Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 1 of 51
`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 1 of 51
`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF MASSACHUSETTS
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`Case No. 1:18-cv-12029-ADB
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`Leave to File Under Seal Granted on
`May6, 2022 (ECF No.341)
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`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBHand
`TEVA PHARMACEUTICALSUSA,INC.,
`
`Plaintiffs,
`
`v.
`
`ELI LILLY AND COMPANY,
`
`Defendant.
`
`DEFENDANT ELI LILLY AND COMPANY’S RESPONSE TO PLAINTIFFS’
`LR 56.1 STATEMENT OF UNDISPUTED MATERIAL FACTS IN SUPPORT OF
`
`THEIR MOTION FOR SUMMARY JUDGMENT REGARDING JUDICIAL ESTOPPEL
`
`Pursuant to Local Rule 56.1, Defendant Eli Lilly and Company (“Lilly”) submits this
`
`Response to Plaintiffs’ Statement of Undisputed Material Facts in Support of Plaintiffs’ Motion
`
`for Summary Judgment Regarding Judicial Estoppel (ECF No. 316). Numerous items within
`
`Plaintiffs’ Statement of Undisputed Material Facts consist of arguments, characterizations, legal
`
`conclusions, statements or characterization of laws or rules, hypothetical scenarios, or otherwise
`
`contain little or no factual matter. Lilly disputes any alleged fact unlessit is specifically undisputed
`
`below. Lilly further disputes the arguments Plaintiffs provide in their headings and sub-headings
`
`but have not provided a separate response because Plaintiffs did not provide evidence in support.
`
`I.
`
`BACKGROUND
`
`Teva ownsU.S. Patents 8,586,045 (“the 045 Patent”), 9,884,907 (“the ’907
`1.
`Patent”), and 9,884,908 (“the ’908 Patent’) (together, the “Method of Treatment Patents”’), as
`well as U.S. Patents 9,346,881 (“the ’881 Patent”), 9,890,211 (“the ’211 Patent’’), 8,597,649
`(“the ’649 Patent”), 9,340,614 (“the 614 Patent’’), 9,266,951 (“the ’951 Patent”), and 9,890,210
`(“the ’210 Patent’’) (together, the “Composition of Matter Patents,” and together with the Method
`of Treatment Patents, the ““Patents-in-Suit”). The Patents-in-Suit share a specification, claim
`priority to the same original application, and claim the samepriority date.
`
`LILLY’S RESPONSE: Disputed. Teva has the burden of proving patent ownership but
`
`

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`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 2 of 51
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`cited no evidence that it “owns” the listed patents. Further, this statement provides a legal
`
`conclusion as opposed to a factual statement. As such, it cannot be put forth as an “undisputed
`
`fact.” Moreover, the Composition of Matter Patents are not “Patents-in-Suit.” On February 18,
`
`2020, the PTAB held that the Composition of Matter Patents were unpatentable as obvious. Eli
`
`Lilly & Co. v. Teva Pharms. Int’l GmbH, 2020 WL 806932 (PTAB Feb. 18, 2020); Eli Lilly & Co.
`
`v. Teva Pharms. Int’l GmbH, 2020 WL 808240 (PTAB Feb. 18, 2020). The Federal Circuit
`
`affirmed the PTAB’s decisions. Teva Pharms. Int’l GmbH v. Eli Lilly & Co., 8 F.4th 1349 (Fed.
`
`Cir. 2021); Teva Pharms. Int’l GmbH v. Eli Lilly & Co., 856 F. App’x 312 (Fed. Cir. 2021). In
`
`light of these decisions, the parties stipulated and agreed to dismiss with prejudice “[a]ll claims,
`
`counterclaims, and defenses relating to U.S. Patent Nos. 8,597,649; 9,266,951; 9,340,614;
`
`9,346,881; 9,890,210; and 9,890,211” (i.e., the Composition of Matter Patents). ECF No. 164 at
`
`3–4. The Composition of Matter Patents, therefore, are no longer at issue in this lawsuit. Id.
`
`A person of ordinary skill in the art as of the priority date of the Method of
`2.
`Treatment Patents would have had “(1) a Ph.D. in a relevant field, such as immunology,
`biochemistry, or pharmacology, with several years of post-doctoral experience in antibody
`engineering, pharmacokinetics, and pharmacodynamics, or (2) an M.D. with a residency or
`specialty in neurology, and several years of experience studying CGRP or treating patients with a
`CGRP-related disease, such as migraine headaches.” Ex. 1 (Sept. 16, 2021 Opening Expert
`Report of Dr. James McDonnell, Ph.D.) ¶ 12.
