12
`
`A. Van Wagenen ...................................................................................... 12
`
`B.
`
`C.
`
`HPE (3rd Ed.) ....................................................................................... 14
`
`General Knowledge of POSITA ......................................................... 16
`
`VII. Ground 1 – Van Wagenen, HPE, and General Knowledge of
`POSITA ......................................................................................................... 19
`
`A.
`
`B.
`
`“General Knowledge of POSITA” is not a Patent or
`Printed Publication and May Not Establish the Presence
`of Claim Elements ............................................................................... 20
`
`Petitioner Fails to Demonstrate a Reason to Combine or a
`Reasonable Expectation of Success .................................................... 21
`
`1.
`
`Petitioner Has Not Offered Any Reason to Select
`Cinacalcet Over Other Calcimimetic Compounds ................... 23
`
`- i -
`
`

`

`
`
`2.
`
`3.
`
`4.
`
`Petitioner Has Not Offered Any Reason to Select
`the Six Claimed Excipients over Many Other
`Options ...................................................................................... 24
`
`Petitioner Has Failed to Establish Any Reason
`Why a POSITA Would Have Selected the Specific
`Claimed Weight Ranges ........................................................... 28
`
`a.
`
`b.
`
`Active Ingredient Weight Range .................................... 28
`
`Excipient Weight Ranges ............................................... 30
`
`Petitioner Has Failed to Establish a Reasonable
`Expectation of Success In Formulating a
`Pharmaceutical Composition .................................................... 31
`
`C.
`
`Petitioner Applies the Wrong Burden of Proof ................................... 33
`
`VIII. Real Party In Interest ..................................................................................... 34
`
`IX. Conclusion ..................................................................................................... 36
`
`- ii -
`
`

`

`
`
`
`Case
`
`TABLE OF AUTHORITIES
`
`2Wire, Inc. v. TQ Delta LLC,
`IPR2015-00239, Paper 18 (P.T.A.B. May 29, 2015) ....................................25
`
`ActiveVideo Networks, Inc. v. Verizon Communications, Inc.,
`694 F.3d 1312 (Fed. Cir. 2012) .....................................................................27
`
`Amgen, Inc. v. Abbvie Biotechnology Ltd., IPR2015-01514,
`Paper No. 9 (P.T.A.B. Jan. 14, 2015) ...........................................................32
`
`Bumble Bee Foods, LLC v. William R. Kowalski,
`IPR2014-00224, Paper No. 18 (P.T.A.B. June 5, 2014) .................. 11, 22, 30
`
`Coalition for Affordable Drugs VII LLC v. Pozen Inc.,
`IPR2015-01241, Paper No. 22 (P.T.A.B. Dec. 8, 2015) ...............................36
`
`Coalition for Affordable Drugs VII LLC v. Pozen Inc.,
`IPR2015-01344, Paper No. 22 (P.T.A.B. Dec. 17, 2015) .............................10
`
`Cuozzo Speed Techs., LLC v. Lee,
`No. 15-446 (Jan. 15, 2016) .............................................................................. 9
`
`Eizo Corp. v. Barco N.V.,
`IPR2014-00358, Paper No. 11 (P.T.A.B. July 23, 2014) ..............................21
`
`Eli Lilly and Co. v. Zenith Goldline Pharms., Inc.,
`471 F.3d 1369 (Fed. Cir. 2006) .....................................................................11
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013), cert denied, 134 S. Ct.
`2740 (2014) ............................................................................................. 33, 34
`
`Grain Processing Corp. v. Am. Maize-Prods. Co.,
`840 F.2d 902 (Fed. Cir. 1988) .......................................................................28
`
`Heart Failure Techs., LLC v. Cardiokinetix, Inc.,
`IPR2013-00183, Paper No. 12 (P.T.A.B. July 31, 2013) ..............................22
`
`In re Kahn, 441 F.3d 977 (Fed. Cir. 2006) .............................................................10
`
`- iii -
`
`

