UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`APOTEX INC. and APOTEX CORP.,
`ARGENTUM PHARMACEUTICALS LLC, ACTAVIS ELIZABETH LLC,
`TEVA PHARMACEUTICALS USA, INC., SUN PHARMACEUTICAL
`INDUSTRIES, LTD., SUN PHARMACEUTICAL INDUSTRIES, INC.,
`and SUN PHARMA GLOBAL FZE,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`____________
`
`Case IPR2017-00854
`Patent 9,187,405 B2
`____________
`
`Record of Oral Hearing
`Held: May 11, 2018
`____________
`
`Before CHRISTOPHER M. KAISER, ROBERT A. POLLOCK, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`
`
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`APOTEX INC. and APOTEX CORP.,
`ARGENTUM PHARMACEUTICALS LLC, ACTAVIS ELIZABETH LLC,
`TEVA PHARMACEUTICALS USA, INC., SUN PHARMACEUTICAL
`INDUSTRIES, LTD., SUN PHARMACEUTICAL INDUSTRIES, INC.,
`and SUN PHARMA GLOBAL FZE,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`____________
`
`Case IPR2017-00854
`Patent 9,187,405 B2
`____________
`
`Record of Oral Hearing
`Held: May 11, 2018
`____________
`
`Before CHRISTOPHER M. KAISER, ROBERT A. POLLOCK, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`
`
`
`Case IPR2017-00854
`Patent 9,187,405 B2
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER, APOTEX:
`
`
`JAD A. MILLS, ESQUIRE
`STEVEN W. PARMELEE, ESQUIRE
`Wilson Sonsini Goodrich & Rosati, LLP
`701 Fifth Avenue, Suite 5100
`Seattle, Washington 98104-7036
`
`
`
`ON BEHALF OF THE PETITIONER, THE SUN ENTITIES:
`
`
`SAMUEL S. PARK, ESQUIRE
`Winston & Strawn, LLP
`35 W. Wacker Drive
`Chicago, Illinois 60601
`312-558-7931 spark@winston.com
`
`
`
`ON BEHALF OF THE PETITIONER, TEVA PHARMACEUTICALS
`USA, INC.
`
`
`EUGENE GORYUNOV, ESQUIRE
`Kirkland & Ellis, LLP
`300 North LaSalle Drive
`Chicago, Illinois 60654
`312-883-7059 eugene.goryunov@kirkland.com
`
`
`
`ON BEHALF OF THE PETITIONER, ARGENTUM
`PHARMACEUTICALS LLC.
`
`
`TYLER LIU, J.D., ESQUIRE
`Argentum Pharmaceuticals, LLC
`134 Spring Street
`New York City, New York
`646-405-6300 tliu@agpham.com
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`Case IPR2017-00854
`Patent 9,187,405 B2
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`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`JANE M. LOVE, ESQUIRE
`ROBERT W. TRENCHARD, ESQUIRE
`ANDREW BLYTHE, ESQUIRE
`Gibson, Dunn & Crutcher, LLP
`200 Park Avenue
`New York, New York 10166-0193
`212-351-4000 jlove@gibsondunn.com rtrenchard@gibsondunn.com
`ablythe@gibsondunn.com
`
`and
`
`GRACE WINCHELL
`Wilson, Sonsini, Goodrich & Rosati
`
`PETER WAIBEL, ESQUIRE
`U.S. Head of Patent Litigation
`Novartis
`
`DREW HOLMES, ESQUIRE
`Novartis U.S.
`
`CONRAD ARNANDER , ESQUIRE
`Novartis, Basel, Switzerland
`
`
`
`
`The above-entitled matter came on for hearing on Friday, May 11,
`
`2018, commencing at 1:30 p.m., at the U.S. Patent and Trademark Office,
`600 Dulany Street, Alexandria, Virginia.
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`P R O C E E D I N G S
`- - - - -
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`MR. DILL: All rise.
`JUDGE POLLOCK: Please be seated. Just give us a minute to set
`up. Good afternoon. This is the final hearing in IPR 2017-00854, and
`joined cases 2017-01550, 01946 and 01929.
