Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 1 of 42
`
`
`
`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,
`
`
`
`
`Civil Action No.
`1:18-cv-12029-ADB
`
`
`
`
`
`
`
`
`
`
`
`Defendant.
`
`
`
`
`
`
`
`PLAINTIFFS’ OPPOSITION TO ELI LILLY AND COMPANY’S MOTION FOR
`JUDGMENT AS A MATTER OF LAW UNDER FED. R. CIV. P. 50(B) AND/OR
`A NEW TRIAL UNDER FED. R. CIV. P. 59
`
`
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 2 of 42
`
`
`
`C.
`
`TABLE OF CONTENTS
`INTRODUCTION .............................................................................................................. 1
`FACTUAL BACKGROUND ............................................................................................. 1
`A.
`Evidence At Trial Relating To Written Description and Enablement .................... 1
`B.
`Evidence Presented at Trial Concerning Future Lost Profits .................................. 4
`ARGUMENT ...................................................................................................................... 5
`A.
`Legal Standard ........................................................................................................ 5
`B.
`Lilly Bore the Burden on Invalidity Yet Relied on Flawed Expert Opinions ........ 5
`1.
`Lilly Bore the Burden of Proof by Clear and Convincing Evidence .......... 5
`2.
`A Reasonable Jury Could Have Discredited Lilly’s Experts’ Opinions ..... 6
`Lilly Is Not Entitled to JMOL of Invalidity for Lack of Written Description ........ 9
`1.
`Written Description Is a Case-Specific Fact Question ............................... 9
`2.
`There Is No Legal Rule That Claims to a Class of Functionally-Defined
`Antibodies Lack Written Description ................................................................... 10
`3.
`Lilly Failed to Prove That the Claimed Antibody Genus Is “Broad” ....... 11
`4.
`The Specification Discloses a Representative Number of Species ........... 13
`5.
`Lilly Failed to Carry Its Burden as to Common Structural Features ........ 22
`6.
`Lilly Failed to Carry Its Burden as to the Treatment Aspects of the
`Claims ................................................................................................................... 23
`Lilly Is Not Entitled to JMOL of Invalidity for Lack of Enablement ................... 25
`D.
`Lilly’s Alternative Argument for a New Trial on Validity Should Be Denied .... 28
`E.
`The Jury’s Future Lost Profits Award Was Reasonable ....................................... 28
`F.
`CONCLUSION ................................................................................................................. 30
`
`
`
`I.
`II.
`
`III.
`
`IV.
`
`
`
`i
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 3 of 42
`
`
`
`TABLE OF AUTHORITIES
`
`
`
`Page(s)
`
`Cases
`
`AbbVie Deutschland GmbH v. Janssen Biotech, Inc.,
`759 F.3d 1285 (Fed. Cir. 2014)....................................................................................10, 12, 16
`
`Ajinomoto Co. v. Archer-Daniels-Midland Co.,
`228 F.3d 1338 (Fed. Cir. 2000)................................................................................................25
`
`Ajinomoto Co. v. ITC,
`932 F.3d 1342 (Fed. Cir. 2019)............................................................................................9, 16
`
`In re Alonso,
`545 F.3d 1015 (Fed. Cir. 2008)..........................................................................................14, 15
`
`Amgen Inc. v. Sanofi,
`872 F.3d 1367 (Fed. Cir. 2017)....................................................................................10, 12, 16
`
`Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010)..............................................................................10, 19, 20, 25
`
`Ascion, LLC v. Ashley Furniture Indus., Inc.,
`2022 WL 1197338 (Fed. Cir. Apr. 22, 2022) ..........................................................................10
`
`BASF Plant Science, LP v. CSIRO,
`28 F.4th 1247 (Fed. Cir. 2022) ........................................................................................ passim
`
`Bayer Healthcare LLC v. Baxalta Inc.,
`989 F.3d 964 (Fed. Cir. 2021)....................................................................................................9
`
`Bd. of Trs. of Leland Stanford Junior Univ. v. Chinese Univ. of H.K.,
`860 F.3d 1367 (Fed. Cir. 2017)..................................................................................................9
`
`Brooktree Corp. v. Advanced Micro Devices, Inc.,
`977 F.2d 1555 (Fed. Cir. 1992)................................................................................................30
