CONFIDENTIAL TESTIMONY
`
`Transcript of Stuart Allen Jones
`
`Friday, February 21, 2020
`
`Nalox-1 Pharmaceuticals, LLC v. Adapt Pharma Operations Ltd.
`
`Alderson Court Reporting
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`Alderson Reference Number: 91002
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`Nalox1248
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`Stuart Allen Jones
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`Confidential
`Washington, DC
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`2/21/2020
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`- - - - - - - - - - - - - - - - - X
`NALOX-1 PHARMACEUTICALS, LLC :
` Petitioner, : Case No.
` v. : IPR2019-00685
`ADAPT PHARMA OPERATIONS LTD., and : IPR2019-00688
`OPIANT PHARMACEUTICALS, INC., : IPR2019-00694
` Patent Owners. :
`- - - - - - - - - - - - - - - - - X
` Friday, February 21, 2020
` Washington, DC
` CONFIDENTIAL TESTIMONY
` Deposition of STUART ALLEN JONES, a
`witness herein, called for examination by the
`Petitioner in the above-entitled matter, pursuant to
`notice, the witness being duly sworn by Desirae S.
`Jura, a Notary Public in and for the District of
`Columbia, taken at Williams & Connolly LLP, at 9:33
`a.m., Friday, February 21, 2020, and the proceedings
`being taken down by stenotype by Desirae S. Jura,
`RPR, and transcribed under her direction.
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`Stuart Allen Jones
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` 1 APPEARANCES:
` 2
` 3 On behalf of the Petitioner:
` 4 RICHARD J. BERMAN, ESQUIRE
` 5 YELEE Y. KIM, ESQUIRE
` 6 Arent Fox LLP
` 7 1717 K Street, NW
` 8 Washington, DC 20006
` 9 (202) 857-6000
`10 richard.berman@arentfox.com
`11 yelee.kim@arentfox.com
`12
`13 On Behalf of Patent Owners Adapt Pharma
`14 Operations Ltd., and Opiant Pharmaceuticals,
`15 Inc.:
`16 JESSICA TYRUS MACKAY, ESQUIRE
`17 Green, Griffith & Borg-Breen, LLP
`18 676 North Michigan Avenue
`19 Suite 3900
`20 Chicago, Illinois 60611
`21 (313) 883-8000
`22 jmackay@greengriffith.com
` 1 APPEARANCES (Continued):
` 2
` 3 On behalf of the Patent Owner Adapt Pharma
` 4 Operations Limited:
` 5 DAVID M. KRINSKY, ESQUIRE
` 6 JESSAMYN S. BERNIKER, ESQUIRE
` 7 JESSICA PALMER RYEN, ESQUIRE
` 8 Williams & Connolly LLP
` 9 725 12th Street, NW
`10 Washington, DC 20005
`11 (202) 434-5338
`12 dkrinsky@wc.com
`13 jberniker@wc.com
`14 jryen@wc.com
`15
`16 ALSO PRESENT:
`17 JOSHUA H. HARRIS
`18 Burford Capital
`19 350 Madison Avenue
`20 New York, New York 10017
`21 (646) 849-6410
`22 jharris@burfordcapital.com
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` 1 C O N T E N T S
` 2 WITNESS PAGE
` 3 STUART ALLEN JONES
` 4 BY MR. BERMAN 6
` 5
` 6 Afternoon session - Page 83
` 7
` 8
` 9 E X H I B I T S
`10 EXHIBIT NO. PAGE
`11 1 - Pharmacokinetic Properties and Human
`12 Use Characteristics of an FDA-Approved
`13 Intranasal Naloxone Product for the
`14 Treatment of Opioid Overdose 58
`15 2 - Pharmacokinetic Interaction between
`16 Naloxone and Naltrexone Following
`17 Intranasal Administration to Healthy
`18 Subjects 66
`19 3 - Quaternary Ammonium Compounds: Simple
`20 In Structure, Complex in Application 71
`21 4 - Chemical Stability of Pharmaceuticals
`22 A Handbook for Pharmacists 89
`Page 5
` 1 E X H I B I T S (Continued):
` 2 EXHIBIT NO. PAGE
` 3 5 - Bentley and Dyke: 512. The Structure
` 4 of pseudoMorphine 92
` 5 6 - Stability of Morphine in Aqueous Solution
