Filed on behalf of: Par Pharmaceutical, Inc. et al.
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`Entered: October 10, 2017
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________
`
`PAR PHARMACEUTICAL, INC., ARGENTUM PHARMACEUTICAL LLC,
`AND WEST-WARD PHARMACEUTICALS INTERNATIONAL LIMITED,
`Petitioners
`v.
`NOVARTIS AG
`Patent Owner
`_______________________
`Case IPR2016-014791
`U.S. Patent No. 9,006,224
`_______________________
`
`Before LORA M. GREEN, CHRISTOPHER L. CRUMBLEY, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`
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`PETITIONERS’ RESPONSE TO PATENT OWNER’S
`MOTION FOR OBSERVATIONS
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`
`
`1 Argentum Pharmaceutical LLC was joined as a party to this proceeding via a
`Motion for Joinder in IPR2017-01063; West-Ward Pharmaceuticals International
`Limited was joined as a party via a Motion for Joinder in IPR2017-01078.
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`Entered: October 10, 2017
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________
`
`PAR PHARMACEUTICAL, INC., ARGENTUM PHARMACEUTICAL LLC,
`AND WEST-WARD PHARMACEUTICALS INTERNATIONAL LIMITED,
`Petitioners
`v.
`NOVARTIS AG
`Patent Owner
`_______________________
`Case IPR2016-014791
`U.S. Patent No. 9,006,224
`_______________________
`
`Before LORA M. GREEN, CHRISTOPHER L. CRUMBLEY, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`
`
`PETITIONERS’ RESPONSE TO PATENT OWNER’S
`MOTION FOR OBSERVATIONS
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`
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`
`
`1 Argentum Pharmaceutical LLC was joined as a party to this proceeding via a
`Motion for Joinder in IPR2017-01063; West-Ward Pharmaceuticals International
`Limited was joined as a party via a Motion for Joinder in IPR2017-01078.
`
`
`
`IPR2016-01479
`U.S. Patent No. 9,006,224
`
`Table of Contents
`
`I.
`
`II.
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`The Board should deny Novartis’s motion because each observation
`presents impermissible additional argument ................................................... 1
`Responses to observations ............................................................................... 2
`A. Mot. 1 “PNETS and Carcinoids . . . .” .................................................. 2
`B. Mot. 1-5: “Evidence [of] Resistance To Second-Line Therapy
`In Advanced PNETs . . .” ...................................................................... 3
`C. Mot. 5-8: “Duran and Oberg 2004 . . . Reasonable Expectation
`of Success” ............................................................................................ 6
`D. Mot. 8-9 “RADIANT-3 Results . . .” .................................................... 7
`E. Mot. 9 “Sunitinib . . .” ........................................................................... 7
`F. Mot. 9 “The Inventors . . .” ................................................................... 7
`
`i
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`
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`I.
`The Board should deny Novartis’s motion because each observation
`presents impermissible additional argument
`The Board should deny Novartis’s motion for observations of Dr. Ratain’s
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`deposition (Paper 34, “Mot.”) in its entirety because Novartis impermissibly argues
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`its case rather than concisely pointing out relevant testimony and its relevance as
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`required by the Trial Practice Guide. 77 Fed. Reg. 48756, 48767-68 (Aug. 14,
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`2012). That is, Novartis’s argumentative observations impermissibly characterize
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`the subject testimony rather than quoting it or accurately summarizing it, address
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`multiple passages in a single observation, characterize other exhibits, and re-argue
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`old arguments and introduce new ones. Actelion Pharm. v. Icos, IPR2015-00561,
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`Paper 33 at 2-3 (Mar. 18, 2016) (examples of offending observations are in
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`Actelion Ex. 1049 at 14-15); LG Elecs. v. ATI Techs., IPR2015-00325, Paper 52 at
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`3-4 (Jan. 25, 2016); Medtronic v. Nuvasive, IPR2013-00506, Paper 37 at 3-4 (Oct.
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`15, 2014) (dismissing motion that included argument).
