`
` A. ROSE
`UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
` _____________________________
`MICRO LABS LIMITED and MICRO LABS USA INC.
` Petitioners
` v.
` SANTEN PHARMACEUTICAL CO., LTD. and
` ASAHI GLASS CO., LTD.
` Patent Owners
` _____________________________
`
` Case IPR2017-01434
` U.S. Patent No. 5,886,035
` _____________________________
`
` DEPOSITION OF DR. ARON ROSE
` Washington, DC
` July 16, 2018
`
`Reported by: Mary Ann Payonk
`Job No. 143914
`
`TSG Reporting - Worldwide 877-702-9580
`
`1
`2
`3
`
`4 5
`
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`IPR Page 1/123
`
`Santen/Asahi Glass Exhibit 2062
`Micro Labs v. Santen Pharm. and Asahi Glass
`IPR2017-01434
`
`
`
` A. ROSE
`
`Page 2
`
` July 16, 2018
` 9:03 a.m.
`
` Deposition of DR. ARON ROSE, held at the
`law offices of Pillsbury Winthrop Shaw Pittman
`LLP, 1200 Seventeenth Street, NW, Washington,
`DC, pursuant to Notice before Mary Ann
`Payonk, Nationally Certified Realtime Reporter
`and Notary Public of the District of Columbia,
`Commonwealth of Virginia, and State of New
`York.
`
`TSG Reporting - Worldwide 877-702-9580
`
`1
`
`2 3 4 5
`
`6
`
`7 8
`
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`IPR Page 2/123
`
`
`
`Page 3
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`APPEARANCES:
`ON BEHALF OF PATENT OWNERS SANTEN
`PHARMACEUTICAL CO., LTD., and ASAHI GLASS CO.,
`LTD:
` ERNEST YAKOB, ESQUIRE
` HOGAN LOVELLS US
` 875 Third Avenue
` New York, New York 10022
`
`ON BEHALF OF PETITIONERS:
` CEDRIC TAN, ESQUIRE
` SOPHIE WEI, ESQUIRE
` ALTON HARE, ESQUIRE
` PILLSBURY WINTHROP SHAW PITTMAN
` 1200 Seventeenth Street, NW
` Washington, DC 20036
`
`ALSO PRESENT:
` Christopher Parker, Legal Video
` Specialist
` Ian Wahrenbrock, summer associate
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 3/123
`
`
`
`Page 4
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` THE VIDEOGRAPHER: This is the
`start of tape labeled number 1 of the
`videotaped deposition of Dr. Aron Rose
`in the matter of Micro Labs Limited and
`Micro Labs USA, Inc. versus Santen
`Pharmaceutical Company et al., in the
`United States Patent and Trademark
`Office before the Patent Trial and
`Appeal Board, case IPR2017-01434. This
`deposition is being held at 1200
`17th Street, Northwest, Washington, D.C.
`on July 16, 2018, at approximately 9:03.
` My name is Christopher Parker from
`TSG Reporting, Inc., and I'm the legal
`video specialist. The court reporter is
`Mary Ann Payonk, in association with
`TSG Reporting.
` Will counsel please introduce
`yourselves?
` (Whereupon, counsel placed their
`appearances on the video record.)
` MR. YAKOB: And just for the record
`there's also an additional person here.
`Do you want to state who that is for the
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 4/123
`
`
`
`Page 5
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` record?
` MR. TAN: Correct. We also have
` with us a summer associate with the
` Pillsbury law firm, and I'll let him
` introduce himself. His name is.
` MR. WAHRENBROCK: Ian Wahrenbrock.
`ARON ROSE,
` EXAMINATION
`BY MR. YAKOB:
` Q. Good morning, Dr. Rose.
` A. Good morning.
` Q. Some preliminary things to get
`started. Do you have any medical condition
`that would impair your ability to testify today
`truthfully and accurately?
` A. I do not.
` Q. And so the record goes smoothly and
`record appears smoothly, we can agree that
`you'll wait for me to ask my question and then
`you'll begin your answer; correct? So we don't
`overlap?
` A. Yes.
