Trials @uspto.gov Paper 62
`Tel: 571-272-7822 Entered: May 9, 2014
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`GNOSIS S.p.A., GNOSIS BIORESEARCH S.A.
`and GNOSIS U.S.A., INC.,
`Petitioners,
`
`v.
`
`SOUTH ALABAMA MEDICAL SCIENCE FOUNDATION and
`MERCK & CIE,
`Patent Owners.
`____________
`
`Case IPR2013-00116 (Patent 5,997,915)
`Case IPR2013-00117 (Patent 6,011,040)
`Case IPR2013-00118 (Patent 6,673,381)
`Case IPR2013-00119 (Patent 7,172,778)
`____________
`
`RECORD OF ORAL HEARING
`
`Before: JACQUELINE WRIGHT BONILLA, SCOTT E. KAMHOLZ,
`and SHERIDAN K. SNEDDEN, Administrative Patent Judges.
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`JOSEPH E. CWIK, ESQ.
`
`
`Husch Blackwell
`
`
`120 South Riverside Plaza, Suite 2200
`
`
`Chicago, Illinois 60606
`
`
`
`
`
`and
`
`
`Tel: 571-272-7822 Entered: May 9, 2014
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`GNOSIS S.p.A., GNOSIS BIORESEARCH S.A.
`and GNOSIS U.S.A., INC.,
`Petitioners,
`
`v.
`
`SOUTH ALABAMA MEDICAL SCIENCE FOUNDATION and
`MERCK & CIE,
`Patent Owners.
`____________
`
`Case IPR2013-00116 (Patent 5,997,915)
`Case IPR2013-00117 (Patent 6,011,040)
`Case IPR2013-00118 (Patent 6,673,381)
`Case IPR2013-00119 (Patent 7,172,778)
`____________
`
`RECORD OF ORAL HEARING
`
`Before: JACQUELINE WRIGHT BONILLA, SCOTT E. KAMHOLZ,
`and SHERIDAN K. SNEDDEN, Administrative Patent Judges.
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`JOSEPH E. CWIK, ESQ.
`
`
`Husch Blackwell
`
`
`120 South Riverside Plaza, Suite 2200
`
`
`Chicago, Illinois 60606
`
`
`
`
`
`and
`
`
`
`
`
`
`
`
`JONATHAN J. KRIT, ESQ.
`Amin Talati LLC
`55 West Monroe Street, Suite 3400
`Chicago, Illinois 60603
`
`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
`
`
`
`
`
`
`ON BEHALF OF PATENT OWNER:
`
`
`THOMAS J. PARKER, ESQ.
`
`
`ANDREW STERLING, ESQ.
`
`
`JITENDRA “JITTY” MALIK, ESQ.
`
`
`Alston & Bird, LLP
`
`
`90 Park Avenue
`
`
`New York, New York 10016
`
`
`
`
`
`
`
`The above-entitled matter came on for hearing on Thursday,
`March 20, 2014, commencing at 10:02 a.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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`- - - - -
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`JUDGE KAMHOLZ: Good morning. We will hear
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`argument this morning in Case Numbers IPR2013-00116, 118, 119,
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`Gnosis versus South Alabama Medical Science Foundation. We will
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`hear argument this afternoon for Case Number IPR2013-00117, Gnosis
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`versus Merck. Counsels for the parties please introduce yourself,
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`starting with petitioner?
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`MR. CWIK: Yes, Your Honor. My name is Joe Cwik, and
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`I'm here on behalf of petitioners. With me is my co-counsel Jonathan
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`Krit. Jonathan Krit has been designated lead counsel as of record.
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`JUDGE KAMHOLZ: Good morning.
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`MR. PARKER: Good morning, Your Honors. My name is
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`Thomas Parker. I'll be speaking on behalf of the University of South
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`Alabama, and with me is my associate colleague, Andrew Sterling, who
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`will be assisting with the presentation.
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`JUDGE KAMHOLZ: Who is here for Merck?