`
`LILLY’S RESPONSE: Undisputed, and to further clarify: “A person of ordinary skill
`
`would also have been able to draw upon the knowledge and experience of a multi-disciplinary
`
`antibody development team comprising individuals with expertise outside her primary training.
`
`These
`
`individuals
`
`could
`
`include
`
`immunologists, biochemists,
`
`antibody
`
`engineers,
`
`pharmacologists, pharmacists, and medical doctors.” ECF No. 296, Ex. 48 [Charles Op.] at ¶ 74;
`
`see also ECF No. 296, Ex. 15 [McDonnell Op.] at ¶ 13; Ex. A1 [Hale Resp.] at ¶ 20; ECF No. 70
`
`1 Exhibits A–C referenced herein are exhibits to the Declaration of Emily Gabranski in Support of
`
`2
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 3 of 51
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`at ¶ 24.
`
`On August 8, 2018, Eli Lilly and Company (“Lilly”) filed six IPR petitions with
`3.
`the Patent Trial and Appeal Board of the United States Patent and Trademark Office (the
`“Board”) alleging that the Composition of Matter Patents—the ’649 Patent, ’951 Patent, ’614
`Patent, ’881 Patent, ’210 Patent, and ’211 Patent—were invalid as obvious. ECF No. 43 (Order
`Staying Case Pending IPR) at 7.
`
`LILLY’S RESPONSE: Disputed. On August 8, 2018, Lilly filed six IPR petitions with
`
`the Patent Trial and Appeal Board of the United States Patent and Trademark Office (the “PTAB”)
`
`alleging that only certain challenged claims in the Composition of Matter Patents were
`
`unpatentable as obvious, as follows:
`
`
`
`
`
`
`
`
`
`
`
`
`
`’614 patent, claims 1–7 and 15–20;
`
`’951 patent, claims 1–6 and 14–19;
`
`’881 patent, claims 1–6 and 14–19;
`
`’210 patent, claims 1–15;
`
`’211 patent, claims 1–15; and
`
`’649 patent, claims 1–9.
`
`See ECF No. 43 at 7 nn.7–8. Lilly did not challenge, for example, any patent claims limited to
`
`particular antibody amino acid sequences.
`
`On February 18, 2020 the Board determined that Lilly had established by a
`4.
`preponderance of the evidence that the instituted claims of the Composition of Matter Patents
`were unpatentable as obvious. See Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, 2020 WL
`806932 (PTAB Feb. 18, 2020); Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, 2020 WL 808240
`(PTAB Feb. 18, 2020).
`
`LILLY’S RESPONSE: Undisputed.
`
`The Federal Circuit affirmed the Board’s decision, holding that substantial
`5.
`evidence supported the Board’s decision that a POSA would have had a motivation to combine
`the prior art references—including Tan, Queen, and Doods—to achieve the claimed humanized
`
`Defendant Eli Lilly and Company’s Opposition to Plaintiffs’ Motion for Partial Summary
`Judgment Regarding Judicial Estoppel, filed concurrently with this Response.
`
`3
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`

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`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 4 of 51
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`anti-CGRP antibodies, and a reasonable expectation of success in doing so. See Teva Pharms.
`Int’l GmbH v. Eli Lilly & Co., 8 F.4th 1349 (Fed. Cir. 2021); Teva Pharms. Int’l GmbH v. Eli
`Lilly & Co., 856 F. App’x 312 (Fed. Cir. 2021).
`
`LILLY’S RESPONSE: Disputed. Teva’s plural “claimed humanized anti-CGRP
`
`antagonist antibodies” is inaccurate. The Federal Circuit affirmed the PTAB’s decision, finding
`
`that a POSA “would have been motivated to combine the teachings of the references to make a
`
`humanized anti-CGRP antibody.” Teva Pharms. Int’l GmbH v. Eli Lilly & Co., 8 F.4th 1349, 1356
`
`(Fed. Cir. 2021) (citing Lilly, 2020 WL 806932, at *16–27);2 id., at 1359 (“We agree with Lilly
`
`that substantial evidence supports a motivation to make a humanized anti-CGRP antibody to study
`
`its therapeutic potential for use in treatment of human disease.”); Teva Pharms. Int’l GmbH v. Eli
`
`Lilly & Co., 856 F. App’x 312, 313 (Fed. Cir. 2021) (affirming the PTAB’s unpatentability holding
`
`“for the reasons set forth in” Teva Pharms. Int’l GmbH v. Eli Lilly & Co., 8 F.4th 1349 (Fed. Cir.