`
`Capon v. Eshhar,
`418 F.3d 1349 (Fed. Cir. 2005)................................................................................................13
`
`Centocor Ortho Biotech, Inc. v. Abbott Lab’ys,
`636 F.3d 1341 (Fed. Cir. 2011)................................................................................................19
`
`Cephalon, Inc. v. Watson Pharms., Inc.,
`707 F.3d 1330 (Fed. Cir. 2013)................................................................................................26
`
`ii
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`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 4 of 42
`
`
`
`Cummins-Allison Corp. v. SBM Co.,
`584 F. Supp. 2d 916 (E.D. Tex. 2008) .....................................................................................28
`
`Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co.,
`276 F. Supp. 3d 629 (E.D. Tex. 2017) ............................................................................. passim
`
`Fail-Safe, L.L.C. v A.O. Smith Corp.,
`744 F. Supp. 2d 870 (E.D. Wis. 2010) .....................................................................................30
`
`Fiskars, Inc. v. Hunt Mfg. Co.,
`221 F.3d 1318 (Fed. Cir. 2000)................................................................................................28
`
`Fresenius USA, Inc. v. Baxter Int’l, Inc.,
`582 F.3d 1288 (Fed. Cir. 2009)................................................................................................28
`
`Halliburton Oil Well Cementing Co. v. Walker,
`329 U.S. 1 (1946) ...............................................................................................................10, 11
`
`In re Herschler,
`591 F.2d 693 (C.C.P.A. 1979) .................................................................................................13
`
`Hologic, Inc. v. Smith & Nephew, Inc.,
`884 F.3d 1357 (Fed. Cir. 2018)................................................................................................25
`
`Hyatt v. Dudas,
`551 F.3d 1307 (Fed. Cir. 2008)................................................................................................17
`
`Idenix Pharms. LLC v. Gilead Scis. Inc.,
`941 F.3d 1149 (Fed. Cir. 2019)..........................................................................................16, 27
`
`Immunex Corp. v. Sandoz Inc.,
`964 F.3d 1049 (Fed. Cir. 2020)................................................................................................22
`
`Juno Therapeutics, Inc. v. Kite Pharma, Inc.,
`10 F.4th 1330 (Fed. Cir. 2021) ..........................................................................................12, 16
`
`Lam, Inc. v. Johns-Manville Corp.,
`718 F.2d 1056 (Fed. Cir. 1983)..........................................................................................28, 30
`
`Lochner Techs., LLC v. Vizio, Inc.,
`567 F. App’x 931 (Fed. Cir. 2014) ..........................................................................................17
`
`Lockwood v. Am. Airlines, Inc.,
`107 F.3d 1565 (Fed. Cir. 1997)................................................................................................20
`
`Marine Polymer Techs., Inc. v. HemCon, Inc.,
`672 F.3d 1350 (Fed. Cir. 2012)..................................................................................................5
`
`iii
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`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 5 of 42
`
`
`
`New Railhead Mfg., L.L.C. v. Vermeer Mfg. Co.,
`298 F.3d 1290 (Fed. Cir. 2002)................................................................................................25
`
`Nuvo Pharm. (Ir.) Designated Activity Co. v. Dr. Reddy’s Lab’ys Inc.,
`923 F.3d 1368 (Fed. Cir. 2019)................................................................................................24
`
`Oiness v. Walgreen Co.,
`88 F.3d 1025 (Fed. Cir. 1996)..................................................................................................29
`
`Pernix Ir. Pain DAC v. Alvogen Malta Operations Ltd.,
`323 F. Supp. 3d 566 (D. Del. 2018) .........................................................................................15
`
`PPG Indus., Inc. v. Guardian Indus. Corp.,
`75 F.3d 1558 (Fed. Cir. 1996)..................................................................................................26
`
`Regents of the Univ. of California v. Eli Lilly & Co.,
`119 F.3d 1559 (Fed. Cir. 1997)................................................................................................18