`

`
`
`In re Sang Su Lee,
`277 F.3d 1338 (Fed. Cir. 2002) ...................................................... 1, 9, 20, 21
`
`Insite Vision Inc. v. Sandoz, Inc.,
`783 F.3d 853 (Fed. Cir. 2015) .......................................................................11
`
`Kinetic Techs., Inc. v. Skyworks Solutions, Inc.,
`IPR2014-00529, Paper 8 (P.T.A.B. Sept. 23, 2014) .....................................29
`
`KSR Int’l. Co. v. Teleflex Inc.,
`550 U.S. 398 (2007)............................................................................... passim
`
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) .....................................................................11
`
`Par Pharm., Inc. v. TWI Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) .....................................................................11
`
`Perfect Web Techs., Inc. v. InfoUSA, Inc.,
`587 F.3d 1324 (Fed. Cir. 2009) .......................................................... 9, 20, 21
`
`RPX Corp. v. Virnetx, Inc., Case
`IPR2014-00171, Paper 52 (P.T.A.B. June 5, 2014) ......................................34
`
`TRW Auto. U.S. LLC v. Magna Elecs. Inc.,
`No. IPR2014-00293, Paper No. 19 (P.T.A.B. July 1,
`2014) .................................................................................................. 12, 30, 31
`
`TRW Auto. U.S. LLC v. Magna Elecs. Inc.,
`No. IPR2014-1351, Paper No. 7 (P.T.A.B. Feb. 10, 2015) ..................... 34, 36
`
`Unigene Labs., Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) ........................................................ 11, 23, 25
`
`Statues
`
`35 U.S.C. § 311(b) .......................................................................................... 1, 9, 20
`
`35 U.S.C. § 312(a)(2) ........................................................................................ 34, 36
`
`35 U.S.C. § 314(a) ...................................................................................................10
`
`35 U.S.C. § 316(e) ...............................................................................................3, 33
`
`- iv -
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`

`

`
`
`37 C.F.R. § 42.104(b)(2) ............................................................................................ 9
`
`37 C.F.R. § 42.104(b)(4) ..........................................................................................10
`
`37 C.F.R. § 42.108(c) ...............................................................................................10
`
`Cal. Corporations Code § 17702.09 .........................................................................35
`
`Other
`
`Office Patent Trial Practice Guide,
`77 Fed. Reg. 48,756 (Aug. 14, 2012) ............................................................34
`
`
`
`
`- v -
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`

`
`
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`EXHIBITS
`
`Product Label for Sensipar® (cinacalcet) tablets, for oral use,
`revised: 11/2014
`(“Ex. 2001” or “Sensipar® Label”)
`Orange Book: Approved Drug Products with Therapeutic
`Equivalent Evaluations, FDA, available at
`http://www.accessdata.fda.gov/scripts/cder/ob/ (“search by
`active ingredient” for “cinacalcet”)
`(“Ex. 2002”)
`Excerpts from Herbert A. Lieberman, Leon Lachman, Joseph
`B. Schwartz, Pharmaceutical Dosage Forms Tablets Vol. 1
`(2nd ed. 1989)
`(“Ex. 2003” or “Lieberman I”)
`Excerpts from James Swarbrick & James C. Boylan,
`Encyclopedia of Pharmaceutical Technology Vol. 2 (2nd ed.
`2002)
`(“Ex. 2004” or “Swarbrick II”)
`Excerpts from Arthur H. Kibbe, Handbook of
`Pharmaceutical Excipients (3rd ed. 2000)
`(“Ex. 2005” or “HPE”)
`Excerpts from James Swarbrick & James C. Boylan,
`Encyclopedia of Pharmaceutical Technology Vol. 1 (2nd ed.
`2002)
`(“Ex. 2006” or “Swarbrick I”)
`File History for U.S. Patent No. 7,829,595 (“’595 patent”),
`Office Action (dated April 30, 2009)
`(“Ex. 2007” or “Office Action”)
`File History for ’595 patent, Notice of Allowance (dated
`June 14, 2010)
` (“Ex. 2008” or “Notice of Allowance”)
`ISBN Search, available at http://www.isbnsearch.org/
`(search for “1582120226”) (visited Jan. 27, 2016)
`(“Ex. 2009”)
`Excerpts from Arthur H. Kibbe, Handbook of
`Pharmaceutical Excipients (4th ed. 2003)
` (“Ex. 2010 or “HPE 4th ed.”)
`2003 USP NF The Official Compendium of Standards, U.S.
`Pharmacopeia (2002)
`
`- iv -
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`

