`571-272-7822
`
`Paper 78
`Date: February 18, 2020
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`ELI LILLY AND COMPANY,
`Petitioner,
`v.
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH,
`Patent Owner.
`
`IPR2018-01424 (Patent No. 9,346,881 B2)
`IPR2018-01426 (Patent No. 9,890,211 B2)
` IPR2018-01427 (Patent No. 8,597,649 B2)1
`
`
`
`
`
`
`
`
`
`Before JENNIFER MEYER CHAGNON, JAMES A. WORTH, and
`RICHARD J. SMITH, Administrative Patent Judges.
`Per Curiam
`
`
`
`JUDGMENT
`Final Written Decision
`Determining All Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`
`
`
`
`
`1 The proceedings have not been consolidated. The parties are not
`authorized to use a combined caption unless an identical paper is being
`entered into each proceeding and the paper contains a footnote indicating the
`same.
`
`
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`INTRODUCTION
`I.
`This is a Final Written Decision addressing three inter partes reviews
`challenging claims 1–6 and 14–19 of U.S. Patent No. 9,346,881 B2 (“the
`’881 patent”) (IPR2018-01424), claims 1–15 of U.S. Patent No. 9,890,211
`B2 (“the ’211 patent”) (IPR2018-01426), and claims 1–9 of U.S. Patent No.
`8,597,649 B2 (“the ’649 patent”) (IPR2018-01427).2 We have jurisdiction
`under 35 U.S.C. § 6(b). This Final Written Decision is issued pursuant to
`35 U.S.C. § 318(a). Having reviewed the arguments of the parties and the
`supporting evidence, we find that Petitioner has demonstrated by a
`preponderance of the evidence that all of the challenged claims are
`unpatentable.
`A. Procedural History
`Eli Lilly and Company (“Petitioner” or “Lilly”) filed three Petitions
`(Paper 1,3 “Pet.”) requesting an inter partes review of the respective
`challenged claims of the ’881 patent, the ’211 patent, and the ’649 patent.
`Teva Pharmaceuticals International GmbH (“Patent Owner” or “Teva”) filed
`a Preliminary Response to each of the Petitions. Paper 8 (“Prelim. Resp.”).
`
`
`2 All of the respective challenged claims are referred to collectively as the
`“challenged claims,” and the ’881 patent, the ’211 patent, and the ’649
`patent are referred to collectively as the “challenged patents.”
`IPR2018-01424 (“1424 IPR”), IPR2018-01426 (“1426 IPR”), and
`IPR2018-01427 (“1427 IPR”) are referred to herein as “the three inter partes
`reviews.”
`3 Unless this Decision otherwise indicates, all citations are to the Papers and
`Exhibits in IPR2018-01426. Similar Papers and Exhibits were filed in each
`of the three inter partes reviews.
`
`2
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`We entered our three Decisions on Institution (Paper 14, “Inst. Dec.”
`or “Institution Decision”)4 instituting inter partes review of all challenged
`claims under the only ground asserted in each of the three petitions. In each
`of the three inter partes reviews, Patent Owner filed a substantially similar
`Response (Paper 24, “PO Resp.”), Petitioner filed a substantially similar
`Reply (Paper 37, “Reply”), and Patent Owner filed a substantially similar
`Sur-reply (Paper 49, “Sur-reply”).
`In each of the three inter partes reviews, Patent Owner filed a
`substantially similar Motion to Strike (Paper 43, “Mot. Strike”) and
`Petitioner filed a substantially similar Opposition to the Motion to Strike
`(Paper 45, “Opp. Strike”). In each of the three inter partes reviews, Patent
`Owner also filed a substantially similar Motion to Exclude (Paper 56, “Mot.
`Excl.”), Petitioner filed a substantially similar Opposition to the Motion to
`Exclude (Paper 58, “Opp. Excl.”), and Patent Owner filed a substantially
`similar Reply to Petitioner’s Opposition to the Motion to Exclude (Paper
`59).
`
`Petitioner and Patent Owner requested an oral hearing. Papers 50, 51.
