Filed on behalf of: Eli Lilly and Company
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`______________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________
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`ELI LILLY AND COMPANY
`Petitioner
`v.
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH
`Patent Owner
`______________________
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`Case IPR2018-01710 (Patent No. 8,586,045)
`Case IPR2018-01711 (Patent No. 9,884,907)
`Case IPR2018-01712 (Patent No. 9,884,908)1
`_____________________
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`PETITIONER’S REPLY TO PATENT OWNER’S
`PRELIMINARY RESPONSE
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`1 Lilly was authorized to file this Reply pursuant to the Board’s email sent on January
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`16, 2019. The word-for-word identical paper is filed in each proceeding identified
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`in the caption, pursuant to the Board’s previous order. For convenience, citations
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`refer to papers filed in IPR2018-01710 involving Teva’s Patent No. 8,586,045.
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`Emphases are added unless otherwise noted. Lilly does not acquiesce to any of
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`Teva’s arguments not specifically addressed herein.
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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 IPR2018-01710 (Patent No. 8,586,045)
`Case IPR2018-01711 (Patent No. 9,884,907)
`Case IPR2018-01712 (Patent No. 9,884,908)1
`_____________________
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`PETITIONER’S REPLY TO PATENT OWNER’S
`PRELIMINARY RESPONSE
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`1 Lilly was authorized to file this Reply pursuant to the Board’s email sent on January
`
`16, 2019. The word-for-word identical paper is filed in each proceeding identified
`
`in the caption, pursuant to the Board’s previous order. For convenience, citations
`
`refer to papers filed in IPR2018-01710 involving Teva’s Patent No. 8,586,045.
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`Emphases are added unless otherwise noted. Lilly does not acquiesce to any of
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`Teva’s arguments not specifically addressed herein.
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`IPR2018-01710, -01711, -01712
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`I.
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`Introduction
`Teva’s § 325(d) arguments are unavailing. First, none of Lilly’s asserted
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`references—Olesen, Tan or Queen—was used to reject any claims of the ’045, ’907,
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`or ’908 method-of-treatment patents during prosecution. Second, the asserted
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`references are not cumulative of the Frobert and Pisenga references used to reject
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`composition claims. Indeed, Lilly’s asserted references and expert testimony2
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`establish an explicit motivation to make humanized anti-CGRP antagonist
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`antibodies to treat migraine, which Teva argues was missing during prosecution.
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`Third, Lilly specifically addressed how Teva’s one-sided arguments regarding Tan
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`were incorrect. Thus, the Becton factors strongly favor institution.
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`II. Lilly’s Asserted References Were Not Used to Reject Any Claims
`During prosecution of the ’045, ’907, and ’908 patents, the Examiner did not
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`make any art-based rejections. Ex. 2034, 459-73; Ex. 2044, 172-78; Ex. 2045,
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`185-92. In fact, Olesen and its key teaching that blocking the CGRP pathway
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`effectively treated migraine in human patients was not even of record in the ’045
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`patent. POPR, 16. Because the Office did not consider Olesen, much less in a
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`2 Teva’s reliance on Invidior, Argentum, Dorco, Hologic, Siemens, and Telebrands
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`(POPR, 28) is misplaced because those cases did not involve new, noncumulative
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`references and disclosures in addition to undisputed expert testimony.
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`1
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`IPR2018-01710, -01711, -01712
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`combination with Tan and Queen, a § 325(d) denial is not warranted.
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`III. Lilly’s Asserted References Are Not Cumulative
`Olesen is not cumulative of any purported consideration by the Examiner of
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`the specification’s limited disclosures about BIBN4096BS. See POPR, 17. Olesen
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`itself was never cited, and BIBN4096BS itself is referred to in the Background
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`section only once. Ex. 1001, 2:14-18. Moreover, Lilly’s use of Olesen is not
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`restricted to “its [alleged] teaching that a small molecule CGRP-receptor antagonist
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`BIBN4096BS could be used to treat migraine,” as Teva incorrectly contends. POPR,
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`16-17. Instead, Lilly and its unrebutted evidence3 demonstrates that Olesen’s proof-
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`of-concept study (1) “established that blocking the CGRP pathway reduced the
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`incidence of migraine;” (2) “demonstrates that CGRP itself—and not only its
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`receptors—was also a therapeutic target;” and (3) “confirmed the reasonable
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`expectation that a CGRP antagonist could be successfully used to reduce incidence
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`of or treat migraine.” E.g., Pet., 25-26, 38 (emphases added); see also id., 1, 15.
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`Teva’s reliance on Example 6 is also misplaced. Example 6 merely compares
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`3 Teva did not respond to Lilly’s background references except to incorrectly argue
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`that the Board should ignore them. POPR, 33-34; Genzyme Therapeutic Prods. Ltd.
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`P’ship v. Biomarin Pharm. Inc., 825 F.3d 1360, 1369 (Fed. Cir. 2016) (the Board
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`should consider references illustrating the state of the art under § 103).
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`2
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`IPR2018-01710, -01711, -01712
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`the effects of BIBN4096BS and a murine—not humanized—monoclonal anti-CGRP
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`antibody in an in vivo animal model. Ex. 1001, 68:64-67, 69:25-27; see also id.,
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`10:62-11:7. Olesen, by contrast, demonstrates that blocking the CGRP pathway had
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`already been shown to effectively treat migraine in humans. Teva’s brief discussion
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`of Example 6 in response to an enablement rejection (Ex. 2034, 497) did not inform
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`the Examiner of Olesen’s successful treatment of migraine in humans.
