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`Page 1
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS,
`
`|NC., WOCKHARDT
`
`BIO AG and TEVA PHARMACEUTICALS USA,
`
`INC.,
`
`Petitioners,
`
`v.
`
`ASTRAZENECA AB,
`
`Patent Owner.
`
`|PR2015-01340
`
`Patent RE44,186
`
`CROSS-EXAMINATION OF ANN E. WEBER, Ph D.
`
`Washington, D.C
`
`October 27, 2016
`
`&
`
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`GregoryEdwards, LLC I Worldwide Court Repo
`GregoryEdwards.com I 866-4Team GE
`
`rting
`
`MYLAN - EXHIBIT 1073
`
`Mylan et al. V. AstraZeneca
`
`IPR2015-01340
`
`
`
`Ann E. Weber, Ph D. - October 27, 2016
`
`Page 2
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`i
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`O~O®\lO~U1-l>0Ol\)
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`Cross-Examination of ANN E. WEBER,
`
`Ph.D., a witness herein, called for examination by
`
`counsel for Petitioners in the above-entitled
`
`matter, was taken on Thursday, October 27, 2016,
`
`commencing at 8:07 a.m. at the law offices of
`
`Wilson Sonsini Goodrich & Rosati, 1700 K Street,
`
`N.W., Fifth Floor, Washington, D.C. 20006
`
`before Cappy Hallock, Registered Professional
`
`Reporter, Certified Realtime Reporter, Certified
`
`Livenote Reporter and Notary Public in and for the
`
`District of Columbia.
`
`GregoryEdwards, LLC I Worldwide Court Reporting
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`
`
`Ann E. Weber, Ph D. - October 27, 2016
`
`Page 3
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`A P P E A R A N C E S
`
`On behalf of Petitioner Mylan
`
`Pharmaceuticals,
`
`Inc:
`
`DOUGLAS H. GARSTEN, ESQUIRE
`
`Wilson, Sonsini, Goodrich & Rosati
`
`12235 El Camino Real, Suite 200
`
`San Diego, California 92130
`
`858-350-2300 (P)
`
`858-350-2399 (F)
`
`dcarsten@wsgr.com
`
`i
`
`2 3 4 5 6 7 8 9 0
`
`RICHARD TORGZON, ESQUIRE
`
`DAVID KNAPP, ESQUIRE
`
`Wilson, Sonsini, Goodrich & Rosati
`
`1700 K Street NW, 5th Floor
`
`Washington, D.C. 20006
`
`202-973-8800 (P)
`
`202-973-8899 (F)
`
`rtorczon@wsgr.com
`
`dknapp@wsgr.com
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph D. - October 27, 2016
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`Page 4
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`A P P E A R A N 0 E 3 (Continued)
`
`On behalf of Petitioner Teva Pharmaceuticals
`
`USA,
`
`Inc.
`
`GARY J. SPEIER, ESQUIRE
`
`Carlson Caspers Vandenburgh Lindquist &
`
`Schuman, P.A.
`
`226 South Sixth Street, Suite 4200
`
`Minneapolis, Minnesota 55402
`
`612-36-9600 (P)
`
`612-436-9605 (F)
`
`gspeier@car|soncaspers.com
`
`On behalf of Patent Owner AstraZeneca AB:
`
`JOHN D. LIVINGSTONE, ESQUIRE
`
`M. DAVID WEINGARTEN, ESQUIRE
`
`Finnegan, Henderson, Farabow, Garrett
`
`& Dunner, LLP
`
`271 17th Street NW, Suite 1400
`
`Atlanta, Georgia 30363
`
`404-653-6400 (P)
`
`404-653-6444 (F)
`
`john.|ivingstone@finnegan.com
`
`david.weingarten@finnegan.com
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
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`Ann E. Weber, Ph D. - October 27, 2016
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`Page 5
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`O~O®\IO~U1-I>0Ol\)
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`C 0 N T E N T S
`
`Deposition of ANN E. WEBER, Ph.D.
`
`October 27, 2016
`
`EXAMINATION BY:
`
`By Mr. Carsten
`
`By Mr. Livingstone
`
`-000-
`
`E X H I B I T S
`
`PREVIOUSLY MARKED EXHIBITS
`
`Mylan
`
`Description
`
`Exhibit 1001 U.S. Reissued Patent Number
`
`RE44,186
`
`Exhibit 1007 2-Cyanopyrrolidides as
`
`Potent, Stable Inhibitors of
`
`Dipeptidyl Peptidase IV
`
`Exhibit 1010 Hanessian reference
`
`///
`
`///
`
`///
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`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph D. - October 27, 2016
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`Page 6
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`i
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`O~O®\IO~U1-I>0Ol\)
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`E X H I B I T S (Continued)
`
`PREVIOUSLY MARKED EXHIBITS
`
`AstraZeneca
`
`Description
`
`Exhibit 2056 8-3-16 Weber Declaration
`
`Exhibit 2161 Article: Discovery of
`
`JANUVIA (Sitag|iptin) ...
