Page 1
`
` UNITED STATES PATENT AND TRADEMARK OFFICE
`--------------------
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
`--------------------
`NALOX-1 PHARMACEUTICALS, LLC
`Petitioner,
`v.
`OPIANT PHARMACEUTICALS, INC.,
`Patent Owner.
`--------------------
`Case No. IPR2019-000685
`Patent No. 9,211,253
`
`DEPOSITION OF MAUREEN DONOVAN, PH.D.
`Washington, D.C.
`Friday , November 22, 2019
`
`Reported by:
`MATTHEW GOLDSTEIN, RPR
`JOB NO. 172400
`
`TSG Reporting - Worldwide - 877-702-9580
`
`1 2
`
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 1
`
`

`

`Page 2
`
`Page 3
`
`A P P E A R A N C E S:
`
` ARENT FOX
` Attorneys for Plaintiffs
` 1717 K Street Northwest
` Washington, DC 20006
` BY: BRADFORD FRESE, ESQ.
` YELEE KIM, ESQ.
`
` WILLIAMS & CONNOLLY
` Attorneys for Defendants
` 725 Twelfth Street Northwest
` Washington, DC 20005
` BY: ANA REYES, ESQ.
` KEVIN HOAGLAND-HANSON, ESQ.
` JESSAMYN BERNIKER, ESQ.
`
`123
`
`45
`
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`November 22, 2019
`9:01 a.m.
`
` Deposition of MAUREEN DONOVAN, PH.D.,
`held at the offices of Arent Fox LLP 1717 K
`Street, NW, Washington, D.C. 20006, pursuant to
`notice, before Matthew Goldstein, a Registered
`Professional Reporter and Notary Public of the
`District of Columbia.
`
`Page 4
`
`Page 5
`
`A P P E A R A N C E S (CONT'D):
`
` GREEN GRIFFITH & BORG-BREEN LLP
` Attorneys for Plaintiffs
` 676 N Michigan Avenue
` Suite 3900
` Chicago, Illinois 60611
` 312.882.8000
` BY: JESSICA TYRUS MACKAY, ESQ.
`
` ALSO PRESENT:
` JOSHUA H. HARRIS - BURFORD
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`M. DONOVAN, PH.D.
` MS. REYES: Do you want to state
`appearances?
` Ana Reyes for the respondents.
` MS. BERNIKER: Jessamyn Berniker and
`Kevin Hoagland-Hanson, also for the respondents,
`patent owners.
` MS. MACKAY: Jessica Tyrus Mackay from
`Green Griffith & Borg-Breen, also on behalf of the
`patent owners.
` MR. FRESE: Bradford Frese from the firm
`of Arent Fox on behalf petitioner and the witness.
` MS. KIM: Yelee Kim from Arent Fox on
`behalf of petitioner.
` MR. HARRIS: Joshua Harris, Burford
`Capital, for Nalox-1.
`Whereupon,
` MAUREEN DONOVAN, PH.D.,
`being first duly sworn or affirmed to testify to
`the truth, the whole truth, and nothing but the
`truth, was examined and testified as follows:
` EXAMINATION BY COUNSEL FOR THE PATENT OWNER
`BY MS. REYES:
`Q. Ma'am, you did not attend medical
`school; correct?
`
`2 (Pages 2 to 5)
`TSG Reporting - Worldwide - 877-702-9580
`
`12345
`
`6
`
`789
`
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`12
`
`34
`
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 2
`
`

