Trials@uspto.gov
` 571-272-7822
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`
`
`
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` Paper 29
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` Entered: September 24, 2020
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`SANDOZ INC.,
`Petitioner,
`v.
`PHARMACYCLICS LLC,
`Patent Owner.
`____________
`
`IPR2019-00865
`Patent 9,795,604 B2
`____________
`
`
`Before SHERIDAN K. SNEDDEN, SUSAN L. C. MITCHELL, and
`DAVID COTTA, Administrative Patent Judges.
`
`COTTA, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`Determining Some Challenged Claims Unpatentable
`Denying in Part and Dismissing in Part Motion to Strike
`35 U.S.C. § 318(a); 37 C.F.R. § 42.5; 37 C.F.R. § 42.20
`
`
`
`
`
`
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`IPR2019-00865
`Patent 9,795,604 B2
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`
`I.
`
`INTRODUCTION
`
`Sandoz Inc. (“Petitioner”) filed a Petition requesting an inter partes
`review of claims 1, 4, 6–10, 13, 15, 24, 28–31, 35, 39, 43–46, 50–53, and 55
`of U.S. Patent No. 9,795,604 B2 (Ex. 1001, “the ’604 patent”).1 Paper 2
`(“Pet.”). Pharmacyclics LLC (“Patent Owner”) filed a Preliminary
`Response to the Petition. Paper 6 (Prelim. Resp.).2 We determined, based
`on the information presented in the Petition and Preliminary Response, that
`there was a reasonable likelihood that Petitioner would prevail in showing
`that at least one of the challenged claims was unpatentable over the cited art.
`Pursuant to 35 U.S.C. § 314, the Board instituted trial on September 26,
`2019. Paper 8 (“Institution Decision” or “Inst. Dec.”).
`Patent Owner filed a Response to the Petition (Paper 13, “PO Resp.”),
`Petitioner filed a Reply to Patent Owners’ Response (Paper 17, “Reply”),
`and Patent Owner filed a Sur-Reply (Paper 24, “Sur-Reply”). With our prior
`authorization, Patent Owner filed a Motion to Strike Improper Reply
`Arguments (Paper 25, “Mot.”), Petitioner filed an Opposition to Patent
`Owner’s Motion to Strike (Paper 26, “Mot. Opp.”), and Patent Owner filed a
`Reply in Support of its Motion to Strike (Paper 27, “Mot. Reply”).
` On March 21, 2019, the parties presented arguments at an oral
`hearing. The transcript of the hearing has been entered into the record.
`Paper 28 (“Tr.”).
`We have jurisdiction under 35 U.S.C. § 6. We issue this Final Written
`Decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. Based on
`
`
`1 Petitioner identifies Sandoz Inc. and Lek Pharmaceuticals D.D. as the real
`parties in interest. Pet. 2.
`2 Patent Owner identifies Pharmacyclics LLC, AbbVie Inc, and Janssen
`Biotech, Inc. as the real parties in interest. Paper 4, 1.
`2
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`the record before us, we conclude that Petitioner has demonstrated, by a
`preponderance of the evidence, that claims 1, 6–10, 24, 35, 39, and 55 of the
`’604 patent are unpatentable, but that Petitioner has not demonstrated, by a
`preponderance of the evidence, that claims 4, 13, 15, 28–31, 43–46 and 50–
`53 are unpatentable. We deny in part and dismiss in part Patent Owners’
`Motion to Strike.
`
`A.
`
`Related Proceedings
`
`Petitioner and Patent Owner represent that the ’604 patent was
`asserted in Pharmacyclics LLC v. Zydus Worldwide DMCC, Civ. No. 1:18-
`cv-00275-CFC (D. Del.), which has been consolidated with Pharmacyclics
`LLC v. Fresenius Kabi USA, LLC, 1:18-cv-00192-CFC (D. Del). Pet. 2;
`Paper 4, 1. Petitioner and Patent Owner also represent that U.S. Patent
`Application No. 15/586,058, filed May 3, 2017, is related to the ’604 patent.
`Pet. 2; Paper 4, 1.
`
`B.