`A combined5 oral hearing was granted, and scheduled for November 22,
`2019. Paper 57.
`On November 21, 2019, Patent Owner filed the following documents,
`in each of the three inter partes reviews, regarding our denial of its request
`
`
`4 IPR2018-01424 was instituted on February 19, 2019, and IPR2018-01426
`and IPR2018-01427 were instituted on February 25, 2019. See also
`1424 IPR Paper 14; 1427 IPR Paper 14.
`5 In addition to the three inter partes reviews addressed in this Decision, the
`oral hearing included IPR2018-01422, IPR2018-01423, and
`IPR2018-01425. Those cases are addressed in a separate decision.
`
`3
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`to file a motion to stay based on the Federal Circuit decision in Arthrex, Inc.
`v. Smith & Nephew, Inc., 941 F.3d 1320 (Fed. Cir. 2019) (“Arthrex”):
`Patent Owner’s Request for Rehearing Pursuant to 37 C.F.R.
`§ 42.71(d) on Denial of Authorization to File a Motion to Stay
`and Supplemental Brief Addressing Arthrex (Paper 67);6
`Patent Owner’s Petition to Expedite Under 37 C.F.R. § 1.182
`(Paper 65); and
`Patent Owner’s Petition Under 37 C.F.R. § 1.181(a)(3) Invoking
`the Supervisory Authority of the Director (Paper 64).
`No decision was reached on Patent Owner’s filings (Papers 64, 65,
`67) prior to the hearing scheduled for the following day. Accordingly, we
`held a combined oral hearing on November 22, 2019, and the transcript of
`that hearing has been entered into the record. Paper 69 (“Tr.”). Patent
`Owner’s request for rehearing (Paper 67) was denied on February 18, 2020.
`On December 18, 2019, the U.S. Court of Appeals for the Federal
`Circuit issued an opinion in Fox Factory, Inc. v. SRAM, LLC, 944 F.3d 1366
`(Fed. Cir. 2019). In Fox Factory, the court “address[ed] the Board’s
`application of the presumption of nexus” to certain claims as issue. Id. at
`1374. Because Patent Owner argued a presumption of nexus with respect to
`its proffered evidence of objective indicia of nonobviousness, we authorized
`both of the parties to file, in each of the three inter partes reviews, a
`supplemental brief, and a brief responsive to the other party’s supplemental
`brief, addressing the application, if any, of Fox Factory to the three inter
`partes reviews. Paper 70. Petitioner filed a substantially similar
`supplemental brief and responsive brief (Paper 71, “Pet. Supp. Br.,”
`
`
`6 Patent Owner also requested Precedential Opinion Panel (POP) review of
`the requests for rehearing. See Ex. 3002 (e-mail dated November 21, 2019).
`That request was denied on February 13, 2020. Paper 75.
`
`4
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`Paper 74, “Pet. Supp. Rep. Br.”), and Patent Owner filed a substantially
`similar supplemental brief and responsive brief (Paper 72, “PO Supp. Br.,”
`Paper 73, “PO Supp. Rep. Br.”) in each of the three inter partes reviews.
`B. Real Parties-in-Interest
`Petitioner identifies Eli Lilly and Company as the real party-in-
`interest. Pet. 64.
`Patent Owner identifies Teva Pharmaceuticals International GmbH
`and Teva Pharmaceuticals USA, Inc. as the real parties-in-interest. Paper 4,
`1.
`
`C. Related Matters
`Petitioner identifies a declaratory judgment action filed by Patent
`Owner on October 24, 2017, in the District Court for the District of
`Massachusetts (“the first DJ action”). Pet. 65. According to Petitioner, the
`first DJ action seeks a declaration that Petitioner’s investigational drug
`galcanezumab will infringe U.S. Patent Nos. 8,586,045; 9,266,951;
`9,340,614; the ’649 patent; and the ’881 patent, and Patent Owner filed an
`amended complaint in the first DJ action on January 16, 2018. Id. Petitioner
`also identifies a declaratory judgment action filed by Patent Owner on
`February 6, 2018, seeking a declaration that Petitioner’s product will
`infringe U.S. Patent Nos. 9,884,907 and 9,884,908 (“the second DJ action”).
