`1408
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`IN THE UNITED STATES DISTRICT COURT
`
`IN AND FOR THE DISTRICT OF DELAWARE
`
`ELAN PHARMA INTERNATIONAL
`LIMITED ,
`
`Civil Action
`
`Plaintiff,
`
`v.
`
`ABRAXIS BIOSCIENCE INC. ,
`
`Defendant.
`
`No. 06-438-GMS
`
`Wilmington , Delaware
`Tuesday, June 10 , 2008
`8:45 a.m.
`SEVENTH DAY OF TRIAL
`
`BEFORE: HONORABLE GREGORY M. SLEET, Chief Judge,
`and a Jury
`
`APPEARANCES:
`
`JOHN G. DAY, ESQ .
`Ashby & Geddes
`-and-
`STEPHEN SCHEVE, ESQ. ,
`LINDA M. GLOVER , ESQ .,
`JEFFREY SULLIVAN, ESQ. ,
`ROBERT RIDDLE , ESQ., and
`PAUL FEHLNER , ESQ .
`Baker Botts LLP
`(Houston, TX)
`-and(cid:173)
`GREGORY BOKAR, ESQ.
`Counsel - Elan Drug Delivery
`
`Counsel for Plaintiff
`
`Apotex v. Abraxis - [PR20 18-00 [53, Ex . [01 3, p.O I of 222
`
`
`
`Case 1:0 cv-00438-GM S Document 625 Filed 06/24/08 Page 2 of 222 PagelD #: 10196
`1409
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`APPEARANCES CONTINUED:
`
`ELENA C. NORMAN , ESQ., and
`MICHELLE SHERETTA BUDlCAK, ESQ.
`Young Conaway Stargatt & Taylor, LLP
`-and-
`MICHAEL A. JACOBS , ESQ.,
`EMILY A. EVANS, ESQ. ,
`ERIC S. WALTERS , ESQ.,
`LISA CHIARINI, ESQ.,
`DIANA KRUZE I ESQ. , and
`ERIK J. OLSON, ESQ.
`Morrison & Foerster
`(San Francisco, CA)
`
`Counsel for Defendant
`
`THE COURT: Good morning.
`
`(Counsel respond "Good morning . ")
`
`THE COURT:
`
`I understand we have an issue .
`
`MR . JACOBS: A couple of things , Your Honor .
`
`THE COURT:
`
`I hope they are short .
`
`MR . JACOBS: Two are short and one may take a
`
`few minutes. No. I, we have reac hed a stipulation on a
`
`person of ordinary skill in the art .
`
`THE COURT: Good.
`
`I was wondering whether we
`
`were going to hear about that mystic person .
`
`MR . JACOBS: Procedurally , Your Honor , would you
`
`like Ms . Kruze to read it? It would have come up ~n
`
`Dr. Amiji's testimony . Ms . Kruze could just read the
`
`stipulation into the record , if that would be appropriate.
`
`MR. SCHEVE: Fine.
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 101 3, p.02 of 222
`
`
`
`Case 1:0 cv-00438-GMS Document 625 Filed 06/24/08 Page 3 of 222 PagelD #: 10197
`1410
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`MR. JACOBS: No.2, documents in evidence. How
`
`do we work?
`
`I am still a little confused.
`
`I know we have
`
`heard several times how this is supposed to work but we are
`
`at the level of mechanics, understanding what is in and what
`
`isn't, especially documents that are --
`
`THE COURT: All objections were overruled to
`
`documentary exhibits, unless raised again.
`
`I have not
`
`entertained any additional objections. So it's in.
`
`MR. JACOBS: On the original exhibits list, all
`
`those exhibits are in evidence.
`
`THE COURT: Are in. What you want the jury to
`
`consider is another matter.
`
`Is that where we are going with
`
`this?
`
`MR. JACOBS: No.
`
`I think there are documents
`
`THE COURT:
`
`For your record, they are in.
`
`MR. JACOBS: For closing --
`
`THE COURT: That's evidence.
`
`MR. JACOBS: Terrific.
