`Filed: January 3, 2019
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`GRÜNENTHAL GMBH,
`
`Petitioner,
`
`v.
`
`ANTECIP BIOVENTURES II LLC,
`
`Patent Owner.
`____________
`
`U.S. Patent No. 10,052,338
`____________
`
`PETITION FOR POST GRANT REVIEW
`
`
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`

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`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ........................................................................................... 1
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8 ................................... 4
`
`A.
`
`B.
`
`C.
`
`D.
`
`Real Parties-in-Interest (§ 42.8(b)(1)) ................................................... 4
`
`Related Matters (§ 42.8(b)(2)) .............................................................. 5
`
`Lead and Back-up Counsel (§ 42.8(b)(3)) ............................................ 7
`
`Service Information (§ 42.8(b)(4)) ........................................................ 7
`
`III.
`
`PAYMENT OF FEES ..................................................................................... 7
`
`IV. TIME FOR FILING PETITION...................................................................... 7
`
`V. GROUNDS FOR STANDING ........................................................................ 8
`
`VI. CHALLENGED CLAIMS AND RELIEF SOUGHT ..................................... 8
`
`VII. THE ’338 PATENT PROSECUTION HISTORY .......................................... 9
`
`VIII. THE PERTINENT ART AND THE PERSON OF ORDINARY
`SKILL IN THE ART ..................................................................................... 13
`
`IX. CLAIM CONSTRUCTION .......................................................................... 14
`
`A.
`
`B.
`
`The Preambles of Claims 1-30 Should Be Construed as
`Non-Limiting ....................................................................................... 16
`
`Alternatively, the Preambles Should Be Construed in
`Accordance with the Broad Definition of “Treating” in
`the Specification .................................................................................. 18
`
`X.
`
`THE ’338 PATENT IS ELIGIBLE FOR PGR.............................................. 19
`
`A.
`
`B.
`
`Claims 10-12, 26-28 ............................................................................ 21
`
`Claims 13, 29 ....................................................................................... 22
`
`i
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`

`

`
`
`XI. HOW THE CHALLENGED CLAIMS ARE
`UNPATENTABLE ........................................................................................ 24
`
`A. Ground 1: Claims 1-16 Are Obvious under 35 U.S.C. §
`103 based on Varenna 2011 and/or Gatti and/or
`Muratore, in combination with Harden ............................................... 24
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Claim 1 ...................................................................................... 24
`
`Claims 2 and 3 ........................................................................... 37
`
`Claim 4 ...................................................................................... 38
`
`Claim 5 ...................................................................................... 39
`
`Claims 6 and 7 ........................................................................... 42
`
`Claim 8 ...................................................................................... 42
`
`Claim 9 ...................................................................................... 44
`
`Claims 10-12 ............................................................................. 45
`
`Claim 13 .................................................................................... 47
`
`10. Claims 14-16 ............................................................................. 48
`
`11. No Objective Indicia of Nonobviousness Support
`Patentability of Claims 1-16 ..................................................... 49
`
`B.
`
`C.
`
`Ground 2: Claims 17-30 Are Unpatentable for
`Indefiniteness under 35 U.S.C. § 112 ................................................. 50
`
`Ground 3: Claims 17-30 Are Obvious under 35 U.S.C. §
`103 based on Varenna 2011 and/or Gatti and/or
`Muratore, in Combination with Harden and Drummond .................... 52
`
`1.
`
`2.
`
`3.
`
`4.
`
`Claim 17 .................................................................................... 52
`
`Claims 18 and 19....................................................................... 62
`
`Claim 20 .................................................................................... 63
`
`Claim 21 .................................................................................... 64
`
`ii
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`

