UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`WOCKHARDT BIO AG
`Petitioner
`
`v.
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`JANSSEN ONCOLOGY, INC.,
`Patent Owner
`________________________
`
`Case IPR2016-01582
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`U.S. Patent No. 8,822,438
`________________________
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`PETITIONER'S REPLY TO PATENT OWNER RESPONSE
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`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, Virginia 22313–1450
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`
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`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`WOCKHARDT BIO AG
`Petitioner
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`Patent Owner
`________________________
`
`Case IPR2016-01582
`
`U.S. Patent No. 8,822,438
`________________________
`
`PETITIONER'S REPLY TO PATENT OWNER RESPONSE
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, Virginia 22313–1450
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`
`
`
`
`
`
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`
`
`I.
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`II.
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`TABLE OF CONTENTS
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`INTRODUCTION .......................................................................................... 1
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`ARGUMENT .................................................................................................. 2
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`A.
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`The'438 patent claims would have been prima facie obvious .............. 2
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`1.
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`Obviousness does not require "safety and effectiveness"
`or "FDA approval," as Patent Owner suggests .......................... 2
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`(a) Gerber taught the combination of ketoconazole and
`prednisone as treating prostate cancer ....................................... 3
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`(b) O'Donnell teaches abiraterone as a potent, more specific
`CYP17 inhibitor than ketoconazole, and provides a
`motivation for maintaining prednisone ...................................... 5
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`(c)
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`Sartor provides further, independent evidence that
`prednisone "treats" under the Board's construction ................. 10
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`2. Wockhardt's Petition is materially different than the
`Amerigen and Mylan Petitions ................................................ 12
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`3.
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`4.
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`5.
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`6.
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`Gerber, O'Donnell, and Sartor provide more than a
`reasonable expectation that abiraterone with prednisone
`"treats" prostate cancer ............................................................. 13
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`Janssen's experts' testimony should be entitled to little or
`no weight .................................................................................. 15
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`The prior art's use of docetaxel does not "teach away" ........... 15
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`Alleged concerns over prednisone's side-effects do not
`"teach away." ............................................................................ 17
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`B.
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`Secondary considerations do not weigh in favor of patentability ....... 19
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`1.
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`The alleged unexpected results are illusory and have no
`nexus to the challenged claims ................................................ 20
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`i
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`2.
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`3.
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`There is no relevant skepticism, failure of others, or long-
`felt need .................................................................................... 23
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`Janssen has not demonstrated commercial success ................. 24
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`III. CONCLUSION ............................................................................................. 26
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`ii
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`INTRODUCTION
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`I.
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`Wockhardt's Petition presented irrefutable evidence that the '438 patent
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`claims are obvious. Before August 2006, the prior art taught that abiraterone1 and
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`prednisone independently had "treatment" activity against prostate cancer, as
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`construed by this Board. The '438 patent claims merely recite the co-administration
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`of two well-known drugs—abiraterone (a CYP17 enzyme inhibitor) with
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`prednisone (a steroid)—for a known and established use (prostate cancer). The
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`'438 patent, thus, is nothing more than the "predictable use of prior art elements
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`according to their established functions." KSR Int'l Co. v. Teleflex Inc., 550 U.S.
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`398, 417 (2007).
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`Patent Owner's ("Janssen") Response ("POR") has not credibly rebutted this
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`obviousness showing. Wockhardt's Petition established that the '438 patent claims
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`are obvious over the following prior art:
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`
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`Gerber, which teaches the combination of ketoconazole (another
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`CYP17 enzyme inhibitor) and prednisone for the treatment of prostate
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`cancer;
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`
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`O'Donnell, which expressly teaches that abiraterone is a potent and
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`1 Unless otherwise specified, "abiraterone" is used throughout the Reply to mean
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`"abiraterone acetate" and "abiraterone" in vivo.
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`1
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`more selective CYP17 enzyme inhibitor than ketoconazole; and
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`Sartor, which teaches prednisone as an independent, stand-alone
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`treatment for prostate cancer.