`
`Thornberry and Weber
`
`Exhibit 2096 Article: Dipeptidy|-
`
`peptidase IV hydrolyses ...
`
`Mentlein, Gallwitz and Schmidt
`
`Exhibit 2013 U.S. Patent No. 6,166,063
`
`Exhibit 2151 Article: Pyrrolidides:
`
`64
`
`synthesis and structure-activity
`
`relationship ... Augustyns
`
`Exhibit 2007 Article:
`
`The Unique
`
`Properties of Dipeptidy|-
`
`peptidase IV ... Augustyns
`
`Exhibit 2001 Article: 4-Cyanothiazolidides
`
`76
`
`as Very Potent, Stable ...
`
`Ashworth
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`Ann E. Weber, Ph D. - October 27, 2016
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`Page 7
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`E X H I B I T S (Continued)
`
`PREVIOUSLY MARKED EXHIBITS
`
`AstraZeneca
`
`Description
`
`Exhibit 2210 Curriculum Vitae
`
`Page
`
`107
`
`Exhibit 2098 Article: Dipeptidyl Piptidase
`
`114
`
`IV Inhibitors for the Treatment
`
`of ... Weber
`
`i
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`2 3 4 5 6 7 8 9 0
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`Ann E. Weber, Ph.D. - October 27, 2016
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`Page 8
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`P R 0 G E E D I N G S
`
`WHEREUPON,
`
`ANN E. WEBER, Ph.D.,
`
`A Witness called for examination, having
`
`been first duly sworn, was examined and testified
`
`as follows:
`
`BY MR. CARSTEN:
`
`EXAMINATION
`
`Good morning, Dr. Weber.
`
`Good morning.
`
`It's very nice to see you again.
`
`Nice to see you.
`
`So we met before.
`
`Yes, we have.
`
`I had the great pleasure of conducting
`
`your cross examination at trial
`
`in a district
`
`court action pertaining to saxagliptin.
`
`Now, when we
`
`last had occasion to talk
`
`we were talking about
`
`invalidity of a particular
`
`patent, correct,
`
`the RE'186 patent?
`
`A
`
`Correct.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
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`Page 9
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`i
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`O~O®\lO~U1-l>0Ol\)
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`Q
`
`And we were discussing it in the
`
`context of an opinion or series of opinions by
`
`Dr. Powers, correct?
`
`A
`
`0
`
`Correct.
`
`You understand that today we are going
`
`to be talking also about the validity or
`
`invalidity of the RE'186 patent,
`
`right?
`
`A
`
`Q
`
`Yes.
`
`But this time we will be focused on a
`
`slightly different set of opinions relating to the
`
`alleged invalidity of that patent,
`
`right?
`
`A
`
`0
`
`That's my understanding.
`
`And those are the ones that have been
`
`tendered by Dr. Rotella, correct?
`
`A
`
`Q
`
`Yes.
`
`You understand that you took an oath
`
`here today to tell the truth, correct?
`
`A
`
`Q
`
`Yes.
`
`And there is no reason you would have
`
`any difficulty in testifying completely and
`
`accurately and truthfully today;
`
`is that fair?
`
`A
`
`That's correct.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 10
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`O~O®\IO~U1-I>0OI\)
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`MR. LIVINGSTONE:
`
`I don't want to
`
`interrupt the examination. Did you take an oath?
`
`THE WITNESS: Yes.
`
`MR. LIVINGSTONE:
`
`Sorry.
`
`I was over
`
`here writing something down.
`
`My apologies.
`
`It's
`
`early morning.
`
`0
`
`Dr. Weber,
`
`I have tons of materials
`
`here.
`
`So, as you know, Dr. Rotella had a
`
`declaration that had a bunch of exhibits,
`
`right?
`
`A
`
`Q
`
`Yes.
`
`And you had a declaration that had a
`
`bunch of exhibits;
`
`is that fair?
`
`A
`
`0
`
`There were exhibits, yes.
`
`Sure.
`
`I have done my
`
`level best to have at
`
`our fingertips, should you need them,
`
`the lion's
`
`share of the exhibits.
`
`If for some reason there
`
`is something else that you want to look at that
`
`I
`
`don't have here,
`
`just ask and we can take a quick
`
`break and I can get whatever you need to look at
`
`printed.
`
`This isn't designed to be a memory test.
`
`It's not designed to trick you in any way.
`
`If you
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
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`Page 11
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`i
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`O~O®\IO~U1-I>0Ol\)
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`need to see something in order to fully and
`
`completely answer a question,
`
`just feel free to
`
`ask. Okay?
`
`A
`
`Q
`
`Okay.
