Trials@uspto.gov
`571-272-7822
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`
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`Paper 7
`Entered: March 14, 2019
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`ALVOGEN PINE BROOK LLC,
`Petitioner,
`
`v.
`
`CELGENE CORP.,
`Patent Owner.
`____________
`
`Case IPR2018-01714
`Patent 7,968,569 B2
`____________
`
`
`Before GRACE KARAFFA OBERMANN, TINA E. HULSE,
`and CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`OBERMANN, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
`

`

`IPR2018-01714
`Patent 7,968,569 B2
`
`
`I. INTRODUCTION
`
`Petitioner filed a Petition (Paper 1, “Pet.”) requesting institution of an
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`inter partes review of claims 1–15 of U.S. Patent No. 7,968,569 B2
`
`(Ex. 1001, “the ’569 patent”). Patent Owner filed a Preliminary Response.
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`Paper 6 (“Prelim. Resp.”). We have jurisdiction under 35 U.S.C. § 314(a),
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`which provides that an inter partes review may be instituted only where
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`“there is a reasonable likelihood that the petitioner would prevail with
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`respect to at least 1 of the claims challenged in the petition.” Petitioner does
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`not meet that threshold showing. Accordingly, we deny the Petition and do
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`not institute an inter partes review.
`
`A. Related Proceedings
`
`Both parties identify as related matters five pending actions involving
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`the ’569 patent, none of which involves Petitioner as a named party. Pet. 2–
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`3; Paper 4, 1–2. Petitioner identifies a sixth action, which was dismissed on
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`January 4, 2016, and in which Petitioner was not a named party. Pet. 3.
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`B. Overview of the ’569 Patent (Ex. 1001)
`
`The ’569 patent describes a combination cancer therapy that
`
`encompasses administering an immunomodulatory compound1 with one or
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`more other therapeutically active agents to a patient having “relapsed
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`multiple myeloma,” a type of blood cancer. Ex. 1001, 18:40–61; Pet. 12;
`
`
`1 The ’569 patent defines “immunomodulatory compounds” to encompass
`“small organic molecules that markedly inhibit,” for example, TNF-α, which
`“is an inflammatory cytokine produced by macrophages and monocytes
`during acute inflammation.” The inventors theorize that a biological effect
`of immunomodulatory compounds may be “the reduction of synthesis of
`TNF-α,” which “is responsible for a diverse range of signaling events within
`cells” and “may play a pathological role in cancer.” Ex. 1001, 5:28–42.
`
`2
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`

`

`IPR2018-01714
`Patent 7,968,569 B2
`
`Preliminary Resp. 2. The specification also describes cycling therapy,
`
`wherein therapeutic agents “are cyclically administered to a patient” in a
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`dosing regimen that includes a rest period during which therapy is halted.
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`Id. at 24:19–25:9. Specifically, the ’569 patent describes “[c]ycling therapy”
`
`as involving “the administration of an active agent for a period of time,
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`followed by a rest for a period of time, and repeating this sequential
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`administration.” Id. at 24:20–24.
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`The specification explains that the incorporation of a rest period into a
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`dosing regimen for the administration of a combination of therapeutic agents
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`“can reduce the development of resistance to one or more of the therapies,
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`avoid or reduce the side effects of one of the therapies, and/or improves the
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`efficacy of the treatment.” Id. at 24:25–28. One cycling therapy discussed
`
`in the specification is a method of treating multiple myeloma in which
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`3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidin-2,6-dione (an
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`immunomodulatory compound) is administered in combination with
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`dexamethasone (an anti-cancer drug). Id. at Title, Abstract, 9:34–37, 9:54–
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`56, 14:19, 14:50, 18:40–61, 19:42–52, 32:17–33. The ’569 patent identifies
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`that immunomodulatory compound by its commercial name REVIMID. Id.
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`at 9:54–65. The parties also refer to that compound as REVLIMID. Pet. 1;
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`Prelim. Resp. 9. We adopt the parties’ further convention of referring to that
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`compound as lenalidomide.2 Pet. 20; Prelim. Resp. 2.
