12/15/2020
`
`Mukund Chorghade, Ph.D.
`Page 3
`
`In Re: Sitagliptin Phosphate Patent Litigation
`Page 1
` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
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`-------------------------------x
`MYLAN PHARMACEUTICALS INC., )
`TEVA PHARMACEUTICALS USA, INC.,)
`WATSON LABORATORIES INC., )
`DR. REDDY'S LABORATORIES, INC.,)
`DR. REDDY'S LABORATORIES, LTD.,)
`and SUN PHARMACEUTICALS )
`INDUSTRIES LTD., )
` )
` PETITIONER, )
` ) Case IPR
` v. ) 2020-00040
` )
`MERCK SHARP & DOHME CORP., ) U.S. Patent
` ) 7,326,708
` PATENT OWNER. )
`-------------------------------x
`
` VIDEOTAPED DEPOSITION OF MUKUND CHORGHADE, PH.D.
` APPEARING REMOTELY
`
` Tuesday, December 15, 2020
` 9:57 a.m.
`
`Reported by: Lori J. Goodin, RPR, CLR, CRR
` RSA, California CSR #13959
`______________________________________________________
` DIGITAL EVIDENCE GROUP
` 1730 M Street, NW, Suite 812
` Washington, D.C. 20036
` (202) 232-0646
`
`Page 2
`
` REMOTE APPEARANCES
`
`For Patent Owner:
` WILLIAMS & CONNOLLY LLP
` STANLEY E. FISHER, ESQUIRE
` BRUCE R. GENDERSON, ESQUIRE
` SHAUN P. MAHAFFY, ESQUIRE
` JINGYUAN LUO, ESQUIRE
` 725 Twelfth Street, Northwest
` Washington, D.C. 20005
` 202-434-5289
` sfisher@wc.com
` bgenderson@wc.com
` smahaffy@wc.com
` jluo@wc.com
`
`For Petitioner Mylan:
` KATTEN MUCHIN ROSENMAN LLP
` JITTY MALIK, PH.D. ESQUIRE
` ALISSA M. PACCHIOLI, ESQUIRE
` 550 South Tryon Street
` Suite 2900
` Charlotte, North Carolina 28202
` 704-344-3185
` jitty.malik@katten.com
` alissa.pacchioli@katten.com
`
`ALSO PRESENT:
` Henry Marte, Video/Document Technician
`
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` INDEX TO EXAMINATION
`
`WITNESS: MUKUND CHORGHADE, PH.D.
`
`EXAMINATION BY PAGE
`MR. FISHER 6
`MR. MALIK 91
`
` * * *
`
` INDEX TO EXHIBITS
` Mukund Chorghade, Ph.D.
` Mylan Pharmaceuticals Inc., et al. V. Merck Sharp
` & Dohme Corp.
` Tuesday, December 15, 2020
` Lori J. Goodin, RPR, CLR, CRR,
` RSA, California CSR #13959
`
`(No exhibits were marked in today's proceedings.)
`
` * * *
`
`Page 4
` TUESDAY, DECEMBER 15, 2020, 9:57 A.M.
` PROCEEDINGS
`
` THE VIDEOGRAPHER: We are now on the
` record. My name is Henry Marte, videographer
` on behalf of Digital Evidence Group. Today's
` date is December 15, 2020, and the time is
` 9:57 a.m.
` This videotaped deposition is being
` held by remote Zoom in the matter of In Re:
` Sitagliptin Phosphate Patent Litigation. The
` deponent today is Dr. Mukund Chorghade. The
` parties to this deposition are appearing
` remotely and have agreed to the witness being
` sworn in remotely.
` Will counsel please introduce
` themselves for the record and then the court
` reporter will administer the oath to the
` witness.
` MR. MALIK: Go ahead, Stan.
` MR. FISHER: Sure. Stan Fisher for
` Patent Owner, Merck, with the law firm of
`1 (Pages 1 to 4)
`202-232-6046
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`Merck Exhibit 2283, Page 1
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
`
`In Re: Sitagliptin Phosphate Patent Litigation
`Page 5
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` Williams & Connolly.
