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`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 1 of 156 PageID #: 3919
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`:
`:
`:
`
`CIVIL ACTION
`
`NO. 14-1453-LPS
`
`::
`
`::
`
`- - -
`Wilmington, Delaware
`Tuesday, December 13, 2016
`Bench Trial - Volume A
`- - -
`HONORABLE LEONARD A. STARK, Chief Judge
`- - -
`
`BEFORE:
`APPEARANCES:
`
`RICHARDS LAYTON & FINGER, P.A.
`BY: FREDERICK L. COTTRELL, III, ESQ., and
`SELENA E. MOLINA, ESQ.
`and
`STERNE KESSLER GOLDSTEIN & FOX, LLP
`BY: UMA N. EVERETT, ESQ.,
`DENNIES VARUGHESE, ESQ.,
`RAMI BARDENSTEIN, ESQ.,
`ADAM C. LaROCK, ESQ.,
`JOSHUA I. MILLER, ESQ.,
`JOSEPHINE J. KIM, ESQ.,
`STEPHANIE NGUYEN, ESQ., and
`MARK FOX EVENS, ESQ.
`(Washington, District of Columbia)
`Counsel for Plaintiffs
`
`Valerie Gunning
`Official Court Reporter
`
`Brian P. Gaffigan
`Official Court Reporter
`
`MEDA PHARMACEUTICALS, INC.,
`and CIPLA LTD.,
`Plaintiffs,
`
`v.
`APOTEX INC. and APOTEX CORP.,
`Defendants.
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 1
`
`

`

`2
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 2 of 156 PageID #: 3920
`
`APPEARANCES: (Continued)
`
`PROCTOR HEYMAN ENERIO, LLP
`BY: DOMINICK GATTUSO, ESQ.
`and
`WINSTON & STRAWN, LLP
`BY:
`GEORGE C. LOMBARDI, ESQ.,
`SAMUEL S. PARK, ESQ.,
`KEVIN E. WARNER, ESQ., and
`RYAN B. HAUER, ESQ.
`(Chicago, Illinois)
`and
`WINSTON & STRAWN, LLP
`BY: CHARLES B. KLEIN, ESQ., and
`ILAN WURMAN, ESQ.
`(Washington, District of Columbia)
`Counsel on behalf of Defendants
`
`- oOo -
`P R O C E E D I N G S
`(REPORTER'S NOTE: The following bench trial was
`held in open court, beginning at 3:32 p.m.)
`THE COURT: Good afternoon.
`(The attorneys respond, "Good afternoon, Your
`
`Honor.")
`
`THE COURT: Please have a seat.
`On this first day of trial, let's begin by
`noting your appearances for the record, starting with
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 2
`
`

`

`3
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 3 of 156 PageID #: 3921
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`plaintiffs.
`
`MS. EVERETT: Your Honor, Uma Everett on behalf
`of plaintiffs. With me this week, you will hear from my
`colleagues, Mark Evens.
`MR. EVENS: Good afternoon, Your Honor.
`MS. EVERETT: Dennies Varughese.
`MR. VARUGHESE: Good afternoon, Your Honor.
`THE COURT: Good afternoon.
`MS. EVERETT: And Adam LaRock.
`MR. LaROCK: Good afternoon.
`THE COURT: Good afternoon.
`MS. EVERETT: Your Honor, we also have client
`representatives here this week to attend trial. We have
`client represents from Meda. From your left, Your Honor we
`have Marten Osterlund from Sweden.
`MR. OSTERLUND: Good afternoon.
`MS. EVERETT: We have Gabrielle Endler from
`
`Germany.
`
`Jersey.
`
`MS. ENDLER: Good afternoon.
`MS. EVERETT: We have Matthew Polley from New
`
`MR. POLLEY: Good afternoon.
`MS. EVERETT: We also have representatives from
`Cipla Limited.
`Again, from your left, Your Honor, we have
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 3
`
`

