Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 1 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 1 of 53
`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF MASSACHUSETTS
`
`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBHand
`TEVA PHARMACEUTICALSUSA,INC.,
`
`Case No. 1:18-cv-12029-ADB
`
`eeeeaeeeeeeeeeeea
`
`Plaintiffs,
`
`Vv.
`
`ELI LILLY AND COMPANY,
`
`Defendant.
`
`Leaveto File Granted on
`Feb. 22, 2022 (ECF No. 272)
`
`Leave to File Under Seal Granted on
`Mar. 28, 2022 (ECF. No. 285)
`
`L.R. 56.1 STATEMENT OF MATERIAL FACTS IN SUPPORT OF
`DEFENDANT ELI LILLY AND COMPANY’S MOTION FOR
`
`PARTIAL SUMMARY JUDGMENT OF NON-INFRINGEMENT
`
`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 2 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 2 of 53
`
`Short Cite
`°045 patent
`
`°210 patent
`
`°211 patent
`
`°614 patent
`
`°649 patent
`
`°881 patent
`
`°907 patent
`
`°908 patent
`
`°951 patent
`
`AbdicheTr.
`
` _=
`
`TABLE OF ABBREVIATIONS
`
`
`
`Description & Other Names/References
`Patent-in-suit. U.S. Patent No. 8,586,045 to Joerg Zeller et al., issued
`November19, 2013, entitled “Methods of Using Anti-CGRP Antagonist
`Antibodies” currently assigned to Teva Pharmaceuticals International
`GmbH
`US. Patent No. 9,890,210 to Joerg Zeller et al., issued February 13, 2018,
`entitled “Antagonist Antibodies Directed Against Calcitonin Gene-
`Related Peptide” currently assigned to Teva Pharmaceuticals International
`GmbH
`USS. Patent No. 9,890,211 to Joerg Zeller et al., issued February 13, 2018,
`entitled “Antagonist Antibodies Directed Against Calcitonin Gene-
`Related Peptide” currently assigned to Teva Pharmaceuticals International
`GmbH
`USS. Patent No. 9,340,614 to Joerg Zeller et al., issued May 17, 2016,
`entitled “Antagonist Antibodies Directed Against Calcitonin Gene-
`Related Peptide and Methods Using Same”currently assigned to Teva
`Pharmaceuticals International GmbH
`USS. Patent No. 8,597,649 to Joerg Zeller et al., issued December3, 2013,
`entitled “Antagonist Antibodies Directed Against Calcitonin Gene-
`Related Peptide and Methods Using Same”currently assigned to Teva
`Pharmaceuticals International GmbH
`U.S. Patent No. 9,346,881 to Joerg Zeller et al., issued May 24, 2016,
`entitled “Antagonist Antibodies Directed Against Calcitonin Gene-
`Related Peptide and Methods Using Same”currently assigned to Teva
`Pharmaceuticals International GmbH
`Patent-in-suit. U.S. Patent No. 9,884,907 to Joerg Zeller et al., issued
`February 6, 2018, entitled “Methods for Treating Headache Using
`Antagonist Antibodies Directed Against Calcitonin Gene-Related
`Peptide” currently assigned to Teva Pharmaceuticals International GmbH
`Patent-in-suit. U.S. Patent No. 9,884,908 to Joerg Zeller et al., issued
`February 6, 2018, entitled “Methods for Treating Headache Using
`Antagonist Antibodies Directed Against Calcitonin Gene-Related
`Peptide” currently assigned to Teva Pharmaceuticals International GmbH
`US. Patent No. 9,266,951 to Joerg Zeller et al., issued February 23, 2016,
`entitled “Antagonist Antibodies Directed Against Calcitonin Gene-
`Related Peptide and Methods Using Same”currently assigned to Teva
`Pharmaceuticals International GmbH
`Transcript of deposition of Yasmina Noubia Abdiche, named inventor of
`the patents-in-suit, dated August 17, 2021
`
` Blood-brain barrier
`
`BBB
`
`— |
`
`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 3 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 3 of 53
`
`
`
`
`
`Expert Report of Mark P. Berkman, on behalf of Teva, served September
`16, 2021
`Transcript of deposition of fact witness Marcelo Eduardo Bigal, defended