`This hearing is open to the public, and a full transcript of the hearing
`will be made part of the record in each case.
`I am Judge Pollock. Here with me are Judge Sawert and, remotely,
`Judge Kaiser.
`Before we begin with the substance of the hearing, I would ask the
`parties to introduce themselves. Counsel for lead Petitioner, Apotex, would
`you please introduce yourself and your colleagues?
`MR. MILLS: Yes, Your Honor. Jad Mills. Here with me, Counsel
`Steve Parmelee with the law firm Wilson, Sonsini, Goodrich & Rosati,
`representing Apotex Inc., and Apotex Corp. With us we have Grace
`Winchell also of Wilson Sonsini who is beginning law school this fall.
`JUDGE POLLOCK: Counsel for Petitioner Argentum?
`MR. PARK: Sam Park from Winston & Strawn, here on behalf of all
`The Sun Entities.
`JUDGE POLLOCK: Counsel for Petitioner Teva?
`MR. GORYUNOV: Eugene Goryunov, on behalf of the Petitioner
`
`Teva.
`
`
`
`JUDGE POLLOCK: And Counsel for Petitioner Sun Pharma?
`MR. PARK: Oh. I'm the Counsel for Petitioner Sun Pharma?
`JUDGE POLLOCK: Pardon me.
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`MR. LIU: Yes, I'm Tyler Liu, Counsel for Argentum.
`JUDGE POLLOCK: Counsel for Patent Owner Novartis, would you
`please introduce yourself and your colleagues?
`MS. LOVE: Yes, Your Honor. Good afternoon. I'm Jane Love, and
`with me is -- Robert Trenchard and Andrew Blythe. We are from Gibson,
`Dunn & Crutcher representing Novartis. We also have with us today Peter
`Wybell, who is the U.S. Head of Patent Litigation at Novartis, and with him
`are two other litigators, Drew Holmes, from Novartis in the U.S.; and
`Conrad Arnander from Basel, Switzerland.
`JUDGE POLLOCK: Welcome to you all this afternoon. In an
`attempt to put some order on the record for this proceeding, we will follow
`the following format. Petitioner will begin by presenting arguments
`regarding the claims for which the Board instituted trial and its motions to
`exclude, if desired. Petitioner may reserve time for rebuttal arguments.
`Patent Owner will then respond to Petitioner's arguments and present
`its arguments regarding its motion to amend, and its motions to exclude, if
`desired. Patent Owner may reserve time for rebuttal arguments as to its
`motion to amend, and motion to exclude.
`Petitioner may then respond to Patent Owner's motion to amend and
`motions to exclude, and present rebuttal arguments regarding the challenged
`claims.
`Patent Owner may present rebuttal arguments as to its motion to
`amend and motion to exclude.
`It seems a little complicated. Are there any questions regarding the
`order of argument?
`MS. LOVE: No, Your Honor.
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`MR. MILLS: No, Your Honor.
`JUDGE POLLOCK: Okay. Great. As set forth in the hearing order,
`each side will have 45 minutes, and considering the complexity of the issues
`before us, we will extend the allotted time to a total of 60 minutes. Although
`you may allocate your time as you see fit, I hope that you will direct an
`appreciable portion of it to discussing the pharmacokinetic arguments
`relating to, for example, Webb, Kahan , Park and Kataoka.
`A few additional matters of housekeeping: when discussing any
`particular demonstrative please refer to it by slide or page number to help
`maintain a clear transcript. This is particular important today as we have
`Judge Kaiser attending remotely and he cannot view what you have on the
`screen.
`When introducing the demonstrative slide for the first time, please
`note whether the information on that slide is subsumed within your
`opponent's motions to exclude evidence. Counsel may not interrupt an
`opposing party during the proceeding. To the extent the party feels they
`must lodge an objection for the record, they may do so during their next
`allotted time, or, if no time remains, at the end of the presentations. Any
`objections will be taken under advisement.
`Petitioner, you have the burden of showing unpatentability to the
`challenged claims. How much time would you like to allot to this portion of
`your presentation?
`MR. MILLS: Your Honor, we ask that the clock be set at 30 minutes,
`and then any time remaining after the initial presentation be reserved for
`rebuttal.
