Horizon Exhibit 2046
`Par v. Horizon
`IPR2017-01767
`
`1
`
`Deposition of NEAL SONDHEIMER, called by the Counsel
`for the Patent Owner, held before a stenographic court
`reporter at the offices of Victory Verbatim, Suite 900,
`222 Bay Street, Toronto, Ontario, Canada, on Thursday,
`the 19th day of April, 2018, at 9:00 a.m.
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner
`
`v.
`
`HORIZON THERAPEUTICS, LLC,
`
`Patent Owner
`
`__________
`
`Case IPR2017-01768
`Patent 9,095,599
`
`__________
`
`BARRETT GUNN COURT REPORTERS
`
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`Page 1 of 181
`
`
`Par v. Horizon
`IPR2017-01767
`
`1
`
`Deposition of NEAL SONDHEIMER, called by the Counsel
`for the Patent Owner, held before a stenographic court
`reporter at the offices of Victory Verbatim, Suite 900,
`222 Bay Street, Toronto, Ontario, Canada, on Thursday,
`the 19th day of April, 2018, at 9:00 a.m.
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner
`
`v.
`
`HORIZON THERAPEUTICS, LLC,
`
`Patent Owner
`
`__________
`
`Case IPR2017-01768
`Patent 9,095,599
`
`__________
`
`BARRETT GUNN COURT REPORTERS
`
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`Page 1 of 181
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`2
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`PAR PHARMACEUTICAL, INC.,
`Petitioner
`
`v.
`
`HORIZON THERAPEUTICS, LLC,
`
`Patent Owner
`
`__________
`
`Case IPR2017-01767
`Patent 9,254,278
`
`__________
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner
`
`v.
`
`HORIZON THERAPEUTICS, LLC,
`
`Patent Owner
`
`__________
`
`BARRETT GUNN COURT REPORTERS
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`3
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`Case IPR2017-01769
`Patent 9,326,966
`__________
`
`A P P E A R A N C E S:
`
`For Petitioner:
`Axinn, Veltrop & Harkrider LLP
`950 F Street, NW
`WASHINGTON, DC 20004
`202-721-5417
`
`BY: Aziz Burgy,
`David H. Silverstein
`aburgy@axinn.com
`dsilverstein@axinn.com
`
`For the Patent Owner:
`GREEN GRIFFITH
`676 N. Michigan Avenue
`Suite 3900
`Chicago, IL 60611
`312.883.8000
`
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`BY: Robert F. Green
` Ann K. Kotze
` rgreen@greengriffith.com
` akotze@greengriffith.com
`
`Also present, Gina R. Gencarelli,
` Par Pharmaceutical
`
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`INDEX OF PROCEEDINGS
`
`
`NEAL SONDHEIMER:
`EXAMINATION PAGE
`By Mr. Green:
`6
`By Mr. Burgy:
`159
`
`QUESTIONS WITNESS INSTRUCTED NOT TO ANSWER: None
`INFORMATION TO BE SUPPLIED: None
`
`
`INDEX OF EXHIBITS
`
`
`NO./ DESCRIPTION PAGE
`
`none
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`--- Toronto, Ontario,
`--- Upon commencing at 9:00 a.m. ---
`
`NEAL SONDHEIMER, after having been duly affirmed was
`examined and testified as follows:
`EXAMINATION
`
`BY MR. GREEN:
`Q.
`Good morning, Dr. Sondheimer.
`A.
`Good morning.
`Q.
`Good to see you again.
`So I'm going to start by handing
`Dr. Sondheimer the three declarations that he has
`prepared with respect to the three IPRs that are
`the subject of today's testimony. So I'm going to
`hand you your declaration in the IPR related to US
`Patent No. 9,095,559, and for purposes of the
`clarity today, I'm going to refer to that to your
`'559 Declaration, if that's okay with you.
`MR. BURGY: Yes.
`BY MR. GREEN:
`Q.
`And similar fashion, we have your
`declaration with respect to the IPR related to
`U.S. Patent 9,254,278, and I intend to refer to
`that as your '278 Declaration, if that's again
`fine with you.
