·1· · · · · ·IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`·2
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`·3
`· · · · · · · · ·BEFORE THE PATENT TRIAL AND APPEAL BOARD
`·4
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`·5
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`·6
`· · · · · · · · · · · · · · ·GRUNENTHAL GMBH,
`·7· · · · · · · · · · · · · · · Petitioner
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`·8· · · · · · · · · · · · · · · · · v.
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`·9· · · · · · · · · · ·ANTECIP BIOVENTURES II LLC,
`· · · · · · · · · · · · · · · ·Patent Owner
`10
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`11
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`12
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`13· · · · · · · · · · · · · Case PGR2017-00022
`· · · · · · · · · · · ·U.S. Patent No. 9,408,862 B2
`14
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`15
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`16
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`17· · · · · ·The deposition of STEPHEN BRUEHL, a witness in the
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`18· · · ·above-entitled cause, taken before Cynthia Odom,
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`19· · · ·Licensed Court Reporter and Notary Public in and for
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`20· · · ·Davidson County, Tennessee, at 511 Union Street, Suite
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`21· · · ·2700, Nashville, Tennessee, on the 9th day of January,
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`22· · · ·2018, commencing at 9:00 a.m., pursuant to the Rules
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`23· · · ·governing U.S. Patent and Trademark Procedure.
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`24
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`25 Job No. 441881
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`ANTECIP EXHIBIT 2026
`Grunenthal GmbH v. Antecip Bioventures II LLC
`PGR2017-00022
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`Page 1
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`Page 2
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`·1· ·APPEARANCES:
`·2· · ·FITZPATRICK, CELLA, HARPER & SCINTO
`· · · · ·1290 Avenue of the Americas
`·3· · · ·New York, New York 10104-3800
`· · · · ·For Grunenthal GMBH
`·4· · · ·BY:· JAMES R. TYMINSKI, ESQ.
`· · · · ·(212) 218-2520
`·5· · · ·jtyminski@fchs.com
`·6· · ·MASCHOFF BRENNAN
`· · · · ·1389 Center Drive, Suite 300
`·7· · · ·Park City, Utah 84098
`· · · · ·For Antecip Bioventures II, LLC
`·8· · · ·BY:· R. PARRISH FREEMAN, JR., ESQ.
`· · · · ·(435) 575-1419
`·9· · · ·pfreeman@mabr.com
`10· ·ALSO PRESENT:
`11· · · ·Brent A. Johnson, Ph.D., Esq.
`· · · · ·William Solander, Esq.
`12
`13
`· · · · · · · · · · · · · · ·INDEX
`14· ·Witness· · · · · · · · · · · · · · · · · · · · ·Page
`15· ·Stephen Bruehl
`16· ·Direct Examination. . . . . . . . . . . . . . . . 3
`17· ·Cross Examination. . . . . . . . . . . . . . . . 59
`18
`· · · · · · · · · · CONFIDENTIAL DESIGNATION
`19
`· · ·Page 46, Line 6, through
`20· ·Page 47, Line 9
`21
`22· · · · · · · · · · · · · EXHIBITS
`23· ·No.· Description· · · · · · · · · · · · · · · · Page
`24· ·No Exhibits Marked.
`25
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`Page 3
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`·1· · · · · · · · · · S T I P U L A T I O N
`·2· · · ·The deposition of STEPHEN BRUEHL taken by
`·3· ·agreement at 511 Union Street, Suite 2700, Nashville,
`·4· ·Tennessee, beginning at 9:00 A.M., January 9, 2018, on
`·5· ·behalf of the Patent Owner pursuant to the provisions
`·6· ·of the Rules governing U.S. Patent and Trademark
`·7· ·Procedure.
`·8· · · ·Formalities as to notice, caption, certificate,
`·9· ·and filing are waived.
`10· · · ·All objections, except as to the form of the
`11· ·question, are reserved to the hearing.· The reporter,
`12· ·being a notary public, may swear the witness.
`13· · · · · · · · · · ·STEPHEN BRUEHL,
`14· ·having first been duly sworn, testified as follows:
`15· · · · · · · · · ·DIRECT EXAMINATION
`16· ·BY MR. FREEMAN:
`17· · · Q.· · Dr. Bruehl, you're testifying today as an
`18· ·expert in the area of methods of treating knee pain;
`19· ·is that correct?
`20· · · A.· · That's correct, pain and -- chronic pain and
`21· ·chronic pain treatment.
`22· · · Q.· · And you have training in methods of treating
`23· ·knee pain?
`24· · · A.· · I have training in methods of evaluating and
`25· ·treating chronic pain.
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`Page 4
`·1· · · Q.· · Do you have education in treating knee pain?