`
`THE COURT: Mr. Scheve, do you have any
`
`questions?
`
`MR. SCHEVE: That's exactly what I have
`
`understood, Your Honor.
`
`MR. JACOBS: Dr. Brittain, two alternative
`
`paths, from our standpoint.
`
`No.1, we put him on the stand, he is here in
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.03 of 222
`
`
`
`Case 1:0 cv-00438-GM S Document 625 Filed 06/24/08 Page 4 of 222 PagelD #: 10198
`1411
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`the courtroom, by the way. We put him on the stand, and we
`
`examine him pursuant to the sec ond Bench memo we filed
`
`yesterday , in which we elicit only -- I can hand Your Honor
`
`a copy.
`
`yesterday.
`
`Mr. Scheve?
`
`Honor .
`
`THE COURT:
`
`I got it yesterday , you say?
`
`MR . JACOBS: Yes. We didn't focus on it
`
`THE COURT: Have you seen the Bench memo ,
`
`MR . SCHEVE: Yes.
`
`MR . JACOBS: We gave it to them yesterday, Your
`
`The ma in point of this Bench memo, Your Honor ,
`
`is that when we ask him questions , we do not want him
`
`volunteering, we do not want counsel for Elan eliciting
`
`testimony beyond the specific and narrow facts that are
`
`already in the record from his deposition or from the
`
`documen ts .
`
`THE COURT: You know , coun s e~ and those in the
`
`well , you can sit .
`
`It seems like this is going to take a
`
`few minutes. There is no reason for you to have to stand.
`
`Mr . Jacobs.
`
`MR. JACOBS: There is only one question from the
`
`deposition that I need to ask him, which is, Did you perform
`
`studies on Abraxane? Beyond that ,
`
`I don't believe counsel
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 101 3, p.04 of 222
`
`
`
`Case 1:0 cv-00438-GM S Document 625 Filed 06/24/08 Page 5 of 222 PagelD #: 10199
`1412
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`for Elan should be allowe d to elicit additional testimony
`
`about what he did because he was instruc ted not to answer a
`
`whole range of questions about what he actually did at his
`
`deposition .
`
`Actually, the second path is that we do not put
`
`Dr. Brittain on the stand, and the Court explains to the
`
`jury what happened with the privilege log and why we are
`
`where we are .
`
`I prepared and gave to counsel for Elan
`
`yesterday a proposed statement from the Bench that would
`
`just layout, very briefly, layout exactly what happened.
`
`That way , we don't have to deal with uncertainties about
`
`what Dr . Brittain might say when he testifies on this issue.
`
`THE COURT:
`
`I got to believe that Mr. Scheve
`
`probably doesn't want the jury hearing about that from me.
`
`Maybe I am wrong about that.
`
`MR. SCHEVE: Well, after all day yesterday
`
`asking witness es, What did you have for breakfast? , and
`
`hearing , Well, I had eggs right next to an order of
`
`amorphous paclitaxel contained in Abraxis, all day, and now
`
`to have counsel say, We really don't want any gratuitous
`
`answers , or to go beyond -- they are now the sponsoring
`
`witness , Your Honor . There i s no expert report from him .
`
`If they are going to ask fact que s tions, you know , it's my
`
`decision , I would think , whether or not I wade into
`
`something.
`
`I will be very cautious about that. The idea
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 101 3, p.05 of 222
`
`
`
`Case 1:0 cv-00438-GMS Document 625 Filed 06/24/08 Page 6 of 222 PagelD #: 10200
`1413
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`that counsel can say, in advance, that I am restricted to
`
`what I may ask --
`
`THE COURT:
`
`I am not going to do that,
`
`Mr. Jacobs. You will have to object.
`
`MR. JACOBS: To be clear, Mr. Scheve instructed
`
`Dr. Brittain at his deposition not to answer additional
`
`questions.
`
`THE COURT:
`
`I think both sides know what the
`
`issue is with Dr. Brittain. We have had an extensive
`
`discussion about this.
`
`I am tired of it. Let's move on.
`
`Let's get this trial back underway.
`
`Ms. Walker, bring in this jury.