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`Petitioners therefore bring Novartis’s improper motion to the Board’s
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`attention in its response and ask the Board to dismiss or deny it in its entirety
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`without leave to correct. Green Cross v. Shire Human Genetic Therapies,
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`IPR2016-00258, Paper 78 (Dec. 21, 2016) (ordering petitioner to do the same);
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`Zhonghan at 32-33 (no leave to correct); LG Elecs. at 3-4 (also no leave).
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`1
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`II. Responses to observations
`Novartis’s impermissible arguments and characterizations include all of its
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`section headings and each observation as detailed in the following paragraphs with
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`Petitioners’ responses.
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`A. Mot. 1 “PNETS and Carcinoids . . . .”
`Novartis cites Ex. 2111, 25:9-11, 28:18-25, and 30:8-15 and Reply 6:
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`Novartis argues that the cited testimony and argument are relevant to whether
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`therapies were administered to both PNETs and carcinoids and that “clinical trials
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`typically evaluated them separately.” (Mot. 1.) Ex. 2111, 30:16-31:21 is relevant
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`to Novartis’s argument regarding the responses to treatment of PNETs and
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`carcinoids. (Mot. 1; POR 7-10.)
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`Novartis paraphrases Ex. 2111 at 254:16-255:10 and 256:19-257:8: Ex.
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`2111 at 251:5-254:12 is relevant to Dr. Ratain’s reliance and citation to Ex. 1096,
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`where he states that he “do[es]n’t know what a POSA would understand in 2005
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`on this topic. I’ve not considered that.” He further states “I only cited this
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`reference in the context of paragraph 34 of my supplemental declaration to support
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`my opinion that a POSA would have expected any cell tumor that had been
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`previously treated with nitrosourea, including advanced PNETs, to fail to respond
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`to another nitrosourea as a prior art explicitly identified.” Finally, Dr. Ratain states
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`“I cited page 81 of this document” and “I did not cite page 77 of this document.”
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`2
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`B. Mot. 1-5: “Evidence [of] Resistance To Second-Line Therapy In
`Advanced PNETs . . .”
`Novartis cites 49:7-52:18 (Mot. 1-2) to argue that molecularly targeted
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`therapies were not effective after prior cytotoxic chemotherapy. Novartis further
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`argues that Ex. 2015 and Ex. 2050 show that “temsirolimus failed to effectively
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`treat tumors treated with prior cytotoxic chemotherapy.” (Mot. 2.) Ex. 2015 at
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`1047 does not identify any difference in results between tumors previously treated
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`with chemotherapy and chemotherapy-naïve tumors, stating “[t]he results of our
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`clinical trial demonstrated that CCI-779 given at the dose and schedule. . . did not
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`have sufficient antitumor activity in melanoma to warrant further evaluation as a
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`single agent,” which is relevant to Novartis’s reliance on this reference as allegedly
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`supporting temsirolimus’s different activity in PNET after failure of cytotoxic
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`chemotherapy versus PNETs that are chemotherapy-naïve. See also Ex. 2050 at
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`359 (“This phase II study sought to evaluate the efficacy of CCI-779 . . . in patients
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`with recurrent GBM irrespective of the use of EIAEDs. Unfortunately, despite
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`good tolerance of the agent, CCI-779 did not demonstrate sufficient antitumor
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`activity to warrant further study as a single agent.”). Further, Ex. 1078 at Table 3
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`and Ex. 2111 at 275:24-276:25 indicate that prior cytotoxic chemotherapy does not
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`result in any difference in response.
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`Novartis cites 52:19-55:17, 57:7-14, 59:2-13, 62:25-63:9, 63:20-64:4 as
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`identifying certain exhibits discussing treatment of tumors that are not PNETs and
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`3
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`are treated differently than PNETs. No response is necessary as this testimony
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`does not impact the argument in Petitioners’ Reply that the prior art identified the
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`use of molecularly targeted therapies after failure of cytotoxic chemotherapy.
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`Reply 11.
