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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. IPR2018-01423
`Patent No. 9,266,951
`______________________
`
`PETITIONER’S OPPOSITION TO
`PATENT OWNER’S MOTION TO STRIKE
`
`
`
`IPR2018-01423
`Patent No. 9,266,951
`
`I.
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`Introduction
`Lilly’s Reply, accompanying exhibits, and supporting declarations respond to
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`new issues raised in Teva’s POR and by Teva’s experts and therefore are within the
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`proper scope of a reply. Teva claims that Lilly’s Reply and exhibits “present new
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`evidence and theories of invalidity,” but there is nothing to support those conclusory
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`statements. Instead, Teva uses its Motion to argue its substantive validity positions
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`and level unsupported attacks on Lilly’s experts. Teva’s Motion should be denied.
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`II. Argument
`A petitioner in an IPR proceeding may introduce arguments at the reply stage
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`in response to arguments raised in a POR. Anacor Pharm., Inc. v. Iancu, 889 F.3d
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`1372, 1380-81 (Fed. Cir. 2018); 37 C.F.R. § 42.23(b). The Board routinely allows
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`new evidence, including declarations from new experts, in reply. See e.g., Belden
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`Inc. v. Berk–Tek LLC, 805 F.3d 1064, 1078 (Fed. Cir. 2015). New reply evidence is
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`also appropriate if it is used “to document the knowledge that skilled artisans would
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`bring to bear in reading the prior art identified as producing obviousness.” Anacor,
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`889 F.3d at 1380-81.
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`Striking portions of a party’s brief is “an exceptional remedy” not warranted
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`here. A reply or reply evidence may be excluded if it introduces an entirely new
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`theory of obviousness or new evidence that is necessary to make out a prima facie
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`case of patentability. Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d
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`1
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`IPR2018-01423
`Patent No. 9,266,951
`1359, 1369-70 (Fed. Cir. 2016). By contrast, exclusion is inappropriate where, as
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`here, a reply “expands the same argument made in its Petition.” Ericsson Inc. v.
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`Intellectual Ventures I LLC, 901 F.3d 1374, 1381 (Fed. Cir. 2018).
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`A. Exhibit 1287 and Related Sections of Lilly’s Reply
`Exhibit 1287 and Lilly’s related argument (Reply, 3, 11-12) are directly
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`responsive to assertions newly made in Teva’s POR. Teva and its experts incorrectly
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`argued that Tan 1995, an asserted reference, was a “basic research paper” that would
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`not have motivated a POSA to make humanized antibodies. POR, 2, 4, 14, 42, 45;
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`Ex. 2211, ¶¶ 61, 63-64; Ex. 2229, ¶¶ 50, 77. Teva further alleged to have personal
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`knowledge of co-authors of the Tan references, implying they never considered
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`antibody humanization. POR, 45; Ex. 2211, ¶¶ 70, 76. Teva also argued that certain
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`blood pressure data presented in Tan 1995 would have discouraged further research.
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`POR, 22-25, 41-42.
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`Exhibit 1287, which was written by Dr. Tan in 1994 and describes his and his
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`co-authors’ work in Tan 1995, directly contradicts Teva’s arguments. With first-hand
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`knowledge of the blood pressure results in Tan 1995, Dr. Tan wrote there was “no
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`reason” why humanized anti-CGRP monoclonal antibodies should not be
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`investigated and used as “therapeutic agents” for migraine and other diseases.
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`Ex. 1287, 247; Reply, 11-12. Exhibit 1287 is therefore proper reply evidence.
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`Teva’s Motion mischaracterizes Lilly’s Reply as using Ex. 1287 as “an alleged
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`IPR2018-01423
`Patent No. 9,266,951
`‘contemporaneous’ teaching of motivation.” The actual text of Lilly’s Reply is clear:
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`for “further motivation,” it cites only the Petition, Tan 1994 (Ex. 2021), Tan 1995
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`(Ex. 2022), and Ex. 1303. Reply, 3. Exhibit 1287 is included to provide contextual
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`information, made necessary by Teva’s allegations that blood pressure readouts
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`reported in Tan 1995 would have raised safety concerns. See, e.g., Ex. 2229, ¶¶ 77-
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`82. This is explained at pages 11-12 of Lilly’s Reply, which Teva fails to address.
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`Thus, Ex. 1287 and its use in Lilly’s Reply are plainly proper rebuttal. Belden,
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`805 F.3d at 1082 (“the function of rebuttal [is] to explain, repel, counteract, or
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`disprove the evidence of the adverse party”).
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`B.
