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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`--------------------------------)
`PAR PHARMACEUTICAL, INC., )
`BRECKENRIDGE PHARMACEUTICAL, )
`INC., and ROXANE LABORATORIES, )
`INC., )
` Petitioners, )
` )
` vs. ) Case IPR2016-00084
` ) U.S. Patent No.
`NOVARTIS AG, ) 5,665,772
` )
` Patent Owner. )
`--------------------------------)
`
` DEPOSITION OF ALEXANDER M. KLIBANOV, Ph.D.
` New York, New York
` November 14, 2016
`
`Reported by: BONNIE PRUSZYNSKI, RMR, RPR, CLR
`JOB NO. 115233
`
`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0001
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`--------------------------------)
`PAR PHARMACEUTICAL, INC., )
`BRECKENRIDGE PHARMACEUTICAL, )
`INC., and ROXANE LABORATORIES, )
`INC., )
` Petitioners, )
` )
` vs. ) Case IPR2016-00084
` ) U.S. Patent No.
`NOVARTIS AG, ) 5,665,772
` )
` Patent Owner. )
`--------------------------------)
`
` DEPOSITION OF ALEXANDER M. KLIBANOV, Ph.D.
` New York, New York
` November 14, 2016
`
`Reported by: BONNIE PRUSZYNSKI, RMR, RPR, CLR
`JOB NO. 115233
`
`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0001
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`Page 2
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` November 14, 2016
` 9:11 A.M.
`
` DEPOSITION OF ALEXANDER M.
` KLIBANOV, Ph.D., held at the offices of
` Fitzpatrick, Cella, Harper & Scinto, 1290 Avenue
` of the Americas, New York, New York, before Bonnie
` Pruszynski, a Registered Professional Reporter,
` Registered Merit Reporter, Certified Livenote
` Reporter, and Notary Public of the State of New
` York.
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0002
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`Page 3
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`A P P E A R A N C E S:
`
`FITZPATRICK CELLA HARPER & SCINTO
`Attorneys for Patent Owner
` 1290 Avenue of the Americas
` New York, New York
`BY: CHRISTINA SCHWARZ, ESQ.
` JARED STRINGHAM, ESQ.
` LISA BUTLER, ESQ.
`
`LATHAM & WATKINS
`Attorneys for Par Pharmaceuticals
` 330 North Wabash Avenue
` Chicago, Illinois 60611
`BY: DANIEL BROWN, ESQ.
` BRENDA DANEK, ESQ.
` JONATHAN STRANG, ESQ.
`
`MERCHANT & GOULD
`Attorneys for Breckenridge Pharmaceutical, Inc.
` 1900 Duke Street
` Alexandria, VA 22314
`BY: MARY BRAM, ESQ. (telephonic appearance)
`
`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0003
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`Page 4
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` A. Klibanov
` (Witness sworn.)
` ALEXANDER M. KLIBANOV, Ph.D.,
` called as a witness, having been first
` duly sworn, was examined and testified
` as follows:
`EXAMINATION
`BY MR. BROWN:
` Q. Good morning, Dr. Klibanov.
` A. Good morning, Mr. Brown. 09:11
` MR. BROWN: Could we just go ahead
` and mark his declaration.
` A. Thank you.
` Q. So, Doctor, I have shown you what's
` been marked as Novartis 2092. Do you 09:11
` recognize this document?
` A. It seems to be a portion of my
` declaration.
` Q. And by a portion of your
` declaration, do you mean excluding the 09:12
` exhibits?
` A. Yes.
` Q. And other than excluding the
` exhibits, does this appear to be the textual
` portion of your declaration? 09:12
`
`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0004
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` A. Klibanov
` A. It seems that way. Of course, I
` haven't compared it with what I recall my
` declaration to be. But the signature on
` page 99 is clearly a facsimile of my 09:12
` signature. It seems to be my declaration.
` And on this note, sir, at your
` convenience, as I was reviewing my
` declaration in my hotel room yesterday, I
` found a couple of clerical errors that I 09:12
` would like to correct when it's convenient
` for you.
` Q. Why don't you show me what those
` are now.
` A. Sure. 09:13
` (Discussion held off the record.)
` (Mary Bram is present by phone.)
` MS. SCHWARZ: Is there anyone else
` on the line?
`BY MR. BROWN: 09:15
` Q. Could you find -- oh, let's -- I'm
` sorry. Where we were before the break, you
` were going to point out clerical issues or
` other errors in your report.