` I will just note for the record that
` this deposition is relating to the IPR
` proceeding. It is the second deposition of
` Dr. Chorghade. It is not noticed in the
` District Court patent litigation.
` Go ahead, Jitty.
` MR. MALIK: Dr. Jitendra Malik.
` With me is Alissa Pacchioli. Representing
` Mylan. Alissa and I are both from the law
` firm of Katten.
` And I concur with Mr. Fisher's
` description of the deposition.
` THE WITNESS: I am Mukund Chorghade.
` I am here to give a reply declaration and be
` questioned on it.
` * * *
` Whereupon,
` MUKUND CHORGHADE, PH.D.,
` a witness called for examination, having been
` first duly sworn, was examined and testified as
` follows:
`
`Page 6
`
` * * *
` EXAMINATION
` BY MR. FISHER:
` Q. Good morning, Dr. Chorghade. How
` are you today?
` A. Good morning. I am very fine.
` Thank you.
` Q. All right. Great. Let me know if
` you don't understand any of my questions and I
` will try to be efficient with your time today.
` Okay?
` A. Thank you so much.
` Q. Dr. Chorghade, you have not yourself
` done any experimental work in this case. Right?
` A. Not in this case, no.
` Q. And when I asked you previously at
` your first deposition, you said you weren't
` relying on any experimental work for your
` opinions in this case. Right?
` A. That is correct. Yes.
` Q. You told me you didn't do any
` experimental work yourself showing that every
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`Mukund Chorghade, Ph.D.
`Page 7
` time there is contact between sitagliptin and
` phosphoric acid, a 1 to 1 salt of sitagliptin is
` made, right? You didn't do any work?
` A. I did not do any work, no.
` Q. You also told me that you weren't
` relying on anybody's work for the purpose of
` expressing your opinions about a 1 to 1 salt
` being made. Right?
` MR. MALIK: Object to form.
` THE WITNESS: I wasn't relying on
` anybody else's work.
` BY MR. FISHER:
` Q. Right. And you didn't cite any of
` Dr. Chyall's work in your first declaration,
` right?
` A. No, I did not.
` Q. And you didn't mention Dr. Chyall in
` your first declaration?
` A. I did not, I believe. No.
` Q. Okay. Were you aware at the time of
` your first deposition that petitioner Teva had
` submitted a declaration by Dr. Chyall, dated
`
`Page 8
` June 9, 2020, that was essentially a copy of your
` first declaration.
` Were you aware of that?
` A. No. I was not.
` Q. Were you aware that Dr. Chyall's
` June 2020 declaration on behalf of Teva didn't
` mention any of his Israeli work?
` MR. BROGAN: Object to form,
` foundation.
` THE WITNESS: No, I was not aware at
` the time.
` BY MR. FISHER:
` Q. Okay. And Dr. Chyall at that time
` in his June 2020 declaration never told the Board
` that he did a rework of Example 7 of the WO'498.
` You weren't aware of that, right?
` MR. MALIK: Objection. Object to
` form. Speculation. Foundation.
` THE WITNESS: I was not aware of any
` additional work he had done or not done.
` BY MR. FISHER:
` Q. Are you aware that Mylan said in
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`2 (Pages 5 to 8)
`202-232-6046
`
`Merck Exhibit 2283, Page 2
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
`
`Mukund Chorghade, Ph.D.
`Page 11
`
`In Re: Sitagliptin Phosphate Patent Litigation
`Page 9
` June 2020 that it wasn't relying on Dr. Chyall in
` support of its position?
` MR. MALIK: Object to form. Outside
` the scope.
` THE WITNESS: I, I have not
` mentioned any of this in my reply
` declaration. I am not depending on any of
` that work.
` BY MR. FISHER:
` Q. Right. And you weren't aware at the
` time that Mylan said you were its expert, not
` Dr. Chyall, right?
` MR. MALIK: Objection to the extent.
` It is outside the scope and
` mischaracterizes -- and to the extent it
` mischaracterizes Mylan's statement.
` THE WITNESS: I was not aware. I
` am -- I was deposed essentially in these
` proceedings as a witness.
