Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 1 of 38
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF MASSACHUSETTS
`
`
`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBH and
`TEVA PHARMACEUTICALS
`USA, INC.,
`
`Plaintiffs,
`
`
`v.
`
`ELI LILLY AND COMPANY,
`Defendant.
`
`
`
`
`
`Civil Action No.
`1:18-cv-12029-ADB
`
`
`
`
`
`
`
`FILED UNDER SEAL
`LEAVE TO FILE GRANTED
`05/06/2022 (ECF NO. 340)
`
`LEAVE TO FILE EXCESS
`PAGES GRANTED 02/22/2022
`(ECF NO. 272)
`
`
`PLAINTIFFS’ OPPOSITION TO ELI LILLY AND COMPANY’S MOTION FOR
`SUMMARY JUDGMENT OF INVALIDITY FOR LACK OF WRITTEN DESCRIPTION
`
`

`

`I.
`II.
`
`III.
`
`IV.
`
`V.
`
`
`
`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 2 of 38
`
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION ............................................................................................................. 1
`BACKGROUND ............................................................................................................... 1
`A.
`The claimed inventions and the asserted claims .................................................... 1
`B.
`The specification, viewed by a POSA ................................................................... 3
`C.
`The IPR proceedings .............................................................................................. 8
`LEGAL STANDARDS ................................................................................................... 10
`A.
`Summary judgment .............................................................................................. 10
`B. Written description............................................................................................... 10
`ARGUMENT ................................................................................................................... 12
`A.
`Lilly’s motion papers violate Local Rule 56.1..................................................... 13
`B.
`Lilly’s species-genus argument fails, because the patents claim methods of using
`anti-CGRP antagonist antibodies to treat headache, not the antibodies themselves.
`.............................................................................................................................. 15
`The record contains ample evidence allowing a factfinder to conclude that the
`specification describes the genus of antibodies used in the claimed methods. .... 18
`1.
`The parties dispute whether the disclosed species are representative of the
`claimed genus.18
`The parties dispute whether the specification disclosed structural features
`common to members of the genus. 24
`Neither reduction to practice nor clinical results are required to satisfy the written
`description requirement and the parties dispute whether the named inventors
`reduced the inventions to practice. ....................................................................... 25
`The parties dispute whether the specification describes the claimed methods. ... 27
`Lilly’s Motion does not show that summary judgment is appropriate for the
`dependent claims and the claims of the ’907 and ’908 patents............................ 30
`CONCLUSION ................................................................................................................ 30
`
`C.
`
`2.
`
`D.
`
`E.
`F.
`
`i
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`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 3 of 38
`
`TABLE OF AUTHORITIES
`
`
`
`
`
`Page(s)
`
`Cases
`
`Abbott GmbH & Co. v. Centocor Ortho Biotech, Inc.,
`870 F. Supp. 2d 206 (D. Mass. 2012) .............................................................................. passim
`
`AbbVie Deutschland GmbH v. Janssen Biotech, Inc.,
`759 F.3d 1285 (Fed. Cir. 2014)..........................................................................................20, 23
`
`Acantha LLC v. DePuy Orthopaedics Inc.,
`2018 WL 2431852 (E.D. Wis. 2018) .......................................................................................14
`
`Alcon Rsch. Ltd. v. Barr Lab’ys, Inc.,
`745 F.3d 1180 (Fed. Cir. 2014)................................................................................................28
`
`Allergan, Inc. v. Sandoz Inc.,
`796 F.3d 1293 (Fed. Cir. 2015)..........................................................................................25, 26
`
`Alsina-Ortiz v. Laboy,
`400 F.3d 77 (1st Cir. 2005) ......................................................................................................14
`
`Anderson v. Liberty Lobby,
`477 U.S. 242 (1986) .................................................................................................................10
`
`Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) (en banc)........................................................................ passim
`
`Boston Sci. Corp. v. Johnson & Johnson,
`647 F.3d 1353 (Fed. Cir. 2011)....................................................................................10, 11, 24
`
`In re Brana,
`51 F.3d 1560 (Fed. Cir. 1995)..................................................................................................26
`
`Brown v. Armstrong,
`957. F. Supp. 1293 (D. Mass. 1997), aff’d 129 F.3d 1252 (1st Cir. 1997) ..............................13
`
`Camona v. Toledo,
`215 F.3d 124 (1st Cir. 2000) ....................................................................................................15
`
`Capon v. Eshhar,
`418 F.3d 1349 (Fed. Cir. 2005)................................................................................................19
`
`CMI Capital Market Inv., LLC v. González-Toro,
`520 F.3d 58 (1st Cir. 2008) ......................................................................................................13
`
`ii
`
`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 4 of 38
`
`
`
`Cortes-Irizarry v. Corporacion Insular de Serguros,
`111 F.3d 184 (1st Cir. 1997) ....................................................................................................14
`
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`2020 WL 1540364 (PTAB Mar. 31, 2020), aff’d, 8 F.4th 1331 (Fed. Cir.
