1
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 1 of 373 PageID #: 9463
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`RESEARCH FOUNDATION OF STATE
`UNIVERSITY OF NEW YORK, et al., :
`:
`Plaintiffs,
`
`CIVIL ACTION
`
`::
`
`::
`
`::
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`:
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`v.
`MYLAN PHARMACEUTICALS, INC.,
`Defendant.
`---------------------------------
`MYLAN PHARMACEUTICALS, INC.,
`Plaintiff,
`v.
`:
`GALDERMA LABORATORIES,INC.,
`GALDERMA LABORATORIES, L.P., and :
`SUPERNUS PHARMACEUTICALS, INC.,
`:
`:
`Defendants.
`- - -
`Wilmington, Delaware
`Tuesday, July 5, 2011
`BENCH TRIAL - VOLUME A
`
`NO. 09-184-LPS
`
`CIVIL ACTION
`
`:
`
`::
`
`::
`
`NO. 10-892-LPS
`
`BEFORE:
`APPEARANCES:
`
`- - -
`HONORABLE LEONARD P. STARK, U.S.D.C.J.
`- - -
`MORRIS NICHOLS ARSHT & TUNNELL, LLP
`BY: JACK B. BLUMENFELD, ESQ.
`and
`
`Brian P. Gaffigan
`Kevin Maurer
`Official Court Reporters
`
`
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 1 of 373 PageID #: 9463
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`RESEARCH FOUNDATION OF STATE
`UNIVERSITY OF NEW YORK, et al., :
`:
`Plaintiffs,
`
`CIVIL ACTION
`
`::
`
`::
`
`::
`
`:
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`
`v.
`MYLAN PHARMACEUTICALS, INC.,
`Defendant.
`---------------------------------
`MYLAN PHARMACEUTICALS, INC.,
`Plaintiff,
`v.
`:
`GALDERMA LABORATORIES,INC.,
`GALDERMA LABORATORIES, L.P., and :
`SUPERNUS PHARMACEUTICALS, INC.,
`:
`:
`Defendants.
`- - -
`Wilmington, Delaware
`Tuesday, July 5, 2011
`BENCH TRIAL - VOLUME A
`
`NO. 09-184-LPS
`
`CIVIL ACTION
`
`:
`
`::
`
`::
`
`NO. 10-892-LPS
`
`BEFORE:
`APPEARANCES:
`
`- - -
`HONORABLE LEONARD P. STARK, U.S.D.C.J.
`- - -
`MORRIS NICHOLS ARSHT & TUNNELL, LLP
`BY: JACK B. BLUMENFELD, ESQ.
`and
`
`Brian P. Gaffigan
`Kevin Maurer
`Official Court Reporters
`
`
`
`2
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 2 of 373 PageID #: 9464
`
`APPEARANCES (Continued):
`
`PAUL HASTING JANOFSKY & WALKER, LLP
`BY: GERALD J. FLATTMANN, ESQ.,
`CHRISTINE WILLGOOS, ESQ.,
`JOSEPH M. O'MALLEY, JR., ESQ., and
`MELANIE R. RUPERT, ESQ.
`(New York, New York)
`Counsel for Research Foundation of
`State University of New York, Galderma
`Laboratories, Inc., New York University,
`Galderma Laboratories, L.P., and
`Supernus Pharmaceuticals, Inc.
`
`POTTER, ANDERSON & CORROON, LLP
`BY: RICHARD L. HORWITZ, ESQ.
`and
`WILSON SONSINI GOODRICH & ROSATI, PC
`BY: DAVID S. STEUER, ESQ.,
`MATTHEW R. REED, ESQ., and
`KIRIN K. GILL, ESQ.
`(Palo Alto, California)
`and
`WILSON SONSINI GOODRICH & ROSATI, PC
`BY: TUNG-ON KONG, ESQ.
`(San Francisco, California)
`and
`WILSON SONSINI GOODRICH & ROSATI, PC
`BY: LORI P. WESTIN, ESQ.,
`(San Diego, California)
`Counsel on behalf of
`Mylan Pharmaceuticals, Inc.
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`3
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 3 of 373 PageID #: 9465
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`- oOo -
`P R O C E E D I N G S
`(REPORTER'S NOTE: The following trial
`proceedings was held in open court, beginning at 8:35 a.m.)
`THE COURT: Good morning, everyone.