` 6 III Kinetics of Morphine Degradation in
` 7 Aqueous Solution 95
` 8 7 - Investigation of 4,5-epoxymorphinan
` 9 degradation during analysis by HPLC 98
`10 8 - Differences between opioids:
`11 Pharmacological, experimental, clinical
`12 and economical perspectives 100
`13 9 - Research Article, Effect of Formulation
`14 Variables on the Nasal Permeability and
`15 Stability of Naloxone Intranasal
`16 Formulations 125
`17 - - -
`18
`19
`20
`21
`22
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`Confidential
`Washington, DC
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`Stuart Allen Jones
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` 1 P R O C E E D I N G S
` 2 Whereupon,
` 3 STUART ALLEN JONES
` 4 was called as a witness by counsel for the
` 5 Defendants, and having been duly sworn, was examined
` 6 and testified as follows:
` 7 EXAMINATION BY COUNSEL FOR THE PETITIONER
` 8 BY MR. BERMAN:
` 9 Q. Good morning, Dr. Jones. My name is Rich
`10 Berman. I'm counsel for petitioner Nalox-1
`11 Pharmaceuticals, LLC.
`12 Can you recite your full name and home
`13 address for the record.
`14 A. Stuart Allen Jones. 42 Fairlawns Langley
`15 Road, Watford, United Kingdom.
`16 Q. We'll go over some ground rules. Let me
`17 know if you don't hear or understand the question.
`18 If you answer, we'll assume you heard and understood
`19 the question. Okay?
`20 A. Okay.
`21 Q. Let me know if you don't know or can't
`22 remember the information sought by the question. If
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` 1 with certain IPRs, correct?
` 2 A. Yes.
` 3 Q. I'm showing you what's been previously
` 4 marked as Exhibit 2201 for the IPRs in the '253,
` 5 '747, and '965 patent matters.
` 6 Do you see that?
` 7 MR. KRINSKY: And I'd like to note for the
` 8 record that you've passed out copies marked
` 9 Protective Order Material. We can sort out
`10 confidentiality designations afterwards, but at least
`11 on an interim basis, let's mark the transcript
`12 confidential.
`13 MR. BERMAN: Sure.
`14 BY MR. BERMAN:
`15 Q. Do you see that?
`16 A. Yes.
`17 Q. I am going to use for questioning today
`18 the '253 IPR. Okay?
`19 A. Okay.
`20 Q. And if any answer you give today would be
`21 different for either of the other two IPRs, the '747
`22 or '965, will you let me know that?
` 1 MR. KRINSKY: Objection to form.
` 2 THE WITNESS: Can you repeat the question,
` 3 please?
` 4 BY MR. BERMAN:
` 5 Q. Sure. I'm going to use the '253 as the
` 6 basis of going through and asking you some questions.
` 7 But if, in the context of answering those questions,
` 8 if your answer would be different depending on which
` 9 of the three patents we're talking about, can you let
`10 me know the difference?
`11 MR. KRINSKY: If I could just state for
`12 the record, I believe these are all the same exact
`13 documents under the cover sheet.
`14 MR. BERMAN: Right. I understand that.
`15 BY MR. BERMAN:
`16 Q. What I'm saying is, inartfully, if an
`17 answer you're going to give would be different if we
`18 were talking about the '253 patent declaration versus
`19 the '747 or the '965 patent, will you let me know if
`20 there's any difference in your answer?
`21 MR. KRINSKY: Object to the form of the
`22 question. Vague.
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`Page 9
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`Page 7
` 1 you answer, we will assume that you know and remember
` 2 the information sought. Okay?
` 3 A. Okay.
