`
`UNITED STATES PATENT AND TRADEMARK OFFICE.
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`--------------------------------------------X
`NOVEN PHARMACEUTICALS INC.,
`
` Petitioner,
`
` -against-
`
`NOVARTIS AG AND LTS LOHMANN THERAPIE-SYSTEME
`AG,
`
` Patent Owners.
`--------------------------------------------X
`
` VIDEOTAPED DEPOSITION OF
` DR. AGIS KYDONIEUS
` New York, New York
` Tuesday, January 13, 2015
`
`Reported by:
`Rebecca Schaumloffel, RPR, CLR
`Job No: 88980
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`NOVEN EXHIBIT 1030
`Noven v. Novartis and LTS Lohmann
`IPR2014-00549
`Page 1 of 132
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` January 13, 2015
` 9:35 a.m.
`
` Videotaped deposition of AGIS
`KYDONIEUS, held at the offices of KENYON
`& KENYON, One Broadway, New York, New
`York, before Rebecca Schaumloffel, a
`Registered Professional Reporter, Certified
`Livenote Reporter and Notary Public of the
`State of New York and the State of New
`Jersey.
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`A P P E A R A N C E S:
`
` KENYON & KENYON
` Attorneys for the Petitioner
` One Broadway
` New York, New York 10004
` BY: CHRISTOPHER COULSON, ESQ.
` MICHAEL LEVY, ESQ.
`
` FITZPATRICK CELLA HARPER & SCINTO
` Attorneys for the Patent Owners
` 1290 Avenue of the Americas
` New York, New York 10104
` BY: CHARLOTTE JACOBSEN, ESQ.
` DOMINICK CONDE, ESQ.
`
` KNOBBE MARTENS
` Attorneys for Mylan
` 1717 Pennsylvania Avenue
` Washington, D.C. 20006
` BY: CHRIS KENNEDY, ESQ.
`
` ALSO PRESENT:
`
` Robert Rinkewich, videographer
`
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`NOVEN EXHIBIT 1030
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` A. KYDONIEUS
` THE VIDEOGRAPHER: This is the
`start of tape labeled number 1 of the
`videotaped deposition of
`Agis Kydonieus, ph.D in the matter of
`Noven Pharmaceuticals, Inc. versus
`Novartis AG, et al, in the United
`States Patent and Trademark Office
`before the Patent Trial and Appeal
`Board.
` This deposition is being held at
`1 Broadway, New York, New York on
`January 13th, 2015, at approximately
`9:35 a.m.
` My name is Robert Rinkewich from
`TSG Reporting, Incorporated, and I am
`the legal video specialist. The Court
`Reporter is Rebecca Schaumloffel in
`association with TSG Reporting.
` Will counsel please introduce
`yourselves.
` MS. JACOBSEN: Charlotte
`Jacobsen from Fitzpatrick Cella on
`behalf of the patent owners.
` MR. CONDE: Dominick Conde from
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` A. KYDONIEUS
`Fitzpatrick Cella on behalf of the
`patent owners.
` MR. COULSON: Chris Coulson with
`Kenyon & Kenyon. With me is my
`colleague Mike Levy on behalf of
`Petitioners.
` I'm not sure I heard in the
`intro, but my understanding is this
`dep is for, maybe you are covering
`this, but for 2014-'549 and 2014-'550,
`the two IPRs, all the testimony will
`be applicable to both of those IPRs.
` MS. JACOBSEN: That's correct.
` MR. KENNEDY: Let me just get my
`name on the record. Chris Kennedy
`from the law firm Knobbe Martin here
`on behalf of Mylan. By agreement of
`the parties, Mylan has motions for
`joinder pending.
` THE VIDEOGRAPHER: Will the
`Court Reporter please swear in the
`witness.
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` A. KYDONIEUS
`A G I S K Y D O N I E U S, called as a
`witness, having been first duly sworn by a
`Notary Public of the State of New York, was
`examined and testified as follows:
`CROSS-EXAMINATION BY
`MS. JACOBSEN:
` Q. Good morning, Dr. Kydonieus.
` A. Good morning.
` Q. I know you have been deposed
`before. But I am just going to remind you of
`a couple of things. First is I am going to
`be asking you a series of questions, and I
`need you to try and answer them to the best
`of your ability.