`
`The ’604 Patent (Ex. 1001)
`
`The ’604 patent issued October 24, 2017, identifying John C. Byrd,
`Jason A. Dubovsky, Natarajan Muthusamy, Amy Jo Johnson, and David
`Miklos as inventors. Ex. 1001, at codes (45), (72). The patent teaches:
`Chronic graft versus host disease (cGVHD) is the most
`common long-term complication following allogeneic stem cell
`transplant (SCT), affecting 30-70% of patients who survive
`beyond the first 100 days. cGVHD and its associated immune
`deficiency have been identified as a leading cause of
`non-relapse mortality (NRM) in allogeneic SCT survivors.
`Id. at 1:29–36. The ’604 patent discloses “methods for treating and
`preventing graft versus host disease using . . . an ACK inhibitor such as
`ibrutinib.” Id. at Abstract.
`
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`
`C.
`
`Challenged Claims
`
`Petitioner challenges claims 1, 4, 6–10, 13, 15, 24, 28–31, 35, 39, 43–
`46, 50–53, and 55 of the ’604 patent. Claim 1 is representative and is
`reproduced below:
`
`A method of treating chronic graft versus host disease
`1.
`(GVHD) comprising administering to a patient having chronic
`GVHD a therapeutically effective amount of a compound of the
`structure:
`
`
`thereby treating the chronic GVHD in the patient.
`
`Ex. 1001, 75:41–68.
`
`D.
`
`Prior Art and Asserted Grounds
`
`We instituted trial based on each challenge to the patentability of the
`’604 patent presented in the Petition. The Petition challenged the
`patentability of claims 1, 4, 6–10, 13, 15, 24, 28–31, 35, 39, 43–46, 50–53,
`and 55 of the ’604 patent on the following grounds:
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`
`Claims Challenged
`1, 4, 6–10, 13, 15, 24,
`28–31, 35, 39, 43–46,
`50–53, 55
`1, 4, 6–10, 13, 15, 24,
`28–31, 35, 39, 43–46,
`50–53, 55
`1, 4, 6–10, 13, 15, 24,
`28–31, 35, 39, 43–46,
`50–53, 55
`1, 4, 6–10, 13, 15, 24,
`28–31, 35, 39, 43–46,
`50–53, 55
`
`35 U.S.C. §
` 102
`
`Reference(s)/Basis
`The ’085 publication3
`
` 103
`
` 103
`
` 103
`
`The ’085 publication
`
`The ’085 publication,
`Shimabukuro-Vornhagen,4
`Herman5
`The ’085 publication,
`Shimabukuro-Vornhagen,
`Uckun6
`
`Pet. 30–31.
`Petitioner submits the Declaration of Dr. James L. Ferrara (Ex. 1006)
`in support of the Petition. Patent Owner submits the Declaration of Dr. John
`Koreth (Ex. 2055) in support of its Response to the Petition.
`
`E.
`
`Person of Ordinary Skill in the Art
`
`Factual indicators of the level of ordinary skill in the art include “the
`various prior art approaches employed, the types of problems encountered in
`
`
`3 Goldstein, US Patent Publication No. 2015/0140085 A1, published May
`21, 2015 (Ex. 1002, “the ’085 publication”).
`4 Shimabukuro-Vornhagen, et al., The Role of B Cells in the Pathogenesis of
`Graft-Versus-Host Disease, 114(24) BLOOD 4919–4927 (2009) (Ex. 1003,
`“Shimabukuro-Vornhagen”).
`5 Herman, et al., Bruton Tyrosine Kinase Represents a Promising
`Therapeutic Target for Treatment of Chronic Lymphocytic Leukemia and is
`Effectively Targeted by PCI-32765, 117(23) BLOOD 6287–6296 (2011)
`(Ex. 1004, “Herman”).
`6 Uckun, et al., Bruton’s Tyrosine Kinase as a Molecular Target in
`Treatment of Leukemias and Lymphomas as well as Inflammatory Disorders
`and Autoimmunity, 20(11) EXPERT OPIN. THER. PATENTS 1457–1470 (2010)
`(Ex. 1005, “Uckun”).