`2021) ..........................................................................................................................................9
`
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`2020 WL 806932 (PTAB Feb. 18, 2020) ..............................................................................8, 9
`
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`2020 WL 808240 (PTAB Feb. 18, 2020) ..............................................................................8, 9
`
`In re Engers v. AT&T,
`2005 WL 6460846 (D.N.J. Sept. 9, 2005) ...............................................................................14
`
`Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co.,
`2016 WL 6138124 (E.D. Tex. Oct. 21, 2016) (UroPep I) .................................................15, 16
`
`Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co.,
`276 F. Supp. 3d 629 (E.D. Tex. 2017), aff’d, 739 F. App’x 643 (Fed. Cir.
`2018) (UroPep II) ..............................................................................................................16, 21
`
`Feliciano v. Rhode Island,
`160 F.3d 780 (1st Cir. 1998) ..............................................................................................10, 14
`
`In re Herschler,
`591 F.2d 693 (C.C.P.A. 1979) .....................................................................................16, 17, 18
`
`In re Hogan,
`559 F.2d 595 (Fed. Cir. 2017)..................................................................................................22
`
`Invitrogen Corp. v. Clontech Labs., Inc.,
`429 F.3d 1052 (Fed. Cir. 2005)................................................................................................18
`
`Juno Therapeutics, Inc. v. Kite Pharma, Inc.,
`10 F.4th 1330 (Fed. Cir. 2021) ..........................................................................................23, 24
`
`Kinetic Concepts, Inc. v. Smith & Nephew, Inc.,
`688 F.3d 1342 (Fed. Cir. 2012)................................................................................................29
`
`Merck Sharp & Dohme Corp. v. Genentech,
`PGR2021-00036, Paper 10 (July 24, 2021) .............................................................................17
`
`Microsoft Corp. v. i4i Ltd. P’ship,
`564 U.S. 91 (2011) ...................................................................................................................30
`
`iii
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`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 5 of 38
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`
`
`Motfort-Rodriguez v. Rey-Hernandez,
`504 F.3d 221 (1st Cir. 2007) ....................................................................................................10
`
`Noelle v. Lederman,
`355 F.3d 1343 (Fed. Cir. 2004)................................................................................................24
`
`Resolution Trust Corp. v. Fidelity & Deposit Co.,
`1998 WL 2030798 (D.N.J. 1998) ............................................................................................14
`
`Rosco, Inc. v. Mirror Lite Co.,
`304 F.3d 1373 (Fed. Cir. 2002)................................................................................................30
`
`S3 Inc. v. NVIDIA Corp.,
`259 F.3d 1364 (Fed. Cir. 2001)................................................................................................11
`
`Sandt Tech., Ltd. v. Resco Metal & Plastics Corp.,
`264 F.3d 1344 (Fed. Cir. 2001)................................................................................................30
`