`
`MR. SCHEVE:
`
`I do have an issue, Your Honor.
`
`They have tendered something they want to either read to the
`
`jury or give to them that talks about your ruling that says,
`
`Your Honor has ruled
`
`THE COURT: That was the second path that he was
`
`just talking about. Right?
`
`MR. SCHEVE: They have offered an instruction
`
`which would
`
`THE COURT:
`
`I just rejected --
`
`MR. SCHEVE:
`
`It is a separate issue. On this
`
`inference, they have offered an instruction, and they also
`
`now want to read or show the jury, in writing, that Your
`
`Honor has found that Elan, my client, has willfully or
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.06 of 222
`
`
`
`Case 1:0 cv-00438-GM S Document 625 Filed 06/24/08 Page 7 of 222 PagelD #: 10201
`1414
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`wrongfully
`
`THE COURT: We are not going to do that , either.
`
`MR . SCHEVE:
`
`It would be two comments on the
`
`inference. That should be in the jury instructions .
`
`THE COURT: That is where it will be.
`
`MR . JACOBS:
`
`I need to know what you have
`
`decided on the jury instructions.
`
`THE COURT: Are you talking about the final jury
`
`instructions?
`
`MR . JACOBS:
`
`I am sorry , Your Honor .
`
`I
`
`thought
`
`you said to Mr. Scheve, on the jury ins tructions
`
`THE COURT:
`
`I am instructing this jury at this
`
`p o int o n Dr. Brittain .
`
`I am going t o give an ins truction on
`
`the final jury instruction -- you are going to be trial
`
`lawyers and we are going to try this case with this witnes s
`
`on the stand . You will interpose objections .
`
`I will rule
`
`on those objec tions .
`
`It is not unduly complicated .
`
`MS . KRUZE: Your Honor , shall I read into the
`
`record the person of ordinary s kill?
`
`THE COURT: Don ' t you want the jury to hear it?
`
`MS . KRUZE: Yes .
`
`THE COURT:
`
`I certainly would like to hear it.
`
`I think the jury would like to hear it .
`
`We had a witness on the stand, Dr. Amiji.
`
`Dr . Amiji , please.
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 101 3, p.07 of 222
`
`
`
`Case 1:0 cv-00438-GM S Document 625 Filed 06/24/08 Page 8 of 222 PagelD #: 10202
`1415
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Doctor , you are still under oath. Good morning.
`
`(Jury enters courtroom at 9:07 a.m.)
`
`THE COURT: Good morning on yet another hot day ,
`
`ladies and gentlemen. Have a s eat. You will be comfortable
`
`today, hopefully.
`
`Ms . Kruze , you may continue with Dr . Amiji.
`
`MANSOOR AMIJI, having been previously sworn
`
`as a witness, was examined and testified further as .
`
`follows .. .
`
`THE COURT: Do you want to start out with a
`
`stipulation?
`
`We have arrived at one of those stipulations I
`
`talked with y o u about in the pre liminary instruc tions , that
`
`is an agreement, one of those rare events in this case
`
`between the parties . Ms. Kruze is now going to tell you who
`
`the ordinary person of skill in the art is , that is , give
`
`you the definition of this person you have heard about , this
`
`person of s kill .
`
`MS. KRUZE: The person of ordinary skill in the
`
`art would have a Ph . D. or the equivalent in pharmaceutical
`
`s c iences , chemistry, chemic al engineerinq , or biological
`
`sciences , and at least two year s of prac tic al experience in
`
`formulating drug compositions at the time the application
`
`for the '363 patent was filed.
`
`Alternatively , the person of ordinary skill in
`
`Apotex v. Abraxis - IPR20 IS-OO 153 , Ex . 101 3, p.OS of 222
`
`
`
`Case 1:0 cv-00438-GMS Document 625 Filed 06/24/08 Page 9 of 222 PagelD #: 10203
`1416
`
`Amiji
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`the art could be someone with a Master's degree in
`
`pharmaceutical sciences, or the equivalent, with two or more
`
`years of practical experience, specifically in the
`
`development of nanoparticulate pharmaceutical compositions.