`

`
`
`2012
`
`2013
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`2019
`
`2020
`
`(“Ex. 2011” or “USP-NF”)
`California Secretary of State – Business Search, available at
`http://kepler.sos.ca.gov/ (search for “Complex Innovations
`LLC”) (visited on Jan. 27, 2016)
`(“Ex. 2012”)
`Dun & Bradstreet Inc. Comprehensive Report on “Complex
`Innovations LLC” (received Nov. 5, 2015)
`(“Ex. 2013”)
`WhitePages, available at www.whitepages.com (search for
`“1032 Riverside Dr., Los Altos, CA 94024”) (visited on Jan.
`27, 2016)
`(“Ex. 2014”)
`Corporations Service Company, Request from CA Secretary
`of State for Annual Reports on “Complex Innovations LLC”
`(received on Nov. 6, 2015)
`(“Ex. 2015”)
`Email String between Justin Oliver and Vivek Ganti from
`Dec. 10, 2015 to Dec. 26, 2015
`(“Ex. 2016”)
`Marcello Filpanti et al., Pharmacology of the Calcium
`Sensing Receptor, Clinical Cases in Mineral and Bone
`Metabolism, 10(3):162-165 (2013)
`(“Ex. 2017”)
`Excerpts from Physicians’ Desktop Reference, 57th edition
`(2003)
`(“Ex. 2018”)
`File History for ’595 patent, Patent Owner’s Submission
`Under 37 CFR 1.115 (dated April 15, 2010)
`(“Ex. 2019” or “Response to Office Action”)
`Excerpts from Stephen Kokoska and Daniel Zwillinger, CRC
`Standard Probability and Statistics Tables and Formulae,
`Student Edition (2000)
`(“Ex. 2020”)
`
`
`
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`- v -
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`