`
`
`2 Lenalidomide is an analog of thalidomide, a drug that, in the 1950s, was
`employed “in Europe as a remedy for morning sickness in pregnant women,
`but was withdrawn from the market because of reports of teratogenicity
`(birth defects) associated with its use.” Pet. 8 (citations omitted); see id.
`at 8–11 (for a discussion of lenalidomide as an analog of thalidomide).
`
`3
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`

`IPR2018-01714
`Patent 7,968,569 B2
`
`
`The claimed invention is directed to a cycling therapy that includes
`
`the administration of lenalidomide and dexamethasone. Ex. 1001, 9:34–37,
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`9:54–65, 14:19, 14:50; see id. at 38:64–39:12 (claim 1)3, 40:7–25 (claim 13).
`
`In the claimed cycling therapy, lenalidomide is administered for 21
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`consecutive days (with variable dosing of dexamethasone, as discussed in
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`the next paragraph) followed by a 7-day rest period. Id. at 38:64–39:12,
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`40:7–25 (claims 1 and 13); see Ex. 1001, 32 (certification of correction).
`
`In one embodiment of the claimed invention, about 5 to about 25 mg
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`per day of lenalidomide is administered cyclically “in combination with 40
`
`mg per day of dexamethasone.” That combination is administered “for 21
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`consecutive days followed by seven consecutive days of rest from
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`administration of” lenalidomide “during a 28 day cycle.” Id. at 38:64–39:12
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`(claim 1); see Ex. 1001, 32 (certification of correction). In a second
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`embodiment, about 25 mg of lenalidomide is administered cyclically “for 21
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`consecutive days followed by seven consecutive days of rest from
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`administration of” lenalidomide, where “40 mg per day of dexamethasone”
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`is administered “on days 1-4 every 28 days.” Ex. 1001, 40:7–25 (claim 13).
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`We adopt Patent Owner’s convention of referring to the claimed
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`feature of the invention, which requires a cyclic administration of
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`lenalidomide for a 21-day period followed by a 7-day rest period, as
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`“the 21+7 cyclic dosing regimen.” Prelim. Resp. 3 n.1.
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`C. Illustrative Claim
`
`Claims 1 and 13 are the only independent claims. Claim 1 is
`
`illustrative of the subject matter and reproduced below:
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`
`
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`3 The language of claim 1 is modified by a certificate of correction. See
`Ex. 1001, 32 (citation is to the page number added by Petitioner).
`
`4
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`

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`IPR2018-01714
`Patent 7,968,569 B2
`
`
`1. A method of treating multiple myeloma, which comprises
`cyclically administering to a patient having multiple myeloma about 5
`to about 25 mg per day of a compound of the formula:
`
`
`or a pharmaceutically acceptable salt thereof, for 21 consecutive days
`followed by seven consecutive days of rest from administration of
`said compound during a 28 day cycle, in combination with 40 mg per
`day of dexamethasone.
`
`Ex. 1001, 38:64–39:13 (claim 1); see also id., 32 (Certificate of Correction).
`
`Claim 13, like claim 1, specifies a 21+7 cyclic dosing regimen. Id.
`
`at 40:7–25 (claim 13). Claim 13, however, limits the lenalidomide dosage to
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`“about 25 mg per day” and requires administration of “40 mg per day of
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`dexamethasone” only “on days 1-4 every 28 days.” Id. at 40:7–25
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`(claim 13). Each of the other patent claims inherits the 21+7 cyclic dosing
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`regimen by direct or indirect dependence from claim 1 or claim 13. Id.
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`at 39:14–40:6, 26–31 (claims 2–12, 14, and 15).
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`D. Asserted Grounds of Unpatentability
`
`Petitioner challenges the patentability of claims 1–15 (all claims) of
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`the ’569 patent on two grounds, both of which are based on obviousness
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`under 35 U.S.C. § 103(a). Pet. 2. Specifically, Petitioner alleges that the
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`subject matter of the claims would have been obvious over the combined
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`5
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`IPR2018-01714
`Patent 7,968,569 B2
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`disclosures of (1) Palumbo4, the May Press Release5, and the August Press
`
`Release6; and (2) Palumbo, Hideshima7, and the ’230 patent8. Id.