`(The attorneys respond, "good morning, your
`
`Honor.")
`
`THE COURT: Let's begin today with noting your
`appearances on the record.
`MR. BLUMENFELD: Good morning, your Honor.
`THE COURT: Good morning.
`MR. BLUMENFELD: Jack Blumenfeld for the
`Galderma parties, along with Gerald Flattmann, Christine
`Willgoos, Joe O'Malley, Melanie Rupert, all of Paul
`Hastings.
`
`We have a lot of other people in the back. One
`is in-house counsel at Galderma, Quinton Cassidy.
`THE COURT: Welcome to all of you.
`(The attorneys respond, "good morning, your
`
`Honor.")
`
`MR. HORWITZ: Good morning, your Honor.
`THE COURT: Good morning.
`MR. HORWITZ: Rich Horwitz from Potter Anderson
`on behalf of Mylan.
`I think you know everyone at counsel table but,
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 4 of 373 PageID #: 9466
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`David Steuer, Tung-On Kong, Matthew Reed, all from Wilson
`Sonsini.
`
`Also in front of the bar, Lori Westin from
`Wilson Sonsini, and Joseph Divinagracia from Mylan.
`THE COURT: Thank you. Good morning to all of
`
`you as well.
`
`So we are here for trial. Before I bring up one
`issue, I did want to see if there are any issues either of
`the parties wish to raise before we get started this
`morning. Is there anything from the plaintiffs?
`MR. FLATTMANN: No, your Honor.
`THE COURT: And anything from the defendant?
`MR. STEUER: No, your Honor. We do have a few
`document issues but I don't think we need to take them up
`yet.
`
`THE COURT: Okay. They're not for today?
`MR. STEUER: They are for today.
`THE COURT: If they are for today, then we
`should take them up now.
`MR. STEUER: Okay. Mr. Reed will take care of
`
`that.
`
`THE COURT: Okay. Give me your name again.
`MR. REED: Matthew Reed.
`THE COURT: Reed.
`MR. REED: Yes. There are two categories of
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`5
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 5 of 373 PageID #: 9467
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`documents that the plaintiffs have identified as exhibits
`they intend to use today. On the first, we really just seek
`clarification from the Court. The first category consists
`of the Court's claim construction orders and stipulation
`between the parties regarding claim construction. We had
`indicated that we didn't believe that those documents should
`be admitted into evidence. I'm not sure of the plaintiffs'
`position on that. We have no problem with the use of those
`documents obviously at the trial but do not believe that
`they should be admitted into evidence.
`THE COURT: Go on to the second one.
`MR. REED: The second category of documents
`include documents that have been identified as ones they
`intend to use with several of their expert witnesses today.
`Those documents consist of documents that again we have no
`issue with their admission into evidence, but we do take
`issue with their experts testifying regarding those
`documents because they had never previously been identified
`as documents that the experts had considered relied upon or
`intended to offer opinions on.
`THE COURT: So is that an objection that any
`testimony by those experts about those documents would be
`beyond the scope of the experts disclosed?
`MR. REED: Exactly.
`THE COURT: Let me see what Mr. Flattmann or
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`6
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 6 of 373 PageID #: 9468
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`whomever from the plaintiffs have to say about these two
`categories.
`
`MR. FLATTMANN: Ms. Willgoos will address the
`
`objections.
`
`THE COURT: I didn't mean to cut you off,
`Ms. Willgoos. I just saw Mr. Flattmann rising. Go ahead.
`MS. FLATTMANN: No problem, your Honor. As for
`the first category of documents, those are on the record
`already. We have no intent to put those into evidence.
`As for the second category of documents, I
`believe there are only two at issue that we intend to use
`that had been objected to. One of those may have been
`resolved. I'm not entirely clear on Mylan's position on
`that. But DTX-2267 is in Dr. Rudnic's report, was cited at
`paragraph 52 and PTX-221 was also cited in Dr. Rudnic's
`report and we do intend to put that into evidence as well.
`That is PTX, yes, 221. Thank you.
`THE COURT: Thank you. On the first one, it
`seems there is no dispute. No one is going to offer them
`into evidence so there is nothing to decide there.
`On the expert documents, I'll just reiterate the
`standard approach of this court to all objections of expert
`testimony beyond the scope of what has been disclosed
`previously by the expert, which is if you believe, if they
`go ahead and offer that evidence, it will be admitted today.