`

`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 6
`
`M. DONOVAN, PH.D.
`A. No, I didn't.
`Q. You're not a medical doctor; correct?
`A. No, I'm a registered pharmacist.
`Q. You're not a clinician?
`A. Could you define what you mean by
`"clinician."
`Q. You're not a medical doctor who treats
`patients in clinics; correct?
`A. That's correct.
`Q. You never treated a patient for any
`purpose; correct?
`A. Not in a medical sense, no.
`Q. You have never administered Naloxone to
`a patient; correct?
`A. No, I have not.
`Q. You have never observed the withdrawal
`effects of treating a patient with Naloxone;
`correct?
`A. Not directly, no.
`Q. You have never had to treat a patient
`suffering withdrawal effects from the
`administration of Naloxone; correct?
`A. Again, I'm not able to treat patients.
`Q. So you have never treated a patient
`
`Page 8
`
`M. DONOVAN, PH.D.
`Q. Your work is not focused on trying to
`develop FDA-approved products; correct?
`A.
`It's not focused on it, no.
`Q. Before preparing your report, you did
`not consult with a medical doctor concerning the
`administration of Naloxone; correct?
`A. That's correct.
`Q. Before preparing your report, you did
`not consult with a medical doctor concerning any
`of the opinions in your report; correct?
`A. That's correct.
`Q. You have reviewed the expert report of
`Güenther Hochhaus; correct?
`A.
`I have.
`Q. Güenther Hochhaus is not a medical
`doctor; correct?
`A.
`It's my understanding he's not.
`Q. He's not a clinician; correct?
`A.
`I expect he's not a clinician.
`Q. He does not indicate anywhere in his
`report that he consulted with a medical doctor in
`preparing his report; correct?
`A.
`I didn't see anything about that during
`my review.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 7
`
`M. DONOVAN, PH.D.
`suffering withdrawal effects from the
`administration of Naloxone; correct?
`A. No, I have not.
`Q. You're not a clinical pharmacologist;
`correct?
`A. Not by formal education, but I have
`certainly education in areas related to clinical
`pharmacology.
`Q. Do you consider yourself an expert
`clinical pharmacologist?
`A. I have an awareness of the field, but I
`would not say that I am an expert.
`Q. Since 1991, you have never worked for
`any pharmaceutical company; correct?
`A. I'd have to look at my CV to look at
`dates, but if I -- that's probably about right.
`Q. Okay. Your work is not focused on
`trying to develop FDA-approved products; correct?
`A.
`I participate in early-phase development
`in conjunction with other sponsors whose goals is
`to develop an FDA-approved product, but most of
`the time in my research, my goals are not to
`develop products that would be moved forward for
`FDA approval.
`
`Page 9
`
`M. DONOVAN, PH.D.
`Q. You're not an economist; correct?
`A.
`I'm not an economist.
`Q. You do not have any advanced training in
`economist [sic]; correct?
`A. No, I don't.
`Q. Before preparing your report, you did
`not consult with an economist concerning any of
`the opinions in your report; correct?
`A.
`I did not.
`Q. You agree that each pharmaceutical
`product is a formulation unique onto itself;
`correct?
` MR. FRESE: Objection; form.
` THE WITNESS: Well, each pharmaceutical
`product has -- may or may not have unique
`materials compared to other products. They may
`have unique properties, or they may have
`measurable properties that are quite similar to
`other products.
`Q. But each pharmaceutical product is a
`formulation unique onto itself; correct?
` MR. FRESE: Objection; cumulative.
` THE WITNESS: It may or may not be. It
`may actually be an identical formulation, and it
`
`3 (Pages 6 to 9)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 3
`
`