`

`4
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 4 of 156 PageID #: 3922
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`Bhakti Patil.
`MS. PATIL: Good afternoon.
`MS. EVERETT: And we have Aarti Deodhar.
`MS. DEODHAR: Good afternoon.
`MS. EVERETT: From India.
`THE COURT: Welcome to all of you.
`All right. Mr. Cottrell, do you want to put
`your appearance on the record?
`MR. COTTRELL: I'm sorry. Fred Cottrell from
`Richard Layton, Delaware counsel. Thank you.
`THE COURT: Thank you. And now the other side
`
`of the room.
`
`MR. GATTUSO: Good afternoon, Your Honor.
`THE COURT: Good afternoon.
`MR. GATTUSO: Dominick Gattuso from Proctor
`Heyman Enerio on behalf of Apotex.
`I also have with me George Lombardi.
`MR. LOMBARDI: Good afternoon.
`MR. GATTUSO: Charles Klein.
`MR. KLEIN: Good afternoon, Your Honor.
`MR. GATTUSO: Ilan Wurman.
`MR. WURMAN: Good afternoon.
`MR. GATTUSO: Kevin Warner.
`MR. WARNER: Good afternoon.
`MR. GATTUSO: And in the back, we have Ryan
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 4
`
`

`

`5
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 5 of 156 PageID #: 3923
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`Hauer who isn't with us now but will be before Your Honor.
`And then from the client Apotex, we have Robert
`Shapiro, senior patent counsel.
`(Mr. Shapiro nods greetings.)
`THE COURT: Welcome and good afternoon to all of
`
`you.
`
`MR. GATTUSO: Thank you.
`THE COURT: Thank you very much. So we are here
`for trial. As I think you all know, I have another trial
`going on upstairs I guess that is. And so that is,
`hopefully you're aware, moving along at the pace we
`anticipated, meaning as of now we expect we will close the
`evidence tomorrow some time. I'll certainly be with you by
`3:30 tomorrow.
`If it turns out that I could be here sooner than
`that, we'll let you know. If it works out for all of you,
`we'll start sooner, but since that is a little bit up in the
`air, we won't force you all to come in before 3:30 but if
`it does work for me and it works for all of you and your
`witnesses, we might be able to get started earlier than
`3:30.
`
`We plan to have closing argument in the jury
`trial Thursday morning, and so if all goes according to
`plan, we'll get the case to the jury by around lunchtime
`Thursday, which means we could start early in the afternoon
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 5
`
`

`

`6
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 6 of 156 PageID #: 3924
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`on Thursday and hopefully be with you most of Friday, all
`subject to if the jury has a question or needs me for some
`other reason.
`Are there any questions about any of that? No?
`
`No.
`
`Before we get started with openings, any issues
`from plaintiffs?
`MS. EVERETT: No, Your Honor.
`THE COURT: And from defendant?
`MR. LOMBARDI: No, Your Honor.
`THE COURT: And do both sides intend to give an
`
`opening?
`
`MR. LOMBARDI: Yes, Your Honor.
`MS. EVERETT: Yes, Your Honor.
`THE COURT: Then we'll I believe we were going
`to hear from defendants first.
`MR. LOMBARDI: Your Honor, I do have copies of
`slides. I'm not sure how many copies.
`THE COURT: If you have three, that would be
`very helpful. Thank you.
`(Demonstratives passed forward.)
`MR. LOMBARDI: And, Your Honor, one note. And
`for the record, George Lombardi on behalf of Apotex. One
`note about the slides, Your Honor.
`In order to correct some objections or respond
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 6
`
`

