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Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 1 of 157 PageID #:5316
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`280
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`IN THE UNITED STATES DISTRICT COURT
`NORTHERN DISTRICT OF ILLINOIS
`EASTERN DIVISION
`
`Docket Nos. 16 C 651
` 17 C 7903
`
`Chicago, Illinois
`July 17, 2018
`1:36 p.m.
`
`)))))))))
`
`HOSPIRA, INC.,
`
`Plaintiff,
`
`vs.
`
`FRESENIUS KABI USA, LLC,
`
`Defendant.
`
`VOLUME 2B
`TRANSCRIPT OF PROCEEDINGS - Bench Trial
`BEFORE THE HONORABLE REBECCA R. PALLMEYER
`
`APPEARANCES:
`
`For the Plaintiff:
`
`For the Defendant:
`
`Court Reporter:
`
`JENNER & BLOCK LLP
`BY: MR. BRADFORD P. LYERLA
`MR. YUSUF ESAT
`MR. AARON A. BARLOW
`MS. SARA T. HORTON
`353 North Clark Street
`Chicago, Illinois 60654
`
`SCHIFF HARDIN LLP
`BY: MR. IMRON T. ALY
`MR. JOEL M. WALLACE
`MS. TARA L. KURTIS
`MR. KEVIN M. NELSON
`233 South Wacker Drive, Suite 6600
`Chicago, Illinois 60606
`
`SCHIFF HARDIN LLP
`BY: MR. AHMED M.T. RIAZ
`666 Fifth Avenue, 17th Floor
`New York, New York 10103
`
`FRANCES WARD, CSR, RPR, RMR, FCRR
`Official Court Reporter
`219 S. Dearborn Street, Suite 2144D
`Chicago, Illinois 60604
`(312) 435-5561
`frances_ward@ilnd.uscourts.gov
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 2 of 157 PageID #:5317
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`Also Present:
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`Mr. Michael P. Bauer, Hospira
`Mr. Ryan Daniel, Fresenius Kabi
`Mr. Ali Ahmed, Fresenius Kabi
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 3 of 157 PageID #:5318
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`(Proceedings heard in open court:)
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`THE COURT: Okay. I'll ask the witness to resume the
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`witness stand, and we'll proceed with further direct
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`examination.
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`(Witness resumes witness stand.)
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`THE COURT: All right. You're welcomed to proceed,
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`Mr. Aly.
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`MR. ALY: Thank you, Your Honor.
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`THE WITNESS: All right.
`
`JAMES E. KIPP, DEFENDANT'S WITNESS, PREVIOUSLY SWORN
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`DIRECT EXAMINATION (Resumed)
`
`BY MR. ALY:
`
`Q. All right. Dr. Kipp, before the break, we talked about
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`some references CSHP and Fanikos about ready to use; is that
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`right?
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`A. Correct.
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`Q. Now, in the prior art for dexmedetomidine, in particular,
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`were hospitals already trying to make their own premixes?
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`A. Yes, in fact, they were.
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`Q. How do you know that?
`
`A. Well, there's a reference by Cain, which I talk about in my
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`opening report.
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`Q. Let's look at JTX16. Who is the author of the article?
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`A. The author is James Gordon Cain, M.D.
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`Q. And what publication is it in?
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`A. This is in "International Trauma Care."
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`Q. What is the date of the publication?
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`A. Okay. The date of the publication is 2007.
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`Q. Now, if we can go back to the title in the first page,
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`Dr. Cain is obviously an M.D.
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`Why does that matter to a POSA?
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`A. Well, again, as I say, a POSA would want to understand how
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`the products -- how the company's products are being used, what
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`the end -- who the end customer is to decide -- to decide what
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`desirable features one should have in their products.
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`Q. What is the Cain article about?
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`A. Well, the Cain article is about -- well, as the title says,
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`the use of dexmedetomidine and Hextend, which is a form of
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`hetastarch, which is a plasma expanding solution, hydroxyethyl
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`starch. And so he's talking about the use in trauma care.
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`Q. What does the Cain reference teach about using a
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`ready-to-use formulation?
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`A. Okay.
`
`Q. I'm sorry. Let me ask a different question.
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`What does the Cain reference teach about using a
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`premixed solution?