`
`What
`
`I would like to do as the first
`
`order of business,
`
`though,
`
`is put your declaration
`
`in front of you.
`
`MR. CARSTEN: This has been marked
`
`previously as AstraZeneca Exhibit 2056.
`
`(Previously marked AstraZeneca Exhibit
`
`No. 2056, first referral.)
`
`BY MR. CARSTEN:
`
`Q
`
`If
`
`I could trouble you to look at that
`
`document and make sure it is accurate to the best
`
`of your knowledge.
`
`A
`
`0
`
`A
`
`Q
`
`Yes,
`
`this looks like my report.
`
`Okay.
`
`It's a declaration, correct?
`
`Excuse me, my declaration.
`
`And your declaration,
`
`if you turn
`
`to -- there are two series of pages at the bottom.
`
`There is a set that actually has the page number
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 12
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`i
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`O~O®\IO~U1-I>0Ol\)
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`of the document,
`
`so I,
`
`II, and then 1, 2,
`
`et cetera.
`
`And there is another series that says
`
`Page X of 129.
`
`We might have some difficulties
`
`here.
`
`I will do my best to make clear which I
`
`am
`
`referring to.
`
`If you turn to Page 126 of the
`
`document.
`
`It's the last page.
`
`It's also 129 of
`
`129.
`
`So 126 of 129 -- no, 129 of 129.
`
`Yup,
`
`the very last page.
`
`Yes.
`
`And that's your signature?
`
`It
`
`is.
`
`Okay, and you say,
`
`"In signing this
`
`declaration," reading from Paragraph 1265,
`
`"I
`
`understand that the declaration will be filed as
`
`evidence in a contested case before the Patent
`
`Trial and Appeal Board of the United States
`
`Patent & Trademark Office."
`
`Have I
`
`read that correctly?
`
`Yes.
`
`And you say,
`
`"I acknowledge I may be
`
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`Ann E. Weber, Ph D. - October 27, 2016
`
`Page 13
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`subject to cross-examination in the case, and that
`
`cross-examination will
`
`take place within the
`
`United States." Correct?
`
`A
`
`0
`
`Correct.
`
`And, "If cross-examination is required
`
`of me,
`
`I will appear for cross-examination within
`
`the United States during the time allotted for
`
`cross-examination." Correct?
`
`A
`
`Q
`
`Correct.
`
`And then Paragraph 264 says,
`
`"I
`
`declare under penalty of perjury that the
`
`foregoing is true and correct." Right?
`
`A
`
`0
`
`Correct.
`
`Are there any corrections you would
`
`like to make to this declaration?
`
`A
`
`0
`
`No.
`
`To the best of your knowledge,
`
`it is
`
`truthful and accurate?
`
`A
`
`0
`
`Yes.
`
`Let's turn to some of the legal
`
`standards that you were asked to apply in this
`
`document.
`
`So I'm looking at, starting at Page 14
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`GregoryEdwards, LLC I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 14
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`i
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`of 129.
`
`And there there is a Section V called
`
`Legal Standards.
`
`Do you see that?
`
`I do.
`
`You said that you've relied upon
`
`A
`
`0
`
`AstraZeneca's counsel for the applicable legal
`
`standards governing your analysis and opinions,
`
`right?
`
`A
`
`Q
`
`That's correct.
`
`And if you turn to the following page,
`
`Paragraph 41,
`
`there you say,
`
`"I understand that
`
`for a prima facie case of obviousness, structural
`
`similarity between the claimed compound and the
`
`prior art compound is not enough.
`
`The prior art
`
`must also have suggested making the specific
`
`modifications necessary to achieve the claimed
`
`invention."
`
`A
`
`0
`
`Have I
`
`read that correctly?
`
`You have.
`
`Is that the legal standard that you
`
`were directed by AstraZeneca's counsel
`
`to apply in
`
`this case?
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph D. - October 27, 2016
`
`Page 15
`
`That
`
`is part of the legal standard,
`
`0
`
`And you did use that
`
`legal standard in
`
`forming your opinions with respect to the opinions
`
`you have tendered in this case?
`
`A
`
`0
`
`I did.
`
`The next paragraph, Paragraph 42 says,
`
`"I understand that a 'lead' compound is one that
`
`is most promising to modify and that selection of
`
`a lead compound is guided by all of the compound's
`
`pertinent properties."
`
`I have read that correctly?
`
`You have.
`
`Is that a legal standard that you were
`
`A
`
`0
`
`asked to rely upon by AstraZeneca's counsel?
`
`A
`
`Q
`
`Yes,
`
`it is.
`
`And is that a -- is that a legal
`
`standard that you did apply in forming your
`
`opinions in this case?
`
`A
`
`0
`
`I did.
