Transcript of Graham Buckton,
`Ph.D.
`
`Date: September 26, 2023
`Case: Apotex Inc. -v- Celgene Corporation (PTAB)
`
`Planet Depos
`Phone: 888.433.3767
`Email: transcripts@planetdepos.com
`www.planetdepos.com
`
`CELGENE 2050
`APOTEX v. CELGENE
`IPR2023-00512
`
`WORLDWIDE COURT REPORTING & LITIGATION TECHNOLOGY
`
`
`Ph.D.
`
`Date: September 26, 2023
`Case: Apotex Inc. -v- Celgene Corporation (PTAB)
`
`Planet Depos
`Phone: 888.433.3767
`Email: transcripts@planetdepos.com
`www.planetdepos.com
`
`CELGENE 2050
`APOTEX v. CELGENE
`IPR2023-00512
`
`WORLDWIDE COURT REPORTING & LITIGATION TECHNOLOGY
`
`
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` - - - - - - - - - - - - x
`APOTEX, INC., :
` Petitioner, :
`v. : Case No. IPR2023-00512
`CELGENE CORPORATION, : U.S. Patent No.
` Patent Owner. : 8,846,628
` - - - - - - - - - - - - x
`
` Videotaped Deposition of GRAHAM BUCKTON, PH.D.
` New York, New York
` Tuesday, September 26, 2023
` 8:47 a.m.
`
` Job No.: 506502
` Pages: 1 - 161
` Reported By: Anita M. Trombetta, RMR, CRR
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`Transcript of Graham Buckton, Ph.D.
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`2
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` Videotaped deposition of Graham Buckton, Ph.D.,
`held at the offices of:
`
` Steptoe & Johnson LLP
` 1114 Avenue of the Americas
` 35th floor
` New York, NY 10036
` 212.506.3900
`
` Pursuant to notice, before Anita M. Trombetta,
`RMR, CRR, Notary Public in and for the State of
`New York.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`3
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`A P P E A R A N C E S
`
` ON BEHALF OF PETITIONER AND THE WITNESS:
` VISHAL C. GUPTA, ESQUIRE
` TYLER DOH, Ph.D., ESQUIRE
` MICHAEL I. GREEN, ESQUIRE (via
` teleconference)
` STEPTOE & JOHNSON LLP
` 1114 Avenue of the Americas
` New York, New York 10036
` (212) 506-3900
`
`ON BEHALF OF PATENT OWNER:
` HEATHER PETRUZZI, ESQUIRE
` LAURA MACRO, ESQUIRE, Ph.D.
` GABRIEL ROSANIO, ESQUIRE, Ph.D.
` WILMER CUTLER PICKERING HALE and DORR LLP
` 2100 Pennsylvania Avenue NW
` Washington, DC 20037
` (202) 663-6000
`
`(Appearances continued on next page.)
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`4
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`A P P E A R A N C E S C O N T I N U E D
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` ALSO PRESENT:
` Bo Han, BMS (via teleconference)
` Enrique Casas, Videographer
` Muskaan Zaidi, Planet Depo
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`5
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` ------------------I N D E X-----------------------
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` WITNESS EXAMINATION BY PAGE
`Graham Buckton, Ph.D. Ms. Petruzzi 7
` Mr. Gupta 147
` Ms. Petruzzi 156
`
` -----------------E X H I B I T S------------------
` EXHIBIT DESCRIPTION PAGE
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` INFORMATION REQUESTED
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`6
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` P R O C E E D I N G S
` THE VIDEOGRAPHER: Here begins Media No. 1
`in the videotaped deposition of Graham Buckton,
`Ph.D., in the matter of Apotex Inc. vs. Celgene
`Corporation PTAB, in the United States Patent and
`Trademark Office, Case Number IPR 2023-00512.
` Today's date is September 26, 2023. And
`the time on the video monitor is 8:47 a.m.
` Today -- the videographer today is Enrique
`Casas representing Planet Depos. This video
`deposition is taking place at 1114 Avenue of the
`Americas, New York, New York.
` Would counsel please voice identify
`themselves and state who they represent.
` MS. PETRUZZI: Heather Petruzzi from
`WilmerHale representing the patent owner Celgene
`Corporation and BMS. I'm joined by my colleagues
`Laura Macro and Gabriel Rosanio, also from
`WilmerHale and Bo Han from BMS.
` MR. GUPTA: Vishal Gupta from the law firm
`of Steptoe & Johnson. I'm joined by Tyler Doh
`from my firm and at some point, potentially,
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
`
`7
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`Michael Green may call in.