`
`THE COURT: Let me see counsel for just a second
`
`before I say what I am thinking about saying. It doesn't
`
`need to be on the record.
`
`(Sidebar conference not reported.)
`
`THE COURT:
`
`Perhaps Ms. Kruze will direct you to
`
`the place. You don't have to worry about having made notes
`
`as to that definition. It has been or will be provided to
`
`you.
`
`BY MS. KRUZE:
`
`DIRECT EXAMINATION CONTINUED
`
`Q .
`
`A.
`
`Q .
`
`Good morning, Dr. Amiji.
`
`Good morning, Ms. Kruze.
`
`Yesterday we were discussing enablement of the patent
`
`relating to drug and surface modifier combinations.
`
`I
`
`believe where we left off was Defendant's Exhibit 193. This
`
`was the memo from Sarptodar and your comparison of that memo
`
`to the patent claims.
`
`A.
`
`Q .
`
`Yes.
`
`And we were discussing, did the patent applicants
`
`disclose, for example, that Tween 80 reached 3,000
`
`nanometers?
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.09 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 10 of 222 PagelD # : 10204
`1417
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`A.
`
`Q.
`
`NO, they did not.
`
`Let's take a quick look at what the patentees did tell
`
`the Patent Office. That's JX-Bl at Columns 3 through 4.
`
`I
`
`believe it's in Column 4, in the second paragraph.
`
`Did the patentees tell the Patent Office that
`
`Tween 80 was a particularly preferred surface modifier?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Yes, they did.
`
`But internally, that surface modifier had failed?
`
`That's correct, yes.
`
`Let's switch to D0106.
`
`Did you review any other documents regarding
`
`Elan's efforts to make a nano-piposulfan product?
`
`A.
`
`Q.
`
`Yes, I reviewed several other documents.
`
`Could you read some of the statements that you found
`
`in those documents? This, for the record, is JX-47, JX-55,
`
`JX-81 , DX-2S8 and DX-286.
`
`MR. SCHEVE: Your Honor, I object to just
`
`reading documents. It's inappropriate form.
`
`THE COURT:
`
`I will sustain the objection.
`
`BY MS. KRUZE:
`
`Q.
`
`Did you review any other documents regarding Elan's
`
`efforts to make a piposulfan project?
`
`A.
`
`Q.
`
`A.
`
`Yes, I did.
`
`What did those documents say to you?
`
`So here we can see from the different time points, we
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.1 0 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 11 of 222 Page lD #: 10205
`1418
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`have, in the case of August of '92, the '363 inventors
`
`discuss that piposulfan is physically unstable.
`
`In '93 , the
`
`inventors of piposulfan , was difficult to stabilize.
`
`In '96
`
`here, again, same problems with generating a stable
`
`nanocrystalline suspension proved to be challenging.
`
`In '96, formulation doe s have its problems .
`
`And even today, in 2008 , we still do not have a
`
`nano-piposulfan product.
`
`Q .
`
`Dr. Amiji , did Elan also try to make a NanoCrystal
`
`formulation of pac litaxel using albumin?
`
`A.
`
`Q.
`
`Yes.
`
`Did you review laboratory noteboo ks regarding those
`
`experiments?
`
`A.
`
`Yes , I reviewed several different laboratory
`
`notebooks .
`
`Q.
`
`Was Elan successful in making a NanoCrystal version of
`
`pac litaxel in albumin?
`
`A.
`
`Q.
`
`No , they were not .
`
`What is the significance to you that as late as 2006,
`
`Elan couldn't make a NanoCrystal version of paclitaxel in
`
`albumin?
`
`A.
`
`Well , because of the technology involved in the
`
`milling process ,
`
`I believe that a protein s tabilizer such as
`
`albumin would not be very effective in making a
`
`nanocrystalline because of the fact that it requires 120
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.11 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 12 of 222 Page lD #: 10206
`1419
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`hours of milling. The protein, typic ally, would not be a
`
`very effective stabilizer under those c onditions , having to
`
`have to mill for that long a time.
