Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 1 of 120
`H1UsKOW1
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`1653
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF NEW YORK
`------------------------------x
`
`KOWA PHARMACEUTICALS AMERICA, INC., et al.,
`
`
`
`
`
` Plaintiffs,
`
`14 Civ. 2758 (PAC)
`14 Civ. 5575 (PAC)
`14 Civ. 7934 (PAC)
`15 Civ. 3935 (PAC)
`
`
`
` v.
`
`
`AMNEAL PHARMAEUTICALS, LLC, et al.,
`
`
`
` Defendants.
`
`------------------------------x
` New York, N.Y.
` January 30, 2017
` 9:30 a.m.
`
`Before:
`
`
`HON. PAUL A. CROTTY,
`
`
`
` District Judge
`
`
`APPEARANCES
`
`
`MINTZ LEVIN COHN FERRIS GLOVSKY & POPEO, P.C.
` Attorneys for Plaintiffs Kowa and Nissan
`BY: KATHLEEN B. CARR
` DAVID G. CONLIN
` JENNIFER L. DEREKA
` PETER J. CUOMO
`
`MADDOX EDWARDS, PLLC
` Attorneys for Defendant Amneal
`BY: STEVEN A. MADDOX
` JEREMY J. EDWARDS
`
`FLEMMING ZULACK WILLIAMSON ZAUDERER, LLP
` Attorneys for Defendant Sawai
`BY: CRAIG S. KESCH
` -and-
`SUGHRUE MION, PLLC
` Attorneys for Defendant Sawai
`BY: MICHAEL DZWONCZKY AZY S. KOKABI
`
`
` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`H1UsKOW1
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`1653
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF NEW YORK
`------------------------------x
`
`KOWA PHARMACEUTICALS AMERICA, INC., et al.,
`
`
`
`
`
` Plaintiffs,
`
`14 Civ. 2758 (PAC)
`14 Civ. 5575 (PAC)
`14 Civ. 7934 (PAC)
`15 Civ. 3935 (PAC)
`
`
`
` v.
`
`
`AMNEAL PHARMAEUTICALS, LLC, et al.,
`
`
`
` Defendants.
`
`------------------------------x
` New York, N.Y.
` January 30, 2017
` 9:30 a.m.
`
`Before:
`
`
`HON. PAUL A. CROTTY,
`
`
`
` District Judge
`
`
`APPEARANCES
`
`
`MINTZ LEVIN COHN FERRIS GLOVSKY & POPEO, P.C.
` Attorneys for Plaintiffs Kowa and Nissan
`BY: KATHLEEN B. CARR
` DAVID G. CONLIN
` JENNIFER L. DEREKA
` PETER J. CUOMO
`
`MADDOX EDWARDS, PLLC
` Attorneys for Defendant Amneal
`BY: STEVEN A. MADDOX
` JEREMY J. EDWARDS
`
`FLEMMING ZULACK WILLIAMSON ZAUDERER, LLP
` Attorneys for Defendant Sawai
`BY: CRAIG S. KESCH
` -and-
`SUGHRUE MION, PLLC
` Attorneys for Defendant Sawai
`BY: MICHAEL DZWONCZKY AZY S. KOKABI
`
`
` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 2 of 120
`H1UsKOW1
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`1654
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`APPEARANCES
`(Continued)
`
`
`KELLEY DRYE & WARREN, LLP
` Attorneys for Defendant Lupin
`BY: DOUGLASS C. HOCHSTETLER
` CONSTANTINE KOUTSOUBAS
`
`ALSO PRESENT:
`
`ANDY CEPREGI, technician
`GEOFF ROBERTS, technician
`BRIAN SPARKS, technician
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` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 3 of 120
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`1655
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`(Trial resumed; in open court)
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`THE COURT: Good morning. Dr. Byrn is going to
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`testify, is that right?
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`MR. CONLIN: Yes, your Honor.
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`THE COURT: With regard to Mr. Maddox's letter of
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`January 26, the response of January 29; the letters of
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`January 28 and the response of January 29 dealing with PTX 735,
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`14B, and 74, the objection is sustained.
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`Call Dr. Byrn.