`Teva Pharms. Int’l GmbH v. Eli Lilly & Co.,
`8 F.4th 1349 (Fed. Cir. 2021) ....................................................................................................9
`
`Trustees of the Univ. of Pa. v. Eli Lilly & Co.,
`2021 WL 7918978 (E.D. Pa. Nov. 19, 2021) (Penn) .........................................................17, 22
`
`In re Varrasso,
`37 F.3d 760 (1st Cir. 1994) ......................................................................................................10
`
`Statutes
`
`35 U.S.C. § 112 ............................................................................................................................1, 3
`
`Other Authorities
`
`Fed. R. Civ. P. 56(c) ......................................................................................................................10
`
`Fed. R. Evid. 801 ...........................................................................................................................14
`
`Local Rule 56.1 ........................................................................................................................13, 14
`
`
`
`
`
`
`iv
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`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 6 of 38
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`
`
`TABLE OF ABBREVIATIONS
`
`
`Description
`U.S. Patent No. 8,586,045 (Ex. E)
`U.S. Patent No. 9,884,907 (Ex. AL)
`U.S. Patent No. 9,884,908 (Ex. AO)
`Declaration of Yasmina Abdiche, Ph.D. in Support of Teva’s Oppositions to
`Lilly’s Motions for Summary Judgment of Invalidity for (1) Lack of
`Enablement, and (2) Lack of Written Description
`Blood-brain barrier
`Responsive Expert Report of Andrew Blumenfeld, M.D. Regarding Validity
`(Nov. 1, 2021) (Ex. L)
`Calcitonin gene-related peptide
`Transcript of Dr. Andrew Charles (Jan. 27, 2022) (Ex. R)
`ECF No. 314 (Plaintiffs Teva Pharmaceuticals International GmbH and Teva
`Pharmaceuticals USA, Inc.’s Memorandum of Law in Support of Motion for
`Partial Summary Judgment Regarding Judicial Estoppel)
`Food and Drug Administration
`Final Written Decision of IPR2018-01427 (Feb. 18, 2020) (Ex. C)
`Responsive Expert Report of Geoffrey Hale, Ph.D., Regarding Validity
`(Nov. 1, 2021) (Ex. S)
`Rebuttal Expert Report of Raymond Hill, Ph.D. Regarding Validity (Nov. 1,
`2021) (Ex. V)
`Inter partes review
`Eli Lilly and Company
`ECF No. 294 (Eli Lilly and Company’s Memorandum in Support of its
`Motion for Summary Judgment of Invalidity for Lack of Written Description)
`ECF No. 320 (Plaintiffs’ Memorandum in Support of its Motion to Exclude
`the Expert Testimony of Dr. Diane Mould)
`U.S. Patent Nos. 8,586,045; 9,884,907; and 9,884,908
`Person of ordinary skill in the art
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`Shaw, et. al., The effect of monoclonal antibodies to calcitonin gene-related
`peptide (CGRP) on CGRP-induced vasodilation in pig coronary artery rings,
`106 British Journal of Pharmacology 196 (1992) (Ex. AM)
`ECF No. 295 (L.R. 56.1 Statement of Material Facts in Support of Defendant
`Eli Lilly and Company’s Motion for Summary Judgment of Invalidity for
`Lack for Written Description)
`Plaintiffs’ Responsive Statement of Material Facts
`Tan, “Application of Monoclonal Antibodies to the Investigation of the Role
`of Calcitonin Gene-Related Peptide as a Vasodilatory Neurotransmitter,”
`Dissertation Submitted to the University of Cambridge (1994) (Ex. AT)
`Teva Pharmaceuticals International GmbH and Teva Pharmaceuticals USA,
`Inc.
`
`
`
`Abbreviation
`’045 patent
`’907 patent
`’908 patent
`Abdiche Decl.
`
`BBB
`Blumenfeld Resp.