`by Teva counsel, dated June 10, 2021
`Opening Expert Report of Pamela Blake, M.D., FAHS, Regarding
`Infringement, on behalf of Teva, served September 16, 2021
`Reply Expert Report of Pamela Blake, M.D., FAHS, Regarding
`Infringement, on behalf of Teva, served December 7, 2021
`Transcript of deposition of expert Pamela Blake, M.D., FAHS,on behalf
`of Teva, dated January
`10, 2022
`Responsive Expert Report of Andrew Blumenfeld, M.D. Regarding
`Validity, on behalf of Teva, served November1, 2021
`Transcript of deposition of expert Andrew Blumenfeld, M.D., on behalf of
`Teva, dated January
`26, 2022
`
`
`
`
`Opening Expert Report of Dr. Andrew Charles Regarding Invalidity of
`US. Patent Nos. 8,586,045, 9,884,907, and 9,884,908, on behalf ofLilly,
`served September 16, 2021
`Rebuttal Expert Report of Dr. Andrew Charles Regarding
`Noninfringement, on behalf of Lilly, served November 1, 2021
`Reply Expert Report of Dr. Andrew Charles Regarding Invalidity of U.S.
`Patent Nos. 8,586,045, 9,884,907, and 9,884,908, on behalf of Lilly,
`served December 7, 2021
`
`
`
`
`
`
`Berkman Op.
`
`Bigal Tr.
`
`Blake Op.
`
`Blake Reply
`
`Blake Tr.
`
`Blumenfeld Resp.
`
`Blumenfeld Tr.
`
`CGRP
`Charles Op.
`
`Charles Reb.
`
`Charles Reply
`
`ECF No.
`
`Ex.
`FDA
`Ferrari Decl.
`
`Foord Decl.
`
`Foord Tr.
`
`=
`
`Hale Supp.
`
`Hale Tr.
`
`Documents from the public docketfiled through the CM/ECFsystem.
`Unless otherwise noted, citations are to the public docket of Case No.
`1:18-cv-12029-ADB, D. Mass.
`Exhibits to concurrently-filed Attorney Declaration
`Food and Drug Administration
`Declaration of expert Dr. Michel D. Ferrari, M.D., Ph.D., on behalf of
`Teva,filed July 3, 2019 in IPR2018-01710, Eli Lilly & Co. v. Teva
`Pharms. Int’] GmbH
`Declaration of expert Steven M. Foord, Ph.D., on behalf of Teva, filed
`July 3, 2019 in IPR2018-01710, Eli Lilly & Co. v. Teva Pharms. Int’l
`GmbH
`Transcript of deposition of expert Steven M. Foord, Ph.D., on behalf of
`
` Teva, dated September 27, 2019
`
`United States Patent and Trademark Office Patent Trial and Appeal Board
`
`on behalf of Teva, served November 1, 2021
`Supplemental Responsive Expert Report of Geoffrey Hale, Ph.D.,
`Regarding Validity, on behalf of Teva, served Janu
`7, 2022
`Transcript of deposition of expert Geoffrey Hale, Ph.D., on behalf of
`Teva, dated January
`25, 2022
`
`i
`
`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 4 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 4 of 53
`
`
`
` POSA
`
`Harnish Tr.
`
`Hill Reb.
`
`Hill Tr.
`
`ICHD-Il
`
`IPR
`
`IPR2018-1710
`Vasserot Decl.
`
`IPR2018-1711
`Vasserot Decl.
`
`IPR2018-1712
`Vasserot Decl.
`
`LR.
`McDonnell Op.
`
`McDonnell Reb.
`
`McDonnell Reply
`
`McDonnell Supp.
`
`Mould Op.
`
`Mould Reply
`
`Pons Decl.
`
`Pons Tr.
`
`POR
`
`
`
`Transcript of deposition of fact witness Douglas Harnish, Ph.D., defended
`by Teva counsel, dated July 29, 2021
`Rebuttal Expert Report of RaymondHill, Ph.D., Regarding Validity of
`US. Patent Nos. 8,586,045, 9,884,907, and 9,884,908, on behalf of Teva,
`served November 1, 2021
`Transcript of deposition of expert Dr. Raymond Hill, on behalf of Teva,
`dated January
`20, 2022
`International Classification of Headache Disorders, 2nd edition
`Inter partes review proceedingsat the United States Patent and
`Trademark Office
`Declaration of expert Dr. Alain P. Vasserot, Ph.D., on behalf of Lilly,
`dated September 9, 2018 in IPR2018-01710, Eli Lilly & Co. v. Teva
`Pharms. Int’] GmbH
`Declaration of expert Dr. Alain P. Vasserot, Ph.D., on behalf of Lilly,
`dated September 27, 2018 in IPR2018-01711, Eli Lilly & Co. v. Teva