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`MR. MADDOX: Your Honor, just a quick question with
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`respect to demonstratives for Dr. Byrn.
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`We have objected to several because they contain --
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`you talked about those exhibits.
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`THE COURT: When we get to them, we will take them.
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`MR. MADDOX: Thank you.
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`THE COURT: Come on up, Dr. Byrn.
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`Dr. Byrn, you have been in the courtroom throughout
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`the proceeding, haven't you?
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`THE WITNESS: Yes.
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`THE COURT: Let me remind you, you're still under
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`oath. We are not going to swear you again.
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`THE WITNESS: OK.
`
` STEPHEN R. BYRN, resumed.
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`THE COURT: Mr. Bauer.
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`MR. BAUER: Good morning, your Honor.
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` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 4 of 120
`H1UsKOW1 Byrn - direct
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`DIRECT EXAMINATION
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`BY MR. BAUER:
`
`Q. Good morning, Dr. Byrn.
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`A. Good morning.
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`MR. BAUER: Your Honor, we previously heard from
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`Dr. Byrn in terms of his qualifications. I would like, with
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`the court's permission, to just read in Mr. Byrn's
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`qualifications as an expert to see if there is any objection.
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`THE COURT: Mr. Maddox, do you have any objection?
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`He's already been qualified as an expert. He's filed
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`expert reports.
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`He's an expert, isn't he?
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`MR. MADDOX: Absolutely.
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`THE COURT: He is qualified as an excerpt. Prior
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`qualification is good enough for this particular episode as
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`well.
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`MR. BAUER: He's an expert in solid state chemistry,
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`drug formulation, and manufacture of composition of
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`pharmaceutical drug products.
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`THE COURT: OK.
`
`BY MR. BAUER:
`
`Q. Dr. Byrn, you have been here for the past two weeks and you
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`have listened to all the testimony and seen the exhibits in the
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`case?
`
`A. Yes.
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 5 of 120
`H1UsKOW1 Byrn - direct
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`1657
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`Q. And have you rendered an opinion in this case concerning
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`the validity of the '993 claims?
`
`A. Yes.
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`Q. Based on evidence that you've seen in this case and the
`
`testimony that you've heard, has anything changed your opinion?
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`A. No. I still believe that the '993 patent is valid.
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`Q. For the court, could you please summarize the bases for the
`
`reasons that you believe that the claims of the '993 patent are
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`valid?
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`A. Yes. I've got --
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`Q. And could you go to slide two, please.
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`A. So, first, form A, claims 1 and 22 to 25, are
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`non-anticipated. That's still my opinion, and this is because
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`there's insufficient information in the EP '406 and example
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`three, and I'll describe that.
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`And second, that a person of skill could get -- and
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`this is a key element -- could get different polymorphic forms
`
`of pitavastatin calcium following example three of the '406.
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`That means that example three doesn't necessarily inevitably
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`produce form A.
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`Q. And with respect to obviousness, Dr. Byrn?
`
`A. And then for obviousness, form A of claims 1 and 22 to 25
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`are not obvious.
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`In my opinion, the defendants' position is based on
`
`hindsight and that polymorphs are not at all predictable. And
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` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 6 of 120
`H1UsKOW1 Byrn - direct
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`a POSA would not have been able to predict whether a specific
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`polymorph will be produced, much less that it will be form A.
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`And also, a person of skill would have understood that
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`a polymorph screen is anything but routine and could involve
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`thousands of experiments.
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`Finally, performing such a comprehensive screen
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`wouldn't have provided a person of skill with a reasonable
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`expectation of success that a specific polymorph would have
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`been produced, much less it would have been form A.
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`Q. Now, if we can go to slide three.
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`Turning to the '993 patent, what is the general
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`subject matter of the '993 patent, Dr. Byrn?
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`A. The '993 patent addresses the preparation of forms A, B, C,
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`D, E, F, and the amorphous form of pitavastatin calcium. And
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`form A, this general description gives a general framework for
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`making form A. It says form A can generally be prepared from
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`pitavastatin sodium upon reaction with calcium chloride in an
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`aqueous reaction medium.