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`7
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 7 of 373 PageID #: 9469
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`And if you believe following trial that they have gone
`beyond the scope of what previously had been disclosed, you
`can renew that objection post-trial, and if you prevail on
`that objection and a new trial is necessitated, they will
`bear all the costs for the new trial.
`Anything else from defendants?
`MR. REED: I think that resolves it.
`THE COURT: Okay. Fine. The only issue that I
`had was you all provided me with objections for just one
`deposition witness who, in this case, the plaintiffs intend
`to offer today. And this is the deposition testimony of
`Mr. Talton and Mylan has several objections which is listed
`in the letter of July 3rd. We've reviewed the objections
`and the proposed testimony and all of those objections are
`overruled. In the Court's view the testimony of Mylan's
`Vice President of Regulatory Affairs, Mr. Talton who signed
`Mylan's proposed ANDA's testimony about the label and his
`knowledge and Mylan's knowledge of its contents and veracity
`of the label, in the Court's view, that is relevant and not
`hearsay.
`
`The Court will give it the weight it deserves
`after hearing the testimony from Mr. Talton and all other
`evidence that is in the record, including from the person
`who Mylan evidently designated as their 30(b)(6) witness on
`these topics, so those objections are overruled.
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`8
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 8 of 373 PageID #: 9470
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`With that, I think we can begin with the trial.
`I'll call first on the plaintiff if you wish to
`have an opening statement.
`MR. FLATTMANN: Yes, your Honor, we do. With
`the Court's permission, I'll hand up a binder of the slides
`we used during the opening.
`THE COURT: And you provided those to defense I
`
`assume?
`
`MR. FLATTMANN: I am right now, your Honor.
`THE COURT: Okay.
`MR. FLATTMANN: Two copies, your Honor.
`THE COURT: Thank you.
`(Slides passed forward.)
`MR. FLATTMANN: Your Honor, this case is about
`the first orally available treatment for rosacea, Galderma's
`Oracea product. Oracea was approved by the FDA in July of
`2006. As your Honor heard at the preliminary injunction
`hearing, rosacea is a disease that affects millions of
`Americans. As you can see from this picture, patients from
`rosacea often endure red pimple-like lesions on their faces.
`These are known as the as the papules and pustules of
`rosacea.
`
`In 2000, Dr. Robert Ashley, the inventor of the
`Ashley patents discovered the surprising fact that
`sub-antimicrobial amounts of tetracycline compounds can be
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`9
`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 9 of 373 PageID #: 9471
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`used to effectively treat rosacea, and that revolutionized
`the treatment of this disease.
`Your Honor, Oracea is covered by three sets of
`patents which are each directed to a different aspect of the
`invention and the product here.
`First, the two Ashley patents. Whoops.
`First, the two Ashley patents which you heard
`about in the preliminary injunction hearing. They cover
`Oracea's novel method of treating the papules and pustules
`of rosacea and reducing side effects by administering
`doxycycline at sub-antimicrobial doses. And you will hear
`about these patents from plaintiffs' expert dermatologist,
`Dr. Guy Webster.
`Second, the Chang '532 patent covers Oracea's
`unique once daily formulation of doxycycline without
`antibiotic effects.
`And Oracea, as you know, is comprised of
`30 milligrams of immediate release, or IR, doxycycline and
`10 milligrams of delayed release, or DR, doxycycline.
`And you are going to hear about this patent from
`plaintiffs' formulation expert Dr. Edward Rudnic.
`And finally the two Amin patents which you heard
`about from the first claim construction hearing. They
`covered Oracea's novel use of doxycycline to reduce the
`inflammatory lesions of Oracea by inhibiting the production
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 10 of 373 PageID #: 9472
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`of nitric oxide. And you will hear about those patents from
`plaintiffs experts', Dr. Matthew Grisham and Dr. Jim Oates.
`Let me just introduce some of these witnesses to
`you since most of them are in the courtroom today.
`First -- and I will ask them to stand when I
`
`name them.
`
`First, Dr. Guy Webster. Dr. Guy Webster is a
`renowned clinical dermatologist and he will testify about
`the Ashley patents.
`Next up is Dr. Edward Rudnic. And he is one of
`the world's leading formulation experts. And, in fact, an
`inventor or driving force behind many of Mylan's supposedly
`invalidating prior art references. He will testify about
`the Chang patent.
