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`Case IPR 2016-00318
`Patent 7,772,209
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`SANDOZ INC.,
`APOTEX INC., and APOTEX CORP.,
`EMCURE PHARMACEUTICALS LTD.,
`HERITAGE PHARMA LABS INC.,
`HERITAGE PHARMACEUTICALS INC.,
`GLENMARK PHARMACEUTICALS, INC., USA,
`GLENMARK HOLDING SA,
`GLENMARK PHARMACEUTICALS, LTD., MYLAN LABORATORIES
`LIMITED, TEVA PHARMACEUTICALS,
`FRESENIUS KABI USA, LLC, and WOCKHARDT BIO AG
`Petitioners,
`
`v.
`
`ELI LILLY & COMPANY,
`Patent Owner.
`__________________
`
`Case No: IPR2016-003181
`Patent No. 7,772,209
`__________________
`
`PATENT OWNER’S MOTION FOR OBSERVATIONS ON THE
`DEPOSITION OF PETITIONER SANDOZ’S EXPERT
`PATRICK J. STOVER, PH.D.
`
`
`
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`1 Cases IPR2016-01429, IPR2016-01393, and IPR2016-01340 have been joined
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`with the instant proceeding.
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`
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`Case IPR 2016-00318
`Patent 7,772,209
`Pursuant to 77 Fed. Reg. 48756, Patent Owner Eli Lilly & Company
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`(“Lilly”) submits this motion for observations regarding cross-examination of
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`Petitioner Sandoz’s reply declarant Patrick J. Stover, Ph.D.
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`Observation 1. Dr. Stover agreed that he does not “have any particular
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`experience in the area of oncology”; he has not “done work directly on human
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`cancer treatment”; and he does not treat patients. Ex. 2137 at 10:8-10, 10:25-11:5,
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`24:15-16. Dr. Stover further agreed that he is “not providing opinions in this case
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`from the perspective of the person of ordinary skill in the art” to the extent that the
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`POSA “is a person who is a clinician who treats patients” and that he cannot
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`“opine about the knowledge of an oncologist.” Id. at 23:14-19, 26:4-8. This
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`testimony is relevant in assessing Dr. Stover’s expertise and ability to opine on
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`nutritional issues involving the administration of pemetrexed, a chemotherapy drug
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`for treating cancer.
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`Observation 2. Dr. Stover testified:
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`Q. Are you familiar with a particular toxicity
`called neutropenia?
`A. I am not an expert in neutropenia, no.
`Q. Okay. So do you know how pemetrexed causes
`neutropenia?
`A. I -- I am not an expert in how pemetrexed
`causes neutropenia, no.
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`
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`2
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`Case IPR 2016-00318
`Patent 7,772,209
`Q. Okay. So to the extent other experts in this case
`have opined that pemetrexed can cause neutropenia by
`inhibiting DNA synthesis, you don't agree with that
`opinion?
`A. I have –
`*
`*
`*
`A. I have no opinion on that.
`
`Ex. 2137 at 15:21-16:11 (objection omitted). This testimony is relevant because it
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`undermines Dr. Stover’s opinion that folic acid will act differently to counteract
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`pemetrexed’s toxicity than to counteract its efficacy against cancer cells, Ex. 1091
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`¶¶ 19-23, because Dr. Stover has no understanding of the mechanisms by which
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`pemetrexed causes the toxicities that had been observed in the prior art and that,
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`according to Petitioner, would have motivated the POSA to administer folic acid.
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`Likewise undermining his opinion that folic acid will act differently to counteract
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`pemetrexed’s toxicity than its efficacy, Dr. Stover testified that “one would infer
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`that pemetrexed would have an effect [on cancer] both through its effect on TYMS
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`[TS] as well as through DHFR” and agreed that “pemetrexed may have an effect
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`on rapidly dividing healthy cells through the inhibition of one or both of those
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`enzymes.” Ex. 2137 at 19:25-20:9.
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`Observation 3. Dr. Stover testified:
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`Q. And I understand there is a debate among the
`experts about the incidence of these toxicities, but there
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`Case IPR 2016-00318
`Patent 7,772,209
`had been toxicities reported to rapidly dividing cells as of
`1999?
`A. Correct.
`Q. That would have been understood by the person
`of ordinarily skill to be arising from the inhibition of
`some combination of these same enzymes?
`A. I'm not a clinician, so I can't speak to what a
`POSA would -- would infer.
`Q. But it was -- it was -- from your standpoint as a
`biochemist and based on what was known in the art as of
`1999, it was -- it was understood that pemetrexed had an
`impact on rapidly dividing healthy cells, at least in part
`by inhibiting these same enzymes that contribute to its
`anticancer effects?
`A. I -- that would be an accurate statement, yes.
`One has to be concerned.
