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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`______________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________
`
`ELI LILLY AND COMPANY,
`Petitioner,
`v.
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH,
`Patent Owner.
`______________________
`
`Case No. IPR2018-01710
`Patent No. 8,586,045
`______________________
`
`PETITIONER’S RESPONSE TO TEVA’S SUPPLEMENTAL BRIEF
`REGARDING FOX FACTORY, INC. v. SRAM, LLC
`
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`
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`
` IPR2018-01710
`Patent No. 8,586,045
`
`Table of Contents
`
`
`I.
`Teva Failed to Establish that Amino Acid Sequence Is Insignificant ........... 1
`Teva Failed to Meet Its Burden of Establishing Coextensiveness................. 2
`II.
`III. Teva Failed to Distinguish Fox Factory ....................................................... 3
`IV. Teva Failed to Address Its Unchallenged Claims Reciting Sequence ........... 4
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`i
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` IPR2018-01710
`Patent No. 8,586,045
`
`GLOSSARY
`
`FDA
`
`IPR
`
`U.S. Food and Drug Administration
`
`Inter partes review
`
`Italicized text
`
`Emphasis added unless otherwise indicated
`
`Lilly or Petitioner Eli Lilly and Company
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`pM
`
`picomolar
`
`Teva or Patent
`Owner
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`’045 patent
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`’614 patent
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`Teva Pharmaceuticals International GmbH
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`U.S. Patent No. 8,586,045 (Ex. 1001)
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`U.S. Patent No. 9,340,614 (Ex. 1001 in IPR2018-01422)
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`’614 Hearing Tr.
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`Record of Oral Hearing (Paper 71 in IPR2018-01422)
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`’951 patent
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`’881 patent
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`’794 patent
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`U.S. Patent No. 9,266,951 (Ex. 1001 in IPR2018-01423)
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`U.S. Patent No. 9,346,881 (Ex. 1001 in IPR2018-01424)
`
`U.S. Patent No. 8,007,794 (Ex. 2024)
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`ii
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`I.
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` IPR2018-01710
`Patent No. 8,586,045
`Teva Failed to Establish that Amino Acid Sequence Is Insignificant
`Having represented to the FDA that it engineered Ajovy®’s amino acid
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`
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`sequence to achieve its therapeutic profile, Teva’s repeated failure to address the
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`criticality of sequence confirms that no presumption applies. Ex. 2217, 8-9; Reply,
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`21-22; Fox Factory, Inc. v. SRAM, LLC, 944 F.3d 1373, 1375-76 (Fed. Cir. 2019).
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`Teva’s mere attorney argument that sequence is insignificant is baseless. Br., 5.
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`Depending on their specific sequence, anti-CGRP antibodies within the broad
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`scope of the claims would have (1) binding affinity orders of magnitude worse than
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`Ajovy® and Emgality®, (2) strong effector functions having the undesired side effect
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`of killing cells, (3) an antibody fragment format that Dr. Tomlinson testified would
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`be useless as a therapeutic, and/or (4) an antibody class never successfully used
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`before in any FDA-approved antibody. Reply, 21-24; Ex. 1301, 27:25-28:6, 134:14-
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`25, 34:9-35:1, 36:16-39:11, 101:15-104:19; Ex. 1014, ¶175. These unclaimed
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`features would lead to materially different properties (e.g., no efficacy or significant
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`adverse events) compared to Emgality® and Ajovy® and were identified by FDA as
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`directly bearing on “critical quality attributes” (CQAs). Ex. 2216, 17; Ex. 2217, 6-9.
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`Teva’s unsupported argument that “sequences are not driving the praise”
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`(because Emgality® and Ajovy® have different sequences) is therefore inconsistent
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`with the admissions of its expert, contrary to its representations to FDA, and contrary
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`1
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` IPR2018-01710
`Patent No. 8,586,045
`to the fundamental principle of antibody biology that sequence determines function.
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`
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`Br., 5; Ex. 1063, 59, 63; Ex. 1062, 41; Ex. 1301, 93:14-20; Reply, 21-22.
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`II. Teva Failed to Meet Its Burden of Establishing Coextensiveness
`In an effort to argue away its admission that Ajovy® and Emgality® are not
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`“coextensive” with its overbroad claims, Teva contends they form a representative
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`number of species within the claimed genus. ’614 Hearing Tr., 63; Br. 2, n.1, 5-7.
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`But this is mere attorney argument, unsupported by any evidence.1
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`Teva’s argument also lacks merit. Two sequence-engineered, FDA-approved
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`antibody drugs are not representative of broad genus claims seeking to cover using
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`all human or humanized anti-CGRP antibodies, regardless of sequence, for treating
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`migraine (among at least 250 other forms of headache). Ex. 1304, 74:17-75:12.
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`Indeed, as held in Celltrion, Inc. v. Genentech, Inc., a sequence-engineered, FDA-
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`approved antibody drug lacks nexus to even sub-genus claims reciting specific
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`mutations. IPR2017-01374, Paper 85 at 45, 48 (PTAB Nov. 29, 2018) (relying on
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`1 Teva’s representative species argument is waived, as Teva failed to raise it before
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`the oral argument. See POR, 55-56; Sur-reply, 27; Cablz, Inc. v. Chums, Inc., 708 F.
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`App’x 1006, 1011-12 (Fed. Cir. 2017). Moreover, Teva’s new arguments alleging
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`praise and success for Alder’s antibody are also waived, as Teva argued Alder only
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`in the context of a license agreement. POR, 63-64.
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`2
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` IPR2018-01710
`Patent No. 8,586,045
`“one (or a small number of) species” is “inadequate proof” for nexus). Teva’s claims
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`
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`are much broader because they are not limited by sequence. Reply, 22.