`
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`the art, the rapidity with which innovations are made, the sophistication of
`the technology involved, and the educational background of those actively
`working in the field.” Jacobson Bros., Inc. v. U.S., 512 F.2d 1065, 1071
`(Ct. Cl. 1975); see also Orthopedic Equip. Co., v. U.S., 702 F.2d 1005, 1011
`(Fed. Cir. 1983) (quoting with approval Jacobson Bros.).
`Petitioner contends that the person of ordinary skill “would have had
`an advanced degree in the field of medicine with additional, specialized
`training, such as a fellowship in Hematology/Oncology as well as several
`years’ experience specializing in transplantation.” Pet. 31; Ex. 1006 ¶¶ 53.
`Petitioner also contends that the POSA would “preferably have had some
`experience with pharmaceutical compositions for treating GVHD or related
`conditions.” Pet. 31–32.
`In our Institution Decision, we accepted Petitioner’s definition of the
`POSA. Inst. Dec. 5–6. Patent Owner does not challenge the definition set
`forth by Petitioner and adopted in our Institution Decision. See generally
`PO Resp, Sur-Reply. The fully developed trial record supports that this
`definition is consistent with the level of skill reflected in asserted prior art
`references and in the ’604 patent. Accordingly, in this decision, we apply
`Petitioner’s definition of the POSA.
`
`F.
`
`Claim Construction
`
`We construe claims “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).” 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, 51,340, 51,358 (Oct. 11, 2018) (amending
`37 C.F.R. § 42.100(b) effective November 13, 2018) (now codified at 37
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`C.F.R. § 42.100(b) (2019)). Therefore, we construe the challenged claims
`under the framework set forth in Phillips v. AWH Corp., 415 F.3d 1303,
`1312–19 (Fed. Cir. 2005) (en banc). Under this framework, claim terms are
`given their ordinary and customary meaning, as would have been understood
`by a person of ordinary skill in the art, at the time of the invention, in light of
`the language of the claims, the specification, and the prosecution history of
`record. Id. Only those terms that are in controversy need be construed, and
`only to the extent necessary to resolve the controversy. See Nidec Motor
`Corp. v. Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed.
`Cir. 2017) (citing Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795,
`803 (Fed. Cir. 1999)).
`Patent Owner requests that we construe what it terms “efficacy
`limitations” in claims 6, 7, 8, 29, 30, 31, 44, 45, 46, 51, 52, 53, and 55.
`PO Resp. 5–16. These limitations recite particular patient outcomes
`resulting from the administration of ibrutinib in dependent claims 6, 7, 8, 29,
`30, 31, 44, 45, 46, 51, 52, and 53. The particular patient outcomes recited in
`these dependent claims are summarized in the Table below.
`Dependent Claims
`Text of limitations
`6, 29, 44, 51
`“wherein, following administration
`of the compound, the patient
`achieves partial response (PR),
`wherein the PR is an objective
`response in one involved organ in
`the patient with no evidence of
`progression elsewhere and no
`requirements for additional systemic
`therapy.”
`
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`Patent 9,795,604 B2
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`
`Dependent Claims
`7, 30, 45, 52
`
`8, 31, 46, 53
`
`Text of limitations
`“wherein, following administration
`of the compound, the patient
`achieves complete response (CR),
`wherein the CR is a complete
`restoration of symptoms attributable
`to GVHD.”
`“wherein, following administration
`of the compound, the severity of the
`GVHD is reduced.”
`
`
`Patent Owner also requests that we construe the terms “method of treating,”
`which is recited in claims 1 and 55, and the limitation “thereby treating the
`chronic GVHD in the patient,” which is recited in claim 1. PO Resp. 6.
`In its Petition and in its Reply, Petitioner argues that these claim
`limitations merely state the result of performing the method set forth in the
`claim and add nothing to the patentability or substance of the claim. Pet. 40;
`Pet. Reply 2. Accordingly, Petitioner contends that these limitations are not
`entitled to patentable weight. Id. Patent Owner contends that the recited
`patient outcomes should be given patentable weight because they “are
`material to patentability and express the inventive aspect of the claimed
`invention.” PO Resp. 6.