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`II. ANALYSIS
`
`
`
`We organize our analysis into three parts. First, we address claim
`
`construction. Second, we resolve the level of ordinary skill in the art. Third,
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`we identify an evidentiary gap in the Petition, pertaining to the 21+7 cyclic
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`dosing regimen, which compels a denial of review.
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`A. Claim Construction
`
`We interpret claims in an unexpired patent using the “broadest
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`reasonable construction in light of the specification of the patent in which
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`[they] appear[].” 37 C.F.R. § 42.100(b) (2016).9 Under that standard, claim
`
`
`4 Palumbo, et al., “Low-dose thalidomide plus dexamethasone is an
`effective salvage therapy for advanced myeloma,” Hematologica, 86(4):399-
`403 (April 2001) (Ex. 1015).
`
`5 Press Release, Celgene Corp., Positive Interim Results Presented at the
`VIIIth International Myeloma Workshop on Celgene Corporation’s Lead
`IMiD(TM) (REVIMID(TM)) (May 8, 2001) (Ex. 1012).
`
`6 Press Release, Celgene Corp., Celgene Corporation Awarded Additional
`Patent Protection for Lead IMiD(TM), REVIMID(TM): Comprehensive
`Patent Protection for REVIMID Includes Coverage of the Active Ingredient,
`Pharmaceutical Compositions, and Therapeutic Uses (Aug. 28, 2001)
`(Ex. 1013).
`
`7 Hideshima, et al., “Thalidomide and its analogs overcome drug
`resistance of human multiple myeloma cells to conventional
`therapy,” Blood, 96:2943-2950 (2000) (Ex. 1016).
`
`8 Muller, et al., U.S. Patent No. 6,281,230 B1 (Ex. 1028).
`
`9 A recent amendment to this rule does not apply here, because the Petition
`was filed before November 13, 2018. See “Changes to the Claim
`Construction Standard for Interpreting Claims in Trial Proceedings Before
`
`6
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`IPR2018-01714
`Patent 7,968,569 B2
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`terms are given their ordinary and customary meaning in view of the
`
`specification, as understood by a person of ordinary skill in the art at the
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`time of the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257
`
`(Fed. Cir. 2007). We resolve disputed claim terms only to the extent
`
`necessary to our decision. Nidec Motor Corp. v. Zhongshan Broad Ocean
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`Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (“we need only construe
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`terms ‘that are in controversy, and only to the extent necessary to resolve the
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`controversy’” (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d
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`795, 803 (Fed. Cir. 1999))).
`
`Petitioner asserts that “[n]o terms require construction for purposes of
`
`this” proceeding, “and the claims terms should be given their plain and
`
`ordinary meaning.” Pet. 7. Patent Owner, for purposes of institution only,
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`“stipulates that no term in the challenged claims requires construction.”
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`Prelim. Resp. 20. We agree that no explicit construction of any claim term
`
`is necessary to determine whether to institute review in this case.
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`B. The Level of Ordinary Skill in the Art
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`For purposes of this decision, we find that the prior art itself is
`
`sufficient to demonstrate the level of ordinary skill in the art at the time of
`
`the invention. See Okajima v. Bourdeau, 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 definition is required, we
`
`adopt Petitioner’s definition, because that definition is not disputed by Patent
`
`Owner for purposes of this decision and, further, is consistent with the
`
`disclosures of the asserted prior art. Pet. 7; Prelim. Resp. 20.
`
`
`the Patent Trial and Appeal Board,” 83 Fed. Reg. 51,340 (Oct. 11, 2018
`(amending 37 C.F.R. § 42.100(b) effective November 13, 2018).