`·2· · · A.· · Yes, I do.
`·3· · · Q.· · Do you have experience in methods of treating
`·4· ·knee pain?
`·5· · · A.· · Not personally but in the research context,
`·6· ·yes.
`·7· · · Q.· · Would you say you have skill in the area of
`·8· ·methods of treating knee pain?
`·9· · · A.· · I have skill in the area of chronic pain,
`10· ·which encompasses knee pain.
`11· · · Q.· · And you have knowledge of methods of treating
`12· ·knee pain?
`13· · · A.· · Yes.
`14· · · Q.· · Do you have any training with regard to oral
`15· ·zoledronic acid?
`16· · · A.· · My training from that comes from reading
`17· ·about bisphosphonates and writing about them in the
`18· ·context of treating other conditions.
`19· · · Q.· · So I'm asking specifically with regard to
`20· ·training; do you have any specialized training?
`21· · · A.· · Like educational training?
`22· · · Q.· · Yes.
`23· · · A.· · No, I do not.
`24· · · Q.· · So my next question is any education in the
`25· ·area of oral zoledronic acid, and I believe you said
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`Page 5
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`·1· ·no?
`·2· · · A.· · No, be the same issues.
`·3· · · Q.· · And do you have any experience with oral
`·4· ·zoledronic acid?
`·5· · · A.· · In the research context I've written about it
`·6· ·before, read about it.
`·7· · · Q.· · Would you say you have any specialized skill
`·8· ·with regard to oral zoledronic acid?
`·9· · · · · · · · · MR. TYMINSKI:· Object to form.
`10· · · A.· · Skill in what capacity?
`11· ·BY MR. FREEMAN:
`12· · · Q.· · Skill -- you can define it however you like.
`13· · · · · · · · · MR. TYMINSKI:· Object to form.
`14· · · A.· · Yeah, I have some knowledge of that based on
`15· ·reading that I've done, scientific literature.
`16· ·BY MR. FREEMAN:
`17· · · Q.· · Would you say you have skill in excess of
`18· ·others in the field?
`19· · · · · · · · · MR. TYMINSKI:· Object to form.
`20· · · A.· · I would say that I have knowledge of
`21· ·bisphosphonates and zoledronic acid based on reading
`22· ·that would make me comparable to other people in that
`23· ·situation.
`24· ·BY MR. FREEMAN:
`25· · · Q.· · So your skill is based on your knowledge,
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`Page 2
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`Page 6
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`·1· ·which is based on reading?
`·2· · · A.· · Correct, and working with other people who
`·3· ·use bisphosphonates.
`·4· · · Q.· · Do you have any specialized training with
`·5· ·regard to nonoral applications of zoledronic acid?
`·6· · · A.· · Such as intravenous?
`·7· · · Q.· · Yes.
`·8· · · A.· · It would be the same issue, just based on
`·9· ·reading literature.
`10· · · Q.· · So no specialized training?
`11· · · A.· · No.
`12· · · Q.· · No education?
`13· · · A.· · No, no specific education on that.
`14· · · Q.· · And your experience is based on what you've
`15· ·read?
`16· · · A.· · What I've read and then talking with other
`17· ·people who do use it clinically.
`18· · · Q.· · And would you say you have any skill with
`19· ·regard to the uses of nonoral zoledronic acid?
`20· · · · · · · · · MR. TYMINSKI:· Object to form.
`21· · · A.· · Skills in terms of what?
`22· ·BY MR. FREEMAN:
`23· · · Q.· · Using it.
`24· · · A.· · No special skills beyond what I've read and
`25· ·discussed with other people who do use it.
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`Page 7
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`·1· · · Q.· · And your knowledge of the uses and
`·2· ·applications of nonoral zoledronic acid come from that
`·3· ·same source, your reading and speaking with others who
`·4· ·have used it?
`·5· · · A.· · That's correct.
`·6· · · Q.· · So is it fair to say with regard to both oral
`·7· ·and nonoral zoledronic acid that you don't have any
`·8· ·firsthand experience with using it?
`·9· · · A.· · I don't use it clinically, that's correct.
`10· · · Q.· · You said you don't use it clinically; do you
`11· ·use it non-clinically?
`12· · · A.· · No, not -- no, I don't have pragmatic use of
`13· ·administering the drug.
`14· · · Q.· · Do you have any firsthand experience with any
`15· ·use of the drug?
`16· · · A.· · I'm not sure what other uses would be.
`17· · · Q.· · Well, you said pragmatic, so I'm just --
`18· · · A.· · Oh, pragmatic meaning like actually hands-on
`19· ·administering to patients using for clinical purposes,
`20· ·I don't do that.