` THE VIDEOGRAPHER: The court reporter
`today is Anita Trombetta representing Planet
`Depos.
` The witness will now be sworn in.
`G R A H A M B U C K T O N, P H.D.,
` called as a witness, having been duly
` sworn by a Notary Public, was examined and
` testified as follows:
`EXAMINATION BY
`MS. PETRUZZI:
` Q Good morning, Dr. Buckton.
` A Good morning.
` Q Thank you for being here today.
` Do you understand why you're being deposed
`today?
` A Yes.
` Q And what is that understanding?
` A To explain my evidence in relation to this
`case for the patent brought.
` Q Okay. And you've submitted a declaration
`in connection with IPR 2023-00512, correct?
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
`
`8
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` A I haven't memorized the number, but that
`sounds right, yes.
` Q Okay. Have you been deposed before?
` A Yes.
` Q How many times have you been deposed?
` A Quite a few. I don't know exactly, maybe
`20 or more.
` Q Okay. Do you understand that your
`testimony here is given under oath?
` A Yes.
` Q Is there any reason that you cannot
`provide complete and accurate testimony here
`today?
` A No.
` Q Did you bring anything with you to the
`deposition today?
` A No, there's a report here, which I didn't
`technically bring, but that is an unmarked copy of
`my report.
` Q Okay. So you have next to you an unmarked
`copy of your report?
` A I do.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
`
`9
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` Q Okay. Thank you. Anything else with you
`today?
` A No.
` Q Okay. You are an expert in formulations,
`right?
` A Yeah, amongst other things, yes.
` Q Okay. Have you ever formulated
`5-azacytidine before?
` MR. GUPTA: Objection to form.
` You can answer.
` A I don't believe so, but in my company
`we've formulated a lot of things. I don't believe
`it was this compound, but it may have been. I
`don't think so though.
` Q Have you personally worked with
`5-azacytidine before?
` A Same answer.
` Q In your declaration you attached a copy of
`your CV; is that right?
` A Yes.
` Q Your CV does not describe any research you
`completed concerning 5-azacytidine, correct?
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
`
`10
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` A No. Inevitably, an academic CV covers
`nonproprietary things, and you talk about other
`stuff than the drug substance.
` Q Had you heard of 5-azacytidine before your
`work on this case?
` A I'd heard of it as a drug, yes.
` Q In what context have you heard of it?
` A As an anticancer drug.
` Q When did you first heard of 5-azacytidine?
` A I don't know the date. It's just a drug
`name that I happen to know. I don't know the
`date.
` Q Okay. Were you familiar with the
`literature on 5-azacytidine before your work on
`this case?
` A By literature, you mean prior art of this
`patent, as it were. I wasn't familiar with the
`literature particularly.
` Q Your CV notes that you're an emeritus
`professor of pharmaceutics; is that right?
` A Emeritus, yes.
` Q What does that mean?
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
`
`11
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` A It essentially means that I have retired,
`but I have an honorary position at the university.
` Q When did you retire from the university?
` A 2015.
` Q You're currently working; is that correct?
` A I am largely retired, and I have over the
`last year or so kind of been stepping down from
`other things that I do. So I have some expert
`witness work, and outside of that, largely
`retired.
` Q Okay. And so how much of your work is
`related to being an expert witness at this point?
` A Just about all of it is, but the amount of
`my time that's work is, thankfully, rather small.
` Q How much of your time are you spending
`working right now?
` A Well, this week isn't very good because
`I've been working more than I've been golfing, for
`example, but other weeks are rather better in
`terms of the golf-work balance. But it isn't
`consistent. It varies. There could be months I
`will do nothing, like several months when I will
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`12
`
`do nothing. And then there could be months when I
`do something, I work quite a lot. So it varies
`quite a lot.
` Q I'm going to hand you what's previously
`been marked as Exhibit 1002 in this proceeding.
` A You can take that one away.
` Q Do you recognize this document?
` A Yes, yes, I do.
` Q What is it?
` A It is the report I submitted with my CV
`attached at the end of it.
` Q And this is concerning Celgene patent
`8,846,628, correct?
` A I don't recognize -- I haven't memorized
`the number, but the last three digits are right.
` Q Okay. It's right on the first page -- on
`the cover page of your declaration there.
` Do you see it?
` A I really don't.
` Q U.S. patent number?
` A Oh, yeah, it's in the middle. I've got
`it.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
`
`13
`
` Q You see it?
` A Yes, I've got it now.