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`7
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`IPR2018-01714
`Patent 7,968,569 B2
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`
`C. The Evidentiary Gap in the Petition
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`We discern, on this record, a failure of objective proof on the
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`dispositive question whether a method of administering lenalidomide,
`
`incorporating a 21+7 cyclic dosing regimen, would have been obvious at the
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`time of the invention. We expressly confine our decision, denying review,
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`to the following analysis of that defect in the patentability challenge.10
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`Specifically, in that regard, we find that the information advanced in support
`
`of the patentability challenge is deficient in at least three key respects,
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`resulting in an evidentiary gap in the Petition
`
`First, none of the five references identified in the asserted grounds of
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`unpatentability remotely suggests the 21+7 cyclic dosing regimen required
`
`by each challenged claim. See Pet. 2 (grounds chart); Ex. 1001, 38:64–
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`40:31 (claims 1–15); see also Ex. 1001, 32 (certificate of correction).
`
`Second, the Petition advances background references and opinion
`
`
`10 We decline to address the other arguments advanced by Patent Owner in
`support of a denial of review. See Prelim. Resp. 5–8 (seeking discretionary
`denial in view of the advanced nature of co-pending litigation), 8–11
`(requesting discretionary denial given the balance struck by the Hatch-
`Waxman Act or, alternatively, based on a failure to name a time-barred real
`party-in-interest), 15 n.5 (asserting that the references and argument
`advanced in the Petition “are cumulative to those evaluated during
`prosecution” and urging the Board to “exercise its discretion” to deny review
`on that basis). Nor do we resolve any factual issue that Patent Owner
`reserves a right to contest in the event of institution of review. See, e.g.,
`Prelim. Resp. 17 n.6, 27 n.11 (reserving a right to contest that an ordinarily
`skilled artisan would have understood that REVIMID was, at the time of the
`invention, the compound having the structure of lenalidomide), 17 n.7, 18
`n.8 (reserving a right to contest that certain references identified in the
`grounds of unpatentability are prior art to the challenged claims), 23 n.10
`(reserving a right to contest that other limitations, beyond the 21+7 cyclic
`dosing regimen, “are also missing from the alleged prior art”).
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`8
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`IPR2018-01714
`Patent 7,968,569 B2
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`testimony11 insufficient to show that an ordinarily skilled artisan would have
`
`recognized a 21+7 cyclic dosing regimen as “particularly common” or
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`“routine” in cancer therapies, much less in a combination therapy including
`
`lenalidomide and dexamethasone. Pet. 27–28 (bridging sentence). Third,
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`the Petition does not show sufficiently that the 21+7 cyclic dosing regimen
`
`would have been resolved for lenalidomide through “routine optimization.”
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`Id. at 28. Taken together, those deficiencies represent an evidentiary gap in
`
`the Petition that compels a denial of review. We address each in turn below.
`
`(a) The Five Asserted Prior Art References
`
`Our decision on institution is informed primarily by the combined
`
`disclosures of the asserted prior art references identified in the grounds of
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`unpatentability stated in the Petition. See 35 U.S.C. § 312(a)(3) (for each
`
`ground, a petition must identify supporting evidence “with particularity”);
`
`37 C.F.R. § 42.104(b)(2) (a petition must identify “the patents or printed
`
`publications relied upon for each ground”). Accordingly, we focus on the
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`five references identified in the grounds chart, set forth in the Petition, when
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`evaluating the sufficiency of the patentability challenge. Pet. 2 (grounds
`
`chart, identifying five references forming the basis for the challenge).
`
`Our reading of those five references substantiates Patent Owner’s
`
`view that none “teaches or suggests cyclic dosing of any agent—let alone
`
`the compound that was later known as lenalidomide—for 21 consecutive
`
`
`
`11 The Petition is supported by the Declaration of Dr. Guido Tricot.
`Ex. 1003. Based on Dr. Tricot’s statement of experience and qualifications,
`for purposes of this decision, we find that he is qualified to opine about the
`perspective of a person of ordinary skill in the art at the time of the invention
`claimed in the ’569 patent. Id. ¶¶ 4–9, Ex. A (appended to Ex. 1003).
`
`9
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`IPR2018-01714
`Patent 7,968,569 B2
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`days followed by a 7-day rest period.” Prelim Resp. 2–3. None of the five
`
`references mentions a rest period of any duration. See generally Ex. 1015
`
`(Palumbo); Ex. 1012 (the May Press Release); Ex. 1013 (the August Press
`
`Release); Ex. 1016 (Hideshima); Ex. 1028 (the ’230 patent).