`Dr. Grisham is also here. He is a renowned
`scholar in the field of molecular and cellular physiology
`and he will tell us all about the Amin patents.
`Dr. Oates is a renowned scholar in the field of
`clinical rheumatology and also in the biological functions
`of nitric oxide. He is not here today but you will hear
`from him later in the trial concerning the Amin patents.
`And, lastly, Dr. John Murray, who is Galderma's
`marketing expert and economist here. And he will testify
`about the secondary considerations of nonobviousness,
`including the undisputed commercial success of this drug.
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 11 of 373 PageID #: 9473
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`Your Honor, in the course of the trial, you will
`hear about the problems both short term and long term that
`have historically been associated with prescribing chronic
`doses of antibiotics. Before Oracea, tetracycline compounds
`were used to treat rosacea only in very high antimicrobial
`doses, and because rosacea is a chronic condition, patients
`were prescribed chronic courses of antibiotics as treatment
`for the rosacea and that created two significant risks.
`First, it created a short term risk of
`undesirable side effects, such as phototoxicity, digestive
`problems and others that you will hear about. And,
`Two, it created a long term risk of antibiotic
`resistance which is a severe public health problem and
`concern.
`
`But conventional wisdom at the time was still to
`use greater doses for greater effect. Kill the bugs, so to
`speak.
`
`So no one considered giving a lower dose at that
`time, let alone giving a sub-antimicrobial dose. That was
`counterintuitive, and nobody did that until Ashley and his
`colleagues at CollaGenex came along.
`Now, while it was known that tetracycline
`compounds had certain antiinflammatory properties, it wasn't
`known that rosacea could be treated with doses that were low
`enough to avoid these undesirable antibiotic effects but
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 12 of 373 PageID #: 9474
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`still high enough to maintain efficacy. Oracea found that
`surprising middle ground and that was counterintuitive.
`CollaGenex basically conceived of harnessing the
`antiinflammatory properties of tetracyclines to treat the
`inflammatory lesions of rosacea.
`And you can see from the figure, the subsequent
`six month clinical trial by Skidmore that you will hear
`about during the course of the trial showed that
`sub-antimicrobial dosing of doxycycline significantly
`reduced lesion count in these patients and that was the
`basis or the discovery that was the basis for the Ashley
`patents.
`
`Now, the invention of the two Ashley patents was
`initially tested using immediate release formulation of
`doxycycline, administered as 20 milligrams twice a day. And
`the Ashley patents embody and they claim those inventions.
`And while the 20-milligram twice daily dosage
`regime was believed to be safe and effective, there was an
`unmet need still for a once-daily dosage of doxycycline that
`didn't have antibiotic effect. And as you will hear, a
`once-daily dose is especially important in treating a
`chronic disease like rosacea because it's more convenient
`for the patients and as a result, it increases patient
`compliance.
`
`Mylan's own asserted prior art in this case,
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 13 of 373 PageID #: 9475
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`that it recently put on to its revised 282 notice tells us
`that there was a long felt need for such a dose.
`Okay. CollaGenex sought to work with a company
`that specialized in dosage formulations to develop a
`once-a-day formulation, and it's first partner was an
`Australian company called Faulding. It completely failed to
`come up with once daily formulation despite three tries, and
`despite its significant experience in the formulation area.
`Faulding's failure really highlights the
`challenges that were inherent of developing a once daily
`formulation of this particular drug. They couldn't make it
`work. It always lacked enough bioavailability to be
`efficacious.
`
`However, the Chang inventors who were working at
`Supernus, a division of Shire at the time, came along and
`they were ultimately successful in developing the once daily
`formulation that is Oracea today and that discovery is the
`discovery of their patent.
`Indeed, it was Supernus's formulation that came
`over the once-a-day formulation challenges that were
`presented by doxycycline. Mylan is going to tell you
`throughout the course of the trial that the Chang patent is
`invalid because the Chang inventors supposedly derived their
`invention through CollaGenex, but according to Robert
`Ashley, who was CollaGenex's vice president at the time,
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 14 of 373 PageID #: 9476
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`CollaGenex just didn't come up with this particular
`invention of Chang. CollaGenex didn't have the expertise to
`formulate a once-daily doxycycline as claimed in the Chang
`patent. It was Supernus and the Chang inventors that
`finally pulled that off.