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`And then it also says there's an alternative that
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`form A can also be prepared using the lactone and calcium
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`hydroxide.
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`Q. Is this passage here sufficient to always get form A?
`
`A. No. That's what I'll be testifying about. But this is not
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`enough information to necessarily and inevitably make form A.
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`Q. Now, would you characterize this as just a general
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 7 of 120
`H1UsKOW1 Byrn - direct
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`1659
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`framework?
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`A. That's right. It's a general overall procedure to make
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`form A.
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`Q. And in this patent, is there a more specific procedure that
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`teaches a POSA how to obtain form A?
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`Could we go to the next slide, please.
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`A. Yes. This is example one. This would give a recipe to a
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`person of skill, a way to make form A, and it's specific. It
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`gives you enough information to make form A.
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`And it starts with a compound using the chemical
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`compound 4.15 grams, the chemical compound, and it's actually
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`what's called a tert-butyl ester, which is a different
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`derivative from some of the others we will see, but a specific
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`derivative.
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`And then it says it was suspended in a solvent. It is
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`called a mixture of methyl tert-butyl and methanol, and then
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`you add to that solution an aqueous solution of sodium
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`hydroxide, and then it makes a yellow color, yellow solution,
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`which is stirred for a given time.
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`And then you cool -- I'm about in the middle now --
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`you cool the mixture to room temperature and add 50 mls of
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`water and stir, and then you do a separation. There is some
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`organic solvents, so the water and the organic solvents
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`separate a little bit like vinegar and oil. So they separate
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`and you carry out that separation. It says the aqueous phase
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` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 8 of 120
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`was separated.
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`And then to this solution you add the calcium
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`chloride, and you stir the suspension for 16 hours. And then
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`you filter the suspension, and then here is the drying, which
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`is key. You dry at 40 degrees C and 50 millibar, which is a
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`given pressure, for 16 hours, and then it tells you you get
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`form A and it is characterized by the X-ray pattern.
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`Then also, it says there is further characterization
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`by some other analytical methods, thermogravimetry, FT-IR, and
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`then it tells you that the water content is 10 percent. And it
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`tells you the differential scanning calorimetry, which is a
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`measurement, another analytical measurement, showing a melting
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`point of 95. So this is a specific procedure that a person of
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`skill could follow.
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`Q. For the record, this is PTX 143 as the '993 patent, and
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`this is based on Bates number 844714. It is column eight,
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`line 28 through 53.
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`Thank you, Dr. Byrn.
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`And if we could go to the next slide, which is still
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`in the '993 patent, PTX 143 at Bates number 844711.
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`What is shown on this slide, Dr. Byrn?
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`A. This shows -- and it is in column one of the patent -- and
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`it shows that the patent disclosed that the prior art made
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`crystalline pitavastatin calcium. It says there is a synthetic
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`procedure for the preparation of pitavastatin calcium, that
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` SOUTHERN DISTRICT REPORTERS, P.C.
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`Case 1:14-cv-02758-PAC Document 163 Filed 02/24/17 Page 9 of 120
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`means the synthesis of the solvent, and it says that it is a
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`white crystalline material what a melting point 190 to 192.
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`Q. And in terms of the disclosure, where is this information
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`found, the front or the back of the patent?
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`A. Yes. So it is in column one, right at the bottom. You can
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`see that on the left side of the slide. So it is right up
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`front for the reader.
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`Q. Now, turning to the next slide, slide six.
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`MR. BAUER: For the record, your Honor, this
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`reference, this citation to this is in the slide DTX 1359, but
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`the binders are using PTX 1337. It is the same file history,
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`and having what was originally produced to us, 1359, is missing
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`some pages, so we submitted PTX 1337. But the Bates numbers
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`that we are relying on and the documents that we are relying on
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`in this exhibit are the exact same.
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`MR. MADDOX: Your Honor, there appears to have been
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`some sort of error in the copying and so forth. We are going
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`to work that out and get it properly submitted.
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`We have been told that the testimony won't involve any
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`of the pages that they believe are missing, so we should just
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`go ahead just for now, and we will sort it out.
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`THE COURT: Thank you, Mr. Maddox.
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`Mr. Bauer, go ahead.
