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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`______________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________
`
`ELI LILLY AND COMPANY,
`Petitioner,
`v.
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH,
`Patent Owner.
`______________________
`
`Case No. IPR2018-01423
`Patent No. 9,266,951 B2
`______________________
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`PETITIONER’S RESPONSE TO TEVA’S SUPPLEMENTAL BRIEF
`REGARDING FOX FACTORY, INC. v. SRAM, LLC
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`IPR2018-01423
`Patent No. 9,266,951
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`I.
`II.
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`Table of Contents
`Teva Failed to Meet Its Burden of Establishing Coextensiveness................. 1
`Teva Failed to Meet Its Burden of Showing Insignificance of
`Unclaimed Features and Other Patents ......................................................... 1
`III. Teva Failed to Establish Nexus .................................................................... 4
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`I.
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`IPR2018-01423
`Patent No. 9,266,951
`Teva Failed to Meet Its Burden of Establishing Coextensiveness
`Fox Factory rejected changing the coextensiveness requirement to an analysis
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`of whether a claim “cover[s]” products cited for secondary considerations. Fox
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`Factory v. SRAM, LLC, 744 F.3d 1373, 1377 (Fed. Cir. 2019). Yet in its substantive
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`briefing, Teva merely alleged that the claims “cover one or both of Ajovy® and
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`Emgality®” without addressing coextensiveness, the broad scope of the claims, or
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`the materiality of unclaimed features. POR, 48; Sur-reply, 25; Ex. 2223, ¶106.
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`Although Teva reaffirmed at the oral hearing that its position was that the
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`claims “cover” the products and that the claims are not coextensive, Teva now
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`contends that coextensiveness exists because Ajovy® and Emgality® “are humanized
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`anti-CGRP antagonist antibodies” within the broad scope of the claims. Br., 1-2, 5;
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`Paper 68, 63 (“Your Honor, I’m not saying they’re co-extensive”). This is a
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`distinction without a difference, as Teva fails to address the incredible breadth of the
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`claims or its many admissions that unclaimed features materially impact function.
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`II. Teva Failed to Meet Its Burden of Showing Insignificance of Unclaimed
`Features and Other Patents
`Lilly identified multiple features encompassed by the claims but not recited
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`as limitations that materially affect function—such as amino acid sequence, pM-
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`level binding affinity, antibody format, and antibody class. Reply, 21-24. Despite
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`bearing the burden of establishing that unclaimed features are “insignificant,” Fox
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`Factory, 944 F.3d at 1374-75, Teva offered no response. Sur-reply, 25.
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`1
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`IPR2018-01423
`Patent No. 9,266,951
`Indeed, Teva fails to offer any evidence contradicting the universally
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`understood principle that sequence is critical and dictates antibody function. Teva
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`represented to the FDA that it introduced multiple specific mutations into Ajovy®—
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`out of more than 20220 possible mutations—to achieve pM-level binding affinity and
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`eliminate ADCC and CDC. Ex. 2217, 8-9; Ex. 1023, 2:17-27 (affinity is “critical[]”
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`for an antibody’s biological function); Ex. 1301, 91:25-92:22. This is highly
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`analogous to Fox Factory, where a patentee’s representations in its marketing
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`materials confirmed lack of nexus due to unclaimed features. 944 F.3d at 1375-76.
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`Emgality®’s specific sequence and resulting properties, with mutations to eliminate
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`ADCC and CDC, were likewise highlighted to the FDA. Ex. 2216, 17, 21-22, 41.
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`Teva concedes that Ajovy® and Emgality® have different sequences, but fails
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`to support its baseless (and belated) assertion that sequence is insignificant to its
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`secondary considerations evidence. Br., 4-5. Sequence matters: depending on their
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`specific sequence, anti-CGRP antibodies within the broad scope of all challenged
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`claims would have (1) binding affinity orders of magnitude worse than Ajovy® and
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`Emgality®, (2) strong effector functions having the undesired side effect of killing
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`cells (cytotoxicity), (3) an antibody fragment format that Dr. Tomlinson testified
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`would be useless as a therapeutic, and/or (4) an antibody class never successfully
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`used before in any FDA-approved antibody. Reply, 21-24; Ex. 1301, 27:25-28:6,
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`134:14-25, 34:9-35:1, 36:16-39:11, 102:1-104:19; Ex. 1004, ¶168. These unclaimed
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`2
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`IPR2018-01423
`Patent No. 9,266,951
`features would lead to materially different properties (e.g., no efficacy or significant
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`adverse events) as compared to Ajovy® and Emgality®. Reply, 21-24. Notably, even
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`these antibodies have fundamentally different properties: Lilly’s Emgality® is FDA-
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`approved to treat cluster headache while Teva’s Ajovy® failed clinically. Ex. 2153, 1.