`
`
`I.
`
`Introduction
`
`For an Inter Partes Review (“IPR”) trial to be instituted, the proposed ground
`
`must be based on patents and/or printed publications and, in the context of
`
`obviousness, the Petitioner must establish a reason to modify or combine the prior
`
`art in the proposed manner. The present Petition fails on both accounts.
`
`First, Petitioner’s sole proposed ground improperly relies on the “General
`
`Knowledge” of a person of ordinary skill in the art (“POSITA”) in combination
`
`with published documents. While the general knowledge of a POSITA may be
`
`applied to understand the prior art, it may not be used as a substitute for the prior
`
`art. In re Sang Su Lee, 277 F.3d 1338, 1345 (Fed. Cir. 2002). Petitioner, however,
`
`relies on the alleged “General Knowledge” not to explain how a POSITA would
`
`have understood the cited publications, but as alleged evidence of claim elements
`
`admittedly not disclosed or suggested by the publications. Thus, the lone ground
`
`of the Petition is not based solely on patents and printed publications, as required
`
`by statute. 35 U.S.C. § 311(b). For this reason alone, the Petition should be
`
`denied.
`
`Second, the Petition does nothing more than establish that the building
`
`blocks of the claimed pharmaceutical composition existed in the prior art.
`
`Specifically, U.S. Patent No. 7,829,595 (“’595 patent”) claims a pharmaceutical
`
`composition comprising a specific active ingredient (cinacalcet) in combination
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`- 1 -
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`with six different excipients, as well as the various weight ranges for each.
`
`Petitioner fails to establish any reason why a POSITA would have (i) chosen
`
`cinacalcet from among the compounds disclosed in U.S. Patent No. 6,211,244
`
`(“Van Wagenen”), (ii) then selected the specific claimed combination of six
`
`excipients, and (iii) determined the particular weight ranges for all the claimed
`
`pharmaceutical composition components from among a myriad of other
`
`possibilities.
`
`It is well established that obviousness requires more than a mere showing of
`
`the existence of the individual claim elements in the prior art. KSR Int’l. Co. v.
`
`Teleflex Inc., 550 U.S. 398, 418 (2007). Rather than address this issue, Petitioner
`
`merely offers that “cinacalcet hydrochloride was known in the art,” and then cites
`
`to select excerpts of the 3rd Edition of the Handbook of Pharmaceutical Excipients
`
`(“HPE”) to argue that a POSITA would have appreciated that the excipients “may
`
`be used with cinacalcet.” (Petition at 14; Ex. 1021 at ¶ 95). But Petitioner fails to
`
`mention that Van Wagenen discloses other calcimimetic compounds and provides
`
`no incentive to select cinacalcet as a lead compound over those other compounds.
`
`Further, Petitioner fails to mention that the HPE lists hundreds of other excipient
`
`options and is not even the only source of potential excipients. In fact, the
`
`truncated copy of the HPE provided by Petitioner shows only the pages
`
`corresponding to the six excipients claimed.
`
`- 2 -
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`
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`Thus, not only does the Petitioner fail to inform the Board about the
`
`existence of the hundreds of other possible excipients, but it also fails to offer any
`
`theory as to why a POSITA would have chosen cinacalcet from Van Wagenen and
`
`then selected the specific excipient combination claimed in the specific weight
`
`ranges recited. Absent any alleged reason to pick cinacalcet as the lead compound
`
`and to select the claimed combination of six excipients, and to determine the
`
`ranges claimed, to the exclusion of a myriad of other possible combinations, the
`
`Petition fails as a matter of law.
`
`Further exacerbating this problem, Petitioner applies the wrong burden of
`
`proof by alleging that Patent Owner has the burden to show the claims are non-
`
`obvious. Specifically, Petitioner argues that “Applicants cannot meet their burden
`
`to show that the claimed sub-ranges and sub-ratios disclosed in the 595 Patent are
`
`non-obvious.” (Petition at 13; see also id. at 9). Of course, in an IPR, the burden
`
`of proof rests with the Petitioner. 35 U.S.C. § 316(e).
`
`For at least these reasons, Petitioner has not demonstrated a reasonable
`
`likelihood of showing that any challenged claim is unpatentable. Accordingly,
`
`Patent Owner requests that the Board deny institution of the IPR against the ’595
`
`patent.
`
`
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`- 3 -
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`
`
`II. Background
`
`A. The ’595 Patent
`
`
`
`The ’595 patent is directed to a pharmaceutical composition for the active
`
`ingredient cinacalcet. Cinacalcet has now been demonstrated to be a calcimimetic
`
`agent, meaning it mimics the action of calcium on tissues. (Sensipar® Label, Ex.
`
`2001 at 9). Cinacalcet acts by binding to calcium-sensing receptors on parathyroid
`
`glands. (Id. at 10). This binding increases the sensitivity of calcium-sensing
`
`receptors to extracellular calcium ions, and as a result, fewer calcium ions are
`
`required to activate the calcium-sensing receptors. (Id.) Once activated, the
`
`calcium-sensing receptors diminish parathyroid hormone (PTH) secretion. (Id.)
`
`Through this mechanism, cinacalcet helps to manage excess PTH secretion in
`
`clinical disorders such as hyperparathyroidism. (Id. at 2, 12-16).
`
`
`
`Cinacalcet is the only calcimimetic approved for secondary
`
`hyperparathyroidism in people with chronic kidney disease on dialysis and
`
`hypercalcemia in people with parathyroid carcinoma. (Ex. 2017 at 162, col. 1,
`
`lines 11-14; Sensipar® Label, Ex. 2001 at 2). Amgen received FDA approval for
`
`cinacalcet on March 8, 2004 and markets it in North America under the trade name
`
`Sensipar®. (Ex. 2002). Amgen also markets cinacalcet in Australia under the
`
`trade name Sensipar® and in Europe under the trade name Mimpara®. While
`
`cinacalcet is now widely distributed in its tablet form, at the time of the ’595 patent
`
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`- 4 -
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`invention it had not yet been approved, and there were significant difficulties
`
`associated with creating a stable tablet formulation.
`
`
`
`In particular, cinacalcet is soluble in acidic solutions but only minimally
`
`soluble in water, particularly in its non-ionized state. (’595 patent, Ex. 1001 at
`
`1:10-15). Its low solubility affects its dissolution rate and bioavailability,
`
`increasing the challenge to finding suitable formulations and delivery options. (Id.
`
`at 1:15-20). No prior art disclosed a formulation that could maximize the
`
`dissolution profile and improve bioavailability of cinacalcet to achieve a
`
`therapeutically effective dosage formulation. (Id. at 1:21-25). In fact, similar
`
`types of medications were delivered to a patient intravenously or through a
`
`hemodialysis port, rather than through formulations delivered orally. (See e.g. Ex.
`
`2018 at Abbott/515-516, Bone Care/1061-1062 (Zemplar® and Hectorol®
`
`injections were indicated for the treatment of hyperparathyroidism)).
`
`
`
`Given the formulation challenges with cinacalcet, particularly the solubility
`
`problem, developing an effective formulation required consideration of a large
`
`array of variables, which interact in complex ways. (See Ex. 1014 at 76-77). At
`
`the most basic level, assuming that the skilled artisan would have selected
`
`cinacalcet as a starting point and assuming preformulation studies sufficiently
`
`characterized the physical, chemical, and biological characteristics of cinacalcet, a
`
`formulator would have also needed to consider the characteristics and
`
`- 5 -
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`

