`
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` CASE NO.: IPR2013-00401
` Patent 5,527,533
`
`CYANOTECH CORPORATION,
` Petitioner,
`vs.
`THE BOARD OF TRUSTEES
`OF THE UNIVERSITY OF
`ILLINOIS,
` Patent Owner.
`___________________________________/
`
`DEPOSITION OF: Shalesh Kaushal, M.D., Ph.D.
`DATE TAKEN: May 2, 2014
`TIME: 9:09 a.m. - 4:13 p.m.
`PLACE: Hilton - University of Florida
` Conference Center
` 1714 S.W. 34th Street
` Gainesville, Florida 32607
`REPORTED BY: Lori Francis, RPR, FPR and
` Notary Public
`
`www.firstchoicereporting.com
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`First Choice Reporting & Video Services
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`Electronically signed by Lori Junker (401-110-943-3328)
`Electronically signed by Lori Junker (401-110-943-3328)
`
`800.939.0093
`CYAN EXHIBIT 1079
`d2240619-8142-4724-9279-ef15a4ff13d0
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`
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 2
`APPEARANCES:
`
` APPEARING ON BEHALF OF THE PETITIONER:
` JOHN A. BOUDET, ESQUIRE
` Roetzel & Andress, LPA
` 420 South Orange Avenue
` 7th Floor
` Orlando, Florida 32801
` jboudet@ralaw.com
`
` GEORGE DARBY, ESQUIRE
` Darby Law Corporation
` 95-1045 Alakaina Street
` Mililani, Hawaii 96789
` darbypatent@teleport-asia.com
`
` APPEARING ON BEHALF OF THE PATENT OWNER:
` TODD S. WERNER, ESQUIRE
` Carlson, Caspers, Vandenburgh,
` Lindquist & Schuman, P.A.
` 225 South Sixth Street
` Suite 4200
` Minneapolis, Minnesota 55402
` twerner@carlsoncaspers.com
`
`
`
`
`
`
`ALSO PRESENT: John Minatelli, Ph.D.
` Steve Hill
`
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 3
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` I N D E X
` EXAMINATIONS
` DIRECT CROSS REDIRECT RECROSS FURTHER
`Mr. Darby 6 144
`Mr. Werner 136
`
`Certificate of Reporter........................... 149
`Certificate of Oath............................... 150
`Errata Sheet...................................... 151
`Read and Sign Letter.............................. 152
`
` EXHIBITS
` Page Line
`Cyan Exhibit 1050............................ 35 24
`(Article from Nature Genetics)
`Cyan Exhibit 1051............................ 39 21
`(Article from Experimental Eye Research - 2013)
`Cyan Exhibit 1052............................ 41 21
`(Article from The Journal of Neuroscience)
`Cyan Exhibit 1053............................ 49 14
`(Article from Investigative Ophthalmology
`& Visual Science - Friedenwald Lecture)
`Cyan Exhibit 1054............................ 72 20
`(Article from Comparative Biochemistry
`& Physiology)
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 4
`Cyan Exhibit 1055............................ 107 21
`(Article from Molecular Vision)
`Cyan Exhibit 1056............................ 110 5
`(Article from Experimental Eye Research - 2003)
`Cyan Exhibit 1057............................ 112 6
`(Article from the American Academy
`of Ophthalmology)
`Cyan Exhibit 1058............................ 121 10
`(Article from Canadian Journal of
`Physiology & Pharmacology)
`Cyan Exhibit 1059............................ 123 12
`(Article from Transactions of the American
`Ophthalmological Society on - 1990)
`Cyan Exhibit 1060............................ 126 3
`(Article from Eye)
`Cyan Exhibit 1061............................ 127 17
`(Article from Age and Ageing)
`Cyan Exhibit 1062............................ 128 6
`(Article from Transactions of the American
`Ophthalmological Society - 1987)
`Cyan Exhibit 1063............................ 129 12
`(Article from Brain Research)
`Cyan Exhibit 1064............................ 130 7
`(Article from American Journal of Hematology)
`Cyan Exhibit 1065............................ 132 1
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 5
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`(Article from Journal of Free Radicals in
`Biology and Medicine)
`Cyan Exhibit 1066............................ 132 15
`(Article from The Jouranl of Biological
`Chemistry)
`
` (Previously marked Cyan Exhibits 1001, 1002, 1004,
`1008, 1010, 1012, 1014, 1020, 1025, 1026 and University
` Exhibit 2015 have been attached.)