`Now, while it was surprising that rosacea could
`be effectively treated with sub-antimicrobial dose of
`doxycycline that was administered once daily, one of the
`antiinflammatory uses by which Oracea works was the subject
`of an unexpected and surprising discovery. Specifically,
`researchers at the State University of New York and at NYU
`discovered that tetracyclines, including doxycycline, could
`be used to reduce the production of nitric oxide by
`inhibiting expression of inducible nitric oxide synthase,
`which is the enzyme that makes nitric oxide. And, in
`particular, the inventors realized that tetracyclines could
`be effective in treating chronic inflammatory diseases
`mediated by inducible nitric oxide synthase, and that novel
`use of tetracycline compounds to reduce the production of
`nitric oxide was the basis for the Amin patents.
`Now, you will be hearing about all three of
`these sets of patents in the case, your Honor. And each
`represents a distinct aspect of the inventions covering the
`novel drug Oracea. Each patient is listed by Galderma in
`the FDA's Orange Book. Each patent is important to the
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 15 of 373 PageID #: 9477
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`success of this product and, tellingly, even though Mylan
`already markets a 50-milligram antibiotic doxycycline drug,
`Mylan wants to market this 40-milligram once-a-day
`sub-antibiotic drug and make a generic copy of Oracea.
`If Oracea isn't novel, then why would Mylan want
`to take the time and experience to market a generic version
`of it when it already has a 50 milligram drug on the market?
`And I think that is telling.
`The issues to be tried, there are only two:
`Whether Mylan infringes the asserted claims of
`the Ashley and Amin patents and two dependent claims of the
`Chang patent. And,
`Second, whether Mylan has proven by clear and
`convincing evidence whether it can meet that high burden of
`proving that the asserted claims of these three patents, all
`of them, are anticipated or obvious.
`Let's take infringement first.
`Here, your Honor, Mylan infringes all three sets
`of patents at issue, and you will hear evidence proving
`that. In fact, it's not even clear what noninfringement
`defenses Mylan has left at this stage.
`First, the Chang patent. Mylan has already
`conceded infringing numerous claims of the Chang patent. As
`per the stipulation that was signed by your Honor, Mylan is
`not asserting noninfringement of claims 1 to 3, 5, 7 to 9,
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 16 of 373 PageID #: 9478
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`13 to 17, or 19 to 21 of the Chang patent. Nor could it.
`It copied the formulation.
`Now, only one -- only asserted claims 4 and 18
`remains in terms of the question of infringement, but the
`evidence is clear that Mylan infringes both of them. As you
`can see from the claim language here, the relevant language
`concerning whether Mylan infringes is whether it falls
`between the steady state blood levels of .3 microgram per
`mil to .8 microgram per mil. Your Honor heard about that.
`In fact, it was a central issue in the last Markman hearing.
`And the clinical data will show that patients taking Mylan's
`drug will definitely meet those blood levels.
`Mylan relies on CollaGenex's pharmacokinetic
`studies in its proposed ANDA and package insert. Those
`studies tell us that Mylan's patients will have steady state
`plasma concentrations between .3 and .8 micrograms per ml.
`That is all that is required for infringement of these
`dependent claims.
`You are going to also hear from Galderma's
`formulation expert, Dr. Rudnic, who is one of the most
`successful formulators in the industry, and he is going to
`testify that patients taking a once-daily Oracea doxycycline
`formulation will fall within this range.
`But it is better than that. Mylan has already
`admitted infringement of these claims on multiple occasions
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 17 of 373 PageID #: 9479
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`before this Court. Going back all, all the way back to the
`preliminary injunction hearing last May, Mylan's counsel
`acknowledged that the parties agree that Mylan doxycycline
`concentration value achieved in the patient is .6 micrograms
`per milliliter. .6, right in the middle of the range.
`And that position has been unwavering and has
`not changed. As recently as a few weeks ago, in its portion
`of the pretrial order, Mylan acknowledged that the mean
`trough -- that means the low part, Cmin -- of the doxycycline
`serum concentration of Mylan's proposed ANDA product is .3
`micrograms per ml.
`If that is the bottom number for Mylan's
`patients, they fall within the range. They certainly do.
`So I don't see how Mylan can now dispute this at trial.
`Mylan should concede infringement right now and not put us
`to our proofs. But if it does, we will make them.