`
`2021)).
`
`II.
`
`LILLY’S POSITIONS REGARDING ANTI-CGRP ANTAGONIST ANTIBODIES
`AND METHODS FOR PREPARING THEM
`
`A.
`
`Lilly’s Positions in the Inter Partes Review Proceedings
`
`In its petition seeking inter partes review of the ’210 Patent, Lilly asserted that
`6.
`“[a]nti-CGRP [a]ntagonist [a]ntibodies [w]ere [w]ell [k]nown in the [a]rt.” Ex. 2 (Eli Lilly & Co.
`v. Teva Pharms. Int’l GmbH, IPR2018-01425, Paper 1, Petition (Aug. 8, 2018)) at 11 (citing
`“several publications” that “described anti-CGRP antagonist antibodies”).
`
`LILLY’S RESPONSE: Disputed to the extent Teva’s modified and excerpted quotations
`
`mischaracterize Lilly’s assertions in its petition seeking inter partes review of the ’210 patent.
`
`Here, Teva generally pulls language from a section header and provides no surrounding context.
`
`Lilly did not assert that humanized or human anti-CGRP antagonist antibodies were well known
`
`in the art. See Lilly, 2020 WL 806932, at *26 (“Although these exhibits (Tan, Tan 1994, Frobert,
`
`2 Emphases added unless otherwise noted.
`
`4
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`

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`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 5 of 51
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`Wong, and Andrew) refer to anti-CGRP antibodies that target rat or human CGRP, Petitioner does
`
`not assert that these antibodies themselves were humanized.”). Lilly also cited only five
`
`publications disclosing murine (mouse and rat) anti-CGRP antibodies, which contained no
`
`structure or sequence information. ECF No. 317, Ex. 2 at 11 (citing IPR Exs. 1021, 1022, 1032,
`
`1033, 1055); see also ECF No. 296, Ex. 13 [Hale Tr.] at 168:3-23. Those publications collectively
`
`disclosed, at most, six murine antibodies reported as inhibiting CGRP’s biological activity in vitro
`
`or in vivo, i.e., as measured in assays conducted in rats. Ex. A [Hale Resp.] at ¶¶ 119-122; ECF
`
`No. 296, Ex. 45 [McDonnell Reply] at ¶ 21. Moreover, “[a]ll claims, counterclaims, and defenses
`
`relating to” the Composition of Matter Patents, including the ’210 patent, were dismissed with
`
`prejudice from the above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`In its petition seeking inter partes review of the ’210 Patent, Lilly asserted that
`7.
`“murine monoclonal anti-CGRP antagonist antibod[ies] that bind[] to human CGRP . . . . were
`extensively described in the prior art.” Id. at 30–31.
`
`LILLY’S RESPONSE: Disputed. Teva’s modified and excerpted quotation
`
`mischaracterizes Lilly’s assertions in its petition seeking inter partes review of the ’210 patent. In
`
`its petition, Lilly stated the following:
`
`The first step in making a humanized anti-CGRP antagonist
`antibody that specifically binds to human αCGRP or βCGRP would
`have been to make a murine monoclonal anti-CGRP antagonist
`antibody that binds to human CGRP. Such antibodies, and
`techniques for making them, were extensively described in the
`prior art. As a result, a POSA would have reasonably expected to
`succeed in making an anti-CGRP antagonist antibody that
`specifically bound human CGRP like those reported in Tan 1995
`and elsewhere.
`
`ECF No. 317, Ex. 2 at 30–31 (internal citations omitted). Lilly also cited only five publications
`
`disclosing murine (mouse and rat) anti-CGRP antibodies, which contained no structure or
`
`sequence information Id. at 11 (citing IPR Exs. 1021, 1022, 1032, 1033, 1055); see also ECF No.
`
`296, Ex. 13 [Hale Tr.] at 168:3-23. Those publications collectively disclosed, at most, six murine
`
`5
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 6 of 51
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`antibodies reported as inhibiting CGRP’s biological activity in vitro or in vivo. Ex. A [Hale Resp.]
`
`at ¶¶ 119-122; ECF No. 296, Ex. 45 [McDonnell Reply] at ¶ 21. Moreover, “[a]ll claims,
`
`counterclaims, and defenses relating to” the Composition of Matter Patents, including the ’210
`
`patent, were dismissed with prejudice from the above-captioned lawsuit and are no longer at issue.