` BY MR. FISHER:
` Q. Now, as I understand your reply
` declaration, you were now relying on some of
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` Q. Are you aware of Dr. Chyall
` mentioning the WO'498 in either his lab notebook
` or his declaration?
` MR. MALIK: Object to form. Outside
` the scope.
` THE WITNESS: I don't have a copy of
` his declaration. Can you show me please
` where that is stated?
` BY MR. FISHER:
` Q. Sure. So, do you have a box of
` material that you received?
` A. Yes, I did. Actually, I did. This
` is it here.
` Q. Yes, go ahead and open it.
` MR. FISHER: And you can go ahead,
` Jitty, as well.
` THE WITNESS: The box, yes, I did
` open it. And I have a big folder with me.
` BY MR. FISHER:
` Q. Okay. So, just for the record I
` have provided a binder of some of the exhibits
` that we will be discussing today.
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`Page 10
` Dr. Chyall's Israeli litigation-related work; is
` that right --
` MR. MALIK: Object to form.
` THE WITNESS: I am -- I have
` reviewed some of Dr. Chyall's work. I don't
` know whether it was part of any particular
` litigation. But I have seen his report. And
` that is what I am relying on, in addition to
` '498 --
` BY MR. FISHER:
` Q. -- right.
` A. -- the patent.
` Q. You don't know the context in which
` Dr. Chyall did the work that you are relying on?
` A. Not exactly, no.
` Q. So, you are not aware that that work
` was originally done back in 2010 relating to
` Israeli patent proceedings?
` A. Not in so many words, no. But, I --
` the work was done to determine whether the
` process reported in '498 does give a 1 to 1
` stoichiometric salt in methanol.
`
`Page 12
` If there is another exhibit that you
` need to see that I don't have in the binder we
` can always put it up on the screen.
` But, there are various tab numbers.
` And Dr. Chyall's declaration in 2010, which is
` Exhibit 2225, is the declaration that you seem to
` be primarily relying on in your reply report.
` So, go ahead and turn to Tab 6.
` A. Okay. I am at Tab 6.
` Q. Okay. And is this the Chyall
` declaration from 2010 that you cite and discuss
` in your reply declaration?
` A. Give me one minute please because I
` want to make sure that the NMRs and all that I
` saw are in here.
` It just seems to be, this has some
` NMRs and other pieces of spectroscopy data.
` Q. And so my question to you was, do
` you see anywhere in this declaration where
` Dr. Chyall discusses the WO'498 or the '871
` patent.
` A. It might be easier for you to point
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`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`3 (Pages 9 to 12)
`202-232-6046
`
`Merck Exhibit 2283, Page 3
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
`
`In Re: Sitagliptin Phosphate Patent Litigation
`Page 13
` me to the page and the paragraph, because this is
` really extensive. It may take --
` Q. Understood. I have reviewed the
` declaration and I did not see any reference to
` WO'498 or the '871 patent in the declaration.
` And I'm wondering if I missed that
` and you, in fact, saw a reference to one of those
` two prior art references.
` A. I reviewed -- I glanced at the first
` dozen pages, but I don't see a specific reference
` to '498.
` Q. Right. And Dr. Chyall never said
` that he reworked Example 7 of WO'498 in his
` declaration. Right?
` A. Not explicitly, no.
` Q. And he doesn't mention WO'498 as far
` as you can tell sitting here today, right?
` A. He does not specifically mention
` '498.
` Q. Now, one of the other documents that
` you rely on in your reply declaration is
` Dr. Chyall's notebook, which is Exhibit 1035.
`
`Mukund Chorghade, Ph.D.
`Page 15
` that I did not have access to at the time.
` Q. Understood. In that WO'498
` reference, which is Exhibit 1004, did not include
` an example where sitagliptin was contacted with
` phosphoric acid, right?
` MR. MALIK: Object to form.
` THE WITNESS: It did not include a
` reference. It did not include anything about
` phosphoric acid.
` What it did demonstrate was that
` contacting with an excess of a strong acid
` still gives the 1 to 1 salt.
` BY MR. FISHER:
` Q. And that strong acid was
` hydrochloric acid, right?