`Although the parties dispute the proper claim construction of these
`claim terms, we determine that no explicit construction of these terms is
`necessary to resolve this dispute because, as discussed infra 11–12 and 27–
`30, we find that these limitations are inherently present in the cited art. See
`Nidec, 868 F.3d at 1017 (“[W]e need only construe terms ‘that are in
`controversy, and only to the extent necessary to resolve the controversy’”
`(quoting Vivid Techs., 200 F.3d at 803)); Wellman, Inc. v. Eastman Chem.
`
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`Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only be
`construed ‘to the extent necessary to resolve the controversy’”).
`
`II. GROUND 1: ANTICIPATION BY THE ’085 PUBLICATION
`
`Petitioner asserts that the ’085 publication anticipates claims 1, 4, 6–
`10, 13, 15, 24, 28–31, 35, 39, 43–46, 50–53, and 55 of the ’604 patent.
`Pet. 34–44. Patent Owner opposes. PO Resp. 16–21, 53–56. We have
`reviewed Petitioner’s and Patent Owner’s assertions, as well as the evidence
`of record, and, for the reasons discussed below, we conclude that Petitioner
`has demonstrated by a preponderance of the evidence, that claims 1, 6–10,
`24, 35, 39, and 55 of the ’604 patent are anticipated by the ’085 publication,
`but that Petitioner has not demonstrated, by a preponderance of the evidence,
`that claims 4, 13, 15, 28–31, 43–46 and 50–53 are anticipated by the ’085
`publication.
`
`Disclosures of the Asserted Prior Art
`
`A.
`The ’085 Publication
`
`The ’085 publication discloses “[o]ral pharmaceutical formulations of
`ibrutinib . . . and use of these formulations for the treatment of diseases
`treatable by ibrutinib such as . . . autoimmune diseases.” Ex. 1002, Abstract.
`Among the autoimmune diseases disclosed as treatable using the oral
`pharmaceutical formulations of the ’085 publication is graft versus host
`disease. Id. ¶ 98 (“In another embodiment of this aspect, the patient in need
`is suffering from a heteroimmune condition or disease, e.g., graft versus host
`disease.”). According to the ’085 publication, “[t]he therapeutically
`effective amount of ibrutinib . . . can be from about 20 mg per day to about
`450 mg/day, or 20 mg/day to about 420 mg/day; or about 20 mg/day or 30
`mg/day to about 300 or 350 mg/day; or about 30 or 50 mg/day to about 200,
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`or 220 or 250 mg/day; or about 30 or 50 mg/day to about 100 or 150 mg/day
`and can be administered in single or multiple doses.” Id. ¶ 30.
`
`B.
`
`Analysis
`
`Claim 1
`
`Petitioner contends that the ’085 publication discloses all of the
`limitations of claim 1. Petitioner acknowledges that the ’085 publication
`discloses treating graft versus host disease rather than chronic graft versus
`host disease, as claimed. Pet. 35. However, Petitioner contends that there
`are only two types of graft versus host disease – chronic and acute. Id.
`Supported by the testimony of Dr. Ferrara, Petitioner asserts that a POSA
`would have “at once envisaged that this disclosure pertains to both acute and
`chronic GVHD.” Id. (citing Ex. 1006 ¶ 77). Petitioner thus contends that
`the ’085 publication anticipates treatment of chronic GVHD. Id. Petitioner
`cites Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356,
`1361 (Fed. Cir. 2012) and Kennametal, Inc. v. Ingersoll Cutting Tool Co.,
`780 F.3d 1376, 1381 (Fed. Cir. 2015) as supporting the proposition that a
`species within a genus is anticipated where the genus was of “such a defined
`and limited class that one of ordinary skill in the art could ‘at once envisage’
`each member of the genus.” Pet. 35.
`With respect to the requirement of claim 1 for “administering . . . a
`
`therapeutically effective amount,” Petitioner points to the disclosure in the
`’085 publication of “therapeutically effective” amounts of ibrutinib.