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`MR. PARKER: I'll also be here for Merck as well for the
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`afternoon session, and with that, Your Honor, I just wanted to raise one
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`housekeeping item, and I spoke with counsel as well. Can we have one
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`single transcript and possibly captioned with all four IPRs? Because
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`what that will do is in the afternoon, we may be referring back to
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`statements that were made in the morning session, and we can just
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`simply refer back to the morning session, and if we have it in the same
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`transcript, it may be a bit more clearer to do that as oppose to two
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`certain transcripts, if that's okay with the panel.
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`JUDGE SNEDDEN: Is that acceptable to you?
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`MR. CWIK: Your Honor, that's fine, if we have one
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`transcript. I think that will eliminate some duplication when we're
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`talking in the afternoon. I mean, I think it would not be proper to use
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`the afternoon session to make arguments about the morning patents. I
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`don't think that's the intent of it, but I think a single transcript is
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`acceptable to us.
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`JUDGE KAMHOLZ: Well, to the extent that you've briefed
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`it, any arguments you make at any time in any session are applicable to
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`all cases, but where argument is focused on one case or fewer than all
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`cases, it will perhaps help if you indicate that when making argument.
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`With that in mind, I think that's fine with us to have a single
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`transcript.
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`MR. PARKER: Thank you.
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`MR. CWIK: Thank you, Your Honor.
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`JUDGE KAMHOLZ: Thank you. Per our order dated
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`March 7, 2014, each side will have a total of two hours to argue, one
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`hour in the morning, one hour in the afternoon. The petitioner will go
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`first for each session and should begin by indicating how much time, if
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`any, will be reserved for rebuttal. I'll remind the parties that the
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`petitioner bears the burden of proving any proposition of
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`unpatentability by a preponderance of the evidence.
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`Although motions to seal have been granted and others are
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`pending in these cases, this hearing is public. The final reminder, when
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`referring to demonstratives, please mention the slide number you are
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`referring to so that it's clear in the record.
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`Are there any questions?
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`MR. PARKER: No, Your Honors.
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`MR. CWIK: Your Honor, regarding the slides, I do have
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`hard copies for the judges, if they want them at this time.
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`JUDGE KAMHOLZ: Yes, please.
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`MR. CWIK: May I approach the Bench?
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`JUDGE KAMHOLZ: Of course.
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`MR. PARKER: Your Honors, may I approach the Bench,
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`please? Would you like your copies as well?
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`JUDGE KAMHOLZ: Yes, please.
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`MR. PARKER: Your Honors, we only made one copy to
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`cover all three of the IPRs relating to -- I'll refer to the same set of
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`patents if that's okay.
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`JUDGE KAMHOLZ: Parties, are there any particular set of
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`slides we should we referring to?
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`MR. CWIK: Your Honor, I expect I will primarily be
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`relying on the 116 case, the '915 patent case. The slides are very
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`similar for most of the slides, except for some of the claim charts in the
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`beginning of the slide, and if we get that far -- I'm not sure we will get
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`that far, but if we do, I'll make that indication. I'll even have to change
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`the slides on the computer.
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`So if we can start with the '915 in the 116 case is the one I
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`plan on starting with.
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`JUDGE KAMHOLZ: You may begin when ready.
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`MR. CWIK: Good morning, Your Honors. My name is Joe
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`Cwik, and for the record I'm here on behalf of the petitioners. Your
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`Honors, I would like to give you a brief outline of what petitioners plan
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`on doing with their oral argument today. I am going to start with 20
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`minutes to discuss our prima facie case with respect to the '915, the
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`'381, '778 patents. The parties have collectively called those patents the
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`Bailey patents.
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`Patent owners will then have their one hour of response time,
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`and petitioners will reserve 40 minutes for rebuttal, and the reason we
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`broke out the time that way is, as you can see in the briefing so far,
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`there's been much more briefing and time spent on the issues
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`surrounding the prima facie case than the actual prima facie case itself.
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`When we get to the rebuttal period, Mr. Krit and I will be
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`splitting that time, depending on the issue. We've tried to break up the
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`issues, and we'll be splitting that time.
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`Your Honors, I see my key job today is to explain to you, to
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`the best of my ability, what the petitioner's positions are in this case, so
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`at any time I'm making my presentation you don't understand
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`something and want to interrupt me, please feel free to do so.