`21· · · Q.· · You don't have any personal experience with
`22· ·the use of zoledronic acid in --
`23· · · A.· · No.
`24· · · Q.· · -- either form, oral or nonoral?
`25· · · A.· · That's correct.
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`Page 8
`·1· · · Q.· · How about with regard to bioavailability, do
`·2· ·you know what I mean when I say that?
`·3· · · A.· · Yes, I do.
`·4· · · Q.· · Can you tell me what you think I mean?
`·5· · · A.· · That means that the amount of the drug that
`·6· ·is ingested in whatever route, it's the percentage of
`·7· ·the drug that actually gets processed in the body and
`·8· ·can have an active effect.
`·9· · · Q.· · And that which is not processed stays in the
`10· ·GI tract; right?
`11· · · · · · · · · MR. TYMINSKI:· Object to form, outside
`12· ·the scope.
`13· · · A.· · Are you referring to IV or oral?
`14· ·BY MR. FREEMAN:
`15· · · Q.· · Well, there's no real bioavailability issue
`16· ·with IV, is there, it's 100 percent absorbed, is it
`17· ·not?
`18· · · A.· · That is correct.
`19· · · Q.· · So I'm referring to non-IV uses.
`20· · · A.· · Okay.
`21· · · Q.· · And I guess specifically oral.
`22· · · A.· · Okay.· So oral stays in the GI tract?· No,
`23· ·it's -- all of it ends up getting excreted or absorbed
`24· ·into the bone.
`25· · · Q.· · Well, I'm trying to distinguish between --
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`Page 9
`·1· ·you know, in terms of a bioavailability percentage, do
`·2· ·you have an understanding of what that percentage
`·3· ·would be based on?
`·4· · · A.· · Yes, it would be like doing a study of the
`·5· ·pharmacokinetics where they would administer a certain
`·6· ·amount of drug and then follow how much is excreted
`·7· ·over time.
`·8· · · Q.· · But it's the amount that goes into the system
`·9· ·versus the amount that stays in the GI tract; is it
`10· ·not?
`11· · · · · · · · · MR. TYMINSKI:· Object to form, and
`12· ·outside the scope of the direct.
`13· · · A.· · I guess on a very brief time scale that would
`14· ·be correct because it would end up getting excreted
`15· ·from the GI tract.
`16· ·BY MR. FREEMAN:
`17· · · Q.· · Do you have any specialized training with
`18· ·regard to bioavailability?
`19· · · A.· · No, I do not.
`20· · · Q.· · So you have no specialized education with
`21· ·regard to bioavailability?
`22· · · A.· · No, I'm not, and in this case I'm relying on
`23· ·Dr. Wilson for that expertise.
`24· · · Q.· · So no experience with bioavailability?
`25· · · A.· · In the context of reading articles that have
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`Page 10
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`·1· ·discussed that.
`·2· · · Q.· · Any other context?
`·3· · · A.· · No.
`·4· · · Q.· · Any specialized skill with regard to
`·5· ·bioavailability?
`·6· · · · · · · · · MR. TYMINSKI:· Object to form.
`·7· · · A.· · No.
`·8· ·BY MR. FREEMAN:
`·9· · · Q.· · Any specialized knowledge with regard to
`10· ·bioavailability?
`11· · · A.· · No.
`12· · · Q.· · Can you tell me what you did today in
`13· ·preparation for this deposition?· I'm sorry, let me
`14· ·back up.
`15· · · · · · · · · MR. FREEMAN:· Scratch that question.
`16· · · Q.· · Did you do anything in preparation for your
`17· ·testimony today?
`18· · · A.· · Yes, I did.
`19· · · Q.· · What did you do?
`20· · · A.· · I read my declaration; Dr. Wilson's
`21· ·declaration; the patent office response to the initial
`22· ·filing; I read the response filed by your client and
`23· ·their expert, Dr. Papopolous, I believe, in response
`24· ·to the patent office response; I looked at the
`25· ·articles that were in my reference list in my
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`Page 12
`·1· · · Q.· · Did they hand you anything that looked to be
`·2· ·like notes or work product?
`·3· · · A.· · No.
`·4· · · Q.· · No summaries or charts or anything like that?
`·5· · · A.· · Just charts that are embedded in the context
`·6· ·of those things that were filed as exhibits.
`·7· · · Q.· · Did you meet with your lawyers?
`·8· · · A.· · Yes.
`·9· · · Q.· · How much time did you spend with them?
`10· · · A.· · Haven't tallied it up, about 12 hours total.
`11· · · Q.· · Yesterday?
`12· · · A.· · Sunday and Monday.
