IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`ALCON RESEARCH, LTD.
`
`Plaintiff.
`
`v.
`
`WATSON LABORATORIES, INC.
`
`Defendant
`
`Civil Action No. 16-129 (LPS)(SRF)
`
`REPLY REPORT OF MAUREEN DONOVAN, Ph.D.
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`1
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`Opiant Exhibit 2053
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00685
`Page 1
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`TABLE OF CONTENTS
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`I.
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`Professional Background and Qualifications ..................................................................3
`
`II. Materials Considered .........................................................................................................4
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`III.
`
`IV.
`
`V.
`
`VI.
`
`VII.
`
`Legal Principles Relied Upon ............................................................................................5
`
`Summary Of Opinions .......................................................................................................6
`
`Bioavailability .....................................................................................................................7
`
`’295 Patent ........................................................................................................................12
`A.
`Ilevro® Does Not Embody the Claimed Inventions ..............................................12
`B.
`Unexpected results .................................................................................................13
`
`B.
`
`’337 Patent and ’398 Patent ............................................................................................43
`A.
`Ilevro® Does Not Embody the Claimed Inventions ..............................................43
`1.
`Particle Size ...............................................................................................43
`2.
`“Guar” and “Native Guar” .........................................................................46
`Unexpected Results ................................................................................................48
`1.
`Nepafenac Concentration ...........................................................................53
`2.
`Particle Size ...............................................................................................67
`3.
`Sodium CMC .............................................................................................95
`4.
`Guar-Borate Gelling in Addition to Carbomer ........................................107
`5.
`Conclusion ...............................................................................................138
`Failure of Others ..................................................................................................143
`
`C.
`
`VIII. Commercial Success .......................................................................................................147
`
`Long-felt need .................................................................................................................150
`
`IX.
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`
`
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`2
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`I, Maureen Donovan, Ph.D., submit this Reply Expert Report on behalf of Defendant
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`Watson Laboratories, Inc. (“Watson”) to set forth the basis for my opinion regarding the validity
`
`of the Asserted Claims of U.S. Patent No. 7,947,295 (“the ’295 patent”), U.S. Patent No.
`
`8,921,337 (“the ’337 patent”), and U.S. Patent No. 9,662,398 (“the ’398 patent”). I understand
`
`that Alcon Research, Ltd. (“Alcon” or “Plaintiff”) asserts that the products for which Watson
`
`seeks approval for in ANDA No. 208816 (“the Watson ANDA products”) infringe the Asserted
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`Claims of the ’295, ’337 and ’398 patents. This report responds to certain issues raised in the
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`reports of Alcon’s experts, including the expert reports of Dr. Bellantone (referred to as
`
`Bellantone Opening, Supplemental and Rebuttal Reports), Dr. Fuller (referred to as the Fuller
`
`Report), and Dr. Majumdar (referred to as the Majumdar Report). This report, together with my
`
`Expert Report on Invalidity dated November 11, 2017 (referred to as my Opening Report) set
`
`forth the basis for my opinions. I understand that, since my Opening Report, Alcon has reduced
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`the number of asserted claims in this matter, and now accuses Watson of infringing claims 13
`
`and 19 of the ’295 patent, claims 1-13 and 15 of the ’337 patent, and claims 1-14 and 16-32 of
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`the ’398 patent (“the Asserted Claims”).
`
`I.
`
`PROFESSIONAL BACKGROUND AND QUALIFICATIONS1
`
`1.
`
`I am an expert in the field of drug delivery systems, including ophthalmic
`
`compositions. I have worked in the field of drug delivery system development since 1982. My
`
`background and qualifications are set forth in my Opening Expert and Exhibit A attached
`
`thereto.
`
`
`1 Headings are used in this Report for convenience and organizational purposes only; I reserve
`the right to rely on any part of this Report for any purpose notwithstanding any section
`headings.
`
`
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`3
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`II. MATERIALS CONSIDERED
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`2.