`
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`compatibilities of any excipients that were to be possibly added. (Swarbrick II, Ex.
`
`2004 at 1138-39).
`
`
`
`The HPE listed hundreds of known excipients available for use and was
`
`intended to “help the formulator develop a list of possible materials for use in a
`
`new dosage form or product.” (HPE, Ex. 2005 at Preface xv, col. 2, lines 1-3).
`
`The HPE 3rd edition cited by Petitioner listed 210 excipients and provided general
`
`characteristics for each. (Id. at Contents v-vi).
`
`
`
`However, the HPE was at best only a list of starting materials for addressing
`
`a problem and offered no particular guidance on the compatibility of excipients
`
`with any particular active ingredient. Nor did it provide guidance on the
`
`compatibility between excipients themselves. The HPE merely listed available
`
`excipients. To arrive at any formulation using some subset of those excipients, a
`
`formulator was required to “carefully and critically evaluate the combinations of
`
`the drug with each of the contemplated excipients and must [have] ascertain[ed]
`
`compliances of each ingredient with existing standards and regulations.”
`
`(Lieberman I, Ex. 2003 at 152).
`
`
`
`A formulator was also required to develop a suitable formulation in view of
`
`the nature of the specific active ingredient and taking into account “general and
`
`specific toxic effects of the excipients, allergic reactions to excipients, disease-
`
`specific intolerance to excipients and interactions between the excipient and the
`
`- 6 -
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`