` Q. And so that the stenographer can
`capture the questions and the answers
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 5/123
`
`
`
`Page 6
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`correctly, we also agree that you will
`verbalize your answers rather than, for
`example, saying "uh-huh" or nodding?
` A. Yes.
` Q. Okay. Now, did you meet with counsel
`to prepare for your deposition today?
` A. I did.
` Q. Okay. And when was that?
` A. Yesterday, most recently.
` Q. Okay. And how long did you meet with
`counsel yesterday?
` A. Roughly eight hours.
` Q. Okay. Prior to yesterday's meeting,
`did you have any other preparation for this
`particular deposition?
` A. Yes.
` Q. Okay. And when was that?
` A. It was not in person. It was by
`telephone.
` Q. Okay. And approximately when was
`that?
` A. Scattered time periods since the last
`deposition.
` Q. Okay. And how long did you overall
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 6/123
`
`
`
`Page 7
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`meet with counsel to prepare for the deposition
`today?
` MR. TAN: Objection to form.
` A. Are you asking how many hours in
`total?
` Q. How many hours, yeah, in total.
` A. Including yesterday's time?
` Q. Including yesterday's time.
` A. I can only give you a rough estimate.
` Q. Okay.
` A. 20 hours.
` Q. Okay. And was any of that prior to
`you submitting your supplemental declaration in
`this matter?
` MR. TAN: Objection to form.
` A. I don't recall exactly.
` Q. I'll represent that you submitted
`your supplemental declaration -- or, excuse me,
`strike that.
` I'll submit that you signed your
`supplemental declaration on June 1, 2018.
` Do you agree with that?
` A. That's correct.
` Q. After June 1, 2018, how many hours
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 7/123
`
`
`
`Page 8
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`approximately did you spend preparing for this
`deposition?
` A. The great -- let me restate. The
`majority of the roughly 20 hours was spent
`after preparation of the supplemental
`declaration.
` Q. Okay. And the majority, do you mean
`more than 10 hours?
` MR. TAN: Objection to form.
` A. More than 50 percent.
` Q. Okay. Was it more than 15 hours that
`you spent preparing?
` A. I can't say with assurance.
` Q. And during your preparation with
`counsel for the deposition, did you review
`documents?
` MR. TAN: Objection to form.
` A. Yes, I did.
` Q. Okay. What documents did you review?
` MR. TAN: I'm going to make an
` objection; instruct the witness not to
` answer on the basis of privilege. What
` he may or may not have reviewed during
` his deposition preparation is protected
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 8/123
`
`
`
`Page 9
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` and privileged.
` MR. YAKOB: It's not a
` communication. I'm asking what
` documents did he review in preparation
` for his deposition. It's really not a
` proper instruction, counsel.
` MR. TAN: My objection stands. I
` am -- I stated my objection. It relates
` to documents that he may or may not have
` reviewed during his preparation. That
` is not a proper focus of your question
` and I'll instruct the witness not to
` answer.
` MR. YAKOB: I suggest you
` reconsider that over the break because
` it's really not a proper instruction.
` MR. TAN: My objection stands.
` MR. YAKOB: Okay.
`BY MR. YAKOB:
` Q. Did you communicate with anyone other
`than counsel to prepare for your deposition?
` A. I did not.
` Q. And you've prepared -- strike that.
` In terms of the drafting of your
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 9/123
`
`
`
`Page 10
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`declaration, your most recent declaration was a
`supplemental declaration that you signed on
`June 1, 2018; right?
` A. Correct.
` Q. You also previously submitted a
`declaration in this matter; correct?
` A. That's correct.
` Q. Do you understand when I refer to the
`supplemental declaration for purposes of our
`questioning I'll be referring to the one that
`you signed on June 1, 2018? Can we agree on
`that?
` A. I do.
` Q. Okay. When was the first draft of
`the supplemental declaration prepared?
` MR. TAN: Objection to form.
` A. I can't recall exactly.
` Q. Okay. And who prepared the first
`draft of the supplemental declaration?
` A. It was a collaboration between
`counsel and myself.
` Q. And did you review any other draft
`declarations while preparing your draft
`supplemental declaration?
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 10/123
`
`
`
`Page 11
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` MR. TAN: Objection to form.