`
`That point is borne out by the Petition, which directs us to no
`
`disclosure within any of the five asserted references for a teaching or
`
`suggestion of a rest period, much less the 7-day rest period included in
`
`the 21+7 cyclic dosing regimen of the claimed invention. See Pet. 11–12,
`
`14–23 (discussing the disclosures of the five asserted references, without
`
`identifying a suggestion for a rest period). In fact, the asserted “prior art is
`
`silent on the specific dosing” regimen applicable to the administration of
`
`lenalidomide. Prelim. Resp. 15. That gap in the teachings of the asserted
`
`prior art is not bridged by the background references or the opinion
`
`testimony advanced in the Petition, as discussed in the next section.
`
`(b) The Background References and Opinion Testimony
`
`Petitioner attempts to bridge the gap in the asserted prior art by
`
`directing us to an extensive list of background references and the opinion
`
`testimony of Dr. Tricot. Pet. 25–29, 34–35, 49; see Ex. 1003 ¶¶ 83–86, 99,
`
`100, 124. That effort falls short of satisfying the threshold showing
`
`necessary to support institution of an inter partes review. Specifically,
`
`Petitioner’s contention that “28-day treatment cycles and rest periods
`
`(including 7-day rest periods, in particular) were common practices in cancer
`
`treatments” is not supported adequately by objective proof. Pet. 49.
`
`The asserted background references do not establish that the 21+7
`
`cyclic dosing regimen would have been a “particularly common” or
`
`“standard” technique applied in cancer treatments. Pet. 27–28 (discussing
`
`10
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`IPR2018-01714
`Patent 7,968,569 B2
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`drug cycling in cancer treatments), 34–35 (attempting to map the 21+7
`
`cyclic dosing regimen of claim 1 to “standard techniques” in the art), 49
`
`(same for claim 13). On the contrary, although citing a plethora of
`
`background references, the Petition identifies only one that discloses a 21+7
`
`cyclic dosing regimen—and we agree with Patent Owner that the isolated
`
`“reference has nothing to do with any thalidomide analog, let alone
`
`lenalidomide; it is likewise silent on dexamethasone.” Prelim. Resp. 36; see
`
`Pet. 26 (identifying Exhibit 1048 as a background reference). We refer to
`
`that reference as Oken.12 Ex. 1048, 807–808 (disclosing a 21+7 cyclic
`
`dosing regimen for hexamethylmelamine).
`
`Oken administers hexamethylmelamine “as a single agent” in a
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`dosage of “200 mg/m2/day for the first 3 weeks of each 4-week cycle” in
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`“[p]atients with an established diagnosis of multiple myeloma.” Ex. 1048,
`
`807–808.13 In a modification of that regimen, Oken increases “the dose of
`
`hexamethylmelamine to 280 mg/m2/day orally on Days 1–21” with the
`
`addition of “pyridoxine at 100 mg orally three times a day.” Id. at 808. In a
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`“final modification” of the dosing regimen, 75 mg of prednisone is added
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`“orally on Days 1–7.” Id. Oken describes “hexamethylmelamine” as
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`“structurally related to triethylenemelamine” and within “a new class of
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`drugs with potential for the treatment of multiple myeloma.” Id. at 807.
`
`
`12 Oken, et al., “Contribution of Prednisone to the Effectiveness of
`Hexamethylmelamine in Multiple Myeloma,” Cancer Treatment Reports,
`71:807–811 (1987) (Ex. 1048).
`
`13 In our analysis, we cite the original page numbers of exhibits, not the page
`numbers added by a party.
`
`11
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`IPR2018-01714
`Patent 7,968,569 B2
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`Petitioner does not explain adequately how or why Oken’s dosing
`
`regimen, designed for the administration of hexamethylmelamine in
`
`combination with pyridoxine and prednisone, would have been recognized
`
`by an ordinarily skilled artisan at the time of the invention as applicable to
`
`the administration of lenalidomide in combination with dexamethasone.