`Pharms. Int’| GnbH
`Declaration of expert Dr. Alain P. Vasserot, Ph.D., on behalf of Lilly,
`dated September 27, 2018 in IPR2018-01712, Eli Lilly & Co. v. Teva
`
`Pharms. Int’| GnbH
`
`patents-in-suit, dated August 20, 2021
`
`Local Rule
`Opening Expert Report of James M. McDonnell, Ph.D., Regarding
`Invalidity of U.S. Patent Nos. 8,586,045, 9,884,907, and 9,884,908, on
`behalf of Lilly, served September 16, 2021
`Rebuttal Expert Report of James M. McDonnell, Ph.D., Regarding
`Noninfringementof U.S. Patent Nos. 8,586,045, 9,884,907, and
`9,884,908, on behalf of Lilly, served November 1, 2021
`Reply Expert Report of James M. McDonnell, Ph.D., Regarding Invalidity
`of U.S. Patent Nos. 8,586,045, 9,884,907, and 9,884,908, on behalf of
`Lilly, served December 7, 2021
`Supplemental Reply Expert Report of James M. McDonnell, Ph.D.,
`Regarding Invalidity of U.S. Patent Nos. 8,586,045, 9,884,907, and
`9,884,908, on behalf of Lilly, served January 21, 2022
`
`Opening Expert Report of Diane R. Mould, Ph.D., FCP, FAAPS, on
`behalf of Lilly, served September 16, 2021
`Reply Expert Report of Diane R. Mould, Ph.D., on behalf of Lilly, served
`December7, 2021
`Declaration of Jaume Pons, Ph.D., named inventor of the patents-in-suit,
`on behalf of Teva, filed July 3, 2019 in IPR2018-01710, Eli Lilly & Co.v.
`Teva Pharms. Int’] GmbH
`Transcript of deposition of Jaume Pons, Ph.D., named inventor of the
`
`Patent Owner Response in an Jnter Partes Review proceeding before the
`United States Patent and Trademark Office Patent Trial and Appeal Board
`Person ofordinary
`skill in the art
`
`ill
`
`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 5 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 5 of 53
`
`
`
`Transcript of deposition of Kristian T. Poulsen, named inventorof the
`patents-in-suit, dated August 5, 2021
`
`Office
`
`by Teva counsel, dated August 10, 2021
`Transcript of deposition of expert Alan M. Rapoport, M.D., on behalf of
`Teva, dated August 22, 2019
`Expert Declaration of Jeffrey V. Ravetch, M.D., Ph.D. (ECF No. 70), on
`
`behalf of Teva, filed September 11, 2020
`
`
`Pharms. Int’l GmbH Tomlinson Tr.
`
`Transcript of deposition of expert Jeffrey V. Ravetch, M.D., Ph.D., on
`behalf of Teva, dated September 30, 2020
`Declaration of Dr. Jeffrey V. Ravetch in Support of Petition for Post
`Grant Review of U.S. Patent Number 10,611,836 filed January 7, 2021 in
`PGR2021-00036, Merck Sharp & Dohme Corp. v. Genentech, Inc.
`Opening Expert Report of Jeffrey V. Ravetch, M.D., Ph.D., Regarding
`Infringement, on behalf of Teva, served September 16, 2021
`Reply Expert Report of Jeffrey V. Ravetch, M.D., Ph.D., Regarding
`Infringement, on behalf of Teva, served December7, 2021
`Request for Admission
`
`Poulsen Tr.
`
`™
`
`Rapoport Tr.
`
`Ravetch CC Decl.
`
`Ravetch CC Tr.
`
`Ravetch
`Declaration
`
`Ravetch Op.
`
`Ravetch Reply
`
`RFA
`
`
`
`Stratton Tr.
`
`Tomlinson Decl.
`
`USPTO
`Walter Tr.
`
`Zeller Tr.
`
`
`
`Transcript of deposition of fact witness Jennifer Renee Stratton, Ph.D.,
`defended by Teva counsel, dated June 29, 2021
`Declaration of expert Dr. Ian M. Tomlinson, M.A., Ph.D., on behalf of
`Teva,filed July 3, 2019 in IPR2018-01710, Eli Lilly & Co. v. Teva
`
`Transcript of deposition of expert Ian M. Tomlinson, M.A., Ph.D., on
`behalf of Teva, dated August 7, 2019
`United States Patent and Trademark Office
`Transcript of deposition of fact witness Sarah Walter, Ph.D., defended by
`Teva counsel, dated June 4, 2021
`Transcript of deposition of Jéerg Zeller, named inventor of the patents-in-
`suit, dated August 11, 2021
`
`iv
`
`