`
`In reaching my conclusions and opinions set forth in this report, I have relied on
`
`my knowledge, education, training and experience, as well as the documents identified herein
`
`and the documents listed in Exhibit A. This Exhibit A is intended to supplement the Exhibit B
`
`listing materials considered and attached to my Opening Report. The documents that I cite to in
`
`this report comprise the information upon which I am specifically relying to support the opinions
`
`stated in this report. However, these documents are not the sole bases for my opinions, and I
`
`reserve the right to rely on additional documents and further information contained in Exhibit A
`
`as necessary. Further, citations to documents are exemplary; I reserve the right to rely on any
`
`portions of the documents cited in this Report, whether or not those portions are specifically
`
`cited.
`
`3.
`
`I have considered what I understand to be the opinions of Drs. Flanagan, Amiji,
`
`Hofmann and Tanna, in reaching my conclusions. I have also considered the reports of Drs.
`
`Bellantone, Majumdar, and Fuller, as well as materials cited in these reports. I reserve the right
`
`to rely on any portion of these reports and their materials considered or cited, whether or not
`
`those materials or portions are cited in this Report.
`
`4.
`
`My opinions are based on information currently known to me. Should additional
`
`information become available to me, I reserve the right to amend and/or supplement my
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`opinions. To the extent I am provided additional documents or information, including any
`
`reports, expert opinions, testimony, or any ruling or order by the Court, I may offer further
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`opinions. Examples of such additional information may include, for example: (i) any matters or
`
`information raised by Alcon or its experts; and (ii) documents presented by Alcon or its experts.
`
`Furthermore, I reserve the right to evaluate and testify about any issue raised by Alcon or its
`
`experts in submissions made after the date of this Report, or at trial. I also reserve the right to
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`4
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`supplement this Report in view of any further depositions taken in this case or document
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`production, including any which occur at, about or after the time of filing of this Report.
`
`III. LEGAL PRINCIPLES RELIED UPON
`
`5.
`
`As I explained in my Opening Report, I am not an expert in patent law. Counsel
`
`has informed me of the following legal standards, which I have applied in conducting my
`
`analysis and in reaching my conclusions. I understand that an issued patent is presumed to be
`
`valid, and a party challenging the validity of a patent claim must prove invalidity by clear and
`
`convincing evidence.
`
`6.
`
`To the extent a claim construction has been ordered by the Court (Dkt. 147),
`
`recommended in the Report & Recommendation (Dkt. 150), or agreed to by the parties, I have
`
`applied that specific definition, instead of the ordinary and customary meaning, when performing
`
`my analysis. For terms that have not been interpreted and recommended to the Court, I have
`
`applied what I consider to be the understanding of the person having ordinary skill in the art
`
`(POSA) as of the appropriate time period. I provide in my Opening Report the definition of the
`
`POSA and the appropriate time period.
`
`7.
`
`I have been informed by counsel that obviousness of a patent claim is determined
`
`by an objective standard considering:
`
`a) the scope and content of the prior art;
`
`b) the differences between the prior art and the claimed invention;
`
`c) the level of ordinary skill in the art; and
`
`d) any objective indicia of nonobviousness if present (including unexpected
`results, commercial success, long felt but unsolved needs, failure of others)
`
`8.
`
`I have considered whether a person of skill in the art would have one must have a
`
`motivation to combine or modify the prior art accompanied by a reasonable expectation of
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`5
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`achieving what is claimed in the patent-at-issue. The question of obviousness is determined
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`from the point of view of a hypothetical person having ordinary skill in the art as of the time the
`
`alleged invention was made. A person having ordinary skill in the art is to be understood as one
`
`who has knowledge of all the prior art. The person of skill in the art is not an automaton but
`
`instead is deemed to be a person of ordinary creativity.
`
`9.
`
`Alcon has set forth certain evidence or objective indicia as allegedly indicative
`
`non-obviousness; this includes the following so-called “secondary considerations:” (i) long-felt
`
`need, (ii) unexpected results, (iii) teaching away from the invention, (v) commercial success, and
`
`(vi) failure by others. I understand that there must exist a causal correlation or “nexus” between
`
`any alleged secondary consideration and the claimed inventions. In other words, the secondary
`
`consideration must be attributable to one or more claimed features and must be commensurate in
`
`scope with the claimed subject matter. When the claim scope is broad and encompasses many
`
`embodiments, evidence of secondary considerations for a single embodiment may not be
`
`sufficient to show that the secondary consideration is applicable to the entire group of
`
`embodiments included in the claim. If the secondary consideration is attributable to aspects of
`
`the claimed invention already in the prior art, then there is no nexus.
