`
`
`
`
`
`
`
`
` Paper 7
`
`
` Entered: May 7, 2019
`
`Trials@uspto.gov
`571-272-7822
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`GRÜNENTHAL GMBH,
`Petitioner,
`
`v.
`
`ANTECIP BIOVENTURES II LLC,
`Patent Owner.
`
`
`Case PGR2019-00003
`Patent 9,867,839 B2
`
`
`
`Before TONI R. SCHEINER, GRACE KARAFFA OBERMANN, and
`SHERIDAN K. SNEDDEN, Administrative Patent Judges.
`
`SCHEINER, Administrative Patent Judge.
`
`
`DECISION
`Instituting Post Grant Review of Claims 1–30
`35 U.S.C. § 324
`
`
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`I. INTRODUCTION
`Grünenthal GMBH (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
`requesting post grant review of claims 1–30 of U.S. Patent No. 9,867,839 B2
`(Ex. 1001, “the ’839 patent”). Antecip Bioventures II LLC (“Patent
`Owner”) did not file a preliminary response. Applying the standard set forth
`in 35 U.S.C. § 324(a), which requires demonstration that it is more likely
`than not that at least one challenged patent claim is unpatentable, we
`institute a post grant review of the challenged claims based on the grounds
`of unpatentability identified in the Petition. Pet. 8–9 (statement of grounds).
`The following preliminary findings of fact and conclusions of law are
`made for the sole purpose of determining whether Petitioner meets the
`threshold for initiating review. Any final decision shall be based on the full
`trial record, including any response timely filed by Patent Owner. Taking
`account of the information presented, we determine that Petitioner shows
`sufficiently the following facts for the purposes of trial institution.
`A. Related Proceedings
`In addition to this Petition, Petitioner has filed post-grant review
`
`petitions against five patents closely related to the ’839 patent, albeit from
`two different families:
`US Patent 9,283,239 (Case PGR2017-00008);
`US Patent 9,408,862 (Case PGR2017-00022);
`US Patent 9,539,268 (Case PGR2018-00001);
`US Patent 9,707,245 (Case PGR2018-00062); and
`US Patent 9,820,999 (Case PGR2018-00092).
`
`2
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`Pet. 5; Paper 3, 2. “All of these patents have the same inventor as the ’839
`patent” (Pet. 5), and all are directed to treating pain with bisphosphonate
`drugs. Post-grant review was instituted in all five cases, and final decisions
`have been entered in PGR2017-00008, PGR2017-00022, and PGR2018-
`00001.
`Petitioner represents that “the ’839 patent is not currently involved in
`any other judicial or administrative matters that would affect, or be affected
`by, a decision in this proceeding.” Pet. 6.
`
`B. The ’839 Patent (Ex. 1001)
`The ’839 patent is titled “Osteoclast Inhibitors for Joint Conditions”
`(Ex. 1001, (54)), and issued on January 16, 2018 from application number
`15/438,513 (“the ’513 application”), filed February 21, 2017. According to
`the specification of the ’839 patent, bisphosphonate compounds, such as
`neridronic acid and zoledronic acid, “are potent inhibitors of osteoclast
`activity, and are used clinically to treat bone-related conditions such as
`osteoporosis and Paget’s disease of bone; and cancer-related conditions
`including multiple myeloma, and bone metastases from solid tumors.” Id. at
`1:46–50. In addition, according to the Specification, “neridronic acid and
`zoledronic acid, in an acid or a salt form, can be used to treat or alleviate
`pain or related conditions, such as joint conditions” (id., Abstract), including
`osteoarthritis, rheumatoid arthritis, and complex regional pain syndrome
`(CRPS) (id. at 14:21–24).
`
`3
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`“Commonly used measures of pain intensity include the visual analog
`scale (VAS) and the numerical rating scale (NRS).” Id. at 8:61–62. “With
`the VAS approach, patients rate the severity of their pain by marking a point
`on a 10-cm (or 100 mm) VAS . . . [w]ith the NRS approach, patients rate the
`severity of their pain by verbally responding to a 10-pt NRS.” Id. at 8:62–
`67. With either approach, 0 equals no pain, and 10 equals the worst possible
`pain. Id. at 8:67–9:1. “Knee pain in a person with a VAS score of 5 cm . . .