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`Novartis characterizes nearly four pages of testimony at 101:13-104:7
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`(Mot. 2-3) as not related to resistance to molecularly targeted agents. No response
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`is necessary as the cited testimony does not impact Petitioners’ arguments at Reply
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`11.
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`Novartis characterizes 24:5-14 and 25:9-26:7 (Mot. 3) as contradicting a
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`POSA’s expectations that a difference in response would be reported if identified
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`in the data. No response is necessary as the cited testimony does not impact
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`Petitioners’ arguments at Reply 11-12.
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`Novartis characterizes 117:17-24 and 120:11-122:19 (Mot. 3) as
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`indicating that certain cytotoxic chemotherapies have different mechanisms of
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`action. Ex. 1070 at 15:13-25 and 158:8-15 is relevant to how a POSA would
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`understand the “class of drugs that we call cytotoxic chemotherapies” to be
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`different from the class of drugs considered “targeted therapies,” and which
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`include mTOR inhibitors.
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`Novartis paraphrases 111:13-113:5 (Mot. 4) as indicating resistance to
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`chemotherapy may have different mechanisms and somehow contradicting that a
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`4
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`POSA would not reasonably expect a tumor resistant to chemotherapy to be
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`resistant to a targeted therapy such as everolimus. Ex. 1070 at 103:19-106:25,
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`where Dr. Kulke acknowledges that all the papers he relies on to support his
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`assertion that a POSA would expect PNETs previously treated with cytotoxic
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`chemotherapy would be “more resistant” only identify the use of a second-line
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`cytotoxic chemotherapy and not any targeted therapies, is relevant to Novartis’s
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`argument that a POSA would not expect everolimus to overcome a resistance to
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`cytotoxic chemotherapy.
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`Novartis paraphrases 106:13-107:23 and 109:2-113:5 (Mot. 4) as
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`identifying multiple factors relating to drug resistance. No response necessary
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`because the testimony does not impact Petitioners’ arguments at Reply 11.
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`Novartis paraphrases 114:3-25 (Mot. 4-5) as identifying that “failure of
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`cancer cells to engage in apoptosis could underlie resistance.” Novartis presents a
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`new argument that certain genes were associated with apoptosis and rapamycin
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`resistance. Novartis inappropriately conflates “changes in the expression of BCL2
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`and p53 genes” with mutations in these genes. (Mot. 5.) No other response is
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`necessary because the testimony does not impact Petitioners’ arguments at Reply
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`10-11.
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`5
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`C. Mot. 5-8: “Duran and Oberg 2004 . . . Reasonable Expectation of
`Success”
`Novartis points to 24:5-14 and 23:14-24 and 128:11-129:15 (Mot. 5) as
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`relevant to whether a POSA would “draw reasonable conclusions regarding
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`efficacy after cytotoxic chemotherapy.” No response is necessary because the
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`testimony does not impact Petitioners’ arguments at Reply 1, 21.
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`Novartis cites 129:20-130:12, 131:7-16, 14:22-15:24, 178:12-179:3,
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`147:15-23 (Mot. 5-7) as identifying that the patient with tumor shrinkage in Duran
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`would not qualify as a partial response and would not indicate antitumor activity.
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`Ex. 1011 (Duran) identifies that patients were enrolled with progressive disease
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`and concludes temsirolimus has antitumor activity. Further, at Ex. 1119, ¶ 68, Dr.
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`Ratain testified that a POSA would consider Duran as supporting that temsirolimus
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`has antitumor activity. Dr. Kulke also testified that treatment of NETs, including
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`PNETs, with a targeted therapy that resulted in stable disease generated
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`“tremendous excitement” and supported additional clinical studies, contradicting
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`Novartis’s assertion that a POSA would not consider stable disease as relevant to
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`antitumor activity. (Ex. 1095, 789:1-24.)
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`Novartis cites 132:14-133:21 (Mot. 7) as identifying that Duran does not
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`report progression free survival. No response is necessary as this testimony does
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`not impact Petitioners’ arguments at Reply 21.