` A. Hydrochloric acid, yes. And they
` used it in one thousandfold excess.
` Q. You had no firsthand knowledge of
` Dr. Chyall's experimental work that you cite,
` correct?
` A. Other than review of this notebook
` and all, I don't know what we can define as
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`Page 14
` Do you see that in your binder?
` A. Do you mean in the binder that you
` just sent to me?
` Q. Yes, sir.
` A. Yes, I do see it.
` Q. Okay. And you are relying on
` experiments in this notebook in support of your
` opinions; is that right?
` A. I reviewed some of the experiments,
` yes.
` Q. Okay. Neither of those two
` exhibits, Exhibit 2225 or 1035 were cited in your
` first declaration. Correct?
` A. That is correct. I had no access to
` that, but more importantly in '498, it was
` already documented and demonstrated that the
` reaction between the sitagliptin free base and at
` that time the hydrochloric acid gave a 1 to 1
` salt.
` Q. There was no --
` A. But, it was not necessary for me at
` the first declaration to use any of the this data
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`Page 16
`
` firsthand knowledge.
` I have not had any discussions with
` the gentleman or anything like that. But, I did
` read this report and reviewed some of the
` notebook.
` Q. Right. So, you hadn't discussed
` Dr. Chyall's experimental work with him, you
` indicated, right?
` A. That is correct.
` Q. You didn't direct Dr. Chyall's
` experimental work, right?
` A. No, I did not.
` Q. You weren't in the laboratory with
` Dr. Chyall when he did the work?
` A. No, I was not. No, sir.
` Q. You didn't, yourself, repeat any of
` Dr. Chyall's experimental procedures, right?
` A. No, not at any time.
` Q. And you didn't know this work had
` been done at the time of your first declaration.
` Right?
` MR. MALIK: Asked and answered.
`4 (Pages 13 to 16)
`202-232-6046
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`Merck Exhibit 2283, Page 4
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
`
`In Re: Sitagliptin Phosphate Patent Litigation
`Page 17
`
`Mukund Chorghade, Ph.D.
`Page 19
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` BY MR. FISHER:
` Q. Correct?
` A. That is correct, yes.
` Q. You are taking Dr. Chyall's
` statements in his declarations about his work at
` face value, right?
` A. Not just at face value. I have
` reviewed some of the spectra, some of the data
` that went with it. And I am rather confident
` that it supports the chemical structure of the
` molecule -- of the other molecules that he made.
` And the fact that he did many
` experiments, the sole product of which was all
` very nicely demonstrated to be the appropriate
` 1 to 1 salt.
` Q. Okay. Now, Dr. Chyall did his work
` in 2010 or later than that. Right?
` A. Let's see. He has -- the dates on
` here are roughly -- some of them are July 21,
` October 19 of 2010. I cannot answer whether he
` did any work after 2010.
` Q. Fair enough. As far as you are
`
`Page 18
` aware, Dr. Chyall's work is not prior art to the
` '708 patent, right?
` A. It is not prior art. It starts with
` exactly duplicating. And it is a very accurate
` determination of the production of the procedures
` that were used for sitagliptin hydrochloride in
` Example 7 in '498.
` Q. Even though as far as you are aware
` W0'498 and Example 7 aren't referenced in the
` declaration or the notebooks; right?
` A. That is correct.
` MR. MALIK: Asked and answered.
` BY MR. FISHER:
` Q. You don't normally rely on
` litigation related opinions in your work in the
` pharmaceutical industry, right?
` MR. MALIK: Object to form.
` THE WITNESS: Work in pharmaceutical
` industry or drug discovery and development,
` and I have never relied on litigation related
` documentation.
` I have gone to the primary
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` literature.
` BY MR. FISHER:
` Q. Okay. Now I want to turn to
` Dr. Chyall's declaration, Exhibit 2225 which you
` discuss in your reply declaration.
` Would you turn to Paragraph 23.
` A. In my declaration or his?
` Q. No, his. I'm sorry, his, which is
` Exhibit 2225.
` A. Did you say Paragraph 23?
` Q. Yes.
` A. Yes, I am there please.