`or higher, or an NRS score of 5 or higher, may be referred to herein as
`moderate to severe knee pain.” Id. at 9:6–9.
`Finally, the specification teaches that “the daily oral dose of
`neridronate[1] is about 10 mg to about 1,000 mg, about 50 mg to about 500
`mg, about 100 mg to about 500 mg, or about 150 mg to about 300 mg,” and
`“the parenteral dose . . . is about 5 mg to about 500 mg, about 5 mg to about
`200 mg, or about 10 mg to about 150 mg.” Id. at 30:17–22.
`
`
`
`C. Illustrative Claim
`Claims 1 and 15, the only independent claims, are illustrative:
`1. A method of treating pain associated with a joint
`comprising: administering neridronic acid in an acid form or
`a salt form to a patient who has suffered for at least 3
`months with 1) pain associated with a joint and 2) a pain
`intensity of 5 or greater measured using the 0–10 numerical
`rating scale (NRS) or 5 cm or greater using the 10 cm visual
`analog scale (VAS).
`
`1 Dr. Poree explains that “‘neridronate’ is synonymous with neridronic
`acid.” Ex. 1003 ¶ 150 (citing Ex. 1001, 32:6).
`4
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`
`15. A method of treating pain associated with a joint
`comprising: orally administering zoledronic acid in an acid
`form or a salt form to a patient having 1) pain associated
`with a joint and 2) a pain intensity of 5 or greater measured
`using the 0–10 NRS or 5 cm or greater using the 10 cm
`VAS, wherein a total of about 400 mg to about 600 mg of
`zoledronic acid is administered in 2 or 3 individual doses
`within a period of about a month.
`Ex. 1001, 105:38–44, 106:14–21.
`
`D. Evidence Relied Upon
`M. Varenna et al., Treatment of complex regional pain syndrome type I with
`neridronate: a randomized, double-blind, placebo-controlled study, 52
`RHEUMATOLOGY 534–42 (2012) (Ex. 1005, “Varenna 2012”).
`M. Muratore et al., Il neridronato nel trattamento dell’algodistrofia
`simpatico riflessa del’anca: confront in aperto con il clodronato, 5
`PROGRESSI IN RHEUMATOLOGIA, ABSRACT BOOK VII CONGRESSO
`NATIONALE COLLEGIO DEI REUMATOLOGI OSPEDALIERI 89 (2004) (certified
`English translation: Neridronate in the treatment of reflex sympathetic hip
`algodystrophy: open comparison with clodronate) (Ex. 1006, “Muratore”).
`D. Gatti et al., Neridronic acid for the treatment of bone metabolic diseases,
`5 EXPERT OPIN. DRUG METAB. TOXICOL. 1305–11 (2009) (Ex. 1007,
`“Gatti”).
`G.S.E. Dowd et al., Complex regional pain syndrome with special emphasis
`on the knee, 89-B JOURNAL OF BONE AND JOINT SURGERY 285–290 (2007)
`(Ex. 1009, “Dowd”).
`M. Walsh, WO 2007/092338 A2, published August 16, 2007 (Ex. 1010,
`“Walsh”).
`D. Thompson at al., WO 2005/107751 A1, published November 17, 2005
`(Ex. 1011, “Thompson”).
`Fox et al., US 2004/0063670 A1, published April 1, 2004 (Ex. 1012, “Fox”).
`5
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`M. Rossini et al., Intra-articular clodronate for the treatment of knee
`osteoarthritis: dose ranging study vs hyaluronic acid, 48 RHEUMATOLOGY
`773–78 (2009) (Ex. 1013, “Rossini”).
`M. Varenna, Efficacy Study of Neridronate to treat Painful Osteoarthritis of
`the Knee With Bone Marrow Lesions (2013) available at
`https://clinicaltrials.gov/ct2/show/record/NCT01803360?view=record (Ex.
`1014, “Varenna Protocol”).