`
`Lilly’s Evidence and Discussion of Aptamers Is Properly
`Responsive to Teva’s POR
`Teva incorrectly seeks to strike evidence and reply briefing concerning
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`CGRP-binding aptamers (Reply, 9; Ex. 1240; Ex. 1309; Ex. 1321, ¶¶ 38, 51, 52, 54,
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`60, 69; Ex. 1322, ¶¶ 17, 31, 74, 77). But anti-CGRP aptamer evidence was originally
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`presented with the Petition. Pet., 39, 58. Lilly also properly used that evidence to
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`directly respond to multiple Teva arguments.
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`Teva argued that a POSA would have had safety concerns associated with
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`directly antagonizing CGRP, particularly for compounds with a long half-life. POR,
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`19-29; Ex. 2229, ¶ 73-82; Ex. 2211, ¶¶ 12, 27-70. Teva further argued a POSA would
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`not have targeted CGRP, as opposed to its receptor, because of (1) hypothetical safety
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`concerns about preventing CGRP from binding to receptors other than the CGRP-
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`IPR2018-01423
`Patent No. 9,266,951
`receptor (cross-binding) and (2) hypothetical efficacy concerns based on the “spare
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`receptor theory.” POR, 29-31; Ex. 2229, ¶¶ 23-42, 88-95.
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`Lilly rebuts those positions in part with evidence that CGRP-binding
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`aptamers—recognized in the prior art as “analogs to antibodies”—were being
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`developed to treat migraine. These aptamers had long half-lives yet displayed no
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`safety risks. Reply, 9; Ex. 1240; Ex. 1309; Ex. 1321, ¶¶ 48-70; Ex. 1322, ¶¶ 17, 31,
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`74, 77. Lilly’s Reply further cites this aptamer evidence to illustrate the unsupported
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`and hypothetical nature of Teva’s “spare receptor” and cross-binding arguments, as
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`notwithstanding Teva’s purported concerns researchers were actually developing
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`anti-migraine agents targeting CGRP directly. Reply, 16-19; Ex. 1321, ¶¶ 40-47; Ex.
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`1322, ¶¶ 17, 65-75.
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`Teva misleadingly refers to Lilly’s rebuttal evidence related to aptamers as
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`“an entirely new aptamer-based theory.” Teva is incorrect. The fact that evidence
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`related to aptamers contradicts more than one of Teva’s new arguments does not
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`make it a “new theory.” Moreover, Teva ignores Dr. Charles’s (and Tan’s) position
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`that targeting the CGRP ligand or its receptor were “alternative, complementary
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`strategies.” Ex. 1004, ¶ 124; Ex. 1022, 566, 571. Researchers’ pursuit of CGRP-
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`binding aptamers provides further objective evidence that CGRP antagonism and
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`CGRP-receptor antagonism were in fact considered alternatives.
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`Thus, Lilly’s Reply arguments and evidence relating to aptamers are wholly
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`IPR2018-01423
`Patent No. 9,266,951
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`proper and there is no basis to strike them.
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`C. Dr. Balthasar’s Declaration and Related Sections of Lilly’s Reply
`Teva raised new arguments related to antibody distribution to the synaptic
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`cleft (POR, 40; Ex. 2229, ¶¶ 49-55), and now incorrectly seeks to strike portions of
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`Lilly’s Reply and Dr. Balthasar’s declaration addressing this issue (Reply, 20; Ex.
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`1321, ¶¶ 15-34).
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`The record does not support Teva’s criticism of Dr. Charles or its argument
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`that Dr. Balthasar’s testimony is used to “shore up” Lilly’s invalidity arguments. Dr.
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`Balthasar, an antibody pharmacology expert, responds to arguments raised in Dr.
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`Foord’s declaration, as Teva has acknowledged. See Ex. 2262, 10:7-11. Dr.
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`Balthasar’s declaration properly contradicts Dr. Foord’s unsupported opinions,
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`explaining how Tan’s encouraging results were consistent with known antibody
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`pharmacokinetics and how access to the synaptic cleft would not have been a
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`concern to a POSA. Ex. 1321, ¶¶ 15-34. Moreover, Teva’s admission that Drs.
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`Charles’s and Balthasar’s testimony is consistent undercuts Teva’s view of Dr.
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`Charles, as both his opinions and those of Dr. Balthasar are rooted in the prior art.
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`III. Conclusion
`Teva’s Motion to Strike should be denied.
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`Respectfully submitted,
`
`Date: October 9, 2019
`
`By: / William B. Raich /
`William B. Raich (Reg. No. 54,386)
`
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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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`Opposition to Patent Owner’s Motion to Strike was served electronically via
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`email on October 9, 2019, in its entirety on the 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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`
`
`By: / William Esper /
`William Esper
`Litigation Legal Assistant
`
`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
`
`
`
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`Date: October 9, 2019
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