`
`10.
`
`I understand that in order to prove unexpected or surprising results, the patentee
`
`must show that the claimed invention exhibits these unexpected or surprising results over the
`
`closest prior art.
`
`IV.
`
`SUMMARY OF OPINIONS
`
`11.
`
`I have been retained to give my opinion as to the validity of the Asserted Claims.
`
`As part of my analysis, I have considered the state of the art from the perspective of the person
`
`having ordinary skill in the art (POSA) as of the appropriate time period. I provide in my
`
`
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`6
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`Opening Report the definition of the POSA and the appropriate time period. I have also
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`considered evidence that I am aware of regarding secondary considerations.
`
`12. My opinions regarding the invalidity of the Asserted Claims presented in my
`
`Opening Report have not changed. It is still my opinion that the Asserted Claims are invalid as
`
`obvious in view of the prior art.
`
`13.
`
`I reserve the right to review any reports and/or other materials submitted by
`
`Plaintiff subsequent to my report, any depositions of witnesses that have yet to take place, and
`
`any reports submitted by other persons on behalf of Watson or otherwise related to the
`
`information contained in this report and to supplement my report and/or provide additional
`
`testimony as necessary.
`
`V.
`
`BIOAVAILABILITY
`
`14.
`
`Bioavailability is a measure of the rate and extent of drug absorption.
`
`(Schoenwald & Flanagan, WAT_NEPA_00081256 at WAT_NEPA_00081262.) In order to
`
`determine the rate and extent of drug absorption, the drug concentration in a systemic fluid (such
`
`as blood or plasma) is measured over time. (Id.) In the case of ophthalmics, systemic fluids are
`
`not a relevant site for the measurement of drug concentrations that are obtained locally (in/at the
`
`eye) for local action compared to the systemic concentrations resulting from the drug that left the
`
`local region by being transferred to the bloodstream. (Id. at WAT_NEPA_00081267.) Thus, the
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`drug concentrations in the aqueous humor (or in other ophthalmic tissues) of rabbit eyes is used
`
`to calculate or compare ocular bioavailabilities. (Id.) A typical concentration-time curve
`
`following absorption is reproduced below:
`
`
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`7
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`(Id. at WAT_NEPA_00081262.) Several parameters from this curve are used to characterize the
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`absorption of a drug. For example, the maximum concentration (Cmax) is the concentration that
`
`is reached at a tmax, which describes the rate of absorption. The area under the curve, or AUC,
`
`describes the extent of the absorption. (Id.) As can be seen from the curve above, the area under
`
`the curve can be increased in multiple ways, e.g., by increasing the amount of absorbed drug or
`
`the length of time over which drug is able to be absorbed. Both of these effects will increase
`
`drug exposure. Comparison of AUC values is the primary measure of differences in
`
`bioavailability between ophthalmic products. (Id. at WAT_NEPA_00081267.) When this
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`comparison is made, AUC values are normalized by any difference in dosing according to the
`
`following:
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`
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`8
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`
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`(Schoenwald, R., Pharmacokinetic Principles of Dosing Adjustments: Understanding the Basics
`
`(2001) at p. 127) This takes into account the fact that differences in dose amount or in dosing
`
`frequency need to be accounted for when comparing AUC values since these changes will
`
`impact the amount of drug absorbed. Differences in the dosing regimen or drug concentration
`
`may result in differences in the AUC values obtained but these may not cause an increase in the
`
`relative bioavailability—which is a comparison of the extent of absorption following a single
`
`administration. Thus, AUC values can be compared directly only if there are no dosing
`
`differences between the products being compared.
`
`15.