`

`
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Claims 22 and 23....................................................................... 66
`
`Claim 24 .................................................................................... 67
`
`Claim 25 .................................................................................... 69
`
`Claims 26-28 ............................................................................. 70
`
`Claim 29 .................................................................................... 72
`
`10. Claim 30 .................................................................................... 73
`
`11. No Objective Indicia of Nonobviousness Support
`Patentability of Claims 17-30 ................................................... 74
`
`D. Ground 4: Alternatively, Claims 1-30 Are Unpatentable
`Under 35 U.S.C. § 112 for Lack of Written Description .................... 75
`
`1.
`
`2.
`
`Claims 1-16 ............................................................................... 76
`
`Claims 17-30 ............................................................................. 77
`
`XII. GROUNDS ARE NOT REDUNDANT ........................................................ 78
`
`XIII. CONCLUSION .............................................................................................. 79
`
`
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`
`iii
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`
`
`TABLE OF AUTHORITIES
`
`
`Cases
`Allen Eng'g Corp. v. Bartell Indus., Inc.,
`299 F.3d 1336 (Fed. Cir. 2002) .....................................................................16
`
`Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) ........................................................ 21, 75, 76
`
`Bosch Auto. Serv. Sols., LLC v. Matal,
`878 F.3d 1027 (Fed. Cir. 2017) .....................................................................33
`
`Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) .....................................................................17
`
`Catalina Mktg. Int’l, Inc. v. Coolsavings.com, Inc.,
`289 F.3d 801 (Fed. Cir. 2002) .......................................................... 16, 17, 18
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ................................................................ 40, 65
`
`In re Boesch,
`617 F.2d 272 (C.C.P.A. 1980) ................................................................ 40, 65
`
`In re Hoeschele,
`406 F.2d 1403 (C.C.P.A. 1969) .............................................................. 40, 65
`
`In re Packard,
`751 F.3d 1307 (Fed. Cir. 2014) .....................................................................50
`
`In re Wertheim,
`541 F.2d 257 (C.C.P.A. 1976) ................................................................ 47, 72
`
`In re Williams,
`17 C.C.P.A. 718 (C.C.P.A. 1929) ........................................................... 40, 65
`
`Inguran, LLC v. Premium Genetics (UK) Ltd.,
`PGR2015-00017, Paper 8 (P.T.A.B. Dec. 22, 2015) ....................................20
`
`Liberty Mutual Ins. Co. v. Progressive Casualty Ins. Co.,
`CBM2012-00003, Paper No. 11 (P.T.A.B. Nov. 26, 2012) ..........................78
`
`iv
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`

`

`
`
`Liberty Mutual Ins. Co. v. Progressive Casualty Ins. Co.,
`CBM2012-00003, Paper No. 8 (P.T.A.B. Oct. 25, 2012) .............................79
`
`Lockwood v. Am. Airlines,
`107 F.3d 1565 (Fed. Cir. 1997) .............................................................. 21, 76
`
`Merck & Co., Inc. v. Biocraft Labs., Inc.,
`874 F.2d 804 (Fed. Cir. 1989) ................................................................ 40, 65
`
`Nautilus, Inc. v. Biosig Instruments, Inc.,
`134 S. Ct. 2120 (2014) ...................................................................................50
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .....................................................................15
`
`Tinnus Enter., LLC v. Telebrands Corp.,
`No. 2017-1726, slip op. (Fed. Cir. May 30, 2018) ........................................50
`
`Warner Chilcott Co. v. Teva Pharms. USA, Inc.,
`594 F. App’x 630 (Fed. Cir. 2014) ......................................................... 41, 65
`
`Statutes
`
`35 U.S.C. § 103 ......................................................................................... 8, 9, 24, 52
`
`35 U.S.C. § 112 ................................................................................................ passim
`
`Regulations
`
`37 C.F.R. § 42.15 ....................................................................................................... 7
`
`37 C.F.R. § 42.200 ...................................................................................................15
`
`37 C.F.R. § 42.202 ..................................................................................................... 7
`
`37 C.F.R. § 42.203 ..................................................................................................... 7
`
`37 C.F.R. § 42.204 ..................................................................................................... 8
`
`37 C.F.R. § 42.8 ................................................................................................ 4, 5, 7
`
`v
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`
`
`EXHIBIT LIST
`
`
`Description
`
`U.S. Patent No. 9,931,352
`
`U.S. Patent No. 10,039,774
`
`U.S. Patent No. 10,052,338
`
`Abbreviation
`
`’352 patent
`
`’774 patent
`
`’338 patent
`
`Declaration of Lawrence Poree, M.D., Ph.D.
`
`Curriculum Vitae of Lawrence Poree, M.D., Ph.D.
`
`
`
`
`
`M. Varenna, L’inquadramento clinico della sindrome
`
`Varenna 2011
`
`Exhibit
`(Ex.)
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`algodistrofica (Complex Regional Pain Syndrome di
`
`tipo I). Recenti Acquisizioni, The clinical framework
`
`of algodystrophy (Complex Regional Pain Syndrome
`
`type I). An Update, GIOT Ottobre 2011 37:227-234
`
`1007
`
`M. Muratore et al., Il neridronato nel trattamento
`
`Muratore
`
`dell’algodistrofia simpatica riflessa dell’anca:
`
`confronto in aperto con il clodronato, PROGRESSI IN
`
`REUMATOLOGIA, ABSTRACT BOOK VII CONGRESSO
`
`NAZIONALE COLLEGIO DEI REUMATOLOGI
`
`OSPEDALIERI 5(Suppl. 1):89 (April 16-18, 2004)
`
`vi
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`