`
`CGRP
`Charles Tr.
`Estoppel Mem.
`
`FDA
`FWD
`Hale Resp.
`
`Hill Reb.
`
`IPR
`Lilly
`Mot.
`
`Mould Daubert Mem.
`
`Patents-in-suit
`POSA
`PTAB
`PTO
`Shaw 1992
`
`SOF
`
`RMF
`Tan Thesis
`
`Teva
`
`
`
`
`v
`
`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 7 of 38
`
`
`
`I.
`
`INTRODUCTION
`
`Lilly’s argument that the asserted claims are invalid for lack of written description is wrong
`
`on the law and rests on Lilly’s version of the facts—a version that is heavily disputed. Lilly’s core
`
`argument is that the anti-CGRP antagonist antibodies used in the claimed methods are not
`
`adequately described because the specification does not provide enough examples of the
`
`antibodies. This argument misses the mark, because the claims here are for methods of using
`
`antibodies to treat headache, not for the antibodies themselves. In any event, the description is
`
`adequate: the specification discloses representative examples of the antibodies used in the claimed
`
`methods, along with a description of the claimed methods and animal data (i.e., in vivo
`
`experiments) that would demonstrate to a POSA that the claimed methods would be effective in
`
`humans. This description satisfies 35 U.S.C. § 112, especially in light of a POSA’s extensive
`
`knowledge about anti-CGRP antagonist antibodies at the time of the invention. At the very least,
`
`disputed issues of fact preclude deciding the written description question at this stage.
`
`Lilly makes a host of other arguments—for example, that the inventors did not practice the
`
`invention, report clinical results, or understand how anti-CGRP antagonist antibodies work in the
`
`human body to treat migraine. But these arguments are irrelevant to the question of whether the
`
`specification adequately describes the claimed methods. And even if they were relevant, Lilly’s
`
`arguments are the subject of vigorous factual disputes that preclude summary judgment.
`
`For these reasons and the reasons given below, the Court should deny Lilly’s motion and
`
`send the written description issue to trial.
`
`II.
`
`BACKGROUND
`
`A.
`
`The claimed inventions and the asserted claims
`
`Teva asserts twenty claims from three patents: the ’045, ʼ907, and ʼ908 patents. The
`
`inventions involve the use of human or humanized anti-CGRP antagonist antibodies to treat
`
`1
`
`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 8 of 38
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`
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`headache. RMF ¶ P30. At the time of the inventions, anti-CGRP antagonist antibodies were well-
`
`known in the art. RMF ¶¶ P5, P31, P44, P58–59, P67–71, P89–91, P107. It was also well-known
`
`in the art that CGRP (a neurotransmitter) played a role in headache and that drugs that target the
`
`CGRP pathway were effective for treating headache. RMF ¶¶ P45–48, P76–83, P92. The
`
`inventors discovered, however, that anti-CGRP antagonist antibodies—as opposed to other
`
`mechanisms for targeting the CGRP pathway, like small molecules that target CGRP receptors
`
`rather than CGRP itself—were effective for treating headache.
`
`The ’045 Patent: Claim 17, the only asserted independent claim of the ’045 patent, recites:
`
`A method for reducing incidence of or treating headache in a human, comprising
`administering to the human an effective amount of anti-CGRP antagonist antibody,
`wherein said anti-CGRP antagonist antibody is a human monoclonal antibody or a
`humanized monoclonal antibody.
`
`This Court has construed “effective amount” as “an amount sufficient to effect beneficial or desired
`
`results, including but not limited to clinical results.” ECF No. 101 at 31. Teva also asserts seven
`
`dependent claims of the ’045 patent. Claim 19 limits the condition treated to several specific
`
`headache disorders, and claim 24 limits the condition to “migraine.” Claim 30 specifies that the
`
`antibody used is a humanized monoclonal antibody. Claim 20 specifies that the antibody has a
`
`“binding affinity (KD) to human α-CGRP of 50 nM or less.” Claims 18 and 21 specify that the
`
`antibodies have amino acid sequences with a variable region taken from “antibody G1”—an
`
`antibody identified and described in the specification. Claim 27 states that the antibody is
`
`administered “systemically, intravenously, subcutaneously, intramuscularly, and transdermally.”