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`This Board has found obviousness under nearly identical circumstances. See
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`
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`Accord Healthcare Inc., USA v. Daiichi Sankyo Co., Ltd., IPR2015-00865, Paper
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`12 (PTAB Sept. 12, 2016) (holding obvious claims to prasugrel (ADP antagonist)
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`and aspirin over prior art disclosing clopidogrel (ADP antagonist) and aspirin). In
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`Daiichi, the Board found a POSA would have had a reason to substitute
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`clopidogrel with the claimed prasugrel, because it had greater ADP antagonist
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`activity. The '438 patent claims here are no different, and the same reasoning from
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`Daiichi applies.
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`II. ARGUMENT
`A. The'438 patent claims would have been prima facie obvious
`1. Obviousness does not require "safety and effectiveness" or
`"FDA approval," as Patent Owner suggests
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`Wockhardt's petition demonstrated that the '438 patent claims would have
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`been obvious over Gerber, O'Donnell, and Sartor. Janssen's POR tries to
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`undermine the prior art teachings based on legally irrelevant arguments. For
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`example, Janssen argues that the references do not show a "survival benefit," or
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`that their teachings were not confirmed by "placebo-controlled randomized trials,"
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`or that they do not show an "extension of life" in patients, or that regimens in the
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`2
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`references had not been "FDA approved." (POR, pp. 1, 10-12, 27, 30, 63.) But ''no
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`challenged claim requires anything more than "therapeutic effectiveness," or
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`"treatment" activity, which the Board has construed to "include the eradication,
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`removal, modification, management or control of a tumor or primary, regional, or
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`metastatic cancer cells or tissue and the minimization or delay of the spread of
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`cancer." (Institution Decision, p. 6.) The claims do not require the extraneous
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`limitations that Janssen advances, such as any showing of a "survival benefit."
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`(a) Gerber taught the combination of ketoconazole and
`prednisone as treating prostate cancer
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`Janssen attacks Gerber as being merely a "chart review," and not a
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`"controlled clinical trial designed to establish safety or efficacy of a drug or
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`treatment." (POR, 6.) But Janssen provides no authority requiring such a
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`heightened showing for obviousness: and none exists. Gerber is prior art for all that
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`it teaches, whether it be a "chart review" or otherwise. See Duramed Pharm., Inc.
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`v. Watson Labs., Inc., 413 F. App'x 289, 294 (Fed. Cir. 2011) (a reference is "prior
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`art for all that it discloses, and there is no requirement that a teaching in the prior
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`art be scientifically tested, or even guarantee success. Rather, it is sufficient that [a
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`POSA] would perceive from the prior art a reasonable likelihood of success.").
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`Indeed, as Dr. Godley explained, chart reviews are evidence of actual clinical
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`practice, since they analyze data from patients who were actually treated with, in
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`the case of Gerber, the combination of ketoconazole and prednisone. (WCK1104,
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`3
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`¶8.)
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`Janssen also attacks Gerber because it allegedly does not demonstrate
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`enough of a PSA2 reduction, contending that it was "'unlikely [to have] significant
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`impact on survival.'" (POR, 7-8.) But, even if true, that argument fails because a
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`"survival" reduction is not a limitation of any claim, and is not how this Board
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`construed "treatment." Janssen's contention that the combination of ketoconazole
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`and prednisone had not been proven to increase survival (POR, 9-10) is also
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`irrelevant and unpersuasive for the same reason. Janssen cannot escape that
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`Gerber, and other prior art references, show that ketoconazole was used with
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`prednisone to treat prostate cancer. Even Janssen acknowledges that this
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`combination had "modest activity." (POR, 9.) That is all the claims require.
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`Finally, Janssen's argument that ketoconazole had never been "[FDA]
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`approved for the treatment of prostate cancer" is also irrelevant. It is well known
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`that physicians routinely prescribe drugs "off-label" for non-approved uses.