`Pet. 36–37 (citing Ex. 1002 ¶¶ 30, 120). Petitioner argues that the term
`“therapeutically effective amount” in claim 1 must encompass the amounts
`
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`recited in claim 5, which depends from claim 1, and which recites amounts
`corresponding to those disclosed in the ’085 publication. Id. at 14.
`
`With respect to the “thereby treating the chronic GVHD in the
`patient” recitation in claim 1, Petitioner argues that to the extent it is
`limiting, the ‘085 publication discloses it both expressly and inherently. Id.
`at 37.
` Based on the arguments and evidence presented during this review,
`
`we find that Petitioner has shown by a preponderance of the evidence that
`the ’085 publication discloses each and every limitation of claim 1 of the
`’085 publication. As discussed above, the ’085 publication discloses
`treatment of GVHD. See supra p. 9. Although, the ’085 publication does
`not specify whether such GVHD is chronic or acute, Petitioner provides
`evidence that there are only two types of GVHD, acute and chronic.
`Ex. 1006 ¶ 29 (cited at Pet. 7). Accordingly, we understand the ’085
`publication’s reference to GVHD to disclose a genus comprised of acute and
`chronic GVHD. Petitioner offers the testimony of Dr. Ferrara, which we
`credit as supported by the record, that the POSA, “upon seeing the ’085
`Publication’s disclosure directed to treating ‘graft versus host disease,’ . . .
`would have immediately understood and envisioned that the ’085
`Publication’s disclosure of treating GVHD includes specifically chronic
`GVHD.” Id. ¶ 77. The trial record thus supports that the POSA would have
`understood the ’085 publication to disclose treatment of chronic GVHD.
`
`The trial record also supports that the ’085 publication discloses
`administration of a therapeutically effective amount of ibrutinib.
`Ex. 1002 ¶¶ 30, 120; Ex. 1006 ¶¶ 78–82. And, to the extent the recitation
`“thereby treating the chronic GVHD in the patient” is considered to limit
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`claim 1, the ’085 publication discloses such treatment (Ex. 1002 ¶¶ 94, 98,
`117–120) and the trial record supports that administration of a
`“therapeutically effective amount” of ibrutinib will inherently “treat”
`cGVHD (Ex. 1006 ¶ 83; see also, Ex. 1001, 26:47–53 (’604 patent defining
`the term “treating” broadly)).
`Patent Owner no longer disputes that the ’085 publication teaches
`treatment of cGVHD, but instead argues that the ’085 publication does not
`anticipate the ’604 patent because it does not enable treatment of cGVHD
`with ibrutinib. PO Resp. 53–56.7 More specifically, Patent Owner argues
`that the ’085 publication does not enable treatment of cGVHD “because of
`its lack of guidance and working examples in an exceedingly unpredictable
`field.” PO Resp. 53. According to Patent Owner, cGVHD was “poorly
`understood” and “widely recognized as an unpredictable disease that was
`exceedingly difficult to treat.” Id. Research on cGVHD was hampered by
`the absence of “adequate animal models or reliable biomarkers” and “the
`field was inundated with unreliable studies.” Id. Patent Owner contends
`that, as a result, “the prior art recognized that the ‘trial-and-error system’
`was the ‘only way’ to identify drugs effective for cGVHD.” Id. at 53–54.
`
`
`7 In its Preliminary Response, Patent Owner also argued that the ’085
`publication did not anticipate claim 1 because it did not disclose treatment of
`chronic GVHD and because Petitioner’s anticipation arguments required
`picking and choosing among disclosures. Prelim. Resp. 38–41. These
`arguments are waived because Patent Owner did not pursue them in its post-
`institution briefing. See Paper 9, 7 (“Patent Owner is cautioned that any
`arguments for patentability not raised in the response may be deemed
`waived.”). Even if we were to consider these arguments, we would find
`them unpersuasive for the reasons set forth in our Institution Decision at 14–
`16.
`
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`Against this backdrop, Patent Owner contends that the ’085 publication
`provides insufficient guidance to enable the POSA to practice the claimed
`invention. Id. at 31. Patent Owner explains:
`[T]he ’085 Publication contains no in vitro, preclinical, or
`clinical data indicating that ibrutinib could treat cGVHD, which
`it fails even to mention. EX2055, ¶¶124–130. The ’085
`Publication is devoid of working examples for treating any
`disease. See generally EX1002. Instead, each of the six
`examples (five of which are prophetic) relates to formulations
`untethered to treating any particular disease. Supra § VI.A.1.