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`MR. BAUER: Thank you.
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`BY MR. BAUER:
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` SOUTHERN DISTRICT REPORTERS, P.C.
` (212) 805-0300
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`Q. So on Bates number Mylan (Pitav) 014575, what is shown,
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`Dr. Byrn?
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`A. This is shown in the prosecution history that the
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`applicants disclose a third-party observation from December
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`2006, and it is on a letterhead by Wachtershauser & Hartz,
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`December 14, 2006.
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`Q. If we can go to the next slide, which refers to Bates
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`numbers 14586 and 14583.
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`What does this slide show, Dr. Byrn?
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`A. So this also shows -- this is from the prosecution history,
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`and it shows, if you look down the middle, it says: Sir,
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`attached heretofore filing are the following papers. It says,
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`Information disclosure statement third-party observation. So
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`that's being submitted to the patent office. And then the
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`patent office replied with a receipt date of 23rd of June,
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`2008.
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`Q. So, Dr. Byrn, does it appear that the date this December
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`2006 third-party observation was submitted was June 23, 2008?
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`A. That's what it looks like. It's the receipt date at the
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`patent office.
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`Q. OK. If we go to the next slide, which is from PTX 172,
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`Bates numbers 1335157 and 1335159, what is this showing,
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`Dr. Byrn?
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`A. This is showing that the examiner acknowledged the
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`third-party -- the receipt of the third-party observation.
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`H1UsKOW1 Byrn - direct
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`1663
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`There is a call-out that says AAN, and then it gives the name
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`of the third-party submission. And then at the bottom of that
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`page, it's signed and dated by the examiner.
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`Q. That means the examiner saw this document and considered
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`it?
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`A. That's correct.
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`Q. If we go to the next slide, which is also from the file
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`history of PTX 172, and the document on the left-hand side has
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`Bates numbers 1335158.
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`What does this document show, Dr. Byrn?
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`A. It shows the applicant informed the U.S. Patent Office that
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`Hartz & Wachterhauser, who filed the December 3, 2006
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`third-party observation, were representing the patent owner
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`Nissan.
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`Q. And that document on the right is an excerpt bearing Bates
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`numbers 1334204.
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`Is this a communication to the patent office
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`indicating that the Wachterhauser law firm that previously
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`submitted the December 2006 observation is now representing the
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`patent owner?
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`A. Yes. It says, now acting as representative of the new
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`proprietor, Nissan Chemical Industries.
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`Q. And this document was submitted to the United States Patent
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`Office?
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`A. That's my understanding.
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`Q. And is what is shown on the left-hand side of the document
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`under AAA?
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`A. That's right. That's my understanding.
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`Q. If we now can turn to the next slide, which is EP '406
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`patent, which is DTX 0034, it is also tab four in the binders.
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`We have heard a lot about this patent, Dr. Byrn. What
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`does it describe?
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`A. So this patent describes a very general synthesis of
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`pitavastatin calcium. And I've got a slide on the next page.
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`Q. And if we go back, just spend a little more time on the.
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`'406.
`
`What, if any, solid form is described in EP '406?
`
`A. The only solid form that's described are white crystals
`
`with a melting point of 190 to 192.
`
`Q. Does the '406 patent provide any diffractograms?
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`A. No.
`
`Q. Does the '406 patent provide any peak lists?
`
`A. No.
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`Q. You mentioned the white crystals of example three, is that
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`correct?
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`A. Yes.
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`Q. And you said that was the only solid form described in
`
`EP '406?
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`A. That's right.
`
`Q. So let's take a look at EP '406, example three, which is on
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`slide 11, tab four, at Mylan 01494.
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`Could you walk us through what that example describes?
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`A. Sure. So it starts with 12 grams, and then there is a long
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`chemical name, which is the name of pitavastatin. And then it
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`says, D(+) phenylethylamine salt compound, and it has some
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`symbols, including a minus and a plus. That is the cryo salt,
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`mix salt of the phenylethylamine compound. It tells you that
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`was obtained from example one of that patent.