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`(WCK1104, ¶14.) In fact, even Janssen's expert, Dr. Rettig, admitted that he, too,
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`co-prescribed ketoconazole and prednisone together for prostate cancer.
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`2 Ironically, Janssen relies on PSA levels to make its "unexpected results"
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`point (POR, 50-51), but then tries to dismiss it for purposes of assessing Gerber's
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`teaching. Janssen cannot have it both ways.
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`(WCK1097, 26:15-23.) Moreover, FDA approval is neither a requirement of the
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`claims, nor is it a relevant consideration for determining obviousness. "There is no
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`requirement in patent law that the [POSA] be motivated to develop the claimed
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`invention based on a rationale that forms the basis for FDA approval." Allergan,
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`Inc. v. Sandoz Inc., 726 F.3d 1286, 1291-92 (Fed. Cir. 2013).
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`(b) O'Donnell teaches abiraterone as a potent, more
`specific CYP17 inhibitor than ketoconazole, and
`provides a motivation for maintaining prednisone
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`Janssen' wrongly suggests that Wockhardt must provide some independent
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`teaching in O'Donnell to show that a POSA would continue prednisone treatment
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`after substituting Gerber's ketoconazole with O'Donnell's abiraterone. But the law
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`does not require Wockhardt to make such a showing. And, in any event, O'Donnell
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`does provide sufficient basis to maintain co-therapy with prednisone.
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`A POSA's motivation for replacing ketoconazole with the potent, more
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`specific CYP17 inhibitor abiraterone here is squarely consistent with the Board's
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`similar finding in Daiichi. See IPR2015-00865, Paper 104, 22 (citing Novo Nordisk
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`A/S v. Caraco Pharm. Labs., Ltd., 719 F.3d 1346, 1351 (Fed. Cir. 2013)
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`(recognizing a reason to modify a well-known combination therapy of two drugs
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`having different mechanisms of action by substituting one drug in the combination
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`with a similar new drug having its same mechanism of action). And Gerber
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`'already had co-therapy with prednisone. Janssen has not provided any compelling
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`5
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`reason why a POSA would suddenly stop prednisone when replacing ketoconazole
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`with abiraterone following O'Donnell's teaching. And Dr. Godley provides many
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`reasons why a POSA would continue prednisone treatment. (WCK1002, ¶¶68, 83-
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`84.)
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`Janssen's additional arguments fail as well. First, Janssen asserts that
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`O'Donnell was not "designed" to assess survival benefit as a clinical endpoint for
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`abiraterone acetate as a prostate cancer treatment. (POR, 11-12.) But that is
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`inconsequential because, as Janssen acknowledges, O'Donnell assessed abiraterone
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`for "testosterone suppression in castrate and non-castrate men with prostate
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`cancer," which is a goal of prostate cancer treatment. (POR, 12; WCK1002, ¶26.)
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`So, a POSA had more than adequate grounds to rely on O'Donnell's teachings.
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`Second, Janssen and its experts endeavor mightily to show alleged
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`differences in the "steroid biosynthesis pathway" between abiraterone and
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`ketoconazole. But those differences are inconsequential and irrelevant. What
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`matters is that it was known that both ketoconazole and abiraterone were CYP17
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`inhibitors used for the treatment of prostate cancer, and that abiraterone was known
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`in the art to be a potent, more selective inhibitor of CYP17 than ketoconazole.
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`(WCK1002, ¶37-39, 62-65.) Any other alleged differences do not negate
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`obviousness. And, in any event, Janssen's expert, Dr. Rettig relies on scientifically-
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`flawed figures to show alleged differences. (JSN2038, ¶100, Figures 4-5.) As Dr.
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`Godley explains, these figures fail to indicate abiraterone's inhibition of certain
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`enzymes in the pathway for production of cortisol. (WCK1104, ¶16.)