`
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`A.
`Okay.
`Q.
`And finally, I am going to hand
`to you your declaration in the IPR related to U.S.
`Patent 9,326,966, and I will refer to that as the
`your '966 Declaration.
`A.
`That's fine, thank you.
`Q.
`Okay. If we could start by
`turning to the '559 Declaration at paragraph 42,
`and in paragraph 42, you set forth your definition
`of a person of ordinary skill in the art; is that
`correct?
`
`A.
`Q.
`
`Yes.
`As part of that you state that:
`"In my opinion, a person of
`ordinary skill in the art as of
`September 30, 2011 (the date of the
`alleged invention) would have been
`a physician or a scientist with a
`Ph.D. or M.D. degree and had
`specialized training in the
`diagnosis or treatment of inherited
`metabolic disorders such as urea
`cycle disorders ("UCDs") and other
`nitrogen retention disorders."
`Did I read that correctly?
`
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`A.
`Yes.
`Q.
`So addressing that particular
`sentences in paragraph 42, it's correct then, is
`it not, that, in your view, the person of ordinary
`skill in the art could be an M.D. or a Ph.D. who
`could either have specialized training in the
`diagnosis or specialized training in the treatment
`of inherited metabolic disorders; is that correct?
`A.
`I go on to qualify that by
`pointing to the credentials that I would expect
`such a person to have, which is the next sentence:
`"Today, such a person may have
`post-graduate training to fulfill
`the requirements of the American
`Board of Medical Genetics and
`Genomics in the disciplines of
`clinical genetics, clinical
`biochemical genetics or medical
`biochemical genetics."
`Q.
`So in that sentence you use the
`term "may". You now interpret that to mean that's
`a requirement for a --
`--- Reporter query ---
`Q.
`For the record, you understand
`that POSA refers to a person of ordinary skill in
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`the art, correct?
`A.
`I do.
`Q.
`Okay.
`MR. BURGY: Object to form.
`THE WITNESS: I was describing what
`qualifications I would expect a person
`to have today.
`BY MR. GREEN:
`Q.
`So just for clarity sake, when
`you say: "Today, such a person may have..." do
`you then mean that for a person to be a POSA, in
`your view, that person would then be required to
`have the post-graduate training to fulfill the
`requirements of the American Board of Medical
`Genetics and Genomics in the disciplines of
`clinical genetics, clinical biochemical genetics
`or medical biochemical genetics?
`A.
`There are several older
`physicians and Ph.D's in the field that have a
`different named certification, which is why I use
`the term "may".
`Q.
`And those older practitioners in
`the profession that don't have the same identified
`credentials would still have, in your view, then
`equivalent credentials due to their prior
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`training; is that correct?
`MR. BURGY: Object to form.
`THE WITNESS: Yes.
`BY MR. GREEN:
`Q.
`So with respect to the POSA
`definition in your first sentence again, it
`indicates that the specialized training could be
`either with respect to diagnosis or treatment,
`correct?
`
`A.
`That's what I've written, yes.
`Q.
`So in your definition for a POSA,
`a person would not need to have specialized
`training in the treatment of inherited metabolic
`disorders; is that correct?
`MR. BURGY: Object to form.
`THE WITNESS: No, as a practical matter,
`that wouldn't be possible.
`BY MR. GREEN:
`Q.
`Okay. Again, the reason for
`raising that question is the use of the term "or"
`here, so your testimony then is it you do really
`mean that the POSA would have some background then
`in specialized training with respect to treatment
`as a requirement?
`A.
`As a practical matter, you can't
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`train to do a diagnosis without having
`understanding of treatment. It's not possible to
`do that.
`
`Q.
`So when you applied your
`definition of a POSA with respect to the prior art
`in coming to the various conclusions that you have
`expressed in your declarations, did you then use a
`definition that required the POSA to have had
`specialized training with respect to the treatment
`of metabolic disorders?
`A.
`I use the definition that I've
`written here.
`Q.