`
`Rodríguez-Valentin v. Doctors’ Ctr. Hosp. (Manati), Inc.,
`27 F.4th 14 (1st Cir. 2022) ...................................................................................................1, 28
`
`Sanchez v. Foley,
`972 F.3d 1 (1st Cir. 2020) ..........................................................................................................6
`
`Sebastino v. Springfield Terminal Ry.,
`530 F. Supp. 3d 81 (D. Mass. 2021) ..........................................................................................5
`
`Shockley v. Arcan, Inc.,
`248 F.3d 1349 (Fed. Cir. 2001)..........................................................................................28, 29
`
`Tech. Licensing Corp. v. Videotek, Inc.,
`545 F.3d 1316 (Fed. Cir. 2008)..................................................................................................5
`
`TQ Delta, LLC v. CISCO Sys., Inc.,
`942 F.3d 1352 (Fed. Cir. 2019)..................................................................................................5
`
`Valmont Indus., Inc. v. Reinke Mfg. Co.,
`983 F.2d 1039 (Fed. Cir. 1993)................................................................................................10
`
`In re Wands,
`858 F.2d 731 (Fed. Cir. 1988)............................................................................................25, 26
`
`Warner-Jenkinson Co. v. Hilton Davis Chem. Co.,
`520 U.S. 17 (1997) ...................................................................................................................10
`
`WBIP, LLC v. Kohler Co.,
`829 F.3d 1317 (Fed. Cir. 2016)............................................................................................5, 23
`
`iv
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`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 6 of 42
`
`
`
`Wyeth & Cordis Corp. v. Abbott Lab’ys,
`720 F.3d 1380 (Fed. Cir. 2013)................................................................................................27
`
`Statutes
`
`35 U.S.C. § 112 ....................................................................................................................1, 17, 25
`
`Other Authorities
`
`37 C.F.R. § 1.53 .............................................................................................................................25
`
`37 C.F.R. § 1.78 .............................................................................................................................25
`
`MPEP § 2139.01(C) .......................................................................................................................25
`
`
`
`
`
`
`v
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`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 7 of 42
`
`
`
`BBB
`Br.
`
`cAMP
`CCW
`CGRP
`G1
`Gmab
`IPR
`JMOL
`Lilly
`POSA
`PTAB
`PTO
`Teva
`
`Tr.
`
`TABLE OF ABBREVIATIONS
`Blood-Brain Barrier
`Memorandum in Support of Eli Lilly and Company’s Motion for Judgment as a
`Matter of Law Under Fed. R. Civ. P. 50(B) and/or a New Trial Under Fed. R.
`Civ. P. 59 (ECF No. 650)
`Cyclic Adenosine Mono-Phosphate
`Closed Cranial Window
`Calcitonin Gene-Related Peptide
`Fremanezumab or “Fmab”
`Galcanezumab
`Inter Partes Review
`Judgment as a Matter of Law
`Eli Lilly & Co.
`Person of Ordinary Skill in the Art
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`Plaintiffs Teva Pharmaceuticals International GmbH and Teva Pharmaceuticals
`USA, Inc.
`Trial Transcript†
`
`
`
`
`
`
`
`† Citations to the Trial Transcript indicate the trial day followed by a hyphen, then page and line
`numbers.
`
`vi
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 8 of 42
`
`
`
`TABLE OF ADMITTED EXHIBITS
`Title
`
`U.S. Patent No. 8,586,045
`
`U.S. Patent No. 9,884,907
`
`U.S. Patent No. 9,884,908
`
`US Patent No. 6,180,370 (“Queen”)
`“Preventing Headaches,” Time Magazine (2002)
`Review of Study 8227-046: Blood Flow LDI Rat Blinded
`Antibodies
`
`Email from
`Email from
`
` (Apr. 7, 2014)
` (Mar. 14, 2019)
`
`Trial
`Exhibit
`TX-0001‡
`
`TX-0002
`
`TX-0003
`
`PTX_107
`PTX_111
`PTX_130
`
`PTX_332
`PTX_342
`
`Declaration Exhibit
`Number
`Frederickson Decl.§
`Ex. 1
`Frederickson Decl.
`Ex. 2
`Frederickson Decl.
`Ex. 3
`Blais Decl.** Ex. 1
`Blais Decl. Ex. 2
`Blais Decl. Ex. 3
`
`Blais Decl. Ex. 4
`Frederickson Decl.
`Ex. 5
`Blais Decl. Ex. 5
`Blais Decl. Ex. 6
`
`Blais Decl. Ex. 7
`
`Blais Decl. Ex. 8
`Blais Decl. Ex. 9
`
`Blais Decl. Ex. 10
`
`PTX_372
`PTX_474
`
`PTX_531
`
`“Competitor anti-CGRP Ab” Presentation
`Andrew et al., Monoclonal Antibodies Distinguishing a and B
`Forms of Calcitonin Gene-Related Peptide, 154 J.