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`Third, Janssen alleges that a POSA would have perceived worse side effects
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`with ketoconazole compared to abiraterone and, therefore, would "have found no
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`justification to co-administer prednisone with abiraterone." (POR, 16-17.) Janssen
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`is wrong here also. Janssen, albeit carefully, does admit that a POSA would have
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`expected abiraterone to inhibit cortisol production, but then backtracks, saying
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`such inhibition would not translate into "clinically meaningful reductions in
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`glucocorticoid production." (Id.)
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`Even if true, a skilled physician in this case would have had reason to
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`continue prednisone after replacing ketoconazole with abiraterone; and afterward
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`employed medical judgment to make adjustments, if necessary. Indeed, Dr. Rettig
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`admitted that the basis for administering a glucocorticoid with ketoconazole was to
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`replace cortisol lost due to ketoconazole's inhibitory activity on CYP17.
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`(WCK1097, 27:9-28:5.) So, a POSA would have sought to keep prednisone when
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`administering abiraterone, expecting a decrease in cortisol due to inhibition of
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`CYP17 by abiraterone. (WCK1104, ¶20.) That a POSA might have perceived less
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`loss of cortisol from abiraterone as compared to ketoconazole does not change this
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`fact. In addition, a POSA would have been aware that prednisone had long been
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`used for treating prostate cancer and replacing cortisol, and therefore would not
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`have been dissuaded from administering daily, low-dose prednisone. (Id., ¶¶21-
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`22.) And a POSA would have considered prednisone's benefits on balance with any
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`of its possible side effects. (Id., ¶¶22-27.)
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`Fourth, Janssen's argument that O'Donnell "would have led a skilled person
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`to believe mineralocorticoid excess would not occur with abiraterone acetate
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`treatment," is misleading for at least two reasons. (POR, 19.) First, as Dr. Godley
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`explained, a POSA would have predicted that abiraterone drive the production of
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`excess mineralocorticoids. (WCK1002, ¶¶35, 79-81; WCK1104, ¶¶33-36.) Second,
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`Janssen's own witness, Dr. Auchus, infers that mineralocorticoid excess could
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`occur in patients administered abiraterone, admitting that, even if cortisol
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`production was inhibited by abiraterone, corticosterone levels would increase and
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`compensate for the lack of cortisol. (JSN2040, ¶47.) And the prior art taught that
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`abiraterone does not inhibit the production of corticosterone. (WCK1030, 25:45-
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`48; WCK1035, 2467; WCK1104, ¶35; WCK1002, ¶39.)
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`However, as Dr. Auchus admitted at his deposition, for corticosterone to
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`reach sufficient levels to replace cortisol there would be a concomitant rise in the
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`mineralocorticoid 11-deoxycorticosterone ("DOC"). (WCK1089, 79:2-80:22.) This
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`rise in DOC is similar to what is seen in patients with congenital 17α-
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`hydroxylase/17,20-lyase deficiency, who often develop symptoms of
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`mineralocorticoid excess. (WCK1090, 104-105; WCK1089, 91:10-93:10;
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`WCK1104, ¶¶33-35.) And Dr. Auchus's own publication states that glucocorticoid
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`supplementation is part of the "cornerstone of therapy" in such patients.
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`(WCK1090, 114.) Likewise, he also admitted that the rationale for glucocorticoid
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`therapy in patients with 17-hydroxlyase deficiency is to treat mineralocorticoid
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`excess (WCK1115, 88:25-89:16.)
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`Fifth, Janssen's argument that "O'Donnell establishes no need for
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`glucocorticoid replacement with abiraterone," is wrong for several reasons. Gerber
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`already teaches combining prednisone with a CYP17 inhibitor, so a POSA would
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`naturally have continued prednisone when switching to the more selective
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`abiraterone. (wck1002, ¶¶83-84.) But O'Donnell also shows some patients
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`reporting abnormal ACTH tests, which, as Dr. Godley explains, a POSA would
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`have equated with decreased cortisol production, thus providing additional
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`motivation to co-prescribe prednisone. (WCK1104, ¶¶29-30, 36; WCK1002, ¶83.)