`A. de Castro et al., Zoledronic acid to treat complex regional pain syndrome
`type I in adult, 12 REV DOR. SÃO PAULO 71–73 (2011) (Ex. 1015, “de
`Castro”).
`J. Zaspel et al., Treating CRPS I in the early stage – cortisone (methyl
`prednisone) versus bisphosphonate (zoledronic acid), GERMAN CONGRESS
`FOR ORTHOPEDICS AND TRAUMA SURGERY (2007) (Ex. 1016, “Zaspel”).
`M. Hanna et al., WO 2011/097269, published August 11, 2011 (Ex. 1017,
`“Hanna”).
`
`The Petition is supported by the Declaration of Lawrence Poree,
`M.D., Ph.D. Ex. 1003. For purposes of this decision, we find that Dr. Poree
`is qualified to opine about the perspective of a person of ordinary skill in the
`art at the time of the invention. See Ex. 1004 (Dr. Poree’s curriculum vitae).
`
` F. The Asserted Grounds of Unpatentability
`Petitioner asserts that the challenged claims are unpatentable on the
`
`following grounds:
`
`
`
`1
`
`2
`
`Claims
`
`Statutory Basis
`
`Prior Art References
`
`1–14
`
`1–14
`
`35 U.S.C. § 112(a),
`Written Description
`35 U.S.C. § 112(a),
`Enablement
`
`
`
`
`
`6
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`
`
`Claims
`
`Statutory Basis
`
`Prior Art References
`
`Varenna 2012, Muratore,
`Gatti 2009, Dowd
`Varenna Protocol, Rossini
`Walsh, Thompson, Fox,
`Gatti, Rossini
`De Castro, Zaspel, Dowd,
`Hanna
`
`1–14
`
`35 U.S.C. § 103
`
`1–9, 13, 14 35 U.S.C. § 103
`
`1–9, 13, 14 35 U.S.C. § 103
`
`15–30
`
`35 U.S.C. § 103
`
`3
`
`4
`
`5
`
`6
`
`
`
`II. ANALYSIS
`We organize our analysis into four main sections. First, we address
`
`the eligibility of the ’839 patent for post-grant review. Second, we address
`the level of ordinary skill in the art at the time of the invention. Third, we
`discuss claim construction. Finally, taking the information presented into
`account, we consider whether Petitioner meets the threshold showing for
`post-grant review under the asserted grounds of unpatentability. In that
`fourth section, we further divide our analysis into subparts, addressing the
`asserted grounds based on lack of written description, lack of enablement,
`and obviousness.
`
`A. Eligibility for Post Grant Review
`The post-grant review provisions set forth in Section 6(d) of the AIA2
`apply only to patents subject to the first-inventor-to-file provisions of the
`
`
`2 Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
`(2011) (“AIA”).
`
`7
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`AIA. See AIA § 6(f)(2)(A) (“The amendments made by subsection (d)
`. . . shall apply only to patents described in section 3(n)(1).”). Transitional
`provision AIA section 3(n)(1) is as follows:
`
`(n) EFFECTIVE DATE.—
`
`(1) IN GENERAL.—Except as otherwise provided in this
`section, the amendments made by this section shall take effect
`upon the expiration of the 18-month period beginning on the date
`of the enactment of this Act, and shall apply to any application
`for patent, and to any patent issuing thereon, that contains or
`contained at any time—
`(A) a claim to a claimed invention that has an effective
`filing date as defined in section 100(i) of title 35, United
`States Code, that is on or after the [March 16, 2013]
`effective date . . . ; or
`(B) a specific reference under section 120, 121, or 365(c)
`of title 35, United States Code, to any patent or application
`that contains or contained at any time such a claim.
`AIA § 3(n)(1), 125 Stat. 293.
`The term “effective filing date” for a claimed invention in a patent or
`application for patent means “the filing date of the earliest application for
`which the patent or application is entitled, as to such invention, to a right of
`priority under section 119, 365(a), or 365(b) or to the benefit of an earlier
`filing date under section 120, 121, or 365(c).” 35 U.S.C. § 100(i)(1)(B); see
`also AIA § 3(a), 125 Stat. 285 (amending 35 U.S.C. § 100).