`

`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 10
`
`M. DONOVAN, PH.D.
`may actually have an identical manufacturing
`sequence to another pharmaceutical product.
`BY MS. REYES:
`Q. A pharmaceutical formulation can contain
`therapeutic and nontherapeutic ingredients;
`correct?
`A. Yes.
`Q. The formulation must be such that all
`components are compatible?
` MR. FRESE: Objection; form.
` THE WITNESS: The formulation and the
`product itself need to meet compendial quality
`standards and standards specified by the
`manufacturer and understood by the FDA.
`Q. They have to be compatible with each
`other?
`
`MR. FRESE: Objection; form.
`THE WITNESS: They have to meet
`compendial requirements for pharmaceutical
`quality.
`Q. The active therapeutic agents, the
`pharmaceutical ingredients and the packaging
`containers must all be compatible; correct?
` MR. FRESE: Objection to form.
`
`Page 12
`
`M. DONOVAN, PH.D.
`I've referred to it, certainly. I don't
`A.
`know that my students have, but I don't recall all
`of the references in all of their dissertations
`and papers we've written.
`Q. Have you looked at your website
`recently?
`A. To tell you the truth, not recently.
`Q.
`It's a reference book listed on your
`website. Would that surprise you?
`A. On my personal website?
`Q. On the Iowa website for your graduate
`school, the one that you participate in.
`A.
`I guess I'd like to see what you're
`actually talking about.
`Q. Sure. No problem.
`(Deposition Exhibit 2040, University of
`Iowa Printout, was marked for identification and
`attached to the transcript.)
` MR. FRESE: I object to this document.
`It's outside the scope of the deposition.
` MS. REYES: Okay. You do that.
` I'm going to introduce Exhibit 1, which
`is -- Exhibit 2040, which is a portion of the Iowa
`graduate school website.
`
`Page 11
`
`M. DONOVAN, PH.D.
` THE WITNESS: All of the things you've
`listed, the pharmaceutical product, the
`ingredients in that, the container, the packaging
`system, again, they must meet quality
`specifications as determined by the developer.
`And they have been evaluated by the FDA and
`approved for the characteristics of that
`particular product and its packaging.
`BY MS. REYES:
`Q. And that would include that they would
`have to be compatible with each other; correct?
`A. Not in an infinite sense.
`Q. What about in a finite sense?
`A. The quality standards define the finite
`sense --
`Q. Okay. Ma'am --
`A.
`-- by which materials are compatible or
`interact with one another or don't interact with
`one another.
`Q. Ansel's Pharmaceutical Dosage Forms and
`Drug Delivery is a textbook in your field?
`A.
`I'm familiar with that, yes.
`Q.
`It is a textbook in your field that you
`and your students refer to; right?
`
`Page 13
`
`M. DONOVAN, PH.D.
`BY MS. REYES:
`Q. Here you go.
`A. Actually, I don't think you correctly
`characterized where this came from.
`Q. Okay. You tell me where it comes from.
`A. This appears to me to be a hard copy of
`the web page -- of a web page that is curated by
`our University of Iowa libraries. And it also
`appears to be in the subsection that is likely the
`guides or the subset of materials that our
`university libraries have placed into sort of an
`easy access site based on subject matter.
`Q.
`If you turn to page 5 of this, ma'am, do
`you see that it says, "Compounding reference
`resources"?
`A. Yes.
`Q. And that one of the compounding
`reference resources is Pharmaceutical Dosage Forms
`and Drug Delivery, which is the Ansel's that I
`just cited to you?
`A.
`It doesn't indicate that it's the Ansel
`text. It just --
`Q. Was there a different text that's
`Pharmaceutical Dosage Forms and Drug Delivery,
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`4 (Pages 10 to 13)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 4
`
`

`

`Page 14
`
`M. DONOVAN, PH.D.
`
`ma'am?
`A. There actually may be.
`Q. But do you know, sitting here today?
`A.
`I'm not aware of exact titles of all the
`reference texts in the area.
`Q. You just don't know? You've been doing
`this for how long? How many decades have you been
`teaching?
` MR. FRESE: Objection to form.
`Q. How many decades have you been teaching
`in this area, ma'am?
`A.
`I've been teaching about 30 years.
`Q. Okay. In the 30 years that you've been
`teaching, you know that there's an Ansel's
`Pharmaceutical Dosage Forms and Drug Delivery
`textbook; correct?
`A.
`I believe the name actually for the
`series of textbooks that Ansel has edited actually
`may have changed during the time period of those
`texts, but I will -- I will choose to believe that
`you've given me the correct title.
`Q. Thank you.
`And this Pharmaceutical Dosage Forms and
`Drug Delivery, if we could turn to that, that is
`
`Page 16
`
`M. DONOVAN, PH.D.
`Q. And it's the ninth edition. And if you
`look at the -- if you look at this page right
`here, it's a 2011 date.
`A. Oh, so you've indicated the most recent
`copyright date as 2011.
`Q. And this would be prior art?
`A.
`It's my understanding it would be prior
`art.
`Q. Okay. And if we could --
`MS. REYES: Now it's back in the scope.
`Q. Now, if we could please turn to page 2.
`If you could go to the second column, third
`paragraph, it says, "Each particular
`pharmaceutical product."
` Do you see that?
`A. Yes.
`Q. So Ansel's, the prior art textbook
`referenced at the Iowa library, says, "Each
`particular pharmaceutical product is a formulation
`unique onto [sic] itself."
` Do you see that?
`A.
`I see that statement. However --
`Q. Okay. Ma'am, that's all I asked you.
`That's all I asked you, if you saw it.
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 15
`
`M. DONOVAN, PH.D.
`what your library tells people is a reference
`book.
` MR. FRESE: Is this marked as an
`exhibit?
` MS. REYES: Yeah, 2041.
` (Deposition Exhibit 2041, Ansel's
`Pharmaceutical Dosage Forms and Drug Delivery
`Systems 9th Edition, was marked for identification
`and attached to the transcript.)
` MR. FRESE: Okay. I'm going to object
`to this as outside the scope of the deposition and
`an improper excerpt of a larger reference.
` MS. REYES: Okay.
`BY MS. REYES:
`Q. Ma'am, Exhibit 2041 is an excerpt from
`Ansel's Pharmaceutical Dosage Forms and Drug
`Delivery Systems, the ninth edition.
` Do you see that?
`A. Well, I see the cover page that looks
`like the cover page that I've seen.
`Q. Okay.
`A. And certainly this title page indicates
`what I would expect from the title page of that
`textbook series.
`
`Page 17
`
`M. DONOVAN, PH.D.
`A. Okay.
`Q. And that is prior art that the POSA
`would be aware of; correct?
`A.
`I don't know. I haven't had a chance to
`review this. It's a single sentence that you've
`asked me about.
`Q. And I'm asking you --
`A.
`I see that sentence on the page.
`Q. Yes, the sentence is on the page.
`And the POSA would see that sentence on
`the page; correct?
`A. The POSA would see the sentence on the
`page --
`Q. Okay. Thank you.
`A.
`-- but the POSA would understand that
`they read single sentences in the context of the
`full document.
`Q. Sure. Fair enough.
`"In addition to the" -- and it goes on,
`"In addition to the active therapeutic
`ingredients, a pharmaceutical formulation contains
`a number of nontherapeutic or pharmaceutical
`ingredients."
` And I think you gave me that one.
`
`5 (Pages 14 to 17)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 5
`
`