`JUDGE POLLOCK: Very good.
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`MR. MILLS: We also ask, Your Honor, if we could approach at this
`point to give you hard copies of our demonstratives.
`JUDGE POLLOCK: Certainly.
`MR. MILLS: Can I have slide 2, please? And as Your Honors know,
`in this case all grounds have been instituted on all claims, and Ground 1 and
`2 proceed on the basis of obviousness under 35 U.S.C. 103, Ground 3
`regards anticipation under 35 U.S.C. 102.
`Can I have slide 3, please? The claims of the ’405 Patent are directed
`to administering the immune compound to known subjects with a prior art
`dose. The claims are not directed to the design of a clinical trial or to
`carrying out a clinical trial, but to the administration of the active compound.
`Can I have slide 4, please? Ground 1 proceeds based on the Kovarik
`reference and the Thomson reference, Kovarik discloses a daily oral
`administration of 0.5 milligrams of FTY720 for treating autoimmune
`disease, including multiple sclerosis.
`And just taking an aside to explain, as discussed in our papers
`FTY720 frequently in the literature refers to the hydrochloride (inaudible)
`fingolimod which is specifically claimed in the dependent claims in the ’405
`Patent.
`As Dr. Giesser explained in her declaration for the support of the
`petition, a person of ordinary skill in the art reading the Kovarik reference,
`would be motivated to look at the clinical trial literature administering
`fingolimod for the treatment of RRMS, and for that reason would look at the
`Thomson reference which provided a state-of-the-art review of
`administration of fingolimod for the purpose of treating RMS in 2006. The
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`Thomson reference discloses daily oral administration of FTY720 for
`treating RMS, by reducing relapses and slowing disease progression.
`If I can skip ahead to slide 9, please? The Kovarik reference discloses
`a method for treating autoimmune disease in a subject in need thereof. And
`specifically discloses a daily dosage of FTY720 of about 0.1 to 0.5
`milligrams, and discloses that fingolimod is useful for the treatment of
`autoimmune disease, and it discloses that medications containing the S1P1
`receptor, fingolimod, the preferred medications are for patients suffering
`from autoimmune diseases, with multiple sclerosis being the first example.
`May I have slide 10, please? Kovarik discloses specifically that the
`0.5-milligram dose is a maintenance therapy, and on Kovarik 15 specifically
`gives 0.5 milligrams as an example, the specific example of embodiment of
`the invention where the maintenance therapy is 0.5 milligrams as a daily
`dosage.
`Can I have slide 13, please? In the petition, as well as in Dr. Giesser's
`declaration, Dr. Giesser explained that a person of ordinary skill in the art
`reading the Kovarik reference would understand that for the purpose of
`treating RRMS, a maintenance dose is not required, the reason being that
`maintenance dose is not dependent on the loading -- I may have misspoken a
`moment ago, I want to make sure -- a loading dose is not required for the
`treatment of RRMS, the reason being that a maintenance dose is not
`dependent on a loading dose.
`Doctors Jusko and Steinman, the Patent Owners' experts, have agreed
`in the case that the purpose of a loading dose, as Dr. Giesser explained, is to
`achieve the effect of the drug faster, not to determine its efficacy, they are
`used -- loading doses when the effect of the drug is treating an acute
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`condition. For example, alleviating an ongoing relapse, or at the beginning
`of a transplant to prevent rejection of the transplant, but that during the
`chronic administration of a disease-modifying therapy, such as fingolimod,
`for treating RMS, that there would be no requirement to use a loading dose.
`The Board's Institution decision correctly found that one of ordinary
`skill would understand that a maintenance dose of 0.5 milligrams were cited
`in the Kovarik reference will provide therapeutic benefits absent a loading
`dose.
`Dr. Benet, who Patent Owner's expert has described as an eminent
`pharmacologist, confirmed that the Board's conclusion in the institution
`decision was correct. The therapeutic efficacy against multiple sclerosis of
`the 0.5 milligram daily dose maintenance therapy disclosed in the Kovarik
`reference would not be dependent on the loading dose.