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`Teva contends that Ajovy® and Emgality® have the “structure and properties”
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`required by the claims (Br., 6), but fails to identify any claimed structure or claimed
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`properties that confer the therapeutic profiles driving Teva’s alleged praise and other
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`secondary considerations. Regardless, Dr. Tomlinson’s consideration of just one
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`sequence-dependent property—pM-level binding affinity—led him to contradict
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`Teva’s “representative species” argument, conceding that Ajovy® and Emgality® “do
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`not represent” the full scope of the claims. Ex. 1301, 103:25-104:19 (“They’re just
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`two antibodies within [the claimed] range.”); Ex. 2217, 8-9.
`
`III. Teva Failed to Distinguish Fox Factory
`As discussed, the sequences of Ajovy® and Emgality® dictate their therapeutic
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`function, and are thus responsible for Teva’s alleged secondary indicia. Regardless,
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`contrary to Teva’s arguments, Fox Factory does not require unclaimed features to be
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`directly “responsible for” alleged praise and success to find the presumption
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`inapplicable. Br., 3. Rather, it was sufficient that any one of four unclaimed features
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`“materially impacts the functioning” of the cited chainring products, contributing to
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`their praise and success. Fox Factory, 944 F.3d at 1376 (“For each of these features
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`… nexus can only be presumed … if the claim includes limitations relating to [it].”).
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`Here, multiple features not recited in the challenged claims each materially impact
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`3
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` IPR2018-01710
`Patent No. 8,586,045
`the efficacy and safety profile of Ajovy® and Emgality® in treating headache, which
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`
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`contributes to (and is indeed “responsible for”) Teva’s alleged secondary indicia.
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`Teva’s diagram betrays its fundamental misunderstanding of Fox Factory and
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`the coextensiveness requirement. Br., 4. As an initial matter, it misrepresents the
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`facts of this case, as the cited antibodies constitute, at most, mere specks within the
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`vast expanse of claims encompassing countless different sequences. More
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`fundamentally, Teva incorrectly depicts the unclaimed features in Fox Factory (e.g.,
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`80% gap-filling) as outside the scope of the claims. Id. In Fox Factory, products with
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`those material, unclaimed features were fully within the scope of the claims—the
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`problem was that no limitations reciting those material features narrowed the claims
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`to a scope coextensive with the cited products. 944 F.3d at 1375-76. Here, Teva’s
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`challenged claims similarly lack any limitations narrowing the claims to a scope
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`where coextensiveness might be plausible (e.g., for claims reciting sequences).
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`IV. Teva Failed to Address Its Unchallenged Claims Reciting Sequence
`Ascribing little weight to the ’045 patent’s method-of-treatment recitations,
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`which do not require any particular levels of safety or efficacy, Teva argues that the
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`six challenged antibody patents and three method-of-treatment patents “generally
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`cover the same invention” without any significant differences. Br., 6.
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`Ignoring its burden, however, Teva never established that only the challenged
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`claims of these nine patents are relevant for nexus. Teva obtained 188 patents in 8
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`4
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`Patent No. 8,586,045
`patent families. Ex. 1302, 45:3-46:19. Teva never explained how the ’045 patent had
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`any specific nexus to Teva’s purported secondary considerations in view of the other
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`187 patents, as required. Fox Factory, 944 F.3d at 1378. Moreover, Teva flatly
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`ignored the unchallenged sequence-specific claims of the ’794, ’045, ’614, ’881, and
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`’951 patents. Teva’s large patent portfolio further shows that no presumption applies.
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`Alleging that the only critical feature is that the cited products are “humanized
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`anti-CGRP antagonist antibodies” for treating migraine, Teva forecloses any
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`possibility of establishing nexus. Br., 3-4. Indeed, this is not novel—multiple
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`references taught exploring humanized anti-CGRP antagonist antibodies to treat
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`migraine. Ex. 1096, 567, 570; Ex. 1287, 247. Furthermore, the only property Dr.
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`Rapoport considered for nexus is the ability of antibodies to “block the CGRP
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`pathway,” which is a mechanism of action previously known to treat migraine.
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`Reply, 24. As stated by the Federal Circuit, it is a “fundamental requirement” that
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`secondary indicia must result from something that is “both claimed and novel in the
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`claim.” In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (emphasis in original).
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`Because Teva relies exclusively on a non-novel feature, there can be no nexus.
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`Respectfully submitted,
`
`Date: January 31, 2020
`
`By: / William B. Raich /
`William B. Raich (Reg. No. 54,386)
`
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`5
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` IPR2018-01710
`Patent No. 8,586,045
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`CERTIFICATE OF SERVICE
`The undersigned certifies that a copy of the foregoing Petitioner’s
`
`Response to Teva’s Supplemental Brief Regarding Fox Factory, Inc. v. SRAM,
`
`LLC was served electronically via email on January 31, 2020, in its entirety on the
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`following:
`
`Deborah A. Sterling
`Robert C. Millonig
`Gaby L. Longsworth
`Jeremiah B. Frueauf
`Olga A. Partington
`Dennies Varughese
`STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
`1100 New York Avenue, NW
`Washington, DC 20005
`dsterling-PTAB@sternekessler.com
`bobm-PTAB@sternekessler.com
`glongs-PTAB@sternekessler.com
`jfrueauf-PTAB@sternekessler.com
`opartington-PTAB@sternekessler.com
`dvarughe-PTAB@sternekessler.com
`
`
`Patent Owner has consented to service by email.
`
`
`Date: January 31, 2020
`
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`
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`By: / William Esper /
`William Esper
`Litigation Legal Assistant
`
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
`
`
`
`
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