`Petitioner represents that challenged claims 1–14 and 26–30 of the
`’839 patent “are not entitled to a priority date earlier than March 16, 2013.”
`Pet. 18. Petitioner contends that the ’839 patent claims priority to ten
`8
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`provisional applications filed before March 16, 2013 (Pet. 16 (listing “pre-
`AIA applications,” Exs. 1030–1039)), but none of those applications
`describes zoledronic acid “in the form of a molecular complex with an
`amino acid,” as required by claims 26–30 of the ’839 patent (id. at 18). On
`this record, we are satisfied that claims 26–30 are not entitled to a priority
`date earlier than March 16, 2013, and the ’839 patent is an AIA first-
`inventor-to-file patent under AIA section 3(n)(1)(A). Patent Owner is free
`to dispute that finding in a timely filed response.
`Petitioner further represents that the pre-AIA applications fail to
`describe the “suffered for at least 3 months limitation of claims 1–14.” Pet.
`20. Petitioner contends that “[t]he pre-AIA applications do not describe any
`duration of pain symptoms, let alone 3 months specifically” (id.), that
`“statements concerning pain duration were not introduced to specifications
`in the ’839 patent family until Application No. 14/063,979, filed October 25,
`2013” (id.), and “the specific duration of 3 months did not appear until the
`’513 application was filed on February 21, 2017” (id.). On this record, we
`are satisfied that claims 1–14 are not entitled to a priority date earlier than
`March 16, 2013 because the pre-AIA applications do not describe the
`“suffered for at least 3 months limitation of claims 1–14.” Again, Patent
`Owner is free to dispute that finding in a timely filed response.
`An additional requirement for post-grant review eligibility is that “[a]
`petition for a post-grant review may only be filed not later than the date that
`is 9 months after the date of the grant of the patent.” 35 U.S.C. § 321(c); see
`
`9
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`37 C.F.R. § 42.202(a). The Petition was accorded a filing date of October
`16, 2018 (Paper 5), exactly nine months from the grant of the ’839 patent.
`See 35 U.S.C. § 321(c). Petitioner further certifies that it has standing to
`seek a post-grant review of the ’077 patent. Pet. 8.
`Accordingly, on this record, we determine that the ’839 patent is an
`AIA first-inventor-to-file patent and is eligible for post-grant review.
`B. Level of Ordinary Skill in the Art
`We consider the grounds of unpatentability in view of the
`
`understanding of a person of ordinary skill in the art at the time of the
`invention. Petitioner argues that a person of ordinary skill in the art would
`have had “an M.D. or a Ph.D. in a pain-medicine-relevant discipline, such as
`clinical health psychology or neuroscience, and at least 3–5 years of
`experience in the treatment of joint pain and/or other related types of pain, or
`in the study of joint pain and/or other related types of pain.” Pet. 13–14
`(citing Ex. 1003 ¶¶ 18–21).
`
`Petitioner’s definition is not challenged at this stage of the proceeding
`and is comparable to the level of skill reflected in the asserted prior art
`references. On this record, we find that the prior art itself is sufficient to
`demonstrate the level of ordinary skill in the art at the time of the inventions.
`See Kadima v. Boudreau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (the prior art
`itself can reflect the appropriate level of ordinary skill in the art). To the
`extent a more specific declaration is required, for purposes of this decision,
`we adopt the unopposed definition advanced in the Petition. Pet. 13–14.
`
`10
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`C. Claim Construction
`For petitions filed before November 13, 2018, we interpret claims in
`an unexpired patent using the “broadest reasonable construction in light of
`the specification of the patent in which [they] appear[].” 37 C.F.R.
`§ 42.300(b) (2018).3 Under this standard, we interpret claim terms using
`“the broadest reasonable meaning of the words in their ordinary usage as
`they would be understood by one of ordinary skill in the art, taking into
`account whatever enlightenment by way of definitions or otherwise that may
`be afforded by the written description contained in the applicant’s
`specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997); see In re
`Smith Int’l, Inc., 871 F.3d 1375, 1382–83 (Fed. Cir. 2017) (“[The] broadest
`reasonable interpretation . . . is an interpretation that corresponds with what
`and how the inventor describes his invention in the specification.”). “Under
`a broadest reasonable interpretation, words of the claim must be given their
`plain meaning, unless such meaning is inconsistent with the specification
`and prosecution history.” Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062
`(Fed. Cir. 2016).