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`The first patent I want to talk about is the '915 patent. The
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`'915 patent is generally directed towards the dietary use of a
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`substantially, chirally pure (6S)-5-MTHF, in addition to another
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`vitamin for the purpose of treating folate deficiency.
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`The patent owner has requested to cancel many of the claims
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`that were instituted, and the claims remaining in the '915 patent are
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`claims 94 through 97, 99, 100, 110, 111.
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`JUDGE BONILLA: Explain what “substantial” means when
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`you say substantially chirally pure.
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`MR. CWIK: Substantially chirally pure is the Board in its
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`institute to instigate the case said it was meaning essentially free of the
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`(6R) isomer, so the claims of course are entitled to the broadest
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`reasonable interpretation under the rules here, and we think that -- we
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`agree with the construction that substantially chirally pure would mean
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`an isomer form that would be substantially free of the 6R-5-MTHF
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`form.
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`JUDGE BONILLA: How much can be in there?
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`MR. CWIK: Well, there's no -- I don't think the parties have
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`come up with any hard number. 99 percent, 99 -- it's really just
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`essentially free as a person of ordinary skill in the art would interpret
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`that. I think the word essentially implies that there may be trace
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`amounts of a 6R isomer. The language was not completely free, so
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`there possibly may be 1, 2, maybe up to 5 percent.
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`Does that answer your question, Your Honor?
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`JUDGE BONILLA: Yes, thank you.
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`MR. CWIK: With respect to the '915 patent claims, it's our
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`position that the pending claims are obvious in light of the Serfontein
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`and Marazza reference.
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`The first reference I want to talk about is the Serfontein
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`reference and referring to slide 2 of the 116 case, demonstrative
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`exhibits, for the record this is demonstrative Exhibit 1148. Here we
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`have a cut and paste right out of Serfontein of the first claim of
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`Serfontein, and we think this provides a clear example, a clear teaching
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`of the core teaching of Serfontein, but it's not everything Serfontein
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`teaches, but it's the core teaching which we rely on, and claim 1 claims:
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`"The use in the manufacture of a pharmaceutical preparation for
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`lowering levels of homocysteine or for the prophylaxis or treatment of
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`elevated levels of homocysteine or of clinical conditions associated
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`therewith in a patient of a combination comprising vitamin B6; folate
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`or a suitable active metabolite of folate or a substance which release
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`folate in vivo, and vitamin B12."
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`JUDGE BONILLA: You talk in your brief about how
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`suitable active metabolite refers to basically eight compounds. What
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`about the fact that folate or the substances that release folate in vivo,
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`how many compounds does the word folate and the substance that
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`releases folate -- how many compounds is that?
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`MR. CWIK: Your Honor, we think folate, as it's used in this
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`claim 1 and other examples in the Serfontein refers to folic acid, so that
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`would be one.
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`JUDGE BONILLA: So it doesn't refer to anything else; the
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`term folate only refers to folic acid?
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`MR. CWIK: That's our interpretation of what Serfontein was
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`saying, yes, and as far as a substance which releases folate in vivo,
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`we're not positive what that means. I don't think any of the experts
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`have been able to opine on that. We understand there are two different
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`acids which can be combined to be precursors to folic acid, so if
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`anything, we think that phrase would be limited to additional
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`compounds.
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`JUDGE KAMHOLZ: What about patent owners'
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`contentions about salts, and in effect there's thousands of compounds
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`that fall within this group?
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`MR. CWIK: Right, right, Your Honor. On the issue of the
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`many salts, patent owner I think is misapplying the holdings of In re
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`Petering and In re Schaumann by making that argument.
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`The In re Petering and In re Schaumann argument is this
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`genus species framework, and it's our contention that the genus of
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`active metabolites and folates are eight compounds, and those eight
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`compounds are the same eight compounds that are identified by Dr.
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`Miller. They're identified in figure 21-4 in the Modern Nutrition
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`Handbook that Dr. Miller relied upon, and with respect to those eight
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`compounds, we don't understand patent owners to disagree that those,
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`in fact, are the eight active metabolites that are involved in the folate
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`metabolism process.