`

`
`
`
`
`
`1008
`
`D. Gatti et al., Neridronic acid for the treatment of
`
`Gatti
`
`bone metabolic diseases, EXPERT OP. ON DRUG
`
`METABOLISM & TOXICOLOGY 5(10):1305-11 (Sept.
`
`2009)
`
`1009
`
`Harden et al., Validation of proposed diagnostic
`
`Harden
`
`criteria (the “Budapest Criteria”) for Complex
`
`Regional Pain Syndrome, PAIN 150:268–274 (2010)
`
`1010
`
`P. Drummond, Sensory Disturbances in Complex
`
`Drummond
`
`Regional Pain Syndrome: Clinical Observations,
`
`Autonomic Interactions, and Possible Mechanisms,
`
`PAIN MEDICINE 11:1257-66 (2010)
`
`Excerpt of U.S. Patent Application No. 13/894,274
`
`Excerpt of U.S. Patent Application No. 14/063,979
`
`Excerpt of U.S. Patent Application No. 14/279,229
`
`Excerpt of U.S. Patent Application No. 14/536,526
`
`Excerpt of U.S. Patent Application No. 14/967,224
`
`Excerpt of U.S. Patent Application No. 14/604,524
`
`Excerpt of U.S. Patent Application No. 15/217,773
`
`Excerpt of U.S. Patent Application No. 15/360,886
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`vii
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`

`

`
`
`
`
`
`1019
`
`S. Bruehl, An update on the pathophysiology of
`
`complex regional pain syndrome, ANESTHESIOLOGY
`
`11: 713-25 (2010)
`
`1020
`
`Merskey et al., CLASSIFICATION OF CHRONIC PAIN
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`(Merskey & Bogduk eds. 1994)
`
`U.S. Provisional Patent App. No. 61/646,538
`
`U.S. Provisional Patent App. No. 61/647,478
`
`U.S. Provisional Patent App. No. 61/654,383
`
`U.S. Provisional Patent App. No. 61/654,292
`
`U.S. Provisional Patent App. No. 61/655,527
`
`U.S. Provisional Patent App. No. 61/655,541
`
`U.S. Provisional Patent App. No. 61/762,225
`
`U.S. Provisional Patent App. No. 61/764,563
`
`U.S. Provisional Patent App. No. 61/767,647
`
`U.S. Provisional Patent App. No. 61/767,676
`
`A. de Castro et al., Zoledronic acid to treat complex
`
`regional pain syndrome type I in adult. Case report,
`
`REV. DOR. SÃO PAULO 12(1): 71-73 (Jan.-Mar. 2011)
`
`
`
`
`
`
`
`
`
`
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`
`
`viii
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`