` A. I'm not sure I understand your
`question.
` Q. Sure. Do you understand that
`Dr. deLong has also submitted a supplemental
`declaration in this proceeding?
` A. Yes.
` Q. Did you review any drafts of
`Dr. deLong's supplemental declaration while
`preparing your supplemental declaration?
` A. No, I did not.
` Q. Have you ever reviewed Dr. deLong's
`supplemental declaration?
` A. No.
` Q. Did you review Dr. deLong's original
`declaration in this proceeding?
` MR. TAN: Objection to form.
` A. I don't recall reviewing his original
`declaration.
` Q. And just to clarify for the record,
`I'm going to just -- so your supplemental
`declaration is Exhibit 1032, and Dr. deLong's
`supplemental declaration is Exhibit 1031, so
`that we're all clear here.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 11/123
`
`
`
`Page 12
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` Do you know if Dr. deLong reviewed
`your supplemental declaration?
` MR. TAN: Objection to form.
` A. I have no information regarding this.
` Q. Okay.
` A. So I do have a distant recollection
`of reviewing Dr. deLong's original declaration.
` Q. And you reviewed that when?
` A. I can't recall.
` Q. Did you review Dr. deLong's original
`declaration in connection with the preparation
`of your supplemental declaration?
` A. I don't recall.
` Q. Do you recall anything in
`Dr. deLong's declaration that informed any of
`the opinions in either of your declarations?
` MR. TAN: Objection to form.
` A. Can you restate the question?
` Q. Sure. Why did you review
`Dr. deLong's original declaration?
` MR. TAN: Objection to form.
` A. As a member of a team constituting a
`person of ordinary skill in the art, it was
`important that I understood his area of
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 12/123
`
`
`
`Page 13
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`expertise. I recall now reviewing his original
`declaration, specifically because I was
`impressed by his depth of experience in the
`field.
` Q. Did you review his declaration to
`obtain any information for purposes of your own
`declarations?
` MR. TAN: Objection to form.
` A. Can you be more specific?
` Q. Did you rely on anything you read in
`Dr. deLong's declaration with respect to the
`opinions you rendered in your declaration?
` MR. TAN: Objection to form.
` A. As a comember of a team constituting
`a person of ordinary skill in the art, I looked
`to Dr. deLong's expertise as a medicinal
`chemist.
` Q. Okay. And the -- teams of
`individuals relying on each other's particular
`expertise is common in this field; correct?
` MR. TAN: Objection to form.
` A. I'm unable to answer that question.
` Q. That's the reason you reviewed -- you
`reviewed Dr. deLong's declaration because you
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 13/123
`
`
`
`Page 14
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`were relying on his expertise as a medicinal
`chemist; correct?
` MR. TAN: Objection to form.
` A. That's not exactly what I said. I
`did not use the phrase "relied on his
`expertise."
` Q. You looked to Dr. deLong's expertise
`as a medicinal chemist as a comember of a team
`constituting a person of ordinary skill in the
`art; correct?
` A. That's correct.
` MR. YAKOB: I'm going to hand you
` an exhibit that has been previously
` marked as Exhibit 2015 in this matter.
` (Exhibit No. 2015, previously marked, was
` referenced and indexed.)
`BY MR. YAKOB:
` Q. Dr. Rose, Exhibit 2015 is titled
`"Initial Clinical Studies with Prostaglandins
`and their Analogues."
` Do you see that?
` A. I do.
` Q. And this is at the top a February
`1997 paper by Camras and Albert Alm; is that
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 14/123
`
`
`
`Page 15
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`correct?
` A. That's correct.
` Q. Have you reviewed this paper before?
` MR. TAN: Objection to form.
` A. Yes.
` Q. The authors, as I mentioned, are
`Camras and Alm. Do you agree that both authors
`were at the forefront of the development of
`prostaglandin analogs as of December 26, 1996?
` MR. TAN: Objection to form.
` A. That's my understanding.
` Q. Let's look at the abstract of the
`paper. I'm going to direct your attention to I
`guess the fifth line down in the abstract on
`the first page. And it says: "Although
`PGF2alpha tromethamine salt,
`PGF2alpha-isopropyl ester," and then in
`parentheticals "(PGF2alpha-IE), and
`15-propionate-PGF2alpha-IE are all very
`effective in reducing IOP, they produce
`unacceptable side effects including
`conjunctival hyperemia and ocular irritation."