`Again, I don't want to belabour
`the topic, but the definition does use the term
`"or," that's my problem, trying to understand
`whether that definition that you applied then
`included those that did not have specialized
`training with respect to treatment.
`A.
`I'm sorry, I'm not sure what the
`question is.
`Q.
`Sure. Let me just repeat it. So
`the question is when you were forming your
`opinions as expressed in your declarations, you
`were viewing the prior art from the standpoint of
`a POSA, correct?
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`A.
`That's correct.
`Q.
`All right. And the POSA
`definition that you used in that instance then
`required that the POSA had specialized training in
`the treatment of inherited metabolic disorders; is
`that correct?
`A.
`No, I applied the definition that
`I've written there.
`Q.
`Okay. So a POSA -- the POSA
`definition that you used then would cover a
`situation where a person had specialized training
`in diagnosis, but without specialized training in
`the treatment of inherited metabolic disorders?
`MR. BURGY: Object to form.
`THE WITNESS: So I've already answered
`that question, I think, that as a
`practical matter it's not possible to
`have specialized training in the
`diagnosis without having knowledge of
`the treatment of disorders.
`BY MR. GREEN:
`Q.
`And without trying to argue with
`you, this seems to be a bit of a disconnect in how
`we are communicating.
`If what you are saying is that it's not
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`possible for a POSA to really exist who has not
`had training in the treatment of inherited
`metabolic disorders if they have also had training
`with respect to diagnosis, then POSA definition
`you use would include someone that had both
`skills; is that right?
`MR. BURGY: Object to form.
`THE WITNESS: So the POSA definition
`would certainly include people who had
`both skills, yes.
`BY MR. GREEN:
`Q.
`And would it include a person who
`has not had specialized training in the treatment
`of inherited metabolic disorders?
`A.
`So I've already answered that
`question that as a practical matter you can't have
`training in one and not the other.
`Q.
`So I need a yes or a no response.
`So does it include then a person who has had
`specialized training in diagnosis but not
`treatment?
`MR. BURGY: Object to form.
`THE WITNESS: I've already answered that
`question.
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`BY MR. GREEN:
`Q.
`Is it yes or no?
`MR. BURGY: Same objection.
`THE WITNESS: So I'm happy to have it
`read back, but the answer is going to be
`the same.
`BY MR. GREEN:
`Q.
`Well, again, Dr. Sondheimer, I'm
`not trying to be argumentative, I'm just trying to
`understand whether -- how broad your treatment
`definition was. You say from a practical matter
`today that's the case, that a POSA -- to be a POSA
`would have specialized training in both diagnosis
`as well as the treatment. And is that the way you
`viewed the prior art from the eyes of a POSA would
`have had both, and not from the eyes of a POSA who
`would not have had specialized training and
`treatment?
`MR. BURGY: Object to form.
`THE WITNESS: I'm sorry, I'm not sure
`what the question is.
`BY MR. GREEN:
`Q.
`Yes, I guess I'm not sure I can
`make it any more clear, so I might try it one more
`time.
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`Would a POSA who did not have
`specialized training in the treatment of inherited
`metabolic disorders been a person that you would
`have considered to be a POSA when you reached your
`conclusions as expressed in your declarations?
`MR. BURGY: Object to form.
`THE WITNESS: So I've answered that
`question I think four times now.
`BY MR. GREEN:
`Q.
`I don't think you have given me a
`clear yes or no, and to me that's a yes or no
`question. I mean if you are not going to give me
`the answer, then that's fine, I'll pass on.
`MR. BURGY: Object to form.
`THE WITNESS: So the answer will remain
`the same.
`BY MR. GREEN:
`Q.
`Okay. Just for the record, the
`definition that you have expressed in paragraph 42
`of the '559 Declaration is expressed in the same
`language in paragraph 40 of the '278 Declaration;
`is that correct?
`A.
`Yes.
`Q.
`And that same language is
`expressed in paragraph 47 of the '966 Declaration;
`
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`16
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`is that correct?
`A.
`Yes.
`Q.
