1004
`
`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`__________________________________
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
` Plaintiffs,
`-vs-
`FRESENIUS KABI USA, LLC,
`Defendant.
`
`CIVIL ACTION NUMBER:
`3:14-cv-07869-MAS-LHG
`3:14-cv-08082-MAS-LHG
`3:15-cv-02631-MAS-LHG
`
`3:15-cv-02522-MAS-LHG
`3:16-cv-02259-MAS-LHG
`
` TRIAL
`
` VOLUME 6
`
`3:15-cv-02523-MAS-LHG
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
` Plaintiffs,
` -vs-
`DR. REDDY'S LABORATORIES,
`INC., et al.,
` Defendants.
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
` Plaintiffs,
`
` -vs-
`
`GLENMARK GENERICS INC. et
`al.,
` Defendants.
`_____________________________
`
`1 2 3 4 5 6 7 8 9
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`11
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`United States District Court
`Trenton, NJ
`
`Sanofi Exh. 2023
`Neptune v. Aventis
`IPR2019-00136
`
`
`
`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`__________________________________
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
` Plaintiffs,
`-vs-
`FRESENIUS KABI USA, LLC,
`Defendant.
`
`CIVIL ACTION NUMBER:
`3:14-cv-07869-MAS-LHG
`3:14-cv-08082-MAS-LHG
`3:15-cv-02631-MAS-LHG
`
`3:15-cv-02522-MAS-LHG
`3:16-cv-02259-MAS-LHG
`
` TRIAL
`
` VOLUME 6
`
`3:15-cv-02523-MAS-LHG
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
` Plaintiffs,
` -vs-
`DR. REDDY'S LABORATORIES,
`INC., et al.,
` Defendants.
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
` Plaintiffs,
`
` -vs-
`
`GLENMARK GENERICS INC. et
`al.,
` Defendants.
`_____________________________
`
`1 2 3 4 5 6 7 8 9
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`11
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`13
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`
`United States District Court
`Trenton, NJ
`
`Sanofi Exh. 2023
`Neptune v. Aventis
`IPR2019-00136
`
`
`
`1005
`
`3:14-cv-08079-MAS-LHG
`3:15-cv-02520-MAS-LHG
`
`3:14-cv-08081-MAS-LHG
`3:15-cv-02521-MAS-LHG
`
`3:15-cv-00287-MAS-LHG
`3:15-cv-01835-MAS-LHG
`
`_____________________________
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
`
`Plaintiffs,
`
` -vs-
`ACCORD HEALTHCARE, INC.
` Defendant.
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI
`
` Plaintiffs,
` -vs-
`BPI LABS, LLC and BELCHER
`PHARMACEUTICALS, LLC
` Defendants.
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI
` Plaintiffs,
` -vs-
`APOTEX CORP. and APOTEX, INC.
` Defendants.
`_____________________________
`
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`United States District Court
`Trenton, NJ
`
`
`
`1006
`
`3:15-cv-00776-MAS-LHG
`3:15-cv-03107-MAS-LHG
`
`3:15-cv-01863-MAS-LHG
`3:15-cv-00289-MAS-LHG
`
`3:15-cv-00290-MAS-LHG
`3:15-cv-03392-MAS-LHG
`
`_____________________________
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI
` Plaintiffs,
` -vs-
`
`ACTAVIS LLC and ACTAVIS
`ELIZABETH LLC,
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI
`
` Plaintiffs,
`
` -vs-
`BRECKENRIDGE PHARMACEUTICAL,
`INC.
`
` Defendant.
`
`SANOFI-AVENTIS U.S. LLC,
`AVENTIS PHARMA S.A. and
`SANOFI,
`
` Plaintiffs,
`
` -vs-
`
`MYLAN LABORATORIES LTD.
`
` Defendant.
`__________________________________
`
`United States District Court
`Trenton, NJ
`
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`
`
`1007
`
`Clarkson S. Fisher United States Courthouse
` 402 East State Street
`Trenton, New Jersey 08608
` September 27, 2017
`
`B E F O R E: HONORABLE MICHAEL A. SHIPP
` UNITED STATES DISTRICT JUDGE
`A P P E A R A N C E S:
`WALSH, PIZZI, O'REILLY, FALANGA LLP, ESQS.
`BY: LIZA M. WALSH, ESQUIRE
` and
` KATELYN O'REILLY, ESQUIRE
`Attorneys for the Plaintiffs Sanofi-Aventis, U.S., LLC
`and Aventis Pharma, S.A.