`13· · · Q.· · So that's yesterday and the day before
`14· ·yesterday?
`15· · · A.· · Yes, correct.
`16· · · Q.· · I'm going to hand you what has already been
`17· ·marked in the case as Exhibit 1003, which is a copy of
`18· ·your declaration.· Do you want a clip?
`19· · · A.· · Yeah, please.
`20· · · Q.· · Do you have Exhibit 1003 in front of you?
`21· · · A.· · Yes, I do.
`22· · · Q.· · So paragraph 1, if you'll follow me, you make
`23· ·reference to the references cited in this declaration;
`24· ·do you see that?
`25· · · A.· · Yes.
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`Page 11
`·1· ·declaration and saw at least one article from the
`·2· ·filing that you had -- that your client had included
`·3· ·in their response.
`·4· · · Q.· · What do you mean when you say that?
`·5· · · A.· · There was a Conte reference that I did not
`·6· ·reference in my declaration that was cited in your
`·7· ·client's response.
`·8· · · Q.· · The response in this case?
`·9· · · A.· · Yes, the response to the patent office, there
`10· ·was a citation for a Conte article.
`11· · · Q.· · Is that an exhibit in this case?
`12· · · A.· · I would -- I'm assuming so, it was cited in
`13· ·one of the responses I read.
`14· · · · · · · · · MR. TYMINSKI:· I can represent it's an
`15· ·exhibit in this case, it's the Conte article that's
`16· ·referenced in Dr. Papopolous' declaration.
`17· · · A.· · And I also looked over the patents, the 862
`18· ·patent, the Leonard, the Fox, the Marian poster.
`19· ·BY MR. FREEMAN:
`20· · · Q.· · Your lawyers provided you with these
`21· ·documents?
`22· · · A.· · Yes.
`23· · · Q.· · To your knowledge is everything that they
`24· ·provided you of record in this case?
`25· · · A.· · To my knowledge, yes.
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`Page 13
`·1· · · Q.· · Grunenthal's counsel provided those to you;
`·2· ·is that correct?
`·3· · · A.· · No, not in all cases.
`·4· · · Q.· · You found some yourself?
`·5· · · A.· · I did, I found many of them myself.
`·6· · · Q.· · Which ones did you find yourself?
`·7· · · A.· · Let's see, and this is just by recollection
`·8· ·so I'm not 100 percent sure this is accurate.
`·9· · · Q.· · Okay.
`10· · · A.· · I believe 1017 -- do you want me to go by
`11· ·number?
`12· · · Q.· · Yes, please.
`13· · · A.· · 1017, 1018, 1019, 1020, 1021, 1022, 1023,
`14· ·1024, 1025, 1029, 1030, 1045, 1046, 1047, 1048, 1049,
`15· ·1050, 1051, 1053, 1055, 1056, 1057.· I guess that's it
`16· ·on my sheet; are there others?· I just want to make
`17· ·sure I'm not missing a page.
`18· · · Q.· · No, I don't think there are others relevant
`19· ·to your declaration.
`20· · · A.· · Okay.· All right.
`21· · · Q.· · So is it fair to say that the other exhibits
`22· ·that you referred to -- the other references that you
`23· ·referred to in your declaration that you did not just
`24· ·list for me as having been found by you were provided
`25· ·to you by your counsel?
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`Page 4
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`Page 14
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`·1· · · A.· · Yes, that's correct.
`·2· · · Q.· · And --
`·3· · · A.· · I'm sorry, did I say 1008?
`·4· · · Q.· · You did not.
`·5· · · A.· · Okay.· 1008 was one I found also.
`·6· · · Q.· · And to be clear, when I say your counsel I'm
`·7· ·referring to Grunenthal's legal counsel; is that your
`·8· ·understanding as well?
`·9· · · A.· · That is how I interpret that, yeah.
`10· · · Q.· · Have you been deposed before?
`11· · · A.· · Yes.
`12· · · Q.· · Just one quick reminder, we have to be
`13· ·careful not to speak over each other.
`14· · · A.· · I understand, and I'll do my best not to.
`15· · · Q.· · Fair enough.· So you mentioned that you've
`16· ·done some reading on the area of zoledronic acid; is
`17· ·that correct?
`18· · · A.· · That's correct.
`19· · · Q.· · And oral zoledronic acid?
`20· · · A.· · That's correct.
`21· · · Q.· · Would you say you stay informed of efforts to
`22· ·make oral zoledronic acid?
`23· · · A.· · I think that might go a little far, but I
`24· ·have read quite a bit of material that is relevant to
`25· ·that over the past several years.
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`Page 16
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`·1· ·May rather of 2014; is that correct?