`Okay. I'm going to hand you
`what's been referred to I believe in your
`declarations as the Fernandes exhibit, which in
`this litigation has Exhibit No. 1011 -- sorry,
`1015. I'm also going to hand you a complimentary
`copy of that same document, which I believe will
`be easier for your use in responding to questions
`due to the fact that the Exhibit 1015 that has
`been provided to us as well as the PTAB has very
`small and almost illegible types, files, so,
`again, this is Exhibit 1015 as is present in all
`three of the IPRs, and I'm giving you a copy for
`your reference purposes of that same document, but
`with a little clearer type style -- a little bit
`easier to read, I would say.
`MR. BURGY: Counsel, are you
`representing that this copy that is
`easier to read is a exact copy of the
`exhibit that's entered?
`BY MR. GREEN:
`Q.
`Yes, we are. Dr. Sondheimer,
`feel free to take a look at the copy to see if you
`see any difficulties.
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`A.
`No.
`Q.
`Okay. So in your declaration,
`Dr. Sondheimer, you have made the statement that
`this Fernandes reference Exhibit 1011 suggests to
`a POSA that measuring plasma ammonia following a
`meal would likely result in an inaccurate
`assessment of the patient's plasma ammonia level.
`Do you recall making that statement?
`A.
`Can you point know which
`declaration and what line?
`Q.
`Sure. In the 559 in front of
`you, it's paragraph 54.
`A.
`Thank you.
`Q.
`So I would like to turn your
`attention actually to the Fernandes exhibit at the
`page numbered 217, and under the section that's
`captioned, "Diagnostic Tests, Biochemical Test,"
`is that where you derived your statement in the
`'559 Declaration at page 54?
`A.
`Yes.
`Q.
`Okay. And if we look at the
`paragraph under "Diagnostic Tests" subheading
`"Biochemical tests," the paragraph reads:
`"The most important diagnostic test
`in urea cycle disorder is
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`measurement of the plasma ammonia
`concentration. Normally, this is
`less than 50 umol/l, but may be
`slightly raised as a result of a
`high protein intake, exercise,
`struggling or a haemolysed blood
`sample."
`Correct?
`A.
`A haemolysed blood sample.
`Q.
`Thank you. Now in this is
`complete sentence from this portion of the
`Fernandes reference, the reference to 50 umol/l,
`that's the upper limit of normal as applied in
`Fernandes, correct?
`A.
`No.
`Q.
`So based on your reading of this
`sentence, the reference to "50 umol/l" in the
`context of the statement, "... the plasma ammonia
`concentration. Normally, this is less than
`50 umol/l," does not connote that Fernandes
`considered 50 umol/l to be the upper limit of
`normal" --
`MR. BURGY: Objection, lack of
`foundation.
`THE WITNESS: Sorry.
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`BY MR. GREEN:
`Q.
`Read in the context of the
`sentence I just discussed, you do not believe that
`the 50 umol/l designation is an indication by
`Fernandes that 50 umol/l in fact is the upper
`limit of normal, correct?
`MR. BURGY: Same objection.
`THE WITNESS: I'm sorry, I'm not sure
`which of the two questions you were
`asking.
`BY MR. GREEN:
`Q.
`Okay. Rather than have it read
`back, I'll try one more time. In this context,
`Fernandes used a 50 umol/l to you does not connote
`that Fernandes considered 50 umol/l to be the
`upper limit of normal; is that correct?
`MR. BURGY: Same objection, and
`objection to form.
`THE WITNESS: No.
`BY MR. GREEN:
`Q.
`not correct?
`A.
`I'm not sure what you mean.
`Q.
`Let's take it one easy step at a
`time. 50 umol/l, in your view, is not the upper
`
`In what respect is my question
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`limit of normal as used by Fernandes in this
`reference, correct?
`MR. BURGY: Same objections.
`THE WITNESS: No.
`BY MR. GREEN:
`Q.
`So 50 umol/l, as used in the
`Fernandes reference, is used as the upper limit of
`normal, correct?
`MR. BURGY: Object to form.