` 4 Q. We have a court reporter who is making a
` 5 transcript, so be sure to answer in a way that the
` 6 court reporter can record in the transcript. And
` 7 you'll need to answer out loud. The court reporter
` 8 cannot record nodding or shaking of the head. Also,
` 9 please say yes rather than uh-huh. Okay?
`10 A. Yes.
`11 Q. And let me know if you want to take a
`12 break for any reason. Okay?
`13 A. Yes.
`14 Q. And let me know if you realize that an
`15 answer you previously gave is inaccurate or
`16 incomplete. Just say that you want to correct or
`17 supplement a previous answer. Okay?
`18 A. Okay.
`19 Q. Is there any reason why you cannot give
`20 full and complete answers today?
`21 A. No.
`22 Q. You submitted declarations in connection
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` 1 THE WITNESS: I believe the three
` 2 documents are identical.
` 3 BY MR. BERMAN:
` 4 Q. Okay. Let's go to paragraph 7 of your
` 5 declaration. And you see, there is a summary of the
` 6 asserted grounds of obviousness for all three of the
` 7 IPRs?
` 8 MR. KRINSKY: Counsel, did you mean page
` 9 7?
`10 MR. BERMAN: Paragraph 7.
`11 MR. KRINSKY: Thank you.
`12 THE WITNESS: In paragraph 7, it says, "I
`13 understand that each proceeding Nalox-1 argues that
`14 the challenged claims of the Adapt patents are
`15 obvious over a combination of references, as set
`16 forth in the charts below."
`17 And the charts below mention asserted
`18 grounds of obviousness. Yes.
`19 BY MR. BERMAN:
`20 Q. And you see the main reference is the Wyse
`21 reference?
`22 A. Can you explain what you mean by "main"?
`Page 11
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` 1 Q. Well, under the asserted grounds of
` 2 obviousness, it says Wyse and HPE, Wyse, Djupesland,
` 3 and HPE, and so on and so forth. Do you see that?
` 4 A. I can see there's four references
` 5 mentioned in those tables.
` 6 Q. You're familiar with the Wyse patent, are
` 7 you not?
` 8 A. Yes.
` 9 Q. Can you turn to paragraph 22 on page 13.
`10 And the last sentence there says, "The Adapt patents
`11 disclose formulations, devices, and methods for nasal
`12 delivery of pharmaceutical compositions comprising
`13 naloxone." Do you see that?
`14 A. I see those words at the bottom of the
`15 page 13, yes.
`16 Q. And turning onto paragraph 27, here you
`17 recite three categories of claims covered by the
`18 Adapt patents. Do you see that?
`19 A. At the bottom of page 15, I note, "In
`20 general, the claims of the Adapt patents fall into
`21 three categories: (1) claims directed to
`22 pharmaceutical formulations for intranasal
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` 1 administration of an opioid antagonist - in
` 2 particular, naloxone; (2) claims directed to
` 3 single-use, pre-primed devices adapted for nasal
` 4 delivery of such pharmaceutical formulations; and,
` 5 (3) methods of treating opioid overdose and symptoms
` 6 thereof by nasally administering naloxone using
` 7 those" -- and it continues on the next page --
` 8 "devices and formulations." Yes.
` 9 Q. And in paragraph 28, you recite what the
`10 formulations in the Adapt patents generally comprise.
`11 Do you see that?
`12 A. Yes.
`13 Q. In your opinion, which of the features
`14 distinguish the Adapt patents from the prior art?
`15 MR. KRINSKY: Object to the form of the
`16 question. Vague.
`17 THE WITNESS: Can you explain what you
`18 mean by the word "distinct"?
`19 BY MR. BERMAN:
`20 Q. What features, in your opinion, are
`21 different between the Adapt patents and the prior
`22 art?
`
`Page 13
` 1 MR. KRINSKY: Object to the form of the
` 2 question. Vague.
` 3 THE WITNESS: Can you explain what you
` 4 mean by "features," please?
` 5 BY MR. BERMAN:
` 6 Q. Let's do it this way. I'm showing you
` 7 what's been previously marked as Exhibit Nalox 1007.
` 8 This is the Wyse '570 patent. Do you see that?