` Okay?
` A. Correct.
` Q. And I need you to give audible
`answers so that we have a clear record of
`today's proceedings. Okay?
` A. Very well.
` Q. And so that the record is clear,
`as well, I ask that you wait until I have
`finished answering my question -- I'm sorry,
`I ask that you wait until I finish asking my
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` A. KYDONIEUS
`question before you start answering it.
`Okay?
` A. Correct.
` Q. Okay.
` A. And one comment, if I can make
`it, that I have gone just gone through a
`cold. So as you can hear probably, my throat
`is a little sore. So if I cough or if you
`can't hear anything right, please let me know
`and I will be happy to repeat it or do
`whatever it takes.
` Q. Okay. Thank you. Then, the
`final thing is that if you don't understand
`anything in my question, please ask me for
`clarification. Okay?
` A. Sure.
` Q. And if you don't ask for
`clarification, I am going to assume that you
`understood my question. Is that fair?
` A. Fair.
` Q. All right. Now, you understand
`that you are here today to be cross examined,
`do you understand that?
` A. Correct.
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` A. KYDONIEUS
` Q. And unlike the District Court
`proceedings, it is unlikely that you will
`give live testimony before the Board of the
`Patent Office in relation to these
`proceedings.
` Do you understand that?
` A. Yes.
` MR. COULSON: Objection to
` foundation.
` Q. And you understand that the whole
`transcript of today's deposition will go
`before the Patent Office Board, do you
`understand that?
` A. Yes.
` Q. And they will have the
`opportunity to read everything that you have
`said during the deposition today?
` A. Correct.
` Q. And you understand that they may
`have the opportunity to see the video of
`today's deposition?
` MR. COULSON: Objection.
` Just pause to let me object, if
` you don't mind.
`
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` A. KYDONIEUS
` THE WITNESS: Sure.
` MR. COULSON: I just object on
` foundation.
` But you can answer.
` Q. You understand they may see the
`video of today's deposition?
` A. Okay.
` MS. JACOBSEN: All right. I am
` going to mark a few documents. And by
` agreement, I am just going to give
` them an exhibit number and then we
` will provide you properly stamped
` copies tomorrow. One stamped with
` each IPR number and an updated exhibit
` list.
` Is that okay?
` MR. COULSON: Let's see how it
` goes. There is a number of rules that
` sounds fine. Let's see how it goes.
` MS. JACOBSEN: What is your
` concern?
` MR. COULSON: I don't have a
` concern at this point. But I haven't
` seen any exhibits yet. So it
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` A. KYDONIEUS
` sounds -- what you are proposing
` sounds fine to me from what I can see
` in front of me right now.
` MS. JACOBSEN: Okay. So this is
` going to be Exhibit 2006.
` (Whereupon, Exhibit 2006,
` Declaration of Agis Kydonieus in
` Patent No. 6,335,031 was marked for
` identification as of this date by the
` Reporter.)
` MS. JACOBSEN: That's going to
` be 2007.
` (Whereupon, Exhibit 2007,
` Declaration of Agis Kydonieus in the
` Patent 6,316,023 was marked for
` identification as of this date by the
` Reporter.)
` MR. COULSON: 2006 is the '031.
` 2007 is the '023.
`BY MS. JACOBSEN:
` Q. So, Dr. Kydonieus, you have been
`handed two exhibits. The first one should be
`labeled number Exhibit 2006. Do you have
`that?
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` A. KYDONIEUS
` A. Yes.
` Q. And is that your Declaration that
`you submitted in one of the IPR proceedings?
` A. Correct.
` Q. Exhibit 2006 relates to IPR
`2014-00550?
` A. Yes.
` Q. You see that it concerns the '031
`Patent?
` A. Correct.
` Q. Okay. If I refer to the '031
`Patent, you will know that's a reference to
`U.S. Patent No. 6,335,031?
` A. Correct.
` Q. And the other Declaration is
`marked 2007?
` A. Yes.
` Q. Is that the Declaration you
`submitted in Inter Partes Review No.
`2014-00549?
` A. Correct.
` Q. Does that relate to U.S.
`Patent 6,316,023?
` A. Correct.