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`A. It teaches a premixed solution in that Dr. Cain has used
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`prefilled syringes at a concentration of 4 micrograms per mil
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`that are already mixed and available in prefilled syringes for
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`use in the operating room.
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`284
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`Q. Let's look at page 2 on the right-hand column, bottom of
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`the first paragraph, "At This Author's Institution."
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`What is Dr. Cain explaining in the article happens at
`
`his hospital?
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`A. Okay. So as you can see on this excerpt, he has the
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`hospital pharmacy provide -- providing prefilled syringes or
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`premixed syringes of dexmedetomidine, 10 milliliter syringes
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`with 4 micrograms per milliliter for use as both a component in
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`the balanced anesthetic and in preventing post-anesthesia
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`agitation and delirium.
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`Q. What would a POSA take away from the Cain disclosure?
`
`A. Well, I mean, this just strengthens the point I made
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`earlier that it's desirable to have a ready-to-use premix form
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`of dexmedetomidine available for use.
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`Q. Now, as of the prior art 2012, were there other commercial
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`products that were ready to use, already diluted?
`
`A. Well, yes, there were.
`
`Q. Which one?
`
`A. Well, one would be Dexdomitor.
`
`Q. Let's look at DTX288. What is Dexdomitor?
`
`A. Okay. Dexdomitor is a veterinary product. But, again, the
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`patents-in-suit only disclose a subject, not necessarily a
`
`human. So this would be applicable as a ready-to-use product
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`that does not require further dilution.
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`Q. What year was Dexdomitor published and available?
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`A. Okay. It was published in 2002.
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`Q. And it says EMEA?
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`A. It's the European -- it's the equivalent of FDA, but in
`
`Europe -- European's medicine evaluation.
`
`Q. And when you were referring about the claims in the patent,
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`how do you know that it includes animals?
`
`A. Well, if we -- we can look at that and see what's in the
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`actual claims.
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`Q. Let's look -- have you prepared a slide with the claim
`
`constructions?
`
`A. Yes.
`
`Q. Let's look at that. DDX209. I'm sorry.
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`DDX2 -- hold on.
`
`(Counsel conferring.)
`
`MR. ALY: I apologize, Dr. Kipp, and Your Honor.
`
`BY MR. ALY:
`
`Q. DDX211, what is the agreed definition for the word
`
`"subject"?
`
`A. Okay. At the bottom you can see where it's spelled out
`
`that subject means a human, a nonhuman mammal, or a nonhuman
`
`animal. Basically any animal.
`
`Q. Let's look back at the Dexdomitor document, DTX288, and the
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`product specification and the introduction.
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`What does it teach about the product Dexdomitor?
`
`A. Well, it teaches the dosages. It teaches a shelf life. It
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`teaches that the active substance is the hydrochloride salt.
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`It shows the dosage form or the strength as being .5
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`milligrams or 500 micrograms per milliliter as the salt.
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`And it also says at the bottom that it's indicated
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`for sedation and analgesia for dogs and cats.
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`Q. What is the concentration for Dexdomitor?
`
`A. Okay. The concentration, again, as to salt is .5
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`milligrams per milliliter, which is the same as 500 micrograms
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`per milliliter.
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`Q. And are concentrations in the microgram level, is that
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`considered low concentration?
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`A. Yes, it is. In fact, that is expressed as the as -- as the
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`hydrochloride salt. And, in fact, all of the other dosage
`
`forms in the U.S. are referenced in terms of the free-base.
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`So it's actually a lower number on -- if it's on the
`
`same scale, it would be 420, I believe, micrograms per
`
`milliliter.
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`Q. And does the Dexdomitor information tell you what the shelf
`
`life is for the product?
`
`A. Yes, it does. And it says that it has a shelf life of two
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`years.
`
`Q. Now, does the Dexdomitor product information tell you what
`
`kind of container is used for the product?
`
`A. Yes, it does.
`
`Q. Let's look at page 2 of DTX288, the section titled
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`"Container."
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`What's the container that the Dexdomitor product came
`
`in?
`
`A. Okay. It says that Dexdomitor is supplied in 10 milliliter
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`Type 1 glass vials closed with a fluoropolymer coated
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`chlorobutyl rubber stopper.
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`And a POSA would recognize that fluoropolymer coating
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`would be the same as Teflon, in essence.