`

`Page 18
`
`M. DONOVAN, PH.D.
` "It is through their use that a
`formulation achieves its unique composition and
`characteristic physical appearance."
` Do you see that?
`A.
`I see those words on the page.
`Q. Okay. Thank you.
`Now, "A preserved preparation must be
`shelf tested to determine its stability for the
`intended shelf life of the product"; correct?
` MR. FRESE: Objection; form.
` THE WITNESS: I don't know that I would
`agree with the wording to that.
`Q. What do you disagree about that wording?
`A.
`I would like you to repeat it back to
`me, please.
`Q. "A preserved preparation must be shelf
`tested to determine its stability for the intended
`life of product."
`A.
`I don't understand. And I don't use the
`phrase "shelf tested," so I would need to
`understand what the context of that term is.
`Q. Okay. Well, if you could turn to
`page 141 of Ansel's there. If you could go to the
`second column. At the end, the last sentence, "In
`
`Page 20
`
`M. DONOVAN, PH.D.
`entire document and --
`BY MS. REYES:
`Q.
`I'm not asking you about the entire
`document, ma'am. I'm asking you about the phrase
`"shelf tested."
` Are you telling me that in 30 years, you
`can't understand the words "shelf tested"?
` MR. FRESE: Objection to form.
` THE WITNESS: It's not a phrase that I
`use. I --
`Q. Okay. That's fine.
`A.
`I need to understand the phrase choice
`by the author to make sure that I understand and
`can use the term in the same way.
`Q. Got it. Thirty years of [sic] decades
`of experience, and you don't understand the phrase
`"shelf tested." Okay.
` "In a formulation, the active ingredient
`must be bioavailable to the patient throughout the
`expected shelf life of the preparation"; is that
`right?
`I heard about the first two words of
`A.
`that sentence. So if you would read it back
`slowly, I will try to concentrate and determine
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 19
`
`M. DONOVAN, PH.D.
`all instances, the preserved preparation must be
`biologically tested to determine its safety and
`efficacy."
` Do you see that?
` MR. FRESE: Objection to the fact that
`the document doesn't include the pages before 140.
` MS. REYES: That's fine.
`BY MS. REYES:
`Q. "In all instances, the preserved
`preparation must be biologically tested to
`determine its safety and efficacy."
` Do you see that?
`A.
`I see the words on the page.
`Q. "And shelf tested to determine its
`stability for the intended shelf life of the
`product."
`A.
`I see those words on this page.
`Q. With 30 -- decades of experience in the
`pharmaceutical field, you do not understand a
`textbook reference to "shelf tested" of
`pharmaceutical product; is that your testimony?
` MR. FRESE: Objection to form.
` THE WITNESS: After years of experience
`in the field, I learn and I know to read the
`
`Page 21
`
`M. DONOVAN, PH.D.
`whether I can agree with it.
`Q. "In a formulation, the active ingredient
`must be bioavailable to the patient throughout the
`expected shelf life of the preparation"; correct?
`A.
`It depends on the intended use of the
`preparation.
`Q.
`If the intended use of the preparation
`is to treat a patient, say, for example,
`potentially dying of an overdose, the active
`ingredient must be bioavailable to the patient
`throughout the expected shelf life of the
`preparation; correct?
` MR. FRESE: Objection; foundation.
` THE WITNESS: Well, again, it depends on
`the intended use of the product, how it's
`formulated, how it's delivered.
`Q.
`I gave you the intended use, to treat
`someone dying of an overdose.
` You would want the active ingredient in
`a product to treat someone dying of an overdose to
`be bioavailable to the patient throughout the
`expected shelf life of the preparation; correct?
` MR. FRESE: Objection; foundation.
` THE WITNESS: I would need to have -- or
`
`6 (Pages 18 to 21)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 6
`
`