`
`The biology of the eye itself places limitations on the bioavailability obtained
`
`from of ophthalmic dosage forms. For example, as the eye forms tears and the human subject
`
`blinks, the volume of the dose instilled onto the eye surface drains from the eye and further drug
`
`absorption is prevented. (See Opening Report, ¶¶ 120-22; Schoenwald & Flanagan,
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`WAT_NEPA_00081256 at WAT_NEPA_00081299.) The bioavailability of an ophthalmic
`
`suspension is influenced by the residence time of the instilled dose/volume because it impacts the
`
`length of time over which the drug is able to be absorbed. (Lee & Robinson, AILW00084094 at
`
`AILW00084095;
`
`see
`
`also Schoenwald & Flanagan, WAT_NEPA_00081256
`
`at
`
`WAT_NEPA_00081299-300 (“[P]olymers retard the drainage rate of the instilled drop from the
`
`eye and therefore promote a longer retention time of the drug on the cornea. As a result of the
`
`drug’s increased retention time on the cornea, ophthalmic bioavailability is increased whenever
`
`the drug is formulated in a polymeric vehicle as opposed to a vehicle without the addition of a
`
`polymer.”).) (See also Majumdar Report, ¶ 218.) Mechanisms like viscosity, elasticity,
`
`
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`9
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`bioadhesiveness and gelling that can lengthen retention time and contact with the cornea
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`therefore promote improvements in ocular bioavailability when drug absorption is consequently
`
`increased.
`
`16.
`
`For suspensions (including nepafenac ophthalmic compositions), a portion of the
`
`drug molecules exist as a saturated solution while the remaining portion of the drug is in
`
`particulate (solid/undissolved) form, suspended in that solution. (Majumdar Report, ¶ 398.)
`
`When the suspension is administered to the eye, the drug in solution is absorbed by the eye. (Id.)
`
`In order for the drug in particulate form to be absorbed into the eye, those drug molecules must
`
`first go into the solution. (Majumdar Report, ¶ 182.) As the drug in solution is absorbed into the
`
`eye, the drug load in particulate form dissolves and places drug molecules into the solution (this
`
`is referred to as dissolution), and the absorption into the eye continues, as long as some of the
`
`instilled dose is retained in the eye. (Lang et al., REMINGTON (2006), WAT_NEPA_00014439 at
`
`WAT_NEPA_00014447; Hecht, REMINGTON (1995), AILW00532120 at AILW00532125-126.)
`
`17.
`
`The drug particle size is “important because of its relationship to the dissolution
`
`rate as well as retention within
`
`the conjunctival sac.”
`
` (Schoenwald & Flanagan,
`
`WAT_NEPA_00081256 at WAT_NEPA_00081300.) Because the drug will “either dissolve or
`
`[be] expelled out of the eye at the lid margin or at the inner canthus,” the “time required for
`
`dissolution and corneal absorption must be less than the residence time of the drug in the
`
`conjunctival sac in order to take advantage of the retained particles.” (Id.; see also id. (“The
`
`saturated solution of a suspension likely provides the initial response, whereas, the retained
`
`particles maintain the response as particles dissolve and the drug is absorbed.”).) Thus,
`
`mechanisms that can increase dissolution rate, like particle size reduction, also promote
`
`improvements in ocular bioavailability. (WAT_NEPA_00081256 at WAT_NEPA_00081300
`
`
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`(the dissolution rate of drug particles “in relation to their residence time has the most significant
`
`effect on the rate and extent of ocular absorption”).)
`
`18.
`
` These methods of improving ophthalmic bioavailability are rarely considered in
`
`isolation. Instead, these mechanisms are generally considered to be complimentary. For
`
`example, mechanisms for promoting retention time often increase retention time more when
`
`deployed together. Similarly, to take full advantage of increased retention time, other techniques
`
`should be deployed to ensure sufficient drug in solution is available, at a rapid enough rate, to
`
`replace the drug being absorbed. Dr. Majumdar cites Hui & Robinson, who provide an early
`
`analysis of dissolution rate of drugs in ophthalmic suspensions. (Hui & Robinson., Effect of
`
`Particle Dissolution Rate on Ocular Drug Bioavailability, 75 J. PHARM. SCIS. 280, 286 (1986)
`
`(AILW00530810-817).) (Majumdar Report, ¶ 431.) Hui & Robinson state:
`
`In the preceding work, it has been shown that varying the concentration of
`suspension and particle size can lead to improved bioavailability. However, a
`sustained drug level cannot be achieved unless particle retention occurs. Hence, it
`is worthwhile to study the effects of varying drainage and tear turnover rate on the
`ocular bioavailability of a steroid suspension. By intuition, it is expected that
`factors which decrease the magnitude of the precorneal loss of drug particles will
`have a direct effect on aqueous humor drug concentrations and may increase the
`time to reach peak levels. Figure 6 shows that this expectation is correct…. Thus,
`these simulated profiles suggest that if the drug particles can be retained in the
`cul-de-sac, both Cmax and tmax increase, a larger fraction of drug would enter the
`aqueous humor.