`Immunological Methods, 87 (1990) (“Andrew 1990”)
`FDA Guidance, Estimating the Maximum Safe Starting Dose
`(2005)
`Sigma Aldrich Catalog (2004)
`PTX_671
`PTX_865 M. Bendig & S.T. Jones, Rodent to Human Antibodies by CDR
`Grafting, 1996 (“Bendig 1996”)
`H.J. Hong & S.T. Kim, Antibody Engineering, 7 Biotech.
`Bioprocess Eng. 150 (2002) (“Hong 2002”)
`
`PTX_881
`
`
`‡ Teva cites trial exhibit documents using trial exhibit pagination, omitting leading zeroes.
`§ Declaration of Robert Frederickson III In Support Of Teva’s Motion for Post-Trial Relief (ECF
`No. 645).
`** Declaration of Elaine Herrmann Blais In Support of Teva’s Opposition to Eli Lilly and
`Company’s Motion for Judgment As A Matter of Law Under Fed. R. Civ. P. 50(B) and/or A New
`Trial Under Fed. R. Civ. P. 59 (filed concurrently herewith).
`
`vii
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 9 of 42
`
`
`
`Title
`
`Trial
`Exhibit
`PTX_894 A. Mountain & J.R. Adair, Engineering Antibodies for Therapy,
`10 Biotech & Genetic Eng’g Revs. 1 (1992) (“Mountain 1992”)
`IPR2018-01422, Final Written Decision
`IPR2018-01424, Final Written Decision
`IPR2018-01710, Charles Declaration
`
`PTX_923
`PTX_924
`PTX_928
`
`
`
` (Nov. 5, 2009)
`
`
`
`
`
`PTX_1368
`
`
`Email from
`
`PTX_1853
`
`IPR2018-01424, Petition for Inter Partes Review
`
`PTX_1871
`
`IPR2018-01427, Petition for Inter Partes Review
`
`PTX_1877
`
`IPR2018-01710, Petition for Inter Partes Review
`
`PTX_1882
`PTX_1903
`
`PTX_1906
`
`IPR2018-01710, Vasserot Declaration
`Decision of the U.S. Court of Appeals for the Federal Circuit,
`Teva Pharms. Int’l GmBH v. Eli Lilly & Co., Case Nos. 2020-
`1747, 2020-1748, 2020-1750 (Aug. 16, 2021); 8 F.4th 1349
`Decision of the U.S. Court of Appeals for the Federal Circuit,
`Teva Pharms. Int’l GmBH v. Eli Lilly & Co., Case Nos. 2020-
`1749, 2020-1751, 2020-1752 (Aug. 16, 2021); 856 F. App’x 312
`(Fed. Cir. 2021)
`PTX_1909 Decision of the U.S. Court of Appeals for the Federal Circuit, Eli
`Lilly & Co. v. Teva Pharms. Int’l GmbH, Case Nos. 2020-1876,
`2020-1877, 2020-1878 (Aug. 16, 2021); 8 F.4th 1331 (Fed. Cir.
`2021)
`J. Olesen et al., Calcitonin Gene-Related Peptide Receptor
`Antagonist BIBN 4096 for the Acute Treatment of Migraine, 350
`New England J. Med. 1104 (2004) (“Olesen 2004”)
`
`PTX_2012
`
`viii
`
`Declaration Exhibit
`Number
`Blais Decl. Ex. 11
`
`Blais Decl. Ex. 12
`Blais Decl. Ex. 13
`Blais Decl. Ex. 14
`
`
`Blais Decl. Ex. 16
`
`
`Frederickson Decl.
`Ex. 15
`Frederickson Decl.
`Ex. 16
`Frederickson Decl.
`Ex. 18
`Blais Decl. Ex. 17
`18
`
`Blais Decl. Ex. 19
`
`Blais Decl. Ex. 20
`
`Blais Decl. Ex. 21
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 10 of 42
`
`
`
`Trial
`Exhibit
`PTX_2027 A. Bergerot et al., Animal Models of Migraine: Looking at the
`Component Parts of a Complex Disorder, 24 Eur. J.
`Neuroscience 1517 (2006) (“Bergerot”)
`U.S. Patent No. 9,505,838
`K. 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. 565 (1995) (“Tan 1995”)
`TX-3446 N.E. Shaw, The Effect of Monoclonal Antibodies to Calcitonin
`Gene-Related Peptide (CGRP) on CGRP-Induced
`Vasodilatation in Pig Coronary Artery Rings, 106 Br. J.