`

`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 22
`
`M. DONOVAN, PH.D.
`I would need to have the terminology
`"bioavailable" defined for this proceeding.
`Because that terminology gets used in -- within
`the lay public and it has an inaccurate
`understanding by many.
`BY MS. REYES:
`Q. Okay. Let me make this simple, because
`I'm just an English major from a school in
`Kentucky.
` The active ingredient has to work;
`right? It has to work throughout the expected
`shelf life of the preparation. You're not going
`to -- you're really going to fight me on that?
` MR. FRESE: Objection; argumentative.
` THE WITNESS: The FDA has approved the
`product to meet the efficacy standards that were
`described by the developer and that are present in
`the label.
`Q. And that would include an expected shelf
`life for the product; right?
`A. The products themselves have a
`data-driven expiration date placed on each
`manufactured lot.
`Q. Yeah.
`
`Page 24
`
`M. DONOVAN, PH.D.
`Q. The efficacy standard includes that the
`active ingredient has to work; right?
` MR. FRESE: Objection to form.
` THE WITNESS: The product needs to
`meet -- or continue to meet the efficacy and
`product quality standards that were reviewed and
`approved by the FDA --
`Q. Which would include that the product --
`A.
`-- during its shelf life.
`Q. Why won't you just give me that the
`product has to work? I don't understand why this
`is hard. The product has to work; right?
` MR. FRESE: Objection; argumentative.
` THE WITNESS: Because I understand what
`the FDA approves and I understand what
`expectations for the term "work" might be, and
`they might be beyond what the FDA has approved.
`Q. You think the FDA approves drugs that
`don't work.
`A. That is not what I said.
`Q.
`I think that is exactly what you said,
`but we'll move on.
` Now, when you choose excipients, many
`considerations go into deciding which excipients
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 23
`
`M. DONOVAN, PH.D.
` And the active ingredient has to work
`throughout the -- through to the expiration date
`at least; right?
`A. Again, it has to meet the efficacy
`standards that were established during the
`evaluation of that product and presented to the
`FDA.
`Q. Okay. It has to work; right? I mean --
`A.
`It has --
`Q.
`-- are you going to tell me it doesn't
`have to work?
`A.
`It has to meet the efficacy standards
`that were presented to the FDA as the product
`efficacy, and they have to remain in effect under
`the range of effects --
`Q. Okay. So if I --
`A.
`-- through the --
`Q. So if I send --
`A.
`-- shelf life of the product.
`Q. So if I send a product to the FDA and I
`was like, hey, this product doesn't work for its
`entire shelf life, please approve it anyway, the
`FDA would be like, no, it has to work; right?
` MR. FRESE: Objection to form.
`
`Page 25
`
`M. DONOVAN, PH.D.
`to use in a formulation; correct?
` MR. FRESE: Objection to form and
`foundation.
` THE WITNESS: There are considerations
`about the excipients that are selected and
`included in formulations, yes.
`BY MS. REYES:
`Q. Okay. And one of the considerations is
`whether the preservative has adequate stability?
` MR. FRESE: Objection; form and
`foundation.
` THE WITNESS: Whether the preservative
`has adequate stability?
`Q. Uh-huh.
`A. So what type of stability are you
`referring to?
`Q. Okay. I'll withdraw that question.
`Another consideration is whether
`chemical decomposition -- another consideration is
`whether chemical decomposition will reduce the
`preservative's concentration; correct?
` MR. FRESE: Objection; form and
`foundation.
` THE WITNESS: All of the materials that
`
`7 (Pages 22 to 25)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 7
`
`