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`So what patent owners are doing regarding the salts, Your
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`Honor, is we have the genus, and then we have the eight compounds or
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`the eight species, and what they have done is they've taken one step
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`beyond Petering, one step beyond Schaumann and said, Let's take one
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`individual species and see how many different salts we can connect to
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`it, and that was a step that was not taken In re Petering, In re
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`Schaumann. There's the genus, and then there's the identification of the
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`limited class of eight compounds.
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`For them to try to split hairs and take a single species and
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`say, Well, how many variation of one single species can you imagine,
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`we think that's not the holding of those cases, and even in this case, I
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`think that's an unfair step to take given the scope of the claims we have
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`at issue. The '915 patent claims are not limited to a specific salt. It's
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`not limited to calcium salt or some other type of salt.
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`So I think the problem with their argument is they're saying,
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`Well, Serfontein has to disclose what salts you're talking about, but the
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`claims themselves aren't limited to any such salts, and the same
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`argument concerns the polyglutamation forms, is they're interpreting
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`Serfontein and saying, Hey, look at Serfontein, you have to tell
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`us -- Serfontein has to tell us what polyglutamate forms to disclose the
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`'915 patent claims, but the '915 patent claims aren't limited to any
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`polyglutamate forms, so they're requiring Serfontein to say something
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`that is not actually a limitation of the claims, so I think there's not a
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`commensurate scope analysis that they're doing there.
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`So I think that addresses -- and really the salt question,
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`another point on the salt question is even if Serfontein had said the
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`exact language that's used in one of these challenged claims of the '915
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`patent, here's claim 94, slide 5 in my presentation, this is the first
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`challenged claim that's limited to a substantially chirally pure
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`5-methyl-6S-tetrahydrofolic-acid or a polyglutamate derivative thereof.
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`Their essential argument is, Well, even if Serfontein said that
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`and said that exactly, even though that's what the claim says, Serfontein
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`doesn't teach the invention because Serfontein doesn't tell you what
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`salts. That can't be correct. We have to have a commensurate teaching
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`of the prior art of the actual claims at issue. So to argue that all of the
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`salts are -- can be imagined I think is just an unfair argument. Does
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`that answer your question, Your Honor?
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`JUDGE KAMHOLZ: Yes.
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`JUDGE BONILLA: Just to be clear, Serfontein doesn't talk
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`about any of the eight in particular, the suitable active metabolites. It
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`doesn't talk about anything being chirally pure, distinguishing between
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`a racemic mixture and the different isomers. It doesn't get into that at
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`all?
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`MR. CWIK: Correct. It does not expressly say word to
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`word an identification of those eight compounds, right. We are relying
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`on Dr. Miller's analysis in the Modern Nutrition Handbook as a genus
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`of eight compounds that would be immediately envisaged by a person
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`of ordinary art.
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`JUDGE BONILLA: Well, it would have to be more than
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`eight. It would have to be eight times two, right, for each of the
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`isomers? Is that correct?
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`MR. CWIK: Well, no, Your Honor that's not our position,
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`and Dr. Miller's position, and he continues with his analysis, is he says,
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`Well, in the Modern Nutrition Handbook, figure 21-4 has the eight
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`compounds that are involved in the folate metabolism process, and he
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`notes that figure 21-4 doesn't indicate whether that includes the active
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`isomers or the inactive isomers, but what he does say is in the Modern
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`Nutrition Handbook, it also refers to the IUPAC nomenclature rules,
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`which then, if you look at -- and that was part of our exhibits in our
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`original petition -- does identify the eight isomer active forms, and our
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`contention is the active metabolites of folate as disclosed in Serfontein
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`are not the racemic general metabolites, but the actual active natural
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`reduced folates.
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`JUDGE BONILLA: Is there evidence of record that a
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`racemic mixture wouldn't be active, that it wouldn't work?
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`MR. CWIK: No, I don't think there is evidence that a -- I
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`don't recall evidence I should say that a racemic mixture would not
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`work prior to 1996, and I think there is evidence that a racemic mixture
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`would work, and so...
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`JUDGE BONILLA: So the term active metabolite, it
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`couldn't be a racemic mixture is your position. It would have to be the
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`active isomer.