`Now, as to Ashley, the Ashley patents, this
`Court already preliminarily found a strong likelihood that
`Mylan infringed these patents. And all Mylan has done to
`date is repeat its old in vitro arguments, namely, reliance
`on in vitro evidence in an attempt to show non-infringement
`of claims about an in vivo drug.
`This Court rejected those arguments once and I
`submit it should do so again after hearing the evidence.
`This sub-antibacterial amount that we are
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 18 of 373 PageID #: 9480
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`looking at in the Ashley patents is an in vivo amount. That
`is not surprising. The whole point of these inventions is
`that they are administered to human beings, not test tubes.
`Now, Your Honor, again, the focus will be on
`these sub-antibacterial amount limitations that Your Honor
`has defined in the Markman hearing. And Your Honor defined
`that term as a lack of significant inhibition or growth of
`microorganisms, for example, bacteria.
`If we look at Mylan's label again -- we will in
`the course of the trial -- we will see it reads directly on
`that claim limitation. Mylan's label says that it
`demonstrated no detectable long-term effects on bacterial
`flora, that it shouldn't be used for eliminating bacterial
`disease.
`
`It says it shouldn't be used for eliminating any
`microorganism. It says do not treat infections with this
`drug.
`
`That is directly in contradiction to Mylan's
`litigation position. The contrast is remarkable. The label
`says, Should not be used for eliminating microorganisms.
`The litigation position is that it will significantly
`inhibit the growth of many of the identified pathogens.
`The label says do not treat infections caused by
`bacteria. The litigation position of Mylan is that it will
`significantly inhibit the growth of microorganisms.
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 19 of 373 PageID #: 9481
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`It goes on, the label says there is no
`detectible long-term effect on bacterial flora. Mylan will
`tell you today that there is not evidence that it will not
`significantly inhibit the growth of any microorganisms that
`reside in the nose, throat, lungs or eyes.
`So Mylan's positions are directly contradicted
`by its label.
`You will also hear their testimony through Dr.
`Talton that Mylan has no evidence that its drug inhibits
`microorganisms, and has no information contradicting the
`statements in the label. It has already admitted before
`this Court that the statements in the label are true.
`Let's move on to the Amin patents.
`Mylan and its experts are going to fail to rebut
`infringement of the Amin patents.
`You will hear from Galderma's expert in this
`field, Dr. Grisham. He will testify that the use of Mylan's
`ANDA product in accordance with Mylan's label will inhibit
`the production of nitric oxide synthase as per the claims,
`and will do so by inhibiting inducible nitric oxide synthase
`in a way that infringes the patent. Specifically, he will
`testify that the production of nitric oxide and inducible
`nitric oxide synthase to a number of effects, vasodilation,
`erythema, increased vascular permeability, leukocyte
`invasion and edema, which are the causes of the signs and
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 20 of 373 PageID #: 9482
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`symptoms of rosacea, including the papules and pustules of
`rosacea. And he will tie these inextricably together with
`the administration of Mylan's product.
`Mylan's expert, Dr. Robbins, is not going to
`contest the basic facts on this. He is not going to contest
`that the production of nitric oxide and inducible nitric
`oxide synthase will lead to the effects I have just
`described.
`
`They are not going to contest that the use of
`doxycycline decreases the effects of nitric oxide or nitric
`oxide synthase, and they simply can't dispute these basic
`facts in order to overcome our proof of infringement by a
`preponderance of the evidence.
`Indeed, you will see that Dr. Robbins's own
`work, that Dr. Robbins will show that doxycycline inhibits
`nitric oxide and inducible nitric oxide synthase. And if he
`testifies in a manner consistent with his deposition, he
`will admit that as well, because it is right in his
`deposition.
`
`As Your Honor can see, it will be clear that
`Mylan infringes all three sets of patents. Mylan already
`agrees that it infringes most of the claims of the Chang
`patent. And the evidence will show that it infringes the
`other patent claims as well.
`Now, Mylan will fare no better on its invalidity
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 21 of 373 PageID #: 9483
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`defenses. That is because as to all three of these sets of
`patents, Ashley, Chang and Amin, Mylan's proofs fall short
`of its heavy burden of showing invalidity by clear and
`convincing evidence.
`Now, Mylan cites dozens of references, piles of
`art, against all three patents. To my dismay, that hasn't
`changed since I brought up the issue before the Court at the
`pretrial conference.