`
`On the Paragraph 40, which bridges the
`
`two pages we have been discussing here, Pages 14
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 16
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`of 129 and 15 of 129,
`
`the bridging sentence says,
`
`"I have been told by AstraZeneca's counsel
`
`to
`
`assume the ‘time of the invention’ mentioned above
`
`to be no later than October 2000 "
`
`Is that an instruction that you
`
`received from AstraZeneca's counsel with respect
`
`to your opinions in this matter?
`
`A
`
`Q
`
`It
`
`is.
`
`You further say,
`
`"My opinion would not
`
`differ, however,
`
`if the filing date of February
`
`16, 2001 applied." Correct?
`
`A
`
`0
`
`That's correct.
`
`You didn't do any independent analysis
`
`to determine what the appropriate date to frame
`
`your analysis was.
`
`Instead you rather relied
`
`solely upon what AstraZeneca's counsel
`
`told you;
`
`is that correct?
`
`dates.
`
`A
`
`0
`
`That's correct.
`
`I relied on these
`
`So you didn't
`
`look at provisional
`
`applications, et cetera,
`
`to determine when
`
`saxagliptin compound was first included in any of
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 17
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`O~O®\IO~U1-I>0Ol\)
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`those preliminary applications and so forth,
`
`correct?
`
`A
`
`I'm aware of the preliminary
`
`applications, and I certainly had access to them,
`
`but
`
`I did not do that particular analysis.
`
`0
`
`Okay.
`
`We will come back from time to time
`
`over the course of the day to Exhibit 2056, your
`
`declaration.
`
`I put it in front of you early, sort
`
`the first thing out of the gate,
`
`so you would have
`
`it handy in the event you wanted to look at it for
`
`any purpose over the course of the day as well.
`
`Okay?
`
`Okay.
`
`MR. CARSTEN:
`
`So I would like to hand
`
`to you what has been marked as Exhibit 1001.
`
`(Previously marked Mylan Exhibit No.
`
`1001, first referral.)
`
`MR. CARSTEN:
`
`I have copies for you as
`
`MR. LIVINGSTONE:
`
`Thank you.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
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`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 18
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`O~O®\lO~U1-I>0OI\)
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`BY MR. CARSTEN:
`
`Q
`
`I hope and trust this is a document
`
`that
`
`looks familiar to you.
`
`A
`
`0
`
`Yes,
`
`it does.
`
`This is the re-issue '186 patent;
`
`is
`
`that correct?
`
`A
`
`0
`
`Yes,
`
`that's correct.
`
`Okay.
`
`And you considered this document and
`
`reviewed it carefully in connection with rendering
`
`your opinions in this case;
`
`is that fair?
`
`A
`
`Yes,
`
`I considered this document and
`
`reviewed it in the case.
`
`0
`
`A
`
`You reviewed it carefully.
`
`Yes,
`
`I
`
`read it and I
`
`reviewed it.
`
`I
`
`guess it depends on what you mean by carefully.
`
`0
`
`Well --
`
`But yes,
`
`I
`
`read it.
`
`You're tendering opinions --
`
`Yes.
`
`-- relating to the validity of the
`
`claims of the patent, correct?
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 19
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`A
`
`Q
`
`Yes.
`
`You wouldn't do that
`
`if you hadn't
`
`read the document carefully,
`
`I presume;
`
`is that
`
`fair?
`
`A
`
`0
`
`If that's your definition, yes.
`
`Let's turn to Column 88,
`
`if we could.
`
`That's towards the back.
`
`It's in the claims
`
`section.
`
`A
`
`0
`
`Now,
`
`if we
`
`look at -- have you got
`
`I do.
`
`Now,
`
`if you look at claim 8 there are
`
`one,
`
`two,
`
`three,
`
`four,
`
`five, six,
`
`seven, eight
`
`different compounds identified in claim 8 plus
`
`pharmaceutically acceptable salts;
`
`is that
`
`correct?
`
`A
`
`0
`
`That
`
`is correct.
`
`Now, with respect to the first
`
`compound depicted under claim 8,
`
`so that's Column
`
`88 starting around Lines 45 to 52 or so.
`
`Have you
`
`got that compound?
`
`A
`
`I have.
`
`GregoryEdwards, LLC I Worldwide Court Reporting
`GregoryEdwards.com I 866-4Team GE
`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 20
`
`Q
`
`In this patent there's no data
`
`presented for this compound relating to potency
`
`against DPP-4, correct?
`
`I would have to go back and just --
`
`Feel free.
`
`-- glance.
`
`Sure.
`
`I believe that
`
`is correct. Again,
`
`A
`
`0 A Q A
`
`there is likely,
`
`for example, mass spec data.
`
`There may be -- so if you're referring to
`
`biological data --
`
`Q
`
`The question was there is no data
`
`relating to potency of that compound as the DPP-4?
`
`A
`
`0
`
`That
`
`is correct.
`
`And by potency you understand I'm
`
`referring to in vitro data;
`
`is that correct?