` A. There are no other errors. There 09:15
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0005
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` A. Klibanov
` are two clerical errors.
` The first one is on page 20,
` footnote four. The second line of footnote
` four, the third and the fifth words there, in 09:15
` the middle of those words, instead of AC, it
` should be K. So, both of those words should
` read as "hemiketal" or "hemiketals," plural,
` as far as the fifth word is concerned.
` Q. Okay. 09:16
` A. That is number one.
` And for the second one, page 89,
` paragraph 158, the fifth line from the
` bottom, the word "size" there should be
` "surface" instead of "size." And that, so 09:16
` just to explain, this is actually a quotation
` from a book by Ansel, A-N-S-E-L, and the
` typographical error is in the original. So I
` correctly cited the statement from Ansel, but
` there is an error in the original, which I 09:17
` noted at the time, and I meant to provide the
` footnote explaining it, but sadly, I forgot,
` so -- and I apologize for both of these.
` Q. With those two corrections, does
` Novartis Exhibit 2092 accurately reflect the 09:17
`
`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0006
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` A. Klibanov
` opinions you have provided in this matter?
` A. Yes.
` Q. I would like to turn to
` paragraph 22 of the report. 09:17
` A. Yes, sir.
` Q. And in this opinion, you have, or
` in this paragraph, you have provided your
` opinion as to the qualifications of a
` hypothetical person of ordinary skill in the 09:18
` art as of October 9th, 1992, and I want to
` ask you a few questions about that.
` A. Please.
` Q. First you state the individual
` would have had a Ph.D. in medicinal or 09:18
` organic chemistry.
` A. Yes.
` Q. What is medicinal chemistry?
` A. Medicinal chemistry is pretty much
` organic chemistry plus investigations of 09:18
` structure-activity relationships in molecules
` with biological activity. First of all, it's
` an area of organic chemistry that
` specifically concerns medicinally relevant
` compounds, and furthermore, within that area, 09:19
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0007
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` A. Klibanov
` it typically includes investigation of
` structure, structure-activity relationships
` of the molecules involved.
` Q. Does that field, specifically 09:19
` medicinal chemistry, include modifying
` molecules in order to alter their medicinal
` properties?
` A. Yes.
` Q. Doctor, are you a medicinal 09:19
` chemist?
` A. I consider myself a medicinal
` chemist. My Ph.D., back in Russia many years
` ago, was in the area that was called chemical
` enzymology, which involved, among other 09:20
` things, investigation of interactions of drug
` molecules with enzymes that are their targets
` in the body, and similar things.
` So, although they called it
` differently, it was what in this country 09:20
` would be called a portion of medicinal
` chemistry area, and furthermore, a lot of my
` work since I received my Ph.D., which sadly
` was many, many years ago, has involved
` medicinal chemistry, that is, modifying the 09:21
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0008
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`Page 9
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` A. Klibanov
` structure of potential drug candidates or a
` lead candidate to enhance pharmaceutical
` activity. This is both my work at MIT, some
` of which has been published, and also my work 09:21
` with clients or in the companies that I
` myself have started.
` Q. Have you ever modified the
` structure of a pharmaceutical compound with
` the intent of increasing its solubility? 09:22
` A. If you are talking about -- when
` you are saying "solubility," are you
` referring specifically to the solubility in
` water, or you are talking about any kind of a
` solubility? 09:22
` Q. Let's start with any kind of
` solubility. Why don't I reask the question
` so that it's clear.
` A. Sure.
` Q. Have you ever modified the 09:22
` structure of a pharmaceutical compound with
` the intent of increasing its solubility in
` any particular solvent?
` A. Yes.
` Q. What examples can you give me of 09:23
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0009
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` A. Klibanov
` where you have done that?
` A. We have done a lot of work on --
` when I am saying "we," I am referring to my
` laboratory at MIT -- a lot of work on 09:23
` modifying peptides and proteins to enhance
` their solubility in organic solvents.
` Actually, to vary their solubility in organic
` solvents, both to increase it and decrease
` it, and create a structure-activity 09:23
` relationship. This is an example.
` Q. For what reason would you be trying
` to decrease the solubility of a peptide or
` protein in an organic solvent?