`
`
`3 Petitioner filed the Petition on October 16, 2018, prior to the effective date
`of the rule change that replaces the broadest reasonable interpretation
`standard with the federal court claim interpretation standard. See Changes to
`the Claim Construction Standard for Interpreting Claims in Trial
`Proceedings Before the Patent Trial and Appeal Board, 83 Fed. Reg. 51,340
`(Oct. 11, 2018) (“This rule is effective on November 13, 2018 and applies to
`all IPR, PGR and CBM petitions filed on or after the effective date.”).
`
`
`11
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`Petitioner proposes constructions for two terms, listed in the chart
`below.
`
`Term
`“A method of treating
`pain associated with a
`joint”
`
`“pain associated with a
`joint”
`
`Claims Petitioner’s Proposed Construction
`1–30
`Requires that the neridronic acid
`(claims 1–14) or zoledronic acid (claims
`15–30) be administered to a patient
`having pain associated with a joint for
`the purpose of diagnosing, curing,
`mitigating, or preventing pain
`associated with a joint, or for activity
`that otherwise affects the structure or
`any function of the body in a patient
`with pain associated with a joint.
`
`1–30 Any pain related to a joint in any way.
`
`Pet. 14 (chart identifying Petitioner’s proposed claim constructions).
`At this stage of the proceeding, for purposes of this decision, we adopt
`Petitioner’s unopposed constructions, which are supported by citations to the
`specification and the testimony of Dr. Poree. Pet. 14–15 (citing Ex. 1001,
`6:45–51; Ex. 1003 ¶¶ 39–43).
`We emphasize that those constructions are preliminary and invite
`Patent Owner to address them as necessary in a response to the Petition.
`
`D. The Asserted Grounds of Unpatentability
`1. Written Description Support
`Petitioner asserts that claims 1–14 lack written description support
`
`because “the ’839 patent specification nowhere describes . . . administering
`12
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`neridronic acid to a patient having pain associated with a joint measuring ≥5
`cm on the VAS for at least 3 months, as recited in claim 1” (Pet. 22 (citing
`Ex. 1003 ¶ 63)). Petitioner acknowledges that “the ’839 patent specification
`generally discusses administration of bisphosphonates to a patient that has
`‘suffered from [an] inflammatory condition for at least 1 month, at least 2
`months, at least 3 months, at least 6 months, or at least 1 year,’” but
`contends that “disease duration is not the same as pain duration.” Id. at 23
`(citing Ex. 1001, 8:19–25). “Consequently,” Petitioner contends that the
`’839 patent’s disclosure “would not demonstrate to a POSA that the inventor
`was in possession of and actually invented methods of treating patients
`having pain associated with a joint measuring ≥5 cm on the VAS for
`particular periods of time, such as “‘at least 3 months.’” Id. (citing Ex. 1003
`¶¶ 66-68).
`
`Nevertheless, it is well settled that “original claims constitute
`their own description.” In re Koller, 613 F.2d 819, 823 (CCPA 1980);
`see also In re Gardiner, 475 F.2d 1389, 1391 (CCPA 1973) (“[A]n
`original claim, in itself constituted a description in the original
`disclosure equivalent in scope and identical in language to the total
`subject matter now being claimed.”).
`Claim 1, as originally filed, is as follows:
`A method of treating pain associated with a joint comprising:
`administering neridronic acid in an acid or a salt form to a
`patient that has suffered for at least 3 months with 1) pain
`associated with a joint and 2) a pain intensity of 5 or greater
`
`13
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`measured using the 0–10 numerical rating scale (NRS) or 5 cm
`or greater using the 10 cm visual analog scale (VAS).