`May I have slide 16, please? Dr. Giesser also explained that a person
`of ordinary skill in the art reviewing the Kovarik reference would understand
`that MS, treating MS with fingolimod means treating RRMS for several
`reasons. One of those reasons is that RRMS is the predominant form of MS,
`this is not a case where the claims are directed to treating an unusual or
`difficult to treat form of the disease, this is a case where the claims are
`directed to treating the form of the disease that was known at the time to be
`treatable.
`In fact, there were no medications approved for treating the
`progressive forms of MS for approximately 12 years, according to Dr.
`Steinman's testimony, in 2017.
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`So, in other words, Dr. Giesser testified that a person of ordinary skill
`in the art would understand, based on the predominance and the treatability
`of RRMS, that the Kovarik reference was directed towards the RRMS form.
`She also testified that the mechanism of action attributed to
`fingolimod in the Kovarik reference as well as in the clinical literature
`would confirm that. And specifically that fingolimod has an
`immunomodulating potential, the ability to sequester lymphocytes, and in
`particular T cells, which were taught to be responsible for inflammation.
`The inflammation leading to relapses in RRMS patients eventually to
`demyelination, and that demyelination leading to progression. And for that
`reason that fingolimod was understood be used to treat RRMS to reduce
`relapses and to slow progression of the disease.
`And can I have slide 17, please? It's been confirmed in the process of
`the case that the default understanding of a person of ordinary skill in the art
`was indeed exactly what Dr. Giesser said, that MS in this context means
`RRMS.
`May I have slide 11, please? The Thomson reference confirms that in
`the context of treating RRMS that there is no need for an immediately
`preceding loading dose, meaning that it would be obvious to administer the
`maintenance therapy from Kovarik without an immediately preceding
`loading dose.
`The Thomson reference also provides -- confirms the validity of
`Kovarik's teaching to use lower 0.5 milligram dose. Although Thomson
`reference reports specifically on a Phase II clinical trial in RMS patients
`where doses of 1.25 and 5 milligrams were administered, those doses were
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`shown to have substantially equivalent efficacy, in other words, that they
`were on the plateau of the dose response curve.
`The Thomson reference also teaches that a relevant pharmacodynamic
`property of fingolimod, specifically lymphocyte sequestration was observed
`at lower doses, specifically at the 0.5 milligram dose.
`And Thomson reports, based on the Budde reference which is also at
`Ground 2 of the patent, that there was no clear dose response, and there was
`no linear dose response.
`If I can have slide 12, please? Thomson specifically says that
`although there were doses above 2 milligrams that had a more rapid and
`sustained lymphocyte sequestration, the actual degree of this property was
`similar across the range of doses used in the study. And if I can have slide
`25, please?
`JUDGE SAWERT: Excuse me, Counsel. I have a question.
`MR. MILLS: Yes.
`JUDGE SAWERT: On slide 11, the testimony goes to treatment of
`RRMS, does the testimony also apply to the other claims reducing, or
`preventing, or alleviating relapses and slowing progression?
`MR. MILLS: Yes. So first of all, the claims are to administering
`fingolimod to a subject in need of reducing relapses -- reducing, alleviating,
`or preventing relapses, or in need of slowing progression, which, each of
`those claims is satisfied, were rendered obvious or anticipated by
`administration to an RRMS patient. The Thomson reference in the Kappos
`2005 reference each disclose that that is the effect of fingolimod, it's the
`means by which fingolimod treats RRMS.
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`In other words, the genus of treating is satisfied by the relapse-
`reducing potential capability of fingolimod. Reducing relapses has an effect
`on slowing progression because progression is caused as the inflammation
`leads to lesions, leads to demyelination.
`So, in other words, by reducing the relapses, reducing the
`inflammation, fingolimod is understood to both -- treat RRMS both by
`reducing relapses and by slowing progression of the disease. Does that
`answer your question?
`JUDGE SAWERT: Yes. Thank you.
`MR. MILLS: Thank you. If we can go back to slide 25? This is
`Table 3 from the Budde reference, this table appears in the Budde reference,
`and it's referenced in the Thomson reference. As you can see here, the dose
`is 2 milligrams and above, in other words, doses higher than the doses found
`to be substantially equivalently efficacious in the Phase II study.