` A. We were -- among other things, we 09:24
` were specifically interested in how the
` biological activity, in particular enzymatic
` activity, say, correlates with the solubility
` in organic solvents. So, we would measure on
` the one hand, for example, enzymatic 09:24
` activity, and on the other hand the
` solubility of an enzyme in organic solvents,
` with the goal being to ascertain whether
` enzymatic activity is affected by whether the
` enzyme is dissolved or merely suspended in an 09:24
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0010
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` A. Klibanov
` organic solvent.
` Q. Have you ever modified the
` structure of a pharmaceutical compound with
` the intent to increase its water solubility? 09:25
` A. Yes.
` Q. Can you give me examples of when
` you have done that?
` A. Some of the examples I may not be
` able to describe the specifics, because they 09:25
` were done under confidentiality agreements
` with companies that I have consulted for.
` One example that I can give you is that some
` years ago, I would say maybe 15, 18 years
` ago, one of the companies I started, I think 09:26
` it was company number five that I started
` over the years, a company called EnzyMed,
` E-N-Z-Y capital M-E-D, we had a contract from
` a pharmaceutical company that wanted to
` explore approaches to increase the solubility 09:26
` in water of the drug taxol, T-A-X-O-L, I
` guess. I'm not a great speller. I have to
` apologize in advance.
` Q. What chemical modification did you
` make or propose to increase the solubility of 09:27
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0011
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` A. Klibanov
` taxol?
` A. Again, it was many years ago. My
` memory is necessarily a little foggy. But as
` I recall, the approach that we explored was 09:27
` introducing a charge in a taxol molecule in
` order to hopefully enhance its solubility in
` water.
` Q. In your work on taxol, did you
` ever -- let me restate the question. 09:28
` In your work on taxol, were you
` directly responsible for the synthesis of the
` compound, or were you making recommendations
` to someone else?
` A. I have to say that I haven't done 09:28
` anything noteworthy in the lab with my own
` hands over the last at least quarter of a
` century, and I am sure the same applies to
` Dr. Jorgensen. So, I was a scientific
` advisor and part-time research director, so I 09:28
` was making suggestions to the folks who were
` actually doing experiments in the lab.
` Q. And do you recall what specific
` substitutions you recommended to taxol?
` A. I remember that -- again, I don't 09:28
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`Ex. 1114-0012
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` A. Klibanov
` have a vivid recollection of what functional
` groups we modified at the moment, but I do
` remember that I suggested, and that's what I
` would suggest today as well, is introducing 09:29
` amino groups and carboxyl groups into the
` molecule by appropriate means in order to
` create either an acid or a base out of the
` molecule, so that at the physiologically
` relevant pH, it will be either negatively 09:29
` charged, in the case of an acidic group
` introduced, or positively charged, in the
` case of an amino group introduced.
` Q. Do you recall approximately how
` many drug candidates were made using taxol as 09:29
` a lead compound in that effort that you
` discussed?
` A. We were a small company. We just
` had a few researchers. I want to say a few,
` certainly more than one, but I would say 09:30
` probably less than ten. So, somewhere in
` that range.
` But again, the -- the project
` didn't reach its full fruition, if you will,
` because for better or worse, EnzyMed was 09:30
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0013
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` A. Klibanov
` bought by another company while this project
` was in progress, and what the other company
` did, I don't know. I did not establish a
` relationship with it. 09:30
` Q. In the time period of October 9th,
` 1992, what were you doing professionally at
` that time?
` A. I am sure I was doing a lot of
` things, but what might be helpful is if I 09:31
` could take a look at my curriculum vitae and
` the list of publications, and this will give
` me some ideas of what I was doing at MIT.
` Thank you.
` Q. So, I have handed you Novartis 09:31
` Exhibit 2402. Do you recognize this
` document?
` A. Yes. It seems to be a copy of my
` curriculum vitae.
` Q. And with this document in front of 09:32
` you, can you tell me professionally what you
` were doing in the time period around
` October 9th, 1992? Let me be a little more
` general. The time period of 1991-1992.
` A. Okay. Well, I will just mention 09:32
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0014
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` A. Klibanov
` several things that we were doing at MIT, and
` at that time I had a fairly large group at
` MIT.
` So, we were using enzymes as 09:32
` catalysts in organic synthesis. We were also
` investigating stability of lyophilized or
` freeze-dried, it's an equivalent term,
` proteins, including some pharmaceutically
` active proteins. 09:33
` We were investigating properties of
` enzymes in organic solvents. We were also
` exploring the properties of proteins in
` organic media. We were studying stability of
` biologically active molecules in various 09:34
` media. Examining selective modification of
` bioactive molecules. We were doing modeling
` of biological processes in organic solvents.