` Q. Okay. So the declaration states
` that "12 salt formation experiments were
` conducted by varying common parameters used in
` screening potential salts in pharmaceutical APIs."
` Do you see that?
` A. I do. Yes, I do.
` Q. Okay. And, one of the common
` parameters that Dr. Chyall varied was the
` composition of the solvent. Is that right?
` MR. MALIK: Object to form.
`
`Page 20
` THE WITNESS: I have stated this in
` my own reply declaration. He was essentially
` replicating, and he has done complete and
` accurate replication of what was described in
` '498.
` The amount of perturbation he has
` made in changing the solvent is only three
` experiments where he has added 12.5 percent
` water.
` But, everything else is done in
` methanol as was everything else reported in
` '498.
` BY MR. FISHER:
` Q. Okay. I had a more straightforward
` question.
` There was a statement that says,
` after the first sentence of Paragraph 23,
` discussing his varying common parameters.
` He says that these include the
` composition of the solvent, the temperature
` during the reaction, and the molar ratio of acid
` to base.
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`5 (Pages 17 to 20)
`202-232-6046
`
`Merck Exhibit 2283, Page 5
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
`
`In Re: Sitagliptin Phosphate Patent Litigation
`Page 21
`
`Mukund Chorghade, Ph.D.
`Page 23
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` Do you see that?
` A. Yes, I do. Thank you.
` Q. Okay. So, the composition of the
` solvent was a common parameter that Dr. Chyall
` varied. Right?
` MR. MALIK: Object to form. Asked
` and answered.
` THE WITNESS: He varied it in three
` of the 12 experiments. And just water extra.
` He did not choose different solvents.
` BY MR. FISHER:
` Q. He could have used different
` solvents but he didn't, right?
` A. He could have used any solvent, but
` he was trying to see what happens as an accurate
` determination of what was reported in '498. And
` '498 is very unerring in saying that the
` reactions were done in methanol.
` Q. Dr. Chyall never stated that he was
` trying to understand what an accurate
` reproduction of '498 looked like, right?
` A. I have no firsthand knowledge of
`
`Page 22
`
` that or his intentions.
` Q. Right. One of the other common
` parameters that Dr. Chyall varied was the
` temperature during the reaction. Correct?
` A. That is correct.
` Q. And he also varied the molar ratio
` of acid to base?
` A. That is correct.
` Q. And he doesn't mention in this
` paragraph or the paragraphs that follow Example 7
` of WO'498. Right?
` MR. MALIK: Object to form.
` THE WITNESS: He does not
` specifically mention that, though, in his
` statement, that these experiments were a
` deliberate attempt to obtain some phosphate
` salt, others.
` I assume -- or, I would guess that
` this would be related to the litigation at
` hand, which focuses on whether a reaction
` between phosphoric acid and sitagliptin free
` base yields the 1 to 1 stoichiometric salt
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` and nothing else.
` BY MR. FISHER:
` Q. Right. And -- okay.
` But you see no reference or
` discussion that he was trying to follow Example 7
` of WO'498. Right?
` A. I do not see any in these particular
` pages that you have provided to me, no.
` Q. And you are not aware of anything
` like that in his declaration. Right?
` A. I am not aware of that, no.
` Q. And he says that he performed a
` screen to see whether a phosphate salt would form
` by varying common parameters used in screening
` some salts of pharmaceutical APIs. That is what
` he says, right?
` A. Yes, that is what is stated.
` Q. And you agree that a person of skill
` in the art wouldn't be forced to try to alter
` Example 7 of WO'498 in order to try to make a
` phosphate salt. Right?
` MR. MALIK: Objection to form.
`
`Page 24
` THE WITNESS: '498, any POSA moment,
` they have understood that. They have
` realized -- they would realize that the
` reaction between sitagliptin free base and a
` strong acid, whichever it may be, will yield
` the 1 is to 1 salt.
` Any screening they would do with
` other acids will be with that understanding
` in mind.
` BY MR. FISHER:
` Q. Why don't you turn to Paragraph 24
` in Exhibit 225 -- excuse me, Exhibit 2225, which
` is the Chyall declaration. And let me know when
` you are at Paragraph 24.