`
`Q .
`
`Did you review any other documents regarding Elan's
`
`efforts to make a NanoCrystal version of just paclitaxel in
`
`general?
`
`A.
`
`Q .
`
`Yes , I have.
`
`Can you please bring up , Mr. Broyles , OD41 .
`
`Are you familiar with this interrogatory , this
`
`is a legal question that Abraxis asked Elan?
`
`A.
`
`Q .
`
`A.
`
`Yes ,
`
`I am .
`
`What did Abraxis ask Elan?
`
`Abraxis asked Elan if they had made a NanoCrystal
`
`paclitaxel formulation.
`
`Q .
`
`A.
`
`Q .
`
`Are you familiar with Elan's answer to that?
`
`Yes.
`
`Can you bring up D042, Mr . Broyles .
`
`Is this the answer that Elan gave that you are
`
`familiar with?
`
`A.
`
`Yes. This is the respons e to the interrogatory that,
`
`for almost 20 years Elan has been trying to make
`
`nanocrystalline paclitaxel. And these are the different
`
`types of products that have been tried.
`
`Q .
`
`And we have
`
`MR. SCHEVE: Your Honor , if I may , since the
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.12 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 13 of 222 PagelD #: 10207
`1420
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`rules allow us under Rule 34, in response to a discovery
`
`request , to provide citation to specific documents ,
`
`I would
`
`ask that at least that be explained to the jury . Because
`
`what this is --
`
`THE COURT: Let me see counsel for a moment.
`
`(The following took place at sidebar . )
`
`THE COURT:
`
`I really don't want to get into
`
`having to describe and explain to the ladies and gentlemen
`
`of the jury the Federal Rules of Civil Procedure. It
`
`shouldn't be necessary in the case.
`
`MS. KRUZE: Maybe I should explain where I am
`
`going with this.
`
`Basically, what we want to do is we want to
`
`enter into evidence DX-44 , which is a compilation of all
`
`those documents, whi c h Elan, it's a party admission , has
`
`admitted with all their paclitaxel documents . That's what I
`
`am trying to get a c ross.
`
`THE COURT: But i s there something more
`
`expressive , more des c riptive , more helpful that you might
`
`have?
`
`MS. KRUZE : We have the documents.
`
`THE COURT:
`
`I am not sure the documents are
`
`helpful.
`
`I am not sure it is really worth the trouble . You
`
`try the case the way you want to try it.
`
`But why don ' t you react to this .
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.1 3 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 14 of 222 PagelD #: 10208
`1421
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`MR. SCHEVE: My objection is they have shown an
`
`interrogatory answer where my client under Rule 33 and 34
`
`referred them to the specific documents in this list.
`
`THE COURT:
`
`I don't want a discovery dispute in
`
`front of the jury. Go ahead.
`
`MR. SCHEVE:
`
`So we would object that it is
`
`prejudicial, it's confusing, under Rule 403, to just put
`
`that up, if the jury is not allowed to understand that we
`
`satisfied our discovery obligations.
`
`MS. KRUZE: My response is it is a party
`
`admission, Your Honor. We are entitled to use it in court.
`
`It is a binding response that Elan made.
`
`MR. SCHEVE: We don't deny that we made the
`
`response.
`
`It doesn't change the fact that it's confusing to
`
`the jury, likely to mislead the jury, when all you do is
`
`show an answer to interrogatory that is five columns of
`
`citations to Bates numbers of the documents that in any way
`
`might relate to what was done with paclitaxel.
`
`THE COURT:
`
`Is there a contention -- I guess
`
`it's not your contention that there was anything wrong
`
`procedurally with the response.
`
`It's, this is the response,
`
`and we want you to draw an inference from this response,
`
`directly from this response that they had difficulty.
`
`MS. KRUZE: My next question may clear this up.
`
`It was simply are these documents all collected in the
`
`Apotex v. Abraxis -IPR2018-00153 , Ex. 1013, p.14 of222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 15 of 222 Page lD #: 10209
`1422
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`courtroom . Then they c an just s ee the five boxes of
`
`documents . That way they don't have to focus on the
`
`numbers. The idea is that Elan tried very hard to do this.