`
`ECF No. 164 at 3–4.
`
`In its petition seeking inter partes review of the ’614 Patent, Lilly asserted that
`8.
`“[b]y 2005, several publications had described anti-CGRP antagonist antibodies.” Ex. 5 (Eli Lilly
`& Co. v. Teva Pharms. Int’l GmbH, IPR2018-01422, Paper 1, Petition (Aug. 8, 2018)) at 12.
`Lilly further asserted that “[t]he ’614 patent acknowledges the routine nature of generating anti-
`CGRP antagonist antibodies, stating that ‘anti-CGRP antagonist antibodies may be made by any
`method known in the art.’” Id. at 33 (citation omitted) (emphasis in original). Lilly further
`asserted that there were “established and conventional techniques for antibody stimulation and
`production.” Id. at 34 (emphasis in original).
`
`LILLY’S RESPONSE: Disputed. Teva’s modified, excerpted, and strung together
`
`quotations mischaracterize Lilly’s assertions in its petition for inter partes review of the ’614
`
`patent. Lilly did not assert that humanized or human anti-CGRP antagonist antibodies were well
`
`known in the art. See Lilly, 2020 WL 806932, at *26 (“Although these exhibits (Tan, Tan 1994,
`
`Frobert, Wong, and Andrew) refer to anti-CGRP antibodies that target rat or human CGRP,
`
`Petitioner does not assert that these antibodies themselves were humanized.”). Lilly cited only five
`
`publications disclosing murine (mouse or rat) anti-CGRP antibodies, which contained no structure
`
`or sequence information. ECF No. 317, Ex. 5 at 12 (citing IPR Exs. 1021, 1022, 1032, 1033, 1055);
`
`see also ECF No. 296, Ex. 13 [Hale Tr.] at 168:3-23. Those publications collectively disclosed, at
`
`most, six murine antibodies reported as inhibiting CGRP’s biological activity in vitro or in vivo.
`
`Ex. A [Hale Resp.] at ¶¶ 119–122; ECF No. 296, Ex. 45 [McDonnell Reply] at ¶ 21.
`
`That techniques for generating murine (mouse or rat) antibodies were “known” and
`
`“conventional” also does not mean that making a humanized or human antibody was predictable,
`
`not costly, and not labor-intensive.
`
`
`
`6
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`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 7 of 51
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`
`
` ECF
`
`No. 292, Ex. 74 [Tomlinson Decl.] at ¶ 108 (explaining that antibody humanization generally
`
`requires 4–6 months of work at a total cost of $500,000). Indeed, in light of Teva’s expert
`
`testimony before the PTAB, the PTAB found that a POSA would have reasonably expected to
`
`make such a humanized antibody, notwithstanding that humanization is “not a process to be taken
`
`lightly … you’re not guaranteed to be successful.” Lilly, 2020 WL 806932, at *42. Moreover, “[a]ll
`
`claims, counterclaims, and defenses relating to” the Composition of Matter Patents, including the
`
`’614 patent, were dismissed with prejudice from the above-captioned lawsuit and are no longer at
`
`issue. ECF No. 164 at 3–4.
`
`In its petition seeking inter partes review of the ’614 Patent, Lilly asserted that
`9.
`“anti-CGRP antagonist antibodies could be created by known, established, and standard
`techniques.” Id. at 23–24.
`
`LILLY’S RESPONSE: Disputed
`
`to
`
`the extent Teva’s excerpted quotation
`
`mischaracterizes Lilly’s assertions in its petition seeking inter partes review of the ’614 patent.
`
`Lilly did not assert that humanized or human anti-CGRP antagonist antibodies were well known
`
`in the art. Lilly, 2020 WL 806932, at *26 (“Although these exhibits (Tan, Tan 1994, Frobert,
`
`Wong, and Andrew) refer to anti-CGRP antibodies that target rat or human CGRP, Petitioner does
`
`not assert that these antibodies themselves were humanized.”). Moreover, that techniques for
`
`creating murine (mouse or rat) antibodies were “known, established, and standard” does not mean
`
`that making a humanized antibody was predictable, not costly, and not labor-intensive.
`
`
`
`
`
`
`
`at ¶ 108 (explaining that antibody humanization generally requires 4–6 months of work at a total
`
` ECF No. 292, Ex. 74 [Tomlinson Decl.]