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 6
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` P R O C E E D I N G S
` SHALESH KAUSHAL, M.D., Ph.D.,
`having been first duly sworn to tell the truth, was
`examined and testified upon his oath as follows:
` THE WITNESS: Yes.
` DIRECT EXAMINATION
`BY MR. DARBY:
` Q Thank you, Lori.
` Dr. Kaushal, I'm George Darby. I'll be
`asking the questions today.
` A Yes.
` Q First thing I'd like to confirm is whether
`you need to take breaks more frequently than once an
`hour.
` A That's fine.
` Q Okay.
` A I'm on call, so I may every once in a while
`need to look at my cell phone.
` Q Sure.
` A But I put it on silent mode.
` Q Vibrate. Well, if we see you jump, we'll
`know what's happening.
` A Right.
` Q Since we don't have video, it's easy to
`start and stop, so just say -- raise your hand and say
`
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 7
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`I need a break.
` A Okay. Sounds great.
` Q Okay. Some sort of formal questions at the
`beginning, do you have a financial interest in the
`outcome of the case?
` A No, I don't.
` Q Okay. Do you have a financial interest in
`the Tso patent, which I'll refer to --
` A No.
` Q -- as the 533 patent, US patent No.
`5,527,533?
` Do you receive royalties from the patent?
` A No, I don't.
` Q Do you have a consulting agreement or any
`other agreement with the University of Illinois?
` A No, I don't.
` Q Do you have an agreement with Valensa
`International?
` A No, I don't.
` Q Does University of Illinois fund any of your
`projects --
` A No.
` Q -- research projects?
` Does Valensa fund any of the research
`projects?
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 8
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` A No.
` Q Does the University of Illinois -- you are
`employed in a medical practice?
` A Yes.
` Q Does the University of Illinois fund
`anything at your medical practice?
` A No.
` Q Do you have other hats that you wear, a
`consulting company?
` A Yes.
` Q Okay. Does the University of Illinois fund
`any of your projects at your consulting company?
` A No, they don't.
` Q Valensa -- does Valensa fund anything at
`your medical practice?
` A No.
` Q Does Valensa fund anything at your
`consulting companies?
` A No.
` Q May I ask what your compensation is for your
`work as an expert witness in this case?
` A Yes. I receive $450 per hour.
` Q Thank you.
` Without disclosing the substance of the
`discussions, did you confer with plaintiff's attorneys
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 9
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`about the 533 patent before the deposition?
` A Yes.
` Q Okay. Do you have attorneys other than --
`or did you confer with attorneys other than University
`of Illinois attorneys?
` A No.
` Q Did you confer with anyone else about the
`533 patent before the deposition?
` A No.
` Q Have you ever talked with Dr. Moerck at
`Valensa?
` A No.
` Q I guess you've talked with Dr. Minatelli
`since he's here today.
` A Right.
` Q And did those conversations involve the 533
`patent?
` A In a limited way.
` Q Did those conversations involve your
`declaration in the patent owner's response to the IPR?
` A No.
` Q Have you ever corresponded with anyone
`else -- I said talked before.
` Have you ever corresponded with anyone else
`about the 533 patent?
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 10
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` A No.
` Q Have you ever corresponded with anyone else
`about the IPR?
` A No.
` Q And by IPR, I mean IPR 2013-00401
`consolidated with IPR 2013-00404.
` Have you ever talked to Dr. Mark Tso, one of
`the inventors of the 533 patent?
` A Yes.
` Q And did your conversations concern the
`research underlying the 533 patent?
` A No. Mark Tso's a personal friend --
` Q Oh, yes.
` A -- because we move in similar academic
`circles.
` Q You see him at ARVO?
` A Yeah. We're actually in Hong Kong giving
`talks in 2012, so we were chitchatting at that time,
`not about this work. I wasn't aware of this patent.
` Q Oh, really?
` A I was aware of his published papers.
` Q Yes, yes. ARVO sponsors the Friedenwald
`lecture, if I remember correctly.
` A Yes, yes.
` Q So he gave one of those. We'll probably
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 11
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`talk about that a little later.
` Have you ever talked with the coinventor,
`Dr. Lam, Tim-Tak Lam?
` A No.
` Q If you didn't know Mark Tso and you had
`questions about the 533 patent, to whom would you talk?
` Who do you think would have expertise in the
`area of the Tso patent, of the 533 patent?