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`MR. CWIK: Correct. That's how a person of ordinary skill
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`in the art would read it, and again I don't understand patent owners to
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`be disagreeing with that. I don't understand them ever to be saying,
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`Well, the (6R) isomer of the (6S)-5-MTHF. It is the active metabolite
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`of folate. I think that's pretty well established, and I don't remember
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`them contesting that the eight folates are the naturally reduced folates,
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`and another reason that we think the genus is specifically defined as the
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`actual active isomer is that they have a structural similarity.
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`14
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`The seven out of the eight active metabolites have an isomer
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`15
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`form, which has an L configuration on the six carbon position, so not
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`16
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`only would a person of ordinary skill in the art immediately envisage
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`these based on Dr. Miller's testimony and figure 21-4, here, as in
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`Petering, there's actually structural similarity among the reduced
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`natural folates in that they all have this L configuration at the 6 carbon
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`20
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`atom position.
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`So continuing just to give you a broad framework of how
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`22
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`claims read on Serfontein itself, I first have a claim chart on my slide
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`number 3, which looks at claim 37. Claim 37 is not at issue per se in
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`this case, but it's the independent claim upon which the challenged
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`claims depend on, so just to give us a framework of how
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`Serfontein -- how the claims read on Serfontein, I've put this up here.
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`As far as the first element of claim 37, the core idea here is
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`there's "a method of increasing a human subject's dietary intake of
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`folate in a human," and really the two key concepts here is that the
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`claim is limited to a dietary intake and it's for a human, and Serfontein
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`discloses that it is for a patient defined human, and there's two different
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`places in the record of Serfontein where he indicates that -- it's for
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`dietary preparations are disclosed, and then here he indicates that the
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`invention can also be used in a dietary program. So those elements are
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`meant by Serfontein.
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`Continuing on, the next element is "one or more natural
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`isomers of reduced folate selected from the group consisting of," and
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`then I think there's seven of those natural reduced folates that I was just
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`speaking of. Those are the ones that have the L configuration
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`structurally similar at the 6 carbon position, and we believe that those
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`reduced folates again are taught by the suitable active metabolite of
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`folate language that we just talked about before.
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`The claim continues by requiring an additional vitamin in
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`here. Serfontein discloses the additional item minimum being 5
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`milligrams of vitamin B6, and also has the required greater than 25
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`percent of the daily requirement.
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`And as I said before, claim 94 is the first challenged claim in
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`this case, and this claim, among the other claims that are left in this
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`case, are limited to the substantially chirally pure
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`5-methyl-6S-tetrahydrofolic acid.
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`Regarding the active metabolite of folate, this is a summary
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`of -- this is actually the Board's holding with respect to its conclusions
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`in its decision to institute. We thought that this language was a great
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`summary of what Miller said and Modern Nutrition said, all at the same
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`time, and as you can see at the bottom of this slide, this is slide 6, that
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`we begin to see the eight compounds that are involved in the folate
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`metabolism process. These are the compounds identified in figure 21-4
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`of the Modern Nutrition textbook.
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`And as Your Honor noted, these are really probably the
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`racemic versions that are shown in the figure, but as we move on to
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`Modern Nutrition, we see that there's an identification to the IUPAC
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`14
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`nomenclature recommendation, which identifies the natural active
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`15
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`folates as having the same six carbon configuration as the
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`(6S)-tetrahydrofolic, and ultimately, Dr. Miller's conclusion is that the
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`active metabolites of folate embrace no more than dihydrofolate and
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`the naturally occurring stereoisomers, i.e. --
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`JUDGE BONILLA: Wouldn't the racemic measure have the
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`same six carbon configuration, one of each?
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`MR. CWIK: It would for the (6S) isomer. I don't know for
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`the (6R) isomer. I don't know. So that is the summary of the
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`Serfontein reference.
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`We also are relying on the Marazza reference as rendering
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`the claims obvious in light of Serfontein as well. What Marazza is
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`doing, Marazza comes along and Marazza recognize that, Hey, there's
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`an increasing interest in this 5-MTHF compound. There's an increasing
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`interest in using it as a vitamin in folate deficiencies. There's also an
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`interest in using it in cancer therapy.