`

`
`
`
`
`
`
`
`1032
`
`S. Bruehl et al., External validation of IASP
`
`diagnostic criteria for Complex Regional Pain
`
`Syndrome and proposed research diagnostic criteria,
`
`PAIN 81:147-54 (1999)
`
`Excerpt of U.S. Patent Application No. 15/357,932
`
`Grünenthal GmbH v. Antecip Bioventures II,
`
`PGR2017-00008, Paper 19 (Patent Owner Response)
`
`(P.T.A.B. Oct. 2, 2017)
`
`File History of U.S. Patent No. 9,931,352
`
`File History of U.S. Patent No. 10,039,774
`
`File History of U.S. Patent No. 10,052,338
`
`GIOT website print-out
`
`Excerpts of Stedman’s Medical Dictionary, 28th ed.
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`
`
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`
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`
`ix
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`
`
`I.
`
`INTRODUCTION
`
`The claims of U.S. Patent No. 10,052,338 (Ex. 1003, “the ’338 patent”)
`
`concern methods of using neridronic acid, a bisphosphonate drug, to treat
`
`particular symptoms of complex regional pain syndrome (CRPS). The ’338 patent
`
`inventor, Dr. Herriot Tabuteau, did not invent neridronic acid. Neridronic acid was
`
`developed in Italy by real-party-in-interest Abiogen Pharma SpA, and was
`
`described in the art long before the ’338 patent’s earliest possible priority date.
`
`Nor did Dr. Tabuteau invent methods of treating CRPS with neridronic acid. It
`
`was already well known that various bisphosphonate drugs, including neridronic
`
`acid, had demonstrated efficacy for treating CRPS, a severely debilitating pain
`
`syndrome that sometimes develops after trauma such as a fracture or surgery. In
`
`particular, at least three prior art publications plainly and expressly disclosed that
`
`neridronic acid was effective to treat CRPS: a 2011 article by Varenna (“Varenna
`
`2011,” Ex. 1006), a 2004 article by Muratore, et al. (“Muratore,” Ex. 1007), and a
`
`2009 article by Gatti, et al. (“Gatti,” Ex. 1008).
`
`Patent Owner directed the ’338 patent claims to methods of administering
`
`neridronic acid to patients suffering from particular signs and symptoms of CRPS.
`
`Independent claim 1 recites a “method of treating allodynia associated with
`
`[CRPS], comprising parenterally administering neridronic acid in a salt form or an
`
`acid form to a human being suffering from allodynia associated with [CRPS].”
`
`
`
`1
`
`

`

`
`
`Claim 17, the only other independent claim, is identical but for substituting
`
`“autonomic motor change” for “allodynia.”
`
`In fact, the ’338 patent is part of a series of virtually identical patents
`
`belonging to Patent Owner that claim the administration of neridronic acid to
`
`patients suffering from various well-known characteristic symptoms of CRPS,
`
`including U.S. Patent Nos. 9,931,352 (Ex. 1001) and 10,039,774 (Ex. 1002).
`
`Petitioner is also challenging those two patents in separate PGR petitions filed
`
`concurrently with this one.
`
`The ’338 patent claims do not recite anything inventive. A POSA would
`
`have known that CRPS is defined by, and diagnosed based upon, a well-known and
`
`generally accepted set of signs and symptoms known as the “Budapest Criteria.”
`
`These criteria are disclosed in Varenna 2011 and Harden, and include allodynia, as
`
`recited in claim 1.
`
`A POSA also would have known based on Varenna 2011, Muratore, and/or
`
`Gatti that neridronic acid was effective for treating CRPS. Gatti and Muratore
`
`further teach that neridronic acid is effective for improving the symptoms of
`
`CRPS. Knowing that neridronic acid was effective to treat CRPS and its
`
`symptoms, it would have been obvious to a POSA to administer neridronic acid to
`
`patients suffering from allodynia associated with CRPS, a defining sign and
`
`
`
`2
`
`

`

`
`
`symptom of the condition outlined in the Budapest Criteria described in Varenna
`
`2011 and Harden.
`
`Claims 17-30 are invalid for indefiniteness. A POSA would not have
`
`understood what “autonomic motor change” associated with CRPS refers to. The
`
`only mention of “autonomic” in the ’338 patent specification states that CRPS “is
`
`characterized by severe pain in a limb that can be accompanied by edema, and
`
`autonomic, motor and sensory changes.” The specification nowhere defines
`
`“autonomic motor change” and does not describe what autonomic motor changes
`
`are purportedly treated by the claim methods. A POSA simply would not
`
`understand what is covered by claims 17-30.
`
`To the extent a POSA could have understood claims 17-30, they cover
`
`treatment of autonomic dysfunction associated with CRPS, motor changes
`
`associated with CRPS, or both. Regardless of how the claims are interpreted, they
`
`are obvious over Varenna 2011, Muratore, and/or Gatti in combination with
`
`Harden and an article by Drummond. Harden and Drummond teach that both
`
`autonomic dysfunction (such as changes in skin temperature and sweating) and
`
`motor changes (such as decreased range of motion, weakness, tremor, and
`
`dystonia) are characteristic signs and symptoms of CRPS listed in the Budapest
`
`Criteria. Thus, to the extent they can be understood, claims 17-30 are obvious for
`
`all of the same reasons as claims 1-16.
`
`
`
`3
`
`