`·2· · · A.· · What paragraph is that?· I just to want make
`·3· ·sure the date is correct.
`·4· · · Q.· · Paragraph 18.
`·5· · · A.· · 18.
`·6· · · Q.· · Well, that's what has the date.
`·7· · · A.· · That's the filing date?
`·8· · · Q.· · Yeah.
`·9· · · A.· · Yes, paragraph 30.
`10· · · Q.· · Yes, paragraph 30.
`11· · · A.· · Yes, so that's -- yes, I was.
`12· · · Q.· · You didn't envision using oral zoledronic
`13· ·acid to treat knee pain at that time, did you?
`14· · · · · · · · · MR. TYMINSKI:· Object to form.
`15· · · A.· · As of what time?
`16· ·BY MR. FREEMAN:
`17· · · Q.· · May of 2014.
`18· · · · · · · · · MR. TYMINSKI:· Same objection.
`19· · · A.· · I'm having a little trouble, I just want to
`20· ·make sure of the date because I was involved with Thar
`21· ·Pharmaceuticals starting at some point around then, I
`22· ·don't know the exact date, and just to be specific,
`23· ·that they were in the process of trying to develop an
`24· ·oral zoledronic acid.· I'm not sure if it was prior to
`25· ·May 27, 2014.
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`Page 15
`·1· · · Q.· · So have you seen in the literature a trend
`·2· ·toward -- not a trend but an emphasis on obtaining
`·3· ·higher bioavailability?
`·4· · · A.· · Yes, I know that's an issue with the oral
`·5· ·bisphosphonates.
`·6· · · Q.· · Above 2.5 percent?
`·7· · · A.· · Just higher is better basically is my
`·8· ·understanding.
`·9· · · Q.· · Are you aware that Novartis tried to
`10· ·commercialize a high bioavailability oral zoledronic
`11· ·acid and failed?
`12· · · A.· · I believe I have heard that before.
`13· · · Q.· · Are you aware of others that also tried and
`14· ·failed?
`15· · · A.· · With oral bisphosphonates?
`16· · · Q.· · Oral zoledronic acid.
`17· · · A.· · Oral, no, I'm not aware of any others that
`18· ·have failed.
`19· · · Q.· · Are you aware of anyone else that's trying
`20· ·right now?
`21· · · A.· · I think it's -- the two parties in this case
`22· ·are the two that I'm aware of specifically with
`23· ·zoledronic acid.
`24· · · Q.· · So you said you were a person of skill in the
`25· ·art at the time of the invention, that's March -- or
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`Page 17
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`·1· ·BY MR. FREEMAN:
`·2· · · Q.· · And they were trying to achieve a higher
`·3· ·bioavailability; is that right?
`·4· · · A.· · That's correct.
`·5· · · Q.· · Is there any reason why they would ever try
`·6· ·to achieve or anyone would try to achieve a lower
`·7· ·bioavailability?
`·8· · · A.· · My understanding --
`·9· · · · · · · · · MR. TYMINSKI:· Object to form, and
`10· ·outside the scope of the direct.
`11· · · A.· · My understanding is that that is not the
`12· ·desire in terms of bioavailability, that the difficult
`13· ·thing to achieve is to increase bioavailability, and I
`14· ·would assume that there are ways to reduce it that
`15· ·would probably be much easier than increasing
`16· ·bioavailability, but I think Dr. Wilson could answer
`17· ·that better.
`18· ·BY MR. FREEMAN:
`19· · · Q.· · So no one of skill in the art would be
`20· ·motivated to push the bioavailability range lower?
`21· · · · · · · · · MR. TYMINSKI:· Object to form and
`22· ·object as outside the scope of the direct.
`23· · · A.· · Not that I would think, that does not seem
`24· ·obvious to me, although it certainly is possible to do
`25· ·that.
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`Page 18
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`·1· ·BY MR. FREEMAN:
`·2· · · Q.· · Let's look at paragraph 5, please.· Your
`·3· ·background is a bachelor of sciences in psychology
`·4· ·from Belmont; is that correct?
`·5· · · A.· · Correct.
`·6· · · Q.· · And that's here in Nashville?
`·7· · · A.· · That's correct.
`·8· · · Q.· · And then you received a master's in clinical
`·9· ·psychology from Kentucky; is that correct?
`10· · · A.· · That's correct.
`11· · · Q.· · And then you have there that you have a Ph.D.
`12· ·in clinical psychology with a specialization in health
`13· ·psychology?
`14· · · A.· · That is correct.
`15· · · Q.· · And then you say that the Ph.D. is a research
`16· ·degree specifically training the individual to design
`17· ·and conduct research studies and to read and interpret
`18· ·the published literature.