`

`Pursuant to Local Rule 56.1, Defendant Eli Lilly and Company (“Lilly”) submits this
`
`Statement of Material Facts in Support of its Motion for Partial Summary Judgment of Non-
`
`Infringement, showing there is no genuine issue to be tried.
`
`I.
`
`Procedural Posture
`
`1
`
`
`
`
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`

`

`[Hale Resp.] at ¶ 32; Ex. 30 [Ravetch Op.] at ¶ 35; Ex. 15 [McDonnell Op.] at ¶ 36; ECF No. 65
`
`at 4.)
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`2
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`3
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`the antibody that are important in the context of treatment, including specificity, stability, and
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`solubility.” (Ex. 34 [McDonnell Reb.] at ¶ 96.)
`
`4
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`Q. By looking at figure 5, the amino acid sequence of antibody G1 heavy and light
`chains, can a person of ordinary skill in the art determine whether or not
`antibody G1 binds to CGRP?
`
`A. Just looking at the sequences?
`
`Q. Correct.
`
`A. I believe the patent is very clear in characterizing antibody G1 as depicted in
`figure 5 and providing the binding properties and the biological activity of
`antibody G1. But without doing the binding studies and other functional studies
`potentially, I'm not aware of any way looking at a particular sequence can direct
`you to the antigen specificity just by looking at it.
`
`(Ex. 43 [Ravetch CC Tr.] at 163:14-164:5.)3
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`5
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`6
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`7
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`8
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`to put that in the context of the environment and the situation that they find
`themselves in.
`
`Q. If two antibodies bind to different epitopes, would their paratopes have different
`three-dimensional structures?
`
`A. It’s quite common that they would do.
`
`(Ex. 13 [Hale Tr.] at 120:13-121:7.)
`
`III.
`
`Calcitonin Gene-Related Peptide (CGRP)
`
`9
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`(a) an antibody having a CDR H1 as set forth in SEQ ID NO: 3; a CDR
`H2 as set forth in SEQ ID NO: 4; a CDR H3 as set forth in SEQ ID
`NO: 5; a CDR L1 as set forth in SEQ ID NO: 6; a CDR L2 as set forth
`in SEQ ID NO: 7; and a CDR L3 as set forth in SEQ ID NO: 8; or
`
`(b) a variant of an antibody according to (a) as shown in Table 6.
`
`(Ex. 1 [’045 patent] at claim 18.)
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`10
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`11
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 17 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 17 of 53
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`60.
`
`Thespecification of the ’045 patent identifies SEQ ID NO: 7 as the amino acid
`
`sequence of CDR L2 of Antibody G1. (/d.)
`
`61.
`
`The specification of the ’045 patent identifies SEQ ID NO:8 as the amino acid
`
`sequence of CDR L3 of Antibody G1. (/d.)
`
`62.
`
`Teva expert Dr. Pamela Blake has stated “I understand that Dr. Ravetch has
`
`reviewedthe specific sequences identified in claim 18 and confirmed that they correspond to the
`
`CDRs of [Antibody] G1 (which is fremanezumab).” (Ex. 5 [Blake Op.] at § 275.)
`
`63.
`
`Dr. Blake has stated “I understand that Dr. Ravetch has reviewed the sequences
`
`identified in claim 21 and confirmedthat they correspond to the Vy and Vr domains of [Antibody]
`
`G1 (fremanezumab).” (Ex. 5 [Blake Op.] at § 295.)
`
`64.
`
`The specification of the ’045 patent discloses the amino acid sequences of SEQ ID
`
`Nos: 3-8 as follows:
`
`SEQ ID NO: 6
`
`KASKRVTTYVS
`
`SQSYNYPYT
`
`SEQ ID NO: 7
`
`SEQ ID NO: 8
`
`GASNRYL
`
`(Ex. 1 [’045 patent] at cols. 71-72, 77-80.)
`
`65.
`
`The amino acid sequences for the CDRs recited in part (a) of clam 18 (SEQ ID
`
`NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO:6, SEQ ID NO: 7, SEQ ID NO: 8) correspond
`
`to amino acid sequences of the CDRs of Antibody G1 (CDR H1, CDR H2, CDR H3, CDR LI,
`
`CDR L2, and CDRL3, respectively). (Ex. 1 [045 patent] at cols. 71-72, 77-80; Ex. 30 [Ravetch
`
`Op.] at § 199; Ex. 35 [Ravetch Tr.] at 167:8-12.)
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`12
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`13
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`14
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`15
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`USAN Council’ for galcanezumab does not explicitly appear in the Patents-in-Suit.” (Ex. 32 [Teva
`
`Responses to RFAs] at 7.)
`
`V.
`
`Prosecution of the ’045 Patent
`
`16
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`35. The method according to claim 29, wherein the anti-CGRP antagonist antibody
`comprises a VL domain that is at least 90% identical in amino acid sequence to
`SEQ ID NO: 2.
`
`(Ex. 45 [Feb. 11, 2013 Response] at 4-5.)
`
`17
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`94.