`Id. Petitioner states that Patent Owner thereafter filed an amended
`complaint in the second DJ action to incorporate U.S. Patent No. 9,890,210
`and the ’211 patent. Id.
`According to Petitioner, all of the patents in the first DJ action and the
`second DJ action purport to claim priority to the same provisional
`application, and two applications (15/883,218 and 15/956,580) also
`
`5
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`purported to be based on the same provisional application are pending before
`the United States Patent and Trademark Office. Id.
`Patent Owner identifies the first DJ action, the second DJ action, the
`three inter partes reviews, and six other inter partes reviews styled Eli Lilly
`and Co. v. Teva Pharmaceuticals International GmbH, IPR2018-01422,
`IPR2018-01423, IPR2018-01425, IPR2018-01710, IPR2018-01711, and
`IPR2018-01712. Papers 4, 7. Patent Owner also identifies U.S. Patent Nos.
`9,365,648; 9,328,168; 9,115,194; 8,734,802; 8,007,794, in addition to the
`patents and patent applications identified by Petitioner. Paper 5. Patent
`Owner also identifies a litigation styled Teva Pharmaceuticals International
`GmbH v. Eli Lilly and Co., Civ. No. 1-18-cv-12029 (D. Mass.). Paper 7.
`D. The Challenged Patents7
`The ’211 patent is titled “Antagonist Antibodies Directed Against
`Calcitonin Gene-Related Peptide[8]” and “relates to the use of anti-CGRP
`antagonist antibodies for the prevention, amelioration, or treatment of
`vasomotor symptoms, such as CGRP related headaches (e.g., migraine) and
`hot flushes.” Ex. 1001, [54], 1:30–33.
`According to the Specification, CGRP is a 37 amino acid
`neuropeptide, which belongs to a family of peptides that includes calcitonin,
`adrenomedullin and amylin. Id. at 1:37–39. In humans, two forms of CGRP
`with similar activities (α-CGRP and β-CGRP) exist and exhibit differential
`
`
`7 The challenged patents are direct or indirect continuations of U.S. Patent
`Application No. 12/093,638 (now U.S. Patent No. 8,007,794) and share a
`common specification. Ex. 1001, code (60); 1424 IPR Ex. 1001, code (60);
`1427 IPR Ex. 1001, code (60). We refer to the ’211 patent in this Decision
`unless otherwise indicated.
`8 Calcitonin Gene-Related Peptide is abbreviated throughout as CGRP. See
`Ex. 1001, 1:37.
`
`6
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`distribution. Id. at 1:39–42. At least two CGRP receptor subtypes may also
`account for differential activities. Id. at 1:42–43. CGRP is a
`neurotransmitter in the central nervous system, and has been shown to be a
`potent vasodilator in the periphery, where CGRP-containing neurons are
`closely associated with blood vessels. Id. at 1:43–47.
`CGRP-mediated vasodilation is also associated with neurogenic
`inflammation, as part of a cascade of events that results in extravasation of
`plasma and vasodilation of the microvasculature and is present in migraine.
`Id. at 1:47–50. CGRP has been noted for its possible connection to
`vasomotor symptoms. Id. at 1:51–54. Vasomotor symptoms include hot
`flushes and night sweats. Id. at 1:54–55. CGRP is a potent vasodilator that
`has been implicated in the pathology of other vasomotor symptoms, such as
`all forms of vascular headache, including migraines (with or without aura)
`and cluster headache. Id. at 2:16–19.
`According to the Specification, the precise pathophysiology of
`migraine is not yet well understood. Id. at 3:33–34. Dilation of blood
`vessels is associated with and exacerbates the pain symptoms of migraine.