` MR. WERNER: Objection to form.
` MR. DARBY: You answer.
` MR. WERNER: If you can understand the
` question, you can answer. If you need
` clarification, feel free to ask for clarification.
` THE WITNESS: I don't follow what you mean
` by that.
`BY MR. DARBY:
` Q Let's say you're a grad student and you read
`the 533 patent and you wanted to know more but the
`faculty at your school knew nothing about it --
` A Yes.
` Q -- or they were in a different area of
`ophthalmology --
` A Yes.
` Q -- do you know anyone that you would seek
`out to explain the 533 patent?
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 12
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` MR. WERNER: Objection to form.
` THE WITNESS: Yes, myself.
`BY MR. DARBY:
` Q Other than yourself --
` A What I would do first -- I think most
`scientists would do a literature search on Pub Med and
`track down the original references, read the original
`references, and then if you had questions, then seek
`out -- usually what most people do is contact the
`senior author directly. Nowadays with e-mail you can
`do that, and most scientists are more than happy to
`discuss their science.
` Q Does anyone come to mind that has worked in
`the area of antioxidants and retinal degeneration?
` A There's a whole slew of people. Do you want
`a list of people?
` Q The top two or three people on your list.
` MR. WERNER: I'll just object to form.
` THE WITNESS: Peter Campochiaro at Johns
` Hopkins, Emily Chew at National Eye Institute are
` the two I would think of.
`BY MR. DARBY:
` Q Uh-huh. Thank you. And they have published
`in this area?
` A Yes.
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 13
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` Q Have you published in the area of
`antioxidants?
` A Not directly in the area of antioxidants but
`related areas.
` Q Particularly rhodopsin --
` A Yes.
` Q -- genetics of rhodopsin?
` A Yes, and rhodopsin biochemistry.
` Q In your publications about photoreceptor
`degeneration, would you characterize them as
`genetics -- genetic causes of photoreceptor
`degeneration?
` MR. WERNER: Objection to form.
` THE WITNESS: Partially, yes, yes.
` MR. DARBY: Okay.
` THE WITNESS: We use genetics as a tool to
` explore biochemistry of the photoreceptor cell.
` MR. DARBY: Yes. You have a very
` interesting paper on microglia that we'll get to.
` THE WITNESS: Yes.
`BY MR. DARBY:
` Q In your opinion, is all photoreceptor cell
`death apoptotic in nature?
` MR. WERNER: Objection to form, scope.
` THE WITNESS: That's a complicated question.
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 14
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` MR. DARBY: I know.
` THE WITNESS: It's almost an unfair question
` because the answer itself is, you know, five to
` eight hours of discussion.
`BY MR. DARBY:
` Q Uh-huh. So it's a complicated area?
` A It is, so partially. As you may be aware,
`there's other forms of cell death that occur in every
`part of the body, including the retina, so apoptosis is
`just one form of cell damage.
` Q Apoptotic processes and necrotic
`processes --
` A And something called --
` MR. WERNER: I'm going to object to form.
` This is kind of in a conversational mode, but I'm
` objecting to form and scope on this topic.
`BY MR. DARBY:
` Q Are there other degenerative and cell --
`photoreceptor cell death processes other than apoptotic
`and necrotic?
` A Yes.
` MR. WERNER: Objection to scope.
`BY MR. DARBY:
` Q What are those?
` MR. WERNER: Objection to scope. Can I have
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 15
` a running objection to anything about this topic
` that's never been addressed in this IPR
` proceeding?
` MR. DARBY: No. I'm going to ask you to
` object.
` MR. WERNER: Okay. All right.
` MR. DARBY: Thanks.
` THE WITNESS: Necroptosis is another
` recognized form of cell death.
`BY MR. DARBY:
` Q Would you agree that there are many ways in
`which a photoreceptor cell death can be initiated?
` A Yes.
` MR. WERNER: Objection to scope.
`BY MR. DARBY:
` Q In your opinion, does all photoreceptor cell
`death begin with degeneration?
` MR. WERNER: Objection to form and scope.
` THE WITNESS: That's also a difficult
` question to answer, right, because of the
` complexity of the initiating events, right?
`BY MR. DARBY:
` Q Yes, but other than an extirpation
`surgically of a photoreceptor cell, the process of --
`does the process of photoreceptor cell death occur over
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 16
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`a period of time?
` MR. WERNER: Objection to form, scope.