` Q Great. If I refer to it the '628 patent,
`you'll know what I mean?
` A I was there already on the '628.
` Q Perfect. We're on the same page.
` Did you review the '628 patent in its
`entirety before submitting your declaration?
` A Yes, I did.
` Q About how many times did you do that?
` A I don't think I reviewed it in its
`entirety more than once probably. I would have
`looked at that time in its entirety and then
`looked in further detail at sections that are
`relevant to what I was considering.
` Q Okay. All right.
` Your declaration contains Section 4, which
`starts at Page 13. Turn to that: Documents.
` Do you see that?
` A Sorry, what was that? Page 14.
` Q Page 13 of page -- starts with:
`Documents.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`14
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` A Yes.
` Q The section starts with: Documents.
` Do you see that?
` A Yes.
` Q And these are the documents that you
`considered in forming your opinions in this
`declaration; is that right?
` A That's right.
` Q Does Section 4 represent the full set of
`materials you considered in forming your opinions
`contained in the declaration?
` A I think so. I may have -- yeah, there may
`be kind of standard textbooks that maybe I have an
`opinion based on, but I haven't got in here. I
`don't know. But there's nothing that I've written
`in my opinion -- there's nothing I've written in
`my opinion in terms of what's in this report, of
`anything else other than these.
` Q Okay. In forming your opinions for this
`declaration, did you search for any literature
`yourself?
` A I don't think I searched for literature
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`15
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`myself. I knew of literature myself, but I don't
`know if I searched for anything.
` Q How did you know of the literature
`yourself?
` A A quite a bit of literature is related to
`aspects relating to formulation, and I would have
`known about aspects relating to formulation, for
`example.
` Q Okay. So for example, you cite
`Remington's as a reference?
` A Yes.
` Q And Remington's is a common textbook that
`you would have been aware of?
` A I certainly was aware of Remington's
`before this, yes.
` Q Did you talk to anyone other than counsel
`for Apotex in forming your opinions in this
`declaration?
` A No.
` Q Your report cites the -- Dr. Batchelor's
`declaration, correct?
` A It does.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`16
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` Q Did you speak with Dr. Batchelor before
`signing your declaration?
` A Not about this, no.
` Q Do you know Dr. Batchelor?
` A Yes.
` Q Did you talk to her about this case at all
`before forming your opinions in this declaration?
` A No.
` Q Have you talked to her about this case at
`all?
` A No.
` Q Did you consult with a clinician in
`forming your opinions in the declaration?
` A No, I had no need to do that. My opinions
`are my opinions without the need to talk to anyone
`else about them.
` Q Did you review Dr. Batchelor's deposition
`transcript in preparing for today's deposition?
` A Yes, I did.
` Q In preparing for your deposition, did you
`review the Court's claim construction order from
`the district court litigation?
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`17
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` A No, I don't think so.
` Q Did you review Celgene's preliminary
`response filed in this IPR proceeding?
` A I don't believe so. If I'm wrong about
`any of this, I apologize, but my memory is no.
` Q Okay. Did you review Dr. Berkland's
`declaration submitted in support of Celgene's
`preliminary response in this proceeding?
` A Yes, I did.
` Q When did you review that?
` A I reviewed it, I think pretty soon after
`it was submitted, whatever date that was, and then
`I believe I've not looked at it in its entirety,
`but probably looked at in part over the last few
`days.
` Q Did it change any of your opinions?
` A No.
` Q Did you review the board's institution
`decision for this IPR proceeding?
` A Yes, I did.
` Q When did you do that?
` A Pretty much when it came out.
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`Conducted on September 26, 2023
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`18
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` Q Did it change any of your opinions?
` A No.
` Q When did you review Dr. Batchelor's
`deposition transcript?
` A I think on the plane coming over here.
` Q When was that?
` A When was that?
` Q Yes.
` A It was Sunday. No, was it? No, it was
`Saturday. Saturday, yes.
` Q Did it change any of the opinions that you
`offered in your declaration?
` A No.
` Q Did you review any other materials in
`preparation for your deposition besides the
`materials listed in your documents-considered list
`on -- starting on Page 13 of your declaration?
` A I don't know. I haven't checked whatever
`I've reviewed against what's on the list, if I'm
`honest, but I read -- yes, I did. Actually, the
`answer is yes, I've looked at a few papers which
`were cited by Dr. Berkland, although I can't
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`19
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`honestly remember the names of them just now, just
`a few of those which I haven't seen before.
` Q Can you describe those papers that you
`reviewed?