`

`7
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 7 of 156 PageID #: 3925
`
`to some objections, we changed some of the slides. I think
`the copy I just gave you might have a couple of slides that
`actually will be corrected, and we will substitute that
`tomorrow for you so that the slides you will see on the
`screen is the slide that is appropriate.
`THE COURT: Okay. Thank you.
`MR. LOMBARDI: And, again, may it please the
`Court. George Lombardi on behalf of Apotex.
`Your Honor, I want to talk to you a little bit
`about the basics of this case.
`First of all, Apotex is the defendant here and
`the only defendant here. The other parties here are Meda,
`Cipla, and they are, I will describe who they are. But what
`has brought us here is that Apotex has filed an ANDA and is
`seeking the right to sell the generic version of a drug
`called Dymista. And you are going to hear a lot more about
`Dymista obviously as we go long and we go along today.
`Cipla, the Indian company that was introduced
`here before is the patent holder. Meda has an exclusive
`license and is the distributor of the product in the United
`States.
`
`Meda, you will see, from time to time, you will
`see a company called MedPointe in the documents. That Med
`Point is Meda. MedPointe became Meda over time, and it is
`our understanding Meda was acquired by a company called
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 7
`
`

`

`8
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 8 of 156 PageID #: 3926
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`Mylan recently. So that is the corporate layout of the
`various defendants.
`And here is the gist of the case.
`Your Honor, our central defense in this case is
`obviousness. And that is what we're going to spend most of
`our time talking about in this case. The claims cover the
`co-formulation, meaning the combination of two known FDA
`approved drugs combined with known excipients or inactive
`ingredients for a known use.
`So let me talk about that in a little bit more
`detail. The two known FDA drugs here are azelastine
`hydrochloride and fluticasone propionate. They were known
`to treat a condition known as allergic rhinitis, which I
`will talk about a little bit more. It's hayfever is what it
`is commonly known as.
`They both treated it separately. They both
`had separate mechanisms of action for treating allergic
`rhinitis. So they operated in different ways on the same
`condition but they were both treatment for allergic
`rhinitis.
`
`And the evidence here will be it was taught in
`the art specifically to combine azelastine hydrochloride and
`fluticasone propionate together to treat allergic rhinitis.
`As to the excipients, all of the excipients, and
`again, the excipients are the inactive ingredients, as I'm
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 8
`
`

`

`9
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 9 of 156 PageID #: 3927
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`sure Your Honor is aware. All the excipients claimed here
`were known in the art. And, in fact, all of the excipients
`that are part of the claimed formulations were used with
`either azelastine hydrochloride or with fluticasone
`propionate, and the excipients that are used in the claimed
`formulation here operate exactly as they did in the prior
`art, operate in the same way.
`And this combination, this formulation that is
`combined is being used for a known purpose. It is being
`used to treat allergic rhinitis.
`The fluticasone and azelastine hydrochloride --
`and Your Honor, we'll probably have a tomato, tomato thing
`with azelastine and we will try to conform things as we go
`along. But azelastine hydrochloride and fluticasone, as I
`said, were used to treat allergic rhinitis. So there is
`literally nothing new about what has been put together and
`claimed as an invention here. There is no surprising
`results. Everything works as it was taught to work in the
`prior art. And the claims as a result are obvious.
`So let me give you some of the background about
`the dates, background information you are going to hear a
`lot more about as we go along.
`There are two patents at issue in the case. And
`plaintiffs have chosen to assert 15 claims, so we're going
`to have to deal with all 15 claims.
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 9
`
`

`

`10
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 10 of 156 PageID #: 3928
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`The first, the patents are slightly different but
`really go to the same basic principle. So the '620 patent,
`which is the one on the left, is a formulation patent which
`literally sets forth the azelastine hydrochloride, the
`fluticasone, and various excipients together as a combination,
`combination formulation.
`The '428 patent is a method patent, a method of
`treatment patent, but the patent is a method of treatment
`that employs the formulation. So the fundamental issue is
`the same from the method of treatment claims to the claims
`that are for the formulation.
`Now, I'm not going to go through all the claims
`here in detail this morning, but to give you a representative
`example, Your Honor, I took one of the most complete claims in
`terms of the number of elements that it refers to just to give
`you an example.
`And this is from the '428 patent, claim 1 which
`is one of the method of treatment patents for seasonal
`allergic rhinitis. And you can see the first two elements
`there are azelastine hydrochloride and fluticasone
`propionate. Those are the active ingredients I have been
`talking about.
`And from that point down are various excipients
`that have different purposes. Each of them has a different
`purpose. So we'll talk about what the preservatives do,
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 10
`
`