`THE WITNESS: No.
`BY MR. GREEN:
`Q.
`So you have answered "no" to both
`of my questions. Either it is or it isn't.
`So do you believe that 50 umol/l, as
`used in this reference, is referring to the upper
`limit of normal as used by Fernandes?
`MR. BURGY: Same objection.
`THE WITNESS: I need you to read both
`questions back because I thought it was
`the same exact question both times. I
`heard you say "is" both times.
`BY MR. GREEN:
`Q.
`Okay. Well, let's start anew,
`try this question.
`Fifty umol/l, as used by Fernandes in
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`
`this reference, in your opinion, does that refer
`to his view, that is the author's view, that
`50 umol/l is the upper limit of normal?
`A.
`You have to repeat the end of the
`question very carefully, and you skipped a word.
`Q.
`A POSA, reading Fernandes, would
`view that 50 umol/l is the upper limit of normal
`as used in the Fernandes paper, correct?
`MR. BURGY: Object to form.
`THE WITNESS: My understanding of your
`question is that you said "the upper
`limit of normal." I'm having a little
`bit of trouble understanding when you
`say the word "the," and if the question
`is is it the upper limit of normal, the
`answer is no.
`BY MR. GREEN:
`Q.
`So if the reference to 50 umol/l
`is not a reference to the upper limit of normal as
`viewed by the author of this paper, how does a
`POSA interpret the 50 umol/l?
`A.
`They interpret it as one upper
`limit of normal.
`Q.
`Okay. And if that's a reference
`to one upper limit of normal, then does a POSA
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`viewing the Hernandes [sic] reference then view
`the paper as referencing a different upper limit
`of normal, and by "different," I mean other than
`50 umol/l?
`MR. BURGY: Object to form.
`THE WITNESS: Yes.
`BY MR. GREEN:
`Q.
`All right. And what is the other
`upper limit of normal?
`MR. BURGY: Objection to form.
`THE WITNESS: Fernandes -- sorry,
`Fernandes at least mentions another
`upper limit of normal in Figure 17.2.
`BY MR. GREEN:
`Q.
`You are referring to Figure 17.2
`on page 230 of the reference, correct? 220,
`excuse me.
`A.
`Yes.
`Q.
`And in this document, does a
`reference to "80" appear elsewhere?
`MR. BURGY: Object to form.
`THE WITNESS: It appears on page 219 in
`this section marked "General Aspects of
`Therapy." It appears within the
`Figure 17.2 itself. And I believe those
`
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`23
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`are the places that it appears.
`BY MR. GREEN:
`Q.
`So focussing on the reference to
`"80" at the bottom of page 219, "The aim to keep
`plasma ammonia level below 80 micrograms [sic]--
`80 umol/l," that does not state that the 80 umol/l
`is an upper limit of normal, does it?
`MR. BURGY: Object to form.
`THE WITNESS: It does.
`BY MR. GREEN:
`Q.
`Okay. Can you point to me to
`where it says that's the upper limit of normal?
`A.
`That is how a POSA would
`understand that description.
`Q.
`And why would a POSA understand
`that description to mean that 80 is the upper
`limit of normal?
`A.
`describe it.
`Q.
`He says the aim is to keep plasma
`levels below 80 umol/l, correct?
`MR. BURGY: Object to form.
`BY MR. GREEN:
`Q.
`He doesn't say because that's the
`upper limit of normal, does he?
`
`It's the words that he's using to
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`24
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`MR. BURGY: Same objection.
`THE WITNESS: He's describing the upper
`limit of normal, and in the next
`sentence giving reference to the figure
`wherein he's using it.
`BY MR. GREEN:
`Q.
`Going back to the 50 umol/l that
`also was a reference to an upper limit of
`normal --
`
`MR. BURGY: Object to form.
`BY MR. GREEN:
`Q.
`-- is that correct?
`A.
`Yes, this is the description of
`an upper limit of normal.
`Q.
`So, it's your view, sir, that a
`POSA reading the Fernandes reference would read
`the paper as indicating that there are two
`different upper levels of normal discussed in this
`paper; is that correct?