`The text of the ’085 Publication likewise provides no guidance
`for treating cGVHD. Instead, “graft versus host disease” is
`generically identified among over 150 diseases. EX1002,
`[0096]–[0100]. Although the ’085 Publication provides
`generalized disclosures about “therapeutically effective
`amounts,” that disclosure does not specify any particular
`disease and is taught to “vary depending on the compound, the
`disease and its severity[,] and the age, weight, etc. of the
`mammal to be treated.” Supra § VI.A.1; EX1002, [0030],
`[0120]. In other words, while teaching that many factors must
`be considered to determine a “therapeutically effective amount”
`for a particular disease, the ’085 Publication provides no
`guidance as to how one would effectively treat cGVHD,
`especially against the backdrop of unpredictability in this field.
`EX2055, ¶¶121–122.
`PO Resp. 54–55. We are not persuaded.
`
`Prior art publications and patents are presumed to be enabled. In re
`Antor Media Corp., 689 F.3d 1282, 1287–88 (Fed. Cir. 2012); Amgen Inc. v.
`Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003). Here,
`the ’085 publication discloses “[o]ral pharmaceutical formulations of
`ibrutinib and/or a pharmaceutically acceptable salt thereof.” Ex. 1002,
`Abstract. It also discloses that these formulations may be used to treat a
`patient “suffering from a heteroimmune condition or disease, e.g., graft
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`versus host disease” (id. ¶ 98) by “administering to the patient . . . a solid
`oral dosage form disclosed herein.” Id. ¶ 96.
`We acknowledge Patent Owner’s argument that the ’085 publication
`does not include instructions specific to cGVHD. However, per claim 1, all
`that is required to treat cGVHD is to administer a therapeutically effective
`dose of ibrutinib, which the ’085 publication teaches. Ex. 1001, 75:40–67
`(claim 1); see also, Tr. 37–38 (MR. RAICH: “. . . The ’085 Publication as I
`mentioned earlier, has no guidance whatsoever in terms of how to treat the
`disease . . . . JUDGE COTTA: What guidance is needed beyond just
`identifying a dose? MR. RAICH: I would say a dose and a dosing regimen
`would be an appropriate thing to provide in terms of how to actually treat the
`disease.”).
`The ’085 publication provides general guidance – not specific to any
`one disease – on administering therapeutically effective doses of ibrutinib
`and on the frequency with which those doses should be administered. In
`describing one of the disclosed solid oral dosage forms, it states:
`The therapeutically effective amount of ibrutinib and/or a
`pharmaceutically acceptable salt thereof when administered into
`the intestine by bypassing the stomach can be from about 20 mg
`per day to about 450 mg/day, or 20 mg/day to about 420
`mg/day; or about 20 mg/day or 30 mg/day to about 300 or 350
`mg/day; or about 30 or 50 mg/day to about 200, or 220 or 250
`mg/day; or about 30 or 50 mg/day to about 100 or 150 mg/day
`and can be administered in single or multiple doses.
`Ex. 1002 ¶ 30; see also, id. ¶26. Similarly, in defining the term
`“therapeutically effective amount,” the ’085 publication teaches:
`The “therapeutically effective amount” will vary depending on
`the compound, the disease and its severity and the age, weight,
`etc., of the mammal to be treated. The therapeutically effective
`amount of ibrutinib and/or a pharmaceutically acceptable salt
`
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`
`thereof when administered in the intestine can be from about 20
`mg per day to about 450 mg/day, or any permu[t]ations and
`combinations thereof. Such as 20 mg/day to about 420 mg/day;
`or about 20 mg/day or 30 mg/day to about 300 or 350 mg/day;
`or about 30 or 50 mg/day to about 200, or 220 or 250 mg/day;
`or about 30 or 50 mg/day to about 100 or 150 mg/day and can
`be administered in single or multiple doses.