` A. Sorry I am just repositioning my
` chair because of this folder. Okay, please go
` ahead.
` Q. Okay. And if you look at Table 1.
` It is entitled Salt Formation Experiments
` Conducted With Sitagliptin.
` A. Uh-huh.
` Q. And you agree that none of those
`
`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`6 (Pages 21 to 24)
`202-232-6046
`
`Merck Exhibit 2283, Page 6
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
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`In Re: Sitagliptin Phosphate Patent Litigation
`Page 25
` experiments is a reproduction of Example 7 of
` WO'498. Right?
` MR. MALIK: Objection, asked and
` answered.
` THE WITNESS: Actually, the '498 and
` Example 7 depicts very accurately what
` happens when you use an excess of a strong
` acid.
` So, this experiment over here where
` he has used 4063-19-01 will be the closest to
` using sitagliptin, a strong acid, and in
` excess, which is the five equivalents over
` here.
` BY MR. FISHER:
` Q. Right. So, 4063-19-01 is the
` closest to WO'498, but it is not Example 7 of
` WO'498. Correct?
` MR. MALIK: Object to form.
` THE WITNESS: It will not be that,
` because Example 7 uses hydrochloric acid.
` And this one, this experiment uses phosphoric
` acid which is also a strong acid, also used
`
`Mukund Chorghade, Ph.D.
`Page 27
` Q. Sure. Dr. Chyall tried multiple
` different ratios of sitagliptin to phosphoric
` acid in the experiments described in Table 1.
` Right?
` A. Yes, he did. Yes, he did.
` Q. And none of the ratios listed in
` this Table 1 of Exhibit 2225 is the ratio of API
` to acid of Example 7 of WO'498. Right?
` A. None of this is that. In Example 7
` you have a thousandfold excess of hydrochloric
` acid which is indeed a very overwhelming excess.
` In this one the logistics of
` phosphoric acid to base is five equivalents. And
` the other stoichiometries are varying.
` Q. Right. So, Example 7 you indicated
` use a thousandfold excess of HCl to base; is that
` right?
` A. That is correct.
` Q. And the ratio of excess acid to base
` that is highest in Table 1 is 5 to 1. Is that
` right?
` A. Is 5 to 1, yes.
`
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`Page 26
`
` in strong excess, high excess.
` BY MR. FISHER:
` Q. Right. So, none of these
` experiments in Table 1 is a reproduction of
` Example 7 of WO'498, right?
` MR. MALIK: Asked and answered.
` THE WITNESS: The experimental
` conditions have been kept the same.
` Obviously it is not a reproduction, because
` Example 7 used hydrochloric acid. The
` commonalities are it is a strong acid.
` And these experiments are done with
` phosphoric acid which is different and not
` done in pure methanol which is sometimes
` different.
` BY MR. FISHER:
` Q. Uh-huh. So, Dr. Chyall tried
` multiple different ratios of sitagliptin to
` phosphoric acid among the experiments in Table 1.
` Right?
` A. Could you kindly repeat the
` question, please.
`
`Page 28
` Q. And five of the experiments in
` Table 1 included a use of ratio of base to acid
` of 2 to 1 or higher, right?
` A. Correct. And, as he states very
` clearly, that was done to see whether any salt
` other than a 1 to 1 can form. So, he had to vary
` the stoichiometry of the base and phosphoric
` acid.
` Q. And you agree that going from a
` thousandfold excess of HCl to base to a 5 to 1
` excess of acid to base can have a material effect
` on the reaction, right?
` A. No, I would not agree to that one.
` Please remember that hydrochloric acid is bubbled
` into solution and you can do that.
` With phosphoric acid you are doing
` the reaction in solution. And even if you use a
` large amount of water, for example, they have
` very carefully demonstrated that it makes no
` difference.
` If you use 12.5 percent water, the
` water is already in large excess.
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`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`7 (Pages 25 to 28)
`202-232-6046
`
`Merck Exhibit 2283, Page 7
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
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`In Re: Sitagliptin Phosphate Patent Litigation
`Page 29
` Q. You can't use a thousandfold excess
` of phosphoric acid to sitagliptin and create a
` salt. Right?