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`So he also recognizes -- we have this interest in it, but we
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`also recognize that there's two isomers in the 5-MTHF. There's the
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`(6S) isomer and the (6R) isomer. He concludes the (6S) isomer is
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`good, and the (6R) isomer is potentially bad, so what he says is, I have
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`to find a way, I have to find a way to separate these, the good (6S)
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`isomers from the bad (6R) isomers, so he comes up with a separation
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`technique for the entire purpose of being able to give a patient the good
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`(6S) isomer, essentially free, pure and not have any of the bad (6R)
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`isomer.
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`14
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`So the purpose of Marazza is this is where Marazza teaches
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`that the last limitation in claim 94, that you would want the
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`(6S)-5-MTHF isomer to be essentially free or substantially chirally
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`pure of the (6R) isomer.
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`JUDGE KAMHOLZ: So what other evidence in the record
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`establishes before the invention that (6R) was undesirable for whatever
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`reason?
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`MR. CWIK: I think there's multiple references. I think the
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`Wood reference was a reference that talked about the separation
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`technique. The Ambrosini reference I believe was even in the Board's
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`opinion noting that the (6S) isomer was the preferred one, and those are
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`the two I can remember right now, and also on page 200 of the Cooper
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`and Zittoun reference, and for the record, that's Gnosis's Exhibit 1624.
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`JUDGE BONILLA: What's the date of that reference?
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`MR. CWIK: The Zittoun and Cooper, that's before 1996.
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`That I can tell you for sure.
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`JUDGE BONILLA: Are all the ones you cited pre 19 --
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`MR. CWIK: Yes, Your Honor. Zittoun and Cooper is 1989.
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`JUDGE KAMHOLZ: Mr. Cwik, your time has expired.
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`MR. PARKER: We'll just need one minute to switch the
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`computers.
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`JUDGE BONILLA: Actually I would like to ask some
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`questions before we switch over. I was waiting for you to finish before
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`I ask it.
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`There's a footnote in the patent owner's response talking
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`about how statements that Gnosis made about the Marazza reference.
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`Basically I wanted to ask you if this is some kind of omission that
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`there's a problem with the Marazza reference. It's ineffective. It
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`doesn't work. It's not great. It's too expensive.
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`MR. CWIK: Well, Your Honor, I have two points on that.
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`The first point is that is statements ten years after Marazza, so that's
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`commenting on what is known ten years after Marazza, not what a
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`person of ordinary skill in the art knew as Marazza knew at the time.
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`JUDGE BONILLA: What evidence do you have in the
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`record that that was made ten years later?
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`MR. CWIK: They had submitted the actual paperwork I
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`believe when Gnosis made that statement, so I'm assuming the dates on
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`that. I can't recall exactly though.
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`The second point I want to make about that is that our client,
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`Gnosis, was commenting on the separation technique itself, and we're
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`not citing Marazza for the proposition that it was the best or optimal
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`separation technique. What we're citing from Marazza is the fact that
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`Marazza knew that this racemic compound was something that there
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`was a lot of interest in as a vitamin in folate deficiency states, and he
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`thought so strongly about it, he developed a technique to separate the
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`good (6S) isomers from the (6R) isomers, so it's what he did.
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`Whether the separation technique is the best technique or not
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`is really not relevant to our claims because our claim is just showing
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`that he wanted the (6S) to be pure and essentially free of the (6R)
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`isomer.
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`JUDGE BONILLA: Nobody knew how to separate it, right?
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`If they didn't know how to separate it, they didn't think they could
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`separate it very well, they wouldn't have had motivation to do it, right?
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`MR. CWIK: Right so they did think they could be able to
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`separate it, correct, right.
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`JUDGE KAMHOLZ: Thank you.
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`MR. PARKER: Good morning, Your Honors. For the
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`record, my name is Tom Parker. I'll be speaking on behalf of the patent
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`owner in this particular case, which is South Alabama Medical Science
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` 17
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`Foundation.