`Id. at 3:39–40. The variety of pharmacologic interventions that have been
`used to treat migraine and the variability in responses among patients
`indicate that migraine is a diverse disorder. Id. at 3:4–6. Different classes of
`drugs have been used in treatment (and some patients, usually those with
`milder symptoms, are able to control their symptoms with non-prescription
`remedies). See id. at 3:7–19. Some patients respond well to sumatriptan,
`which is a 5HT1 receptor agonist, which also inhibits release of CGRP;
`others are relatively resistant to its effects. See id. at 2:28–30, 3:24–29,
`4:20–22.
`
`7
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`Embodiments described in the ’211 patent are directed, inter alia, to
`methods of treating or preventing a vasomotor symptom, migraine headache,
`or cluster headache in an individual using an effective amount of an anti-
`CGRP antagonist antibody. See id. at 3:53–4:3. Other embodiments of the
`’211 patent are also directed to methods of ameliorating, controlling,
`reducing incidence of, or delaying the development or progression of a
`migraine headache or cluster headache, using an effective amount of an
`anti-CGRP antagonist antibody with or without additional agents. See id. at
`4:4–52. In various embodiments, the antibody is a human antibody or
`humanized antibody; the antibody recognizes a human CGRP; or the
`antibody comprises modified regions. See id. at 4:56–5:52, 8:18–20. Other
`embodiments are directed to a polypeptide which may or may not be an
`antibody. See id. at 7:7–8:17. Other embodiments are directed to a
`polynucleotide encoding a fragment or region of the antibody or its variants,
`or to expression and cloning vectors and host cells comprising any of the
`disclosed polynucleotides. See id. at 8:30–60. Other embodiments are
`directed to methods of making the same. See id. at 9:4–19.
`The ’211 patent includes a Table 4 showing amino acid sequences of
`different variants of human α-CGRP and related peptides. Id. at 51:64–52:2;
`col. 53 (Table 4). Table 4 identifies CGRP 1–37 (WT) as SEQ ID NO: 15
`and CGRP human β (1–37) as SEQ ID NO: 43. See id.
`Figure 5 (not reproduced here) shows the amino acid sequence of the
`heavy chain variable region (SEQ ID NO: 1) and light chain variable region
`(SEQ ID NO: 2) of antibody G1. Id. at 10:24–26. Table 6 provides data on
`binding affinity for G1 variants. See id. at cols. 62–67. Another table (cols.
`72–103) lists additional antibody sequences.
`
`8
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`E. Illustrative Claims
`Claim 1 of the ’211 patent, the only independent claim, is illustrative
`and reproduced below:
`1. A humanized monoclonal anti-Calcitonin Gene-Related
`Peptide (CGRP) antagonist antibody, comprising:
`two human IgG heavy chains, each heavy chain comprising three
`complementarity determining regions (CDRs) and four
`framework regions, wherein portions of the two heavy
`chains together form an Fc region; and
`two light chains, each light chain comprising three CDRs and
`four framework regions;
`wherein the CDRs impart to the antibody specific binding to a
`CGRP consisting of amino acid residues 1 to 37 of SEQ
`ID NO:15 or SEQ ID NO: 43, and wherein the antibody
`binds to the CGRP with a binding affinity (KD) of about
`10 nM or less as measured by surface plasmon resonance
`at 37° C.
`Ex. 1001, 103:32–45.
`Claims 2–15 depend, directly or indirectly, from claim 1. Id. at
`103:46–104:59.
`Claim 1 of the ’881 patent, the only independent claim, is illustrative
`and reproduced below:
`1. A human or humanized, monoclonal anti-CGRP antagonist
`antibody that (1) binds human α-CGRP and (2) inhibits human
`α-CGRP from binding to its receptor as measured by a
`radioligand binding assay in SK-N-MC cells.
`1424 IPR Ex. 1001, 99:14–17.
`Claims 2–6 and 14–19 depend, directly or indirectly, from claim 1.
`Id. at 99:18–35, 100:33–49.
`
`9
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`Claim 1 of the ’649 patent, the only independent claim, is illustrative
`and reproduced below:
`1. An isolated human or humanized anti-CGRP antagonist
`antibody with a binding affinity (KD) to human α-CGRP of
`50 nM or less as measured by surface plasmon resonance at
`37° C.
`1427 IPR Ex. 1001, 101:38–41.