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`Q. And what does a POSA take away from the use of Type 1 glass
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`and a coated rubber stopper in Dexdomitor?
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`A. One would take away that it's feasible with a reasonable
`
`expectation -- expectation of success to formulate a drug
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`product ready to use in a Type 1 glass container vial, sealed
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`with Teflon-coated rubber stoppers, and be able to use that as
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`a premix -- as a ready-to-use product.
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`Q. Does the Dexdomitor label explain what type of interaction
`
`occurs between the drug and the coated stopper?
`
`A. Yes, it does.
`
`Q. Let's look at page 5. Let's highlight that portion. Yep.
`
`A. Okay.
`
`Q. So is there a section on stability tests? What are those?
`
`A. Okay. These are stability tests that were used in the
`
`regulatory -- in the filing, and they list the stability
`
`studies here.
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`Q. And the first row of the stability studies, is that room
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`temperature conditions?
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`A. Yeah, that is a room temperature condition, 25 degrees
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`Celsius, 60 percent relative humidity.
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`And typically for these studies, they store bottles
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`upright -- vials upright and also inverted as a worst case.
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`Q. And let's go to the text underneath Table 3.
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`The second sentence, does the Dexdomitor product
`
`label explain the effect the stoppers have on the formulation?
`
`A. Well, it states clearly that all parameters remained
`
`essentially unchanged at all storage conditions. And, indeed,
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`no difference between inverted and upright containers could be
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`noted.
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`Q. What does that teach to a POSA?
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`A. Well, it teaches that one could effectively use a
`
`Teflon-coated rubber stopper with a Type 1 glass container and
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`see no loss of drug, inverted or upright.
`
`Q. Do you know what kind of stopper the Precedex concentrate
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`used?
`
`A. Yes, the Precedex concentrate likewise used a Type 1 --
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`used a Type 1 glass container with Teflon-coated stoppers.
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`Q. All right. Now, let's talk about the general issue of
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`glass and plastic as materials.
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`In 2012, were there any dexmed products sold in
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`plastic?
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`A. In 2012, there were no dexmed products sold in plastic.
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`Q. But weren't there advantages if somebody wanted to or
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`wished to use plastic?
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`A. Well, yeah, I mean, it's -- there would be advantages to
`
`selling a bag to -- to developing a product in flexible plastic
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`bags. But in point of fact, there was -- there was a block --
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`the blocking patent that any third party would have had to deal
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`with, and they would have had to license the material from
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`Farmos.
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`Q. What about as far as the plastic? You yourself made
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`plastic products for the market?
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`A. Right. It's -- there are numerous hurdles that have to be
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`overcome, and it's not a simple matter of putting a drug in a
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`plastic bag. It takes, in fact, years of work to develop a
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`laminated container that has the clarity, the flexibility, and
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`you have to develop around that a process for binding all those
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`layers together, reliably sealing the bags consistently without
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`any leaks.
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`So -- and then you have to worry about what goes into
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`the bag and what comes back out of the bag. So it would take
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`many years of development just to get to a container -- a
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`product container.
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`Q. When you were developing the plastic containers that you
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`worked on, were you always using glass also?
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`A. Yes, I was. In the cases where we -- where we -- for
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`liquid parenteral products in flexible plastic bags, we would
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`also put up samples in Type 1 glass containers as controls, and
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`we did use Teflon-coated stoppers, knowing that that would
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`provide the most inert surface.
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`Q. Is it common to use Type 1 glass as a control?
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`A. Yes, it's very common. You want to make sure that you
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`don't get any -- any of -- the least possible interaction or no
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`interaction with the container.
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`And you would be assured of that if you went to a
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`Type 1 glass container, especially with a coated rubber
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`stopper.
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`Q. Yesterday we heard about absorption and adsorption.
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`Are those problems that you expect for glass?
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`A. No, I don't, actually. Remember that a glass is a fairly
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`hard matrix. It's very dense.
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`On the other hand, plastic being flexible, a flexible
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`plastic bag is going to be less dense, be more porous. And
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`anything that's in the solution can easily migrate into the
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`plastic; and likewise, things can migrate out of the plastic,
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`so --
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`Q. Okay. What about for dexmed in particular? Is there a
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`reason that glass would be a problem compared to plastic?