` 9 A. Yes, I see that.
`10 Q. You're familiar with this reference?
`11 You've seen it before?
`12 A. Yes, I believe I've seen it before.
`13 Q. So Wyse discloses intranasal
`14 administration of a composition to reverse opioid
`15 overdose, correct?
`16 A. Yes. That's correct.
`17 Q. And Wyse discloses an aqueous solution
`18 containing naloxone hydrochloride, correct?
`19 A. Yes. That's correct.
`20 Q. And Wyse discloses sodium chloride as an
`21 isotonicity agent, correct?
`22 A. Wyse uses sodium chloride, but I can't
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` 1 remember the exact word "isotonicity" being used.
` 2 Q. Wyse discloses the use of sodium chloride
` 3 to adjust the osmolality of the solution, does it
` 4 not?
` 5 A. Yes, that's correct.
` 6 Q. And using sodium chloride to adjust the
` 7 osmolality means that it is being used as an
` 8 isotonicity agent, right?
` 9 A. That's not my understanding of
`10 isotonicity.
`11 Q. What is your understanding?
`12 A. Isotonicity has an implication noting the
`13 same osmolarity as the body's osmolarity; therefore,
`14 it's a particular implication.
`15 Q. And what would that osmolarity be?
`16 MR. KRINSKY: Objection. Scope.
`17 THE WITNESS: It's debatable exactly what
`18 that osmolarity would be. But it would be equivalent
`19 to approximately 1.9 percent sodium chloride, which
`20 is approximately 600 milliosmol.
`21 BY MR. BERMAN:
`22 Q. So is it your opinion that Wyse does not
`Page 15
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` 1 yes.
` 2 Q. And one of the examples of an
` 3 antimicrobial preservative is benzalkonium chloride,
` 4 correct?
` 5 MR. KRINSKY: Object to the form of the
` 6 question.
` 7 THE WITNESS: Could you rephrase the
` 8 question, please?
` 9 BY MR. BERMAN:
`10 Q. Sure. Wyse discloses an example of an
`11 antimicrobial preservative being benzalkonium
`12 chloride, does it not?
`13 A. Wyse in his example 5 uses a number of
`14 compounds in a screening study to detect chemical
`15 stability of naloxone in the presence of those
`16 chemicals. One of those chemicals is benzalkonium
`17 chloride, BZK. And he finds that BZK causes chemical
`18 instability of naloxone and, therefore, he chooses to
`19 use another preservative other than BZK.
`20 Q. But you agree that Wyse does disclose --
`21 is it okay if I also call it BAC or BZK?
`22 A. I'm more familiar with BZK.
`
` 1 disclose sodium chloride as an isotonicity agent?
` 2 MR. KRINSKY: Objection. Scope.
` 3 THE WITNESS: I don't believe Wyse is
` 4 using sodium chloride in this document to make the
` 5 solution isotonic, no.
` 6 BY MR. BERMAN:
` 7 Q. But you agree that Wyse is using sodium
` 8 chloride to adjust the osmolality, correct?
` 9 A. Yes.
`10 Q. Wyse discloses EDTA, correct?
`11 A. Yes.
`12 Q. And Wyse discloses an antimicrobial
`13 preservative, correct?
`14 A. In the claims, Wyse lists a series of
`15 compounds, one of which is a paraben preservative,
`16 which I believe the POSA wouldn't understand being an
`17 antimicrobial preservative in the context of Wyse.
`18 Q. And Wyse discloses other antimicrobial
`19 preservatives in the patent, correct?
`20 A. Yes. There are other compounds in the
`21 Wyse patent that have the properties of
`22 antimicrobial -- of an antimicrobial preservative,
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` 1 Q. Okay. But you do agree that Wyse
` 2 discloses BZK as an example?
` 3 MR. KRINSKY: Objection. Asked and
` 4 answered.