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`Teva newly argues that antibodies with different sequences are “associated
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`with the same praise.” Br., 4. But this alleged praise is directed to only two high-
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`affinity, sequence-optimized antibodies (Ajovy® and Emgality®) and is not
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`representative of the broad challenged claims.1 See AbbVie Deutchsland GmbH v.
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`Janssen Biotech, Inc., 759 F.3d 1285, 1291-92, 1301 (Fed. Cir. 2014) (concluding
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`that even 300 antibodies do not represent a functionally defined genus). Moreover,
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`the alleged praise extends to compounds outside the scope of the claims such as anti-
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`CGRP receptor antibodies and small molecule inhibitors. Reply, 24-25. As Dr.
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`Rapoport admitted, the only property he considered for nexus is the ability of
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`antibodies to “block the CGRP pathway,” which is legally insufficient because this
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`mechanism of action was already disclosed to treat migraine. Reply, 24; Ex. 1304,
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`142:1-8.
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`1 Teva argued Alder only in the context of a license agreement. POR, 56-57. Teva’s
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`new arguments alleging praise and success for Alder’s antibody should be rejected.
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`Cablz, Inc. v. Chums, Inc., 708 F. App’x 1006, 1011-12 (Fed. Cir. 2017).
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`3
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`IPR2018-01423
`Patent No. 9,266,951
`Teva also newly argues that its nine challenged patents “generally cover the
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`same invention” without any significant differences. Br., 5-6. Ignoring its burden,
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`Teva neither analyzed any of the specific combinations of recited features nor
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`established that the challenged claims of these nine patents are the only relevant
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`claims for analyzing nexus. Indeed, Teva flatly ignored the unchallenged sequence-
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`specific claims of the ’794, ’614, ’881, and ’951 patents. Teva also failed to address
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`the 188 patents and 8 patent families listed in the Alder agreement. Ex. 2257, 20-28.
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`Teva’s large patent portfolio further shows that no presumption applies.
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`Teva incorrectly implies that Fox Factory requires an admission of criticality
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`to find the presumption inapplicable, rather than the existence of just one unclaimed
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`material feature. Br., 3. Regardless, Teva and its experts admitted that sequence,
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`antibody format, antibody class, and affinity all materially affect function, and
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`moreover that Teva’s claims are not coextensive with Ajovy® and Emgality®. Paper
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`68, 63; Ex. 2217, 8-9; Ex. 1301, 27:25-28:6, 134:14-25, 102:1-104:19, 34:9-35:1,
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`36:16-39:11. Thus, Fox Factory confirms that the presumption does not apply.
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`III. Teva Failed to Establish Nexus
`Teva chose to rely on the presumption rather than argue that its purported
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`secondary considerations were attributable to what Teva actually claimed. Sur-reply,
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`25. Teva’s belated argument to show nexus outside the presumption is thus waived.
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`It also lacks merit. While Teva cites Drs. Tomlinson and Stoner (Br., 6-7), they
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`4
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`IPR2018-01423
`Patent No. 9,266,951
`merely testified that the claims “cover” Ajovy® and Emgality® and that the Alder
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`license “included”
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`the ’951 patent—not
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`that Teva’s purported secondary
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`considerations evidence is attributable to what is both claimed and novel in the
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`claims. Ex. 2223, ¶106; Ex. 2240, ¶19. Moreover, as explained above, the cited
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`products do not represent the countless number of antibodies encompassed by the
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`claims. As held in Celltrion, Inc. v. Genentech, Inc., therapeutic antibodies lack
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`nexus to broader claims encompassing multiple sequence mutations. IPR2017-
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`01374, Paper 85 at 45, 48 (PTAB Nov. 29, 2018) (relying on “one (or a small number
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`of) species” is “inadequate proof” because “objective evidence … must be
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`commensurate in scope with the claims which the evidence is offered to support.”).
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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,” Teva forecloses any possibility of establishing
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`nexus (irrespective of the presumption). Br., 4-5. Indeed, this is not novel—multiple
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`references taught humanized anti-CGRP antagonist antibodies. Ex. 1096, 567, 570;
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`Ex. 1287, 247. As stated by the Federal Circuit, it is a “fundamental requirement”
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`that secondary indicia must result from something that is “both claimed and novel in
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`the 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,
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`Date: January 17, 2020
`
`By: / William B. Raich /
`William B. Raich (Reg. No. 54,386)
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`5
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`IPR2018-01423
`Patent No. 9,266,951
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`CERTIFICATE OF SERVICE
`The undersigned certifies that a copy of the foregoing Petitioner’s
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`Response to Teva’s Supplemental Brief Regarding Fox Factory, Inc. v. SRAM,
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`LLC was served electronically via email on January 17, 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.
`
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`Date: January 17, 2020
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`By: / William Esper /
`William Esper
`Litigation Legal Assistant
`
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
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