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`Ex. 2137 20:10-21:5. This testimony is relevant because it supports Patent
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`Owner’s point that pemetrexed’s inhibition of certain enzymes both allows it to
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`effectively treat cancer and impacts rapidly-dividing healthy cells, causing toxicity.
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`Paper 36 at 5.
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`Observation 4. Dr. Stover testified:
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`Q. You're not speaking to what would have been
`typical practice by the oncologists?
`A. I'm not speaking, again, to what an oncologist
`would or would not do. I'm speaking to the information
`4
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`that was available to a clinical team giving care to a
`patient.
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`Case IPR 2016-00318
`Patent 7,772,209
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`Ex. 2137 at 109:20-25. This testimony is relevant in assessing the weight to
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`accord Dr. Stover’s opinions involving the administration of pemetrexed, a
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`chemotherapy drug for treating cancer; Dr. Stover has not expressed opinions
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`regarding what the person of ordinary skill in the art would have thought or been
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`motivated to do.
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`Observation 5. Dr. Stover testified:
`
`Q. I think you referred at another point in today's
`testimony to oncologists who you run across at folate
`meetings?
`A. That's correct.
`Q. Would David Goldman be an example of such
`an oncologist?
`A. David Goldman is one. Joe Mason is one. So
`oncologists do attend these -- the various meetings that I
`attend, yes.
`Q. Yeah, I was just wondering about David
`Goldman specifically. He -- he -- is he an example of an
`oncologist who has what you'd consider to be a fulsome
`understanding of one-carbon metabolism?
`A. David is someone who -- who certainly works
`in the area of one-carbon metabolism. He is not a
`metabolic biochemist. He is more on the clinical side. I
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`5
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`Case IPR 2016-00318
`Patent 7,772,209
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`mean, he is not totally on the clinical side either. He
`really spans both -- both research as well as -- as, again,
`being head of these -- of an oncology -- a cancer center.
`Q. But he is -- he is knowledgeable about one-
`carbon metabolism as oncologists go; is that fair?
`A. His focus is on folate transport. That's his
`primary expertise, but he -- which is part of the larger
`community of -- of one-carbon metabolism, yes.
`Q. Are you familiar with his work on pemetrexed?
`A. I'm not.
`Q. If hypothetically I were to tell you that he is of
`the view that the pemetrexed plus folic acid plus vitamin
`B12 regimen that's in use, in that regimen the vitamins
`have a negative effect on efficacy, would you disagree
`with him?
`*
`*
`*
`A. I've never spoken to David about this, so I can't
`speak to that.
`Q. So you wouldn't disagree with that position, if
`that were one he took?
`*
`*
`*
`A. Oh, I would.
`*
`*
`*
`A. Based on my knowledge and my experience of
`mechanism of action and one-carbon metabolism, I do
`not believe that pemetrexed should be given in the
`context of nutritional deficiencies, and that given what
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`Case IPR 2016-00318
`Patent 7,772,209
`we know about both folic acid and vitamin B12 function,
`that they would not be counter indicated for pemetrexed.
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`Ex. 2137 at 184:20-186:25 (objections omitted). Dr. Stover further testified:
`
`Q. Well, I think that's a -- somewhat of a different
`question. The question I have is whether -- if he [David
`Goldman] were of the view that the doses of folic acid
`and vitamin B12 are too high and they have a negative
`effect on efficacy, is that a position that you would
`disagree with?
`*
`*
`*
`A. David and I have had discussions over folate
`fortification and its potential effect on the broad area of
`cancer, and David and I disagree on this. David takes
`more of a focus of perceived harm than an actual
`evidence that there is harm, which is not uncommon in
`the clinical community.
`But I am not -- I understand David's position on
`this, and these are conversations that are had at scientific
`meetings relative to ensuring that there are no adverse
`consequences associated with the type of actions we take
`both at the level of public health as well as at the level of
`the individual patient.
`Some of this relates to the tension between actual
`clinical data showing harm and what I would describe as
`a naive view that, which is not uncommon, that folate
`antagonists, right, inhibit DNA synthesis, that folate
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`7
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`promotes DNA synthesis, hence, folate, you know,
`counteracts the effect of the antifolate.
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`Case IPR 2016-00318
`Patent 7,772,209
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`Id. at 187:2-188:6 (objection omitted). This testimony—which demonstrates Dr.
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`Stover’s opinions are personal ones opposed to other, “not uncommon” opinions
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`held by respected oncologists—is relevant because it undermines Petitioner’s
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`assertion that the POSA would not have been concerned about reducing
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`pemetrexed’s efficacy by administering vitamin pretreatment. Paper 49 at 17-20.
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`Date: February 14, 2017
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`Respectfully submitted,
`
`/David M. Krinsky/
`David M. Krinsky
`Reg. No. 72,339
`Back-up Counsel for
`Patent Owner
`
`Williams & Connolly LLP
`725 Twelfth Street, N.W.
