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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
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`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`·
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`·1· · · · ·IN THE UNITED STATES DISTRICT COURT
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`·2· · · · · · · ·FOR THE DISTRICT OF DELAWARE
`· · ·- - - - - - - - - - - - - - -x
`·3· ·PFIZER INC. and UCB PHARMA· ·:
`· · ·GMBH· · · · · · · · · · · · ·: C. A. No.
`·4· · · · · · · · · · · · · · · · : 1:15-cv-000079(GMS)
`· · · · · · · · · Plaintiffs,· · ·: Consolidated
`·5· ·v.· · · · · · · · · · · · · ·:
`· · · · · · · · · · · · · · · · · :
`·6· ·MYLAN PHARMACEUTICALS INC., :
`· · · · · · · · · · · · · · · · · :
`·7· · · · · · · · Defendant.· · · :
`· · ·- - - - - - - - - - - - - - -x
`·8
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`·9
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`10· · · · · · · ***RESTRICTED, CONFIDENTIAL***
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`11
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`12
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`13· · · · · · ·Videotaped deposition of WILLIAM R. ROUSH,
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`14· ·Ph.D, taken pursuant to notice, held on Friday,
`
`15· ·September 9, 2016, at the office of Kilpatrick
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`16· ·Townsend & Stockton, 1114 Avenue of the Americas,
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`17· ·New York, New York, commencing at 9:01 a.m. before
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`18· ·Jamie I. Moskowitz, RPR, CRR, a Registered
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`19· ·Professional Reporter and Notary Public.
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`20· · · · · · · · · · · ·*· ·*· ·*
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`21
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`22
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`23
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`24
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`25
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
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`800-333-2082800-333-2082
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`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 1
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
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`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 66
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`·1· ·BY MR. STOCKWELL:
`
`·2· · · · Q· · · · Any luck?
`
`·3· · · · A· · · · I've looked.
`
`·4· · · · Q· · · · I'll -- I'll move on.· It's not that
`
`·5· ·important of a question.
`
`·6· · · · A· · · · Okay.
`
`·7· · · · Q· · · · Let me strike that and just move on.
`
`·8· ·We can -- we can try to find another document for
`
`·9· ·you to refresh your recollection.
`
`10· · · · · · · · ·Would you agree that at the time of
`
`11· ·the invention in 1998 that a skilled artisan would
`
`12· ·be reasonable in viewing 5-HMT as more hydrophilic
`
`13· ·than Tolterodine?
`
`14· · · · · · · · ·MS. MORAN:· Objection.
`
`15· · · · · · · · ·THE WITNESS:· Would -- so at the time
`
`16· · · · of invention would a person of ordinary skill
`
`17· · · · have viewed 5-HMT as being more hydrophilic
`
`18· · · · than Tolterodine, that's your question?
`
`19· ·BY MR. STOCKWELL:
`
`20· · · · Q· · · · Yes.
`
`21· · · · A· · · · I think a person of ordinary skill at
`
`22· ·that time would have had access to the sort of
`
`23· ·log P, log D determinations that are commonly used
`
`24· ·to assess lipophilicity, and would have agreed that
`
`25· ·5-HMT was probably a little more hydrophilic.
`
`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
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`800-333-2082800-333-2082
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`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 2
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 71
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`·1· ·context here is not clear.· I'm sort of asking a
`
`·2· ·relative question here.· I think we agreed that the
`
`·3· ·skilled artisan would view 5-HMT as more hydrophilic
`
`·4· ·than Tolterodine, right?
`
`·5· · · · · · · · ·MS. MORAN:· Objection.
`
`·6· · · · · · · · ·THE WITNESS:· I said and I used --
`
`·7· · · · there's a -- it's a little bit more hydrophilic
`
`·8· · · · than Tolterodine.
`
`·9· ·BY MR. STOCKWELL:
`
`10· · · · Q· · · · So the question is:· Would the skilled
`
`11· ·artisan then view 5-HMT as potentially less
`
`12· ·bioavailable than Tolterodine?