`
`A
`
`That's correct.
`
`I would assume that
`
`you are referring to an I050 or a Ki at DPP-4
`
`enzyme.
`
`0
`
`And those would be in vitro measures
`
`of potency?
`
`A
`
`Ki and I050 are in vitro measures of
`
`i
`
`O~O®\IO~U1-I>0OI\)
`
`GregoryEdwards, LLO I Worldwide 0ourt Reporting
`GregoryEdwards.com I 866-4Team GE
`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 21
`
`i
`
`O~O®\lO~U1-I>0Ol\)
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`potency.
`
`0
`
`With respect to the compound we have
`
`been discussing,
`
`the first one under claim 8 in
`
`Column 88,
`
`there is no data presented relating to
`
`activity in any in vivo studies;
`
`is that correct?
`
`A
`
`Actually,
`
`let me just -- can I
`
`just
`
`have a minute to check something?
`
`0
`
`Absolutely. Again, as I said,
`
`it's
`
`not
`
`intended to be a memory contest.
`
`Feel free.
`
`A
`
`So that
`
`is correct.
`
`There is no
`
`in vivo data.
`
`0
`
`Okay.
`
`And there is no information presented
`
`here in the patent relating to the activity of any
`
`metabolites of that compound against DPP-4,
`
`correct?
`
`A
`
`I
`
`think there would be not enough
`
`information in the patent to definitively say that
`
`there was no metabolite of this particular
`
`compound that may have been covered by the patent.
`
`Q
`
`I'm asking about whether there is any
`
`data presented relating to data --
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 22
`
`i
`
`O~O®\lO~U1-i>0Ol\)
`
`A
`
`If you are referring to in vitro
`
`potency data,
`
`then that would be correct.
`
`0
`
`And if I'm describing in vivo activity
`
`of a metabolite of that compound,
`
`that
`
`is also
`
`correct,
`
`right?
`
`A
`
`That would be correct.
`
`There is no in
`
`vivo data for any potential metabolite of that
`
`compound.
`
`0
`
`Okay.
`
`And there is no data provided
`
`regarding the interaction of this compound with
`
`the DPP-4 enzyme in the patent, correct?
`
`A
`
`0
`
`That
`
`is correct.
`
`And there is no data relating to the
`
`safety of this compound, correct?
`
`A
`
`There is no safety data in the patent,
`
`that
`
`is correct.
`
`0
`
`There is no efficacy data relating to
`
`this compound in the patent, correct?
`
`A
`
`That's correct.
`
`There is no efficacy
`
`data for that compound in the patent.
`
`Q
`
`And this compound,
`
`to your knowledge,
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 23
`
`i
`
`O~O®\lO~U1-l>0Ol\)
`
`was never advanced to any clinical trials,
`
`correct?
`
`A
`
`I'm not aware of any clinical trials
`
`that were conducted with that compound.
`
`0
`
`And this compound was never FDA
`
`approved, correct?
`
`A
`
`0
`
`That's correct.
`
`So under your analysis in this case,
`
`and we will get to some of this a little later,
`
`but this compound would be a failure, exhibit a
`
`failure of others in connection with your work in
`
`this case, correct?
`
`A
`
`So this compound by virtue of the fact
`
`that
`
`it was not FDA approved, and that was the
`
`standard I used for failure of others, yes,
`
`this
`
`would be a failure.
`
`0
`
`So just to be clear,
`
`the standard you
`
`applied for your assessment of failure of others
`
`was FDA approval, correct?
`
`A
`
`0
`
`That
`
`is correct.
`
`And was that a legal standard that you
`
`were asked to apply by AstraZeneca's counsel
`
`in
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 24
`
`i
`
`O~O®\lO~U1-l>0Ol\)
`
`connection with forming your opinions in this
`
`case?
`
`A
`
`0
`
`A
`
`That -- can I have a minute, please?
`
`Sure.
`
`So the legal standard that
`
`I was asked
`
`to apply,
`
`this is for the objective evidence of
`
`obviousness, was the failure of others in the
`
`prior art to fill -- to fill the need.
`
`And so the
`
`standard I applied was whether the compounds were
`
`in the prior art and whether they were able to
`
`fill the need for a diabetes medication in the
`
`United States.
`
`So that was FDA approval of
`
`compounds that were in the prior art prior to
`
`that,
`
`to the date of October 2000.
`
`Q
`
`And that
`
`legal standard that you just
`
`described, was that provided to you by Astra's
`
`counsel?
`
`A
`
`0
`
`Yes. Yes,
`
`it was.
`
`So they are the ones that selected the
`
`threshold question or the litmus test of FDA
`
`approval as indicative of failure or nonfailure;
`
`is that fair?
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph D. - October 27, 2016
`
`Page 25
`
`i
`
`O~O®\lO~U1-l>0Ol\)
`
`A
`
`Well,
`
`they provided me with the
`
`understanding that the failure of others in the
`
`prior art to fill the need.