`Ex. 1002, 14 (file history of the ’839 patent). Original claim 1 is
`equivalent in scope and virtually identical in language to the subject
`matter of challenged claim 1. Accordingly, we determine that claim 1
`constitutes its own description.
`
`On this record, we are not persuaded that Petitioner has established
`that claims 1–14 are more likely than not unpatentable for lack of written
`description support.
`
`2. Enablement
`Petitioner contends that claims 1–144 lack enablement because the
`specification does not teach one of ordinary skill in the art how to administer
`neridronic acid to a patient who has suffered for at least 3 months with
`complex regional pain syndrome (CRPS). Pet. 46. Petitioner notes that
`“[t]he ’839 specification does not contain any examples of methods of
`treatment involving neridronic acid, let alone examples of the use of
`neridronic acid to treat pain associated with CRPS wherein the patient has
`been suffering for 3 months from CRPS and a specific pain intensity.” Id. at
`48 (citing Ex. 1003 ¶¶ 72–73). Petitioner further notes that the specification
`
`
`4 Petitioner notes that claims 10, 11, and 12 depend from claims 1, 2, and 3
`respectively and each specifies that the patient to be treated is suffering from
`complex regional pain syndrome (CRPS). Pet. 46. Petitioner contends that
`claims 1–9, 13, and 14 also lack enablement because they encompass
`treatment of CRPS.
`
`14
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`“broadly posits that ‘any suitable amount’ of a bisphosphonate may be
`used,” and “[t]he only disclosure specific to neridronate dosing in the
`specification states only that the daily oral dose may range anywhere from
`about 10 mg to about 1,000 mg and that the parenteral dose may range
`anywhere from about 5 mg to about 500 mg.” Id. (citing Ex. 1001, 32:4–35;
`Ex. 1003 ¶ 74). According to Petitioner, “[t]hat broad dosage range is not
`tied to any particular disease or duration of treatment, and the specification
`mentions various different conditions that may be treated.” Id. at 48–49
`(citing Ex. 1001 30:17–22; Ex. 1003 ¶¶ 75–76).
`Citing In re Wands, 858 F.2d 731 (Fed. Cir. 1988), Petitioner
`contends that “the ’839 patent claims are unpatentable for lack of
`enablement” because “a significant amount of experimentation would be
`required to practice the invention.” Id. at 48.
`“[T]o be enabling, the specification of a patent must teach those
`skilled in the art how to make and use the full scope of the claimed invention
`without ‘undue experimentation.’” In re Wright, 999 F.2d 1557, 1561 (Fed.
`Cir. 1993). “That some experimentation may be required is not fatal; the
`issue is whether the amount of experimentation required is ‘undue.’” In re
`Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991). Some experimentation, even a
`considerable amount, is not “undue” if, for example, the specification
`provides a reasonable amount of guidance as to the direction in which the
`experimentation should proceed. Wands, 858 F.2d at 737.
`The determination of what constitutes undue experimentation in
`a given case requires the application of a standard of
`15
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`reasonableness, having due regard for the nature of the invention
`and the state of the art . . . . The test is not merely quantitative,
`since a considerable amount of experimentation is permissible, if
`it is merely routine, or if the specification in question provides a
`reasonable amount of guidance with respect to the direction in
`which the experimentation should proceed to enable the
`determination of how to practice a desired embodiment of the
`invention claimed.
`Ex parte Forman, 230 USPQ 546, 547 (BPAI 1986). “The key word is
`‘undue,’ not ‘experimentation.’” In re Angstadt, 537 F.2d 498, 504 (CCPA
`1976).
`
`Even accepting that “significant experimentation” would be required
`to determine the appropriate dose of neridronic acid for a given patient, the
`information advanced in the Petition is insufficient to establish that the
`experimentation would have been anything other than straightforward,
`routine, and empirical, for one of skill in the art.
`
`Moreover, the information advanced in the Petition does not account
`adequately for the general knowledge of the ordinarily skilled artisan as
`demonstrated by Varenna 2012 (Ex. 1005, discussed in detail below). Based
`on the information presented at this stage of the proceeding, we find that the
`disclosure of Varenna 2012 would have informed an ordinary artisan, before
`the critical date, exactly how to administer neridronic acid to humans
`suffering from CRPS with a reasonable expectation of mitigating pain
`associated with that condition. See Ex. 1005, 534 (Abstract), 535 (Study
`design), 536 (Results and Efficacy in double-blind phase), 538 (Table 2 and
`
`16
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`discussion of improvement in pain symptoms upon treatment with
`neridronate).