`
`In the March 14, 2013 Office Action, the examiner stated:
`
`The amino acid sequences and conformations of each of the heavy and light chain
`CDRs are critical in maintaining the antigen binding specificity and affinity that is
`characteristic of the parent immunoglobulin. It is expected that all of the heavy and
`light chain CDRs in their proper order and in the context of framework sequences
`which maintain their required conformation, are required to produce a protein
`having antigen-binding function and that proper association of heavy and light
`chain variable regions is required in order to form functional antigen binding sites.
`Even minor changes in the amino acid sequences of the heavy and light [chain]
`variable regions, particularly in the CDRs, may dramatically affect antigen-binding
`function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA 79:1979-1983;
`cited by Applicant). Rudikoff et al. teach that the alteration of a single amino acid
`in the CDR of an antibody resulted in the loss of antigen-binding function. It is
`unlikely that antibodies as defined by the claims which contain less than the full
`complement of CDRs from the heavy and light chain variable regions (set forth as
`SEQ ID NOs:3, 4, 5, 6, 7, and 8) of the antibodies would have the required binding
`function. The specification provides no direction or guidance regarding how to
`produce antibodies as broadly defined by the claims that are also useful for treating
`inflammatory pain. Undue experimentation would be required to produce the
`invention commensurate with the scope of the claims from the written disclosure
`alone.
`
`(Ex. 46 [Mar. 14, 2013 Office Action] at 7-8.)
`
`95.
`
`In the March 14, 2013 Office Action, the examiner stated:
`
`Claims 18, 21-23, 30, and 33-35 are rejected under 35 U.S.C. 112, first paragraph,
`as containing subject matter which was not described in the specification in such a
`way as to reasonably convey to one skilled in the relevant art that the inventor(s),
`at the time the application was filed, had possession of the claimed invention.
`
`(Ex. 46 [Mar. 14, 2013 Office Action] at 9.)
`
`18
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 24 of 53
`
`ID NOs: 6, 7, and 8, respectively, but not the full breadth of the claim meets the
`written description provision of 35 U.S.C. § 112, first paragraph.
`
`(Ex. 46 [Mar. 14, 2013 Office Action] at 12.)
`
`97.
`
`Claim 36 of the ’846 application, which recited “[t]he method according to claim
`
`29, wherein the anti-CGRP antagonist antibody comprises a VH domain comprising SEQ ID NO:
`
`1 and a VL domain comprising SEQ ID NO: 2” (Ex. 45 [Feb. 11, 2013 Response] at 5), was not
`
`rejected for lack of written description in the March 14, 2013 Office Action. (Ex. 46 [Mar. 14,
`
`2013 Office Action] at 9.)
`
`98.
`
`On June 28, 2013, the applicant filed an Amendment and Response to Office Action
`
`in response to the March 14, 2013 Office Action. (Ex. 47 [June 28, 2013 Response].)
`
`99.
`
`In the June 28, 2013 Amendment and Response to Office Action, the applicant did
`
`not attempt to overcome the Examiner’s rejection of, inter alia, claims 30, 33, and 35 for lack of
`
`written description and enablement or argue that antibodies other than Antibody G1 and the “84
`
`variant humanized antibodies” listed in Table 6 of the specification were adequately described or
`
`enabled. (Id.)
`
`100.
`
`In the June 28, 2013 Amendment and Response to Office Action, the applicant
`
`amended claim 30 of the ’846 application as shown below:
`
`(Ex. 47 [June 28, 2013 Response] at 4-5.) Claim 30 was later allowed as amended. (Ex. 29 [Notice
`
`of Allowability] at 3.)
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`19
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`20
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 26 of 53
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`107.
`
`The FDA approved Lilly’s Emgality® (galeanezumab-gnlm) for the preventive
`
`treatment of migraine in adults on September 27, 2018. (Ex. 39 [LLY-GALCA-00263352-60].)
`
`108.
`
`109.
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`ee
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`aa 1
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`10.
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`21
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 27 of 53
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`wowo
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`NIewowo
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 28 of 53
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`HIGHLY CONFIDENTIAL — OUTSIDE COUNSEL ONLY
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`25
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`at item (56).) U.S. Patent Application Publication No. 2009/0220489 names the same inventors
`
`as the ’045 patent. (Ex. 4 [U.S. Patent Application Publication No. 2009/0220489].)
`
`26
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`¶ 154; see also Ex. 15 [McDonnell Op.] at ¶ 155 (describing Teva’s internal analysis); Ex. 34