`

`Page 26
`
`M. DONOVAN, PH.D.
`are included in a formulation, especially those
`that have an actual prescribed function, need to
`maintain that functional ability within the
`product specifications as approved by the FDA and
`that meet the quality standards for that product.
`BY MS. REYES:
`Q. Okay. And another consideration is
`whether the preservative interferes with any of
`the other ingredients in the formulation; correct?
` MR. FRESE: Objection; foundation.
` THE WITNESS: That certainly might be
`something that a formulator would evaluate, but
`there are materials that interact with other
`materials in formulations that are currently
`approved by the FDA and meet quality standards and
`function as were approved for use in that product.
`Q. Okay. And another consideration is
`whether or not the formulation interferes with the
`effectiveness of the preservative; correct?
` MR. FRESE: Objection to form and
`foundation.
` MS. REYES: What exactly is your
`foundation --
` MR. FRESE: You haven't established that
`
`Page 28
`
`M. DONOVAN, PH.D.
`reference source, I'd like to see the reference
`source.
`Q. Let me read it to you again.
`Fair to say that it is essential for the
`research pharmacist to examine all formulative
`ingredients, as one affects the other, to ensure
`that each agent is free to do its job?
`A. Well, that would certainly be a method
`that I would teach to my students as they are
`starting as formulators. I certainly am aware of
`other more senior formulators or other individuals
`who may not always conduct formulation studies in
`that way. But at some point in time, if there are
`reasons to evaluate individual interactions, those
`can and should be done.
`Q. Okay. Another consideration is whether
`the preservative adversely affects the
`preparation's container or closure; correct?
`A. Again, the pharmaceutical quality
`standards give that all of the interactions
`between the container closure and the formulation
`components at least be understood.
`Q. Okay. And fair to say that the
`preservative must not interact with a container or
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 27
`
`M. DONOVAN, PH.D.
`this is a formulation that contains a
`preservative.
` MS. REYES: Okay.
`BY MS. REYES:
`Q. Sorry. Another consideration on whether
`or not to use a preservative in a formulation,
`which I think I started this line of questioning
`with, is whether or not the other ingredients in
`the formulation interfere with the effectiveness
`of the preservative; correct?
`A. Maintaining the effectiveness of the
`preservative is something that is considered and
`is tested and is -- has specifications built
`around it for the final evaluation of the product.
`Q. Okay. Is it fair to say that it is
`essential for the research pharmacist to examine
`all formulative ingredients, as one affects the
`other, to ensure that each agent is free to do its
`job?
` MR. FRESE: Objection; form.
` THE WITNESS: I think I'd like to hear
`that statement again.
`Q. Sure.
`A. And if you're reading it from a
`
`Page 29
`
`M. DONOVAN, PH.D.
`with an enclosure, such as a rubber or plastic cap
`or liner; correct?
`A. No, I don't believe that's correct.
`Q. Okay. Could you turn back to page 140
`of Ansel's, please. All right.
` Do you see the second column of
`page 140? If you start on the second full
`sentence, "In addition," do you see that?
`A. Second column, second sentence?
`Q. "In addition, the preservative must
`not" --
`A. On page 140, my second column, second
`sentence starts "It is essential."
`Q. Second full sentence.
`A. Okay.
`Q. "In addition" -- so this is Ansel's
`again.
`
`"In addition, the preservative must not
`interact with a container" --
` Do you see that?
`A.
`I see those words on this page.
`Q.
`-- "such as a metal ointment tube or a
`plastic medication bottle or with an enclosure,
`such as a rubber or plastic cap or liner."
`
`8 (Pages 26 to 29)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 8
`
`