`At this stage of the proceeding, we are not persuaded that Petitioner
`has established that claims 1–14 are more likely than not unpatentable for
`lack of an enabling disclosure.
`
`3. Obviousness of Claims 1–14 over Varenna 2012, or
`Muratore and Gatti, and Dowd (Ex. 1009)
`Claims 1–14 are directed, in relevant part, to a method of treating pain
`
`associated with a joint comprising administering neridronic acid in acid or
`salt form to a patient who has suffered pain of a specified intensity for at
`least 3 months. Claim 6 depends from claim 1 and specifies that the joint is
`a knee. Claim 10 also depends from claim 1 and specifies that that the
`patient is suffering from complex regional pain syndrome.
`Petitioner argues that the subject matter of claims 1–14 would have
`been obvious because “it was well known in the prior art that neridronic acid
`could be administered to treat CRPS pain, a type of pain that is often
`associated with a joint” (Pet. 24 (citing Ex. 1003 ¶¶ 83–84)), particularly the
`knee (id. at 26 (citing Ex. 1009, 286)).
`
`Varenna (Ex. 1005)
`According to Varenna 2012, complex regional pain syndrome type I
`
`(CRPS-I) “is a severely disabling pain syndrome.” Ex. 1005, 534. Varenna
`2012 discloses the results of a randomized, double blind, placebo-controlled
`human clinical study in which neridronic acid or placebo was administered
`17
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`to eighty-two patients with pain associated with CRPS-I of the hands or feet.
`Id. at 534, 535. Eligibility criteria for the study included disease duration
`“no longer than 4 months” and “spontaneous pain intensity in the affected
`limb of at least 50 mm on a visual analogue scale (VAS) ranging from 0 (no
`pain) to 100 mm (maximal pain).” Id. at 535. Patients in the treatment arm
`of the study received four intravenous infusions of 100 mg neridronic acid
`over ten days. Treatment outcomes were assessed by, among other things,
`“pain evoked by passive motion (ankle for foot involvement and wrist and
`finger joints for hand involvement).” Id.
`
`Varenna 2012 concludes that the clinical study “has shown
`significant, clinically relevant and persistent benefit to patients with acute
`CRPS-I following an [intravenous] neridronate course, providing . . .
`conclusive evidence that the use of bisphosphonates, at appropriate doses, is
`the treatment of choice for CRPS-I.” Id. at 541.
`Muratore (Ex. 1006)
`Muratore teaches that reflex sympathetic algodystrophy5 is a
`
`syndrome characterized by, among other things, the presence of localized
`pain and severe functional limitation. Ex. 1006, 89. Eighteen patients, all
`suffering from femoral head algodystrophy with average duration of the
`
`
`5 According to Dr. Poree, “‘reflex sympathetic algodystropy’ and
`‘algodystrophy’ are synonyms for CRPS.” Ex. 1003 ¶ 31 (citing Ex. 1023,
`713; Ex. 1005, 534, 540).
`
`18
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`disease of 4.1±2.0 months, received either intravenous neridronate every 4
`days, 4 times, or intravenous clodronate daily for 12 days. Id.
`Muratore reports that both drugs were “efficacious in the treatment of
`Reflex Sympathetic Algodystrophy but the speed of improvement of pain
`symptoms with recovery of functional/motor capability . . . was
`demonstrated to be statistically more significant in patients treated with
`Neridronate.” Id.