`
`13· · · · A· · · · And my answer repeatedly to that is,
`
`14· ·no, a person of skill would not have viewed it that
`
`15· ·way.
`
`16· · · · Q· · · · Do you -- at the time of the invention
`
`17· ·in 1998, did skilled persons look at the
`
`18· ·lipophilicity of a drug in assessing the oral
`
`19· ·activity of a potential compound?
`
`20· · · · A· · · · Well, looking at a calculated
`
`21· ·parameter and assessing are two different things.
`
`22· ·Yes, a person of skill would -- would consider the
`
`23· ·lipophilicity values from either measurement or
`
`24· ·calculation.· And if there were a question, if a
`
`25· ·person of skill were motivated to move forward with
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`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 3
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 94
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`·1· ·Detrol label about the pharmacodynamics of 5-HMT?
`
`·2· · · · A· · · · I think the conclusions of the --
`
`·3· ·the -- I think the label indicates that the -- well,
`
`·4· ·the label may not use the term "pharmacodynamic
`
`·5· ·effect," but the effect on patients of the extensive
`
`·6· ·metabolizers, a person of skill would appreciate
`
`·7· ·that for the drug generated -- the drug -- the
`
`·8· ·compound strike drug, the compound 5-HMT generated
`
`·9· ·as it was via Detrol had a pharmacodynamic effect
`
`10· ·seemingly comparable to Tolterodine itself.
`
`11· · · · · · · · ·But the question in the -- that is
`
`12· ·unanswerable in this is:· What would the
`
`13· ·pharmacodynamic be for -- on patients to whom 5-HMT
`
`14· ·is directly delivered?· And that is not answerable
`
`15· ·by anything in the Detrol label.
`
`16· · · · Q· · · · Would the skilled artisan in 1998 have
`
`17· ·had a high level of familiarity with Tolterodine?
`
`18· · · · · · · · ·MS. MORAN:· Objection.
`
`19· · · · · · · · ·THE WITNESS:· A high level of
`
`20· · · · familiarity.· Tolterodine was part of the prior
`
`21· · · · art.· And -- and the skilled artisan -- the
`
`22· · · · knowledge available about Tolterodine would
`
`23· · · · have been part of the knowledge available to
`
`24· · · · the skilled artisan.
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`25· · · · · · · · ·But you said a high level.· More so
`
`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 4
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 95
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`·1· · · · than anything else?· I think not more so than
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`·2· · · · anything else.
`
`·3· ·BY MR. STOCKWELL:
`
`·4· · · · Q· · · · Well, I mean, you've kind of focused
`
`·5· ·on the fact that the -- that the label was issued
`
`·6· ·only a couple of months before the priority date
`
`·7· ·here.
`
`·8· · · · · · · · ·Wouldn't the skilled artisan as of the
`
`·9· ·priority date have been sort of just recently
`
`10· ·looking at and investigating the label and becoming
`
`11· ·familiar with Tolterodine?
`
`12· · · · A· · · · Just recently that given in that
`
`13· ·two-month window, the person of ordinary skill would
`
`14· ·have been aware of the label and would have read it
`
`15· ·in comparison and context with everything else
`
`16· ·that's known for other drugs used to treat OAB.
`
`17· ·And -- and the person of skill would have made his
`
`18· ·or her assessments of an appropriate starting place.
`
`19· · · · · · · · ·And, yeah, the Detrol was coming
`
`20· ·onward, but it wasn't yet in widespread use.· And I
`
`21· ·think all of that -- that's why I said I put
`
`22· ·Tolterodine at the cusp between my bucket two and
`
`23· ·bucket one compounds, where bucket one is the area
`
`24· ·from which a person of skill would select a
`
`25· ·compound.
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`
`
`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 5
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 110
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`·1· ·used within the industry?
`
`·2· · · · · · · · ·MS. MORAN:· Objection.