`(Walsh, Pizzi, et al., does not represent Plaintiff
`(Actavis) in the 15-0776 and 15-3107 matters.)
`
`FITZPATRICK, CELLA, HARPER & SCINTO, ESQUIRES
`BY: WILLIAM SOLANDER, ESQUIRE
` MELINDA E. ROBERTS, ESQUIRE
` DOMINICK A. CONDE, ESQUIRE
` UNA FAN, ESQUIRE
` and
` WHITNEY L. MEIER, ESQUIRE
`Attorneys for the Plaintiffs Sanofi-Aventis U.S. LLC,
`et al.
`TIMOTHY CREAGAN, ESQUIRE
`JIANG LIN, ESQUIRE
`Attorney for the Plaintiffs Sanofi-Aventis U.S. LLC,
`et al.
`PATUNAS & TARANTINO LLC
`BY: MICHAEL E. PATUNAS, ESQUIRE
` and
` ERIC T. ROMEO, ESQUIRE
`Attorneys for the Defendant Fresenius Kabi USA, LLC.
`and Actavis, LLC.
`GOODWIN PROCTER LLP
`BY: DARYL L. WIESEN, ESQUIRE
` BRIAN J. PREW, ESQUIRE
` EMILY L. RAPALINO, ESQUIRE
` and
` AVIV A. ZALCENSTEIN, ESQUIRE
`Attorneys for the Defendant Fresenius Kabi USA, LLC.
`
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`United States District Court
`Trenton, NJ
`
`
`
`1008
`
`A P P E A R A N C E S cont'd
`NATHAN NEWBOLD, ESQUIRE
`ALI I. AHMED, ESQUIRE
`Attorneys for the Defendant Fresenius Kabi USA, LLC.
`JAMES MAHANNA, ESQUIRE
`Attorney for the Defendant Actavis, LLC.
`WILSON, SONSINI, GOODRICH & ROSATI, ESQUIRES
`BY: MATTHEW R. REED, ESQUIRE
` WENDY L. DEVINE, ESQUIRE
` and
` KRISTINA HANSON, ESQUIRE
`Attorneys for Defendant Mylan Laboratories Ltd.
`VINNY LEE, ESQUIRE
`Attorney for the Defendant Mylan Laboratories Ltd.
`SAIBER, LLC
`BY: ARNOLD B. CALMANN, ESQUIRE
`Attorneys for the Defendant Mylan Laboratories Ltd.
`SCHIFF HARDIN, LLP
`BY: HELEN H. JI, ESQUIRE
` and
` IMRON ALY, ESQUIRE
`Attorneys for the Defendant Accord Healthcare, Inc.
`
`TAFT, STETTINIUS & HOLLISTER LLP
`BY: ANDREW M. ALUL, ESQUIRE
` ROSHAN P. SHRESTHA, Ph.D
` and
` RICHARD T. RUZICH, ESQUIRE
`Attorneys for the Defendant Apotex Corp. and Apotex
`Inc.
`HILL WALLACK, LLP
`BY: CHRISTINA L. SAVERIANO, ESQUIRE
`Attorneys for the Defendant Apotex Corp. and Apotex
`Inc.
`Certified as True and Correct as required by Title 28,
`U.S.C., Section 753
`/S/ Cathy J. Ford, CCR, CRR, RPR
`/S/ Megan McKay-Soule, RMR, CRR
`
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`
`
`
`
`WITNESS
`
` I N D E X
`
`HERVÉ BOUCHARD
`DIRECT EXAMINATION BY MR. SOLANDER
`CROSS EXAMINATION BY MR. ALUL
`CROSS EXAMINATION BY MR. ALUL
`REDIRECT EXAMINATION BY SOLANDER
`DR. PATRICIA VRIGNAUD
`DIRECT EXAMINATION BY MS. MEIER
`CROSS EXAMINATION BY MS. RAPALINO
`
`1009
`
`PAGE
`
`1014
`1015
`1061
`1079
`1099
`1103
`1104
`1156
`
` E X H I B I T S
`
`NUMBER
`
`DTX-2679 (key results memo only)
`Plaintiffs' Exhibits JTX-133, 153, 154, and
`155 moved in evidence.
`Defendants' Exhibit DTX-2104 moved in
`evidence.