`
`THE COURT : Do you object to them having a
`
`visual aid , the jury?
`
`MR. SCHEVE: No . That would be the next
`
`question , Your Honor.
`
`I take it question by question.
`
`I
`
`was objecting to put up a dis c overy response .
`
`THE COURT :
`
`I am going to sustain the objection
`
`to this que s tion .
`
`I understand what you are trying to do .
`
`I think you are entitled to do it. Quite frankly, I think
`
`it is a better avenue .
`
`Why d o n't you go a head.
`
`(End of sidebar conference.)
`
`BY MS. KRUZE:
`
`Q.
`
`Dr. Amiji, if I could direc t y our attention to DX-484,
`
`whi c h is the five boxes
`
`THE COURT : We are going to take this down .
`
`BY MS. KRUZE:
`
`Q.
`
`There are five boxes of doc uments.
`
`I don't want to
`
`roll them into the courtroom .
`
`THE COURT : Ladies and gentlemen, may I see a
`
`banker's box , please? Would you di s play one to the jury
`
`that is representative of the boxes of documents that
`
`Ms. Kruze is referenc ing .
`
`Just hold it up , if you would.
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.1 5 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 16 of 222 Page lD #: 10210
`1423
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Amiji - cross
`
`(Banker's box h e ld up.)
`
`That is a banker's box. That is what they are
`
`talking about , five of those filled with paper.
`
`BY MS. KRUZE:
`
`Q.
`
`Do these five boxes of doc uments , do they contain any
`
`failures that Elan had with paclitaxel?
`
`A.
`
`Q.
`
`Yes. There were a lot of failures .
`
`Did Elan disclose those five boxes of failures to the
`
`Patent Office?
`
`A.
`
`Q .
`
`A.
`
`No , they did not .
`
`Why is this important?
`
`Well , because, you know , in the patent itself, there
`
`is an example of the pac litaxel that did work , whereas y o u
`
`had all these other failures that were not disclosed .
`
`Q.
`
`Based on your review of all these Elan documents, how
`
`long has Elan been trying to make a NanoCrystal version of
`
`pac litaxel?
`
`A.
`
`Q.
`
`I believe it's been about 20 years now.
`
`Dr. Amiji, to summarize , c an many o f the possible
`
`c ombinations c overed by the ' 363 patent form usable
`
`pharmaceutical c ompositions?
`
`A.
`
`Q .
`
`No , they cannot.
`
`And in y our opinion, will many o f
`
`thos e c ombinations
`
`of drugs and surface modifiers fail to form usable
`
`compositions?
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.1 6 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 17 of 222 PagelD #: 10211
`1424
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`A.
`
`Q.
`
`Yes, they will.
`
`Do you have an opinion today that is relevant to the
`
`requirement that the '363 patent be enabled like we saw in
`
`the patent video?
`
`A.
`
`Q.
`
`Yes.
`
`And do you hold that opinion to a reasonable degree of
`
`scientific certainty?
`
`A.
`
`Q.
`
`Yes, I do.
`
`At the time the patent was filed, did the '363 patent
`
`enable ordinary scientists to make and use the claimed
`
`inventions without undue experimentation?
`
`A.
`
`Q.
`
`NO, they wouldn't.
`
`Do you have an opinion today that is relevant to the
`
`requirement that the '363 patent have an adequate written
`
`description?
`
`A.
`
`Q.
`
`Yes, I do.
`
`Do you hold that opinion to a reasonable degree of
`
`scientific certainty?
`
`A.
`
`Q.
`
`A.
`
`Q.
`
`Yes, I do.
`
`Could you tell the jury what your opinion is?
`
`That it wouldn't enable.
`
`At the time the patent was filed, did the patent
`
`convey that Elan was actually in possession of the full
`
`scope of the patent claims?
`
`A.
`
`Yes.
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.17 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 18 of 222 Page lD #: 10212
`1425
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`Q.