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`Then they added to that -- that is a different
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`starting material from example one in the '993 patent. And
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`then they added to that sodium hydroxide aqueous solution and
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`water and stirred. It doesn't say yellow solution or anything,
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`they just stirred. And then they added aqueous calcium
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`chloride to that, and it says was dropwise added. Then they
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`say it was stirred overnight, no temperature, and then the
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`white precipitate was collected by filtration. And this is
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`where -- and it gives nine grams of white crystals. So very
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`abbreviated example.
`
`Q. Is the methodology of the melting point described in this
`
`example?
`
`A. No. There is no direction to a person of skill how to
`
`measure that melting point.
`
`Q. Are the stirring conditions provided?
`
`A. No. There is no stirring conditions, no temperature.
`
`Q. Are the drying conditions provided?
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`A. No. There's no dry -- unlike example one, there is no
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`drying whatsoever provided.
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`Q. And if we could turn to slide 12.
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`Is your testimony consistent with that of Dr. Roberts
`
`and Dr. Sessler?
`
`A. Yes. So on this slide, I summarize what Dr. Roberts and
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`Dr. Sessler testified, and I'll cover that some more in the
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`future. But they agree that no stirring temperature, no
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`stirring speed, and no stirring time was provided, in that it
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`was overnight, but it was vague as to what the length of time
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`was. And then they also testified that there was no drying
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`time, temperature, and pressure. And in the drying of a
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`compound like this, time, temperature and pressure are critical
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`to understand those.
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`Q. In terms of drying time, does EP '406 describe whether or
`
`not the pitavastatin calcium obtained in example three is a
`
`high dried?
`
`A. No, it didn't. And the drying time is critical as to
`
`whether a hydrate is produced or not.
`
`Q. Does the EP '406 disclosure anywhere in that disclosure
`
`describe the pitavastatin calcium as a hydrate?
`
`A. No. And we also know that there are many hydrates. There
`
`are several hydrates in which pitavastatin calcium can exist,
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`and it doesn't provide any information on those.
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`Q. But none of those different hydrates were known prior to
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`1667
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`the filing date of the '993 patent, isn't that correct?
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`A. That is correct. We only know that now from the '993
`
`patent.
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`Q. So if we go to the next slide, still further talking about
`
`example three of EP '406, what is this slide saying, Dr. Byrn?
`
`A. This slide outlines the details of the various drying
`
`conditions and shows what I was talking about, that the example
`
`three allows a broad range of drying conditions.
`
`So on the temperature side, example three allows air
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`drying and ambient temperature, moderate temperature drying are
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`putting it in an oven at higher temperature, and then on the
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`pressure side, you could have no vacuum, aspirator vacuum,
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`which is sort of an intermediate, known to a person of skill
`
`known to be intermediate, or you could put it in a vacuum pump
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`and do very low vacuum. And the time is variable, and that is
`
`a critical aspect. So how long you do it is crystal.
`
`Q. And this lack of drying condition information, what,
`
`if any, effect can it have on the water content of the
`
`pitavastatin calcium sample obtained by example three?
`
`A. Well, it can change the water content over a broad range.
`
`Q. And if we could go to slide 14, please.
`
`Were you in court when Dr. Roberts testified about the
`
`broad range of water content of 3 to 15 percent by following
`
`example three?
`
`A. Yes.
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`Q. Do you agree with that testimony?
`
`A. I do. I agree that the pitavastatin calcium product from
`
`'406 can have a water content ranging from 3 to 15 percent.
`
`Q. Could it be more than that, than 3 to 15?
`
`A. I wouldn't think it would be more than that based on the
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`conditions provided, based on the indications provided.
`
`Q. And if we go to slide 16.
`
`What is this showing, Dr. Byrn?
`
`A. This shows an experiment where changing water content
`
`results in different polymorphic forms.
`
`Q. If we go to the next slide. If we go to just number one --
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`and this is from PTX 172, Bates numbers 1334985 through
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`1334995, and box number one appears at 1334985.
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`What does this describe, Dr. Byrn?
`
`A. Well, box number one just describes it. It says patent
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`2006-501997.
`
`Q. OK.
`
`A. And then it says, experimental report and it is dated
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`December 10, 2012.