`
`The ʼ907 Patent: The only independent claim of the ʼ907 patent, claim 1, also recites a
`
`method for treating headache by administering an “effective amount” of anti-CGRP antagonist
`
`antibody. The claim further specifies that the antibody is “humanized” and comprises:
`
`three
`IgG heavy chains, each heavy chain comprising
`two human
`complementarity determining regions (CDRs) and four framework regions,
`
`2
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`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 9 of 38
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`
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`wherein portions of the two heavy chains together form an Fc region; and
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`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
`
`Teva asserts five dependent claims. Claim 6 specifies that the headache is migraine and claim 5
`
`limits the headache to one of several disorders (the same types of headaches in claim 19 of the
`
`ʼ045 patent). Claim 15 states that the “constant regions of the IgG heavy chains are IgG4 constant
`
`regions,” and claim 17 further specifies that the “CDRs … are derived from mouse, rat, or rabbit
`
`CDRs.” Claim 4 states that “the antibody is administered intravenously or subcutaneously.”
`
`
`
`The ʼ908 Patent: The only independent claim of the ʼ908 patent, claim 1, is identical to
`
`claim 1 of the ʼ907 patent, with the additional limitation:
`
`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.
`
`Teva asserts five dependent claims, identical in claim number and language to the dependent
`
`claims asserted in the ʼ907 patent.
`
`B.
`
`The specification, viewed by a POSA
`
`The patents share a specification, which is viewed, for the purposes of the Section 112
`
`inquiry, in light of the knowledge in the field at the time of the invention, as a POSA would view
`
`it. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). The
`
`parties agree that the relevant POSA is highly skilled, and has (1) a Ph.D. in a relevant field, such
`
`as immunology, biochemistry, or pharmacology, with several years of postdoctoral experience in
`
`antibody engineering, pharmacokinetics, and pharmacodynamics, or (2) an M.D. with a residency
`
`or specialty in neurology, and several years of experience studying CGRP or treating patients with
`
`migraine headaches. SOF ¶¶ 181–82; see also RMF ¶¶ P22–29 .
`
`3
`
`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 10 of 38
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`
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`When the evidence is viewed in the light most favorable to Teva, a POSA would have
`
`understood the specification to disclose the following:
`
`Anti-CGRP antagonist antibodies: The specification describes the anti-CGRP antagonist
`
`antibodies used in the claimed methods of treatment. An antibody, the specification explains, is
`
`“an immunoglobulin molecule capable of specific binding to a target . . . through at least one
`
`antigen recognition site, located in the variable region of the immunoglobulin molecule.” Ex. E
`
`(’045 patent) at 12:14–18. An anti-CGRP antagonist antibody is an antibody that is “able to bind
`
`to CGRP” and “inhibit CGRP biological activity and/or downstream pathway(s) mediated by
`
`CGRP signaling.” Id. at 13:62–66; see also ECF No. 101 at 11. The specification states that
`
`“[a]nti-CGRP antagonist antibodies are known in the art.” Id. at 25:59–63. Teva’s experts agree.
`
`For example, Dr. Hill states that
`
`59, P67, P88–90;
`
`
`
`; see RMF ¶¶ P28, P31, P58–
`
`
`
` Indeed, Lilly
`
`argued in the related IPR proceedings (see pp. 8-9, infra) that anti-CGRP antagonist antibodies
`
`were well known at the time of the invention, and the PTAB agreed.