`
`In other words , at the time the patent was filed , was
`
`Elan in possession of all the drug and surface modifier
`
`combinations?
`
`A.
`
`Q.
`
`No , they were not.
`
`And while the patent applic ation was pending, did Elan
`
`tell the Patent Office about these bad tests that we
`
`reviewed or all the failures that you were speaking of?
`
`A.
`
`Q.
`
`No , they did not .
`
`And did these bad tests or failures contradict
`
`statements that Elan was making to the Patent Office?
`
`A.
`
`Q.
`
`Yes.
`
`Dr. Amiji, let's talk about contamination.
`
`Mr. Broyles , if you could bring up JX-81 on the
`
`screen , Column 6 . Do you have testimony today relevant to
`
`the enablement requirement in terms of contamination?
`
`A.
`
`Q.
`
`Yes ,
`
`I do .
`
`What is the method for making nanopartic les that's
`
`disclosed in the ' 3 63 patent?
`
`A.
`
`So the '363 patent mentions this grinding process, the
`
`wet grinding process , whi c h uses the grinding media , and
`
`reduces the partic le size from larger crystals into smaller
`
`c rystals.
`
`Q.
`
`Could you bring up 00107, which is from Elan's
`
`website.
`
`Is this a depiction of how the large crystals
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.1 8 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 19 of 222 Page lD #: 10213
`1426
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`become smaller?
`
`A.
`
`Q .
`
`Yes , it is.
`
`And if you could go to JX-81 again at Column 6. What
`
`types of instruments does the patent tell one to use to make
`
`these crystals go from smaller to -- or bigger to smaller?
`
`A.
`
`So it uses the milling equipment , which is a ball
`
`mill, and then there is the grinding media . The grinding
`
`media or these beads are made from zirconium oxide,
`
`zirconium silicate , and glass.
`
`Q.
`
`And let's turn to Column 7. How long does the patent
`
`teach one to grind?
`
`A.
`
`In the simple screening method, for instance, it says
`
`up to 120 hours , whi c h is more than five days.
`
`Q.
`
`A.
`
`Just to clarify for the jury , what is zirconium oxide?
`
`Zirconium oxide is a metal, a heavy-metal oxide .
`
`It
`
`has this oxygen and a heavy metal .
`
`Q.
`
`A.
`
`Silicate, what is that?
`
`Silicate is, again, a compound from silica . Silica is
`
`one of the major constituents of sand .
`
`Q.
`
`Do you have an animation that illustrates the
`
`manufacturing proc ess of the '363 patent that would help the
`
`jury's understanding?
`
`A.
`
`Q.
`
`Yes ,
`
`I do .
`
`Let's play that animation.
`
`Can you narrate what ' s happening?
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.19 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 20 of 222 PagelD #: 10214
`1427
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`A.
`
`This is Abraxane.
`
`Here is the animation, ladies and gent1emen, for
`
`the NanoCrystal technology based on the documents that I
`
`reviewed from Elan.
`
`This is the ball mill that we are talking about,
`
`which has this report, and these are the grinding media that
`
`we have talked about. And these are about one to three
`
`millimeters in diameter. And they are put inside this ball
`
`mill. The report here is going to be the one that will
`
`basically create the tumbling action.
`
`The next thing here is the premix, which the
`
`inventors call the premix. That is basically water and
`
`these larger drug crystals. These are the starting material
`
`for making the NanoCrystal product. Here we start with
`
`larger crystals. These crystals are then suspended or put
`
`in water. That's what leads to this premix; the product
`
`that is then put inside the ball mill.
`
`Because of the size differences, we depict that
`
`as simply a green hue.
`
`Now we will see the starting of this ball mill.
`
`See them tumbling, the rotor is tumbling and these beads,
`
`the larger grinding beads, are starting to then get
`
`suspended in the premix. As they get suspended, and they
`
`get in contact with the crystal, the drug crystal and these
`
`other grinding beads, they will start to collide with one
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.20 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 21 of 222 Page lD #: 10215
`1428
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`another , as you see. And as these c ollide, they break up
`
`into smaller particles.