`

`
`
`In sum, the ’338 patent claims recite nothing more than the administration of
`
`a known drug for an art-recognized purpose. Patent Owner’s attempts to fabricate
`
`patentable inventions by claiming administration of neridronate to patients having
`
`particular characteristic symptoms of CRPS should be rejected.
`
`In the alternative, to the extent claims 1-30 are found not obvious based on
`
`Petitioner’s cited prior art, then those claims are plainly invalid for lack of written
`
`description. The standard for satisfying the written description requirement is
`
`more exacting than the obviousness standard—mere obviousness is not sufficient.
`
`The prior art contains much more detail concerning the use of neridronic acid to
`
`treat allodynia and autonomic and/or motor changes associated with CRPS in
`
`human patients than is contained in the ’338 patent specification. To the extent the
`
`claims are not obvious, the ’338 patent specification, too, fails to describe using
`
`neridronic acid to treat allodynia or “autonomic motor change.”
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`A. Real Parties-in-Interest (§ 42.8(b)(1))
`The real parties-in-interest are Petitioner Grünenthal GmbH and Abiogen
`
`Pharma SpA. Abiogen Pharma SpA developed neridronic acid and has licensed
`
`the development and marketing rights for North America to Petitioner Grünenthal
`
`GmbH.
`
`
`
`4
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`

`

`
`
`B. Related Matters (§ 42.8(b)(2))
`Petitioner has filed petitions for post-grant review against several U.S.
`
`patents owned by the Patent Owner, as shown in the following table:
`
`Filing Date
`
`Status
`
`May 8, 2017
`
`October 10, 2017
`
`December 14, 2016 Final written decision finding all
`challenged claims unpatentable
`Final written decision finding all
`challenged claims unpatentable
`PGR instituted and currently
`pending
`PGR instituted and currently
`pending
`PGR petition filed
`
`April 18, 2018
`
`August 21, 2018
`
`October 16, 2018
`
`PGR petition filed
`
`January 3, 2019
`
`PGR petition filed concurrently
`with the instant Petition
`PGR petition filed concurrently
`with the instant Petition
`
`PGR
`Patent
`Number
`Number
`9,283,239 PGR2017-
`00008
`9,408,862 PGR2017-
`00022
`9,539,268 PGR2018-
`00001
`9,707,245 PGR2018-
`00062
`9,820,999 PGR2018-
`00092
`9,867,839 PGR2019-
`00003
`
`
`9,931,352
`
`10,039,774
`
`
`
`January 3, 2019
`
`All of these matters are related to the instant PGR in that each of the above
`
`patents shares the same inventor as the ’338 patent and, like the ’338 patent,
`
`concerns the use of bisphosphonate drugs to treat pain conditions. The ’338 patent
`
`
`
`5
`
`

`

`
`
`issued from a continuation of the application that issued as U.S. Patent No.
`
`9,931,352. Moreover, the ’338 patent and some of the above patents are in the
`
`same or related patent families. In particular, the ’338 patent purportedly claims
`
`priority to the patent application that issued as U.S. Patent No. 9,820,999
`
`(PGR2018-00092). And the ’338 patent, U.S. Patent Nos. 9,707,245 (PGR2018-
`
`00062), 9,283,239 (PGR2017-00008), and 9,867,839 (PGR2019-00003) each
`
`purportedly claims priority to many of the same applications, including Provisional
`
`Application No. 61/646,538 filed on May 14, 2012 and U.S. Patent Application
`
`No. 13/894,274, filed on May 14, 2013. Concurrently with this Petition, Petitioner
`
`is filing PGRs challenging U.S. Patent Nos. 10,093,774 (Ex. 1002) and 9,931,352
`
`(Ex. 1001), which also claim methods of treating particular signs and symptoms of
`
`CRPS. The ’338 patent is a continuation of the application that issued as the ’352
`
`patent.
`
`To Petitioner’s best knowledge, the instantly challenged ’338 patent is not
`
`currently involved in any other judicial or administrative matters that would affect,
`
`or be affected by, a decision in this proceeding.
`
`
`
`6
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`