`A.
`A POSA is well aware that there
`are multiple upper limits of normal for ammonia.
`Q.
`And in this paper, is there any
`discussion as to why both an upper limit of
`normal, in your opinion, of 50 umol/l as well as
`one of 80 umol/l is used in the context of this
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`paper?
`
`I'm sorry, I'm not sure what your
`
`A.
`question is.
`Q.
`Can you explain in terms of a
`POSA's view of the Fernandes reference why a POSA
`would believe that Fernandes is using two
`different upper levels of normal with no
`explanation as to why two different levels are
`being expressed?
`MR. BURGY: Object to form.
`THE WITNESS: A POSA would easily
`understand that with no other
`explanation required.
`BY MR. GREEN:
`Q.
`And, in your view, what is the
`understanding of a POSA in that context as to why
`two different upper levels of normal are expressed
`in the same paper without explanation?
`MR. BURGY: Object to form.
`THE WITNESS: I'm going to ask you to
`simplify that question. What are you
`asking?
`BY MR. GREEN:
`Q.
`I'm asking you to tell me why you
`believe a POSA reading this document would believe
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`without the paper explaining why two different
`levels of the upper limit of normal are discussed,
`why a POSA would believe that each represent an
`upper level -- upper limit of normal?
`MR. BURGY: Object to form and lack of
`foundation.
`THE WITNESS: POSAs are well aware that
`there could be multiple upper limits of
`normal for ammonia.
`BY MR. GREEN:
`Q.
`Does this paper indicate that
`studies were conducted under different conditions
`when the 50 umol/l is used versus the 80 umol/l
`limitation for the upper limit of normal?
`MR. BURGY: Objection, lack of
`foundation.
`THE WITNESS: POSAs would not require
`any such information to know that there
`are multiple upper limits of normal.
`BY MR. GREEN:
`Q.
`Turning back to the use of the
`80 umol/l in the flow chart on page 220, the
`reference to the 80 on this flowchart, again, does
`not state that the 80 is an upper limit of normal,
`correct?
`
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`A.
`That's not correct.
`Q.
`On the flowchart where does it
`state that the 80 umol/l is an upper limit of
`normal?
`
`A.
`A POSA reading this chart would
`understand that 80 is being used as an upper limit
`of normal.
`Q.
`Is that the only explanation that
`a POSA would have, when reading a flowchart such
`as this, that's got to be an upper limit of
`normal?
`
`MR. BURGY: Objection to form.
`THE WITNESS: I'm sorry, I'm not sure
`what question you are asking.
`BY MR. GREEN:
`Q.
`Is that the only explanation that
`a POSA would have as to why the 80 umol/l is used
`in this flowchart?
`MR. BURGY: Same objection.
`THE WITNESS: I'm having a hard time
`understanding your question. A POSA
`evaluating this would understand that
`80 micromolar was used as the upper
`limit of normal.
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`BY MR. GREEN:
`Q.
`And my question is is it your
`opinion that a POSA could not have a different
`view that the 80 is something other than the upper
`limit of normal?
`MR. BURGY: Object to form.
`THE WITNESS: No, I think a POSA viewing
`this would use 80 as the upper limit of
`normal as it was being written.
`BY MR. GREEN:
`Q.
`Do all clinicians then always
`consider the upper limit of normal as being the
`value that a patient must reach in order to be
`considered to have acceptable blood levels?
`MR. BURGY: Object to form.
`THE WITNESS: I -- can you repeat that
`question?
`BY MR. GREEN:
`Q.
`
`Let me give you an example,
`
`Doctor.
`
`A.
`Okay.
`Q.
`There's a treating clinician,
`that treating clinician takes a blood level for a
`patient, that blood level is above the upper limit
`of normal. At that point, does the clinician
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`29
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`always then increase or otherwise adjust the
`patient's use of a nitrogen scavenging agent
`because it's above the upper limit of normal?
`MR. BURGY: Object to form. Lack of
`foundation.