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` A. KYDONIEUS
` Q. If I refer to that as the '023
`Patent, will you know what I'm talking about?
` A. Of course.
` Q. Great. Will you agree me that
`there's a great deal of overlap between the
`subject matters of these two declarations?
` A. Yes. I think it is -- a lot of
`overlap.
` Q. Okay. So I am generally going to
`refer just to one of them.
` A. Okay.
` Q. And I am generally going to refer
`to Exhibit 2006 that relates to the '031
`Patent.
` A. Very good.
` Q. I am going to assume the answers
`you give me today will apply equally to the
`'031 and the '023 Patents unless you tell me
`otherwise?
` A. Correct.
` MR. COULSON: Objection.
` Compound and vague.
` Q. I am also going to assume that
`answers you give me today about references
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` A. KYDONIEUS
`that you cite in both of the declarations
`apply to both of the IPR proceedings, okay?
` MR. COULSON: Objection. Vague.
` I have to clarify that in my mind.
` A. If it pertains to both. I don't
`know what references you're talking about, so
`I can't from now tell you that a particular
`reference may or may not apply.
` Q. All right. So to the extent that
`you rely on the same references --
` A. Should, yeah.
` Q. -- in both IPR declarations?
` A. The answer that I will give you
`would be on both, yes.
` Q. Okay. Thank you, Dr. Kydonieus.
`I would like to start with some of the
`statements in your IPR Declaration and that's
`Exhibit 2006, relating to the '031 Patent,
`and if you can turn to paragraph 41. And you
`can take your time to read as much of that,
`if you would like, but the first sentence I
`am interested in is -- it is the last
`sentence of the paragraph and that's on the
`top of page 22 of 49. You see there is a
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` A. KYDONIEUS
`statement there that says, "The person of
`ordinary skill would have understood that
`tocopherol would react with the free radicals
`and the acrylate more readily than the drug
`and thus prevent the oxidation and
`decomposition of the drug substance"?
` A. Okay.
` Q. I misspoke so I'll say it again.
`The sentence says, "The person of ordinary
`skill would have understood that tocopherol
`would react with the free radicals in the
`acrylate more rapidly than the drug and thus
`prevent the oxidation and decomposition of
`the drug substance"?
` A. Right.
` Q. Did I read that correctly?
` A. You read it correctly. And the
`answer to that is --
` Q. I haven't asked you a question
`yet. I just wanted to make sure that we were
`on the same page and you understood the part
`of your report that I want to ask questions
`about.
` A. Okay.
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` A. KYDONIEUS
` Q. So let me ask you my questions
`now.
` A. Ask your question.
` Q. My first question to you is, it's
`right that tocopherol is an antioxidant,
`correct?
` A. Tocopherol is an antioxidant.
` Q. It is a type of antioxidant that
`a POSA would understand to be a free radical
`scavenger?
` A. Yes. No, free -- yes, free
`radical scavenger. It would react, yes, with
`the free radicals, yes.
` Q. So that means that it reacts with
`the free radicals so that they cannot react
`with the drug and cause oxidative degradation
`of the drug; is that correct?
` MR. COULSON: Objection.
` Foundation.
` A. The tocopherol is an antioxidant
`that would stop the reactions of, let's say,
`radicals in the initiation step or in the
`propagation step. This is a little
`difficult, perhaps to understand what is
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` A. KYDONIEUS
`written there. But that -- it's certainly
`not a reducing agent, if that's what you are
`implying.
` Q. That's not what I am implying. I
`am just trying to make sure I understand how
`tocopherol helps to protect a drug from
`oxidative degradation. And in this paragraph
`you say that "tocopherol would react with the
`free radicals in the acrylate," do you see
`that?
` A. Yes.
` Q. So tocopherol reacts with the
`free radicals that cause oxidative
`degradation?
` A. Let me explain. It doesn't
`react, it will give a hydrogen to the -- to
`the free radical of the polymerization step.
`It will stop the reaction.
` Q. Okay. And it does that by -- if
`you don't like my wording react, interact is
`that a better word? It does that by
`neutralizing the free radicals; is that
`correct?
` A. The free radical in the
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` A. KYDONIEUS
`polymerization step.
` Q. The polymerization step or in the
`polymer?