`In the Phase I study only those higher doses showed a greater
`reduction in lymphocyte count. You can see, looking at the percent baseline,
`the second to the most-right column, that those doses are achieving a
`reduction in lymphocytes of approximately 70 percent, whereas the 0.5, 0.75
`and 1 milligram dose are approximately 50 percent.
`What's important here, which we argued in the petition, and the Board
`took note in the institution decision, is Thomson, you know, which clearly is
`not a hindsight-driven reference because it's a 102(b) reference. The
`Thomson reference describes this lyphopenia, and the Budde reference also,
`describes this as comparable, a comparable effect, 50 percent is comparable
`to 70 percent with regard to treating RRMS.
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`JUDGE POLLOCK: Mr. Mills, I noticed in some of the -- in many of
`the references, the degree of lymphopenia changes dramatically over time.
`Why are your experts focused on nadir counts?
`MR. MILLS: So, the references do discuss nadir counts frequently, so
`for instance the Webb reference that Your Honor asked about earlier, the
`only discussion that it has about lymphopenia and the effect on EAE, is
`taking the nadir count. The Kahan 2003 reference focuses on the nadir, on
`page 1084 of that reference it points out that the nadirs achieved, as they
`reached the steady state concentrations at four weeks, and then is sustained
`thereafter.
`So, the nadir shows that the effect is happening, and the other reason I
`think that the Phase I clinical trial is focused on it is because they are trained
`to elucidate this relationship that when they dose the fingolimod, that the
`lymphopenia sets in, indicating that fingolimod is interacting with the S1P1
`receptor, and that when they stop dosing it that lymphopenia stops. It's
`dose-responsive in that sense. That when you give the drug you get that
`effect, and when you stop giving the drug the effect goes away.
`If we can go to slide 26, please? So, the rationale set forth in the
`petition, and supported by Dr. Giesser's testimony, is the reports in the
`literature, contemporaneously at the time, that this level of lymphopenia
`treated even by a single dose of fingolimod was sufficient to indicate that the
`activity of fingolimod, its binding of the S1P1 receptor was on (inaudible),
`and with sufficient cause to motivate a person of ordinary skill in the art to
`administer 0.5 milligrams fingolimod to -- in our MS patient, a patient in
`need of each of the three things mentioned in the claim.
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`Originally, and you can see this in the first level in declaration,
`originally Patent Owner's position was that no one would ever even
`undertake a clinical trial on this. As we'll discuss, perhaps, a little bit later,
`during the process of the trial the Patent Owner submitted a 102(b) prior art
`publication disclosing that the 0.5 milligram dose had been advanced in the
`Phase III Trial on the basis of its ability to achieve some degree of
`lymphopenia.
`And Dr. Lublin's fourth declaration reflects this -- the state-of-the-art
`information from the Chavez reference, the press release reference that's
`Exhibit 2131, 2072, that of course it was known more than one year before
`the critical date that the 0.5 milligram dose was being administered.
`He confirmed the ability of fingolimod at the dose to suppress
`lymphocytes to some extent, he now agrees, was enough to justify testing
`the dose. In other words, it was enough to justify administering the dose,
`just as Dr. Giesser had said.
`JUDGE SAWERT: Counsel?
`MR. MILLS: Yes.
`JUDGE SAWERT: Justified testing the dose, doesn’t necessarily
`mean justified treating patients with it. Correct?
`MR. MILLS: So, first of all, the claims are directed to administering
`fingolimod, the method -- the claims are having a preambular method, say, a
`method for treating a patient or a subject in need thereof, that does not
`import an efficacy requirement or a treatment requirement, there's no
`substantive limitation from the treating language or the reducing language.
`That language which is anteceded basis for the subject who receives the
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`claim, but as shown in the BMS, Bristol-Myers Squibb v. Ben Venue case,
`from the Federal Circuit in 2001, it is in our petition as well as in our reply.
`If you look at the claims in that case, which were very similar, they
`also contain lots of preparatory language about things that people hope
`would happen and would like to see happen, they also provide antecedent
`basis for the description of the subject receiving the compound. But then the
`claims have steps, and those steps define the invention because there's no
`functional step, no functional limitation in addition to what is described in
`those steps.