` 5 THE WITNESS: In example 5 of Wyse, Wyse
` 6 tests a number excipients to understand if those
` 7 excipients cause naloxone degradation. One of those
` 8 excipients is BZK, and he finds that BZK effects
` 9 caused degradation of naloxone and concludes it is
`10 not suitable excipients included in the formulation
`11 and, therefore, uses benzyl alcohol.
`12 BY MR. BERMAN:
`13 Q. And in that example, the concentration is
`14 0.125 percent, correct?
`15 MR. KRINSKY: Object to the form of the
`16 question. Vague.
`17 THE WITNESS: Could you specify the
`18 example, please?
`19 BY MR. BERMAN:
`20 Q. The example 5 you were just referring to.
`21 A. In example 5 where Wyse tests the
`22 stability of naloxone in the presence of a number of
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`Page 18
` 1 excipients, he uses benzalkonium chloride, BZK, in
` 2 0.125 percent and finds it to cause instability.
` 3 Q. And the .125 percent doesn't indicate
` 4 whether that's weight to weight, volume to volume, or
` 5 weight to volume, does it?
` 6 A. No.
` 7 Q. Do you have an understanding of what the
` 8 ratio would be?
` 9 MR. KRINSKY: Object to the form of the
`10 question.
`11 THE WITNESS: Could you reask the
`12 question?
`13 BY MR. BERMAN:
`14 Q. Sure. Do you have an understanding as a
`15 person of ordinary skill in the art as to whether
`16 this .125 percent is typically expressed as weight to
`17 volume, volume to volume, or weight to weight?
`18 MR. KRINSKY: Objection. Outside the
`19 scope of the report.
`20 THE WITNESS: Can you reask the question,
`21 please?
`22 BY MR. BERMAN:
`
` 1 asking.
` 2 A. A person skilled in the art would take --
` 3 looking at the table 13 without any motive or any
` 4 further information, would read the value at face
` 5 value at 0.125 percent.
` 6 Q. But what would the units be? As a person
` 7 of ordinary skill in the art, how would a person of
` 8 ordinary skill in the art interpret what that
` 9 percentage was of?
`10 MR. KRINSKY: Objection. Outside the
`11 scope of the declaration.
`12 THE WITNESS: I suppose it would take the
`13 value to be not quite 0.125 percent, units percent.
`14 BY MR. BERMAN:
`15 Q. Units percent, is that weight to weight,
`16 weight to volume?
`17 A. I'm sorry. I can't answer that question
`18 without understanding the motive for any kind of
`19 conversion of the unit which is given there, which is
`20 percent.
`21 Q. The motive would be to understand how much
`22 benzalkonium chloride is in the example. That would
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` 1 Q. Sure. In the absence of any indication,
` 2 would a person of ordinary skill in the art typically
` 3 understand the concentration of .125 percent to be
` 4 weight to volume, weight to weight, or volume to
` 5 volume?
` 6 MR. KRINSKY: Objection. Assumes facts.
` 7 Outside the scope of the declaration.
` 8 THE WITNESS: I suppose I would need more
` 9 information to make any conclusion based on the
`10 volume of 0.125 percent what that might indicate.
`11 BY MR. BERMAN:
`12 Q. So as a person of ordinary skill in the
`13 art, do you have any opinion as to whether the
`14 benzalkonium chloride was included as a weight to
`15 weight, volume to volume, or weight to volume in this
`16 table?
`17 MR. KRINSKY: Objection. Outside the
`18 scope of the declaration.
`19 THE WITNESS: Could you explain the motive
`20 for the calculation?
`21 BY MR. BERMAN:
`22 Q. I'm not even sure I understand what you're
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` 1 be the motive. So how would a POSA come to an
` 2 understanding of how much benzalkonium chloride was
` 3 in that solution?
` 4 A. There is enough information in the example
` 5 by 0.125 percent to enable a POSA to understand how
` 6 much of that benzalkonium chloride is within the
` 7 example 5 listed in Wyse.
` 8 Q. Okay. So how much is in there?
` 9 A. 0.125 percent.
`10 Q. And so if you had 100 microliters of
`11 solution, how many milligrams of benzalkonium
`12 chloride would be in there?