`Plaintiffs' Exhibits JTX-44, PTX-1362
`Defendants' Exhibit DTX-2083, DTX-2098,
`DTX-2099, and DTX-2312 in evidence.
`Defendants' Exhibit DTX-2701 in evidence.
`
` EVID.
`
`1101
`1102
`1211
`
`1212
`
`
`
`United States District Court
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`Bouchard - direct - Solander
`
`1042
`
`destroyed the activity in vivo?
`A.
`Right.
`Q.
`Last, but not least, let's look at PDTX-627, and
`can you explain what was done here?
`A.
`So, here are some examples we made in -- after
`the discovery of larotaxel, we wanted to know whether
`this very particular modification here, with this
`small cycle --
`Q.
`With this small cycle.
`A.
`Small cycle -- whether we could improve, still
`improve the potency of this kind of subfamily of
`molecules. So that's why we stay with this
`modification, this cycle, small cycle, and we
`introduce various modification and various function at
`C-10.
`Could I have PDTX-616 just one more time,
`Q.
`please. I got a note that I just -- we need to get
`something into the record.
`Dr. Bouchard, did you testify that some of
`these compounds were made in order to improve the
`water solubility of docetaxel?
`A.
`Right.
`Q.
`Okay. Thank you. Let's look at -- let's talk
`now about your synthesis of cabazitaxel in your
`laboratory notebooks.
`
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`Bouchard - direct - Solander
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`1043
`Could we look at PDTX-628, please. What is
`this, Dr. Bouchard?
`A.
`This is one of my notebooks -- lab notebooks.
`Q.
`Okay. And I notice that there's a little 2 down
`here, what does that refer to?
`A.
`This is my second lab notebook.
`Q.
`Okay. So since you joined the company, you've
`had one other lab notebook before this one?
`A.
`Right.
`Q.
`And when did the experiments in this lab
`notebook start?
`A.
`It started 6th of January, 1993.
`Q.
`Okay. Let's go to Page 186 of notebook number 2
`JTX-153. Can you tell me, what is the date of that
`particular notebook page?
`A.
`So the date was the 15th of October, 1993.
`Q.
`And can you tell me, what is this shown here?
`The sort of chemical scheme that we see here, what is
`that?
`So this is a general scheme. This is a general
`A.
`reaction I intended to do at the beginning.
`Q.
`So this is your plan for this experiment; is
`that right?
`A.
`Right.
`Q.
`Okay. How was your notebook kept? How did you
`
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`Bouchard - direct - Solander
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`1044
`
`do your notebook?
`A.
`Day-by-day writing what I did in the lab.
`Q.
`Okay. So this is what you happen to be doing on
`the 15th of October, 1993?
`A.
`Right.
`Q.
`Okay. So let's look at the scheme if we can.
`So this is the starting material?
`A.
`Right.
`Q.
`And what is the starting material that's
`depicted here?
`A.
`So the starting material here is a protected
`form of Taxotere.
`Q.
`And could you point with the laser pointer where
`the protected -- what you mean by protected?
`A.
`So here, introduce what we call a silyl group
`here in order to protect this alkyl function here.
`Q.
`Okay. So what would this be without the silyl
`group?
`A.
`Well, it could be the direction I want to do, it
`could occur at this position, and I didn't want to.
`Q.
`So you protected this from the reaction that
`you're carrying out so the reaction didn't occur
`there?
`A.
`Right.
`Q.
`Okay. What did you want to do with this
`
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`
`1045
`
`reaction?
`A.
`I wanted to introduce a methoxy group at the C-7
`position here, as I draw here.
`Q.
`So you wanted to do that. All right. What is
`this line and these chemicals above it refer to?
`A.
`So, this refers to the general conditions I will
`use, and also the reactants -- the chemical reactants
`I will use for this direction. Chemical reactants.
`Q.
`So, these are the chemical reactants you will
`use to perform this reaction, and what does the
`20-degree celsius refer to?
`A.
`Well, it means the direction will be run at, at
`room temperature.
`Q.
`Okay. Was this -- were these reagents
`considered mild or aggressive?
`A.
`These could be considered as mild.
`Q.
`Okay. Was this reaction successful?
`A.
`No, it was a failure.
`Q.
`Okay. And do you know what happened?
`A.
`Yes. I observed epimerization and degradation
`products.
`Q.
`Epimerization?
`A.
`Epimerization.
`Q.
`Yeah. E-P-I-M-E-R-I-Z-A-T-I-O-N.
`A.
`Yes.