` Do you see that?
` A. I read that line, yes.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 15/123
`
`
`
`Page 16
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` Q. So in February 1997, Camras and Alm
`are associating, for example, PGF2alpha and
`PGF2alpha-isopropyl ester with unacceptable
`side effects including conjunctival hyperemia;
`right?
` MR. TAN: Objection to form.
` A. PGF2alpha tromethamine salts,
`PGF2alpha-isopropyl esters and
`15-propionate-PGF2alpha-isopropyl ester are
`stated to produce unacceptable side effects
`including conjunctival hyperemia and ocular
`irritation.
` Q. Okay. And neither PGF2alpha nor
`PGF2alpha-isopropyl ester were ever
`commercialized as a glaucoma drug; is that
`correct?
` MR. TAN: Objection to form.
` A. Could you repeat the question?
` Q. Sure. Start with this.
`PGF2alpha-isopropyl ester has never been
`commercialized as a glaucoma medication;
`correct?
` A. Not to my knowledge.
` MR. YAKOB: Okay. You can set that
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 16/123
`
`
`
`Page 17
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`aside. I'm going to mark as a new
`exhibit, as Exhibit 2058, a journal
`article from the British Journal of
`Ophthalmology from 1994 titled "Additive
`Effect of Latanoprost, a Prostaglandin
`F2 Alpha Analog, and Timolol in Patients
`with Elevated Intraocular Pressure."
`The authors are Rulo, R-U-L-O, Greve,
`G-R-E-V-E, and Hoyng, H-O-Y-N-G.
`(Exhibit No. 2058 was marked for
`identification.)
` MR. TAN: I'm going to make an
`objection to this particular exhibit
`that you're going to question the
`witness on. It doesn't bear any
`markings indicating it was something
`that was filed with any of the papers
`with the PTAB. It is also outside the
`scope of the supplemental declaration as
`it does not look like it is a document
`that was part of his list of materials
`considered.
` MR. YAKOB: Can we have a standing
`objection to any newly marked exhibits?
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 17/123
`
`
`
`Page 18
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` MR. TAN: Sure.
` MR. YAKOB: Thanks.
` MR. TAN: And just to be clear,
` standing objection with respect to any
` exhibits that were not part of his list
` of materials considered and not part of
` any filing by either party with respect
` to the PTAB.
` MR. YAKOB: Okay.
`BY MR. YAKOB:
` Q. Dr. Rose, please take a moment to
`review that article and then I'm going to ask
`you if you've ever read this paper before.
` A. I've read the abstract.
` Q. Have you read this paper before?
` A. I don't recall.
` Q. Okay. And for the record, the title
`is "Additive Effect of Latanoprost, a
`Prostaglandin F2 Alpha Analog, and Timolol in
`Patients with Elevated Intraocular Pressure."
` Do you see that?
` A. Yes.
` Q. And this is in the British Journal of
`Ophthalmology from 1994; correct?
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 18/123
`
`
`
`Page 19
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` A. Yes.
` Q. And the first author is Rulo,
`R-U-L-O?
` A. Yes.
` Q. I'm going to ask you to take a look
`at the second page of the paper. This is page
`900 of the original article. In the right-hand
`column under the discussion, do you see the
`statement: "Previous studies using other
`prostaglandin analogs such as PGF2alpha-IE were
`hampered by clinically unacceptable grades of
`conjunctival hyperemia, local irritation, and
`pain sensation when optimal IOP-lowering doses
`were administered"?
` Do you see that?
` A. Yes.
` Q. So here again the authors are
`describing PGF2alpha-IE as hampered by
`clinically unacceptable hyperemia. Is that
`right?
` MR. TAN: Objection to form.
` A. That's what is written.
` Q. Okay. Now, please take a look at the
`references at the end of the article. First
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 19/123
`
`
`
`Page 20
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`direct your attention to the last page. This
`is page 4 of the article, also page 902 of the
`original numbering of the article.