`
`7
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 8 of 51
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`cost of $500,000). Indeed, in light of Teva’s expert testimony before the PTAB, the PTAB found
`
`that a POSA would have reasonably expected to make such a humanized antibody,
`
`notwithstanding that humanization is “not a process to be taken lightly … you’re not guaranteed
`
`to be successful.” Lilly, 2020 WL 806932, at *42. Moreover, “[a]ll claims, counterclaims, and
`
`defenses relating to” the Composition of Matter Patents, including the ’614 patent, were dismissed
`
`with prejudice from the above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`In its petition seeking inter partes review of the ’210 Patent, Lilly asserted that
`10.
`“[g]enerating anti-CGRP antagonist antibodies against human CGRP instead of rat CGRP would
`have been straightforward for several reasons,” including “researchers had already generated
`anti-CGRP antagonist antibodies against human CGRP” and “human CGRP was readily
`available for use in the laboratory, and in fact was commercially available.” Ex. 2 at 31. Lilly
`also asserted that anti-CGRP antibodies were “well-known and readily prepared.” Id. at 44. Lilly
`also asserted that “Tan 1995 describes murine anti-CGRP antagonist antibodies, including a full-
`length antibody, that blocked the effects of CGRP both in vitro and in vivo. Tan 1995 thus
`establishes that an anti-CGRP antagonist antibody with the claimed properties could be readily
`prepared by known, established, and conventional techniques.” Id. at 22 (citation omitted).
`
`LILLY’S RESPONSE: Disputed. Teva’s excerpted, modified, and strung together
`
`quotations mischaracterize Lilly’s assertions in its petition seeking inter partes review of the ’210
`
`patent. Lilly did not assert that humanized or human anti-CGRP antagonist antibodies were well
`
`known in the art. Lilly, 2020 WL 806932, at *26 (“Although these exhibits (Tan, Tan 1994,
`
`Frobert, Wong, and Andrew) refer to anti-CGRP antibodies that target rat or human CGRP,
`
`Petitioner does not assert that these antibodies themselves were humanized.”). Lilly cited only five
`
`publications disclosing murine (mouse or rat) anti-CGRP antibodies, which contained no structure
`
`or sequence information. ECF No. 317, Ex. 5 at 12 (citing IPR Exs. 1021, 1022, 1032, 1033, 1055);
`
`see also ECF No. 296, Ex. 13 [Hale Tr.] at 168:3–23. Those publications collectively disclosed, at
`
`most, six murine antibodies reported as inhibiting CGRP’s biological activity in vitro or in vivo.
`
`Ex. A [Hale Resp.] at ¶¶ 119–122; ECF No. 296, Ex. 45 [McDonnell Reply] at ¶ 21.
`
`That techniques for generating murine (mouse or rat) antibodies were “known,”
`
`8
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 9 of 51
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`“established,” and “conventional” also does not mean that making a humanized or human antibody
`
`was predictable, not costly, and not labor-intensive.
`
`
`
`
`
`
`
` ECF No. 292, Ex. 74 [Tomlinson Decl.] at ¶ 108 (explaining that antibody
`
`humanization generally requires 4–6 months of work at a total cost of $500,000). Indeed, in light
`
`of Teva’s expert testimony before the PTAB, the PTAB found that a POSA would have reasonably
`
`expected to make such a humanized antibody, notwithstanding that humanization is “not a process
`
`to be taken lightly … you’re not guaranteed to be successful.” Lilly, 2020 WL 806932, at *42.
`
`Teva’s statement that “Tan 1995 thus establishes that an anti-CGRP antagonist antibody
`
`with the claimed properties could be readily prepared…” is additionally inaccurate in the context
`
`of this case in which the Antibody Method of Treatment patents are at issue. In the Antibody
`
`Method of Treatment IPRs, the PTAB did not make the statement quoted by Teva and instead
`
`found to the contrary in view of, inter alia, Tan 1995. See, e.g., Eli Lilly & Co. v. Teva Pharms.
`
`Int’l GmbH, IPR2018-01710, 2020 WL 1540364, at *63 (PTAB Mar. 31, 2020) (“We determine
`
`that Tan does not provide any data establishing a successful use of a full-length anti-CGRP
`
`antibody to achieve immunoblockade of endogenous CGRP.”); id. at *59 (finding no reasonable
`
`expectation of success “in using an antibody treatment in view of the … uncertainty in whether
`
`anti-CGRP antibodies needed to cross the blood-brain barrier to reduce incidence of or treat
`
`headache such as migraine.”). Moreover, “[a]ll claims, counterclaims, and defenses relating to”
`
`the Composition of Matter Patents, including the ’210 patent, were dismissed with prejudice from
`
`the above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`In its petition seeking inter partes review of the ’210 Patent, Lilly asserted that
`11.