`
`The specification also discloses prior art methods for making the antibodies used in the
`
`inventions. Ex. E at 12:52–57. As Teva’s experts explain (and as Lilly agrees, see pp. 8-9, infra),
`
`at the time of the inventions, the prior art described how to generate antibodies, including anti-
`
`CGRP antibodies, as well as methods to determine whether the antibodies antagonize CGRP. For
`
`example, Dr. Hale states that
`
` RMF ¶¶ P23, P61, P91, P93–100. He also explains that
`
`
`
`
`
`
`
`4
`
`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 11 of 38
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`Humanized antibodies1: The specification details the steps to humanize an antibody and
`
`references examples of prior art that explain the same. Ex. E at 28:55–4. Teva’s experts have
`
`explained (and Lilly argued in the related IPR proceedings, see pp. 8-9, infra) that humanization
`
`techniques were routine and reliable as of the priority date. For example, Dr. Hale has explained
`
`that
`
`
`
`
`
`
`
`
`
`
`
`Human antibodies: The specification explains that “human” antibodies are antibodies
`
`“having an amino acid sequence corresponding to that of an antibody produced by a human and/or
`
`has been made using any of the techniques for making human antibodies known in the art.” Ex. E
`
`at 13:26–30. It states that they “can be produced using various techniques used in the art,” and
`
`describes those techniques. Id. at 13:34–54. It describes, as an example, technology that can be
`
`used to produce fully human antibodies with commercially available mice that have been
`
`engineered to express human antibodies. Id. at 29:29–38. Teva’s experts have explained that
`
`techniques for deriving human antibodies were well-known in the art. RMF ¶ P66;
`
`
`1 A “humanized antibody,” as defined by this Court, is a “form[] of non-human (e.g., murine)
`antibodies … that contain[s] minimal sequence derived from non-human immunoglobulin.” Ex.
`E at 12:61–65; ECF No. 101 at 16 (adopting this definition).
`
`5
`
`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 12 of 38
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`
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`Exemplary anti-CGRP antagonist antibodies: The specification discloses 85 humanized
`
`anti-CGRP antagonist antibodies that can be used in the claimed methods. RMF ¶ P103. It
`
`discloses “Antibody G1,” a full-length humanized anti-CGRP antagonist antibody that was later
`
`renamed fremanezumab. Id. at 34:6–35:34, Ex. 4, Fig. 5. The specification provides the complete
`
`amino acid sequence of the heavy chain and light chain of Antibody G1, as well as the variable
`
`region and CDR portions of Antibody G1. Id. at Fig. 5; cols. 72–73; RMF ¶ P104. The
`
`specification also lists 84 variants of Antibody G1, referred to as “M1-M84,” which are also
`
`humanized anti-CGRP antagonist antibodies, and differ from Antibody G1 in their amino acid
`
`makeup. Ex. E, Table 6. The specification states that “[t]he invention encompasses modifications
`
`to Antibody G1 or is variants shown in Table 6, including functionally equivalent antibodies which
`
`do not significantly affect their properties.” Id. at 37:35–38:39. “For example, the amino acid
`
`sequence of Antibody G1 or its variants shown in Table 6 may be mutated to obtain an antibody
`
`with the desired binding affinity to CGRP.” Id. at 37:39–42. A POSA would have easily
`
`recognized, using conventional assays, that the variants of Antibody G1 also antagonize CGRP.
`
`RMF ¶ 103.
`
`The specification also discloses that the inventors generated seven murine (mouse) anti-
`
`CGRP antibodies that antagonized CGRP. Ex. E, Table 2; RMF ¶ P102. A POSA would have
`
`recognized that these antibodies could be humanized for use in the claimed methods using routine
`
`humanization techniques. RMF ¶ P64-P65. The inventors state that “[m]odification of
`
`polypeptides is routine practice in the art and need not be described in detail,” but that
`
`“[m]odification of polypeptides is exemplified in the Examples,” and provides examples of
`
`modified polypeptides that have similar functional activity to Antibody G1 and its variants. Ex. E
`
`6
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`

`

`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 13 of 38
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`
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`at 37:35–49.