` Do you see reference 18 as a
`reference to Kerstetter et al. with the title:
`"Prostaglandin F2 Alpha-1-isopropyl Ester
`Lowers Intraocular Pressure Without Decreasing
`Aqueous Humor Flow" in the American Journal of
`Ophthalmology, 1988?
` A. Yes.
` Q. So the authors were aware of the
`Kerstetter reference when they described
`PGF2alpha in their discussion; correct? Sorry,
`strike that.
` The authors were aware of Kerstetter
`in reference 18 when they described
`PGF2alpha-IE in their discussion; correct?
` MR. TAN: Objection to form.
` A. The authors cited the Kerstetter
`study, but I can't testify to their level of
`understanding of his work.
` Q. Okay.
` A. Nor the complexity of the issues
`raised in his paper.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 20/123
`
`
`
`Page 21
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` Q. So let's look also at footnote --
`sorry. Strike that.
` Let's please look at reference 9 on
`page 3 of the article, also page 901 of the
`original numbering of the article.
` Do you see that reference 9 is
`Villumsen, Alm: "Prostaglandin F2
`Alpha-Isopropyl Ester Eye Drops: Effects in
`Normal Human Eyes" in the British Journal of
`Ophthalmology, 1989?
` A. Yes.
` Q. You can set that aside. I'm going to
`hand you what's been previously marked as
`Exhibit 1033, and it is an article entitled
`"Prostaglandin F2 Alpha-1-Isopropyl Ester
`Lowers Intraocular Pressure Without Decreasing
`Aqueous Humor Flow" by Kerstetter, et al.
` (Micro Labs Exhibit No. 1033, previously
` marked, was referenced and indexed.)
`BY MR. YAKOB:
` Q. Dr. Rose, do you recognize this
`paper?
` A. I do.
` MR. TAN: Objection to form.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 21/123
`
`
`
`Page 22
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` Q. Have you reviewed Exhibit 1033 in its
`entirety?
` MR. TAN: Objection to form.
` A. I believe I have.
` Q. Okay. And again, you see the title
`is "Prostaglandin F2 Alpha-1-Isopropyl Ester
`Lowers Intraocular Pressure Without Decreasing
`Aqueous Humor Flow"; correct?
` A. Yes.
` Q. The first author is Kerstetter,
`K-E-R-S-T-E-T-T-E-R?
` A. Yes.
` Q. I'll initially direct your attention
`to the abstract and the description of the
`study that was being done. In the first
`sentence it says: "Using fluorophotometry, we
`performed a randomized, dose-response study of
`the effects of a prostaglandin derivative on
`aqueous humor flow."
` Do you see that?
` A. Yes.
` Q. So the patients here were receiving
`increasing doses of the PGF2alpha-isopropyl
`ester; correct?
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 22/123
`
`
`
`Page 23
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` MR. TAN: Objection to form.
` A. Yes.
` Q. And let's just read the next
`sentence. "Prostaglandin F2 alpha-1-isopropyl
`ester, 0.224 micrograms, 0.448 micrograms, and
`1.120 micrograms, in saline with polysorbate 80
`was instilled into one eye of 20 subjects in
`three separate dose studies." In total in this
`study there were 20 subjects; correct?
` A. That's what the abstract says.
` Q. Okay. Maybe we can confirm that in a
`second as well. Let's look at page 3. And
`this is page 32 of the original numbering of
`the article. And I'm going to direct your
`attention to the Results section. It says:
`"All 20 subjects completed the study of the 1
`and 2-microliter doses."
` Do you see that?
` A. I do.
` Q. Okay. So again, there were 20
`subjects in the study; correct?
` A. Yes.
` Q. Okay. The next sentence says:
`"However, two subjects complained of pain and
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 23/123
`
`
`
`Page 24
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`photophobia and were noted to have marked
`conjunctival hyperemia for several hours after
`instillation of the 2-microliter dose. They
`were excluded from tests of the 5-microliter
`dose."
` Do you see that?
` A. Yes.
` Q. So the authors are describing that
`two of 20 patients could not complete the study
`for all doses because of marked conjunctival
`hyperemia; correct?
` MR. TAN: Objection to form.