`Id. ¶ 120. The doses described in the ’085 publication correlate with those
`identified as “therapeutically effective” in the ’604 patent. Compare id.
`¶¶ 30, 120 with Ex. 1001, 76:7–10 (claim 5).
`
`Patent Owner, through the testimony of Dr. Koreth, observes that the
`’085 publication provides “no dose or doses of ibrutinib as part of [the]
`eighth aspect for treating any particular disease, including GVHD.”
`Ex. 2055 ¶ 125. Dr. Koreth also testifies the ’085 publication’s disclosure of
`a “therapeutically effective amount” of ibrutinib “is insufficient to provide
`any information about a therapeutically effective dose of ibrutinib to treat
`cGVHD, especially as the prior art does not disclose any ibrutinib dose for
`the treatment of patients with cGVHD.” Id. ¶ 126. We do not find this
`persuasive.
`We find that the POSA would readily have connected the disclosure
`in the ’085 publication that in an “eighth aspect of the present disclosure”
`ibrutinib can be used to treat GVHD with the disclosure of dosages of
`ibrutinib provided in elsewhere in the ’085 publication. In this regard, we
`note that the “eighth aspect” is directed to treating an autoimmune disease,
`including GCHD, by “administering . . . a solid oral dosage form disclosed
`herein,” and the “solid oral dosage form[s] disclosed” in the ’085 publication
`specify doses of ibrutinib and frequency of administration. See, e.g., Ex.
`1002, ¶¶ 26 (identifying ranges of dosages for a “forth aspect” of the present
`disclosure, which aspect was previously described as providing a “solid oral
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`dosage” form); 30 (same), 96 (disclosing treatment of autoimmune disease
`by administering “a solid oral dosage form disclosed herein” as an eighth
`aspect of the present disclosure), 98 (specifying that the autoimmune disease
`is graft versus host disease). We are persuaded that the POSA would have
`understood the “solid oral dosage form disclosed herein” (id. ¶ 96) to
`include the solid oral dosage forms disclosed the “forth aspect” of the
`disclosure of the ’085 patent (id. ¶¶ 26, 30), particularly as those doses are
`consistent with the doses described as being therapeutically effective (id. ¶
`120). KSR Intern. Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007) (“A person
`of ordinary skill is also a person of ordinary creativity, not an automaton.”).
`For similar reasons, we are not persuaded that, as Dr. Koreth seems to
`suggest, a POSA would have required a statement specific to ibrutinib in
`order to connect the teaching of the ’085 patent to treat GVHD with the
`disclosure of therapeutically effective amounts of ibrutinib. Ex. 2055 ¶ 126;
`Ex. 1002 ¶¶ 98, 120; see also Ex. 1006 ¶¶ 96–101 (Dr. Ferrara testimony on
`what the POSA would have understood from the disclosure of the ’085
`publication regarding dosing). Rather, we find that a POSA would naturally
`have connected the teaching of treating GVHD with the disclosed
`therapeutically effective amounts of ibrutinib.
`In sum, the record does not support a conclusion that a POSA,
`provided with both information regarding therapeutically effective amounts
`of ibrutinib and the teaching that ibrutinib can be used to treat GVHD,
`would have required undue experimentation to carry out the claimed method
`by selecting a patient appropriate ibrutinib dosage based on age, weight, and
`other disclosed parameters. Indeed, it is not clear that the POSA would have
`required any experimentation, much less undue experimentation, as all that
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`is required to carry out the claimed method is to do what the ’085
`publication suggests – administer a therapeutically effective amount of
`ibrutinib.
`We acknowledge Patent Owner’s argument that cGVHD is a poorly
`understood, unpredictable disease, and that the prior art relied on trial-and-
`error to identify drugs effective for cGVHD. However, we are not
`persuaded that these difficulties, and the other difficulties identified by
`Patent Owner in its briefing (see PO Resp. 53–56), are sufficient to rebut the
`presumptively enabled teaching of the ’085 publication that ibrutinib can be
`used to treat GVHD. In this regard, we are guided by our reviewing court’s
`decision in Rasmussen v. SmithKline Beecham Corp. 413 F.3d 1318 (Fed.