`
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`1046
`
`And degradation.
`Q.
`And degradation products.
`A.
`Thank you. So let's turn to PDTX-630, which is
`Q.
`Page 188 out of JTX-153. What was the date that this
`experiment was carried out?
`A.
`So, the date is 15th of October, 1993.
`Q.
`So this is the same date we saw on the prior
`experiment?
`A.
`Yes, I run both experiments in parallel.
`Q.
`In parallel. And what is the starting material
`in this experiment?
`A.
`So, the starting material in this experiment is
`also a protected form, here you got the same silyl
`group on this function, and we've got an epimerized
`function at C-7 here, as the normal stereochemistry at
`this position is up; this one is epimerized, it means
`it's down.
`Q.
`And what was the purpose of using the starting
`material that had the 7-hydroxyl group in the
`alternative down position?
`A.
`Well, I knew from my personal previous
`experience in this taxane chemistry that the 7
`epimerized position was much less reactive.
`Q.
`And what was the purpose using the compound that
`had a much less reactive hydroxyl group at the 7
`
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`
`position?
`A.
`Well, the intent was to direct reaction only on
`the 10 position, here.
`Q.
`So you wanted it to -- the methoxy group to go
`solely on the 10 position, not on the 7 position, and
`not on the 2 prime position?
`A.
`Right.
`Q.
`Okay. And what were -- the reagents that you
`were using here depicted on the page, were those
`considered mild or aggressive?
`A.
`Mild.
`Q.
`Okay. And it was done at room temperature?
`A.
`Right.
`Q.
`And was this reaction successful?
`A.
`No, failure.
`Q.
`Okay. Now, we're going to switch to another
`notebook. This is -- what notebook number is this?
`A.
`It's my third notebook.
`Q.
`And can you tell me the date that the notebook
`was started?
`A.
`So it the 15th of November, 1993.
`Q.
`So this is JTX-155, and the front page is being
`depicted on PDTX-0631. Let's turn to Page 150 of that
`notebook. Can you tell me the date that this
`experiment was carried out?
`
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`1048
`
`This experiment was done the 11th of April,
`
`A.
`1994.
`And what was the starting material that is
`Q.
`depicted at the top of the page on PDTX-0632?
`A.
`Well, for this particular experiment I use
`baccatin form, a protected baccatin form with silyl
`protective group at C-7 and C-13, here.
`Q.
`And, again, why did you protect these hydroxyl
`groups here at C-7 and C-13?
`A.
`So, the goal here was to prevent any reaction to
`occur at this position and to direct the methylation
`reaction only --
`Q.
`Methylation.
`A.
`-- to direct the methylation reaction only at
`the C-10 position.
`Q.
`And were the reaction conditions here considered
`mild or aggressive?
`A.
`More aggressive.
`Q.
`More aggressive. And was this reaction
`successful?
`A.
`Yes, it was.
`Q.
`Okay. So let's look at the next experiment at
`Page 158 of the notebook JTX-155, and it's depicted
`here on PDTX-0633. What did you do -- what was the
`date of this reaction?
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`1049
`
`So the date of this reaction was the 18th of
`A.
`April, 1994.
`Q.
`Okay. And what was the intent of this reaction?
`A.
`So the intent of this reaction was to remove a
`protective function here, the silyl protective
`function, at C-7 and C-13 to gain the free hydroxyl.
`Q.
`Gain the free hydroxyl. Were you successful in
`gaining the free hydroxyl?
`A.
`Right.
`Q.
`So let's look at the next experiment. This is
`Page 162 of JTX-155 at PDTX-0634. Could you tell us
`the date of this experiment?
`A.
`The date is the 18th of April, 1994.
`Q.
`This is the same date as the prior experiment?
`A.
`Yes.
`Q.
`Okay. And what were you doing here?
`A.
`I'm doing, in fact, a protection of -- a
`selective protection of the C-7 position.
`Q.
`So you're adding a protecting group back onto
`C-7?
`Right.
`A.
`Okay. And was this reaction successful?
`Q.
`Yes.
`A.
`This is page 170 of PTDX-0635. Can you tell us
`Q.
`the date of this experiment?
`
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`1050
`
`So, it was done on 21st of April, 1994.
`A.
`And what were you doing in this experiment?
`Q.
`So, I was introducing a protected form of side
`A.
`chain to the baccatin -- modified baccatin.
`Q.
`And was this reaction successful?
`A.
`Yes, it was.