` A. At concentrations of 2 microliters.
` Q. Just to clarify, but the study is
`saying that two of the 20 patients could not
`complete the study for all doses because of
`marked conjunctival hyperemia; right?
` A. That's correct.
` Q. And two of 20 patients, that's
`10 percent of the patients in the study; right?
` MR. TAN: Objection to form.
` A. Yes.
` MR. YAKOB: Okay. You can set that
` aside. Dr. Rose, I'm going to hand you
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 24/123
`
`
`
`Page 25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` what's been previously marked in this
` proceeding Exhibit 1003. It's a
` European patent application with Peter
` Klimko as the first inventor and the
` publication number is 639563.
` (Micro Labs Exhibit No. 1003, previously
` marked, was referenced and indexed.)
`BY MR. YAKOB:
` Q. Dr. Rose, do you recognize
`Exhibit 1003?
` A. I do.
` Q. Okay. Can we agree to refer to
`Exhibit 1003 as Klimko?
` A. Yes.
` Q. I'm going to direct your attention to
`table 4 on page 18 of Klimko. You're familiar
`with table 4 on page 18 of Exhibit 1003;
`correct?
` A. I am.
` Q. Okay. Klimko doesn't provide any
`percent IOP reduction data for a time point
`later than 16 hours after a dose; is that
`right?
` MR. TAN: Objection to form.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 25/123
`
`
`
`Page 26
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` A. Did you say after a dose?
` Q. After a dose.
` A. And can you repeat the question?
` Q. Sure. So Klimko, Exhibit 1003,
`doesn't provide any percent IOP reduction data
`for a time point later than 16 hours after a
`dose.
` A. Correct.
` Q. For example, there's no measurement
`of a 24-hour time point after a dose; right?
` MR. TAN: Objection to form.
` A. I find your use of the words "a dose"
`to be confusing. Can you be more precise?
` Q. There's no measurement of a 24-hour
`time point after a dose and before another
`dose; correct?
` MR. TAN: Objection to form.
` A. My reading of Klimko is aided by the
`description of the protocol used for this study
`or quoted in this study. That has to do with
`the administration of successive doses at
`specific time periods, and therefore, the use
`of the word "a dose" continues to confuse me.
` Q. There -- all the doses in Klimko were
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 26/123
`
`
`
`Page 27
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`given at time points less than 24 hours apart;
`is that correct?
` MR. TAN: Objection to form.
` A. Apart from each other?
` Q. Yes. So just to rephrase the
`question.
` A. Yes, thank you.
` Q. It was more like restating the
`question, just for clarity of the record. All
`of the doses that were administered for
`purposes of table 4 in Exhibit 1003 were
`administered at less than 24 hours apart from
`each other; correct?
` MR. TAN: Objection to form.
` A. I believe the time points were 0, 8
`hours, 16 hours, 24 hours, and 32 hours, to be
`precise.
` Q. And 48 hours; correct?
` A. The next was at 48 hours.
` Q. And so I'll reask the question again.
`So all the doses that were administered for
`purposes of table 4 in Exhibit 1003 were
`administered at less than 24 hours apart from
`each other.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 27/123
`
`
`
`Page 28
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` MR. TAN: Objection to form.
` A. Less than 24-hour intervals would be
`another way of stating that?
` Q. I'll restate it your way. All the
`doses that were administered for purposes of
`table 4 in Exhibit 1003 were administered at
`intervals of less than 24 hours apart from each
`other; correct?
` A. Yes.
` Q. Therefore, there was no time point --
`strike that.
` Therefore, there is no data in table
`4 of Klimko Exhibit 1003 for a time point at 24
`hours after administration of a particular dose
`and before the administration of a following
`dose?
` MR. TAN: Objection to form.
` A. I'm sorry, I'm very confused.
` Q. Yeah. There's no time point -- given
`the administration schedule in Klimko for
`purposes of table 4, there's no time point for
`24 hours after one dose and before the
`following dose; correct?
` MR. TAN: Same objection.
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 28/123
`
`
`
`Page 29
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` A. So that I understand, is this a
`restatement of the same question in a different
`form?