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`A. Well, for one thing, dexmed, as we were taught earlier, is
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`a lipophilic compound. It has what's called a high logP, and
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`one would expect that it would have a high affinity for organic
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`materials, oily materials, such as a plastic bag.
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`Q. You mentioned the phrase "high logP."
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`What is a high logP? What's a logP? Let's start
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`there.
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`A. Okay. Well, logP is a gauge of lipophilicity of an organic
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`molecule, the small molecule.
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`Basically the higher the logP, the higher the
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`lipophilicity, the higher the affinity for an oil, an organic
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`phase and, thus, a plastic material.
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`Q. And is a low or a high logP better for a plastic material
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`interaction?
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`A. Well, the higher the logP, the more -- the greater the
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`tendency you have for an interaction with plastic.
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`Q. Well, was the logP for dexmedetomidine itself known in the
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`prior art?
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`A. Yes, it was.
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`Q. Where was it published?
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`A. It was published in an earlier patent. And, in fact, it
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`was also published in the Precedex concentrate label.
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`Q. Let's look at the label. JTX15.2 and the description.
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`Where did the 1999 Precedex concentrate label tell
`
`you the logP?
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`A. Well, right below the chemical structure where it starts
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`out, "Dexmedetomidine hydrochloride," describes its physical
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`properties, and among those physical properties on the second
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`line, it says, "Its partition coefficient in octanol water at
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`pH 7.4 is 2.89."
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`Q. And is a logP the same as a partition coefficient?
`
`A. Yes, it's -- yes.
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`Q. What is the reported partition coefficient or logP for
`
`dexmedetomidine?
`
`A. Well, it's -- it's 2.89. It's close to 3.
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`Q. Is that considered low or high?
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`A. That would be considered high.
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`Q. How do you know that?
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`A. Well, there are other drugs that are lipophilic that have
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`to be packaged in glass, such as propofol, for example, which
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`has a logP of 4.
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`Q. And how does the logP tells you the distinction between
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`glass and plastic interaction?
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`A. Well, it teaches that a compound with a logP like 2.89,
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`which is basically 600 times more soluble in an oil phase than
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`in an aqueous phase, tells you that you should be staying --
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`you know, you should be carefully looking at plastic
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`interactions with the drug.
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`It means it has 600 times the solubility in an
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`organic phase potentially than in water.
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`Q. And would that direct somebody to expect problems if they
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`tried to put dexmedetomidine in plastic?
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`A. Yes, definitely.
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`Q. Now, you mentioned propofol as another anesthetic.
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 14 of 157 PageID #:5329
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`293
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`Is there a reason that you know that propofol and
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`dexmed have a high logP?
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`A. Well, generally drugs like propofol, dexmedetomidine, these
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`are the agents that act on the central nervous system.
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`And to get across into the central nervous system,
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`they have to get into the -- across what's known as the
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`blood-brain barrier, and that requires a certain amount of
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`lipophilicity just to achieve that, and so it's consistent with
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`other drugs in that class.
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`Q. What type of container, for example, is propofol found in?
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`A. Yeah, propofol is found in a glass container.
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`Q. Now, what about when there's -- these are drugs for
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`parenteral or IV use, right?
`
`A. Yes.
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`Q. Are there sterility issues and processes that lend
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`themselves to glass versus plastic?
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`A. Well, glass is a lot easier to terminally sterilize. When
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`you heat up a plastic, you have to worry about it, frankly,
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`softening. You cross what's known as a glass transition
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`temperature, and it gets soft. And at that point things can
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`more readily come out of the plastic as well as a drug can
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`go -- migrate into the plastic. It becomes looser.
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`So terminal sterilization by autoclave can be a
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`problem with plastic. So you can see more extractables coming
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`out.
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 15 of 157 PageID #:5330
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`294
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`And with glass, which is a hard, rigid matrix, it's
`
`much easier to do a -- to apply a high heat. And what's more,
`
`you can also what's called depyrogenate glass and take up to
`
`high temperatures to get rid of pyrogens.
`
`Q. Can you explain what is a pyrogen?