` THE WITNESS: Yes.
`BY MR. DARBY:
` Q In your opinion, what is the shortest period
`of time in which a photoreceptor cell dies from
`degeneration after insult or damage?
` MR. WERNER: Objection to form and scope.
` THE WITNESS: It depends on the disease,
` right? There are certain catastrophic diseases of
` the retina like a stroke, central retinal vein
` occlusion, central retinal artery occlusion, even
` retinal detachment where we know beautiful work
` that's been published to demonstrate that
` photoreceptor cells can die within 24 hours or
` less.
` There are other injuries also to the retina
` in which photoreceptor cells can die in a
` catastrophic en masse or ensemble way.
`BY MR. DARBY:
` Q In your opinion, what is the longest period
`required for a photoreceptor cell to die?
` MR. WERNER: Objection to form and scope.
` THE WITNESS: Again, it depends on the
` disease, right? Because it's one of those classic
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
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`Page 17
` circumstances in all of medicine, really, where
` it's the interaction between the genetics of the
` organism; be it, a human, mouse or so on and the
` environment.
` So there are some disorders where a patient
` may be susceptible to a disease, but the process
` itself occurs over decades or a lifetime.
`BY MR. DARBY:
` Q You're familiar with the exposure of
`neonates to bright lights?
` A Yes.
` Q In a typical situation of a neonate being
`exposed to bright light, would it be a matter of days
`or weeks or months -- it would be a matter of days
`before death occurs?
` MR. WERNER: Objection to form and
` incomplete hypothetical and scope. I mean, I have
` no idea how these are relevant to anything that he
` has said in his expert declaration submitted in
` the IPR proceeding and that's the only reason
` we're here today.
` MR. DARBY: You'll see.
` MR. WERNER: I just encourage you to -- at
` some point I'll probably have to shut this down
` because we're wasting time, but I'll object to
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 18
` scope right now and hopefully we can get to topics
` that he's actually offered opinions on.
`BY MR. DARBY:
` Q So in the case of photic insult of a
`neonate -- and photic insult is an element in the
`claims.
` MR. WERNER: Neonate is a word that I
` haven't seen in any entire life and certainly not
` in any documents in the IPR proceeding.
`BY MR. DARBY:
` Q Does it take -- can it take weeks or months
`for the photoreceptor cell to die?
` MR. WERNER: Same objections.
` THE WITNESS: Yes.
`BY MR. DARBY:
` Q Would you agree there are many ways to
`initiate death of a photoreceptor cell?
` MR. WERNER: Same objections.
` THE WITNESS: Yes.
`BY MR. DARBY:
` Q And there are -- would you agree that there
`are many ways to initiate degeneration of a
`photoreceptor cell?
` MR. WERNER: Same objections.
` THE WITNESS: Yes.
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 19
`
`BY MR. DARBY:
` Q In paragraph 28 of your declaration, you
`state: It is my opinion that Cyanotech and Dr.
`Schweigert have failed to demonstrate that vitamin A
`deficiency and/or xerophthalmia involve any damage,
`injury, or disease caused by oxidative attack, free
`radical damage, or photic insult.
` In fact, the literature relied upon by
`Cyanotech indicates that vitamin A does not prevent
`oxidative attack or free radical damage of the eye. As
`I do not believe free radical attack plays a role in
`xerophthalmia or vitamin A deficiency, it is my opinion
`that retinal damage or disease caused by free radical
`attack is not inherent to xerophthalmia or vitamin A
`deficiency.
` Do you agree that that was an accurate
`quote?
` MR. WERNER: Counsel, if you would provide
` the document, he could read along with you.
` THE WITNESS: I was just going to say the
` same thing. If I could take a look at it, that'd
` be great.
` MR. DARBY: Okay. I don't have a printed
` copy with me.
` MR. WERNER: I mean, should I get one?
`
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 20
` Because I assume you would provide the witness
` with his declaration you're deposing him about.
` He's not going to testify by memory. He's going
` to need his expert report today, I'm sure.
` MR. DARBY: Let's take a break and print it
` out.
` (A recess was taken.)
`BY MR. DARBY:
` Q Dr. Kaushal, if you would review your
`paragraph 28 in your declaration.
` A Do you know what page that's on?
` Q Six. Five to six.
` A Uh-huh.
` Q And I'm going to focus on your statement
`that you do not believe free radical attack plays a
`role in xerophthalmia or vitamin A deficiency and that
`retinal damage or disease caused by free radical attack
`is not inherent in vitamin A deficiency.