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`6
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`IPR2016-01479
`U.S. Patent No. 9,006,224
`Novartis cites 95:4-97:8 (Mot. 7-8) as identifying the first Phase I trial for
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`rapamycin. Ex. 1064 published in 2006 and is not prior art. No further response is
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`necessary as this testimony does not impact Petitioners’ arguments at Reply 19-20.
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`D. Mot. 8-9 “RADIANT-3 Results . . .”
`Novartis cites 199:17-200:20 (Mot. 8) as identifying Duran and Oberg 2004
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`as the closest prior art. No response is necessary as this testimony does not impact
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`Petitioners’ arguments at Reply 22-23.
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`Novartis cites 176:5-12 as indicating more was known about PNETs in
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`2011 than in 2005. No response is necessary as this testimony does not impact
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`Petitioners’ arguments at Reply 24.
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`E. Mot. 9 “Sunitinib . . .”
`Novartis cites 194:3-195:2 (Mot. 9) to identify that Dr. Kulke testified that
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`sunitinib satisfied a long-felt need. No response is necessary as this testimony
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`does not impact Petitioners’ arguments at Reply 25.
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`F. Mot. 9 “The Inventors . . .”
`Novartis paraphrases 222:16-23, 226:10-227:11, 228:16-21, and 267:24-
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`269:7 (Mot. 9) to identify that Novartis marketed treatments for PNETs. Ex. 2111
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`223:23-230:6 is relevant because Dr. Ratain testified that he had no basis for
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`testifying about the inventors’ interaction with other Novartis employees not
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`named as inventors of the ’224 patent. Otherwise, no response is necessary as this
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`testimony does not impact Petitioners’ arguments at Reply 2-3.
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`7
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`IPR2016-01479
`U.S. Patent No. 9,006,224
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`Dated: October 10, 2017
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`Respectfully submitted,
`
`/Daniel G. Brown/
`By:
`Daniel G. Brown (Reg. No. 54,005)
`Latham & Watkins LLP
`885 Third Avenue
`New York, NY 10022-4834
`212-906-1200; 212-751-4864 (Fax)
`
`Counsel for Petitioner
`Par Pharmaceutical, Inc.
`
`/Kevin Laurence/
`By:
`Kevin Laurence (Reg. No. 38,219)
`Laurence & Phillips IP Law LLP
`1940 Duke Street, Suite 200
`Alexandria, VA 22314
`703-448-8787
`Counsel for Petitioner
`Argentum Pharmaceutical LLC
`
`/Keith A. Zullow/
`By:
`Keith A. Zullow (Reg. No. 37,975)
`Goodwin Procter LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018-1405
`212-813-8846; 646-558-4226 (Fax)
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`Counsel for Petitioner
`West-Ward Pharmaceuticals
`International Limited
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`8
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`CERTIFICATE OF SERVICE
`Pursuant to 37 C.F.R. § 42.6(e), I certify that on this 10th day of October,
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`2017, a true and correct copy of the foregoing PETITIONERS’ RESPONSE TO
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`PATENT OWNER’S MOTION FOR OBSERVATIONS was served by
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`electronic mail on Patent Owner’s lead and backup counsel at the following email
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`address:
`
`Nicholas N. Kallas (Reg. No. 31,530)
`Charlotte Jacobsen (pro hac vice)
`Fitzpatrick, Cella, Harper & Scinto
`1290 Avenue of the Americas
`New York, NY 10104-3800
`ZortressAfinitorIPR@fchs.com
`
`Peter J. Waibel (Reg. No. 43,228)
`Gregory D. Ferraro (Reg. No. 36,134)
`NOVARTIS PHARMACEUTICALS CORPORATION
`One Health Plaza, Bldg. 430
`East Hanover, NJ 07936-1080
`Tel. 862-778-7838
`ZortressAfinitorIPR@fchs.com
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`By: /Daniel G. Brown/
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`Daniel G. Brown (Reg. No. 54,005)
`Latham & Watkins LLP
`885 Third Avenue
`New York, NY 10022-4834
`212-906-1200; 212-751-4864 (Fax)
`
`Counsel for Petitioner
`Par Pharmaceutical, Inc.
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