`

`11
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 11 of 156 PageID #: 3929
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`with those first two there, what a thickening agent does,
`what a surfactant does and so forth.
`And the claim, while there are 15 claims, all
`of the claims are essentially this or some subset of this.
`Sometimes there is a claim relating to pH in there and
`sometimes there is a claim related to the size of the
`particles in there as well, but this is fundamentally what
`is going to be at issue throughout the entirety of the 15
`claims that are at issue here.
`So what is the fundamental story on the prior
`art? And, Your Honor, this is what fundamentally happened.
`Azelastine hydrochloride was marketed as a drug
`called Astelin, commercially available well before the
`critical date. And just so you have it in mind, Your Honor,
`the critical date here is in 2002.
`And so azelastine hydrochloride, Astelin, was
`available before 2002. It is, azelastine hydrochloride is an
`antihistamine, and antihistamines were known as treatments
`for allergic rhinitis, and azelastine hydrochloride was
`specifically known as that kind of treatment.
`Also on the market before the critical date was a
`drug called Flonase, and Flonase was fluticasone propionate.
`That was the active ingredient. That is a corticosteroid, and
`corticosteroids are known to treat allergic rhinitis as well
`and Flonase, in particular, fluticasone propionate, treats
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 11
`
`

`

`12
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 12 of 156 PageID #: 3930
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`allergic rhinitis.
`Those two, our position is all that happened
`here is that those two formulations were put together to
`create the drug that is at issue here, Dymista. Dymista
`includes azelastine hydrochloride as one active ingredient
`and includes fluticasone propionate as the other active
`ingredient. That is fundamentally what happened here.
`Now, Dymista, as was the case with azelastine
`hydrochloride and fluticasone propionate is a nasal spray,
`sprayed into the nose to treat allergic rhinitis.
`So what is allergic rhinitis? I made reference
`to this before, Your Honor. It is what is commonly known as
`hayfever. And what happen is that the patient, that the
`person who is victimized by allergic rhinitis is exposed to
`allergens like pollen and on exposure to allergens starts to
`experience symptoms, symptoms sneezing, wheezing, coughing
`irritation of the nasal mucous and so forth, and this can go
`on for quite some time.
`And so the way the two prior art drugs worked,
`Astelin and fluticasone -- and Flonase is as follows.
`Astelin was known to be particularly good for the early
`phase response to the allergen. So if somebody with
`allergic rhinitis was exposed to pollen and started to
`react, the antihistamine, Astelin, would have a relatively
`fast effect and would address those early phase symptoms.
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 12
`
`

`

`13
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 13 of 156 PageID #: 3931
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`With respect to Flonase, the fluticasone
`compound, it was known that that would have more of an
`effect on the late phase, the late phase symptoms. And so
`it was actually viewed that Flonase or fluticasone component
`of steroid treatment, what was considered the first line of
`defense.
`
`And the second line of defense was putting in
`the antihistamine because the steroid frequently didn't take
`effect for a few days and the patient would need some relief
`in the few days before this steroid could take effect. That
`was the fundamental way the two worked in the art and not
`surprisingly, given the way I described that to you, it is
`no surprise at all that doctors concluded that these drugs
`should be prescribed together to patients.
`And sometimes you will hear that referred to,
`Your Honor, as conjunctive treatment, meaning the two are
`prescribed together, meaning not as part of the same
`formulation but prescriptions to both together. And what
`I put up on my screen is again in the prior art, and it's
`called the ARIA guidelines, and ARIA stands for Allergic
`Rhinitis Impact on Asthma.
`And there were guidelines put together by
`persons skilled in this art by doctors skilled in the art to
`advise how to treat allergic rhinitis. And you can see, and
`you are going to hear the witnesses talk about this, that
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 13
`
`