`

`Page 30
`
`M. DONOVAN, PH.D.
` Do you see that?
`A.
`I see those words on the page, but --
`Q.
`I'm not -- that's all --
`A.
`-- I would need to understand --
`Q. Ma'am --
`A.
`-- and I may have other --
`Q. Ma'am -- ma'am -- ma'am --
`A.
`I need to be able to answer my
`question -- your question.
`Q. My question was -- my only question to
`you was do you see it. That was my only question
`to you. You either see it or you don't.
`A. No, there are further details I would
`like to include in my questions [sic], and I would
`like to be able to finish --
`Q. That's -- no, we're not doing this
`today. I'm going to ask you a yes-or-no question.
`My question is, do you see it?
` Do you see it or do you not see it?
`A.
`I see words on the page.
`Q. Thank you.
`And a POSA would see those words on the
`page; correct?
`A. And a POSA knows to read words on the
`
`Page 32
`
`M. DONOVAN, PH.D.
`
`order to --
`Q.
`I'm not asking you for the context of
`the document, ma'am. I'm just asking you a
`question.
` Do you agree or disagree with the
`proposition -- forget where it comes from -- that
`appropriate tests should be devised and conducted
`to prevent preservative interaction that leads to
`container decomposition and contamination?
` MR. FRESE: Objection to form.
` THE WITNESS: As a scientist, I know and
`choose not to determine whether I agree or
`disagree with any particular phrase or sentence if
`I don't understand the context in which that
`sentence or phrase appears.
`Q. Okay. Well, forget the context, ma'am.
`I'm just asking you a question.
` When you are testing a formulation, when
`you are testing whether or not a preservative
`works, is part of the testing whether or not the
`preservative decomposes the container in which it
`is in?
`A. You're asking me whether we're concerned
`whether the preservative is going to decompose the
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`24
`25
`
`Page 31
`
`M. DONOVAN, PH.D.
`page in context with the rest of the words in the
`document --
`Q. Fair enough.
`A.
`-- and interpret those words as they
`know -- based on their knowledge as a POSA.
`Q. Fair enough. Let's give you some more
`context.
` "Such an interaction could result in
`decomposition of the preservative or the container
`closure or both causing decomposition and
`contamination."
` Do you see that?
`A.
`I see those words on the page.
`Q. "Appropriate tests should be devised and
`conducted to prevent this type of preservative
`interaction."
` Do you see that?
`A.
`I see those words on the page.
`Q. Okay. Do you believe that appropriate
`tests should be devised and conducted to prevent
`preservative interaction that causes decomposition
`and contamination?
`A.
`I have no opinion on that right now. I
`would need to read the context of this document in
`
`Page 33
`
`M. DONOVAN, PH.D.
`
`container?
`Q. Yeah.
`A. Well, if there was a concern for that or
`an indication that that might occur, further
`testing to look at that would be conducted.
`Q. Okay. Thank you.
`Now, when you begin a nasal formulation
`product, do you first identify the potential dose
`of the formulation or the concentration of the
`active ingredient?
` MR. FRESE: Objection to form.
` THE WITNESS: During the formulation
`development process, it's typical that formulators
`either by -- either themselves or as a group of
`individuals identify what we typically now call
`the target product profile. And it has a number
`of the characteristics of the desired formulations
`identified. The formulator works towards meeting
`those identified goals.
` If during the development process it
`becomes apparent that a goal is unlikely to be
`met, then the target product profile is frequently
`redefined.
`Q. Okay. That's a really good answer, but
`
`9 (Pages 30 to 33)
`TSG Reporting - Worldwide - 877-702-9580
`
`Opiant Exhibit 2065
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 9
`
`

`

`Page 34
`
`M. DONOVAN, PH.D.
`not to my question.
` My question was, when you begin a nasal
`formulation project, when you're thinking about
`the formulation, do you first think about what
`dose, or do you first think about what
`concentration of the active ingredient you need in
`the formulation?
` MR. FRESE: Objection to form.
` THE WITNESS: It depends on what's known
`about the particular agent, and there isn't one or
`the other of those that's always determined first.
`Q. Okay. Well, what do you mean by "It
`depends on what is known about the [active
`ingredient]"?
`A.
`It depends what's known about the active
`ingredient and how the choice of administration is
`going to determine how we present it in a dosage
`form to a patient.
`Q. Okay. Let's say it's an intranasal
`formulation, intranasal preparation.
`A. Okay.
`Q. When you're thinking about an intranasal
`formulation for a drug, do you start with trying
`to figure out what the dose of the drug should be,
`
`Page 36
`
`M. DONOVAN, PH.D.
`target product profile, there would be things that
`would be -- additional things that would need to
`be known, things like the solubility of the drug
`compound itself, something