`
`And so if you were
`
`talking about,
`
`if I was talking about filling the
`
`need for a compound to treat diabetes in the U.S.,
`
`then that would be FDA approval.
`
`0
`
`Now, as of the priority date there had
`
`been no FDA approved DPP-4 treatment for diabetes;
`
`is that fair?
`
`A
`
`There were no FDA approved -- FDA
`
`approved DPP-4 inhibitors for the treatment of
`
`type 2 diabetes as of the priority date?
`
`0
`
`A
`
`0
`
`Yes,
`
`that
`
`is correct.
`
`That
`
`is correct.
`
`In fact,
`
`the first FDA approved
`
`diabetes treatment was sitagliptin;
`
`is that
`
`correct?
`
`A
`
`If you are referring to the first FDA
`
`approved DPP-4 inhibitor for the treatment of
`
`type 2 diabetes and not a compound in the prior
`
`art, yes,
`
`the first one to be approved was
`
`sitagliptin that wasn't
`
`in the prior art.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 26
`
`i
`
`O~O®\IO~U1-l>0Ol\)
`
`Q
`
`A
`
`And sitagliptin is your compound?
`
`Sitagliptin is Merck's compound, and I
`
`did work on that, yes.
`
`0
`
`Your
`
`team won what
`
`I
`
`think you
`
`referred to at trial as the Nobel Prize of
`
`medicinal chemistry for your work on sitagliptin,
`
`correct?
`
`A
`
`0
`
`Yes, we did.
`
`You are a member of the Medicinal
`
`Chemistry Hall of Fame in part because of your
`
`work on sitagliptin?
`
`A
`
`0
`
`I would imagine, yes.
`
`By any measure you would consider
`
`sitagliptin a success?
`
`A
`
`So if you're referring to sitagliptin
`
`as a success because it is FDA approved, yes.
`
`It
`
`would be a success.
`
`0
`
`Well, even taking it away from that
`
`framework, you yourself, you consider sitagliptin
`
`to be a success in your career, don't you?
`
`A
`
`Well,
`
`I would consider sitagliptin to
`
`be a compound that
`
`I worked on that achieved FDA
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 27
`
`i
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`O~O®\IO~U1-I>0Ol\)
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`approval and is being used to treat patients with
`
`type 2 diabetes.
`
`0
`
`You are aware that it's the biggest
`
`selling of the four FDA approved gliptin
`
`compounds, correct?
`
`A
`
`0
`
`That's correct.
`
`And you are aware that it's the
`
`biggest selling of the ten worldwide approved
`
`gliptin compounds, correct?
`
`A
`
`0
`
`That's correct.
`
`Let me just ask.
`
`Is there any way in
`
`which you think sitagliptin is not successful?
`
`A
`
`Not
`
`if you are referring to success in
`
`the marketplace or success in treating patients
`
`with type 2 diabetes, but no.
`
`No.
`
`0
`
`Now, vildagliptin, you are aware of
`
`the compound vildagliptin, correct?
`
`A
`
`0
`
`I
`
`am.
`
`I don't want to quibble with you about
`
`terminology here.
`
`I understand that the compound
`
`that
`
`is now known as vildagliptin is a prior art
`
`compound to saxagliptin;
`
`is that correct?
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 28
`
`i
`
`O~O®\IO~U1-l>0Ol\)
`
`A
`
`0
`
`That
`
`is correct.
`
`Now,
`
`I
`
`recognize that at the time,
`
`October 2000, Vildagliptin was not known commonly
`
`as vildagliptin but rather the structure of the
`
`compound itself was known at that point, correct?
`
`A
`
`0
`
`That
`
`is correct.
`
`Okay.
`
`Vildagliptin, under your standard in
`
`this case,
`
`is a failure, correct?
`
`A
`
`0
`
`That
`
`is correct.
`
`Now, Vildagliptin is approved in
`
`Europe for treatment of type 2 diabetes as a DPP-4
`
`inhibitor, correct?
`
`A
`
`0
`
`Vildagliptin is approved in Europe.
`
`Okay.
`
`Going back to the patent, you were
`
`talking about Exhibit 1001. We were talking about
`
`the compounds
`
`listed under claim 8.
`
`We had just
`
`finished discussing the first compound under
`
`claim 8.
`
`I would like to ask the same series of
`
`questions with regard to the second compound.
`
`So with respect to the second
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 29
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`i
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`O~O®\IO~U1-I>0Ol\)
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`compound,
`
`the one that has the cyclobutane ring in
`
`it, do you have that, Dr. Weber?
`
`A
`
`0
`
`I do.
`
`Is there any data presented in the
`
`specification of the RE'186 patent pertaining to
`
`potency data for that compound against DPP-4?