`
`Gatti (Ex. 1007)
`Gatti teaches that bisphosphonates, particularly neridronic acid, “are
`
`increasingly used for the treatment of reflex sympathetic dystrophy
`syndrome or algodystrophy,” and “the most effective dose is 100 mg diluted
`in 250 ml of saline solution given intravenously over 4 days.” Ex. 1007,
`1305, 1308. According to Gatti, “[w]ith this treatment regimen, the
`proportion of patients experiencing rapid (in 7 – 12 days) > 70%
`symptomatic improvements is close to 80%.” Id. at 1308. “The efficacy
`was assessed by visual analogue scale for spontaneous pain and tenderness
`and by an arbitrary score (from 0 = normal to 4 = worst finding) of motion.”
`Id.
`In addition, Gatti teaches that neridronic acid “has three peculiarities
`
`of some clinical value.” Id. at 1309. For example, “a unique advantage” of
`neridronic acid is that it can be administered intramuscularly, to “patients
`who cannot take oral bisphosphonates” or when “access to hospital services
`for [intravenous] infusions is either cumbersome or too expensive.” Id.
`
`19
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`
`Dowd (Ex. 1009)
`Dowd teaches that complex regional pain syndrome involves “an
`
`exaggerated response to injury of a limb, manifested by intense prolonged
`pain.” Ex. 1009, 285. According to Dowd, CRPS commonly affects the
`knee. Id. Dowd also teaches that pharmacological agents used to treat knee
`pain include bisphosphonates. Id. at 288.
`Discussion
`With respect to claims 1, 6, and 10, Petitioner contends that a person
`
`of ordinary skill in the art “would plainly recognize that Varenna 2012
`discloses that neridronic acid treats CRPS pain, including pain . . . associated
`with a joint.” Pet. 28 (citing Ex. 1003 ¶¶ 94–98; Ex. 1005, 535–538, 541).
`Moreover, Petitioner contends, “the VAS and pain duration ranges taught by
`Varenna 2012 overlap the ≥5 cm on the VAS for at least 3 months ranges
`recited in [the] claims.” Id. (citing Ex. 1003 ¶¶ 91–93). Inasmuch, as Dowd
`“teaches that CRPS can affect the knee and cause knee pain, a type of pain
`associated with a joint” (id. at 31 (citing Ex. 1003 ¶ 89)), Petitioner contends
`a person of ordinary skill in the art “would have been motivated to combine
`the teachings of Varenna 2012 and Dowd because both references concern
`. . . the use of bisphosphonates to treat CRPS.” Pet. 31–32 (citing Ex. 1003
`¶ 110).
`
`In any case, “[t]o the extent they do not independently disclose
`treatment of joint pain,” Petitioner contends one of ordinary skill in the art
`“would have been motivated to apply the teachings of Varenna 2012 or
`
`20
`
`
`
`
`PGR2019-00003
`Patent 9,867,839 B2
`
`Muratore and Gatti 2009, to the teachings of Dowd, and administer
`neridronic acid to a patient suffering from knee pain, where that knee pain is
`caused by CRPS.” Id. at 31 (citing Ex. 1003 ¶ 110).
`Petitioner concludes that it would have been obvious for one of
`ordinary skill in the art “to administer neridronic acid, as disclosed in
`Varenna 2012 or Muratore and Gatti 2009, for the treatment of CRPS pain
`affecting the knee, as taught by Dowd.” Pet. 31 (citing Ex. 1003 ¶¶ 89, 108,
`112).
`Having considered the arguments and evidence presented in the
`Petition, which are unrebutted at this stage of the proceeding, we are
`satisfied that Petitioner demonstrates that it is more likely than not that the
`subject matter of at least claims 1, 6, and 10 of the ’839 patent would have
`been obvious over Varenna 2012, or Muratore and Gatti, and Dowd. Pet.
`24–32, 35 (and evidence cited therein). In addition, having considered the
`arguments and evidence presented regarding dependent claims 2–5, 7–9, and
`11–14, at this stage of the proceeding, we are satisfied that Petitioner shows
`sufficiently that the dependent claims also would have been obvious over
`Varenna 2012, or Muratore and Gatti, and Dowd. Pet. 32–37 (and evidence
`cited therein).
`
`4. Obviousness of Claims 1–9, 13, and 14 over the
`Varenna Protocol and Rossini
`Petitioner contends that claims 1–9, 13, and 14 are also obvious over
`the Varenna Protocol (E
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