`Pharmacology 196 (1992) (“Shaw 1992”)
`P. Goadsby, Calcitonin Gene-Related Peptide Antagonists as
`Treatments of Migraine and Other Primary Headaches, 65
`Drugs 2557 (2005) (“Goadsby 2005”)
`Anti-CGRP LA468 update, Data review and decisions made at
`team meeting (Sept. 18, 2006) [Replacement]
`Email from
` (Mar. 23, 2011)
`
`TX-3053
`TX-3331
`
`TX-3484
`
`TX-5162
`
`TX-5163
`
`Declaration Exhibit
`Number
`Blais Decl. Ex. 22
`
`Blais Decl. Ex. 23
`Blais Decl. Ex. 24
`
`Blais Decl. Ex. 25
`
`Blais Decl. Ex. 26
`
`Blais Decl. Ex. 27
`
`Blais Decl. Ex. 28
`
`Title
`
`ix
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 11 of 42
`
`
`
`I.
`
`INTRODUCTION
`
`The jury reasonably found that Lilly did not prove invalidity under 35 U.S.C. § 112 by
`
`clear and convincing evidence. The jury also reasonably found that Teva did prove its entitlement
`
`to future lost profits by a preponderance of the evidence. The Court should deny Lilly’s motion
`
`for JMOL or new trial.
`
`II.
`
`FACTUAL BACKGROUND
`
`A Rule 50(b) motion turns on the evidence before the jury, and the Court must “view the
`
`evidence in the light most flattering to the verdict and must draw all reasonable inferences
`
`therefrom in favor of the verdict.” Rodríguez-Valentin v. Doctors’ Ctr. Hosp. (Manati), Inc., 27
`
`F.4th 14, 20 (1st Cir. 2022) (citation omitted). Taking that standard into account, Teva provides
`
`this brief summary of what the jury learned from the 36 witnesses and 446 exhibits presented
`
`during the three-week trial.
`
`A.
`
`Evidence at Trial Relating to Written Description and Enablement
`
`The patents-in-suit teach and claim novel methods of using a readily accessible class of
`
`antibodies—humanized anti-CGRP antagonist antibodies—to treat headaches, such as migraine.1
`
`Before the Zeller team’s pioneering work, a connection between CGRP and headache had been
`
`established, and both clinically-effective small molecule drugs targeting the CGRP pathway and
`
`anti-CGRP antagonist antibodies had been described in the scientific literature, but a POSA did
`
`not yet know whether the antibodies could be used to prevent headache.2 The Zeller team obtained
`
`a murine anti-CGRP antagonist antibody from UCLA and developed their own antibodies by
`
`
`1 Tr. 14-281:9–14, 15-16:19–24 (Hill); 15-96:19–97:22 (Hale); 14-188:12–16 (Blumenfeld). See
`generally TX-0001, -0002, -0003.
`2 Tr. 2-93:7–100:24 (Rosenthal); 2-147:11–149:22 (Zeller); 14-197:2–201:1 (Blumenfeld); 14-
`281:15–282:20, 14-283:24–291:3, 15-9:14–16:24, 15-76:20–77:5 (Hill); 15-97:23–102:13 (Hale).
`
`1
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 12 of 42
`
`
`
`immunizing mice.3 They then (1) tested the antibodies using established animal models to see if
`
`they would prevent headache and (2) humanized them using routine techniques.4 It worked, and
`
`the Zeller team obtained patents covering, inter alia, their novel methods of treatment.
`
`The Zeller patents’ specification built on the prior art by disclosing experimental data for
`
`97 different humanized and murine anti-CGRP antibodies, including antibody G1.5 This included
`
`a detailed study of CGRP antagonism using numerous murine antibodies in cell-based and in vivo
`
`functional assays, including the CCW assay—a clinically-validated migraine model that is
`
`predictive for treating migraine in humans.6 The study showed a strong correlation between in
`
`vitro antagonism of CGRP and efficacy in animal models.7 A POSA would understand this to
`
`prove that anti-CGRP antagonist antibodies could treat headache in humans.8 The jury also heard
`
`that a POSA would understand the data in the specification for antibody G1 to be representative
`
`of anti-CGRP antagonist antibodies generally—that once the inventors showed G1 would treat
`
`headache, a POSA would understand that any humanized anti-CGRP antagonist antibody would.9
`
`In addition to its method of treatment patents, the Zeller team also obtained patents
`
`covering the underlying antibodies. However, as the Court knows, those antibody claims were
`
`found to be obvious in IPRs brought by Lilly.10 In those IPRs, Lilly told the PTO that “the prior
`
`art [was] replete with exemplary disclosures of anti-CGRP antagonist antibodies, including
`
`humanized antibodies, to treat human diseases and conditions,” and that the antibodies “were
`
`
`3 Tr. 2-154:16–155:16 (Zeller); 3-91:8–20, 3-94:21–25 (Abdiche); 2-100:19–102:7 (Rosenthal).