`
`A. Yes. Pyrogen is the gram -- is our gram-negative bacteria,
`
`the actual casts from the cell of these dead cells that
`
`actually will elicit a strong immunological response. And you
`
`have to chemically degrade them. You can't just kill -- you
`
`can't just biologically kill bacteria. You have to chemically
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`degrade these particular pyrogens, so you have to heat the
`
`containers up to very high temperatures. That's more readily
`
`achievable with a glass container.
`
`Q. Now, this idea about using glass, was that the exception or
`
`the rule in 2012?
`
`A. Well, the idea of using glass is really the rule.
`
`I mean, because it's used as a control, so you know
`
`that if you've got a problematic drug that can migrate into
`
`plastic, glass would be a go-to type of container. And it's
`
`really a gold standard when it comes to noninteraction of drug
`
`with a container.
`
`Q. Were there treatises available to a POSA that discussed
`
`containers for use in formulations?
`
`A. Yes, there were.
`
`Q. What's a go-to example that you use?
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 16 of 157 PageID #:5331
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`295
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`A. Well, one would be Remington's. That's sort of like the
`
`bible of formulation science.
`
`Q. Let's show JTX20. And what is Remington's?
`
`A. Yeah, Remington's is a general treatise. Well, basically
`
`it's a formulator's bible that contains many chapters on a wide
`
`diversity of topics relating to parenteral or any kind of drug
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`formulation.
`
`Q. And if we look at the second page, when was this version --
`
`this is the 21st version edition -- when was that published?
`
`A. Okay. The latest version here is 2006, but as you can see,
`
`it's been republished many, many times.
`
`Q. How long back has Remington's been available?
`
`A. Since 1889 -- 1885. Sorry.
`
`Q. Do you know any formulators that do not use Remington's
`
`treatise practice?
`
`A. No, I do not, no. It's a very common reference to use.
`
`Q. Do you still refer to it?
`
`A. Yes, I do.
`
`Q. What does Remington's tell us about glass? Let's look at
`
`page 13, and let me repeat the question.
`
`What does Remington's tell us about glass as a
`
`container?
`
`A. Well, as you can see in this excerpt, it says that glass --
`
`that traditionally glass has been the most widely used
`
`container for pharmaceutical products, again, to ensure
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 17 of 157 PageID #:5332
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`296
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`inertness, visibility, strength, rigidity, moisture protection,
`
`ease of reclosure, and economy of packaging.
`
`Q. And was that true, in your experience, as of 2012?
`
`A. Yes, definitely. And as I said, we use glass -- Type 1
`
`glass as control studies to look and examine plastic
`
`absorption.
`
`Q. Well, doesn't Remington's also tell us about plastic,
`
`Dr. Kipp?
`
`A. Yes, it does.
`
`Q. Let's look at that on the right column, first paragraph,
`
`"Plastics."
`
`And what does Remington's tell us about plastics?
`
`A. Okay. It says that, yeah, plastic containers are very
`
`popular for storing pharmaceutical products, and -- but it also
`
`discloses a lot of the -- the disadvantages to -- to using
`
`plastic bags --
`
`Q. Let's look --
`
`A. -- that are associated with the flexibility that you get
`
`from plastics.
`
`Q. Let's look at those.
`
`The fifth paragraph in the Plastics section, what
`
`does Remington's describe as some of the problems of using
`
`plastic containers?
`
`A. Well, this -- this stems from the flexibility of this type
`
`of container and the fact that to get that type of flexibility,
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 18 of 157 PageID #:5333
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`297
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`it has to be more porous than glass, a lot less dense; and
`
`therefore, things from solution can migrate into plastic as
`
`well as additives from the plastic can migrate out. And that's
`
`a significant problem.
`
`Q. Is this the only reference that you considered to tell us
`
`about glass compared to plastic?
`
`A. No, not at all. In fact, there's another reference by
`
`Gregory Sacha and coworkers that I referenced in my reports.
`
`Q. Let's look at JTX24.2. And who are the authors for this
`
`exhibit?
`
`A. Okay. Yeah, these are people I knew at Baxter; Gregory
`
`Sacha, Wendy Clemmer, Karen Abram, and Mike Akers. This is an
`
`article on the fundamentals of glass, rubber, and plastic
`
`sterile packaging systems.
`
`Q. And what's the date of the publication?
`
`A. Okay. The date of the publication is 2010.
`
`Q. And in what publication does it appear?
`
`A. "Pharmaceutical Development and Technology."