` A. Well, in the initiation step and
`in the propagation step of the reaction, or
`if the reaction is completed and you have
`polymer that has some free radicals, it would
`react with those and stop any reaction taking
`place with the drug.
` Q. Okay. So assume that we have a
`polymer that's been created and it still
`contains some free radicals?
` A. Right.
` Q. And we can add an antioxidant
`like tocopherol, which will neutralize the
`free radicals in that polymer so that they
`don't cause degradation of a drug that would
`otherwise undergo oxidative degradation. Is
`that fair?
` A. That's my opinion, yes. Of
`course, you should provide that question to
`Dr. Schöneich, who is the expert in radical
`reactions but that's my opinion.
` Q. Dr. Kydonieus, you are here
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` A. KYDONIEUS
`offering an opinion about the person -- what
`the person of ordinary skill in the art would
`have understood about tocopherol, correct?
` A. Correct.
` Q. Okay. So that's why I am asking
`you questions about how tocopherol works.
` A. Right.
` Q. And a person of ordinary skill in
`the art would understand that tocopherol
`doesn't protect a drug from oxidative
`degradation by directly reacting with the
`drug; is that correct?
` MR. COULSON: Objection.
` Foundation.
` A. By reacting with the drug?
` Q. Yes.
` A. The tocopherol wouldn't react
`with the drug.
` Q. That's not how it protects from
`oxidative degradation. It reacts or it
`neutralizes free radicals rather than
`reacting with the drug; is that correct?
` A. Well, if --
` MR. COULSON: Objection.
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` A. KYDONIEUS
` A. If it reacts with the drug, it
`would not protect the drug. It would
`decompose the drug.
` Q. Right. That's not how tocopherol
`works to protect a drug from oxidative
`degradation?
` A. Let me explain a little bit here.
`Tocopherol cannot react with the drug because
`if it reacted with the drug it would not --
`it would decompose the drug. It would affect
`the drug. So that's not the question.
`Tocopherol is an antioxidant, and
`antioxidants reduce to the oxidation of
`compounds and that's what tocopherol does.
` I don't know how else to explain
`it. You are asking some questions that they
`don't quite make any difference. Tocopherol
`is an antioxidant and by its definition of
`being an antioxidant will protect the drug
`from decomposition, oxidative decomposition.
` Q. Okay. Now, a person of ordinary
`skill in the art in 1998 would know there
`were other types of antioxidants other than
`free radicals scavengers, correct?
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` A. Right. Reducing agents.
` Q. Exactly. A person of ordinary
`skill in the art would understand that the
`reducing agents also protect a drug from
`oxidative degradation by neutralizing the
`oxidizing species in the composition. Is
`that fair?
` A. Yes. Basically, they are
`sacrificial. They react -- those are the
`ones that react basically before the drug can
`react with the oxidizing components.
` Q. And they react with the oxidizing
`agents more rapidly than the drug does with
`the oxidizing agent?
` A. That's the way they work.
` Q. Okay.
` A. The reducing agent antioxidants.
` Q. And they don't protect the drug
`by directly reacting with the drug itself?
` MR. COULSON: Objection.
` Foundation.
` A. I don't understand that question.
`Because you mentioned that two or three
`times. Things don't react with the drug.
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` A. KYDONIEUS
`Because if they reacted with the drug, they
`would decompose the drug. So the
`antioxidants don't react with the drug.
` Q. Okay. That's fine. Now if we
`can turn back to paragraph 40 in your IPR
`Declaration and that's of Exhibit 2006. And
`this is, again, the last sentence of the
`paragraph, and you say, "Sasaki teaches using
`an amount of tocopherol of 0.005 to 5% by
`weight relative to the acrylic adhesive of
`the patch and a preferred amount of 0.05 to
`1% weight percent."
` Did I read that correctly?
` A. Yes.
` Q. Okay. So in Sasaki, the amount
`of antioxidant is a percentage of the amount
`of adhesive; is that right?
` A. Yes, and I have calculated, of
`course, the amount of antioxidant in the
`formulation.
` Q. That means the larger the amount
`of adhesive in the formulation, the larger
`the amount of antioxidant that the
`composition is going to contain?