`Washington, D.C. 20005
`202-434-5338 (Telephone)
`202-434-5029 (Facsimile)
`dkrinsky@wc.com
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`
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`8
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`Case IPR 2016-00318
`Patent 7,772,209
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`CERTIFICATE OF SERVICE
`(37 C.F.R. § 42.6(e))
`
`The undersigned hereby certifies that the foregoing document was served on
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`
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`February 14, 2017 by delivering a copy via electronic mail on the following
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`attorneys of record for the Petitioners:
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`Ralph J. Gabric
`Reg. No. 34,167
`rgabric@brinksgilson.com
`
`Joshua H. James
`Reg. No. 72,568
`jjames@brinksgilson.com
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`Brinks Gilson & Lione
`455 Cityfront Plaza Drive
`Suite 3600 NBC Tower
`Chicago, IL 60611-5599
`T: 312-321-4200; F: 312-321-4299
`
`Bryan T. Richardson, Ph.D.
`Reg. No. 70,572
`brichardson@brinksgilson.com
`
`Brinks Gilson & Lione
`4721 Emperor Blvd.
`Suite 220
`Durham, NC 27703-8580
`T: 919-998-5700; F: 919-998-5701
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`Counsel for Sandoz Inc.
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`John D. Polivick
`Reg. No. 57,926
`jpolivick@rmmslegal.com
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`William A. Rakoczy
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`
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`Laura Lydigsen
`Pro hac vice
`llydigsen@brinksgilson.com
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`Deanne M. Mazzochi
`Reg. No. 50,158
`dmazzochi@rmmslegal.com
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`Patrick C. Kilgore
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`Pro hac vice to be filed
`wrakoczy@rmmslegal.com
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`Rakoczy Molino Mazzochi Siwik LLP
`6 West Hubbard Street, Suite 500
`Chicago, IL
`P: 312-527-2157/F: 312-527-4205
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`Attorneys for Apotex Inc. and Apotex
`Corp.
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`Thomas J. Parker
`Reg. No. 42,062
`thomas.parker@alston.com
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`Alston & Bird LLP
`90 Park Avenue, 15th Floor
`New York, NY 10016
`P: 212-210-9529/F: 212-210-9444
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`Counsel for Mylan Laboratories Limited
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`Gerard A. Haddad
`Reg. No. 41,811
`GHaddad@BlankRome.com
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`Blank Rome LLP
`The Chrysler Building
`405 Lexington Ave.
`New York, NY 10174
`P: 212-885-5135/F: 917-591-6921
`
`Counsel for Glenmark Pharmaceuticals
`Inc., USA, Glenmark Holding SA, and
`Glenmark Pharmaceuticals Ltd.
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`Paul M. Zagar
`Reg. No. 52,392
`PZagar@BlankRome.com
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`Case IPR 2016-00318
`Patent 7,772,209
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`Reg. No. 69,131
`pkilgore@rmmslegal.com
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`Blank Rome LLP
`The Chrysler Building
`405 Lexington Ave.
`New York, NY 10174
`P: 212-885-5290/F: 917-332-3063
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`Counsel for Emcure Pharmaceuticals
`Ltd., Heritage Pharma Labs Inc., and
`Heritage Pharmaceuticals Inc.
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`Patrick A. Doody
`Reg. No. 35,022
`patrick.doody@pillsburylaw.com
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`Pillsbury Winthrop Shaw Pittman LLP
`1650 Tysons Boulevard
`McLean, VA 22102
`P: 703-770-7755/F: 703-770-7901
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`Counsel for Wockhardt Bio AG
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`Gary J. Speier
`Reg. No. 45,458
`gspeier@carlsoncaspers.com
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`Carlson, Caspers, Vandenburgh,
`Lindquist & Schuman
`225 South Sixth Street, Suite 4200
`Minneapolis, MN 55402
`P: 612-436-9600
`F: 612-436-9605
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`Cynthia Lambert Hardman
`Reg. No. 53,179
`chardman@goodwinprocter.com
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`Goodwin Procter LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018-1405
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`Case IPR 2016-00318
`Patent 7,772,209
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`Bryan P. Collins
`Reg. No. 43,560
`bryan.collins@pillsburylaw.com
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`Mark D. Schuman
`Reg. No. 31,197
`mschuman@carlsoncaspers.com
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`P: 212-813-8800
`F: 212-355-3333
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`Attorneys for Teva Pharmaceuticals
`USA, Inc. and Fresenius Kabi USA,
`LLC
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`Case IPR 2016-00318
`Patent 7,772,209
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`/David M. Krinsky/
`David M. Krinsky
`Reg. No. 72,339
`Back-up Counsel for Patent
`Owner
`
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`Date: February 14, 2017
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