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`O'Donnell also specifically suggests three options regarding using
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`glucocorticoids with abiraterone: (1) co-administer a glucocorticoid with
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`abiraterone on a continuous basis, (2) administer a glucocorticoid during times of
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`stress, or (3) no co-administration of a glucocorticoid. (WCK1005, 2323.) Indeed,
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`Dr. Ian Judson, a co-author of O'Donnell, has reiterated these three options in this
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`proceeding. (JSN2028, ¶6.) So, Janssen cannot ignore O'Donnell's express
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`teachings. And importantly, a proper obviousness analysis requires consideration
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`of all disclosures of a prior art reference. That O'Donnell also discusses methods of
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`administering abiraterone without co-administering glucocorticoid does not negate
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`O'Donnell's express suggestion of such a method. Butamax Advanced Biofuels LLC
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`v. Gevo, Inc., IPR2013-00214, Paper 46, 25 (PTAB Sept. 23, 2014) (citing In re
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`Thomas 151 F. App'x 930 (Fed. Cir. 2005)).
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`Sixth, Janssen's "clinical justification" argument actually undermines its
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`position. Janssen quotes O'Donnell, stating "further studies with abiraterone
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`acetate will be required to ascertain if concomitant therapy with glucocorticoid
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`[sic] is required on a continuous basis." (POR, 21-22, emphasis in original.) But,
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`as this Board found in Daiichi, that is an acknowledgement that glucocorticoids
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`can and may be used with abiraterone. And given the high level of skill in this
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`case, a POSA would exercise medical judgment to determine if concomitant
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`prednisone is appropriate.
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`(c)
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`Sartor provides further, independent evidence that
`prednisone "treats" under the Board's construction
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`Janssen has not rebutted that Sartor establishes that prednisone was known
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`to treat prostate cancer before the '438 patent priority date. (WCK1006, Abstract,
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`253-254, Table III; WCK1002, ¶116, JSN2162, 62:18-25.) Janssen contends that
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`the FDA has never approved prednisone as a monotherapy for prostate cancer.
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`(POR, 27.) But FDA approval is not a pre-requisite to showing a reasonable
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`expectation of success. And Janssen's additional arguments against Sartor's
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`teachings are equally irrelevant.
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`First, as it did with Gerber, Janssen attacks Sartor as being a "retrospective"
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`chart review study. (POR, 28.) Again, Janssen provides no authority requiring that
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`clinical data come from a trial "'at the top of the evidence food chain'" before a
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`POSA can reasonably rely on that data. (Id.)
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`Second, Janssen's attack that Sartor shows only a "'relatively modest'"
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`decline in PSA (POR, 29) also misses the point—a decline in PSA, no matter how
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`"modest," still indicates a positive treatment effect from prednisone. (WCK1104,
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`¶5.) Dr. Godley confirmed that more than a third of Sartor's reported patients
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`satisfied the PSA Working Group's definition of "'PSA response,'" which directly
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`correlates to treatment response. (Id., ¶25.) And the claims do not require any
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`particular level of treatment; thus, even a "modest" level of treatment activity is
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`sufficient for obviousness. (Id.; WCK1002, ¶¶76-78.) Janssen is also wrong that a
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`POSA would discount Sartor's teachings because its reported PSA response may be
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`transient in nature; the claims place no time limit on PSA response. (POR, 30-31.)
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`And Janssen pointing to prednisone's "modest" increased survival rate is similarly
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`irrelevant. (POR, 29, 30-31.) Even if the Board's construction of "treatment"
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`required some level of survival—which it does not—Janssen admits that Sartor
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`shows a "modest" survival rate, which would suffice. (POR, 29; WCK1006, 255;
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`JSN2038, ¶202.)
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`Third, whether prednisone was administered concurrently with anti-cancer
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`therapies to treat side effects of those therapies is not dispositive of whether
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`prednisone also has prostate cancer "treatment" activity. (POR, 32-33.)