`
`A
`
`No.
`
`There is no specific IC50 or Ki
`
`for this compound.
`
`0
`
`Is there any data presented with
`
`respect to that second compound under claim 8 with
`
`respect to in vivo data against DPP-4 or type 2
`
`diabetes?
`
`A
`
`That's correct.
`
`No in vivo data
`
`presented in the patent.
`
`Q
`
`And there is no data presented
`
`regarding activity of a metabolite of that
`
`compound against DPP-4?
`
`A
`
`0
`
`That's correct.
`
`And there is no data about the safety
`
`of that compound?
`
`A
`
`No data about the safety of the
`
`compound in the patent.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
`GregoryEdwards.com I 866-4Team GE
`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 30
`
`i
`
`O~O®\IO~U1-I>0Ol\)
`
`0
`
`No data about the efficacy of the
`
`compound in the patent?
`
`A
`
`No data about the efficacy in the
`
`patent.
`
`0
`
`To your knowledge,
`
`it's never advanced
`
`to clinical trials?
`
`A
`
`To the best of my knowledge,
`
`this
`
`compound has not advanced to clinical trials.
`
`0
`
`A
`
`0
`
`And it is not FDA approved?
`
`It
`
`is not FDA approved.
`
`And under your analysis in this case
`
`that compound is also a failure?
`
`A
`
`0
`
`That's correct.
`
`Okay.
`
`With respect to the third compound
`
`under claim 8,
`
`the one at the bottom of Column 88
`
`that has got the cyclohexyl group, do you see
`
`that?
`
`A
`
`0
`
`I do.
`
`There is no data in the patent
`
`pertaining to in vitro activity against DPP-4?
`
`A
`
`That's correct.
`
`No I050 or Ki.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph D. - October 27, 2016
`
`Page 31
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`
`O~O®\lO~U1-l>0Ol\)
`
`Q
`
`And no data presented relating to
`
`in vivo activity of that compound?
`
`A
`
`0
`
`No in vivo activity.
`
`No information provided relating to
`
`interaction of that compound with the DPP-4
`
`enzyme?
`
`A
`
`0
`
`That's correct.
`
`No information provided regarding
`
`activity of a metabolite of that compound against
`
`DPP-4?
`
`A
`
`No information about metabolites of
`
`this compound.
`
`0
`
`No information provided relating to
`
`safety of this compound in the patent?
`
`A
`
`0
`
`No information on safety.
`
`No information about efficacy of this
`
`compound in the patent?
`
`A
`
`0
`
`That's correct.
`
`No efficacy data.
`
`Under your analysis in this case that
`
`compound is also a failure, correct?
`
`A
`
`This compound was not approved by the
`
`FDA and is a failure.
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 32
`
`i
`
`O~O®\lO~U1-l>0Ol\)
`
`Okay.
`
`There are five compounds at the top of
`
`Column 89 which is also part of claim 8, correct?
`
`A
`
`0
`
`That
`
`is correct.
`
`Okay.
`
`Now, one of the five compounds is
`
`saxagliptin;
`
`is that correct?
`
`A
`
`0
`
`That's correct.
`
`With respect to the four compounds
`
`that are not saxagliptin,
`
`I'm just going to ask
`
`the same series of questions for expediency sake.
`
`With respect to those four compounds,
`
`is there any data presented in the specification
`
`of the RE'186 patent relating to in vivo -- excuse
`
`me,
`
`in vitro activity against DPP-4?
`
`A
`
`There is no specific in vitro data
`
`presented.
`
`0
`
`With respect to the four compounds
`
`that are not saxagliptin on the top of Column 89,
`
`is there any in vivo activity information
`
`presented in the specification?
`
`A
`
`There is no data regarding in vivo
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 33
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`activity.
`
`0
`
`With respect to those four compounds
`
`at the top of Column 89,
`
`is there any information
`
`in the patent relating to activity of any
`
`metabolites of these compounds against DPP-4?
`
`A
`
`No,
`
`there is no information on
`
`metabolites.
`
`Q
`
`Is there any data in the patent with
`
`respect to those four compounds at the top of
`
`Column 89, not
`
`including saxagliptin,
`
`regarding
`
`interaction with the DPP-4 enzyme of those
`
`compounds?
`
`A
`
`No data on interaction with the
`
`enzyme.
`
`0
`
`With respect to the four compounds at
`
`the top of Column 89, not
`
`including saxagliptin,
`
`is there any data on the safety of those
`
`compounds?
`
`A
`
`There is no data on the safety of
`
`these compounds.
`
`0
`
`With respect to the four compounds at
`
`the top of Column 89, not
`
`including saxagliptin,
`
`GregoryEdwards, LLC I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 34
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`is there any information in the patent about the
`
`efficacy of those compounds?
`
`A
`
`No,
`
`there is no efficacy information
`
`in the patent on these compounds.