`4 Tr. 2-102:5–104:7 (Rosenthal); 2-161:16–182:3 (Zeller); 3-102:15–105:18, 3-109:17–110:10
`(Abdiche); 15-29:20–30:13, 15-42:17–52:12 (Hill).
`5 See TX-0001 at 50:6–69:67.
`6 TX-0001 at 53:35–57:12, 67:53–69:67; Tr. 15-40:1–19, 15-42:17–24 (Hill); PTX_2027 at 6.
`7 Tr. 15-62:14–64:23 (Hill); 15-158:2–159:18 (Hale).
`8 Tr. 15-62:14–64:18 (Hill); 15-125:7–20, 15-158:2–162:21 (Hale).
`9 Tr. 15-64:6–23 (Hill); 15-161:18–162:21 (Hale).
`10 PTX_923 at 1; PTX_924 at 1. The Federal Circuit affirmed. PTX_1903; PTX_1906.
`
`2
`
`

`

`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 13 of 42
`
`
`
`effective in vivo at eliminating or reducing CGRP’s biological effects linked to migraine.”11 These
`
`prior-art disclosures included antibodies that bind to each of the three major regions of CGRP.12
`
`More generally, methods for making murine anti-CGRP antagonist antibodies were well
`
`known to a POSA.13 A POSA had a high level of skill and, as of the effective filing date, the
`
`ability to readily generate anti-CGRP antagonist antibodies.14 A mouse immunized with CGRP
`
`would reliably generate anti-CGRP antibodies—not antibodies reactive to other antigens.15
`
`Antibodies that antagonize CGRP then could be rapidly identified using routine techniques such
`
`as the cAMP cell assay, in which over a million antibodies could be tested in just a few days.16 A
`
`POSA also could confirm an antibody’s ability to antagonize CGRP in vivo using animal models
`
`like the CCW assay.17
`
`Once murine antibodies were generated, the process of humanizing them also was routine
`
`and predictable as of the filing date.18 Lilly itself argued to the PTO that “humanization was a
`
`well-established and routine procedure by the time Teva filed its application,” so the concept “does
`
`not and cannot provide any patentable weight” to the Zeller patents.19 Dr. Abdiche testified that
`
`she humanized antibodies after “just read[ing] a few textbooks and the scientific literature.”20
`
`
`
`11 PTX_1871 at 39.
`12 TX-0001 at 50:45–52, 66:62–67:15; Tr. 12-80:5–82:7 (McDonnell); 14-290:16–291:3, 15-9:16–
`10:4 (Hill); 15-106:20–107:10 (Hale); PTX_474 at 3; TX-3446 at 196–97.
`13 See TX-0001 at 12:52–60, 27:41–30:57; Tr. 15-103:15–104:15, 15-106:14–107:10, 15-109:13–
`20 (Hale); 14-288:22–289:9 (Hill); 2-154:24–155:8 (Zeller); PTX_474 at 1, 3.
`14 Tr. 11-29:13–30:1 (definition of a POSA); 12-56:17–22 (McDonnell); 14-287:9–291:3 (Hill);
`15-106:14–109:20, 15-125:22–126:5, 15-158:19–159:4 (Hale).
`15 Tr. 14-288:22–289:9 (Hill); 15-129:12–23 (Hale); 12-57:5–11 (McDonnell).
`16 Tr. 2-157:21–158:12 (Zeller); 15-57:20–60:8 (Hill); 15-105:1–106:13 (Hale).
`17 Tr. 2-161:2–182:3 (Zeller); 15-42:17–52:12, 15-63:23–64:5 (Hill); PTX_2027 at 6.
`18 TX-0001 at 28:43–29:28; Tr. 12-52:3–59:5 (McDonnell); 15-109:21–119:9, 15-152:20–156:25
`(Hale); PTX_1853 at 50; PTX_894 at 16; PTX_881 at 1; see generally PTX_107, PTX_865.