`
`Pet. 26–27. Patent Owner observes, and we agree, that Petitioner “has not
`
`argued, because it cannot credibly argue, that hexamethylmelamine and
`
`lenalidomide are related compounds.” Prelim. Resp. 37. Those
`
`“compounds are not even remotely structurally similar,” as shown below.
`
`
`
`Id. at 37–38. The above figures illustrate and contrast the structures of
`
`hexamethylmelamine (on the left) and lenalidomide (on the right).
`
`Nor does Petitioner assert that hexamethylmelamine and lenalidomide
`
`“should be dosed similarly,” would be “similarly effective,” would work by
`
`“similar mechanisms,” or would exhibit a similar “degree of action” in
`
`patients diagnosed with multiple myeloma. Coalition for Affordable Drugs
`
`VIII, LLC v. The Trs. of the Univ. of Pa., Case IPR2015-01835, slip op. at
`
`14–15 (PTAB Mar. 7, 2016) (Paper 7) (instituting review only upon an
`
`adequate showing that the claimed and prior art compounds possessed
`
`“similar mechanisms,” would exhibit a similar “degree of action,” and that
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`12
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`IPR2018-01714
`Patent 7,968,569 B2
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`“existing data suggested that they should be dosed similarly”). The
`
`information presented here suggests the exact opposite.
`
`For example, the compounds are administered in different daily
`
`dosages and in combination with different secondary therapeutic agents.
`
`Compare Ex. 1048, 809, with Ex. 1001, 38:64–39:13 (claim 1); 40:7–25
`
`(claim 13). Further, Patent Owner advances persuasive information that the
`
`compounds would have been recognized as structurally unrelated and would
`
`have exhibited different degrees of action with respect to a serious known
`
`side-effect. See Prelim. Resp. 36 (“Hexamethylmelamine belongs to an
`
`entirely different class of chemicals that has never been disclosed to have
`
`any relationship to lenalidomide (or thalidomide or any thalidomide analog
`
`for that matter)”), 38 (explaining why those two compounds would have
`
`exhibited different degrees of action with respect to a “toxic” side-effect
`
`known as cytopenias14) (citing Ex. 1048, Abstract; Ex. 2010).
`
`The Petition advances two other background references that disclose
`
`a 7-day rest period, but neither suggests a 21-consecutive-day dosing period,
`
`
`14 “Cytopenias are conditions characterized by a shortage of blood cells.”
`Prelim. Resp. 32 n.12 (citing Ex. 1003 ¶ 58; Ex. 1012). Patent Owner
`directs us to persuasive evidence that lenalidomide was known to cause
`profound cytopenias, whereas “hexamethylmelamine was known in the art
`to produce ‘rapidly reversible cytopenias.’” Id. at 32–34, 38. On this
`record, it is unclear why an ordinarily skilled artisan would have selected
`“the dosing schedule for hexamethylmelamine” when seeking “to develop a
`treatment using” lenalidomide. Id. at 38. Even if we accept that Oken
`would have led an ordinarily skilled artisan to consider including a rest
`period when designing a dosing regimen for lenalidomide, on this record, we
`find that lenalidomide’s known tendency to cause profound cytopenias
`would have suggested a longer rest period than the 7-day rest period
`disclosed by Oken for use with hexamethylmelamine. Id. at 35.
`
`13
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`Patent 7,968,569 B2
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`and neither relates to the treatment of a blood cancer, such as multiple
`
`myeloma. Pet. 26–28 (citing Exs. 102015, 102316). Both references relate to
`
`compounds that are not shown to be “remotely structurally similar” to
`
`lenalidomide. Prelim. Resp. 39, 41 (for persuasive information on that
`
`point, including structural comparisons of the compounds). The first
`
`reference “concerns urothelial carcinoma, a solid tumor” that, on this record,
`
`is not shown to be comparable to “a blood cancer like” multiple myeloma,
`
`“where avoidance of myelosuppression is a chief concern.”17 Prelim.