`
`·3· · · · · · · · ·THE WITNESS:· I have not -- so -- so
`
`·4· · · · used within the industry.· So there's -- that
`
`·5· · · · has many dimensions to it.
`
`·6· · · · · · · · ·All I -- I've not seen statements.· So
`
`·7· · · · let me just say I have not seen statements to
`
`·8· · · · that effect.· I did present an appendix looking
`
`·9· · · · at a five-year window from the -- backwards
`
`10· · · · from the priority date looking at all of the
`
`11· · · · drugs that have received FDA approval and --
`
`12· · · · and looking at the numbers of those that were,
`
`13· · · · in fact, prodrugs.
`
`14· · · · · · · · ·I don't recall the fraction, but it
`
`15· · · · was on the order of -- I would say 10 percent
`
`16· · · · perhaps.· And so from the approval level, it's
`
`17· · · · a small fraction of the total.· How that
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`18· · · · translates to research efforts, I don't know.
`
`19· ·BY MR. STOCKWELL:
`
`20· · · · Q· · · · Would you agree that skilled artisans
`
`21· ·knew that the prodrug -- prodrugging is a tool in
`
`22· ·their arsenal in 1998 to develop a compound for a
`
`23· ·particular indication?
`
`24· · · · A· · · · A person of skill would -- would
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`25· ·understand that prodrugs, the whole concept of
`
`
`
`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
`
`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 6
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 111
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`·1· ·making prodrugs is potentially useful in cases where
`
`·2· ·you do have an established drug with a known
`
`·3· ·liability that can be potentially addressed and
`
`·4· ·solved that way.
`
`·5· · · · · · · · ·So I think, yes, persons of ordinary
`
`·6· ·skill would be aware that prodrugs are part of
`
`·7· ·the -- how do you call it, the tool kit, I forget
`
`·8· ·how you framed it -- it would be there.· But I don't
`
`·9· ·see that a person of skill would have selected a
`
`10· ·prodrug approach in this particular instance.
`
`11· · · · Q· · · · Do skilled artisans -- the ordinarily
`
`12· ·skilled artisan that you identified in 1998, do they
`
`13· ·get trained on sort of techniques or sort of case
`
`14· ·studies and how to go about developing a successful
`
`15· ·drug?
`
`16· · · · · · · · ·MS. MORAN:· Objection.
`
`17· · · · · · · · ·THE WITNESS:· Well, from -- in the
`
`18· · · · academic training many do not because the
`
`19· · · · backgrounds of the person of ordinary skill is
`
`20· · · · very varied.· That's why the several years of
`
`21· · · · practical experience as part of the background
`
`22· · · · of a person of ordinary skill is critical
`
`23· · · · because that's really -- it's on-the-job
`
`24· · · · training, if you will, where -- where the -- a
`
`25· · · · lot -- many of the aspects of drug development,
`
`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
`
`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 7
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
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`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 112
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`·1· · · · drug discovery are, you know, learned.
`
`·2· · · · · · · · ·There may be -- there will be some
`
`·3· · · · persons who pick it up academically.· But --
`
`·4· · · · but the majority, I think, receive it from
`
`·5· · · · on-the-job training.
`
`·6· ·BY MR. STOCKWELL:
`
`·7· · · · Q· · · · Is that something you would think a
`
`·8· ·person of ordinary skill in the art, however he
`
`·9· ·received the information, they would sort of
`
`10· ·understand, you know, here's -- here's what's in
`
`11· ·your tool kit for developing a successful drug?
`
`12· · · · · · · · ·MS. MORAN:· Objection.
`
`13· · · · · · · · ·THE WITNESS:· The person of ordinary
`
`14· · · · skill from the academic training would be aware
`
`15· · · · of what prodrugs are and that it's part of
`
`16· · · · what's there.· They'd understand
`
`17· · · · structure-based design.· They'd understand
`
`18· · · · molecular modeling.· They'd understand
`
`19· · · · conceptually many things.