`Q.
`Let's look at Page 176 of JTX-155, depicted on
`PDTX-0636. What is the date of this reaction?
`A.
`SO the date of this reaction is the 27th of
`April, 1994.
`Q.
`And what were -- what did you do in this
`reaction?
`A.
`In this reaction I'm trying to remove the
`protection of the side chain and simultaneously remove
`protecting group at C-7.
`Q.
`And were you successful in this reaction?
`A.
`Yes.
`Q.
`Now, was this a final product that you were
`trying to obtain in this particular series of
`experiments?
`A.
`Yes, it was.
`Q.
`Okay. And what was the final product you
`obtained in this experiment?
`A.
`It was the 10-methoxy Taxotere analog.
`Q.
`Okay. So it's docetaxel with a methoxy group on
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`the 10 position?
`A.
`Right.
`Q.
`Let's look at the last notebook. Can you tell
`me what notebook number JTX-154 is?
`A.
`This is my fourth lab notebook.
`Q.
`Okay. And what is the date that the experiment
`started in this notebook?
`A.
`So it started the 26th of May, 1994.
`Q.
`All right. And let's go to Page 8 of that
`notebook. Can you tell me the date of the experiment
`that's depicted here on PDTX-0638?
`A.
`It was the 4th of July, 1994.
`Q.
`And what were you attempting to do in this
`experiment?
`A.
`I was trying to introduce an ethoxy group at the
`C-10 position here from this protected form of
`baccatin.
`Q.
`And so what's the difference between an ethoxy
`group and a methoxy group?
`A.
`Well, it's -- ethoxy groups have 2 carbon long,
`and methoxy has only 1 carbon long.
`Q.
`One carbon versus two carbon length?
`A.
`Right.
`Q.
`And was this reaction carried out with mild or
`aggressive conditions?
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`Aggressive conditions.
`A.
`And was this reaction successful?
`Q.
`No.
`A.
`I don't know if I asked the date of this
`Q.
`reaction. What date was it?
`A.
`The 4th of July, 1994.
`Q.
`Not a holiday in France?
`A.
`No. Only the 14th.
`Q.
`Let's look at Page 10, also on the same date
`PDTX-0639, and what are you trying to do here?
`A.
`I'm trying to introduce a butoxy group at C-10
`position on the baccatin core.
`Q.
`So what is the different between a butoxy group
`and a methoxy group?
`A.
`The butoxy group has a 4 carbon long chain, and
`methoxy group has only one carbon.
`Q.
`So it's a longer chain of carbons?
`A.
`Right.
`Q.
`Okay. And were the conditions aggressive or
`mild here?
`A.
`Aggressive.
`Q.
`And was this reaction successful?
`A.
`No.
`Q.
`Now, let's go to Page 56. Just a few more.
`This is -- when was this reaction carried out?
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`It was done the 18th of October, 1994.
`A.
`Okay. And what were you attempting to do in
`Q.
`this reaction?
`A.
`Well, I was trying to do two things in the same
`reaction. One was to invert -- one was to invert the
`stereochemistry at C-7 from down to up, and the second
`was to introduce a methoxy group on the C-7 position.
`Q.
`So you want to make -- get rid of the difference
`of orientation of the C-7 hydroxyl group at the same
`time add a methyl group?
`A.
`Right.
`Q.
`Okay. And were the reaction conditions you were
`using here aggressive or mild?
`A.
`More aggressive, yes.
`Q.
`More aggressive. And was there anything unusual
`about the reaction conditions that you did in this
`particular experiment?
`A.
`In this particular experiment, no. No.
`Q.
`Okay. And can you tell me whether this reaction
`was successful or not?
`A.
`No, it was a failure.
`Q.
`It was a failure. All right. Let's look at
`PBX-0641. This is Page 60 of JTX-154. Can you
`describe what was -- first of all, what's the date on
`this reaction?
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`The date is the 19th of October, 1994.
`A.
`And what were you trying to do in this reaction?
`Q.
`So I'm trying to introduce methoxy function at
`A.
`C-7 on this particular baccatin.
`Q.
`And what is also different about this particular
`baccatin here?
`A.
`Because this baccatin already has a methoxy
`group at C-10.
`Q.
`Okay. So you're trying to add second methoxy on
`the C-7?
`A.
`Right.
`Q.
`And as to the reaction conditions, were these
`aggressive or mild?
`A.
`They were much more -- much more aggressive.