`
`Resp. 40 (citing Ex. 1020). The second discloses information about a single
`
`patient “admitted to the hospital for investigation of loosening of a left total
`
`hip replacement.” Ex. 1023, 780. That single-patient case involved an
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`“antimicrobial” treatment designed to combat “chronic inflammation and
`
`infection” following the hip replacement. Id. The Petition does not explain
`
`adequately how or why those two background references suggest a 21+7
`
`cyclic dosing regimen for a combination therapy of lenalidomide and
`
`dexamethasone administered to treat multiple myeloma. Pet. 26–28.
`
`
`15 Gebbia, et al., “Single agent 2',2'-difluorodeoxycytidine in the treatment
`of metastatic urothelial carcinoma: a phase II study,” La Clinica
`Terapeutica, 150(1):11–15 (1999).
`
`16 Koo, et al., “Vancomycin-induced neutropenia,” Drug Intell. Clin.
`Pharm., 20(10):780–782 (1986).
`
`17 If cytopenias persist in a patient for a prolonged period of time, a more
`severe and potentially life-threatening condition known as myelosuppression
`can develop. Prelim. Resp. 32–33 (citing Ex. 2012, 4). Patients requiring
`many chemotherapy cycles “are especially prone to myelosuppression.” Id.
`at 33 (citing Ex. 2013, 5). Multiple myeloma dosing regimens are
`specifically “designed to minimize myelosuppression.” Id. at 33 (citing
`Ex. 2014, 1) (emphasis omitted); see id. (citing Exs. 2015, 2016, 2017) (for
`additional persuasive information on that point).
`
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`IPR2018-01714
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`
`Petitioner advances a host of other background references but none
`
`discloses a dosing regimen for lenalidomide or a therapy for multiple
`
`myeloma. See Pet. 25–28, 34–35, 49. And on the issue of cyclic dosing,
`
`each discloses either (1) no rest period, (2) “the familiar” 2-week rest period,
`
`or (3) a rest period that exceeds three weeks. Prelim. Resp. 43–45 (chart of
`
`background references) (emphasis omitted). Accordingly, on this record, we
`
`find that those background references do not bridge the evidentiary gap in
`
`the disclosures of the five applied references. See supra Section II.C (a).
`
`Nor does Dr. Tricot’s opinion testimony. Dr. Tricot identifies no
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`persuasive objective proof that the 21+7 cyclic dosing regimen for
`
`lenalidomide required by each challenged claim would have been obvious or
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`routine at the time of the invention. See Ex. 1003 ¶¶ 83–86, 99, 100, 124
`
`(relying on the same collection of background references asserted in the
`
`Petition); see especially id. at ¶ 84 (relying on evidence of “the familiar 2-
`
`week interval between cycles” that was known “to accommodate the
`
`recovery time of human bone marrow”). Further, Dr. Tricot’s testimony is
`
`undercut by his own work, which was published at about the time of the
`
`invention. Specifically, during the relevant period, “Dr. Tricot dosed the
`
`compound that Petitioner claims is lenalidomide without using the
`
`purportedly ‘routine’ 7-day rest period.” Prelim. Resp. 27; Ex. 2010, 775a
`
`(abstract, disclosing 4-week dosing cycles without any rest period);
`
`Ex. 2011, 450a (abstract, explaining “[d]ose limiting toxicity was cytopenia”
`
`but disclosing “monthly” lenalidomide “cycles” without any rest period).18
`
`
`18 For purposes of this decision, we infer no deceptive intent from
`Petitioner’s failure to identify Exhibit 2011 in Dr. Tricot’s list of abstracts
`and other publications. Ex. 1003 (Ex. A, 28–71, attached thereto).
`
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`
`On this record, Dr. Tricot’s testimony is insufficient to support
`
`institution of review. His ultimate conclusion that an ordinarily skilled
`
`artisan “would have been motivated to incorporate a 7-day rest period into
`
`[a] 28-day lenalidomide treatment cycle because introduction of rest periods
`
`into cancer treatments was routine in the art” is not supported adequately by
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`objective proof of record. Id. ¶ 99 (for claim 1), ¶ 124 (for claim 13, opining
`
`that the ordinarily skilled artisan “would have considered it obvious to treat
`
`[multiple myeloma] by administering lenalidomide and dexamethasone on a
`
`28-day cycle with a 7-day rest period based on both routine practices in
`
`cancer treatment and on the prior art”); see 37 C.F.R. § 42.65(a) (“Expert
`
`testimony that does not disclose [] underlying facts or data” adequate to
`
`support a stated opinion “is entitled to little or no weight.”).