`
`[McDonnell Reb.] at ¶¶ 77-78.)
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`27
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`28
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`which is also higher than the sequence identity between galcanezumab and
`Antibody G1 (64.5%).
`
`(Ex. 15 [McDonnell Op.] at ¶ 184 (citing Exhibit H); see Ex. 34 [McDonnell Reb.] at ¶¶ 108-109.)
`
`29
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`and the antibody element of claim 21—namely the particular sequences of the VH and VL
`
`domains”); Ex. 16 [Blake Reply] at ¶¶ 31, 40, 157; Ex. 14 [Ravetch Reply] at ¶ 87; Ex. 12 [Blake
`
`Tr.] at 74:23-77:5 (confirming reliance on Dr. Ravetch for “matters that pertain particularly to
`
`amino acid sequences and binding to proteins”).)
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`30
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`31
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 37 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 37 of 53
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`154.
`
`l 1
`
`55.
`
`The specification of the Patents-in-Suit does not disclose any antibodies that bind
`
`to the middle-region or N-terminal end of CGRP.
`
`(Ex. 13 [Hale Tr.] at 175:2-6, 183:22-184:17;
`
`Ex. 26 [Poulsen Tr.] at 193:2-14; Ex. 40 [Pons Tr.] at 191:24-192:7; Ex. 15 [McDonnell Op.] at
`
`{9 94, 97; see generally Ex. 1 [’045 patent].)
`
`156.
`
`In his January 25, 2022 deposition, Dr. Hale testified as follows:
`
`Q. The patents-in-suit do not include any examples of a humanized anti-CGRP
`antibody that binds to an epitope of CGRP other than the C-terminal epitope of
`CGRP,correct?
`
`>. So in terms of the antibodies described in the examplesin these patents, I don’t
`think that they have explicitly described antibodies other than targeting the C-
`terminal epitope. Of course, in the specification and the claims, anti-CGRP
`antagonist antibodies are described, and they could include antibodies against
`all sorts of epitopes.
`
`(Ex. 13 [Hale Tr.] at 184:5-17.)
`
`5rs
`
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 38 of 53
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 39 of 53
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`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 42 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 42 of 53
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`X.
`
`Clinical Differences Between Galcanezumab andthe Antibodies of Claims 18
`
`and 21 of the ’045 Patent
`
`175.
`
`Lilly’s Emgality® (galcanezumab)is the only therapeutic antibody approved by the
`
`FDAto treat episodic cluster headache.
`
`(Ex. 48 [Charles Op.] at § 217 (“Galcanezumab remains
`
`the only anti-CGRP antibody approved for treating episodic cluster headache to date.”); Ex. 49
`
`[Rainey Tr.] at 53:18-20; Ex. 50 [Blumenfeld Tr.] at 195:16-23;
`|| Ex. 5 [Blake Op.] at § 84; Ex. 51 [Blumenfeld Resp.] at § 96.)
`
`176.
`
`The FDA has only approved Teva’s Ajovy® (fremanezumab) for the preventive
`
`treatment of migraine. (Ex. 41 [Ajovy Label]; Ex. 49 [Rainey Tr.] at 53:18-20.)
`
`177.
`
`In his August 10, 2021 deposition, Thomas Rainey, Teva Senior Vice President,
`
`Specialty Sales & Marketing,testified as follows:
`
`Q. Has Ajovy been approved fora cluster headacheindication?
`
`A. It has not.
`
`(Ex. 49 [Rainey Tr.] at 45:16-23; 53:18-20.)
`
`Dr. Blake has opined that “Emgality® was approved by the FDA on September 27,
`
`2018 andis indicated for the preventive treatment of EM [Episodic Migraine] and CM [Chronic
`
`Migraine] in adults and the treatment of episodic cluster headachein adults,” and “[c]linical studies
`
`have demonstrated efficacy of Emgality® in episodic and chronic migraine patients, as well as
`
`episodic cluster headachepatients.” (Ex. 5 [Blake Op.] at § 84.)
`
`es |ee
`
`37
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`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 43 of 53
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`180.
`
`In 2017, Teva initiated a clinical trial to test fremanezumabto treat episodic cluster
`
`headache and the trial did not demonstrate that fremanezumab waseffective to treat episodic
`
`cluster headache.
`
`181.
`
`oo NS
`
`enHi
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`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 44 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 44 of 53
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`183.
`
`
`
`184.
`
`In his January 20, 2022 deposition, Dr. Hill testified as follows:
`
`Q. A study seeking to show that the Teva antibody waseffective in treating cluster
`headache was terminated
`
`correct?
`
`A. Correct.
`
`(Ex. 24 [Hill Tr.] at 270:24-271:4.)
`
`185.
`
`i
`
`Teva’s Infringement Allegations Regarding Claims 18 and 21 of the ’045
`Patent
`
`186.
`
`Teva has disclosed expert opinion testimonyonthe issue of infringement of claims
`
`18 and 21 of the ’045 patent from Dr. Ravetch and Dr. Blake.
`
`(Ex. 30 [Ravetch Op.]; Ex. 14
`
`[Ravetch Reply]; Ex. 5 [Blake Op.]; Ex. 16 [Blake Reply].)
`
`