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`Fourth, Janssen is wrong: Dr. Godley did not agree that a POSA would not
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`have used prednisone to treat prostate cancer. (POR, 33.) Indeed, the very quote
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`Janssen provides directly undermines its assertion: "in my experience no treating
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`physician would prescribe prednisone alone as an anti-cancer agent … except in
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`those patients that had progressed on all other available treatments." (Id., citing
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`WCK1002, ¶116, emphasis added.) Dr. Godley's testimony is clear: regardless of
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`whether he would prescribe prednisone "alone," he maintained that prednisone was
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`shown to have anti-prostate-cancer treatment activity. (Id.; JSN2162, 61:15-62:17,
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`66:17-67:1.)
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`Fifth, Janssen's reliance on Amerigen's and Mylan's witnesses is a red
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`herring. (POR, 33-34.) First, Dr. Serels' and Dr. Garnick's testimonies are
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`inadmissible hearsay to this proceeding. See FRE 801. Second, Dr. Serels admitted
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`that he was not an expert in treating prostate cancer. (JSN2020, 16:15-17.)
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`Moreover, these are not Wockhardt's experts.
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`2. Wockhardt's Petition is materially different than the
`Amerigen and Mylan Petitions
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`Wockhardt's petition is materially different from both Amerigen's and
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`Mylan's petitions in at least two respects. (POR, 6.)
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`First, Amerigen's Petition (which Mylan tried to join) asserts obviousness
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`over O'Donnell in view of Gerber. Thus, Janssen argues that those petitioners must
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`establish a reason why a POSA would add prednisone to O'Donnell's teaching of
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`abiraterone. Wockhardt does not agree with Janssen's contention, but that issue is
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`moot in Wockhardt's obviousness ground, which starts with Gerber, in whose
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`teaching prednisone is already a part of the regimen. A POSA would simply have
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`replaced Gerber's ketoconazole with abiraterone. (WCK1002, ¶¶72-75.) Second,
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`any dispute over whether prednisone needs to be shown to have independent
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`"treatment" activity in the Amerigen and Mylan IPRs is also moot in the
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`Wockhardt IPR because of the Sartor reference, which expressly shows prednisone
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`alone has anti-prostate cancer activity.
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`3. Gerber, O'Donnell, and Sartor provide more than a
`reasonable expectation that abiraterone with prednisone
`"treats" prostate cancer
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`Even giving Janssen the full benefit of its argument, all that Janssen has
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`shown is that a POSA might not have been able to predict with absolute certainty
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`whether prednisone with abiraterone could treat prostate cancer without an
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`unacceptable incidence of side-effects. But obviousness does not require an
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`"absolute predictability" of success. See Daiichi, IPR2015-00865, Paper 12, 13
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`(citing In re O'Farrell, 853 F.2d 894, 903-04 (Fe. Cir. 1988)). "Rather the proper
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`inquiry focuses on reasonable expectations that a [POSA] would gain from the
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`knowledge in the art, along with the teachings or suggestions of the combined prior
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`art." Id., 233 (emphasis added).
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`The combined references here—Gerber, O'Donnell, and Sartor—satisfy that
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`requirement. Gerber established combining prednisone with the CYP17 inhibitor
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`ketoconazole for prostate cancer. And abiraterone's potency and superior
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`selectivity for CYP17 inhibition was well characterized by O'Donnell (as well as
`
`other prior art: Barrie (WCK1030) and Potter (WCK1035)), providing an express
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`motivation to substitute abiraterone for ketoconazole. (WCK1005; WCK1002,
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`¶¶62-65.) And Sartor teaches using prednisone for the treatment of prostate cancer.
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`(WCK1006.) Any risks of using a prednisone were also well appreciated in the art.
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`(WCK1002, ¶93; WCK1104, ¶¶21, 22,) Additionally, it is undisputed that the level
`
`of skill in this case was high. (WCK1002, ¶17; JSN2038, ¶78; JSN2040, ¶3.) Such
`
`person would be familiar with literature relating to prostate cancer treatment and
`
`would know how to evaluate potential drug therapies. (WCK1002, ¶¶17-18, 28-
`
`29.)