`Claims 2–9 depend, directly or indirectly, from claim 1. Id. at
`101:42–102:49.
`F. The Asserted Prior Art and Declaration Evidence
`Petitioner’s asserted grounds of unpatentability rely on the following
`references:
`K.K.C. Tan et al., Calcitonin gene-related peptide as an
`endogenous vasodilator: immunoblockade studies in vivo with
`an anti-calcitonin gene-related peptide monoclonal antibody
`and its Fab' fragment, 89 CLINICAL SCI. 6, 565–73 (1995)
`(“Tan”). Ex. 1022.
`S.J. Wimalawansa, Calcitonin Gene-Related Peptide and its
`Receptors: Molecular Genetics, Physiology, Pathophysiology,
`and Therapeutic Potentials, 17 ENDOCRINE REVIEWS 5, 533–85
`(1996) (“Wimalawansa”). Ex. 1096.
`Queen et al., US 6,180,370 B1, issued Jan. 30, 2001 (“Queen”).
`Ex. 1023.
`Doods et al., Pharmacological Profile of BIBN4096BS, the first
`selective small molecule CGRP antagonist, 129 BR. J.
`PHARMACOL. 420–23 (2000) (“Doods”). Ex. 1024.
`Petitioner relies on the Declaration of Dr. Andrew C. Charles, M.D.
`dated August 7, 2018 (Ex. 1012 “First Charles Declaration”9), the
`
`
`9 The First Charles Declaration is Ex. 1006 in the 1424 IPR, and Ex. 1002 in
`the 1427 IPR.
`
`10
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`Declaration of Dr. Alain P. Vasserot, Ph.D. (Ex. 1013, “Vasserot
`Declaration”10), the Declaration of Dr. Andrew C. Charles, M.D. dated
`September 9, 2019 (Ex. 1328, “Second Charles Declaration”11), and the
`Declaration of Dr. Joseph P. Balthasar, Ph.D. (Ex. 1327, “Balthasar
`Declaration”12).
`Patent Owner relies on the Declaration of Dr. Michael Ferrari, M.D.,
`Ph.D. (Ex. 2214, “Ferrari Declaration”13), the Declaration of Dr. Ian M.
`Tomlinson, M.A., Ph.D. (Ex. 2226, “Tomlinson Declaration”14), the
`Declaration of Steven M. Foord, Ph.D. (Ex. 2232, “Foord Declaration”15),
`the Declaration of Alan M. Rapoport, M.D. (Ex. 2237, “Rapoport
`Declaration”16), and the Declaration of Robert D. Stoner, Ph.D. (Ex. 2243,
`“Stoner Declaration”17).
`G. The Asserted Grounds of Unpatentability
`Petitioner asserts that the challenged claims would have been
`unpatentable on the following grounds:
`
`
`10 The Vasserot Declaration is Ex. 1007 in the 1424 IPR, and Ex. 1003 in the
`1427 IPR.
`11 The Second Charles Declaration is Ex. 1324 in the 1424 IPR, and
`Ex. 1330 in the 1427 IPR.
`12 The Balthasar Declaration is Ex. 1323 in the 1424 IPR, and Ex. 1329 in
`the 1427 IPR.
`13 The Ferrari Declaration is Ex. 2210 in the 1424 IPR, and Ex. 2141 in the
`1427 IPR.
`14 The Tomlinson Declaration is Ex. 2222 in the 1424 IPR, and Ex. 2137 in
`the 1427 IPR.
`15 The Foord Declaration is Ex. 2228 in the 1424 IPR, and Ex. 2054 in the
`1427 IPR.
`16 The Rapoport Declaration is Ex. 2233 in the 1424 IPR, and Ex. 2165 in
`the 1427 IPR.
`17 The Stoner Declaration is Ex. 2239 in the 1424 IPR, and Ex. 2123 in the
`1427 IPR.