`
`20· · · · · · · · ·But the whole -- there's a tool kit,
`
`21· · · · to use your term, of technologies available,
`
`22· · · · not all of which are used in every drug
`
`23· · · · discovery program.· The person of skill needs
`
`24· · · · to learn when and where this technique or that
`
`25· · · · technique or a third or fourth or fifth
`
`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 8
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 113
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`·1· · · · technique will be useful to them.
`
`·2· · · · · · · · ·And there may be some problems where
`
`·3· · · · they use all.· There may be others where they
`
`·4· · · · use only one.· And -- and it will vary.· And --
`
`·5· · · · and there's part of -- this is part of the
`
`·6· · · · learning curve that a person of ordinary skill
`
`·7· · · · will go through.
`
`·8· ·BY MR. STOCKWELL:
`
`·9· · · · Q· · · · Would you agree that 5-HMT was at
`
`10· ·least a reasonable possible candidate for looking at
`
`11· ·in terms of developing a new drug for OAB?
`
`12· · · · A· · · · And -- and I would say no.· I would
`
`13· ·put 5-HMT in my third category.· It's at this point
`
`14· ·a research compound with -- with very little actual
`
`15· ·known about it.
`
`16· · · · · · · · ·What was known about 5-HMT would not
`
`17· ·be sufficient to elevate it up into category 1 as
`
`18· ·a -- as a -- among the pool of -- of drugs that I
`
`19· ·think a person of skill would have selected as a --
`
`20· ·as a starting point.
`
`21· · · · Q· · · · I want to make sure we distinguish
`
`22· ·between a candidate and a re-candidate. I
`
`23· ·understand your opinion that 5-HMT is not a lead --
`
`24· ·reasonable lead candidate for addressing the
`
`25· ·obviousness of the asserted patents.· I'm just
`
`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
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`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 9
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`ConfidentialConfidential
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`PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.PFIZER INC., ET AL. vs. MYLAN PHARMACEUTICALS INC.
`
`William R. Roush, Ph.D. on 09/09/2016William R. Roush, Ph.D. on 09/09/2016
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`Page 133
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`·1· · · · Q· · · · For the -- for the discovery chemist
`
`·2· ·that is doing the salt formation process, you said
`
`·3· ·they have to test it.· You mentioned the inventor
`
`·4· ·tested 50, 100, whatever you said.· Do they not look
`
`·5· ·at the art and see what is frequently used in other
`
`·6· ·pharmaceutical drugs for salts in choosing the 50 or
`
`·7· ·so compounds they're going to test?
`
`·8· · · · · · · · ·MS. MORAN:· Objection.
`
`·9· · · · · · · · ·THE WITNESS:· A person of skill would
`
`10· · · · have access to the Berge articles and these
`
`11· · · · reviews that have listed pharmaceutically
`
`12· · · · acceptable salts.· So they would be aware of
`
`13· · · · that.· And given if you're hoping to make a
`
`14· · · · compound going to a human, I think they would
`
`15· · · · be cognizant and take that into consideration.
`
`16· · · · But -- so they would look for salts that --
`
`17· · · · that they knew had already been part of an --
`
`18· · · · of an approved drug.· You know, the presumption
`
`19· · · · being, then, that that counter iron would not
`
`20· · · · have any negative -- you know, would not be a
`
`21· · · · problem source.
`
`22· ·BY MR. STOCKWELL:
`
`23· · · · Q· · · · Right.
`
`24· · · · A· · · · But having said that, then the Table 1
`
`25· ·or Table 2 or whatever it is in Berge where there's
`
`
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`www.huseby.comwww.huseby.com
`Huseby, Inc.· Regional CentersHuseby, Inc.· Regional Centers
`
`800-333-2082800-333-2082
`
`Charlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San FranciscoCharlotte ~ Atlanta ~ Washington, DC ~ New York ~ Houston ~ San Francisco
`
`YVer1f
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`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1073 - Page 10
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