`Q.
`Okay. And was there anything unusual about the
`way you carried out this experiment?
`A.
`Well, due to my previous failures, as we show
`before, I was to use, in fact, reactant which is
`methyl -- I was to use methyl iodide as a solvent,
`which is completely unusual for an organic chemist.
`Q.
`Did you find that particular procedure that you
`carried out here in the literature anywhere?
`A.
`No.
`Q.
`Was this reaction successful?
`A.
`Yes, but with a very low yield.
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`Okay. And what does it mean to get a low yield?
`Q.
`Well, it means that you have to engage a lot of
`A.
`starting material to gain enough compound to pursue
`your synthesis.
`Q.
`So let's look at the next experiment, PDTX-642,
`which is Page 74 of JTX-154, can you tell me the date
`of this experiment?
`A.
`So the date of this experiment is 25th of
`October, 1994.
`Q.
`Okay. And, again, is this the same starting
`material that we just saw in the prior experiment?
`A.
`Right.
`Q.
`And how do these reaction conditions compare to
`that prior experiment where you were using methyl
`iodide as the solvent?
`A.
`Well, I would say it's almost quite the same
`unusual conditions because I use a very little amount
`of DMF as a co-solvent, but many --
`Q.
`DMF?
`A.
`-- DMF as a co-solvent, many I use the reactant
`as a solvent.
`Q.
`So when you say reactant as the solvent, what
`exactly do you mean?
`A.
`Well, I use, in fact, methyl iodide as almost
`all of the solvent to make the starting material in
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`the solution.
`Q.
`So the chemicals are reacted in a solvent, not
`dry on the table?
`A.
`No, no.
`Q.
`Okay. And you're using the actual reactant
`methyl iodide as your solvent in these --
`A.
`Yes. In this case, yes.
`Q.
`Okay. Was this reaction successful?
`A.
`Not -- well, I obtained the compound, but in
`mixture. I was not able to separate the compound.
`Q.
`So it's in a mixture, but you can't isolate it
`out?
`No.
`A.
`So what did you do?
`Q.
`Well, I decided to pursue and to use this
`A.
`mixture to go further, one step further.
`Q.
`Okay. So we're looking at Page 88 of JTX-154 at
`PDTX-0643, and just to -- what was the date of this
`reaction?
`A.
`So the date of this reaction is the 9th of
`November, 1994.
`Q.
`Now, I see what is depicted here in the middle
`of the page, it looks like a single compound, and
`you're telling me that's not a single compound?
`A.
`No, not this case. It was the mixture we
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`previously saw.
`Q.
`So it's a mixture, but this compound is
`somewhere in that mixture?
`A.
`Yes.
`Q.
`Okay. So what did you do here?
`A.
`So with this mixture I tried to couple the
`protected form of the side chain here -- the protected
`form of the side chain to the baccatin, modified
`baccatin.
`Q.
`And were you successful?
`A.
`Yes. And especially I was successful to
`separate the mixture I had at the beginning.
`Q.
`So you were able -- after you made this compound
`you were able to isolate the one you wanted?
`A.
`Right.
`Q.
`Okay. And so what did you do next?
`A.
`So the next step is to remove your protection on
`the side chain here.
`Q.
`And what's the date of this experiment?
`A.
`This experiment is -- was done on the 15th of
`November, 1994.
`Q.
`And what was the result that you ended up here
`with?
`Well, I obtained the first synthesis of
`A.
`cabazitaxel.
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`So that's cabazitaxel there on the right-hand
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`Q.
`side?
`Right.
`A.
`And that's the first time you ever made that in
`Q.
`the laboratory?
`A.
`Yes.
`Q.
`On the 15th of November, 1994?
`A.
`Right.
`Q.
`On your understanding, were you the first person
`in the world to have made that compound on that --
`A.
`Yes.
`Q.
`Let's look at the biological data, if we could,
`for cabazitaxel. It's on the left-hand side, and we
`have 116258. Is that the code for cabazitaxel?
`A.
`Right.
`Q.
`And on the other side we have docetaxel?
`A.
`Yes.
`Q.
`Okay. So on -- can you compare for us the
`biological data with -- on PTDX-0645?
`A.
`So this new structure has good activity on
`normal cancer cell lines and improved, clearly
`improved activity on registrant cell lines, both on
`IC50 and also on the index factor here. And when
`looking at the in vivo data here, you can see that
`this compound has a very good activity on B16 in vivo
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