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`Q. And if we could pull up from PTX 172, page 922, and zoom in
`
`on that table.
`
`What does this table show, Dr. Byrn?
`
`A. So this shows the result of this experiment, and what it
`
`shows -- and it is also stated in words on the slide -- it
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`shows that if you have low humidity at 49 percent, you observe
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`crystal form A. So at the top it says under low humidity and
`
`it says observe crystal form A. If you go under high humidity,
`
`at least 50 percent, it shows that you have crystal form E.
`
`So this is showing that depending on what humidity you
`
`have, you have either pitavastatin calcium crystal form A or
`
`pitavastatin crystal form E, and this correlates with the
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`drying conditions I was outlying. So if you dry such that you
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`create low humidity, you end up with form A. If you dry such
`
`that you create high humidity, you end up with form E.
`
`So this shows unequivocally, if you follow '406, since
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`it has no drying conditions, you can get either form A or E.
`
`Q. So this table which is shown at 1334986, in fact, shows
`
`that at low humidity, isn't it true there is a lower water
`
`content in the pitavastatin crystal at lower humidity?
`
`A. That's correct. You're drying at lower humidity, you're
`
`drying under conditions where you have lower humidity, and you
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`get lower water content.
`
`Q. So when you're looking at this table, the low humidity, the
`
`water content is lower for crystal form A than the pitavastatin
`
`is under high humidity, which has a higher water content and
`
`transforms to form E.
`
`A. Correct. And it is saying, actually, that, at most,
`
`49 percent. So the low humidity is up to 49 percent and the
`
`high humidity is 50 percent and above.
`
`Q. And the humidity level changes the water content level in
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`the sample, right?
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`A. Correct. And the slide states pita reversibly transforms
`
`between the crystal form A and the crystal form E by the
`
`influence of relative humidity. That is in the report that is
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`the conclusion of the report.
`
`Q. Is that another way of saying that a pitavastatin calcium,
`
`having a lower water content, is form A and having a higher
`
`water content transforms to form E?
`
`A. That's correct. That is known to a person of skill in the
`
`art, and I have seen other information that shows that also.
`
`Q. If you go back to -- you see the header of the slide, it
`
`says changing water content results in different polymorphic
`
`forms.
`
`How does this test show that?
`
`A. So it shows that depending on how you dry or how you follow
`
`example three, you would end up with either different water
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`content and that would produce different forms. So it would
`
`show, like I was saying in the introduction, that a person of
`
`skill can obtain different polymorphic forms of pitavastatin
`
`calcium by following example three.
`
`Q. Can we turn to slide No. 18, which pertains to DTX 034,
`
`which is the '406 patent, and DTX 056, which is Nissan's
`
`third-party 2006 experiment. The DTX 056 is found at tab six
`
`and DTX 0034 is found at tab four.
`
`What is this slide showing, Dr. Byrn?
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`A. This shows the differences between the EP '406 example
`
`three, what's in EP '406, and the actual 2006 experiment that
`
`we've been discussing.
`
`Q. And who carried out this 2006 experiment, Dr. Byrn?
`
`A. This was carried out by Nissan.
`
`Q. And how does the experiment carried out by Nissan differ
`
`from example three of EP '406?
`
`A. So I highlighted the differences. The first is that it
`
`says that the reaction mixture was dissolved overnight at
`
`15 degrees centigrade, so it gave a temperature there. And
`
`then the second difference is, it says it was washed with
`
`water, 50 milliliters. And then the third difference, it says
`
`that the crystals were dried under reduced pressure for
`
`50 minutes and 40 degrees to obtain the target -- and then it
`
`gives the chemical name -- 4.18 grams, 92 percent yield,
`
`moisture content, 10.5 percent. And that is within the ranges
`
`that we have been discussing.
`
`Q. Is 50 degrees centigrade room temperature?
`
`A. No. As we discussed, it is 59 degrees Fahrenheit.
`
`Q. And the step of washing water with 50 milliliters, is that
`
`described in example three of EP '406?
`
`A. No.
`
`Q. And these drying conditions mainly in the 2006 experiment,
`
`is any of that information provided in example three of
`
`EP '406?