`Cir. 2005). The issue in Rasmussen was whether the disclosure of a prior art
`reference, EP ’383, enabled the use of finasteride to treat prostate cancer so
`as to anticipate the patent at issue. Id. at 1325–1326. The Board made
`several findings akin to those argued by Patent Owner here. Specifically, it
`found:
`(1) that in light of the state of the art at the time of the
`publication of EP ‘383 in 1988, there was no reasonable
`scientific basis for a person of ordinary skill in the art to
`conclude that the claimed method would be effective in treating
`prostate cancer, and (2) that given the lack of proof provided in
`the publication itself, a person of ordinary skill in the art as of
`the publication date of EP ‘383 would not have believed that
`the method described in EP ‘383 would be effective.
`Id. at 1326. Our reviewing court found that these findings were “insufficient
`to support the Board’s conclusion that EP ’383 is not an enabling reference
`for purposes of anticipation.” Id; see also, Bristol-Myers Squibb v. Ben
`Venue Laboratories, Inc., 246 F.3d 1368, 1370, 1378 (Fed. Cir. 2001)
`(finding that prior art reference anticipated a claim directed to a “method for
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`reducing hematologic toxicity in a cancer patient undergoing [t]axol
`treatment comprising parenterally administering to said patient an
`antineoplastically affective amount of . . . taxol” even though the reference
`showed that carrying out the method lacked efficacy).
`
`Patent Owner relies on Impax Laboratories, Inc. v. Aventis
`Pharmaceuticals, Inc., 545 F.3d 1312 (Fed. Cir. 2008) to support its
`argument that the ’085 publication does not enable the method it discloses.
`PO Resp. 55–56. Impax, however, is readily distinguishable. In Impax, our
`reviewing court found that a prior art reference did not enable the use of
`riluzole to treat ALS where: 1) “nothing in [the prior art reference] would
`direct one skilled in the art to recognize that riluzole could be used to treat
`ALS,” 2) the “dosage guidelines [were] broad and not specific to any of the
`hundreds of formula I compounds of the claimed invention or to any of the
`listed diseases,” and 3) the prior art reference “tie[d] the dosing information
`to ‘the compounds of the invention’ and specifically exclude[d] riluzole
`from the invention.” Id. at 1315. Here, the ’085 publication specifically
`teaches that ibrutinib can be used to treat GVHD (Ex. 1002 ¶ 98), and limits
`its disclosure to one compound, ibrutinib, rather than the hundreds of
`compounds encompassed by the disclosure in Impax. Moreover, there is
`nothing in the ’085 publication remotely equivalent to Impax’s specific
`exclusion of riluzole from the invention. We acknowledge that the dosage
`guidelines in the ’085 publication are, like those in Impax, not specific to
`any one disease. However, they are specific to ibrutinib and, as discussed
`above, we find that the POSA would have connected the dosage guidelines
`with the teaching that ibrutinib could be used to treat GVHD.
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`Accordingly, because the ’085 publication discloses all of the
`
`elements in the method of claim 1, and because Patent Owner has not
`rebutted the presumption that the ’085 publication is enabled, we find that
`the preponderance of the evidence supports that the ’085 publication
`anticipates claim 1 of the ’865 patent.
`
`Claims 4, 13, 15, 28–31, 43–46, and 50–53
`Claims 4, 13, and 15 depend from claim 1 and provide additional
`limitations concerning the patients to whom ibrutinib is administered.
`Claim 4 specifies that “the patient has steroid-dependent/refractory chronic
`GVHD.” Claim 13 specifies that “the chronic GVHD is steroid resistant
`GVHD.” And claim 15 specifies that “the chronic GVHD is refractory
`GVHD.” Claims 28–31, 43–46, and 50–53 each depend from one of claims
`4, 13, and 15.
`
`Petitioner contends that the ’085 publication anticipates treatment of
`such patients because a POSA “would have known that post-steroid
`treatments – including administering ibrutinib – were started only if steroids
`were not being effective.” Pet. 38–39 (citing Ex. 1006 ¶ 86).
`Patent Owner argues