`It raises these piles of art against all three
`of the patents. It won't be able to present any argument
`that comes close to disclosing all the elements of the
`asserted claims that are making these claims obvious. In
`fact, the citation of this voluminous collection, this
`kitchen-sink-full of art, begs the question. Now, if the
`inventions have been so obvious for so long and in view of
`so many references, why didn't anybody else do it first?
`And why does Mylan need so many references to invalidate
`these patently obvious claims? Because they are not.
`No matter how many references Mylan relies on or
`tries to stack up against Galderma's patents, the results
`are going to be the same, they just don't support the
`arguments.
`
`Now, Mylan has retooled and re-jiggered these
`piles of art in the last couple of weeks, more than once,
`and it has dropped some of the art, three pieces of art
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 22 of 373 PageID #: 9484
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`against Ashley and two against the others. Those are gone.
`It has added other art. But the new
`combinations still don't come close to disclosing the
`elements of the claim or making them obvious. And I will
`take you through them and the evidence that we will be
`presenting.
`
`As Your Honor saw from the previous slide, Mylan
`is now relying on 15 references in its attempt to invalidate
`the Ashley patents alone. We will take a closer look at
`them.
`
`First, Mylan won't even try to show that any one
`of the nine Gilchrest references as we referred to them at
`the PI hearing disclose all the elements of any of the
`asserted claims.
`They are up on Slide 35 here.
`Perhaps realizing the shortcomings of these
`references, Mylan has recently dropped three of them
`entirely, and I have crossed them out on the slide. So we
`are down to six. Here is a timeline of the now six
`Gilchrest references that Mylan relies on. Note the lengthy
`period of time between these references and the Ashley
`patent filing: decades. They were all published decades
`before the Ashley patents were even filed. If the Ashley
`patent was so obvious, why didn't someone rely on this
`reference to make this invention 30 years earlier or even 40
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 23 of 373 PageID #: 9485
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`years earlier when the Murphy article was first published?
`It's because it didn't teach anything. It didn't teach
`antimicrobial amount.
`They suffer from critical failures. They have
`no disclosure of doxycycline at all. They have no
`disclosure of a treatment of rosacea with a
`sub-antibacterial amount of doxycycline. They contain no
`disclosure of any dose of any antibiotic under a hundred
`milligrams a day. And they contain no disclosure whatsoever
`of any failure or non-reduction in bacterial flora.
`You will hear from Galderma's expert, Dr.
`Webster, who will point out these deficiencies in each of
`the six Gilchrest references and show why they fall short of
`anticipating the claims.
`If Dr. Gilchrest, Mylan's expert, testifies
`consistent with her deposition in this case, she will have
`to admit that these references fall short. For instance,
`she will have to admit that none of the references disclose
`tetracycline administered in an amount that is
`sub-antibacterial.
`She will have to admit that none of them
`disclose that they failed to inhibit the growth of
`microorganisms. She will have to admit that none of them
`disclose anything lower than a hundred milligrams a day of
`any antibiotic or any non-reduction of skin microflora.
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`Case 1:09-cv-00184-LPS Document 270 Filed 07/27/11 Page 24 of 373 PageID #: 9486
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`Those are critical failures in Mylan's case.
`These references should have been dropped in
`view of these admissions.
`Now, Mylan primarily relies on that collection
`of references as far as we can glean from the 282 statement.
`But it also continues to rely on the Pflugfelder
`patent, which the PTO considered to be the closest prior art
`to Ashley. But the patents issued over Pflugfelder anyway
`because, as the patent examiner recognized, Pflugfelder did
`not teach methods for treating papules and pustules of
`rosacea by administering tetracycline in an amount ten to 80
`percent of the antibiotic effective amount with no reduction
`of skin microflora. So it basically recognized the failure
`of that art.
`
`But Mylan is stubbornly pushing forward with the
`Pflugfelder references, as far as I can tell.
`Indeed, Mylan's expert admitted during her
`deposition that she doesn't consider the Pflugfelder
`reference as anticipatory art against the Ashley patents but
`only as one of many other references she uses to support her
`obviousness argument.
`Your Honor, as I mentioned a few times, Mylan
`has recently added five new references and even more distant
`references to support its invalidity references against
`Ashley. Now, all those these references were cited long ago
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`in one of Mylan's interrogatories where it listed hundreds
`of references. They only recently resurfaced in the last
`two weeks. And adding more art to the pile at the last
`minute is not going to help Mylan meets its burden because
`none of these new r
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