`19· · · A.· · That is entirely correct.
`20· · · Q.· · So there's two different components of that;
`21· ·right?
`22· · · A.· · Okay.
`23· · · Q.· · I'm asking you, do you agree with me so far,
`24· ·two different components, at least as --
`25· · · A.· · You mean to design and conduct?
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`Page 20
`·1· ·happens after training, because starting in about 19
`·2· ·--
`·3· ·BY MR. FREEMAN:
`·4· · · Q.· · But I am just focused on the training right
`·5· ·now.
`·6· · · A.· · Okay.· Well, restate the question, please.
`·7· · · Q.· · Your Ph.D., your degree, doctor of
`·8· ·philosophy, is in the psychology of treating pain; is
`·9· ·that correct?
`10· · · A.· · That would be a main focus of it, yes.
`11· · · Q.· · Not so much the use of medication or
`12· ·prescribing it, using medication to treat the pain?
`13· · · · · · · · · MR. TYMINSKI:· Objection to form.
`14· · · A.· · In terms of training that's partially true
`15· ·because in graduate school part of my training was
`16· ·being involved in research that was being conducted,
`17· ·and that research did involve administration of drugs.
`18· ·BY MR. FREEMAN:
`19· · · Q.· · You're not a medical doctor, are you?
`20· · · A.· · No, I'm not.
`21· · · Q.· · And you can't prescribe medication, you
`22· ·cannot prescribe medication; is that correct?
`23· · · A.· · That is correct.
`24· · · Q.· · You don't treat patients, do you?
`25· · · A.· · I used to treat patients in the context of a
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`Page 19
`·1· · · Q.· · Okay.· Good point.· What I meant there is you
`·2· ·have designing and conducting research studies and
`·3· ·then read and interpret published literature.
`·4· · · A.· · Those would be two different things.
`·5· · · Q.· · And was that the focus of the Ph.D., those
`·6· ·two goals?
`·7· · · A.· · Yes, that is a big part of the Ph.D., and it
`·8· ·distinguishes it from a Psy.D degree, which is just a
`·9· ·clinical degree that teaches people to see patients.
`10· ·And I would just mention in context, because people
`11· ·outside the area wouldn't necessarily know this, but
`12· ·in the context of medical research it's very common
`13· ·for Ph.D.s, frequently psychologists, to be the ones
`14· ·that are helping direct the research efforts because
`15· ·of those kinds of skills that you develop.
`16· · · Q.· · Well, your Ph.D. is in psychology; is that
`17· ·right?
`18· · · A.· · Yes.
`19· · · Q.· · So is your Ph.D. in the psychology -- I mean
`20· ·to the extent it relates to methods of treating pain
`21· ·is it limited to the psychology of methods of treating
`22· ·pain?
`23· · · · · · · · · MR. TYMINSKI:· Object to form.
`24· · · A.· · I would point out two things, one is that the
`25· ·-- and you have to distinguish training from what
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`Page 21
`·1· ·multidisciplinary team, chronic pain patients. I
`·2· ·didn't prescribe for those patients, however.
`·3· · · Q.· · You didn't prescribe medication to those
`·4· ·patients?
`·5· · · A.· · Yes, that's correct.
`·6· · · Q.· · Would you agree with me that the claims in
`·7· ·this case, claims 2 through 16, involve prescribing
`·8· ·medication?
`·9· · · A.· · They involve medication.
`10· · · Q.· · The medications --
`11· · · A.· · I mean the bioavailability is -- regards to
`12· ·prescribing it, but it involves the treatment of knee
`13· ·pain using oral zoledronic acid.
`14· · · Q.· · To your knowledge is there any
`15· ·over-the-counter oral zoledronic acid available?
`16· · · A.· · No.
`17· · · Q.· · So it would necessarily involve prescribing
`18· ·oral zoledronic acid, would it not?
`19· · · A.· · Yes, or working with somebody who does.
`20· · · Q.· · When you say you treat patients, or you used
`21· ·to treat patients in the context of clinical trials,
`22· ·is that what you said?
`23· · · A.· · I said multidisciplinary care, so it is a
`24· ·team involving a physician, psychologist, frequently
`25· ·physical therapist, occupational therapist.
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`Page 22
`·1· · · Q.· · What would your role be in that context?
`·2· · · A.· · My direct clinical role would be treating the
`·3· ·patients using the psychological perspective, like
`·4· ·skills that they could learn mentally to manage pain
`·5· ·more effectively, but it would frequently involve very
`·6· ·close collaboration with the physicians, and in the
`·7· ·context of team meetings there would be issues
`·8· ·discussed, like medications that were being used and
`·9· ·options for that, and they would sometimes involve me
`10· ·in those discussions, particularly when it involved
`11· ·things like antidepressants and other options like
`12· ·that.