`
`0
`
`Are you aware that any of the four
`
`compounds at the top of Column 89, not
`
`including
`
`saxagliptin, were ever advanced to clinical
`
`trials?
`
`A
`
`My understanding is that these
`
`compounds were not advanced to clinical trials.
`
`0
`
`And are any of the four compounds we
`
`have been discussing FDA approved?
`
`A
`
`0
`
`No, none of these are FDA approved.
`
`And under your analysis in this case
`
`the four compounds at the top of Column 89, not
`
`including saxagliptin, are failures, correct?
`
`A
`
`That's correct.
`
`These would be
`
`failures.
`
`0
`
`With respect to claim 10, Column 89,
`
`have you got that, Dr. Weber?
`
`A
`
`I do.
`
`Okay.
`
`GregoryEdwards, LLC I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 35
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`There are a group of compounds
`
`identified here with respect to variations in R1.
`
`Do you see that?
`
`I do.
`
`But, generally speaking,
`
`there are
`
`A
`
`0
`
`two,
`
`if you will have it, classes of compounds
`
`identified here, and the difference between the
`
`two classes of compounds is the location of the
`
`cyclopropane ring on that five-membered ring
`
`containing a nitrogen.
`
`Do you see that?
`
`I do see that, yes.
`
`And is my loose terminology, would you
`
`A
`
`0
`
`agree with that,
`
`that the difference between those
`
`two sets of compounds has to do with the location
`
`of the cyclopropane ring in that area of the
`
`molecule?
`
`A
`
`Yes.
`
`These two structures differ by
`
`the location of the cyclopropyl
`
`ring.
`
`0
`
`And the one on top has a
`
`4,5-cyclopropane ring where the one on the bottom
`
`has a 3,4-cyclopropane ring?
`
`GregoryEdwards, LLG I Worldwide Court Reporting
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`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 36
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`
`A
`
`Actually that doesn't
`
`look to be
`
`numbered that way in this particular patent.
`
`But
`
`in general
`
`the terminology we have been using on
`
`the case, yes.
`
`This is the 4,5- -- the upper one
`
`is the 4,5- and the lower one is the 3,4-.
`
`0
`
`Thank you.
`
`Now, with respect to the class of
`
`compounds at the bottom, what we have called the
`
`3,4-cyclopropane compounds,
`
`there is no data in
`
`the patent relating to in vitro activity of that
`
`class of compounds relating to DPP-4, correct?
`
`A
`
`That's correct.
`
`There is no specific
`
`in vitro data on these compounds.
`
`0
`
`A
`
`compounds.
`
`No Ki, no I050?
`
`No Ki, no I050 on any of these
`
`0
`
`With respect to -- with respect to
`
`in vivo data,
`
`there is no in vivo data on these
`
`compounds in the patent?
`
`A
`
`That's right.
`
`No in vivo data in the
`
`patent on these compounds.
`
`0
`
`And there is no information relating
`
`GregoryEdwards, LLG I Worldwide Court Reporting
`GregoryEdwards.com I 866-4Team GE
`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 37
`
`i
`
`O~O®\lO~U1-l>0Ol\)
`
`to potential activity of potential metabolite of
`
`any of these compounds in the patent?
`
`A
`
`That's correct, no metabolite
`
`information for these compounds.
`
`0
`
`And there is no data provided in the
`
`patent relating to interaction of any of those
`
`compounds with the DPP-4 enzyme, correct?
`
`A
`
`0
`
`That's correct.
`
`And there is no data relating to
`
`safety of those compounds?
`
`A
`
`That's correct.
`
`No safety data on
`
`these compounds in the patent.
`
`0
`
`No efficacy data in the patent about
`
`these compounds?
`
`A
`
`There is no efficacy data in the
`
`patent on these compounds.
`
`0
`
`Under your analysis those compounds
`
`would be a failure, correct?
`
`A
`
`None of these are FDA approved,
`
`thus a
`
`failure.
`
`0
`
`Let's talk about saxagliptin for a
`
`moment.
`
`In terms of the saxagliptin molecule,
`
`GregoryEdwards, LLG I Worldwide Court Reporting
`GregoryEdwards.com I 866-4Team GE
`
`
`
`Ann E. Weber, Ph.D. - October 27, 2016
`
`Page 38
`
`i
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`O~O®\IO~U1-I>0Ol\)
`
`there is no data in the patent relating to in vivo
`
`activity of saxagliptin against DPP-4,
`
`is there?
`
`A
`
`No,
`
`there is no in vivo data on
`
`saxagliptin in the patent.
`
`Q
`
`And there is no information in the
`
`patent relating to in vivo activity of
`
`saxagliptin, correct?
`
`A
`
`That
`
`is correct.
`
`No in vivo data on
`
`saxagliptin is reported in the patent.
`
`Q
`
`And there is no