`
`Treatment for Headache: The specification also describes how anti-CGRP antagonist
`
`antibodies can be used to treat headache. They are “administered [to a patient] prior to, during
`
`and/or after headache.” Id. at 5:47–48. Administration is by “means known in the art,” and the
`
`antibodies can be formulated with pharmaceutically acceptable carriers using “well known
`
`conventional methods.” Id. at 5:47–57, 19:24–39, 23:13–19.
`
`The specification discloses two experiments or “assays” that report the activity of Antibody
`
`G1 in treating headache,2 the “rat saphenous nerve assay” and the “closed cranial window assay.”
`
`RMF ¶ P117. The rat saphenous nerve assay evaluates the effect of an anti-CGRP antagonist
`
`antibody on the CGRP-dependent increase in skin blood flow in response to electrical stimulation
`
`of the saphenous nerve in a rat’s leg. Ex. E at 55:27–41; Ex. V ¶ 143; RMF ¶¶ P74–75. The assay
`
`tests whether an anti-CGRP antibody can inhibit CGRP biological function in a live animal at the
`
`normal site of action in a context that is physiologically relevant to migraine. Ex. E at 55:27–
`
`57:12; RMF ¶¶ P76–77; Ex. V ¶¶ 143–46. The data disclosed in the specification shows not only
`
`that Antibody G1 is effective in this assay over a range of doses, but that the effects persist for at
`
`least a week after the antibody is administered. Ex. E at 67:53–68:57, Figs. 7–8; RMF ¶¶ P116–
`
`23; Ex. V ¶¶ 209, 273.
`
`The closed cranial window assay measures the effect of an anti-CGRP antagonist antibody
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`on dilation of dural arteries following electrical stimulation. Ex. E at 68:59–68:67; RMF ¶ P78.
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`2 Lilly argues that there are 200 distinct headache disorders. But Lilly counts subclasses of
`headache and terminology that was not widely used in clinical treatment. RMF ¶ P52. The vast
`majority of headaches encountered in clinical practice were associated with CGRP, such as
`migraine, even if they were called by another term (e.g., “chronic daily headache”) or diagnosed
`as another form of headache (e.g., “tension-type headache”). RMF ¶ P131. In other instances, a
`POSA would immediately understand that certain types of headache, like secondary headaches,
`should be treated by treating the underlying condition. RMF ¶ P53.
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`7
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`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 14 of 38
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`Dilation of dural arteries was known to be associated with head pain, and activity of a compound
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`in the closed cranial window assay was understood to be predictive of efficacy for treating
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`migraine in humans. RMF ¶ P79. The specification discloses that Antibody G1 is effective in this
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`assay over a range of doses and for at least a week after administration.
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`As Teva’s experts explain, the results of the two assays in the specification would have
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`demonstrated to a POSA that anti-CGRP antagonist antibodies would be effective for treating
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`migraine. RMF ¶¶ P124–30, P145–47; Ex. V ¶¶ 274–308. The closed cranial window assay
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`would have been particularly instructive, because extensive studies had shown that activity in that
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`assay is highly correlated with efficacy for treating migraine in humans. RMF ¶¶ P80–83.
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`C.
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`The IPR proceedings
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`In addition to the three method patents currently at issue, initially this case also included
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`six composition of matter patents that claimed anti-CGRP antagonist antibodies themselves. In
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`2018, Lilly petitioned for inter partes review of all nine patents. RMF ¶ P1. Lilly argued that the
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`challenged claims were invalid as obvious. The central issue in the IPRs was whether a POSA
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`would have been motivated to combine prior art references that disclosed non-human CGRP
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`antagonist antibodies with other references that discussed humanized antibodies generally, with a
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`reasonable expectation of successfully making a humanized antibody that antagonized CGRP.
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`RMF ¶ P2.