`
`At best, all Janssen and its experts have shown is that the art might reflect
`
`some "concerns" about combining prednisone with abiraterone. But "concern" does
`
`not mean such use is not warranted, beneficial, or would not have been obvious.
`
`See Daiichi, IPR2015-00865, Paper 104, 28 ("We do not find that having a
`
`"concern" about using prasugrel and aspirin … means that such use may not be
`
`
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`14
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`warranted or beneficial.")
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`4.
`
`Janssen's experts' testimony should be entitled to little or no
`weight
`
`Janssen's experts, Drs. Rettig, Auchus, and Vellturo, have testified in this
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`proceeding regarding (1) the state of the art by August 2006, (2) what a POSA's
`
`understanding of the prior art would allegedly be, and (3) alleged objective indicia
`
`of nonobviousness, without citing to any evidence to support their conclusions.
`
`(See JSN2038, ¶¶30-32, 40, 49, 59, 62-63, 67-68, 84, 100, 112, 121, 125, 127-130,
`
`137, 169, 171, 173-185, 194, 198, 200, 203, 219-220, 224, 240, 244-245, and 256;
`
`JSN2040, ¶¶11-13, 16-17, 28, 33-35, 44, 46-47, 51-53, 61, and 66.) Accordingly,
`
`their testimony should be accorded little or no weight. Corning Inc. v. DSM IP
`
`Assets B.V., IPR2013-00048, Paper 94, 33 (PTAB May 9, 2014); see also Kayak
`
`Software Corp. v. IBM Corp., IPR2016-00605, Paper 13, 20 n.3 (PTAB July 27,
`
`2016); 37 C.F.R. § 42.65(a) ("[e]xpert testimony that does not disclose the
`
`underlying facts or data on which the opinion is based is entitled to little or no
`
`weight.").
`
`The prior art's use of docetaxel does not "teach away"
`
`5.
`Janssen incorrectly suggests that the prior art use of docetaxel for prostate
`
`cancer somehow teaches away from the claimed abiraterone-prednisone
`
`combination, contending that a "[POSA] investigating new ways to treat prostate
`
`cancer" would have not have considered Gerber, O'Donnell, and Sartor, and
`
`
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`15
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`"instead … would have focused on [established] therapeutic regimens," namely
`
`docetaxel chemotherapy. (POR, 35-36.) Not so.
`
`First, a POSA investigating "new ways" of treating prostate cancer would of
`
`course look beyond what was then currently the established standard of care. On its
`
`face, therefore, Janssen's argument fails as a matter of common sense.
`
`Second, and moreover, the art taken as a whole does not teach away from
`
`abiraterone and prednisone. The law is settled: to "teach away," a reference or the
`
`prior art as a whole must "criticize, discredit, or otherwise discourage investigation
`
`into [the] invention claimed." Norgren Inc. v. ITC, 699 F.3d 1317, 1318 (Fed. Cir.
`
`2012); In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). Here, Janssen provides
`
`no references that "criticize, discredit, or otherwise discourage" the combination of
`
`abiraterone and prednisone.
`
`Third, neither docetaxel nor any other then-existing therapies for prostate
`
`cancer would have discouraged a POSA from considering the teachings of Gerber,
`
`O'Donnell, and Sartor. Janssen states, "[b]y August 2006, docetaxel chemotherapy
`
`had become the standard of care in treating mCRPC patients." (POR, 36.) But that
`
`would not have precluded a POSA from considering androgen inhibitors, like
`
`abiraterone, as new therapies. Gerber, O'Donnell, and Sartor together provide an
`
`express motivation and teaching for combining abiraterone and prednisone for the
`
`treatment of prostate cancer, and establish that abiraterone and prednisone
`
`
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`16
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`independently have treatment effect under this Board's claim construction.
`
`(WCK1002, ¶¶85-86.)