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` A. KYDONIEUS
` A. That's what I -- I haven't really
`thought about that. But basically that's
`what I think it says in effect.
` Q. Okay. And is that because if you
`have a larger amount of adhesive, you are
`going to have a larger amount of free
`radicals potentially and so you add a larger
`amount of antioxidant?
` MR. COULSON: Objection. Vague.
` A. Reactions are basically, taking
`place when two molecules collide. And the
`reactions are, basically, controlled by
`statistical. Statistics. The
`Maxwell-Boltzmann statistics. So that's why
`the handbook gives us ranges of antioxidants
`-- ranges of amounts of antioxidant that can
`be used. So for each formulation you have,
`you have to do some work in effect to decide
`the exact amount that you have to use, which
`would be the least amount and the one that
`would give you the best performance.
` Q. Right. What -- that's not my
`question, Dr. Kydonieus. What I am trying to
`understand is, your understanding or POSA's
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` A. KYDONIEUS
`understanding of why Sasaki teaches that the
`amount of antioxidant added should be
`calculated based on the amount of adhesive in
`the formulation?
` A. Because the amount of the
`adhesive is the component that has the
`oxidative species on it.
` Q. If I have -- so if I have more
`adhesive, I have the more oxidizing species,
`I want to add more antioxidant; is that
`right?
` MR. COULSON: I object as vague
` without having Sasaki here. Exhibit
` 1005.
` MS. JACOBSEN: I just object to
` that objection as an improper speaking
` objection and comes very close to the
` examples in the practice guideline
` that are expressly prohibited in an
` IPR deposition.
` Q. Go ahead, Dr. Kydonieus.
` A. Could you repeat the question?
` Q. Absolutely.
` A. Between all the questions.
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` A. KYDONIEUS
` Q. My question to you is, so if I
`have more adhesive, I have more oxidizing
`species, I would want to add more
`antioxidant; is that right?
` A. Well, not necessarily. Because
`everything is dependent on the formulation.
`And we have said that many times before.
`Like, if you take the oxygen out, you don't
`need any antioxidant at all or the oxidizing
`species in some way. So it does not say
`that. And the answer I gave you before is
`the real answer, which you said it wasn't the
`answer. But that's the answer.
` Q. Right. But I am -- you referred
`to the handbook. I am not asking you about
`the handbook. I am asking you about Sasaki,
`okay?
` A. Okay.
` Q. And your statement in your
`Declaration that "Sasaki teaches adding an
`amounts of antioxidant relative to the
`acrylic adhesive of the patch."
` And my question to you is, why
`would a POSA understand Sasaki to be teaching
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` A. KYDONIEUS
`that the amount of antioxidant added should
`be based on the amount of acrylic adhesive in
`the composition?
` A. Right.
` MR. COULSON: Objection.
` Compound.
` A. Excuse me.
` Q. You can go ahead.
` A. Because Sasaki says that the
`component that causes the oxidation is in the
`acrylic adhesive. And that is what he
`addresses. I mean, if there is nothing else
`in there, the only oxidative products come
`from the adhesive, that's what you're trying
`to address.
` Q. Okay. Can you turn to
`paragraph 25. You say in the first line
`there, you make a reference to "drug
`excipient interactions," do you see that?
` A. Yes.
` Q. So a POSA in 1998 would be aware
`that a drug and excipient can interact and
`cause degradation of a drug, correct?
` A. Correct.
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` A. KYDONIEUS
` Q. And if that happens, then a POSA
`refers to that as the drug and excipient as
`being incompatible; is that correct?
` A. Correct.
` Q. And you made reference --
` A. Of course incompatibility can be
`other aspects, but this is one aspect of
`incompatibility, if it reacts. Probably the
`worst kind of incompatibility.
` Q. Right. It is a broader term, but
`it encompasses an interaction between the
`drug and the antioxidant and that causing
`degradation of the drug?
` A. Well, what I was trying to say is
`that there are other instabilities, other
`instabilities that could affect in some way
`the increased stability of the drug. It
`could affect other things other than
`oxidation, but we are talking about oxidation
`here. Yes, if you have a real covalent
`reaction taking place between the drug and
`the excipient, you have a real problem.
` Q. The drug could -- the drug and
`excipient interaction could cause degradation
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` A. KYDONIEUS
`other than oxidation degradation, correct?