`“techniques for making” “murine monoclonal anti-CGRP antagonist antibod[ies] that bind[] to
`
`9
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 10 of 51
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`human CGRP” have been “extensively described in the prior art.” Id. at 30–31.
`
`LILLY’S RESPONSE: Disputed. Teva’s excerpted and modified quotations
`
`mischaracterize Lilly’s assertions in its petition seeking inter partes review of U.S. Patent No.
`
`9,890,210 (“the ’210 patent”). In its petition, Lilly stated the following:
`
`The first step in making a humanized anti-CGRP antagonist
`antibody that specifically binds to human αCGRP or βCGRP would
`have been to make a murine monoclonal anti-CGRP antagonist
`antibody that binds to human CGRP. Such antibodies, and
`techniques for making them, were extensively described in the
`prior art. As a result, a POSA would have reasonably expected to
`succeed in making an anti-CGRP antagonist antibody that
`specifically bound human CGRP like those reported in Tan 1995
`and elsewhere.
`
`ECF No. 317, Ex. 2 at 30–31 (internal citations omitted). Lilly also cited only five publications
`
`disclosing murine (mouse and rat) anti-CGRP antibodies, which contained no structure or
`
`sequence information. Id. at 11 (citing IPR Exs. 1021, 1022, 1032, 1033, 1055); see also ECF No.
`
`296, Ex. 13 [Hale Tr.] at 168:3-23. Those publications collectively disclosed, at most, six murine
`
`antibodies reported as inhibiting CGRP’s biological activity in vitro or in vivo. Ex. A [Hale Resp.]
`
`at ¶¶ 119-122; ECF No. 296, Ex. 45 [McDonnell Reply] at ¶ 21.
`
`Further, that techniques for making murine (mouse or rat) monoclonal anti-CGRP
`
`antagonist antibodies were extensively described in the prior art does not mean that making a
`
`humanized or human antibody was predictable, not costly, and not labor-intensive.
`
`
`
`
`
`
`
` ECF No. 292, Ex. 74 [Tomlinson Decl.] at ¶ 108
`
`(explaining that antibody humanization generally requires 4–6 months of work at a total cost of
`
`$500,000). Indeed, in light of Teva’s expert testimony before the PTAB, the PTAB found that a
`
`POSA would have reasonably expected to make such a humanized antibody, notwithstanding that
`
`10
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 11 of 51
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`humanization is “not a process to be taken lightly … you’re not guaranteed to be successful.” Lilly,
`
`2020 WL 806932, at *42. Moreover, “[a]ll claims, counterclaims, and defenses relating to” the
`
`Composition of Matter Patents, including the ’210 patent, were dismissed with prejudice from the
`
`above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`In its petition seeking inter partes review of the ’881 Patent, Lilly asserted that
`12.
`“[a] POSA thus would have expected that a similar antibody [i.e., other anti-CGRP antagonist
`antibodies] could be prepared using routine and conventional antibody preparation methods.” Ex.
`3 (Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, IPR2018-01424, Paper 1, Petition (Aug. 8,
`2018)) at 40.
`
`LILLY’S RESPONSE: Disputed. Teva’s excerpted and modified quotation
`
`mischaracterizes Lilly’s assertions in its petition seeking inter partes review of the ’881 patent.
`
`Lilly did not assert that humanized or human anti-CGRP antagonist antibodies were well known
`
`in the art. Lilly, 2020 WL 806932, at *26 (“Although these exhibits (Tan, Tan 1994, Frobert,
`
`Wong, and Andrew) refer to anti-CGRP antibodies that target rat or human CGRP, Petitioner does
`
`not assert that these antibodies themselves were humanized.”). Moreover, the bracketed “other
`
`anti-CGRP antagonist antibodies” added by Teva is incorrect. The quoted statement referred to
`
`making a singular murine (mouse) anti-CGRP antagonist antibody. ECF No. 317, Ex. 3 at 40.