` So, things like that.
` Q. Have you ever in your career worked 09:35
` with rapamycin?
` A. Yes.
` Q. During what time frame?
` A. It was that same time frame, about
` 15 years ago, maybe 18 years ago. It was 09:35
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`Ex. 1114-0015
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` A. Klibanov
` also at EnzyMed, so it was early in the
` century.
` Q. And in general terms, what were you
` doing research-wise with respect to 09:35
` rapamycin?
` A. At that time, as I just indicated
` when I answered your question about what I
` was doing at that time, we were very
` interested in controlling enzyme selectivity 09:36
` in organic solvents, and in particular, by
` varying the solvent as well as the enzyme
` itself. And several papers that I saw there
` about -- kind of sort of reflected that, but
` this work at EnzyMed started later, because 09:36
` it specifically involved some bioactive
` compounds, and what we were interested in, in
` the case of rapamycin, is rapamycin has
` two -- I'm sorry, it has three hydroxyl
` groups that can be easily, relative easily 09:37
` acylated, and many of the technologies that
` we had previously developed involved
` reactions that are called
` transesterifications, whereby you
` enzymatically react the hydroxyl group with 09:37
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`Ex. 1114-0016
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` A. Klibanov
` an ester, producing an ester of that hydroxyl
` group and an alcohol.
` So, we were interested in exploring
` and did explore to some extent whether by 09:37
` changing either the enzyme itself or the
` solvent, or both, you can modify either one
` hydroxyl group, for example, C40 hydroxyl
` group of rapamycin, or C28, or the third one,
` which I believe is C10 or C12. I don't 09:38
` remember right now.
` So, three hydroxyl groups, and we
` wanted to see whether we can carry out
` selective modification using enzymes, and
` whether we can control the selectivity of 09:38
` this modification. So that was kind of the
` broad focal point of our studies.
` Q. And the time frame of that work was
` around the 2000 time frame?
` A. Yeah. I would say 2000, 2001, 09:38
` 2002. So early in this century.
` Q. Had you ever worked with rapamycin
` before that time frame?
` A. I don't specifically recall one way
` or another, so I don't remember. 09:39
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0017
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` A. Klibanov
` Q. If you could turn to -- can you
` turn to Reference 137 on page 12 of your CV
` in Novartis Exhibit 2402.
` A. Sure. 09:40
` Q. And this is a publication by
` Fitzpatrick, P.A. and yourself, and the title
` of it is, "How can the solvent affect enzyme
` enantioselectivity?"
` A. Yes. 09:40
` Q. Do you recall what you were
` studying in this paper?
` A. Well, I mean, what I recall is
` based on what the title of the paper is, so
` we were clearly investigating 09:40
` enantioselectivity of enzymes in organic
` solvents, and specifically we were
` interested, and I published several papers in
` this area, we were interested -- including
` this one -- we were interested in how one can 09:40
` alter and ideally control the
` enantioselectivity of an enzyme toward a
` given substrate simply by altering the nature
` of the solvent.
` Q. And what is enantioselectivity? 09:41
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`TSG Reporting - Worldwide 877-702-9580
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`Ex. 1114-0018
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` A. Klibanov
` A. Enantioselectivity is the ability
` to distinguish between two optical isomers or
` enantiomers of an organic molecule.
` Q. And in general terms, was the 09:41
` subject of the work in Reference 137 using
` enzymes to synthesize organic molecules?
` A. To synthesize or to modify them
` selectively in the way that is partial, if
` you will, to one enantiomer over the other. 09:42
` Q. Was this work considered to be of
` use in the pharmaceutical industry?
` A. Potentially. At that time, we were
` just setting the -- the general principles of
` that, the principles that we discovered. 09:42
` Later on, this work was widely used, both by
` us and by others in the pharmaceutical
` industry, to catalyze difficult to carry out
` enzymatic transformations, in particular
` those involving chiral molecules, of which 09:42
` many pharmaceutically active molecules are.