`
`Q. Let's look at some of the discussions.
`
`First page 3, the top right, there's a discussion on
`
`ampoules?
`
`A. Yes.
`
`Q. 2010, what is the Sacha reference teaching about glass
`
`ampoules?
`
`A. Well, Sacha acknowledges that for decades glass sealed
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 19 of 157 PageID #:5334
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`298
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`ampoules were the most popular primary packaging system for
`
`small volume injectable products.
`
`Q. And does it give a reason why?
`
`A. Yeah, they're favorable because they -- because of the lack
`
`of interaction with -- with the drug, as I said before.
`
`And you don't have to -- with ampoules, you don't
`
`have to obviously seal it with a rubber stopper.
`
`Q. What does Sacha teach about the possibility or plausibility
`
`of using glass ampoules even as of 2010?
`
`A. Well, it says that it's -- if you want to keep a drug from
`
`migrating into the container, ampoules would be a definite
`
`advantageous type of container to use.
`
`Q. Does an ampoule use a stopper?
`
`A. No, it does not.
`
`Q. Let's look at the bottom of the same column. There's the
`
`section on vials. What does Sacha report about vials?
`
`A. Okay. Sacha says, again, that vials are the most common
`
`packaging for liquid and freeze-dried injectables, and the
`
`glass is -- is used.
`
`Q. Do you agree that's correct as of 2010?
`
`A. Yes.
`
`Q. Does Sacha also describe sections on plastics?
`
`A. Yes.
`
`Q. For example, here there's a mention of plastic vials.
`
`Are those the kind of flexible containers that would
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 20 of 157 PageID #:5335
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`299
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`be considered for dexmed?
`
`A. Well, this is not -- COC. Well, they're not talking about
`
`flexible plastic containers.
`
`What they're talking about here are cyclic olefin
`
`copolymer containers which are rigid, and they come with their
`
`own issues that glass doesn't have. For example, sterile --
`
`terminal sterilization is difficult, and glass is much easier
`
`to terminally sterilize.
`
`Q. What is terminal sterilization?
`
`A. Terminal sterilization is where you apply heat, for
`
`example, by autoclaving to -- at the end of a packaging process
`
`where you sealed the drug solution in a vial or a glass
`
`container. You subject it to high heat to kill off all --
`
`essentially all microorganisms.
`
`Q. Let's look at page 19 for the discussion on plastics.
`
`Does the Sacha reference describe some of the
`
`problems with plastic?
`
`A. Yes, it does. And it iterates what we've said, is that you
`
`can get permeation not just with molecules that are dissolved
`
`in the solution, organics like drugs, but also gases can
`
`permeate. Like oxygen can permeate from the atmosphere through
`
`the bag into the solution.
`
`And leaching, leaching can also occur --
`
`Q. What is leaching?
`
`A. That's when additives to the plastic -- stabilizers that
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 21 of 157 PageID #:5336
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`
`300
`
`are added to the plastic process -- additives that are added to
`
`the plastic actually migrate out of the plastic and into the
`
`solution.
`
`Q. And does Sacha mention another issue with plastic?
`
`A. Also sorption at the end there, which is -- sorption of
`
`the -- we've hit on this earlier -- is that drug molecules can
`
`actually get absorbed by the plastic container.
`
`Q. And these issues of permeation, leaching, and sorption, do
`
`they apply to glass as compared to plastic?
`
`A. Well, glass is obviously the most inert rigid container
`
`that's possible, Type 1 glass especially with Teflon-coated
`
`stoppers, and you would expect to not see very much of a
`
`problem with this.
`
`Q. What would a person of ordinary skill in the art take away
`
`from Sacha about the use of glass versus plastic?
`
`A. Sacha would teach a person of ordinary skill in the art
`
`that if you have a drug that has a high logP, therefore has a
`
`high affinity to flexible plastic bags, one would automatically
`
`go to a glass container if they wanted to package it in an
`
`inert container and not see absorption -- absorption loss.
`
`Q. What about the fact that dexmed -- let me ask you this.
`
`Is dexmed considered a small molecule?
`
`A. Yes, it is.
`
`Q. What does that mean?
`
`A. Well, it has molecular weight of around 200 grams per mole,
`
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 22 of 157 PageID #:5337
`Kipp - direct by Aly
`
`301
`
`which is rather small for a molecule, yes.