`
`11
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`35 U.S.C. §
`103(a)
`
`103(a)
`
`103(a)
`
`Claim(s) Challenged
`IPR2018-01424
`1–6, 14–19
`IPR2018-01426
`1–15
`IPR2018-01427
`1–9
`
`Reference(s)/Basis
`Tan, Wimalawansa, Queen,
`Doods
`Tan, Wimalawansa, Queen
`
`Tan, Wimalawansa, Queen
`
`
`
`II. DISCUSSION
`A. Level of Ordinary Skill in the Art
`In determining the level of skill in the art, we consider the type of
`problems encountered in the art, the prior art solutions to those problems, the
`rapidity with which innovations are made, the sophistication of the
`technology, and the educational level of active workers in the field. Custom
`Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962 (Fed. Cir.
`1986); Orthopedic Equip. Co. v. United States, 702 F.2d 1005, 1011 (Fed.
`Cir. 1983).
`Petitioner proposed a definition of a person of ordinary skill in the art
`(“POSA”) in its Petition. Pet. 22 (citing Ex. 1013 ¶¶ 84–86; Ex. 1012
`¶¶ 78–80). Patent Owner proposed its own definition of a person of skill in
`the art in its Preliminary Response. Prelim. Resp. 29.
`We found in our Institution Decision that we did not discern an
`appreciable difference in the parties’ respective definitions of a person of
`ordinary skill in the art. Inst. Dec. 8. Accordingly, we determined for
`purposes of our Institution Decision that a person of ordinary skill in the art
`would have had (1) a Ph.D. in a relevant field, such as immunology,
`biochemistry, or pharmacology, with several years of post-doctoral
`experience in antibody engineering, pharmacokinetics, and
`
`12
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`pharmacodynamics, or (2) an M.D. with a residency or specialty in
`neurology, and several years of experience studying CGRP or treating
`patients with a CGRP-related disease, such as migraine headaches. See id.
`at 8–9.
`The parties do not contest this definition of a person of ordinary skill
`in the art. See generally Reply; PO Resp. 2 n.3. Accordingly, for purposes
`of this Final Written Decision, we adopt and apply the definition of a person
`of ordinary skill as set forth in our Institution Decision, and restated above.
`See Inst. Dec. 8–9. We also find on this record that Dr. Charles,
`Dr. Vasserot, Dr. Balthasar, Dr. Foord, Dr. Ferrari, Dr. Rapoport, and
`Dr. Tomlinson are persons of at least ordinary skill in the art under this
`standard. See curriculum vitaes at Ex. 1012, Appendix A; Ex. 1013,
`Appendix A; Ex. 1305, Appendix A; Ex. 2055; Ex. 2138; Ex. 2142; and
`Ex. 2160.
`We further note that the prior art itself demonstrates the level of skill
`in the art at the time of the invention. See Okajima v. Bourdeau, 261 F.3d
`1350, 1355 (Fed. Cir. 2001) (explaining that specific findings regarding
`ordinary skill level are not required “where the prior art itself reflects an
`appropriate level and a need for testimony is not shown”) (quoting Litton
`Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir.
`1985)).
`B. Claim Construction
`In an inter partes review filed before November 13, 2018, a claim in
`an unexpired patent is given its broadest reasonable construction in light of
`
`13
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`the specification of the patent in which it appears.18 37 C.F.R. § 42.100(b)
`(2018); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016)
`(affirming applicability of broadest reasonable construction standard to inter
`partes review proceedings). The broadest reasonable construction standard
`applies to the three inter partes reviews because the Petitions were filed on
`August 8, 2018. Paper 6; 1424 IPR Paper 4, 1427 IPR Paper 6. Under that
`standard, and absent any special definitions, we generally give claim terms
`their ordinary and customary meaning, as would have been understood by
`one of ordinary skill in the art at the time of the invention. See In re
`Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any special
`definitions for claim terms must be set forth with reasonable clarity,
`deliberateness, and precision. See In re Paulsen, 30 F.3d 1475, 1480
`(Fed. Cir. 1994).
`Petitioner requested construction of the term “specific binding.”