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
`
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`Your Honors, if I can, I would like to begin with the '778
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`patent, and I would like to just introduce the two inventors of the '778,
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`which is Dr. June Ayling and Steve Bailey of University of South
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`Alabama Medical School, and I would like to focus on claim 15, which
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`is the only claim now that's being challenged in the '778 patents. Here
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`the Board found that petitioner's demonstrated claim 15 is unpatentable
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`as obvious in view of Serfontein, Ueland, Marazza, and that's ground 2
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`in the Board's decision.
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`So, Your Honors, just for the record for shorthand, with
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`respect to 5-methyl-(6S)-tetrahydrofolic acid, I'll be referring to it
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`either as L-5 or L-5-MTHF, and for the racemic mixture of (6S) and
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`(6R), I'll refer to that as the 5-MTHF.
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`Relying on these three references, the Board concluded that
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`claim 15 may be unpatentable stating that a person of ordinary skill in
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`15
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`the art, the POSA, would have had reasonably expected that
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`administering the L-5 would have increased the intercellular pool of
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`L-5, and consequently would have lowered levels of homocysteine for
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`18
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`purposes of treating vascular disease resulting from excess levels of
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`19
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`homocysteine.
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`20
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`Notably, the Board concluded that Serfontein's disclosure did
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`21
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`not include a suitable active metabolite of folate, which I'll refer to as a
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`22
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`SAMOF, S-A-M-O-F, as being substantially chirally pure, including
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`23
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`substantially chirally pure L-5. Now, citing Ueland, the Board noted
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`that Ueland teaches that increasing the intercellular levels of L-5, you
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`will introduce levels of homocysteine in the cells.
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
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`Now, according to patent owner's expert Dr. Gregory, he
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`opined that claim 15 would not have been obvious because a person of
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`ordinary skill in the art would not have believed that when you
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`combined Serfontein, Ueland and Marazza together, that it would
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`produce an operative formulation; that is, the POSA would not expect
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`that L-5 when administered would be accumulated and retained in the
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`cells and would not effectively increase the intercellular pools of L-5,
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`and that being the case, the POSA would not believe or expect that
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`administering L-5 with lower levels of homocysteine in a human
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`patient.
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`JUDGE KAMHOLZ: Isn't Ueland relied on only for that
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`theory?
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`theory.
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`MR. PARKER: Excuse me?
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`JUDGE KAMHOLZ: Ueland is only relied on for that
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`MR. PARKER: Well, in the Board's opinion --
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`JUDGE KAMHOLZ: In the petitioner's challenge.
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`MR. PARKER: Excuse me?
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`JUDGE KAMHOLZ: In petitioner's challenge, Ueland is
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`relied on for that theory that you've produced on that slide.
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`MR. PARKER: Correct.
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`JUDGE SNEDDEN: Doesn't Serfontein already indicate a
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`link between elevated homocysteine levels and vascular disease?
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`Case Nos. IPR2013-00116, IPR2013-00117,
`IPR2013-00118, and IPR2013-00119
`
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`MR. PARKER: Serfontein does express that there's a
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`connection between high levels of homocysteine and vascular disease,
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`correct.
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`JUDGE KAMHOLZ: So is the theory of the mechanism
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`particularly relevant here?
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`MR. PARKER: It is, Your Honor, because Ueland says that
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`the only way to increase the cellular levels of L-5 is by administering
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`folic acid because at the time, it was believed that administering L-5
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`would not be retained, would not be polyglutamated and would not be
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`retained in the cells.
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`JUDGE BONILLA: What's the basis for that?
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`MR. PARKER: That is the Wagner reference, and the
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`Wagner reference --
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`JUDGE BONILLA: What Exhibit is that? I'm sorry.
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`MR. PARKER: Excuse me?
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`JUDGE BONILLA: What exhibit is that?
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`MR. PARKER: The Wagner reference is on slide 9, and
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`that's a reference to -- it's referenced -- it's Exhibit 2061 in the Gregory
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`19
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`declaration of 2075, paragraph 34. Here Wagner shows that exogenous
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`20
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`L-5, even when transported in the cells, remains unpolyglutamated, and
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`therefore it's not being utilized by the cells.
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`Also, we have Dr. Miller's testimony on slide
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