`13 A. So you're asking me to presume that
`14 benzalkonium chloride would be provided as a solid?
`15 Q. Yes.
`16 A. So if you make the assumption of
`17 benzalkonium chloride being there as a solid and
`18 you've worked it out on a mass per volume liquid
`19 basis.
`20 Q. So in 100 microliters of solution, that
`21 would be .125 milligrams?
`22 A. I would need a pen and a piece of paper to
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` 1 perform that calculation, please.
` 2 Q. Sure.
` 3 MR. KRINSKY: I'd like to register an
` 4 objection, asking the witness to draw in the middle
` 5 of a deposition, and question the admissibility of
` 6 this if it is marked as an exhibit.
` 7 THE WITNESS: Can you reask the question,
` 8 please?
` 9 BY MR. BERMAN:
`10 Q. Sure. In 100 microliters of solution,
`11 that would be .125 milligrams of benzalkonium
`12 chloride, correct?
`13 A. I didn't perform this calculation in
`14 giving my opinion. And you're giving me a
`15 hypothetical situation which I'm not sure the context
`16 of, so I'm unable to answer that question.
`17 Q. You're unable to perform the calculation?
`18 MR. KRINSKY: Objection. Asked and
`19 answered. And outside the scope of this declaration.
`20 THE WITNESS: I'm able to perform the
`21 calculation. But I didn't perform that calculation
`22 based upon my opinions and the report which we're
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` 1 here discussing today.
` 2 BY MR. BERMAN:
` 3 Q. So are you refusing to answer the
` 4 question?
` 5 MR. KRINSKY: Objection. Argumentative.
` 6 And outside the scope of the declaration.
` 7 THE WITNESS: I didn't perform the
` 8 calculation in my opinion for this deposition, and
` 9 it's not the basis of any of my opinion that's based
`10 in my report.
`11 BY MR. BERMAN:
`12 Q. Let's go to paragraph 92 of your report.
`13 You say in 92, "Based on Wyse's teachings, the POSA
`14 would have been discouraged from using BZK, or BZK
`15 with EDTA, in a naloxone formulation."
`16 Do you see that?
`17 A. Yes.
`18 Q. And then a few lines down -- three lines
`19 down, it says, "The POSA would expect that even a
`20 much lower concentration of BZK would still cause
`21 stability problems, even if they manifested more
`22 slowly."
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` 1 Do you see that?
` 2 A. Yes.
` 3 Q. What's the basis for your opinion?
` 4 MR. KRINSKY: Objection. Vague.
` 5 THE WITNESS: Could you rephrase the
` 6 question, please?
` 7 BY MR. BERMAN:
` 8 Q. Sure. When you refer to "even a much
` 9 lower concentration of BZK," what are you referring
`10 to?
`11 A. Here, I'm referring to Wyse's stability
`12 study, which was conducted in example 5 of his
`13 patent. In that stability study, he used a number of
`14 different excipients, including BZK, to look at their
`15 effect on naloxone stability. The objective of the
`16 study is generally to look at the possibility of
`17 causing instability.
`18 The concentrations in such stability
`19 studies may not represent the final formulation.
`20 And, therefore, using a given concentration in that
`21 study would indicate that BZK caused instability and
`22 the POSA would have expected that BZK would have
`Page 25
` 1 caused instability even at the lower concentration
` 2 than that used in the Wyse example 5.
` 3 Q. And you already said that concentration in
` 4 this context -- well, let's ask. What do you mean by
` 5 concentration in this context?
` 6 MR. KRINSKY: Objection. Asked and
` 7 answered.
` 8 THE WITNESS: I mean a concentration of
` 9 BZK of less than 0.125 percent.
`10 BY MR. BERMAN:
`11 Q. And a POSA would be able to determine the
`12 concentration of BZK how?
`13 A. A POSA would take the value of 0.125
`14 percent at face value as it reads in the document at
`15 0.125 percent, which needs no further explanation.
`16 Q. As a weight-to-volume measure, correct?
`17 A. The POSA would read that value of 0.125
`18 percent as the value as it stands at 0.125.