` Q. It's a corollary. Given the
`administration schedule that we just discussed,
`correct, where there was no dose that was given
`at an interval of 24 hours apart, there's no
`data point in Klimko for a time point that's 24
`hours after a particular dose yet before the
`following dose.
` MR. TAN: Objection to the form.
` Q. Correct?
` A. The doses were given at hour 8, 16,
`24, 32, and 48. I find it's unconfusing to
`restate that fact. I'm somewhat confused by
`your question.
` Q. The doses that were described in
`Klimko, Exhibit 1003, were 16 hours after the
`fourth dose, 2 hours after the fifth dose, 4
`hours after the fifth dose, and 6 hours after
`the fifth dose; correct?
` A. Correct.
` Q. There were no other percent IOP
`reduction data presented for any other time
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 29/123
`
`
`
`Page 30
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`points other than 16 hours after the fourth
`dose, 2 hours after the fifth dose, 4 hours
`after the fifth dose, and 6 hours after the
`fifth dose; correct?
` A. Correct.
` MR. TAN: Objection to form.
` Q. Now, is it your position that none of
`Compounds A, B, and D in table 4 would provide
`IOP lowering at 24 hours after a single dose?
` MR. TAN: Objection to form.
` A. Can you restate the question?
` Q. Sure. Is it your position -- I can
`say it again, but you let me know --
` A. Uh-huh.
` Q. Is it your position that none of
`Compounds A, B, and D would provide IOP
`lowering 24 hours after the administration of a
`dose?
` MR. TAN: Same objection.
` A. I'm sorry. I remain confused by your
`question. Could you kindly restate it?
` Q. Table 4, the last measured time
`point -- last measured time point in table 4 is
`6 hours after the fifth dose; correct?
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 30/123
`
`
`
`Page 31
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` A. Correct.
` Q. Okay. Is it your position -- strike
`that.
` Is it your position that if the
`percent IOP reduction were measured at 24 hours
`after the fifth dose, there would be no IOP
`lowering for Compounds A, B, and D?
` MR. TAN: Objection to form.
` A. The data suggests that.
` Q. That it would be zero?
` A. I can't predict that.
` Q. So you can't predict what the IOP
`would be at 24 hours after the fifth dose for
`Compounds A, B and D; correct?
` MR. TAN: Objection to form.
` A. The data strongly suggests the
`likelihood, but I cannot give a prediction.
` Q. I'm sorry. You -- I'll reask the
`question again. You can't predict the specific
`percent IOP reduction for Compounds A, B and D
`at 24 hours after the fifth dose; is that
`right?
` MR. TAN: Objection to form.
` A. The data suggests a strong
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 31/123
`
`
`
`Page 32
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
`likelihood, but that is different than a
`prediction.
` Q. Just to clarify, you're saying that
`there is a strong likelihood that the IOP
`reduction would be diminished; is that right?
` A. Can you restate that in a more
`complete form?
` Q. I guess -- you keep saying the
`likelihood is strong.
` A. Yes.
` Q. I'm trying to clarify what you're
`referring to.
` A. Uh-huh.
` Q. My question is not about -- my
`question is a stand-alone question. At 24
`hours after the fifth dose, you can't predict
`what the -- what specific percent IOP reduction
`is for Compounds A, B and D; correct?
` MR. TAN: Objection to form.
` A. I cannot predict the exact IOP at 24
`hours after the fifth dose.
` Q. Okay. Now, let's move to the next
`paper.
` MR. YAKOB: I'm going to ask the
`
`TSG Reporting - Worldwide 877-702-9580
`
`IPR Page 32/123
`
`
`
`Page 33
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
` A. ROSE
` reporter to mark as Exhibit 2059 a paper
` by Villumsen and Alm in the British
` Journal of Ophthalmology, 1992, titled
` "PhXA34 -- A Prostaglandin F2 Alpha
` Analog. Effect on Intraocular Pressure
` in Patients with Ocular Hypertension."
` (Exhibit No. 2059 was marked for
` identification.)
` MR. TAN: My standing objection
` stands here, counsel, just to confirm?
` MR. YAKOB: Yeah.
`BY MR. YAKOB:
` Q. Dr. Rose, please review Exhibit 2059