`
`Q. How does that compare to something like heparin?
`
`A. Heparin is a very large glycosaminoglycan, which is a huge
`
`long polysaccharide with functional groups on it, which can be
`
`thousands in molecular weight.
`
`Q. And is there something known about use of small molecules
`
`in glass, to your knowledge?
`
`A. Well, in my experience, I've never seen small molecules on
`
`this order of molecular weight actually get absorbed to glass.
`
`That would be -- that would -- I've never seen that happen at
`
`all. Because what happens is that even though you have a
`
`reversible equilibrium -- acid-based equilibrium, pronation is
`
`extremely rapid and on the order of nanoseconds.
`
`So if you have one species which can absorb, you lose
`
`a proton; it comes back off again. So you would never see any
`
`kind of absorption occurring with this type of molecule. But
`
`you will definitely -- with a lipophilic species like
`
`dexmedetomidine, it will readily migrate into plastics.
`
`Q. What about the volume of liquid here? If you were using
`
`the Precedex concentrate, that would be 50 milliliters of
`
`liquid after diluted. What does that tell you about glass
`
`versus plastic, if anything?
`
`A. Well, it tells you right there that that would -- I mean,
`
`just the fact that the Precedex -- the Precedex concentrate is
`
`diluted to 5 -- to 50 milliliters, a POSA would have every
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 23 of 157 PageID #:5338
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`
`302
`
`reason to believe -- every reasonable expectation of success
`
`that if you diluted and packaged it in a Type 1 glass container
`
`with Teflon-coated stoppers, that you would have a stable
`
`product that wouldn't adhere or absorb into the glass material.
`
`Q. Is 50 milliliters considered a small volume?
`
`A. Excuse me? Did you say 50?
`
`Q. 50, that's right.
`
`A. Yes, 50 is considered a small volume, yes.
`
`Q. How do you know that?
`
`A. Well, the USP considers small volume injectables as being
`
`any volume up to and including 100 milliliters.
`
`Q. What's the most common type of container for small volume
`
`products?
`
`A. Well, the -- as we were talking about, vials -- glass vials
`
`are the most common, yes.
`
`Q. Now, if I may switch gears, Dr. Kipp, we've talked about
`
`how the prior art had the concentrate; the prior art had people
`
`making premixes; the prior art taught glass and plastic.
`
`Why didn't anyone put this combination together
`
`before Hospira, do you know?
`
`A. Well, it would have been difficult, again, as I was saying,
`
`that for a third party to enter the picture because of the
`
`blocking patent, which is the '214 patent.
`
`Q. What's a blocking patent?
`
`A. Okay. A blocking patent is a patent that claims the use of
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 24 of 157 PageID #:5339
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`303
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`a particular entity that one would have to acquire in -- in
`
`process of developing a new product and would, therefore, have
`
`to license it from the originator of the patent.
`
`Q. Now --
`
`MS. HORTON: Your Honor, I'd object to this line of
`
`questioning as beyond the scope.
`
`And we also are not running a secondary consideration
`
`in this case, as Mr. Aly has mentioned multiple times, which
`
`this seems to be related to.
`
`MR. ALY: As to beyond the scope, it's in the report
`
`at paragraphs 152 to 155.
`
`As to what I understand to be a relevance objection,
`
`it's to defray why no one else would have done it sooner.
`
`If Hospira's not going to make that argument, we will
`
`withdraw it and move on.
`
`THE COURT: You're withdrawing any suggestion that
`
`there was -- that there was no motivation for somebody to make
`
`it earlier, somebody else; is that right?
`
`MS. HORTON: No.
`
`THE COURT: Overruled.
`
`MS. HORTON: I don't understand --
`
`THE COURT: In that case, overruled.
`
`BY MR. ALY:
`
`Q. While at Baxter, had you seen a patent on a compound, did
`
`your team proceed with a premix for that compound?
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`Case: 1:16-cv-00651 Document #: 138 Filed: 08/07/18 Page 25 of 157 PageID #:5340
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`304
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`A. No, we wouldn't even -- we wouldn't bother to do that.
`
`Q. And why is that?
`
`A. Well, I mean, to contest the patent would not be worth our
`

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