`
`In the present study rank-order correlation is observed between increasing drug
`levels and increasing dosing concentration. A similar correlation is also found
`between increasing drug levels and decreasing particle size. However
`manipulation of dosing concentration or particle size cannot lead to a sustained
`concentration-time profile. Fortunately computer simulation suggests that if drug
`particles can be retained in the cul-de-sac, i.e., drug particles will not be drained
`away it is possible to achieve sustained drug level. Indeed, a sustained release
`drug delivery system has been developed for steroid suspension using a
`bioadhesive polymer.
`
`(Id. at AILW00530816-817 (emphasis added).) Thus, Hui & Robinson teach that, in order to
`
`improve the bioavailability of a suspension, the drug concentration/mass load should be
`
`
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`increased, the particle size decreased, and the retention time increased (e.g., by using a polymer).
`
`(See also Akomeah Tr., 69:8-70:1; 72:24-73:19.) These three mechanisms are complimentary.
`
`For example, increasing residence time increases the length of contact time with the cornea,
`
`which extends the time over which dissolution and absorption can occur. Reducing particle size
`
`increases dissolution rate, so that even more drug can be dissolved and absorbed over the same
`
`period of time—making an increased residence time potentially even more impactful. Then,
`
`increasing the concentration increases the drug load available for these other mechanisms.
`
`Throughout
`
`this Report, I discuss
`
`the relationship between drug concentration and
`
`bioavailability, between particle size and bioavailability, and between residence time and
`
`bioavailability.
`
`VI.
`
`’295 PATENT
`A.
`
`Ilevro® Does Not Embody the Claimed Inventions
`
`19.
`
`Dr. Bellantone opines that Ilevro® embodies the Asserted Claims of the ’295
`
`patent. See Bellantone Rebuttal Report, ¶¶ 218-238; see also Bellantone Opening Report;
`
`Bellantone Supplemental Report. I disagree.
`
`20.
`
`In support of his assertion that Ilevro® is an embodiment of claims 13 and 19 of
`
`the ’295 patent, Dr. Bellantone incorporates statements made regarding Ilevro® in his opening
`
`expert report, and further includes a table purportedly showing why Ilevro® meets each claim
`
`element. (Bellantone Rebuttal Report, ¶ 238.)
`
`21.
`
`Drs. Amiji and Flanagan responded to the statements made by Dr. Bellantone in
`
`his opening report. (See generally March 2, 2018 Amiji Report; see also March 2, 2018
`
`Flanagan Report ¶¶ 34-38.) In particular, Drs. Amiji and Flanagan explain that none of the
`
`following documents, cited by Dr. Bellantone, demonstrate that Ilevro® is an embodiment of
`
`claims 13 and 19 of the ’295 patent: AILW00528869–71, AILW00168368 at AILW00168376,
`
`
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`and AILW00350563–87 (collectively “Alcon Viscosity Study I”), and AILW00077975–76, and
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`AILW00166081–91 (collectively “Alcon Viscosity Study II”). There are several reasons that
`
`Drs. Amiji and Flanagan came to this conclusion: (1) Alcon Viscosity Studies I and II lack
`
`information about the conditions used in the studies, which are necessary to analyze the
`
`reliability of the studies; (2) Alcon Viscosity Study I was not tested on the Ilevro® product, but
`
`rather on a composition that did not contain nepafenac;2 (3) Alcon Viscosity Study II includes
`
`results for a product that does not meet the product specification for Ilevro®; and (4) Ilevro
`
`contains a guar-borate complex, and as such, it is not guar gum alone that contributes to the
`
`viscosity of the overall product. (See generally March 2, 2018 Amiji Report; see also March 2,
`
`2018 Flanagan Report ¶¶ 34-38.) I incorporate herein the analysis that Drs. Amiji and Flanagan
`
`performed as it applies to the Ilevro® product. To be clear, I incorporate the analysis of
`
`Viscosity Studies I and II of Drs. Amiji and Flanagan in their March 2, 2018 reports including all
`
`documents cited, as if set forth herein.