`19 PTX_1877 at 10 (emphasis added).
`20 Tr. 3-105:9–18, 3-109:17–23.
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`3
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`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 14 of 42
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`
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`B.
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`Evidence Presented at Trial Concerning Future Lost Profits
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`Teva’s expert Dr. Berkman presented Teva’s future lost profits testimony. He explained
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`that he based his calculations entirely on Lilly’s own internal forecasting documents—Lilly’s
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`strategic plans.21
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`
`
`
`
` Dr.
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`Berkman used Lilly’s own forecasts to determine the (1) size of total CGRP antibody market; (2)
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`number of Emgality units; (3) Emgality revenue; and (4) Emgality net price per unit, all through
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`the expiration of the Zeller patents in 2026.23
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`Teva’s future lost profits claim had two components: lost sales and higher rebates. For lost
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`sales, Dr. Berkman performed a proportional reallocation of the anti-CGRP market to estimate
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`that, in the but-for world, an average of 9.3% of Emgality’s sales through patent expiration will be
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`taken away from Ajovy.24 This was conservatively lower than the 20% he attributed to Teva for
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`past lost profits because “the market has become more crowded over time” due to the introduction
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`of oral CGRP treatment options—the so-called “gepants.”25 Dr. Berkman then calculated future
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`lost profits due to higher rebate costs. Using the 9.3% market share allocation, he calculated the
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`number of future Ajovy units and multiplied this by the difference in net price in a world without
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`Lilly’s infringement.26 As an additional conservative step, he applied a discount rate of 7.5% to
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`Teva’s future lost profits due to higher rebate costs.27 Combining lost sales and higher rebate
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`21 Tr. 8-49:23–51:20 (Berkman).
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`23 Tr. 8-49:23–52:4 (Berkman).
`24 Tr. 8-56:13–18 (Berkman).
`25 Tr. 8-56:19–57:4 (Berkman).
`26 Tr. 8-57:15–60:8, 8-62:5–63:22 (Berkman).
`27 Tr. 8-63:23–65:21 (Berkman).
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`4
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`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 15 of 42
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`costs, Dr. Berkman opined that Teva is entitled to approximately $158.3 million in future lost
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`profits.28 However, after weighing all the evidence—including the same criticisms of Dr.
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`Berkman’s analysis found in Lilly’s JMOL brief—the jury awarded Teva only $49.8 million.
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`III. ARGUMENT
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`A.
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`Legal Standard
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`“[A] jury’s verdict must be upheld unless the facts and inferences, viewed in the light most
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`favorable to the verdict, point so strongly and overwhelmingly in favor of the movant that a
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`reasonable jury could not have reached the verdict.” Marine Polymer Techs., Inc. v. HemCon,
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`Inc., 672 F.3d 1350, 1357–58 (Fed. Cir. 2012) (quoting Astro-Med, Inc. v. Nihon Kohden Am.,
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`Inc., 591 F.3d 1, 13 (1st Cir. 2009)). A “verdict should be set aside only if the jury failed to reach
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`the only result permitted by the evidence.” Sebastino v. Springfield Terminal Ry., 530 F. Supp. 3d
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`81, 85 (D. Mass. 2021) (citation omitted). General or conclusory expert testimony “does not rise
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`to the level of clear and convincing evidence” needed to invalidate a patent. WBIP, LLC v. Kohler
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`Co., 829 F.3d 1317, 1339 (Fed. Cir. 2016); TQ Delta, LLC v. CISCO Sys., Inc., 942 F.3d 1352,
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`1359 n.5 (Fed. Cir. 2019). The Federal Circuit reviews jury findings “[b]ased on what was
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`presented to the jury,” not arguments developed only after trial. WBIP, 829 F.3d at 1338.
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`B.
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`Lilly Bore the Burden on Invalidity Yet Relied on Flawed Expert Opinions
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`1.
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`Lilly Bore the Burden of Proof by Clear and Convincing Evidence
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`Patents are presumed to be valid, and so Lilly needed to prove invalidity by clear and
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`convincing evidence. Id. at 1339. That burden never shifts to the patentee. Tech. Licensing Corp.
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`v. Videotek, Inc., 545 F.3d 1316, 1328–29 (Fed. Cir. 2008). Thus, Lilly’s numerous suggestions
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`that Teva needed to prove validity—e.g., that “Teva’s experts failed to provide legally sufficient
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`28 Tr. 8-68:6–9 (Berkman).