`

`14
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 14 of 156 PageID #: 3932
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`before the critical date, the priority date in this case,
`on the left you can see it is advised to use intranasal
`glucocorticosteroids, that is what fluticasone or Flonase
`is, as a first line treatment.
`And the second column, you can see that you --
`you can see the reference to adding HI antihistamines, and
`that is what kind of product Astelin was, azelastine
`hydrochloride.
`So the prior art specifically suggested adding
`these two types of drugs together to treat an individual
`patient. That was known in the art.
`And you're actually going to hear evidence in
`this case that doctors before the critical date actually did
`prescribe Flonase and Astelin, the prior art compounds here
`together to their patients.
`So the first witness you are going to hear
`from today is Dr. Accetta, and he is going to show you some
`patient records that evidence the fact that back before the
`critical date, you can see at the top, allergic rhinitis is
`what is being treated, and the medicines are Flonase and
`Astelin.
`
`So this was being done in the art, this kind of
`conjunctive treatment using the two drugs was being done in
`the art.
`
`And, again, given all that I have told you, it
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 14
`
`

`

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`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 15 of 156 PageID #: 3933
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`is no surprise that there were calls in the art that if
`we're going to be prescribing these two drugs, conjunctively
`to patients, there ought to be a drug that puts them both in
`the same bottle and treats people from the same bottle with
`those same drugs.
`And so the Spector reference from 1999 sets that
`forth. And you can see there is a reference to the symptoms
`observed in EPR are most effectively managed by an H1
`receptor antagonist.
`EPR is early phase rhinitis which is what we
`referred to before, saying those symptoms from early phase
`rhinitis are most effectively managed by an antihistamine.
`That is what an H1 receptor antagonist is. That is what it
`is talking about as azelastine hydrochloride.
`Whereas the effects of LPR, which stands for
`late phase rhinitis, are best managed with a corticosteroid.
`And that is what fluticasone is, a corticosteroid.
`So here is the important point and what is
`perfectly logical that the art would be saying this is,
`therefore, the ideal pharmacologic therapy would be a drug
`that possessed not only the H1 receptor antagonist activity,
`meaning the antihistamine activity, but also the
`antiinflammatory activity, and that is the activity of the
`corticosteroid.
`So the art was specifically calling for the
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 15
`
`

`

`16
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 16 of 156 PageID #: 3934
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`combination of these types of drugs together. And beyond
`that, Your Honor, the art was specifically calling for and
`teaching the combination of the precise active ingredients
`that are at issue in this case.
`So in 1997, Proctor & Gamble filed an EPO, a
`European patent application; and in that patent application,
`they called for a treatment which consisted of fluticasone
`and azelastine from a very small group of corticosteroids
`and from a very small group of antihistamines to be used
`as an intranasal carrier, to be used to treat allergic
`rhinitis.
`
`So the art specifically taught the use of these
`active ingredients.
`So when plaintiffs talk to you about being the
`first with this, what they'll never be able to establish is
`that they were the first to have the idea. This idea was
`out there in the art. This idea to combine fluticasone
`and azelastine hydrochloride was out there, known in the
`art, taught in the art, and claimed by people like Proctor &
`Gamble. And there are other examples of this as well, Your
`Honor.
`
`So what will plaintiffs say about this?
`Plaintiffs will present, based on what we have seen in
`discovery, Your Honor, plaintiffs will present evidence that
`there are articles out there that teach away. I put
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 16
`
`