`Pet. 23–24. We determined in our Institution Decision that “it is not
`necessary to construe the term ‘specific binding’ on this record and at this
`stage of the proceeding.” Inst. Dec. 11. Neither party pursued construction
`after our Institution Decision, and we decide that it is not necessary to
`construe the term “specific binding” for purposes of this Final Written
`Decision.
`
`
`18 The claim construction standard to be employed in inter partes reviews
`has changed for proceedings in which the petition was filed on or after
`November 13, 2018. 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, 51,343 (amending 37 C.F.R. § 42.100(b)
`effective November 13, 2018) (now codified at 37 C.F.R. § 42.100(b)
`(2019)).
`
`14
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`
`With respect to the 1424 IPR, Petitioner requests construction of the
`following terms: “anti-CGRP antagonist antibody” and “humanized
`antibody” in the ’881 patent.19 1424 IPR Pet. 26. Patent Owner in its
`Preliminary Response requested construction of the claims “according to
`their plain and customary meaning,” but did not address claim construction
`further in its Patent Owner Response or Sur-reply. See 1424 IPR Prelim.
`Resp. 29; see generally 1424 IPR PO Resp., Sur-reply.
`Petitioner argues that the ’881 patent expressly defines “antibody” to
`encompass “not only intact polyclonal or monoclonal antibodies, but also
`fragments thereof (such as Fab, Fab’, F(ab’)2, Fv).” 1424 Pet. 26 (citing
`1424 IPR Ex. 1001, 12:39–45, 26:29–39; 1424 IPR Ex. 1006 ¶ 116; 1424
`IPR Ex. 1007 ¶ 74). The Specification of the ’881 patent states:
`An “antibody” is an immunoglobulin molecule capable of
`specific binding
`to a
`target, such as a carbohydrate,
`polynucleotide, lipid, polypeptide, etc., through at least one
`antigen recognition site, located in the variable region of the
`immunoglobulin molecule. As used herein,
`the
`term
`encompasses not only
`intact polyclonal or monoclonal
`antibodies, but also fragments thereof (such as Fab, Fab', F(ab')2,
`Fv), single chain (ScFv), mutants thereof, fusion proteins
`comprising an antibody portion (such as domain antibodies), and
`any other modified configuration of the immunoglobulin
`molecule that comprises an antigen recognition site. An antibody
`includes an antibody of any class, such as IgG, IgA, or IgM (or
`sub-class thereof), and the antibody need not be of any particular
`class.
`
`
`19 Petitioner also requests construction of these two terms in the 1427 IPR,
`and we analyze the construction of the terms in the 1427 IPR in the same
`manner because the ’649 patent shares the same Specification as the ’881
`patent.
`
`15
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`1424 IPR Ex. 1001, 12:35–48; see also id. at 26:29–50. We agree with
`Petitioner that this constitutes an express definition of the term “antibody”
`and we so construe the term. Paulsen, 30 F.3d at 1480. We agree with
`Petitioner that the defined term “antibody” includes antibody fragments.
`1424 IPR Ex. 1001, 12:35–48.
`Petitioner argues that the ’881 patent expressly defines “humanized”
`antibodies in the same manner, i.e., encompassing “forms of non-human
`(e.g., murine) antibodies that are specific chimeric immunoglobulins,
`immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2
`or other antigen-binding subsequences of antibodies) . . . .” 1424 IPR Pet.
`26 (citing 1424 IPR Ex. 1001, 13:15–20; 1424 IPR Ex. 1006 ¶ 116; 1424
`IPR Ex. 1007 ¶ 75). The Specification of the ’881 patent states:
`As used herein, “humanized” antibodies refer to forms of
`non-human (e.g. murine) antibodies that are specific chimeric
`immunoglobulins, immunoglobulin chains, or fragments thereof
`(such as Fv, Fab, Fab', F(ab')2 or other antigen-binding
`subsequences of antibodies) that contain minimal sequence
`derived from non-human immunoglobulin.
`1424 IPR Ex. 1001, 13:15–20; see also id. at 26:29–50. We agree with
`Petitioner that this constitutes an express definition of the term “humanized
`antibody” and we so construe the term. Paulsen, 30 F.3d at 1480. We agree
`with Petitioner that “humanized antibody” includes antibody fragments.