`THE WITNESS: That's a very complex
`hypothetical. You would need to define
`that patient at least in some way.
`BY MR. GREEN:
`Q.
`Well, I'm defining the patient in
`terms of a fasting blood ammonia level that's
`above the upper limit of normal. So do doctors
`always then change the dosing regimen of a
`nitrogen scavenging agent when the ammonia level
`is above the upper limit of normal?
`MR. BURGY: Same objections.
`THE WITNESS: So, again, that's a
`complex hypothetical, and I need
`multiple more details about the clinical
`situation you are describing to answer
`it.
`BY MR. GREEN:
`Q.
`In your practice, if a patient
`comes in and has a fasting blood ammonia level of
`above the upper limit of normal, then do you make
`
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`30
`
`a change in how the patient is being treated?
`MR. BURGY: Same objections.
`THE WITNESS: Again, this is a
`hypothetical with no details about the
`patient. I can't answer the question.
`BY MR. GREEN:
`Q.
`Okay. If there is a patient, the
`patient is in fine condition, comes in, the upper
`limit of normal is 30, the patient presents at 32,
`and there's no reason to believe that there's any
`problems with the patient's lifestyle, has no
`complaints. So based on the fact that it's 32,
`would you increase the dose?
`MR. BURGY: Same objections.
`THE WITNESS: Again, this hypothetical
`is missing so many details. I can't
`answer the question.
`BY MR. GREEN:
`Q.
`So what details do you need?
`A.
`I don't know what question you
`are trying to ask.
`Q.
`Well, you said I didn't give you
`the details. I just want to know what details you
`are looking for?
`A.
`
`I'm not sure what question you
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`Page 30 of 181
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`
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`31
`
`are trying to ask. I'm sorry.
`Q.
`Okay, I'm not sure how I can make
`this more simple. You have a patient, you have
`dealt with this patient for some time, the patient
`is doing well, you don't see any problems with the
`day-to-day activities of the patient, there's not
`been any hyperammonemic episode recently. The
`patient comes, and in instead of being at 30 which
`if the upper limit of normal, the patient is at
`32, full stop.
`Under those conditions then since the
`upper limit of normal is 30, would you increase
`the dosage of the nitrogen scavenging agent?
`MR. BURGY: Object to form. Lack of
`foundation.
`THE WITNESS: I'm sorry we are having
`difficulty with this, but you are going
`to have to give me details about the
`patient that you are not giving me for
`me to answer this question.
`BY MR. GREEN:
`Q.
`That's why I'm asking you what
`details do you want?
`A.
`I don't know what question you
`are trying to ask at this point, so it's difficult
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`
`
`32
`
`for me to answer that.
`Q.
`Well, you are a practicing
`clinician that treats UCD patients, correct?
`A.
`Yes.
`Q.
`Okay. So do you have residents,
`for example, that work under you?
`A.
`In some context there are
`residents who work with us, yeah.
`Q.
`And do any of those residents
`work in the context of treating UCD patients?
`A.
`Yes.
`Q.
`Okay. So a resident comes in,
`says I've got a patient, the patient has been
`doing fine, don't see any change, they have no
`complaints, their fasting plasma ammonia level is
`32, the upper limit of normal is 30. Should I
`increase the dose? he asks, or she asks you. What
`do you say?
`MR. BURGY: Object to form, lack of
`foundation.
`THE WITNESS: Are they on a medication?
`BY MR. GREEN:
`Q.
`They are taking a nitrogen
`scavenging agent.
`MR. BURGY: Same objections.
`
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`
`THE WITNESS: Okay, is there a question?
`BY MR. GREEN:
`Q.
`Yes, I'm your resident, I've just
`asked, "What should I do? Should I increase the
`dose?"
`
`A.
`I'm sorry, I need a complete
`question to answer.
`Q.
`Again, I'm your resident, I've
`come in to you, I have a patient, been working
`with a patient for a long time, the patient shows
`no complication, no issues from a day-to-day
`lifestyle, I take the patient's fasting blood
`ammonia level and it's 32 umol/l, it's not 30, and
`the 30 is ULN for that particular laboratory.