`13· · · Q.· · But the psychology of using the
`14· ·antidepressants; is that right?
`15· · · A.· · For that particular type drug it would be the
`16· ·impact it would have on their psychological state.
`17· · · Q.· · When you say impact do you mean the medical
`18· ·effect or the psychological impact of the patient
`19· ·perceiving themselves now as someone who takes
`20· ·medication to manage an issue?
`21· · · · · · · · · MR. TYMINSKI:· Object to form.
`22· · · A.· · The issue you just stated there did sometimes
`23· ·come up, but it was primarily dealing with the medical
`24· ·effect of the drug on the symptoms that were
`25· ·psychological in nature, such as depression, which is
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`Page 24
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`·1· · · Q.· · Were you trained with regard to
`·2· ·bisphosphonates generally?
`·3· · · A.· · No, I was not, not in my education.
`·4· · · Q.· · You've gained some understanding regarding
`·5· ·bisphosphonates since obtaining your Ph.D.; is that
`·6· ·correct?
`·7· · · A.· · That's correct.
`·8· · · Q.· · If a person of skill in the art reads
`·9· ·something pertaining to intravenous bisphosphonate
`10· ·that wouldn't really teach that person anything about
`11· ·oral bisphosphonates, would it?
`12· · · · · · · · · MR. TYMINSKI:· Object to form.
`13· · · A.· · No, not necessarily, and you have to factor
`14· ·in the bioavailability issues.
`15· ·BY MR. FREEMAN:
`16· · · Q.· · Looking at paragraph 6, you were a professor
`17· ·of anesthesiology at Vanderbilt; is that correct?
`18· · · A.· · That's correct.· Technically it's Vanderbilt
`19· ·University Medical Center.
`20· · · Q.· · Do you teach currently about using oral
`21· ·zoledronic acid?
`22· · · A.· · Yeah, and some of the educational talks that
`23· ·I give will talk about bisphosphonates in general, I'm
`24· ·not sure necessarily zoledronic acid for treatment of
`25· ·complex regional pain syndrome.
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`Page 23
`·1· ·very common, or anxiety symptoms, but you're correct,
`·2· ·I was not the one prescribing the medication.
`·3· ·BY MR. FREEMAN:
`·4· · · Q.· · And you don't currently treat patients?
`·5· · · A.· · No, I'm 100 percent research funded.
`·6· · · Q.· · When was the last time you were involved in
`·7· ·an interdiscipline -- what did you call it,
`·8· ·multidisciplinary?
`·9· · · A.· · You can call it either, interdisciplinary or
`10· ·multidisciplinary, and that would be 2003, it's been a
`11· ·while.
`12· · · Q.· · So you weren't treating patients in any
`13· ·capacity in May of 2014?
`14· · · A.· · No, the only patient contact I would have
`15· ·would be in the context of research studies where we
`16· ·do deal with chronic pain patients.
`17· · · Q.· · So in your training for your Ph.D. you were
`18· ·trained to design clinical trials; is that correct?
`19· · · A.· · That was part of it, yes.
`20· · · Q.· · Were you trained to design any involving oral
`21· ·zoledronic acid?
`22· · · A.· · No, not specifically.
`23· · · Q.· · Were you trained to design any involving
`24· ·nonoral zoledronic acid?
`25· · · A.· · No, not specifically.
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`Page 25
`·1· · · Q.· · So just to be clear, you're teaching students
`·2· ·-- you don't know whether you are teaching them with
`·3· ·regard to zoledronic acid specifically?
`·4· · · A.· · Well, the reason I used that particular
`·5· ·language was I'm talking about teaching that is not
`·6· ·just like predoctoral students, I'm talking about
`·7· ·teaching residents, people who are already faculty or
`·8· ·practitioners in the community, because I do
`·9· ·continuing medical education talks sometimes, and I
`10· ·know that in the past I have talked about use of
`11· ·bisphosphonates for treatment of complex regional pain
`12· ·syndrome because that is a particular type of
`13· ·treatment that seems to work in that population, and I
`14· ·think at some point I have probably mentioned that
`15· ·there are these other forms in development that I just
`16· ·cannot recall whether I've used zoledronic acid as a
`17· ·specific example of ongoing studies.
`18· · · Q.· · So you're a Ph.D. in clinical psychology, and
`19· ·now you're a professor of anesthesiology, to me that's
`20· ·a big change, but I'm not a doctor or anything like
`21· ·that, so can you help me understand how -- your
`22· ·application of your Ph.D. training in being a
`23· ·professor of anesthesiology?