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`The Board held, in two similar decisions, that the challenged claims in Teva’s six
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`composition of matter patents were unpatentable as obvious. RMF ¶ P3. Eli Lilly & Co. v. Teva
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`Pharms. Int’l GmbH, 2020 WL 806932 (PTAB Feb. 18, 2020); Eli Lilly & Co. v. Teva Pharms.
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`8
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`Case 1:18-cv-12029-ADB Document 437 Filed 07/27/22 Page 15 of 38
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`Int’l GmbH, 2020 WL 808240 (PTAB Feb. 18, 2020).3 Particularly relevant here, the Board held
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`that by 2005, antibodies that antagonize CGRP were “well known in the art,” and that the methods
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`of preparing them were “routine.” RMF ¶ P7; see 2020 WL 808240, *44, *46. The Board also
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`found that the step of humanizing anti-CGRP antagonist antibodies would have been “routine” by
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`2005, and that a POSA could humanize an anti-CGRP antagonist antibody without reducing its
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`ability to bind to its target CGRP. RMF ¶¶ P8–9; see 2020 WL 808240, *27, *46. Finally, the
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`Board found that it was “well established” by 2005 that one could determine whether an antibody
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`inhibits the CGRP pathway by a process that involved measuring “cAMP activation in SK-N-MC
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`cells.” RMF ¶ P6; see 2020 WL 806932, at *13–14. The Federal Circuit affirmed the Board’s
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`decision. Teva Pharms. Int’l GmbH v. Eli Lilly & Co., 8 F.4th 1349 (Fed. Cir. 2021); Teva Pharms.
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`Int’l GmbH v. Eli Lilly & Co., 856 F. App’x 312 (Fed. Cir. 2021). Separately, the Board found
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`that Lilly had not shown that the challenged claims in the method patents at issue in this case were
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`unpatentable, which the Federal Circuit affirmed. RMF ¶¶ P16–17, P20–21; see Eli Lilly & Co. v.
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`Teva Pharms. Int’l GmbH, 2020 WL 1540364 (PTAB Mar. 31, 2020), aff’d, 8 F.4th 1331 (Fed.
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`Cir. 2021).4
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`3 The Board’s decisions (and Lilly’s arguments) in the IPRs are the subject of Teva’s Motion for
`Partial Summary Judgment Regarding Judicial Estoppel. ECF No. 314. In that motion, Lilly asks
`this Court to hold that Teva is judicially estopped from making arguments contrary to those that it
`made in the IPRs and which the Board credited in holding for Lilly. See ECF No. 315.
`4 Lilly is wrong that the Board held that it would be obvious to create “a claimed antibody”
`antibody, as opposed to “the entire scope of the antibody genus.” Mot. at 21. In the IPRs, neither
`Lilly nor the PTAB identified any particular anti-CGRP antagonist antibody as obvious. RMF
`¶¶ P4, P11–12. In fact, the PTAB found that the prior art disclosed and discussed anti-CGRP
`antagonist antibodies “without limitation to any particular anti-CGRP monoclonal antibody.”
`RMF ¶¶ P13–15; Eli Lilly & Co., 2020 WL 806932, at *40.
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`9
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`III. LEGAL STANDARDS
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`A.
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`Summary judgment
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`The Court may grant summary judgment only if the “pleadings, depositions, answers to
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`interrogatories, and admissions on file, together with the affidavits, if any, show that there is no
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`genuine issue as to any material fact and that the moving party is entitled to judgment as a matter
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`of law.” Fed. R. Civ. P. 56(c). “[T]he substantive law”—here, the law of written description—
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`“will identify which facts are material.” Anderson v. Liberty Lobby, 477 U.S. 242, 248 (1986).
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`To determine if a dispute about a material fact is “genuine,” the court must decide whether “the
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`evidence is such that a reasonable [factfinder] could return a verdict for the non-moving party.”
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`Id. The Court considers o