`1424 IPR Ex. 1001, 13:15–20.
`We adopt and apply the foregoing constructions for purposes of this
`Final Written Decision. We determine that no other term requires express
`construction. See Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795,
`803 (Fed. Cir. 1999) (only those terms need be construed that are in
`controversy, and only to the extent necessary to resolve the controversy).
`
`16
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`However, we provide the following additional discussion regarding
`interpretation of the challenged claims.
`The terms “human” and “humanized” as applied to antibodies are
`defined in the Specification by the structure of the antibody (e.g. amino acid
`sequence). 1424 Ex. 1001, 13:15–148. Accordingly, we do not construe the
`claim terms “human” or “humanized” as incorporating a use of the antibody
`into the claims, such as use in humans.20 See Senju Pharm. Co. v. Lupin,
`780 F.3d 1337, 1346 (Fed. Cir. 2015) (“In composition claims 12–16 . . .
`there is no limitation denoting the function of the composition and we
`decline to import this limitation into the claims.”) (citing Phillips v. AWH
`Corp., 415 F.3d 1303, 1323 (Fed. Cir. 2005) (stating that the Court has
`repeatedly warned against confining the claims to particular embodiments in
`the written description)).
`Similarly, we do not construe the claimed antibody as reciting any use
`of the antibody, such as for treatment or prevention of a disease, disorder, or
`symptom. See, e.g., ParkerVision, Inc. v. Qualcomm Inc., 903 F.3d 1354,
`1361 (Fed. Cir. 2018) (“We explained long ago that ‘[a]pparatus claims
`cover what a device is, not what a device does.’”) (quoting Hewlett-Packard
`Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1468 (Fed. Cir. 1990))(alteration
`in original).
`Patent Owner argues that “the utility of the claimed antibody must be
`considered here, namely ‘preventing or treating CGRP associated disorders
`
`
`20 The record reflects that humanized antibodies were administered to
`animals as of November 2005. See Ex. 2128, 1, 5 (discussing the humanized
`monoclonal antibody bevacizumab (Avastin®) and stating that “[t]he safety
`and pharmacokinetics of bevacizumab were evaluated in young adult
`cynomolgus monkeys”).
`
`17
`
`
`
`IPR2018-01424 (Patent No. 9,346,881 B2); IPR2018-01426 (Patent No.
`9,890,211 B2); IPR2018-01427 (Patent No. 8,597,649 B2)
`
`such as vasomotor symptoms, including headaches (e.g., migraine, cluster
`headache, and tension headache) and hot flushes.’” PO Resp. 14–15 (citing
`Ex. 1001, Abstract).21 Patent Owner bases this argument on Otsuka
`Pharmaceutical Co. v. Sandoz Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012).
`Otsuka involved an obviousness challenge in which “the parties’ arguments
`focus on selecting and modifying particular prior art compounds, designated
`as lead compounds.” Id. Here, the parties’ arguments do not focus on
`selecting and modifying particular prior art compounds. Moreover, in a lead
`compound analysis as was at issue in Otsuka, “whether a chemist would
`have selected a prior art compound as a lead . . . is guided by evidence of the
`compound’s pertinent properties.” Id. at 1292 (citing cases). Thus, the
`pertinent properties in a lead compound analysis are those of a prior art
`compound, not properties that are read into the claims. See ParkerVision,
`903 F.3d at 1361.
`We also reject Patent Owner’s argument that Petitioner has read
`“safety and efficacy requirements into the claims” based on arguments in the
`Petition. Sur-reply 3–5. Patent Owner relies on Phigenix v. ImmunoGen,
`IPR2014-00676, Paper 39 at 16 (PTAB Oct. 27, 2017), that addressed a
`particular rationale that the patent challenger advanced for combining the
`teachings of the prior art. Id. Phigenix does not stand for the proposition
`that limitations can be read into claims based on arguments by a party that is
`not the owner of the patent. Here, the challenged claims do not recite any
`safety or efficacy requirements, and we decline to incorporate such
`
`
`21 Immediately