`
`At best, Janssen's argument apparently is that because of docetaxel and other
`
`potential therapies, the combination of abiraterone and prednisone might not have
`
`been the most obvious choice of treatment. That argument fails as a matter of law.
`
`The mere disclosure or existence of more than one alternative does not amount to
`
`teaching away from one of the alternatives where the does not criticize, discredit,
`
`or otherwise discourage the solution claimed. Sightsound Techs. v. Apple Inc., 809
`
`F.3d 1307, 1320 (Fed. Cir. 2015). "[J]ust because better alternatives exist in the
`
`prior art does not mean that an inferior combination is inapt for obviousness
`
`purposes." In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012); see Fulton, 391
`
`F.3d at 1200 (obviousness "need not be supported by a finding that the …
`
`combination claimed by the patent applicant is the preferred, or most desirable,
`
`combination."); In re Gurley, 27 F.3d 551, 551 (Fed. Cir. 1994) (an "obvious
`
`composition does not become patentable simply because it has been described as
`
`somewhat inferior to some other product for the same use.").
`
`6.
`
`Alleged concerns over prednisone's side-effects do not
`"teach away."
`
`Likewise, that glucocorticoids, such as prednisone, had known side-effects is
`
`also unremarkable and does not teach away from the claimed invention, as Janssen
`
`suggests. (POR, 38-40.) All drugs carry some concerns over side-effects, and those
`
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`17
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`concerns are weighed against the benefits of use. (WCK1104, ¶27.) Here, despite
`
`prednisone's known side effects, Janssen has not come forward with any reference
`
`or other evidence that would have prohibited a POSA from using prednisone.
`
`Rather, the overwhelming prior art of evidence shows prednisone and other
`
`glucocorticoids (e.g., dexamethasone and hydrocortisone) routinely being used for
`
`prostate cancer treatment. (WCK1006, WCK1011, WCK1015, WCK1028,
`
`WCK1083.)
`
`This Board soundly rejected similar arguments in Daiichi, and should do so
`
`here. Daiichi, IPR2015-00865, Paper 104, 15-17. As in Daiichi, any references
`
`raising concerns of tolerability of prednisone in treating prostate cancer actually
`
`"may be seen as an acknowledgement" and, at most, "provide a caution (not a
`
`prohibition) regarding a known practice of administering" prednisone for the
`
`treatment of prostate cancer. Id., 17. Moreover, consistent with Daiichi, a POSA
`
`here was cautioned about the side-effects of administering prednisone, "providing
`
`them with an opportunity to weigh such risk and make an effort to decrease that
`
`risk when prescribing." Id., 21-22. A POSA, thus, would be equipped with the
`
`requisite skill to assess and address such risk in a medically acceptable manner.
`
`The risks associated with prednisone would not have deterred a POSA from co-
`
`prescribing prednisone. (WCK1104, ¶27.)
`
`Similarly, Janssen's contention that a POSA would have turned to other
`
`
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`18
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`IPR2016-01582
`Wockhardt's Reply to Patent Owner Response to the Petition
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`drugs, such as eplerenone, for treating symptoms of mineralocorticoid excess fares
`
`no better than its other teaching away arguments. Insofar as Janssen argues that a
`
`POSA would have turned to eplerenone in lieu of prednisone because of the latter's
`
`side effects, Janssen ignores that eplerenone also has side effects, and Janssen
`
`hasn't established why a POSA would prefer one over the other. And, even if
`
`Janssen could establish that eplerenone would have been preferred, that does not
`
`negate obviousness because "mere disclosure of more than one alternative does not
`
`amount to teaching away." SightSound, 809 F.3d at 1320.
`
`B.
`Secondary considerations do not weigh in favor of patentability
`"[A] strong prima facie obviousness showing may stand even in the face of
`
`considerable evidence of secondary considerations." Line Rothman v. Target
`
`Corp., 556 F.3d 1310, 1321-22 (Fed.Cir. 2009). "For obje
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