` Q. In your last answer you stated that
` many pharmaceutically active molecules are
` chiral molecules. Could you just explain for
` the record what that means? 09:44
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0019
`
`
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` A. Klibanov
` A. Well, many pharmaceutically active
` molecules have at least one, frequently more
` than one, chiral carbon. And that includes
` such molecules as rapamycin or everolimus 09:44
` that are relevant to this case. Meaning in a
` simplistic way that you have at least one
` carbon atom in that molecule, where all four
` substituents are different, thereby making
` that carbon chiral or, using the current 09:44
` proper terminology, stereogenic.
` Q. Was it known as of 1991, when you
` were working on enantioselectivity, that the
` chirality of a pharmaceutical molecule could
` be relevant to its activity? 09:45
` A. Yes, it was well known that it was
` relevant to its activity, and not just
` activity, but also other properties, such as
` toxicity, for example, and others.
` Q. I would like to go back to 09:46
` paragraph 22 in your -- I am tempted to call
` it an expert report -- expert declaration.
` A. Yes, sir.
` Q. In the last sentence of
` paragraph 22, you state a person of ordinary 09:46
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0020
`
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` A. Klibanov
` skill in the art here "would be working in
` the field of drug discovery together with
` individuals possessing knowledge and skills
` that he or she might not possess through 09:46
` formal training or personal experience,
` including someone with experience in
` immunology, antitumor agents, and formulation
` development."
` And my first question for you is: 09:47
` Do you have any experience in the field of
` immunology?
` A. Some.
` Q. What experience do you have?
` A. Well, I have worked with antibodies 09:47
` for many years. I have evaluated the
` biological activity of antibodies as a
` function of the environment in which they
` are.
` One of the companies that I 09:48
` founded, company number seven, which was sold
` on Friday, specifically focused on using
` commercial monoclonal antibodies as
` pharmaceuticals, and specifically on
` improving the convenience for the patient in 09:48
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0021
`
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`
` A. Klibanov
` administering those antibodies to patients.
` So, I have done a lot of work with
` antibodies and studying their properties and
` delivery and applications and stability. 09:48
` Q. Do you have any experience in
` immunology other than using antibodies?
` A. I mean I'm not an immunologist
` per se, but I -- if you are asking me whether
` I was ever involved in sort of, you know, 09:49
` basic elucidation of immunological
` properties, again, in some companies that I
` have been involved with, they were
` specifically coupling enzymes -- I'm sorry,
` coupling antibodies with other entities using 09:49
` antibodies as a delivery vehicle, if you
` will, for the delivery of a particular drug.
` So, for example, you can -- and I have been
` involved in such studies -- you can
` covalently couple a drug to an antibody, and 09:49
` the antibody will be specific to an antigen
` present, for example, in the surface of
` cancer cells, and this -- by virtue of this
` selectivity of the antibody to the surface of
` cancer cells, this conjugate will deliver a 09:50
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0022
`
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`
` A. Klibanov
` drug specifically to a cancer cell as opposed
` to a normal cell.
` Q. Have you ever been involved in --
` let me restate the question. 09:50
` Have you ever been involved in
` research regarding an immunosuppressive drug?
` A. Well, I already previously
` indicated to you that I had worked with
` rapamycin. Rapamycin is an immunosuppressive 09:51
` drug, so I guess the answer is yes.
` Q. Did your work with rapamycin
` involve evaluating the activity -- its
` activity or the activity of any derivatives
` you made as immunosuppressants? 09:51
` A. That I do not recall,
` unfortunately.
` Q. Do you have any experience, for
` example, running assays to determine if a
` drug would have immunosuppressant activity? 09:51
` A. I mean, I am familiar with such
` studies. I mean, I obviously follow the
` literature in general in this area, and with
` some of my clients, I have been involved in
` evaluating things like allograft rejection, 09:52
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0023
`
`
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`
` A. Klibanov
` sort of things of that sort. I wouldn't say
` that it's the primary area of my interest or
` my expertise.
` Q. Dr. Klibanov, do you have any 09:52
` financial relationship with Novartis
` Corporation?
` A. None.
` Q. I noticed on your CV at some point
` that your title is the Novartis -- I believe 09:54
` the Novartis Endowed Chair Professor. Can
` you describe what that signifies?
` A. Yes. About 50 years ago, give or
` take, a Swiss company named Ciba-Geigy,
` C-I -- you know, Ciba-Geigy, gave a gift to 09:55
` MIT to establish an endowed professorship for
` one or two professors in the area of
` chemistry to acknowledge their outstanding
` work in the area related to pharmaceutical
` applications. It was a charitable gift, and 09:56
` MIT has dozens, if not hundreds of gifts like
` that from various companies.