`19 Q. But with what?
`20 A. That would depend on other factors.
`21 Q. Such as?
`22 A. Whether the materials supplied were solid
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` 1 goods.
` 2 Q. If it was a solid, what would that be?
` 3 A. In a hypothetical scenario, if
` 4 benzalkonium chloride was provided as a solid, then
` 5 the POSA would work out exactly how much solid they
` 6 need to put into a liquid to get 0.125 percent.
` 7 Q. So in 100 microliters, what would that
` 8 value be?
` 9 A. I didn't do that calculation in forming my
`10 opinion. It doesn't form the basis -- it is not in
`11 the document. So I am unsure right here now what
`12 that would be.
`13 Q. Wyse discloses the use of the Aptar
`14 unitdose to deliver 100 microliters of spray,
`15 correct?
`16 A. In the Wyse patent, it says in one aspect
`17 the nasal spray device is an Aptar unitdose device.
`18 Q. If you look at column 10, lines 53 through
`19 56, it says -- are you there?
`20 A. Yes.
`21 Q. It says, "In one aspect, the
`22 Aptar/Pfeiffer Unitdose delivery device may be used
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` 1 to deliver the disclosed compositions. In one
` 2 aspect, the nasal spray device delivers a volume of
` 3 about 100 microliters per spray."
` 4 Do you see that?
` 5 A. I see those two lines on the page, yes.
` 6 Q. So Wyse discloses the use of the Aptar
` 7 unitdose to deliver 100 microliters per spray,
` 8 correct?
` 9 A. The words on the page say, "In one aspect,
`10 the Aptar/Pfeiffer Unitdose delivery device may be
`11 used to deliver the disclosed compositions." Full
`12 stop. In the second sentence, it then says, "In one
`13 aspect, the nasal spray delivers a volume of about
`14 100 microliters per spray." Those are two separate
`15 sentences. I'm not sure if they're combined.
`16 Q. So as a POSA, you would read those two
`17 sentences independently? You would not have an
`18 understanding that they could be read as one unitary
`19 idea?
`20 MR. KRINSKY: Object to the form of the
`21 question.
`22 THE WITNESS: These are two sentences, and
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` 1 subject of both sentences is an aspect.
` 2 BY MR. BERMAN:
` 3 Q. That doesn't really answer my question.
` 4 So as a POSA, would you have an
` 5 understanding that those two sentences can be read as
` 6 one unitary idea?
` 7 MR. KRINSKY: Objection. Vague.
` 8 Objection. Asked and answered.
` 9 THE WITNESS: You have two separate
`10 sentences. The subject is in one aspect.
`11 BY MR. BERMAN:
`12 Q. So you wouldn't read them together as one
`13 unitary idea?
`14 A. I read them as two separate sentences, but
`15 the subject is one aspect.
`16 Q. Okay. Wyse discloses a concentration of
`17 about 5 to 15 micrograms per milliliter of naloxone,
`18 correct?
`19 A. In Wyse, it states, in one aspect, the
`20 disclosed compositions may comprise from about 5
`21 milligram per mL to 50 milligram per mL, and from
`22 about 10 milligram per mL to about 40 milligram per
`Page 29
` 1 mL, or from 50 milligram per mL to about 30 milligram
` 2 per mL, or from about 10 milligram per mL to 20
` 3 milligram per mL of an opioid antagonist.
` 4 The POSA would have read this list of
` 5 different concentrations and understood from that
` 6 that these concentrations were related to the
` 7 invention which Wyse is disclosing in his examples,
` 8 which is using a concentration of either 10 milligram
` 9 per mL or 20 milligram per mL, and the actual
`10 formulations that he tested which dose naloxone the
`11 dose of 2 milligrams or less.
`12 Q. If you look at Claim 1 of Wyse -- are you
`13 there? It says, "A nasal spray composition
`14 comprising" -- and the first letter A says -- "from
`15 about 5 milligram per milliliter to about 50
`16 milligram per milliliter of naloxone."
`17 Do you see that?