`
`Also, as previously explained, Lilly cited only five publications disclosing murine (mouse and rat)
`
`anti-CGRP antibodies, which contained no structure or sequence information. See ECF No. 317,
`
`Ex. 2 at 11 (citing IPR Exs. 1021, 1022, 1032, 1033, 1055); see also ECF No. 296, Ex. 13 [Hale
`
`Tr.] at 168:3–23. Those publications collectively disclosed, at most, six murine antibodies reported
`
`as inhibiting CGRP’s biological activity in vitro or in vivo. Ex. A [Hale Resp.] at ¶¶ 119-–22; ECF
`
`No. 296, Ex. 45 [McDonnell Reply] at ¶ 21.
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`Further, that techniques for making a murine (mouse or rat) monoclonal anti-CGRP
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`antagonist antibody were “routine and conventional” does not mean that making a humanized or
`
`human antibody was predictable, not costly, or not labor intensive.
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`
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`11
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`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 12 of 51
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`
`
`
`
` ECF No. 292, Ex. 74 [Tomlinson Decl.] at ¶ 108 (explaining that
`
`antibody humanization generally requires 4–6 months of work at a total cost of $500,000). Indeed,
`
`in light of Teva’s expert testimony before the PTAB, the PTAB found that a POSA would have
`
`reasonably expected to make such a humanized antibody, notwithstanding that humanization is
`
`“not a process to be taken lightly … you’re not guaranteed to be successful.” Lilly, 2020 WL
`
`806932, at *42. Moreover, “[a]ll claims, counterclaims, and defenses relating to” the Composition
`
`of Matter Patents, including the ’881 patent, were dismissed with prejudice from the above-
`
`captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`Lilly’s antibody engineering expert in the inter partes review of the ’951 patent,
`13.
`Dr. Alain P. Vasserot, asserted that “[i]n 2005, it was well within a POSA’s capacity to make
`antibodies against a desired antigen. Making an anti-CGRP antagonist antibody that binds to
`human αCGRP would have been no exception. Indeed, a POSA would have been confident in
`making such an antibody.” Ex. 7 (Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, IPR2018-01423,
`Ex. 1005, Declaration of Dr. Alain P. Vasserot, Ph.D. (Aug. 9, 2018)) ¶ 91.
`
`LILLY’S RESPONSE: Disputed
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`to
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`the extent Teva’s excerpted quotations
`
`mischaracterize Dr. Vasserot’s assertions in the inter partes review of U.S. Patent No. 9,266,951
`
`(“the ’951 Patent”). Dr. Vasserot did not assert that it was within a POSA’s capacity to make a
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`genus of humanized or human anti-CGRP antagonist antibodies, as claimed in the Antibody
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`Method of Treatment Patents at issue in this case. Dr. Vasserot’s statement is specifically
`
`referencing a POSA’s confidence in making “an anti-CGRP antagonist antibody that binds human
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`αCGRP.” ECF No. 317, Ex. 7 at ¶ 91. Dr. Vasserot was also discussing making a murine (mouse
`
`or rat) antibody, not a humanized anti-CGRP antagonist antibody. Id. at ¶¶ 91–93 (describing
`
`immunization of mice with αCGRP). Moreover, “[a]ll claims, counterclaims, and defenses relating
`
`to” the Composition of Matter Patents, including the ’951 patent, were dismissed with prejudice
`
`12
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`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 13 of 51
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`from the above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`During the inter partes review of the ’951 patent, Dr. Vasserot testified that “a
`14.
`POSA would have had a reasonable expectation of success in making an anti-CGRP antagonist
`antibody that binds to human αCGRP and inhibits cAMP activation in cells.” Id. ¶ 100.
`
`LILLY’S RESPONSE: Disputed
`
`to
`
`the extent Teva’s excerpted quotation
`
`mischaracterizes Dr. Vasserot’s testimony during the inter partes review of the ’951 patent. Dr.
`
`Vasserot’s quoted excerpt is specifically referencing a POSA’s reasonable expectation of success
`
`in making a singular murine (mouse or rat) “anti-CGRP antagonist antibody that binds to human
`
`αCGRP and inhibits cAMP activation in cells.” ECF No. 317, Ex. 7 at ¶¶ 91–93 (describing
`
`immunization of mice with αCGRP). Further, that there was a reasonable expectation of success
`
`for making a murine (mouse or rat) monoclonal anti-CGRP antagonist antibody does not mean
`
`that making a humanized or human antibody was predictable, not costly, or not labor intensive.