`

`
`
`active ingredient.” (HPE, Ex. 2005 at Preface xv, col.1, lines 11-17). For an oral
`
`delivery formulation, as claimed in the ’595 patent, there were also additional
`
`concerns that needed to be considered such as bioavailability, solubility, and
`
`intestinal permeability of the formulation. (Swarbrick I, Ex. 2006 at 888-892).
`
`
`
`Petitioner emphasizes that active ingredients could have been mixed with
`
`excipients and tested under “accelerated conditions.” (Petition at 12; Chambliss
`
`Dec. at ¶ 26). But the results of accelerated testing could have been “misleading
`
`and thus of very limited value.” (Swarbrick II, Ex. 2004 at 1139). Thus,
`
`determining a suitable formulation for an active ingredient in combination with
`
`several excipients would have been a complex and significant undertaking.
`
`The ’595 patent addressed the need for a calcimimetic formulation by
`
`disclosing and claiming a pharmaceutical composition comprising cinacalcet in
`
`combination with six select excipients: microcrystalline cellulose, povidone,
`
`starch, crospovidone, colloidal silicon dioxide, and magnesium stearate. Claim 1
`
`recites cinacalcet with the specific excipients, and the weight range of each, to
`
`provide a pharmaceutical composition that successfully overcomes problems with
`
`dissolution and bioavailability. Specifically, claim 1 reads as follows
`
`1. A pharmaceutical composition comprising
`
`(a) from about 10% to about 40% by weight of cinacalcet HCl;
`
`
`
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`
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`(b) from about 40% to about 75% by weight of microcrystalline
`
`cellulose;
`
`(c) from about 1% to about 5% by weight of povidone;
`
`(d) from about 5% to about 35% by weight of starch;
`
`(e) from about 1% to about 10% by weight of crospovidone;
`
`(f) from about 0.05% to about 1.5% by weight of colloidal silicon
`
`dioxide; and
`
`(g) from about 0.05% to about 1.5% by weight of magnesium stearate;
`
`wherein the percentage by weight is relative to the total weight of
`
`the composition.
`
`
`Claim 1 is the only independent claim of the ’595 patent and, thus, this
`
`Response focuses on Petitioner’s arguments regarding claim 1.
`
`III. Level of Ordinary Skill in the Art
`
`
`
`Patent Owner does not necessarily agree with Petitioner’s assertion that a
`
`POSITA would have been “a person holding a Bachelor of Science degree (or an
`
`equivalent) in chemistry, pharmacy or a related field with at least two years of
`
`relevant experience in pharmaceutical drug development, including formulation
`
`work.” (Petition at 6-7). Nonetheless, the analysis and outcome for an institution
`
`decision should not be affected by Petitioner’s definition of a POSITA. Given the
`
`deficiencies in the Petition, institution should be denied under any reasonable
`
`definition of a POSITA.
`
`
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`

`

`
`
`IV. Claim Construction
`
`Patent Owner notes that recently, the Supreme Court, in Cuozzo Speed
`
`Techs., LLC v. Lee, No. 15-446 (Jan. 15, 2016), granted certiorari regarding
`
`whether all of the terms in challenged claims should be construed according to
`
`their broadest reasonable interpretation or their plain and ordinary meaning.
`
`Petitioner has not proposed a claim construction that would be affected by this
`
`ruling. For the reasons that follow, under any reasonable claim construction,
`
`Petitioner fails to establish a reasonable likelihood of success in challenging the
`
`validity of the claims of the ’595 patent.
`
`V. Law
`
`A. Evidence
`
`In an IPR, a petitioner may base a ground for unpatentability “only on the
`
`basis of prior art consisting of patents or printed publications.” 35 U.S.C. §
`
`311(b); 37 C.F.R. § 42.104(b)(2).
`
`In an obviousness analysis, the general knowledge of a POSITA may inform
`
`on the significance of prior art or may provide a reason to combine elements in
`
`prior art; however, it is not a substitute for elements missing from the prior art. In
`
`re Sang Su Lee, 277 F.3d at 1345 (holding that common knowledge and common
`
`sense of a POSITA may be applied to an analysis of evidence in the prior art, but
`
`may not substitute for evidence); Perfect Web Techs., Inc. v. InfoUSA, Inc., 587
`
`
`
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`- 9 -
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`