`18 A. I can see those words on the page. And
`19 the POSA would have understood from this
`20 concentration range that this would be combined with
`21 a series of other parameters reading the whole
`22 patent, including dosing volume, device, and other
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` 1 parameters which were equal, an invention which would
` 2 dose naloxone to concentration of 2 milligrams or
` 3 less, as Wyse actually did.
` 4 Q. So, in your opinion, the words from about
` 5 5 milligram per milliliter to about 50 milligram per
` 6 milliliter of naloxone in Claim 1 would be
` 7 interpreted by a POSA to be 2 milligrams or less?
` 8 MR. KRINSKY: Objection. Mischaracterizes
` 9 his testimony.
`10 THE WITNESS: Can you repeat the question,
`11 please?
`12 BY MR. BERMAN:
`13 Q. Sure. In your opinion, the words from
`14 about 5 milligrams per milliliter to about 50
`15 milligrams per milliliter of naloxone in Claim 1
`16 would be interpreted by a POSA to mean 2 milligrams
`17 or less?
`18 A. A POSA would read that statement of a
`19 concentration of 5 milligram per mL to 50 milligram
`20 per mL of naloxone and understood, in the context of
`21 the whole of Wyse, that this would mean a dose of 2
`22 milligram or less as Wyse actually did when he
`
` 1 BY MR. BERMAN:
` 2 Q. Hydrochloric acid can be used for the pH
` 3 adjustment?
` 4 MR. KRINSKY: Counsel, can you repeat the
` 5 question? I think it got cut off.
` 6 MR. BERMAN: Hydrochloric acid can be used
` 7 for the pH adjustment.
` 8 MR. KRINSKY: Object to the form of the
` 9 question. Vague.
`10 THE WITNESS: In what context?
`11 BY MR. BERMAN:
`12 Q. If you look at column 8, lines 1 through
`13 4. It says, "The compositions may further comprise
`14 sodium hydroxide or hydrochloric acid in an amount
`15 sufficient to adjust the pH to from about 3 to about
`16 5.5, or from about 3.5 to about 5, or about 4 plus or
`17 minus 0.5."
`18 Do you see that?
`19 A. Yes.
`20 Q. So Wyse discloses that hydrochloric acid
`21 can be used for pH adjustment, correct?
`22 A. Hydrochloric acid is used to adjust the
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` 1 combined it with the different spray volume and the
` 2 device that they actually used.
` 3 Q. So you're interpreting Claim 1 in the
` 4 context of Wyse's example formulation?
` 5 MR. KRINSKY: Objection. Asked and
` 6 answered. Objection. Mischaracterizes his
` 7 testimony.
` 8 THE WITNESS: A POSA would read the
` 9 statement in Claim 1 stating, from 5 milligram per mL
`10 to about 50 milligram per mL of naloxone, and they
`11 would understand that this is a concentration of
`12 naloxone and that concentration would relate to a
`13 dose of naloxone of less than 2 milligram when
`14 combined with the different parameters of the overall
`15 formulation and device as explained by Wyse and
`16 exemplified by him.
`17 BY MR. BERMAN:
`18 Q. Wyse discloses a pH of 3 to 5.5, correct?
`19 A. Yes.
`20 MR. KRINSKY: Counsel, it's been over an
`21 hour. I don't know if it's a good time for a break.
`22 MR. BERMAN: Just one more question.
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` 1 pH. But Wyse notes, the hydrochloric acid could be
` 2 used to adjust the pH, yes.
` 3 MR. BERMAN: We can take our break.
` 4 (Recess.)
` 5 BY MR. BERMAN:
` 6 Q. You've reviewed Dr. Williams'
` 7 declarations, correct?
` 8 A. Yes.
` 9 Q. I'm showing you what's been previously
`10 marked as Exhibit 2202. It is the second declaration
`11 of Kenneth A. Williams, M.D. If you go to paragraph
`12 33. Are you there?
`13 A. Yes.
`14 Q. And it says, "The POSA, seeking to develop
`15 a community-use naloxon