`So, the Federal Circuit held in that case, that the preambles, even
`though a portion of the preamble, the preamble was in some sense necessary
`to provide the antecedent basis for the claim, that didn’t create an efficacy
`requirement in the claims, it didn’t create an intent requirement, it didn’t
`create an FDA-approval requirement, or any such thing as that. The claims
`were satisfied by the administration, and the same is true here in this case.
`If I could have slide 27, please? So, now with respect to Ground 3,
`the Board instituted Ground 3, and noted correctly that it is not enough to
`demonstrate that it would be obvious in order to establish 112 support. The
`claims as drafted, as issued, (inaudible) directly exclude the use of the
`loading dose. It is certainly Petitioner's position that it would be obvious to
`administer the 0.5 milligram dose to a subject with RMS to the subject in
`need of the things recited in the claims.
`That does not mean that there is written description for categorically
`excluding any loading dose under any circumstances, we can give --
`examples might include if there's administration to deal with an acute attack,
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`which, although not the practice of humans, is exactly what Webb was
`evaluating.
`If we can go to slide 30, please? So, because the dose itself is
`disclosed an administration of the compound at that dose, to the very
`subjects claimed, is obvious and indeed is actually disclosed in an
`anticipatory embodiment in the references that the Patent Owner submitted.
`The Patent Owner's case here, critically focuses on, and hinges on their
`argument that in an article published several years prior, an earlier study in
`animals, would take precedence over what was disclosed in the human
`clinical trial literature.
`Patent Owners latch onto language in one sentence in that article, and
`we would submit that they read that sentence out of context, if you look at
`the slide 30, you can see that they argued repeatedly: Webb's model show
`that at least 70 percent suppression was needed for any efficacy.
`Dr. Steinman even said, generally, the usual case, there's no such
`thing as an on/off switch for efficacy, but here on the basis of this offhand
`comment in Webb, we know that there must be an on/off switch in humans.
`Unless you get to 70 percent efficacy, 70 percent lymphopenia there is no
`effect. That is Patent Owner's position. But that's simply not correct.
`If I can go to slide 31, please? Dr. Giesser did consider the Webb
`reference at her deposition, she was asked questions about it, and she
`answered those questions, and she testified that when you look at Webb, its
`graphs, she focused specifically on Figure 5A, she also looked at Figure 8,
`she said that you can actually see the trend there.
`That all of the doses produce some efficacy including doses that had a
`nadir, Judge Pollock, you asked earlier about the nadir, even though its nadir
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`was only 25 percent lymphopenia, there was still -- in effect there was still
`alleviation of an ongoing relapse. They were using the drug as if it were
`Prednisone, administering it in the middle of a relapse and seeing the clinical
`scores immediately and dramatically improve even at that low, low dose that
`was producing a nadir lymphopenia of 25 percent. She also said that the
`dosage cluster, you have a dose that's 10 times as big, 0.3 milligrams per
`kilograms; that those cluster.
`JUDGE SAWERT: The problem I have with your argument is that, I
`could see if someone was actually delivering that dose, and you had an
`anticipation argument, but these grounds are based on obviousness, so why
`would one who's skilled in the art have a reason to perform these steps?
`That's, the fact that they were done, if they were done would have been the
`obviousness, I mean -- excuse me -- it would be an anticipation argument,
`not an obviousness argument. So when I look at the BMS case I'm not so
`sure how that helps you.
`MR. MILLS: So, the BMS case tell us that there is no efficacy
`requirement in the claims, and a reasonable expectation of success is only
`required for achieving the claim elements. We certainly have discussed the
`reasons why a person of ordinary skill in the art, we've discussed in our
`petition, why the person of ordinary skill in the art, looking at the clinical
`trial data would see Kovarik's 0.5 milligram maintenance therapy dose as a
`plausible dose for achieving efficacy, and that that was motivation to
`administer the dose, which is exactly what Dr. Lublin eventually agreed, that
`that is the case, that the lymphopenia observed in the earlier studies was
`enough to test the dose, meaning to administer the dose.