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`Further, Teva’s § 325(d) position relies heavily on a rejection over Frobert
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`and Pisegna made during prosecution of each of the ’794 and ’649 composition
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`patents. E.g., POPR, 18-19, 22, 24-25. But Teva fails to explain how that one art-
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`based rejection is applicable to method of treatment claims that the Office and Teva
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`treated as separately patentable. Ex. 2033, 391-97, 403-09; Ex. 2034, 331-32;
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`Ex. 2044, 172-78; Ex. 2045, 185-92; Vizio, Inc. v. Nichia Corp., IPR2017-00551,
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`Paper 9 at 8 (PTAB July 7, 2017) (rejecting § 325(d) argument where there was “no
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`evidence that the Examiner considered[] [the prior art] in the context of the claims
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`of the [challenged] patent”). Thus, prosecution of Teva’s composition patents poses
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`no basis for a § 325(d) denial here.
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`Even if Teva’s arguments are considered, however, Olesen is not cumulative
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`of Pisegna or Frobert. Frobert relates to an immunoassay for measuring biological
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`levels of CGRP. Ex. 1032, 275. Pisegna focuses on isolating the CGRP receptor
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`itself, and its antibody disclosure is limited to rat antibodies that were not tested in
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`3
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`IPR2018-01710, -01711, -01712
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`any way. Ex. 1134, ¶ [0002], Example 1. Neither reference discloses successful
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`treatment of migraine in humans with a CGRP antagonizing agent.
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`Nor is Tan cumulative of Frobert and Pisegna.4 Teva attempts to cabin Lilly’s
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`reliance on Tan to its disclosure of murine anti-CGRP antibodies. POPR, 19. But as
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`Lilly and its experts have established, Tan discloses that anti-CGRP antagonist
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`antibodies (1) effectively block the CGRP pathway in vivo, (2) were known
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`alternatives to CGRP receptor antagonists (such as CGRP8-37 or Olesen’s
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`BIBN4096BS) for blocking the CGRP pathway in vivo, and (3) “clearly diffuse[]
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`into the synaptic cleft,” i.e., the site of action that Teva alleges is necessary for in
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`vivo effectiveness. Pet. 24, 26-27, 43-48; Ex. 1014, ¶¶ 111, 118. Neither Frobert nor
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`Pisegna contains these disclosures. Nor do they describe Tan’s guidance to use
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`higher doses and longer distribution times of antibodies to reach the site of action,
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`which Teva followed in its specification. Pet., 43-48; Ex. 1014, ¶¶ 88-100.
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`Instead, Olesen’s disclosure that blocking the CGRP pathway is effective for
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`treating migraine—along with Tan’s disclosure that anti-CGRP antagonist
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`antibodies are a known “alternative” or “complementary” technique to using CGRP-
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`receptor antagonists—establish a motivation to humanize an anti-CGRP antibody
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`4 Contrary to Teva’s assertion, the ’045 patent was allowed before the Examiner
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`received any Tan arguments from Teva. Ex. 2034, 519-24; Ex. 2005, 179-84.
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`4
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`IPR2018-01710, -01711, -01712
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`for treating migraine in humans. Pet., 25-27 (citing Ex. 1014 ¶¶ 31-36, 68-69, 109).
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`That motivation is precisely what Teva contends was a “critical issue” missing
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`during prosecution. POPR, 24. Thus, institution is appropriate.
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`IV. Lilly’s Petition and Experts Addressed the Errors in Prosecution
`Teva incorrectly asserts that Lilly did not explain how the Examiner erred in
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`allegedly evaluating Tan during prosecution of the ’649 composition patent. POPR,
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`25-26. Teva’s assertions are misleading because the Examiner failed to make any
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`statements about Tan (or Olesen or Queen). See Ex. 2005. Nevertheless, Lilly
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`addressed Teva’s one-sided arguments to the Examiner based on selected portions
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`of Tan, explaining that Teva’s arguments were incomplete and incorrect. Pet., 43-48
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`(citing Ex. 1014, ¶¶ 88-100, 135; Ex. 1015, ¶¶ 101-102). Lilly submits that it would
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`be inappropriate to exercise discretion when there is “no evidence that the Examiner
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`considered . . . the particular disclosures [of Tan ] cited by Petitioner in the Petition
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`or addressed arguments similar to those Petitioner now presents” to the Board. Vizio,
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`IPR2017-00551, Paper 9 at 8; see also Navistar, IPR2018-00853, Paper 13 at 18.
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`V. Conclusion
`Lilly respectfully submits that the Becton factors weigh in favor of institution
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`and requests that the Board grant Lilly’s Petitions.
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`Respectfully submitted,
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`Date: January 28, 2019
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`By: /William B. Raich/
`William B. Raich (Reg. No. 54,386)
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`5
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`IPR2018-01710, -01711, -01712
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`CERTIFICATE OF SERVICE
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`The undersigned certifies that a copy of the foregoing Petitioner’s Reply to
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`Patent Owner’s Preliminary Response was served electronically via email on
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`January 28, 2019, in its entirety on the following:
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`Deborah A. Sterling
`Robert C. Millonig
`Gaby L. Longsworth
`Jeremiah B. Frueauf
`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
`
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`Patent Owner has consented to service by email.
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`
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`Date: January 28, 2019
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`
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`By: /William Esper/
`William Esper
`Litigation Legal Assistant
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`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, LLP
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