`

`
`
`C. Lead and Back-up Counsel (§ 42.8(b)(3))
`Lead Counsel
`Back-up Counsel
`Daniel J. Minion
`Bruce C. Haas
`Registration No. 53,329
`Registration No. 32,734
`VENABLE LLP
`VENABLE LLP
`1290 Avenue of the Americas
`1290 Avenue of the Americas
`New York, NY 10104
`New York, NY 10104
`Tel: 212-218-2538
`Tel: 212-218-2290
`Fax: 212-218-2200
`Fax: 212-218-2200
`dminion@venable.com
`bchaas@venable.com
`
`GrunenthalPGR@venable.com
`
`
`Service Information (§ 42.8(b)(4))
`
`D.
`Please direct all correspondence to lead and back-up counsel at the above
`
`addresses and to GrunenthalPGR@venable.com. Petitioner consents to electronic
`
`service to GrunenthalPGR@venable.com and at the e-mail addresses above.
`
`III. PAYMENT OF FEES
`Pursuant to 37 C.F.R. §§ 42.203(a) and 42.15(b), the required fees are
`
`submitted herewith. If additional fees are due during this proceeding, the Office is
`
`authorized to charge Deposit Account No. 22-0261.
`
`IV. TIME FOR FILING PETITION
`The ’338 patent issued on August 21, 2018. This Petition was timely filed
`
`on January 3, 2019, which is no later than the date that is nine months after the date
`
`of the grant of the patent. 37 C.F.R. § 42.202.
`
`
`
`7
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`