`
`22.
`
`Ilevro® therefore has not been shown to contain a viscosity enhancing amount of
`
`a combination of two polymers having a synergistic effect on the composition’s viscosity,
`
`wherein the viscosity of the composition is greater than 150% of the simple sum of two
`
`respective single polymer solutions containing only one of the two polymers.
`
`B.
`
`23.
`
`Unexpected results
`
`Dr. Majumdar argues that “the synergistic enhancement in viscosity that occurs
`
`when carboxyvinyl polymer and guar gum are mixed in an aqueous solution at the concentrations
`
`claimed in the ’295 patent would have been surprising to and unexpected by the POSA, in view
`
`of the closest prior art.” (Majumdar Report, ¶¶ 51, 391.) Dr. Fuller opines that “the POSA
`
`2 While Dr. Amiji makes statements regarding Alcon Viscosity Study I with respect to
`Watson’s ANDA Product, the same analysis applies with respect to Ilevro®, which also
`contains nepafenac.
`
`
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`would not have expected, and would have been surprised to discover, that a combination of
`
`carboxyvinyl polymer and guar gum at the concentrations claimed in the ’295 patent results in a
`
`composition suitable for ophthalmic administration that exhibits a synergistic increase in
`
`viscosity ‘greater than 150% of the simple sum of two respective single polymer solutions
`
`containing only one of the two polymers.’” (Fuller Report, ¶ 38.) I disagree.
`
`24.
`
`As I explain in my Opening Report, the claims of the ’295 Patent, including the
`
`claimed “synergistic effect,” would have been obvious to the POSA. (Opening Report, Section
`
`XI.) For at least those same reasons, the claimed synergistic effect would also not have been
`
`unexpected or surprising, and I incorporate by reference those portions of my Opening Report.
`
`25.
`
`As an initial matter, Dr. Majumdar and Dr. Fuller do not contend that the
`
`compositions claimed by the ’295 patent exhibit an unknown property or result, or that it was
`
`unexpected that guar gum and carboxyvinyl polymer have viscosity enhancing properties. Both
`
`of these polymers were known to increase viscosity as their respective concentrations in an
`
`ophthalmic composition were increased. (E.g., ’295 Patent, 1:19-39, 2:20-21.) Dr. Majumdar
`
`and Dr. Fuller also agree that the combining of polymers was known, in some circumstances, to
`
`produce a synergistic response. (Majumdar Report, ¶ 265; Fuller Report, ¶ 124.) The inventors
`
`also did not find synergy to be unexpected (See Asgharian Tr., 78:23-79:3; 79:6-81:9.) In an
`
`email dated July 22, 2010, inventor Malay Ghosh states that guar and carbopol combination in
`
`Nepafenac NF “exhibits a synergistic viscosity increase (common for certain polymers).”
`
`(AILW00097544 at AILW00097544.) However, Dr. Majumdar and Dr. Fuller contend that the
`
`extension of this known viscosity enhancement to a synergistic effect of 150% or more, for these
`
`particular polymers, was unexpected. The ’295 patent’s claims are directed to a particular,
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`made-up “synergistic effect,” which is when “the viscosity of the composition is greater than
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`150% of the simple sum of two respective single polymer solutions containing only one of the
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`two polymers.” (See, e.g., ’295 Patent, Claim 10; Majumdar Report, ¶ 247.) The degree of
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`synergy—150%—was arbitrarily chosen by the inventors (Chen Tr. at 38:20-40:14; 50:5-
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`52:25.), and Drs. Majumdar and Fuller do not appear to argue that the degree of synergy (i.e.,
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`150%) is what is unexpected.