`
`(c) Routine Optimization
`
`The Petition includes several assertions that the 21+7 cyclic dosing
`
`regimen of the claimed invention would have been resolved by an ordinarily
`
`skilled artisan through “routine optimization.” Pet. 28 (citing Ex. 1003 ¶ 86)
`
`(incorporating a one-week rest period into a cancer drug therapy would have
`
`been “a routine optimization”), 35 (achieving the 21+7 cyclic dosing
`
`regimen of claim 1 would have represented an exercise of “routine
`
`optimization”), 49 (the 21+7 cyclic dosing regimen of claim 13 is “based on
`
`standard techniques and routine optimization”).
`
`The Petition does not show sufficiently that a rest period in a cyclic
`
`dosing regimen for lenalidomide would have been established as a result-
`
`effective variable at the time of the invention. Id. As Patent Owner points
`
`out, and as explained above, the Petition advances no prior art reference, or
`
`combination of references, that discloses or suggests the feasibility or
`
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`IPR2018-01714
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`viability of a rest period in a cyclic dosing regimen for any compound that
`
`would have been recognized as even “remotely structurally similar” to
`
`lenalidomide. Prelim. Resp. 39; see Hospira, Inc. v. Genentech, Inc., Case
`
`IPR2017-00804, slip op. at 23–24 (PTAB Oct. 03, 2018) (Paper 83)
`
`(asserted prior art did not disclose or suggest “the feasibility or viability of a
`
`tri-weekly dosing regimen” of trastuzumab, where “a tri-weekly antibody
`
`dosing regimen of trastuzumab was not found in any prior art reference”).
`
`It is unclear on this record how or why the five asserted prior art
`
`references, which nowhere mention a rest period of any duration, would
`
`have illuminated a path toward a 21+7 cyclic dosing regimen for
`
`lenalidomide as a matter of “routine optimization.” Pet. 28; see id. at 2
`
`(grounds chart, identifying five references as the basis for the patentability
`
`challenge); see also supra Section II.C (a) (for our analysis of the five
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`asserted prior art references, including their failure to disclose a rest period
`
`of any duration). Petitioner’s information, on that point, does not meet the
`
`threshold showing necessary to support institution of an inter partes review.
`
`III. CONCLUSION
`
`Based on the information advanced in the Petition and the Preliminary
`
`Response, for reasons stated above, we find no “reasonable likelihood that
`
`the petitioner would prevail with respect to at least 1 of the claims
`
`challenged in the petition.” 35 U.S.C. § 314(a). Accordingly, we deny the
`
`Petition and do not institute an inter partes review.
`
`IV. ORDER
`
`It is
`
`
`
`ORDERED that under 35 U.S.C. § 314(a), the petition is denied and
`
`no inter partes review is instituted.
`
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`IPR2018-01714
`Patent 7,968,569 B2
`
`PETITIONER:
`
`
`Stephen M. Hash
`Margaret J. Sampson
`Jeffrey S. Gritton
`BOTTS L.L.P.
`stephen.hash@bakerbotts.com
`margaret.sampson@bakerbotts.com
`jeff.gritton@bakerbotts.com
`
`
`PATENT OWNER:
`
`F. Dominic Cerrito
`Frank C. Calvosa
`QUINN EMANUEL URQUHART & SULLIVAN, LLP
`nickcerrito@quinnemanuel.com
`frankcalvosa@quinnemanuel.com
`
`
`J. Patrick Elsevier, Ph.D
`CELGENE CORPORATION
`pelsevier@celgene.com
`
`Anthony M. Insogna
`Christopher J. Harnett
`Cary Miller, Ph.D.
`JONES DAY
`aminsogna@jonesday.com
`charnett@jonesday.com
`cmiller@jonesday.com
`
`
`18
`
`