`
`
`
`
`
` ECF No. 292, Ex. 74 [Tomlinson
`
`Decl.] at ¶ 108 (explaining that antibody humanization generally requires 4–6 months of work at
`
`a total cost of $500,000). Indeed, in light of Teva’s expert testimony before the PTAB, the PTAB
`
`found that a POSA would have reasonably expected to make such a humanized antibody,
`
`notwithstanding that humanization is “not a process to be taken lightly … you’re not guaranteed
`
`to be successful.” Lilly, 2020 WL 806932, at *42. Moreover, “[a]ll claims, counterclaims, and
`
`defenses relating to” the Composition of Matter Patents, including the ’951 Patent, were dismissed
`
`with prejudice from the above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4.
`
`B.
`
`The Board’s Findings
`
`The Board “conclude[ed] that the prior art explicitly suggested the use of anti-
`15.
`CGRP antibodies to treat various human disease conditions” based on prior art “disclosures”
`identified by Lilly in its petitions. Eli Lilly, 2020 WL 806932, at *26 (“based on the disclosures
`
`13
`
`

`

`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 14 of 51
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`discussed above, we conclude that the prior art explicitly suggested the use of anti-CGRP
`antibodies to treat various human disease conditions”).
`
`LILLY’S RESPONSE: Disputed, including to the extent Teva’s excerpted quotations
`
`mischaracterize the PTAB’s conclusions. Teva also does not identify any particular “‘disclosures’
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`identified by Lilly in its petitions” accepted by the PTAB in reaching its conclusion. The quoted
`
`excerpts also relate to the Composition of Matter Patents, which were dismissed with prejudice
`
`from the above-captioned lawsuit and are no longer at issue. ECF No. 164 at 3–4. In its decision
`
`on the Method of Treatment Patents (i.e., those still currently asserted in the lawsuit), the PTAB
`
`“found that neither of th[e prior art] references contained disclosures sufficient to create a
`
`reasonable expectation of success in treating migraine or other headache disorders with a
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`humanized anti-CGRP antibody.” Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, 8 F.4th 1331,
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`*1347 (Fed. Cir. 2021). The Federal Circuit affirmed this finding. Id., at *1349.
`
`One of the disclosures the Board relied on to reach the conclusion in paragraph 13
`16.
`was Lilly’s assertion “that the prior art was replete with exemplary disclosures of anti-CGRP
`antagonist antibodies, including humanized antibodies, to treat human diseases and
`conditions . . . .” Id. at *24.
`
`LILLY’S RESPONSE: Disputed. SUMF 13 does not reference any conclusions from the
`
`PTAB. Rather, SUMF 13 references Dr. Vasserot’s assertions in the inter partes review of U.S.
`
`Patent No. 9,266,951.
`
`To the extent Teva contends that the PTAB relied on the quoted language of SUMF 16 to
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`reach a conclusion in SUMF 15, Teva is also incorrect. The PTAB’s finding in SUMF 15 comes
`
`eight paragraphs after the quoted language of SUMF 16 and after several other findings by the
`
`PTAB. Following Teva’s quoted statement in SUMF 16, the PTAB only stated: “We agree with
`
`Petitioner that Wimalawansa suggests study of anti-CGRP antibodies in migraine and other prior
`
`art of record after Wimalawansa discusses anti-CGRP antibodies in other contexts.” Lilly, 2020
`
`WL 806932, at *24. Nowhere did the PTAB reference any “humanized antibodies” in that finding.
`
`14
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`Case 1:18-cv-12029-ADB Document 358 Filed 05/10/22 Page 15 of 51
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`See also id. at *26 (“Petitioner does not assert that these antibodies themselves were humanized.”).
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`Lilly also disputes SUMF 16 to the extent that Teva’s excerpted quotation mischaracterizes the
`
`PTAB’s conclusions and Lilly’s assertions. The quoted excerpt stems from a sentence that reads
`
`as follows: “[Lilly] asserts that the prior art was replete with exemplary disclosures of anti-CGRP
`
`antagonist antibodies, including humanized antibodies, to treat human diseases and conditions,
`
`that provided express motivation to prepare a humanized anti-CGRP antagonist antibody against
`
`human CGRP suitable for administration to humans.” Id. at *24.
`
`Another disclosure the Board relied on to reach the conclusion in paragraph 13
`17.
`was Lilly’s assertion “that by 2005, several publications had described anti-CGRP antagonist
`antibodies.” Id. at *26 (citing Ex. 5 at 11, 12).
`
`LILLY’S RESPONSE: Disputed. SUMF 13 does not reference any conclusions from the
`
`PTAB. Rather, SUMF 13 references Dr. Vasserot’s assertions