` The condition of the gift is that
` the donor corporation has no say in who gets
` that professorship. It's just a gift to MIT, 09:56
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0024
`
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`
` A. Klibanov
` and then it's MIT's discretion as to who to
` give it to.
` Now, Ciba-Geigy has undergone
` several corporate transformations, and the 09:56
` most recent one, in the most recent
` incarnation, it is Novartis or a fraction of
` it is Novartis. And my distinguished
` colleague at MIT, Professor JoAnne Stubbe,
` S-T-U-B-B-E, and I currently are holders of 09:57
` this chair.
` I -- through this professorship, I
` have not had any interactions with Novartis.
` Now, I have had interactions with Novartis
` through some of the expert witness work that 09:57
` I have done where I have testified both on
` behalf of Novartis and against Novartis or
` its entities. But as far as my MIT title is
` concerned, it has nothing to do and does not
` entail any relationship with Novartis at all. 09:58
` Q. Actually, we need to take just a
` quick break. We have an exhibit malfunction.
` A. Sure.
` Q. We need to take a few minutes to
` fix it. 09:58
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0025
`
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`Page 26
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` A. Klibanov
` (Recess from 9:58 to 10:08 a.m.)
`BY MR. BROWN:
` Q. Doctor, if we could turn -- I have
` shown you Novartis Exhibit 2120. Do you 10:08
` recognize this as a copy of the '772 patent
` that is in suit?
` A. Yes, I do.
` Q. And if you could turn to column
` one. 10:09
` A. Yes.
` Q. And I would like to focus on a
` portion of column one that you discussed in
` your declaration. It runs from line 36 to
` line 40. And I'm going to read the previous 10:09
` sentence to get the antecedent.
` It says, "Rapamycin is an extremely
` potent immunosuppressant and has also been
` shown to have antitumor and antifungal
` activity. Its utility as a pharmaceutical, 10:09
` however, is restricted by its very low and
` variable bioavailability, as well as its high
` toxicity. Moreover, rapamycin is highly
` insoluble, making it difficult to formulate
` stable galenic compositions." 10:10
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0026
`
`
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` A. Klibanov
` And my first question for you is:
` Is it your opinion that Novartis, and
` particularly the '772 patent inventors, were
` the first to discover that rapamycin was 10:10
` highly insoluble?
` MS. SCHWARZ: Objection to form.
` A. My understanding of this particular
` portion of the patent in suit, the '772
` patent, and specifically of the last sentence 10:10
` that you read, the sentence that starts with
` "moreover," is that this statement, the one
` that starts with "moreover," reflects
` Novartis' view based on its own work that led
` to the '772 patent. 10:11
` Q. And how did you come to that
` understanding, specifically that the
` statement that rapamycin is highly insoluble
` reflected Novartis' own work?
` MS. SCHWARZ: Objection to form, 10:11
` lack of foundation.
` A. I have reviewed everything that
` Dr. Jorgensen -- shall I spell Jorgensen?
` J-O-R-G-E-N-S-E-N. I reviewed all the
` references asserted by Dr. Jorgensen, and I 10:12
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0027
`
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` A. Klibanov
` did not see a statement like that there.
` Furthermore, throughout my own
` research and work on this case, I reviewed
` some other references as well. And in them, 10:12
` I also didn't see a statement like that
` there.
` Therefore, I arrived at the
` conclusion that this assessment must
` represent Novartis' own assessment, because 10:12
` as I said, I didn't see it in any prior
` literature, including the three references
` that precede the first statement that you
` read, the references that are listed in
` column one, lines 32 through 34, of the '772 10:13
` patent.
` Q. Did you perform or direct to have
` performed any literature study to see if the
` insolubility of rapamycin was reported in the
` literature? 10:13
` MS. SCHWARZ: Objection to form.
` A. I am not even sure that I would
` agree -- I think the short answer to your
` question is no, but I don't even agree with
` the premise of the question. I don't 10:13
`
`TSG Reporting - Worldwide 877-702-9580
`
`Ex. 1114-0028
`
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` A. Klibanov
` necessarily agree that a person of ordinary
` skill in the art would view rapamycin's
` solubility in water as -- would characterize
` rapamycin in water as highly insoluble. 10:14
` I mean, the prior art, including,
` for example, Morris, M-O-R-R-I-S, reported
` the solubility of rapamycin in water, which
` is roughly
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