`

`40
`
`
`
`
`
`
`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 46 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 46 of 53
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`192. Dr. Ravetch’s opinionsrelating to infringementof claim 18 ofthe ’045 patent under
`
`the doctrine of equivalents compare galcanezumabto the “antibody element” of claim 18. (Ex. 30
`
`[Ravetch Op.] at § 201.)
`
`193. Dr. Ravetch has opinedthat “[g]aleanezumab,the active ingredient in Emgality®,
`
`is equivalent to the antibody element of claim 18 when usedin the claimed method of treating
`
`headachein human patients.” (Ex. 30 [Ravetch Op.] at § 201.)
`
`194. Dr. Ravetch has opined:
`
`Both fremanezumab and galcanezumab are humanized anti-CGRP antagonist
`antibodies with the structural features required by the antibody elementof claim 18
`(i.e., three heavy chain CDRs andthree light chain CDRs), but differ in the amino
`acid sequencesofthese features. Specifically, fremanezumab’s CDRs correspond
`to the particular sequences recited in claim 18 (i.e., SEQ ID Nos. 3-8), while
`
`alcanezumab’s do not. This difference in CDRs is reflected
`
`(Ex. 30 [Ravetch Op.] at § 225.)
`
`195. Dr. Blake groupsall limitations in claim 18 of the 045 patent relating to the amino
`
`acid sequencesof the antibodyinto a single “antibody element.” (Ex. 5 [Blake Op.] at §§ 276, 277
`
`& 0.68.)
`
`196.
`
`Inasection of her opening expert report titled “Claim 18” and referring to claim 18
`
`of the ’045 patent, Dr. Blake opinedthat:
`
`[T]he antibody of claim 18 is narrowerthan the antibody of claim 17, both in terms
`of the structure of the antibody(i.e., the presence of three heavy chain CDRs and
`three light chain CDRs) and in terms of the sequence of the antibody (i-e., the
`specific aminoacids that constitute the six required CDRs).
`
`(Ex. 5 [Blake Op.] at § 276 & n.68 (referring to the “antibody element” of claim 18).)
`
`197.
`
`Inasection of her opening expert report titled “Claim 18” and referring to claim 18
`
`of the ’045 patent, Dr. Blake opinedthat:
`
`es|
`
`4l
`
`