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`26.
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`To be indicative of nonobviousness, Drs. Majumdar and Fuller must show that the
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`result is unexpected over the closest prior art and attributable to a novel aspect of the claims.
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`(See Majumdar Report, ¶ 51.) It is unclear what art Drs. Majumdar and Fuller considered to be
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`the “closest prior art.” However, the prior art discloses the combination of carbomer and guar
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`gum. For example, the ’609 patent and the ’138 patent teach that the disclosed guar-borate
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`ophthalmic compositions should be combined with a carbomer gelling system. (’609 Patent at
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`5:50-6:9, AILW00083368 at AILW00083374; ’138 Patent at 5:48-6:12, WAT_NEPA_00014531
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`at WAT_NEPA_00014537.) The ’928 patent describes ophthalmic compositions with two-
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`polymer systems, where the two polymers are selected from a group of eight excipients including
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`HP Guar and Carbopol®.
`
`
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`(’928 Patent at 3:3-10, WAT_NEPA_00077944 at
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`WAT_NEPA_00077967.) The ’171 patent includes an example formulation with 0.6%
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`Carbopol® and 0.2% guar gum. (’171 Patent at 13:1-13, WAT_NEPA_00077732 at
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`WAT_NEPA_00077741.)
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`27.
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`Because the prior art discloses the combination of guar gum with carbomer, and
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`even in the claimed total concentration, Drs. Majumdar and Fuller appear to be claiming that the
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`mere measurement of the viscosity of these already known combinations and the synergy
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`evidenced by those measurements is the unexpected result. The mere fact that a property of a
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`compound disclosed in the prior art was not also described in the prior art cannot make that
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`otherwise known or obvious composition nonobvious. The measuring of viscosity was
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`commonplace for the POSA, and the measuring (or not) of a property does not change whether
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`or not the composition has that property. There is nothing indicative of nonobviousness about
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`measuring the viscosity of a combination of polymers that is disclosed in the prior art and finding
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`it to be synergistic.
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`28.
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`Drs. Majumdar and Fuller opine that the complexity of polymers teaches away
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`from the claimed polymer combination. (E.g., Fuller Report, ¶ 38; Majumdar Report, ¶ 48.) I
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`disagree. The claimed combination was already found in the prior art, and there are numerous
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`examples in the prior art of ophthalmics with polymer combinations.
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`29.
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`For instance, both the ’609 and the ’138 patents3 expressly describe ophthalmic
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`compositions combining guar gum with other polymers, including carbomer. Although the
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`primary focus of these patents are guar-borate ophthalmic compositions, these patents
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`nonetheless expressly describe combining guar gum with another gelling system and, in
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`particular, with carbomer or HPMC.
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` (’609 Patent at 5:50-6:9, AILW00083368 at
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`AILW00083374; ’138 Patent at 5:48-6:12, WAT_NEPA_00014531 at WAT_NEPA_00014537.)
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`The ’609 and the ’138 patents’ guar-borate system combined with carbomer certainly could be
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`included in the Asserted Claims4 because boric acid is not excluded from the claimed
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`compositions. (Bellantone Rebuttal Report, Section VIII.A & VIII.B.) There is nothing in the
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`3 Several of the prior art references discussed in this Report are prior art against more than one
`of the patents-in-suit. Whether I present my analyses of those references under the heading
`of one patent or the other, I reserve the right to rely on those analyses with respect to any of
`the patents.
`
` I say “could” only to recognize that the claims’ preservative, polymer concentration,
`ophthalmic drug, and synergy elements would also need to be met. But the ’609 and ’138
`patents, and other prior art, disclose and render obvious these limitations as well.
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` 4
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`’609 and the ’138 patents to discourage, discredit or otherwise teach away from combining guar
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`gum (or guar-borate) with carbomer.
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`30.
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`Dr. Fuller’s statement that “the POSA would have doubted that these gelling
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`systems are even compatible …” is wholly unsupported. (Fuller Report ¶ 127.) Lacking any
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`overt or even implied skepticism in these patents, the POSA would have had no reason to doubt
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`combining guar gum with carbomer would have been feasible, since