` A Not terribly well, not really, no, but I
`did read some papers from his declaration.
` Q Okay. And why did you do so?
` A Because I was trying to understand what he
`was talking about. And see whether I agreed with
`what he was talking about or not.
` MS. PETRUZZI: Counsel, I'd ask you to
`provide a list of the papers Dr. Buckton reviewed
`in connection with his preparation for this
`deposition that are not included in the
`documents-considered list.
` MR. GUPTA: He just reviewed the Berkland
`declaration, whatever was cited in there, like I
`don't -- I don't think your -- I'll take it under
`advisement.
` MS. PETRUZZI: Thank you.
`BY MS. PETRUZZI:
` Q Did you review all of the documents
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`Conducted on September 26, 2023
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`20
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`considered in Dr. Berkland's declaration?
` A No. Just a couple.
` MS. PETRUZZI: Counsel, we'd like to know
`the list of what he considered, please.
` MR. GUPTA: I'll take it under
`advisement -- I'll take your request under
`advisement. I don't know if I agree with it.
`BY MS. PETRUZZI:
` Q Dr. Buckton, you've worked in
`pharmaceutics and pharmaceutical formulations for
`a long time, right?
` A Yes.
` Q Okay. When did you begin your work in
`pharmaceutics and pharmaceutical formulations?
` A So my Ph.D. started in '82, 1982.
` Q And you've been working in the field ever
`since?
` A Yes.
` Q You've considered -- strike that.
` In your experience working in
`pharmaceutics and pharmaceutical formulations,
`you've considered the things that one would need
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`21
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`to consider when developing a pharmaceutical
`formulation, correct?
` A That's a very wide question, isn't it, so
`specifically to an individual task, I would
`consider what was necessary to that individual
`task, yes.
` Q And part of the individual task is
`ensuring that the pharmaceutical formulation that
`you develop can administer therapeutically
`effective amount of the drug to a patient?
` A Part of the task would be delivering a
`therapeutic and effective amount, correct.
` Q You agree that the stability of an active
`ingredient is an important consideration in a
`pharmaceutical formulation, right?
` MR. GUPTA: Objection to form. Scope.
`Relevance.
` You can answer.
` A Stabilities, well, every drug substance
`that we know degrades. I don't know of a drug
`substance that we have that doesn't degrade. The
`vast majority of them degrade by hydrolysis; some
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`22
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`of them degrade by oxidation. So I would consider
`those aspects in relation to a specific type of
`formulation and how important they may or may not
`be.
` Q You mentioned degradation in your answer,
`correct?
` A I think I did, yes. I haven't memorized
`it, but I think I -- yeah.
` Q If there is degradation, that's loss of
`the active ingredient, right?
` MR. GUPTA: Objection to form.
` You can answer.
` A Well, degradation of a drug substance
`through shelf life is an inevitability and that's
`why we have a shelf life on all of our drug
`products, and degradation is, as I was talking
`about it, loss of some of the drug substance, over
`shelf life, for example. But that's an example.
`You know, but we're talking in very
`generalizations, but that's an example. And that
`happens with every product. That's why we set a
`shelf life for every product.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`23
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` Q And as you lose some of the drug substance
`during degradation, the product becomes less
`efficacious; is that right?
` MR. GUPTA: Objection to form.
` You can answer.
` A No, that's not right, because within a
`regulatory consideration, you would be -- your
`shelf life would be something where it remained
`efficacious. So it was still just fine. If it's
`gone outside of its shelf life it means it's no
`longer sufficiently efficacious. So then you have
`a problem. But in terms of normal use, there
`would be an acceptable amount of drug loss over a
`shelf life, and every product will have drug loss
`over the shelf life, and that won't affect
`therapeutic performance. Otherwise, it wouldn't
`be allowed to be on the market.
` Q Okay. So the shelf life defines how long
`enough of the drug substance is available to be
`efficacious. Is that correct?
` (Court reporter clarification.)
` Q Strike that. Why don't I just ask it
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`24
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`again.
` I said, so the shelf life defines how long
`enough of the drug substance is available to be
`efficacious; is that right?
` A In part. The shelf life defines how long
`you maintain safety, quality, and efficacy of a
`drug product in terms of what you're going to
`administer to a patient. That's a standard
`regulatory position.
` Q You mentioned that every drug degrades; is
`that right?
` A I don't know of any, sitting here just
`now, that don't. So there may be, I don't know,
`if I went away and thought about it I could
`probably find an example that doesn't degrade over
`time. I've got one. I'll tell you what. I'll
`give you one that doesn't. Medical gases don't
`degrade over time. There you go. Outside of
`that, I think everything else degrades over time,
`yes.