`

`Regarding the specific antibody element in claim 18, galcanezumab is an
`embodiment of such an antibody and is a humanized monoclonal antibody that has
`a heavy chain with three heavy chain CDRs and light chain with three light chain
`CDRs, including a CDR H1, a CDR H2, a CDR H3, a CDR L1, a CDR L2, and a
`CDR L3). The amino acid sequences of galcanezumab’s six CDRs are not the same
`as those enumerated in claim 18. Accordingly, when compared with the antibody
`element of claim 18, galcanezumab has the same structural components (i.e., three
`heavy chain CDRs and three light chain CDRs), but differs in the particular amino
`acid sequences of those components.
`
`(Ex. 5 [Blake Op.] at ¶ 277 (citations omitted).)
`
`42
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`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 48 of 53
`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 48 of 53
`
`antibody (i.e., the specific amino acids of the that constitute the Vy and Vi
`domains).
`
`(Ex. 30 [Ravetch Op.] at § 230; see Ex. 35 [Ravetch Tr.] at 199:6-13.)
`
`202. Dr. Ravetch’s opinionsrelating to infringement of claim 21 ofthe ’045 patent under
`
`the doctrine of equivalents compare galcanezumabto the “antibody element” of claim 21. (Ex. 30
`
`[Ravetch Op.] at § 232.)
`
`203. Dr. Ravetch has opinedthat “[g]alcanezumab,the active ingredient in Emgality®,
`
`is equivalent to the antibody element of claim 21 when used in the claimed method of treating
`
`headachein humanpatients .
`
`.
`
`. .” (Ex. 30 [Ravetch Op.] at § 232.)
`
`204. Dr. Ravetch has opined:
`
`Both fremanezumab and galcanezumab are humanized anti-CGRP antagonist
`antibodies with the structural features required by the antibody element of claim 21
`(i.e., complete Vx and Vy domains), but differ in the amino acid sequencesof these
`features. Specifically, fremanezumab’s Vy and Vy domains correspond to the
`particular sequences recited in claim 21 (i.e., SEQ ID Nos.
`1 and 2), while
`
`aVuandVzdomainsdonot. ThisdifferenceinCDRsisreflected
`
`(Ex. 30 [Ravetch Op.] at § 240 (citations omitted).)
`
`205. Dr. Blake groupsall limitations in claim 21 of the ’045 patent relating to the amino
`
`acid sequencesof the antibody into a single “antibody element.” (Ex. 5 [Blake Op.] at § 296.)
`
`206.
`
`In a section of her opening expert report titled “Claim 21” and referring to claim 21
`
`of the ’045 patent, Dr. Blake opinedthat:
`
`I also understand from Dr. Ravetch that the antibody element in claim 21 is
`narrowerthan the antibody elementin claim 18 because the sequencesidentified in
`claim 21 include the CDR sequenceslisted in claim 18 as well as the specific FR
`sequencesthat are between the CDRsin the Vy and Vi domains (four FR sequences
`in the Vy domain and four in the Vi domain). In addition, the antibody element
`does not include any variants of G1 as claim 18 does. Thus, the antibody element
`of claim 21 is a subset of the antibody element of claim 18. As for claim 17, the
`“antibody” element in claim 21 is narrower than the “antibody” element in claim
`17, both in terms of the structure of the antibody(i.e., the presence of both a Vu
`
`es|
`
`43
`
`

`

`and a VL domain) and in terms of the sequence of the antibody (i.e., the specific
`amino acids of the that constitute the VH and VL domains).
`
`(Ex. 5 [Blake Op.] at ¶ 296.)
`
`44
`
`
`
`
`
`
`

`

`(Ex. 35 [Ravetch Tr.] at 213:24-214:12.)
`
`45
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`
`
`
`
`

`

`antibody’s CDRs, but rather that the antibody binds to and antagonizes CGRP to
`achieve a beneficial effect.
`
`(Ex. 16 [Blake Reply] at ¶ 149 (citations omitted).)
`
`46
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`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 52 of 53
`
`Dated: March 28, 2022
`
`William B. Raich
`Danielle A. Duszczyszyn
`Denise Main
`Pier D. DeRoo
`Matthew Luneack
`Yoonjin Lee
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
`901 New York Avenue, NW
`Washington, DC 20001-4413
`William.Raich@finnegan.com
`Danielle.Duszczyszyn@finnegan.com
`Denise.Main@finnegan.com
`Pier.DeRoo@finnegan.com
`Matthew.Luneack@finnegan.com
`Yoonjin.Lee@finnegan.com
`
`/s/Andrea L. Martin
`Andrea L. Martin (BBO 666117)
`BURNS & LEVINSON LLP
`125 High Street
`Boston, MA 02110-1624
`(617) 345-3000
`amartin@burnslev.com
`
`Charles E. Lipsey
`Ryan O’Quinn
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
`1875 Explorer Street
`Suite 800
`Reston, VA 20190-6023
`Charles.Lipsey@finnegan.com
`Oquinnr@finnegan.com
`
`Emily R. Gabranski (BBO 694417)
`Marta Garcia Daneshvar
`Lulu Wang (BBO 704042)
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
`2 Seaport Lane
`Boston, MA 02210-2001
`Emily.Gabranski@finnegan.com
`Marta.Garcia@finnegan.com
`Lulu.Wang@finnegan.com
`
`Attorneys for Defendant
`Eli Lilly and Company
`
`47
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`

`

`Case 1:18-cv-12029-ADB Document 299 Filed 03/28/22 Page 53 of 53
`
`CERTIFICATE OF SERVICE
`
`I, Andrea Martin, hereby certify that this document filed through the ECF system will be
`sent electronically to the registered participants as identified on the Notice of Electronic Filing
`(NEF) and paper copies will be sent to those indicated as non-registered participants on March 28,
`2022. The unredacted version of this document will be served on all outside counsel of record via
`email.
`
`/s/Andrea L. Martin, Esq.
`Andrea L. Martin, Esq.
`
`