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`A. No. In fact, EP '406 doesn't even use the word dry.
`
`Q. So this is what one skilled in the art could possibly fill
`
`in and try this combination of drying conditions?
`
`A. Well, it is one of a large number or many possible drying
`
`conditions they could fill in, a person of skill could fill in.
`
`Q. Can this filling in of other conditions result in a drying
`
`content of range of 3 to 15 percent?
`
`A. Correct, and that range could result in different solid
`
`forms either E or A. So you could get different forms from
`
`'406.
`
`Q. So if we go to the next slide, is this a summary, Dr. Byrn,
`
`of EP '406?
`
`A. Yes.
`
`Q. And basically, what does it say?
`
`A. So the method that you obtain the material in '406, we're
`
`just told filtration. And then like I've been saying, there is
`
`no drying conditions disclosed. And then the description of
`
`what was obtained is just a white crystalline precipitate.
`
`Q. And how does that compare, if we turn to slide 20, with
`
`Nissan's 2006 experiment?
`
`A. So then a more detailed experiment, Nissan explained, do
`
`filtration and then a water wash, and then drying for
`
`50 minutes at 40 degrees C under reduced pressure. So details
`
`there. And then getting form A, crystalline -- the material
`
`that was obtained was form A.
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`1673
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`Q. I would like to move now to another patent. Let's go to
`
`slide number 25, which references a Mylan application. This is
`
`PTX 0849. This is found at tab number nine.
`
`A. OK. I've got tab nine.
`
`Q. And what does this slide say, Dr. Byrn?
`
`A. So this is a Mylan application for a novel form of
`
`pitavastatin calcium, and it is filed by the Mylan research
`
`group in Hyderabad, India.
`
`Q. If we can go to the next slide, slide number 26. We are
`
`still at PTX 849. Now we are going to page two of that or page
`
`three.
`
`What do we see in terms of the background of the
`
`invention?
`
`A. So on page two --
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`Q. Page three, Dr. Byrn.
`
`A. Pardon?
`
`Q. Page three of the application.
`
`A. OK. On page three is a description of the -- it says,
`
`U.S. 20090172008 -- sorry -- U.S. 2009-0182008, discloses
`
`crystalline forms A, B, C, D, E, and F, and the amorphous form.
`
`So this is post '993 patent.
`
`Q. And what is the 2009-0182008 application?
`
`Can we go to the next slide, please.
`
`What is this demonstrative showing, Dr. Byrn?
`
`A. It shows that that reference to U.S. 2009-0182008
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`1674
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`corresponds to the '993 patent, so they are referencing back to
`
`the '993 patent. And this slide shows the various correlations
`
`of the various numbers to reach that conclusion. This
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`slide 27.
`
`Q. If we now go to PTX 849, page 28 of that document.
`
`Is this the example from the Mylan application,
`
`Dr. Byrn?
`
`A. Correct. This is from page six now of the Mylan
`
`application.
`
`Q. And could you explain to the court what this example shows?
`
`A. Sure. So this -- now this, in that previous slide, this
`
`was called a novel crystalline form because it's different from
`
`A, B, C, D, E, and F. So Mylan is calling this a novel form.
`
`And the procedure that they used is quite similar to
`
`the '406 procedure. And they start with
`
`alpha-methylbenzylamine. And in organic chemistry, we name
`
`compounds sometimes differently, so alpha-methylbenzylamine
`
`here is alpha-methylbenzylamine in the '406.
`
`Q. So the alpha-methylbenzylamine salt in this Mylan
`
`application is the same starting material as the
`
`phenylethylamine salt in EP '406, example three?
`
`A. That's correct.
`
`Q. OK.
`
`A. And then we use 15 grams. '406 uses 12 grams, which is a
`
`very similar procedure. And then we add sodium hydroxide, just
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`1675
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`as is done in the '406. And stirred, again, just as it is done
`
`in the '406. And then to that solution, calcium chloride was
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`added, and the mixture again was stirred, filtered and washed
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`with water. And then the obtained compound was dried below
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`50 to give pitavastatin calcium form P, as in Paul. So not A
`
`or E, not any of the forms in the '993, but a brand new form.
`
`Q
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