` Q And so you agree that degradation must be
`taken into account when formulating drug
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`25
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`substances, correct?
` MR. GUPTA: Objection to form.
` You can answer.
` A I think we would always consider
`degradation in terms of defining a shelf life or
`defining a formulation for every drug substance.
`I agree.
` Q Now, in your declaration, you reference
`Dr. Batchelor's declaration, correct?
` A Yes.
` Q In Dr. Batchelor's declaration she
`discusses how pH can affect degradation.
` Do you recall that?
` A I haven't reviewed it for a long time. So
`I don't recall it particularly, but I suspect she
`probably does.
` Q Okay. Do you know if pH can affect the
`formulation of an active ingredient?
` A I don't understand the question. Can you
`give me a more specific question?
` Q Sure. Do you know if the pH can affect
`how you formulate a drug?
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`26
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` MR. GUPTA: Objection to form. And scope.
` You can answer.
` A I still don't understand the question.
`Can you -- I don't understand -- well, in relation
`to what formulation, what type of thing, how does
`it -- I don't -- I don't understand it as a
`general question.
` Q Do you consider pH when formulating a drug
`substance?
` A You would, as part of a fleet of
`preformulation studies, consider pH. I think
`that's a reasonable thing to do when formulating a
`drug substance, in terms of understanding its
`properties, yes.
` Q Do you know whether degradation processes
`can occur faster depending on pH?
` MR. GUPTA: Objection to form, scope, and
`relevance.
` You can answer.
` A I'd say different drug substances can
`degrade at different rates at different pHs.
`That's a usual thing we would consider, yes.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`27
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` Q All right. By 2008, the degradation
`contents -- strike that.
` By 2008, the degradation constants for
`5-azacytidine hydrolysis in aqueous --
` (Court reporter clarification.)
` Q By 2008, the degradation constants for
`5-azacytidine hydrolysis in a aqueous buffer
`solutions at 37-degree celsius were known,
`correct?
` MR. GUPTA: Objection to form.
` You can answer.
` A I think they were known for some pH values
`in terms of studying long-term stability of a
`liquid formulation, I believe.
` Q Okay. Did you review those degradation
`rate constants in preparing your declaration?
` A I may have looked at them. I don't know.
`Are they on my materials considered? I don't
`know. If they're on there, maybe I did. If
`they're not on there, maybe I didn't. I don't --
`I don't need to -- well, let's -- let's -- if
`they're on there, let's have a look at them.
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`28
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`We'll look at them anyway. Whatever you prefer.
` Q All right. If you will turn to your
`declaration, please, at Page 56. The top of the
`page is the end of paragraph 119. Let me know
`when you're there.
` A Okay.
` Q And here there is -- we see part of a
`sentence, but essentially at the top of the page
`talks about the bioavailability when accounting
`for the level of degradation of 5-azacytadine in
`the stomach.
` Do you see that?
` A On top of the -- I'm not in the right
`place, though. Okay. What page are you on?
` Q Sure. I'm on Page 56.
` A Yes, so am.
` Q And at the very top of the page.
` A Oh, second line.
` MR. GUPTA: Hold on. Let me get there.
` A Okay. Okay.
` What was the question?
` Q Okay. And you see there, you talk about
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`Transcript of Graham Buckton, Ph.D.
`Conducted on September 26, 2023
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`29
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`when accounting for the level of degradation of
`5-azacytidine in the stomach, and cite the
`Batchelor declaration at paragraphs 34 to 36,
`correct?
` A Yes, I do.
` Q Okay. I'm going to hand you what's
`previously been marked as Exhibit 1003 in this
`proceeding.
` Are you familiar with this document?
` A I haven't looked at it in a while, but I
`think it's her declaration. I think it is her
`declaration.
` Q This is the declaration of Dr. Batchelor
`that you relied upon in forming the opinions in
`your declaration, correct?
` A Correct.
` Q And if we turn to paragraphs 34 through
`36, which -- to help you out -- begin on Page 15.
` A Okay.
` Q Are you there?
` A Yes.
` Q Okay. Great.
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`Conducted on September 26, 2023
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`30
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` MR. GUPTA: Hold on. Okay. Thanks.
` MS. PETRUZZI: Sure.
`BY MS. PETRUZZI:
` Q All right. So starting at paragraph 34,
`the second sentence says: "The degradation rate
`constants for
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