` A Yes.
` Q Okay. Do you agree with the statement that
`although the initiating event of photoreceptor cell
`death in vitamin A deficiency is different from photic
`insults as the initiating event of photoreceptor cell
`death, both initiating events share the same sequelae,
`the accumulation of opsin unable to form rhodopsin in
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 21
`
`rods or iodopsin in cones by liganding with
`11-cis-retinal?
` MR. WERNER: Objection to form and scope.
` That was a long question, so if you need her to
` read it back, feel free to do so.
` THE WITNESS: Yeah, yeah, could you?
` MR. DARBY: Read the question back, please.
` (The preceding question was read back by the
` court reporter.)
` MR. WERNER: Objection to form, scope,
` compound.
` THE WITNESS: They're different. The
` sequelae are different and the consequence is
` different because your -- in your question you
` state their inability to form the photo pigment
` with 11-cis-retinal. In the instance of vitamin A
` deficiency, that's true; but in the instance of
` photic damage, it's only a transient event. It
` reaccumulates.
`BY MR. DARBY:
` Q Do I understand correctly that you're saying
`for a period after photic insult, opsin accumulates and
`is unable to form rhodopsin because of the lack of
`11-cis-retinal?
` MR. WERNER: Objection to form, scope.
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 22
` THE WITNESS: For a transient period of
` time, yes. We studied that ourselves.
`BY MR. DARBY:
` Q Yes. So what happens when opsin accumulates
`for a transient period of time or for a longer period
`of time in the photoreceptor cell?
` MR. WERNER: Objection to form, compound,
` objection to scope.
` THE WITNESS: It depends on the state of the
` retina prior to the insult, right?
`BY MR. DARBY:
` Q Let's say that -- okay, a hypothetical --
`the photic insult continues. It's not a transient
`event. Let's say it continues for the period in the
`533 patent for 24 hours. What --
` A Could I interrupt you?
` Q Yes.
` A That's not what is stated in that patent, as
`far as I understood it. The way they induce photic
`injury in that patent and in the papers, right, it's
`the same way we all induce photic injury
`experimentally, is the mice or rats, they live in
`cyclical light, 12 hours on, 12 hours off.
` Q I'm sorry. You're correct.
` A The exposure to light was only for a brief
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 23
`period of time. I believe it was two hours or less.
`You can look -- confirm that in the patent and in the
`Tso paper as well. Some people do it for even shorter
`periods of time, so it's very brief exposure. It
`wasn't a sustained exposure.
` Q Okay. I'll confirm that later. But if
`untreated -- sorry, strike that.
` In this period in which opsin accumulates
`and is unable to form rhodopsin -- we'll talk about
`cones -- sorry, rods, and I believe the same process
`occurs in cones, but there's more research on rods.
`Rods are easier to study.
` What are the sequelae following the -- based
`on the accumulation of opsin and -- and in particular
`address the involvement of reactive oxygen species as a
`result of the accumulation of opsin?
` MR. WERNER: Objection to form, compound.
` Objection to scope.
` THE WITNESS: Your question -- I just would
` say to you -- I mean, the question is so
` complicated and you've asked it at so many
` different levels, so many different things, it's
` hard to answer that.
` If you have a specific question you'd like
` to ask me, I'm happy to answer it. It's such a
`
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`Shalesh Kaushal, M.D., Ph.D. - 5/2/2014
`
`Page 24
` broad question. I mean, people talk about this
` for a whole symposium, right?
` MR. DARBY: Okay.
`BY MR. DARBY:
` Q Following the accumulation of opsin, does --
` A Under what circumstance?
` Q I don't want to limit it to a particular
`initiating event, just the accumulation of opsin.
` Do high concentrations of reactive oxygen
`species appear in the RPE?
` MR. WERNER: Objection to form, scope.
` THE WITNESS: So here's what I'd say to you:
` In the instance of the wild-type retina, right,
` which is an undiseased retina, there is no
` initiation of reactive oxygen species at the level
` of the retinal pigment epithelium.
` Opsin accumulation, as it's nascently formed
` in the rod inner segment, is a natural process,
` and we've studied that in great detail and looked
` at the consequences within the retina
` holistically.
` That's why I asked you under what conditions
` are you asking opsin accumulating. Because in the
` case of a wild-type retina or your and my retina
` right now, we're producing opsin, all of us
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