`

`17
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 17 of 156 PageID #: 3935
`
`asterisks by the articles that are relied on by plaintiffs;
`and we will go through with the experts these articles and
`the conclusion from these articles is that they don't teach
`away, and, in fact, encourage the use of fluticasone and
`azelastine hydrochloride.
`But for simplicity sake, just so you understand
`the timeline, the ARIA guidelines that I referred to that
`call for a combination of these types of drugs came after --
`came before the priority date and after all of those studies
`were issued. So the point is that even given whatever
`plaintiff wants to say about those studies, the ARIA
`guidelines was still recommending them.
`And with that, Your Honor, we believe it is
`beyond obvious that azelastine hydrochloride and fluticasone
`should be suggested in the art and were obvious over the art.
`Your Honor is very aware of the case law on this
`area, and I won't dwell on this at this point. But just as
`a reminder, the Richardson-Vicks case was a case that
`originated in this District and the Federal Circuit, and
`actually the District Judge in this case overturned jury
`verdict of validity.
`It involved a situation where two active
`ingredients had been used separately and prescribed for the
`same purpose and then were put in the same tablet, which
`is the same situation that we have here, and it was ruled
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 17
`
`

`

`18
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 18 of 156 PageID #: 3936
`
`obvious in that instance.
`There are other things as part of the
`formulation. There are excipients that are part of the
`formulation. What effect do these excipients have on the
`obviousness analysis here?
`And the short answer, judge, is it doesn't
`change the analysis. And I'm not going to go through
`everything on this chart, but I'll describe to you what can
`be taken from this chart is we put up the excipients from
`the Flonase label, the prior art fluticasone label, and from
`the Astelin label, the prior art azelastine label, and we
`put adjacent to that one of the claims of the patent.
`What you will find in summary in this case, Your
`Honor, is that with one exception, all of the excipients
`were used with either Flonase -- all the excipients that are
`claimed here were used with either Flonase or azelastine, or
`Astelin, in those two labels. All of them but one of them
`were used.
`
`And with respect to that one, it's an excipient
`that is called a tonicity adjustor, and we're going to talk
`a lot about that, Your Honor. But at a high level, a
`different tonicity adjustor was used and was in the Flonase
`level or the Astelin label, but when you look at the art,
`there is a patent that covers the Astelin product and covers
`azelastine hydrochloride, and that patent specifically
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 18
`
`

`

`19
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 19 of 156 PageID #: 3937
`
`mentions glycerin which was the excipient that was used in
`these claims. So the art completely discloses the use of
`these excipients with these components.
`So at the end of the day, Your Honor, when we
`look at these formulations, and we look at these excipients,
`we are going to find that all the excipients that are used
`were known in the art, all of the excipients were known to
`have particular purposes in their use, and all of the
`excipients as used in Dymista, as used in the claimed
`invention, work in the same way as was taught in the art.
`There was nothing new about the excipients that were used
`here.
`
`So what did plaintiff say about that and
`throughout the discovery and expert portions of this case,
`leading up to this trial?
`Well, they generally said that this is
`formulation, Your Honor. And when you put components
`together, you never know whether they're going to work until
`you actually put them together.
`But that kind of general unpredictability has
`been rejected by the Federal Circuit as a way to avoid
`obviousness, Your Honor.
`The question here is would one reasonably expect
`it to work? And an assertion that generally the art is
`unpredictable or you can't know until you put things
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 19
`
`

`

`20
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 20 of 156 PageID #: 3938
`
`together is not sufficient.
`There will not be any art presented that
`indicates that any of these excipients could not work with
`any of the other excipients or could not work with the
`active ingredients.
`Now, there is another argument that plaintiffs
`are going to make here, Your Honor, about this formulation.
`And they're going to say, well, this formulation, because it
`involves fluticasone, which is a compound that is suspended,
`is in suspension normally when you formulate it. Suspension
`just means the particles, for lack of a better word, are
`suspended in the water, which is the vehicle, and azelastine
`hydrochloride is dissolved, it goes into solution. So those
`are two different ways of being carried.
`They're going to say, well, that creates
`problems for a formula here. But there is nothing in the
`art that teaches that there is any issue with a solution and
`a suspension being in the same formulation. And, in fact,
`the evidence will be to the contrary, and the evidence will
`be that azelastine hydrochloride and fluticasone function
`exactly as one would expect them to function based on how
`they function in the prior art. In other words, azelastine
`is dissolved and fluticasone is in suspension.
`Now, what plaintiffs did when they were in the
`Patent Office and faced with an obviousness rejection in the
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 20
`
`