`24· · · A.· · Yes, yes, and I agree it looks weird to
`25· ·somebody who doesn't know the reasons why.· So chronic
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`Page 26
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`·1· ·pain clinics are most frequently staffed by
`·2· ·anesthesiologists because many of the techniques that
`·3· ·are used beyond pharmacological treatments are various
`·4· ·forms of blocks, like sympathetic nerve blocks or
`·5· ·sematic nerve blocks that anesthesiologists have a
`·6· ·great deal of training in because of what they do in
`·7· ·the operating room, and because the chronic pain
`·8· ·treatment centers are often affiliated with the
`·9· ·anesthesiology departments what that means is other
`10· ·people that work in the area of chronic pain often are
`11· ·housed in anesthesiology departments, so in my
`12· ·particular case it goes back to the issue of the
`13· ·Ph.D., being training and doing research, conducting
`14· ·research and reading research, so my role in our
`15· ·department is to take those skills and develop
`16· ·research projects that can get funding ideally, like
`17· ·from National Institutes of Health, and carry out
`18· ·those research studies using those skills, and while
`19· ·in some cases the studies may be psychological in
`20· ·nature those broad clinical -- broad training and
`21· ·research skills can be applied to medical areas as
`22· ·well, and over time what happens is while I may have
`23· ·started out as a psychologist purely over time the
`24· ·work that I've done has expanded through
`25· ·collaborations and expertise that I've just gained
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`·1· ·capacity; is that right?
`·2· · · A.· · Yes, as a person who is not legally capable
`·3· ·of prescribing then we always have co-investigators
`·4· ·who are physicians who do the actual prescribing, so
`·5· ·in our morphine study we have a couple of faculty in
`·6· ·our department that are the ones who are the physician
`·7· ·of record doing the prescribing.
`·8· · · Q.· · Describe that morphine study for me in just a
`·9· ·little bit more detail.
`10· · · A.· · Well, the one that -- this is one -- there
`11· ·were actually two in the series, but the one that is
`12· ·probably most relevant here was answering a question
`13· ·which the National Institute on Drug Abuse asked me
`14· ·about, they said what do we know about how endogenous
`15· ·opioids, what you would call endorphins, how those
`16· ·relate to how people respond to pain medications
`17· ·because they were concerned with the overuse of
`18· ·analgesic medications in chronic pain patients, and
`19· ·their idea that kind of fits in the broader scope of
`20· ·personalized medicine is that maybe these drugs aren't
`21· ·for everyone and that maybe you want to limit them and
`22· ·target them at people that are going to get a better
`23· ·cost benefit with it, they get better pain relief and
`24· ·lower risks, or lower side effects, so that was what
`25· ·the task was that was given to us to do that, so the
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`·1· ·along the way and to doing studies that have to do
`·2· ·with something very different than psychology, like
`·3· ·dealing with drug responses, and for example right now
`·4· ·one of my grants that is housed through the
`·5· ·anesthesiology department is a grant from the National
`·6· ·Institute on Drug Abuse, looking at predictors of
`·7· ·responses to analgesic drugs, like morphine, in
`·8· ·chronic pain patients.
`·9· · · Q.· · Are you using your psychology background in
`10· ·that capacity?
`11· · · A.· · I'm using my skills that ultimately went back
`12· ·to my Ph.D. in developing good research studies, so I
`13· ·mean that's -- it's like -- the skills that you
`14· ·develop to do a high quality research study in a
`15· ·psychological trial are virtually identical to the
`16· ·skills you would use in developing a drug trial, it's
`17· ·the same issues involved in experimental controls and,
`18· ·you know, confounds to interpretation and those kinds
`19· ·of things, and over time through collaborations I've
`20· ·developed expertise in nonpsychological studies as
`21· ·well, although I started to mention earlier even in
`22· ·graduate school I was doing studies that had an M.D.
`23· ·to do the prescribing, but studies using drugs to
`24· ·probe certain aspects of the stress response.
`25· · · Q.· · But you were working with others in that
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`·1· ·study we did had chronic back pain patients and also a
`·2· ·group of healthy people come in, and they would do
`·3· ·three sessions in the laboratory, one session they got
`·4· ·saline placebo intravenously, another session they got
`·5· ·a drug called Naloxone, which is an opiate receptor
`·6· ·antagonist, and then the third session they got a
`·7· ·weight adjusted dose of morphine, and in each of those
`·8· ·they would undergo a series of pain stimulus
`·9· ·procedures and then they would say -- basically it's
`10· ·like a computer controlled heat stimulus for a g