`

`
`
`F.3d 1324, 1328-29 (Fed. Cir. 2009) (“common knowledge and common sense do
`
`not substitute for facts”).
`
`B.
`
`Burden of Proof
`
`Petitioner bears the burden of establishing a reasonable likelihood of
`
`unpatentability. 35 U.S.C. § 314(a); 37 C.F.R. § 42.108(c); Coalition for
`
`Affordable Drugs VII LLC v. Pozen Inc., IPR2015-01344, Paper No. 22 at 24
`
`(P.T.A.B. Dec. 17, 2015) (“In an inter partes review, the burden is on the
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`petitioner to show a reasonable likelihood that it would prevail on a ground of
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`unpatentability.”). To meet this burden, Petitioner must specify where each
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`element of the claim is found in the prior art relied upon. 37 C.F.R. §
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`42.104(b)(4). Further, “rejections on obviousness cannot be sustained by mere
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`conclusory statements; instead, there must be some articulated reasoning with
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`some rational underpinning to support the legal conclusion of obviousness.” In re
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`Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006); KSR, 550 U.S. at 418.
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`C. Obviousness
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`A patent composed of several elements is not proved obvious “merely by
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`demonstrating that each of its elements was, independently, known in the prior
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`art.” KSR, 550 U.S. at 418. In other words, merely pointing to the presence of all
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`claim elements in the prior art does not support a finding of obviousness. “This is
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`so because inventions in most, if not all, instances rely upon building blocks long
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`since uncovered, and claimed discoveries almost of necessity will be combinations
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`of what, in some sense, is already known.” KSR, 550 U.S. at 418-419.
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`For this reason, “to establish a prima facie case of obviousness based on a
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`combination of elements in the prior art, the law requires a motivation to select the
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`references and to combine them in the particular claimed manner to reach the
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`claimed invention.” Eli Lilly and Co. v. Zenith Goldline Pharms., Inc., 471 F.3d
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`1369, 1379 (Fed. Cir. 2006); see also Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d
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`1352, 1360 (Fed. Cir. 2011). As part of this inquiry, consideration is given to
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`“whether the prior art would also have revealed that in so making or carrying out
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`[the combination], those of ordinary skill would have a reasonable expectation of
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`success.” Par Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1196 (Fed. Cir.
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`2014) (quoting Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1164 (Fed. Cir.
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`2006); see also Insite Vision Inc. v. Sandoz, Inc., 783 F.3d 853, 859 (Fed. Cir.
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`2015).
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`Thus, Petitioner bears the burden to set forth sufficiently articulated
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`reasoning, beyond mere conclusory statements, as to why a POSITA would have
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`been motivated to combine the elements of prior art to derive the claimed invention
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`and would have had a reasonable expectation of success in doing so. See Bumble
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`Bee Foods, LLC v. William R. Kowalski, IPR2014-00224, Paper No. 18 at 25-26
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`(P.T.A.B. June 5, 2014); TRW Auto. US LLC v. Magna Elecs. Inc., No. IPR2014-
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`00293, Paper No. 19 at 16-18 (P.T.A.B. July 1, 2014); KSR, 550 U.S. at 418.
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`VI. References Relied Upon
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`A. Van Wagenen
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`Petitioner relies on Van Wagenen to suggest that pharmaceutical
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`compositions containing cinacalcet were known in the prior art. (Petition at 3, 14).
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`Van Wagenen is cited on the face of the ’595 patent and was considered by the
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`Examiner during prosecution. (’595 patent, Ex. 1001 at (56) References Cited;
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`Office Action, Ex. 2007 at 3-7).
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`Van Wagenen discloses other calcium receptor-active compounds. (See e.g.,
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`Van Wagenen, Ex. 1003 at 14:1-19). Interestingly, Petitioner never identifies
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`where Van Wagenen describes cinacalcet, instead citing to the challenged ’595
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`patent for that proposition. (Petition at 14:10-11). In fact, in its discussion of the
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`application of the sole proposed ground against claim 1, Petitioner provides no
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`citation at all to Van Wagenen. (See Petition at 14-17).
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`Indeed, as Patent Owner successfully argued during prosecution, the prior
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`art, including Van Wagenen, “fails to specifically disclose or render obvious the