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`
`V. GROUNDS FOR STANDING
`Pursuant to 37 C.F.R. § 42.204(a), Petitioner certifies that the ’338 patent is
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`eligible for PGR, and that Petitioner is not barred or estopped from requesting
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`post-grant review of the ’338 patent, challenging the claims on the grounds
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`identified in this Petition.
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`The ’338 patent is available for PGR pursuant to the America Invents Act
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`(“AIA”), Pub. L. No. 112-29, § 3(n)(1), 125 Stat. 284, 293 (2011) because, as
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`explained below in Section X, at least one claim has an effective filing date on or
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`after March 16, 2013.
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`VI. CHALLENGED CLAIMS AND RELIEF SOUGHT
`Petitioner respectfully requests post grant review and cancellation of ’338
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`patent claims 1-30 as unpatentable under 35 U.S.C. §§ 103 and/or 112. It is more
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`likely than not that claims 1-30 are unpatentable on the following grounds:
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`Ground Claims Statutory Basis
`1
`1-16
`35 U.S.C. § 103
`Obviousness
`
`2
`
`17-30
`
`35 U.S.C. § 112
`Indefiniteness
`
`Prior Art References
`Varenna 2011 (Ex. 1006)
`Muratore (Ex. 1007)
`Gatti (Ex. 1008)
`Harden (Ex. 1009)
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`
`
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`8
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`Ground Claims Statutory Basis
`3
`17-30
`35 U.S.C. § 103
`Obviousness
`
`4
`
`1-30
`
`35 U.S.C. § 112(a)
`Lack of Written
`Description
`
`Prior Art References
`Varenna 2011 (Ex. 1006)
`Muratore (Ex. 1007)
`Gatti (Ex. 1008)
`Harden (Ex. 1009)
`Drummond (Ex. 1010)
`
`
`VII. THE ’338 PATENT PROSECUTION HISTORY
`The earliest non-provisional application the ’338 patent claims priority to is
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`13/894,274, filed May 14, 2013. Ex. 1011 at 1-74. In this application Patent
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`Owner sought broad claims to methods of treating CRPS comprising orally
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`administering zoledronic acid. Id. at 75-99. The Examiner rejected the claims
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`multiple times for obviousness based on several references disclosing the use of
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`bisphosphonates, including zoledronic acid, to treat CRPS. Id. at 100-120. The
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`Examiner reasoned that (1) the use of bisphosphonates, including zoledronic acid,
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`to treat CRPS was known in the art; (2) methods for orally administering
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`zoledronic acid were also known in the art; and (3) a POSA would have reasonably
`
`expected that oral zoledronic acid could be used to treat CRPS. Id. Patent Owner
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`was unable to overcome these rejections and appealed to the PTAB. Id. at 121.
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`But before the appeal could be decided, Patent Owner abandoned the application.
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`
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`9
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`Id. at 122-129. At around the same time, Patent Owner also abandoned other,
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`related applications that were the subject of PTAB appeals.
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`Rather than continuing to prosecute 13/894,274, Patent Owner instead
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`turned its focus to its continuation-in-part, 14/063,979, which initially sought broad
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`claims to treating pain with zoledronic acid. Ex. 1012 at 1-89. The same
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`Examiner also rejected these claims based on a similar rationale that it was known
`
`in the art that bisphosphonates could be used to treat pain. Id. at 90-100. Patent
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`Owner cancelled these broad claims and added new, narrower claims directed to a
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`particular salt form of zoledronic acid that purportedly had high oral
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`bioavailability. Id. at 101-110. After again rejecting the claims, the Examiner
`
`ultimately allowed claims to methods of “enhancing the oral bioavailability of
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`zoledronic acid comprising orally administering a dosage form containing
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`zoledronic acid in the disodium salt form” because Patent Owner had allegedly
`
`demonstrated unexpected results with respect to the bioavailability of this
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`particular salt form of zoledronic acid. Id. at 111-126. But no broad claims
`
`covering treatment of pain with bisphosphonates were allowed.
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`Patent Owner next filed another continuation-in-part, 14/279,229, which
`
`sought broad claims to the administration of zoledronic acid to treat low back pain.
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`Ex. 1013 at 1-90. This application was examined by a new Examiner who rejected
`
`the broad claims as obvious over prior art that disclosed treatment of pain with
`
`
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`10
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`zoledronic acid. Id. at 91-111. Patent Owner proffered evidence of purported
`
`unexpected results associated with a particular salt form of zoledronic acid and a
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`particular amount and frequency of administration. Ultimately, the Examiner
`
`allowed amended claims containing the amount and frequency limitations. Id. at
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`112-123. Inexplicably, however, the claims issued without any limitation to the