`
`That collision continues. This milling process
`
`continues for a long time. And each time this leads to more
`
`and more fragmentation of the crystals into smaller and
`
`smaller particles.
`
`Eventually, it creating these very, very tiny
`
`particles or nanoparticles.
`
`Q.
`
`And those grinding beads, again, in terms of the '363
`
`patent, are made out of?
`
`A.
`
`Q.
`
`Zirconium oxide , zirconium silicate, or glass.
`
`Dr. Amiji, can milling with metal or glass beads cause
`
`any problems?
`
`A.
`
`Yes. Again, this milling procedure , especially
`
`because it is ongoing for such a long time , will cause
`
`c ontamination.
`
`Q.
`
`A.
`
`that .
`
`Q.
`
`A.
`
`How does this contamination occur exactly?
`
`So here , again, we have an animation that illustrates
`
`Let's play that.
`
`So the animation here will show you exactly how the
`
`contamination occurs. So we are starting here from where we
`
`left off in the previous animation . The grinding media and
`
`the ball mill with the crystals being basically broken into
`
`smaller and smaller fragments.
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 1013, p.21 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 22 of 222 PagelD #: 10216
`1429
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`But as you e nlarge this, what you observe is
`
`that, yes , there is going to be dec rease in the size of the
`
`crystals. But at the same time, these grinding media will
`
`collide with each other. As they collide with each other,
`
`they fragment as well . Especially as you get into longer
`
`and longer time points.
`
`So this grinding media colliding with each other
`
`causes the contamination bec ause of these metal and glas s
`
`grinding media that is present ins ide this ball mill .
`
`Q.
`
`What were those white flakes or silver flakes that we
`
`just saw?
`
`A.
`
`That is the contamination that occurs because of the
`
`fact that two grinding ,
`
`two or more grinding media colliding
`
`with each other.
`
`Q.
`
`What are some of the problems with contamination in
`
`pharmaceutical c ompositions?
`
`A.
`
`Contamination is a big problem in pharmaceuticals
`
`because you c learly want this produc t to be safe and
`
`effective . And safety, not only from the drug point of
`
`view , but from the purity and from the quality control point
`
`of view. You want to make sure that the produc t will not
`
`have any contamination , any type of contamination .
`
`Pharmaceutical produc ts , espec ially thos e are intended for
`
`administration into the bloodstream you really have to be
`
`very careful about making sure that the quality is as pure
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex . 101 3, p.22 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 23 of 222 PagelD #: 10217
`1430
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`12
`
`13
`
`14
`
`15
`
`16
`
`17
`
`18
`
`19
`
`20
`
`21
`
`22
`
`23
`
`24
`
`25
`
`and as best as possible.
`
`Q.
`
`When we are talking about intravenous administration,
`
`things that go directly into the bloodstream, are the risks
`
`greater with contamination?
`
`A.
`
`Yes, they are, because, first of all, the FDA requires
`
`a much more stringent requirement for any product that is
`
`given into the bloodstream. And the reason is you don't
`
`have any way to reverse the problems.
`
`If you take a pill orally, one could easily
`
`either give another product and have that drug stop being
`
`absorbed. But once you give a product in the bloodstream,
`
`it is always going to be there. There is not an opportunity
`
`to take that product out.
`
`The other thing is that contamination in
`
`product, in pharmaceutical product, even if it occurs in one
`
`product, one vial of a large number of vials, it is not
`
`possible to tell which vial has that contamination and the
`
`patient who will get that.
`
`So it is an unpredictable event and you don't
`
`want that kind of risk.
`
`Q.
`
`What about with drugs that are administered routinely,
`
`like most anticancer drugs?
`
`A.
`
`Again, the problem of contamination becomes even more
`
`magnified, because once you give a product, as it is given
`
`continuously to patients, what you find is that the
`
`Apotex v. Abraxis - IPR20 18-00 153, Ex. 1013, p.23 of 222
`
`
`
`Case 1:06 cv-00438-GMS Document 625 Filed 06/24/08 Page 24 of 222 Page lD #: 10218
`1431
`
`Amiji - cross
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`