` A. Yes.
` Q. You mentioned before the Handbook
`of Pharmaceutical Excipients?
` A. Yes.
` Q. And we can look at it if we need
`to, but it is only one question that I have.
`I believe you mentioned at trial that, there
`is a section in the Handbook of
`Pharmaceutical Excipients that mentions known
`incompatibilities; is that right?
` A. Yes.
` Q. And I think you said there were
`no reported incompatibilities between
`antioxidants and amine drugs; is that right?
` A. No, I didn't say that. I don't
`think I could say that because that means I
`know all the antioxidants and all the
`incompatibilities. So if some that was,
`somebody understood that, it certainly not
`what I said or what I meant to say. Because
`I do not know all the possible
`incompatibilities of all the antioxidants
`with all of the amines.
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` A. KYDONIEUS
` Q. Okay. That's fine.
` Would you agree that the POSA
`could look to the Handbook of Pharmaceutical
`Excipients and see if there were any reported
`incompatibilities?
` A. Yes.
` Q. And would the absence of any
`reported incompatibility in the Handbook of
`Pharmaceutical Excipients give the POSA
`comfort that it was unlikely that they would
`have a problem?
` A. You said the right word.
`Comfort. Because in the end -- if it is an
`excipient, a new excipient, it might cause a
`problem. And the handbook does not
`necessarily -- has also tested all the
`antioxidants or the antioxidants that we are
`talking about with all the drugs to tell us
`what might be a possibility of reaction.
`They have -- they are indicating that from
`knowledge of some work that has been done
`that the antioxidant would work fine with
`amines and with another compound, but it
`doesn't necessarily tell you all the possible
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` A. KYDONIEUS
`compounds and all the possible
`functionalities. Because, honestly, nobody
`knows that.
` Q. So the absence of teaching in the
`handbook that there is no problem with
`incompatibility doesn't tell you or -- sorry.
` A. Necessarily that, yes, it doesn't
`tell you necessarily that you will not have
`an incompatibility.
` Q. So you would have to conduct a
`test with your antioxidant and your drug and
`find out whether in fact you have a problem
`with incompatibility?
` A. Well, there is a lot of
`knowledge. If we are talking about, now,
`antioxidants and drugs, there is a lot of
`knowledge. I was talking generally about
`excipients and drugs. But antioxidants and
`drugs we know quite a bit for each
`antioxidant and incompatibilities with types
`of drugs, so a lot of that, perhaps, is in
`the handbook. This kind of incompatibilities
`and there are, honestly, if these
`incompatibilities we are talking about are
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` A. KYDONIEUS
`few and far between.
` As I think I mentioned previously
`to you, I have worked with BHT, which is my
`preferred antioxidant, and I have worked with
`maybe 20, 25 drugs where I have put BHT, and
`I have never seen incompatibility.
` Q. So with respect to antioxidants,
`because of the work that you say has been
`done, the absence of a reported problem in
`the Handbook of Pharmaceutical Excipients
`would indicate to a POSA that there is
`unlikely to be a problem with
`incompatibility?
` A. I think you have to repeat that
`because there were too many this way and that
`way and I didn't understand the question.
` Q. Sure. With respect to
`antioxidants, the absence of a reported
`problem in the Handbook of Pharmaceutical
`Excipients would indicate to a POSA that it
`is unlikely there would be a problem with
`incompatibility?
` A. To a large degree, yes.
` Q. Okay.
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` A. KYDONIEUS
` A. But, again, not everything,
`right. I think I told you that before in my
`previous discussions. I don't like
`conclusions that encompass everything.
`Because you will always find something that
`does not obey the rule. So if we are going
`to say most, I would like that. In most
`cases.
` Q. Okay.
` MS. JACOBSEN: Mark another
` document.
` (Whereupon, Exhibit 2008, UK
` patent application 2,203,040 A was
` marked for identification as of this
` date by the Reporter.)
`BY MS. JACOBSEN:
` Q. So you have been handed a
`document that's been marked Exhibit 2008; is
`that right?
` A. Yes.
` Q. And it is UK patent application
`GB 2,203,040 A?
` A. Correct.
` Q. Okay. And is this the Enz
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