`

`21
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 21 of 156 PageID #: 3939
`
`Patent Office, they did some testing to try to show that
`there were problems in doing this kind of formulation. And
`the testing that they did in that context came from Cramer,
`which was the Proctor & Gamble patent application I pointed
`out to Your Honor earlier. And they went to an example
`there that involved different components that are at issue
`in this case, and they did the testing based on that example.
`Now, the Patent Office, at the time this testing
`was submitted, had indicated that the claimed invention was
`considered prima facie obvious. And they submitted this
`testing as an attempt to try to overcome the obviousness
`finding.
`
`And they did overcome the obviousness finding
`but not with the testing, Your Honor. The Patent Office
`did not even mention this testing in the reasons for
`allowability of the patent. They are going to mention some
`other things which I'm going to talk about shortly but they
`didn't mention the testing, and that is because the test was
`flawed.
`
`The testing they submitted to the Patent Office
`was incomplete. It was testing that was done with making no
`attempt to optimize the formula, and the criticisms they
`make of the testing are criticisms that don't relate to
`anything other than optimization.
`But this is not a case about optimization or FDA
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 21
`
`

`

`22
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 22 of 156 PageID #: 3940
`
`approval. This is a case, a patent case and about whether
`claims were obvious. So the testing other is not relevant
`as is indicated by the way that the Patent Office handled it.
`You can see that in the notice of allowability,
`there is reference to certain secondary considerations,
`which played a big part in the Patent Office's decision to
`approve the patent to allow the patent here.
`Your Honor I know is supremely familiar with the
`law of secondary considerations, so I'm not going to talk
`about that. And there are a lot, there has been a lot of
`discussion of secondary considerations in various ways
`throughout this case. I'm not going to try to anticipate
`every secondary consideration.
`I will have something to say at the end of the
`case about anything that is referenced, but I do want to
`reference a few things for Your Honor to keep in mind as
`you hear the evidence that is pertinent to secondary
`considerations.
`The first is the existence of blocking patents.
`There is going to be a lot of talk about how Dymista was
`the first drug of this kind to get to the market, to be
`commercially sold, but that is in part explained by the
`patent landscape that existed at the time.
`So the PTO didn't have this patent landscape
`before it, did not consider these blocking patents in
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`Opiant Exhibit 2044
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 22
`
`

`

`23
`Case 1:14-cv-01453-LPS Document 151 Filed 01/09/17 Page 23 of 156 PageID #: 3941
`
`considering the secondary considerations. And this is what
`that landscape was.
`The patent covering -- there was a patent
`covering fluticasone, one of the two active ingredients
`here, that issued way back in 1982 and ran to the early
`2000s.
`
`There was a patent covering Astelin which ran
`from 1992 and, when you include pediatric exclusivity,
`barred people from the market until 2011.
`So anybody who might have considered using a
`combination of those two active ingredients would have been
`faced with those two patents during that period of time.
`And on top of that, Your Honor, on top of that,
`in 2003, in the middle of the screen there, December 24th,
`2003, the application for the patents that matured into --
`for the patents that are in suit today was published. So
`anybody looking at this landscape at the time would know
`that there were two patents out there, one each on
`fluticasone and azelastine, and would know that somebody had
`already gotten a patent on file covering the two together.
`And one thing further to keep in mind, Your
`Honor, is that the azelastine patent was something that
`plaintiffs had rights in, so that didn't

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