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`disodium salt form of zoledronic acid that was associated with the purported
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`unexpected results. See id.
`
`Patent Owner was also unable to overcome the obviousness rejections issued
`
`by a third Examiner in 14/536,526 against broad claims that covered the use of
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`zoledronic acid to treat bone marrow lesions (BMLs), a bone condition associated
`
`with osteoarthritis and other types of pain. Ex. 1014 at 1-112. Patent Owner
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`ultimately abandoned the application without ever overcoming the rejections. Id.
`
`at 113-115.
`
`But at this point in the prosecution of this series of applications, another new
`
`Examiner began to allow Patent Owner’s broad claims without significant
`
`substantive prosecution, and without providing detailed reasons for allowance. For
`
`example, despite the earlier rejections, in 14/967,224, 14/604,524, 15/217,773, and
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`15/360,886, the fourth Examiner issued broad claims to treating BMLs with
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`various bisphosphonates. See Exs. 1015-1018.
`
`
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`In the application that issued as the ’338 patent (15/820,305) and its
`
`immediate predecessor (15/703,891, which issued as U.S. Patent No. 9,931,352),
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`Patent Owner pivoted back to seeking broad claims to the treatment of CRPS with
`
`bisphosphonates, in this case focusing on the use of the bisphosphonate neridronic
`
`acid to treat well-known symptoms and diagnostic criteria associated with CRPS
`
`such as allodynia and “autonomic motor change.” Ex. 1037 at 129-130; 1035 at
`
`129-131. The claims underwent no substantive prosecution based upon the prior
`
`art and were initially rejected only for obviousness-type double patenting over
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`patents and applications having the same inventor as the ’338 patent. Ex. 1037 at
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`261-268; Ex. 1035 at 185-191. Patent Owner responded to these rejections by
`
`filing terminal disclaimers to the patents and applications in question, after which
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`the Examiner allowed the claims. Ex. 1037 at 282-307; Ex. 1035 at 286-293, 297-
`
`304.
`
`At no point during prosecution did Patent Owner ever point out to the
`
`Examiner that previous Examiners had rejected broad claims covering
`
`administration of the bisphosphonate zoledronic acid to treat CRPS, low back pain,
`
`and bone marrow lesions, and that those rejections were never overcome. Patent
`
`Owner also never informed the Examiner that the previous broad claims to
`
`treatment of CRPS were rejected based in part upon a previous Examiner’s
`
`conclusion that it was obvious to use bisphosphonates to treat CRPS. And Patent
`
`
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`12
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`
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`Owner never informed the Examiner that the allowances in 14/279,229 (Ex. 1013)
`
`and 14/063,979 (Ex. 1012), for example, were contingent upon purported
`
`unexpected results demonstrated only with a particular salt form of zoledronic
`
`acid.
`
`As such, the ’338 patent issued with broad claims to treating CRPS
`
`symptoms with a bisphosphonate, despite the fact that similarly broad claims in its
`
`predecessor applications were abandoned due to failure to overcome rejections
`
`based upon the obviousness of treating CRPS with bisphosphonates. As this
`
`petition will show, the broad claims of the ’338 patent are unpatentable for the
`
`reasons given in this Petition.
`
`VIII. THE PERTINENT ART AND THE PERSON OF ORDINARY SKILL
`IN THE ART
`
`Challenged claims 1-16 are directed to methods of treating allodynia
`
`associated with CRPS, and challenged claims 17-30 are directed to methods of
`
`treating “autonomic motor change” associated with CRPS. CRPS is a chronic pain
`
`syndrome that often develops after trauma such as a fracture, surgery, or soft tissue
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`injury. Ex. 1004 ¶20. “It is associated at some point with evidence of edema,
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`changes in skin blood flow, abnormal sudomotor activity in the region of the pain,
`
`or allodynia or hyperalgesia.” Id.; Ex. 1020 at 57. Among the main features of
`
`CRPS is pain that is disproportionate to the inciting event that is “frequently
`
`described as burning and continuous and exacerbated by movement, continuous
`
`
`
`13
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`
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`stimulation, or stress.” Ex. 1004 ¶20; Ex. 1020 at 57. The ’338 patent confirms
`
`that CRPS is “a debilitating pain syndrome . . . characterized by severe pain in a
`
`limb that can be accompanied by edema, and autonomic, motor and sensory
`
`changes.” Ex. 1003 13:23-26.
`
`Thus, challenged claims 1-30 are directed to methods of treating specific
`
`signs and symptoms that are characteristic of the chronic pain syndrome, CRPS,
`
`namely allodynia and autonomic and/or motor changes. Consequently, claims 1-
`
`30 pertain to the field of treatment of chronic pain syndromes and disorders,
`
`specifically to the treatment of CRPS. Ex. 1004 ¶21. A person of ordinary skill in
`
`the art for the ’338 patent (“POSA”) would therefore have an M.D., or a Ph.D. in a
`
`pain-medicine-relevant discipline, such as clinical health psychology or
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`neuroscience, and at least 3-5 years of experience in the treatment of CRPS or
`
`related chronic pain conditions, or in the study of CRPS or related types of chronic
`
`pain. Id.
`
`IX. CLAIM CONSTRUCTION
`“In a post-grant review proceeding, a claim of a patent . . . shall be construed
`
`using the same claim construction standard that would be used to construe the
`
`claim in a civil action under 35 U.S.C. 282(b), including construing the claim in
`
`accordance with the ordinary and customary meaning of such claim as understood
`
`by one of ordinary skill in the art and the prosecution history pertaining to the
`
`
`
`14
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`
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`patent.” 37 C.F.R. § 42.200(b).