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`There's no requirement in the claims that the administration of the
`dose result in any particular effect. In fact, Dr. Steinman, Patent Owner's
`expert, was asked this question: what else must happen, the dose is
`administered 0.5 milligrams, daily dosage, absolutely immediately preceding
`loading dose? How long do we have to wait before we know that the claims
`are practiced? There's no waiting. The claims are practiced at that point.
`JUDGE SAWERT: The testing, how does -- I understand that there's
`no efficacy requirement, but there is -- but it does speak to motivation to
`combine and reasonable expectation of success. Correct? And so just
`having someone say there's reason to test it, does not necessarily translate to
`all the requirements you need to obviousness.
`MR. MILLS: So, Judge, respectfully I would say that it does have to
`do with motivation to administer the dose, and that's the position that we --
`or that's one of the rationales advanced in the petition, is that there has to be
`enough motivation for the physician to actually administer it. That's exactly
`what happens in the (crosstalk).
`JUDGE SAWERT: So you are saying there doesn’t need to be
`motivation to administer it for treating?
`MR. MILLS: There is no claim element that says that it has to be
`treating, or defines what treating is in anyway other than just administering it
`to a person in need of treating. The claims in their plain language say,
`administering the compound to a subject, the subject is in need of treating. It
`doesn’t say, and thereby treats, and treatment is illustrated by this, and then a
`subsequent step is taken based on the observation of treatment occurring.
`But furthermore, administration of an active compound in a clinical
`trial can still constitute treatment, just because its treatment in an
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`experimental context doesn’t make it not treatment, and indeed there is no
`legal exclusion to printed publication prior art simply because it is
`describing something that's happening in clinical trial. The In re
`Montgomery case demonstrates that.
`JUDGE SAWERT: So, maybe I'm getting confused, but I see that
`argument for your anticipation, but for the obviousness grounds, can you
`elaborate because I thought for the obviousness grounds there were not
`actual administration of this drug at that amount in clinical trials. That was
`only for the anticipation ground.
`MR. MILLS: So, with respect to the issued claims, the prior art other
`than Kovarik, does not disclose administration of the -- specifically a 0.5
`milligram dose. The question is whether there was sufficient motivation for
`the administration, and I think the answer is unequivocally, yes, and that's
`borne out by Dr. Giesser's testimony, as well as the facts in the state of the
`art, as they are borne out.
`Even if the Chavez reference and the press release reference are not
`anticipatory embodiments, they still define the scope of the -- the state of the
`art. Under Radall v. Ray, in the area -- Ossa v. Vernadekes case, the Board
`should consider the fact that there isn't anticipatory embodiment, where the
`0.5 milligram dose is administered to the specific patient populations. Not
`as a ground reference, but because it does illustrate the state of the art, it
`does illustrate that the Webb arguments put forward by the Patent Owner are
`incorrect. And that is the state of the art.
`We think it also confirms Dr. Giesser's testimony that the
`lymphopenia observed, and we quoted in the Thomson reference, which
`Thomson these are all comparable levels of lymphopenia, Dr. Lublin has
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`now agreed that this is enough lymphopenia to justify administering the dose
`which is all that's required by the claims, that that is sufficient motivation to
`perform the claims.
`I would submit that reasonable expectation of success is really a
`separate issue because there is no efficacy claim element. The question is
`whether the expectation of efficacy was sufficient for them to simply
`administer the dose regardless of whether it was in a clinical trial context, or
`otherwise.
`JUDGE POLLOCK: Mr. Mills, on one hand you are asking us to rely
`on Kovarik's teaching to use 0.5 milligrams of this drug for a class of
`treatments, including treatment of MS. But on the other, you are telling us
`disregard a very plain statement in Webb which seems to suggest that that
`amount would not be sufficient. How do you justify these two divergent
`positions?
`MR. MILLS: So, I would like to talk to Webb -- talk about Webb. If
`we can go -- are still on slide 31 -- we are, okay. So, Dr. Giesser first of all
`explained why the data in Webb confirms that 70 percent lymphopenia in
`EAE mice, even, is not required to see any efficacy. Doctor Chun and
`Dr. Steinman agreed that that's the case.
`If you look at Figure 5A, th
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