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`combination of components and in the amounts thereof set forth in [issued claim
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`1].” (Notice of Allowance, Ex. 2008 at 2; Response to Office Action, Ex. 2019 at
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`6-7).
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`Elsewhere in the Petition, Petitioner quotes a sentence in Van Wagenen that
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`reads:
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`Suitable dosage ranges, formulations, and dosage forms
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`for other compounds described herein can also be
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`determined by one skilled in the art based on the teachings
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`provided in the application.
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`(Petition at 3; Van Wagenen, Ex. 1003 at 44:41-45). Petitioner seems to suggest
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`that this sentence is sufficient evidence to show that Van Wagenen teaches, or at
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`least motivates a POSITA to pursue, any and all suitable formulations of
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`calcimimetic agents (as that cited section of Van Wagenen does not actually
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`specifically discuss cinacalcet). (See Petition at 3, 13; Chambliss Decl., Ex. 1021
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`at ¶ 19).
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`Van Wagenen does not discuss or address the difficulties with developing a
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`cinacalcet formulation with improved dissolution and bioavailability, as compared
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`to other calcimimetic agents. Indeed, Petitioner fails to demonstrate that Van
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`Wagenen identifies cinacalcet as the lead compound over other calcimimetic
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`agents disclosed.1
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`1 Cinacalcet is a generic name (USAN), for a specific calcimimetic compound,
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`which Amgen submitted to the U.S. Adopted Names Council (“USANC”) for
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`B. HPE (3rd Ed.)
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`The HPE is a resource for information on known pharmaceutical excipients.
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`This edition discloses 210 excipients for use in formulations. (HPE, Ex. 2005 at
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`Preface xv, col. 1, lines 27-30). While Petitioner cites to the 3rd edition of the
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`HPE, the 4th edition of the HPE published in May 2003, and was available to a
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`POSITA. (Ex. 2009). In the 4th edition, there are even more disclosed excipients –
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`250 total. (HPE 4th ed., Ex. 2010 at Preface xvii, col. 1, lines 27-30; see also id. at
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`Contents v-viii).
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`Petitioner relies heavily on the HPE, arguing that the “HPE explains what
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`each [claimed] excipient is and why a POSITA should be encouraged to use it.”
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`(Petition at 16). However, Exhibit 1012, as prepared by Petitioner, provides only a
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`few select pages of the 3rd edition of HPE. Those select pages are limited to the
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`entries for the six excipients claimed. Exhibit 1012 does not show the table of
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`contents, which establishes that the HPE is actually over 600 pages long. (HPE,
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`Ex. 2005 at Contents v-vi). Exhibit 1012 does not contain the table of contents,
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`which also shows that 210 different excipients are disclosed. Exhibit 1012 does
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`not include the preface of the HPE, which indicates that the book is intended to
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`approval. The name cinacalcet for the particular compound was adopted by
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`USANC in 2002.
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`“help the formulator develop a list of possible materials for use in a new dosage
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`form or product.” (HPE, Ex. 2005 at Preface xv, col. 2, lines 1-3 (emphasis
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`added)).
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`
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`The preface of the HPE also indicates that a formulator develops a suitable
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`formulation in view of the nature of the specific active ingredient and taking into
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`account “general and specific toxic effects of the excipients, allergic reactions to
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`excipients, disease-specific intolerance to excipients and interactions between the
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`excipient and the active ingredient.” (Id. at Preface xv, col.1, lines 11-17). Exhibit
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`1012 and the Petition are devoid of any indication concerning how a POSITA
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`would have viewed the 204 other disclosed excipients.
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`Petitioner also offers no explanation as to how the HPE could have led a
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`POSITA to use six excipients, as opposed to some other number, in a cinacalcet
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`formulation. Even assuming, for the sake argument, that six excipients should
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`have been used (not less), the possible number of six-excipient com