`So my question is do I increase the dose
`of the nitrogen scavenging agent?
`MR. BURGY: Same objections.
`THE WITNESS: So, again, I would need
`more information about the patient to
`answer the question.
`BY MR. GREEN:
`Q.
`And, Doctor, that is what I'm
`trying to get out of you. What else do you need
`to know? I'm your resident. Ask me the question.
`What else do you need to know to answer that
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`question?
`
`MR. BURGY: Same objection, sorry.
`THE WITNESS: I'm not sure what question
`you are trying to arrive at, so I can't
`tell you.
`BY MR. GREEN:
`Q.
`Again, I'm your resident, I want
`to know. I'm coming to you, you are the expert, I
`just want to know should I increase the amount of
`the nitrogen scavenging agent?
`A.
`I would not have complete
`information to answer the question at that time.
`Q.
`Well, what additional information
`do you need?
`A.
`I'm uncertain what question you
`are trying to ask. I can't ask it for you.
`Q.
`Let's assume it's HPN, it's
`Ravicti for the present purposes, so I've given
`the patient Ravicti, and the patient is doing
`well, I'm at 32 umol/l, and the upper limit of
`normal is 30, so I come in and say, should I
`increase the dose? I'm the resident, I just want
`to know should I go back and should I increase the
`dose?
`
`MR. BURGY: Object to form, lack of
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`foundation.
`THE WITNESS: I'm sorry, we are having
`difficulty, but I would still need more
`information to answer that hypothetical.
`BY MR. GREEN:
`Q.
`What information, Doctor?
`A.
`Again, I don't know what question
`you are trying to ask yet, so I can't formulate
`your questions for you.
`Q.
`Okay. So let me put this around,
`I come in, I have my patient, patients seems to be
`doing well, no complaints, upper limit of normal
`is 30, I've got 32 on a fasting plasma ammonia
`level, and it's your patient. Do you then
`increase the dose?
`MR. BURGY: Same objections.
`THE WITNESS: This is an incomplete
`hypothetical. I need more information
`about the patient to answer the
`question.
`BY MR. GREEN:
`Q.
`Well, isn't the fact that you
`know that the patient's not even below the upper
`limit of normal with the fasting blood ammonia
`enough to tell you that the patient is otherwise
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`fine, and there's no reason to believe that
`day-to-day life activity is anything other than
`fine for a UCD patient, do you increase the dose?
`MR. BURGY: Object to form.
`THE WITNESS: I'm sorry, I think you
`changed the fundamental part of your
`question.
`MR. GREEN: Okay, which is?
`THE WITNESS: Could you clearly re-ask
`it?
`MR. GREEN: Could I have it read back?
`--- Reporter read back last question ---
`THE WITNESS: I apologize. You were
`asking the same question, and, again,
`it's still an incomplete question.
`BY MR. GREEN:
`Q.
`So based on information you would
`not -- you could not make a decision to increase
`the dose of Ravicti for that patient without some
`additional information; is that correct?
`MR. BURGY: Object to form.
`THE WITNESS: Yes.
`BY MR. GREEN:
`Q.
`So turn back to your paragraph 54
`in the '559 Declaration, you make again the
`
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`statement which I've read once before that
`Fernandes, without reading the entire portion
`here, would suggest to a POSA that measuring
`plasma ammonia following a meal would likely
`result in an inaccurate assessment of the
`patient's plasma ammonia level. Do you see that?
`A.
`Yes.
`Q.
`What do you mean by "inaccurate"
`in this sentence?
`A.
`That you would be less likely to
`reflect the patient's true state.
`Q.
`What do you mean by "true state"?
`A.
`Their medical condition. Again,
`I note that a POSA reading Fernandes would avoid
`obtaining plasma ammonia in the fed state because
`of their variable effect of dietary protein.
`That's what I mean.
`Q.
`So if a plasma ammonia level is
`taken following a meal, and the level is elevated
`above the upper limit of normal, that information
`is not useful then to t
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