` A. You will create a salt, but it will
` not be -- it will not be a reproduction of
` whatever is stated in 7, because now the water
` will be a lot more.
` But, you will get a salt.
` Q. You haven't done that work yourself
` to demonstrate that if you were to use one
` thousandfold excess of phosphoric acid to
` sitagliptin that you would get a salt, right?
` A. No, I have not done that or any
` other experiment related to this subject matter
` in hand.
` Q. And Dr. Chyall didn't do any
` experiment where he used a thousandfold excess of
` phosphoric acid to sitagliptin, right?
` A. I can only go by the words on this
` paper. I have the same table in my reply
` declaration. I did not see any reference to him
` using a thousandfold excess.
`
`Mukund Chorghade, Ph.D.
`Page 31
` performing a salt screen to see what salts of
` phosphoric acid would form as of the priority
` date, right?
` A. Yes, they would have that knowledge,
` yes.
` MR. MALIK: Object to form.
` BY MR. FISHER:
` Q. You agree that changing a reaction
` solvent can have a material effect on the salt
` that is forming out of the reaction?
` A. As I have stated in my reply
` declaration many times, the change of solvent is
` not going to impact materially whether a 1 to 1
` salt forms between the amine and the amine
` hydrochloride -- neither -- I'm sorry. And the
` phosphoric acid to give a monophosphate salt.
` So that there will be no change in
` that one.
` Q. So, you yourself -- go ahead. I'm
` sorry. Finish.
` A. No, sorry. With the temperature and
` all of that, also those factors will not be
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`Page 30
` Q. So, Chyall tried two different
` reaction solvents; is that right?
` A. The basic reaction solvent he tried
` was methanol. And in some cases he added
` 12.5 percent water.
` At that point it is still a methanol
` solution with just some added water. I would not
` call it two different solvents.
` Q. Example 7 did not use methanol
` water, right?
` A. No.
` Q. You previously told me that
` typically you would dissolve an amine in organic
` solvent which is usually one of the lower
` alcohols: methanol, ethanol or isopropyl
` alcohol, in an attempt to create a salt.
` Do you recall that?
` A. Yes, I do. Yes, I still use those
` procedures.
` Q. And a person of skill in the art
` would have understood that they could have tried
` methanol, ethanol and isopropyl alcohol in
`
`Page 32
`
` relevant to the acid base chemistry.
` Q. So your view is it doesn't matter if
` you change the temperature or the reaction
` solvent. You are always going to get a 1 to 1
` salt. That is your opinion?
` A. This is correct. Yes.
` Q. Now, Dr. Chyall tried three
` different temperatures: ambient, 0 degrees and
` 65 degrees Celsius. Do you see that?
` A. I do, yes.
` Q. And, 0, ambient and 65 degrees
` Celsius were all reasonable temperatures that a
` person of skill in the art might use in a screen
` if they were trying to make a phosphoric acid
` salt, right?
` A. This is correct. This is correct.
` So, the ambient causes room temperature. And it
` is very common to try 0 degrees and the reflux
` temperature of your solvent.
` And a person skilled in the art
` would know that.
` Q. And the reflux temperature that you
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`www.DigitalEvidenceGroup.com
`
`Digital Evidence Group C'rt 2020
`
`8 (Pages 29 to 32)
`202-232-6046
`
`Merck Exhibit 2283, Page 8
`Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.
`IPR2020-00040
`
`

`

`12/15/2020
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`In Re: Sitagliptin Phosphate Patent Litigation
`Page 33
` referred to is 65 degrees C. Is that right?
` A. Yes, that is the boiling point of
` methanol.
` Q. And so a person of skill in the art
` would understand that they could try 0, ambient
` and 65 degrees, to understand what salts might
` form. Is that right?
` MR. MALIK: Object to form.
` THE WITNESS: A person skilled in
` the art would try those conditions first.
` BY MR. FISHER:
` Q. Right. And Example 7 of WO'498
` doesn't disclose the use of 0 degrees or
` 65 degrees Celsius as reaction conditions, right?
` A. It does not. It shows clearly the
` reaction to form the hydrochloric salt