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`5
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`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 16 of 42
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`testimony to support written description,” Br. at 15—are a non-starter.
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`2.
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`A Reasonable Jury Could Have Discredited Lilly’s Experts’ Opinions
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`Before addressing Lilly’s specific arguments, three points must be made concerning the
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`quality of the opinions proffered by Lilly’s experts regarding patent validity. “It [is] up to the jury
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`to weigh the credibility of . . . witnesses,” and a court “may not second guess such assessments
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`when reviewing motions for judgment as a matter of law.” Sanchez v. Foley, 972 F.3d 1, 15 (1st
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`Cir. 2020). There are substantial reasons why a reasonable jury could have found that Lilly’s
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`experts lacked credibility and offered unsound opinions, and thus elected not to credit them.
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`First, Lilly’s experts all displayed startling ignorance of the relevant facts and law. Dr.
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`McDonnell was Lilly’s principal validity witness at trial and remains the star of Lilly’s JMOL
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`brief, which cites his testimony dozens of times and asks the Court to find that numerous key facts
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`were established by his testimony alone. Indeed, unlike a typical JMOL brief, which assumes that
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`the jury discredited the moving party’s witnesses and so does not rely on them, Lilly’s JMOL brief
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`largely assumes that the jury needed to credit Dr. McDonnell over Teva’s experts. Under the
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`JMOL standard, that is legal error. Supra, p. 5.
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`A reasonable jury easily could have rejected Dr. McDonnell’s opinions. As just one
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`important example, after testifying on direct that humanization was not routine for a POSA as of
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`the filing date, Dr. McDonnell repeatedly professed that he did not know the Queen reference.29
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`Yet a mountain of evidence showed that a POSA would be very familiar with Queen, a landmark
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`reference in the field that Lilly called the “gold standard” for humanization in the IPRs.30 Indeed,
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`Queen’s teachings are cited by both the Zeller patents and Lilly’s own patent covering Emgality.31
`
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`29 Tr. 12-48:5–22, 12-53:5–14, 12-54:20–55:10, 12-58:9–59:4.
`30 E.g., Tr. 15-112:13–115:2 (Hale); PTX_1877 at 41; PTX_1871 at 32.
`31 TX-3053 at 7:61–66; TX-0001 at 28:55–64.
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`6
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`Case 1:18-cv-12029-ADB Document 673 Filed 02/28/23 Page 17 of 42
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`Dr. McDonnell’s unfamiliarity with Queen means (1) he could not offer reliable opinions
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`concerning the state of humanization as of the filing date, since a POSA (unlike Dr. McDonnell)
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`would know Queen, and (2) the jury could conclude that he lacked credibility as an expert overall,
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`because a true antibody expert would be familiar with Queen.
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`The jury also had reason to discredit Lilly’s other validity experts. Dr. Charles testified he
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`was unaware of the court’s claim construction for “effective amount,” repeatedly stating during
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`cross that he did not consider it.32 While on redirect he testified that two paragraphs in his report
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`contained “consideration” of the claim construction order,33 he never explained how, nor did he
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`retract his testimony that the specific opinions he offered at trial did not account for it. And Dr.
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`Mould both claimed “surprise” at the claim construction and was unaware that the hypothetical
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`POSA knows all the pertinent prior art, even disparaging the governing legal standard as “a bit of
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`stretch.”34 Tellingly, Lilly does not cite Dr. Mould in its JMOL brief even once.
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`Second, it would be reasonable for the jury to take into account the inconsistencies between
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`the positions Lilly and its experts advanced in this lawsuit, and the contradictory positions that
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`Lilly previously—and successfully—advanced in the IPRs. For example, Lilly argued to the
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`PTAB: that the antibodies used in the patented methods were obvious; that by 2005 anti-CGRP
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`antagonist antibodies were well-known in the art; that the generation of such antibodies was
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`routine and conventional; that humanizing such antibodies was well-established and conventional;
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`and that the use of assays to measure antagonism was conventional and routine.35 The PTAB
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`agreed with all of these positions. Before he was confronted with Lilly’s IPR briefing and expert
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`
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`32 Tr. 12-238:19–239:10.
`33 Tr. 13-68:5–7.
`34 Tr. 13-156:24–157:25, 166:9–14; PTX_1909 at 7–8; ECF No. 101 at 31–32.
`35 E.g., PTX_18