Case 1:14-cv-07094-JBS-JS Document 79-1 Filed 11/16/15 Page 1 of 25 PageID: 741
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`
`BAXTER HEALTHCARE CORPORATION,
`BAXTER INTERNATIONAL INC., and BAXTER
`HEALTHCARE S.A.,
`Plaintiffs,
`v.
`
`MYLAN LABORATORIES LTD. and
`MYLAN PHARMACEUTICALS INC.,
`
`Defendants.
`
`BAXTER HEALTHCARE CORPORATION,
`BAXTER INTERNATIONAL INC., and BAXTER
`HEALTHCARE S.A.,
`Plaintiffs,
`v.
`
`C.A. No. 1:14-cv-07094-JBS-JS
`
`SAGENT PHARMACEUTICALS INC.,
`Defendant.
`
`C.A. No. 1:15-cv-01684-JBS-JS
`
`EXPERT DECLARATION OF STEVE J. BANNISTER, Ph.D.
`REGARDING CLAIM CONSTRUCTION
`
`MYLAN V. BAXTER
`IPR2016-00217
`EXHIBIT 2001
`
`

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`TABLE OF CONTENTS
`TABLE OF CONTENTS
`
`
`
`
`I. Introduction ................................................................................................................................. 2
`I. Introduction ............................................................................................................................... .. 2
`II. Expert Qualifications.................................................................................................................. 2
`11. Expert Qualifications ................................................................................................................ .. 2
`A. Educational Background ........................................................................................................ 2
`A. Educational Background ...................................................................................................... .. 2
`B. Professional Experience ......................................................................................................... 2
`B. Professional Experience ....................................................................................................... .. 2
`C. Compensation ......................................................................................................................... 5
`C. Compensation ....................................................................................................................... .. 5
`D. Testimony in Past Four Years ................................................................................................ 5
`D. Testimony in Past Four Years .............................................................................................. .. 5
`E. Review and Use of Documents and Other Materials ............................................................. 6
`E. Review and Use of Documents and Other Materials ........................................................... .. 6
`III. Applicable legal principles ....................................................................................................... 6
`III. Applicable legal principles ..................................................................................................... .. 6
`IV. Background of the patented Technology .................................................................................. 7
`IV. Background of the patented Technology ................................................................................ .. 7
`A. Patents-in-Suit ........................................................................................................................ 7
`A. Patents-in-Suit ...................................................................................................................... .. 7
`B. Representative Asserted Claims ........................................................................................... 12
`B. Representative Asserted Claims ......................................................................................... .. 12
`V. Person of Ordinary Skill in the Art .......................................................................................... 15
`V. Person of Ordinary Skill in the Art ........................................................................................ .. 15
`VI. Meaning of “sterile” ............................................................................................................... 15
`VI. Meaning of “sterile” ............................................................................................................. .. 15
`VII. Meaning of “aqueous” ........................................................................................................... 20
`VII. Meaning of “aqueous” ......................................................................................................... .. 20
`
`- i -
`
`

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`I.
`
`INTRODUCTION
`
`1.
`
`I have been asked by Dechert LLP, counsel for Plaintiffs Baxter Healthcare
`
`Corporation, Baxter International Inc., and Baxter Healthcare S.A. (collectively, “Plaintiffs” or
`
`“Baxter”), to provide my opinion as an expert in conjunction with the construction of the terms
`
`“sterile” and “aqueous” as those terms are used in the asserted claims of U.S. Patent Nos.
`
`6,310,094 (“the ‘094 patent”) (Ex. 1)1 and 6,528,540 (“the ‘540 patent”) (Ex. 2) (collectively,
`
`“the patents-in-suit”). This report reflects my opinions as an expert regarding the meaning of
`
`those terms in the asserted claims of the patents-in-suit to a person of ordinary skill in the art at
`
`the time of the claimed inventions. I anticipate providing testimony, if called to do so, at a
`
`hearing regarding my opinions discussed herein.
`
`II.
`
`EXPERT QUALIFICATIONS
`
`A.
`
`2.
`
`EDUCATIONAL BACKGROUND
`
`I received a B.S. degree in Pharmacy from the University of Georgia in 1975, an
`
`M.S. degree in Pharmaceutical Chemistry from the University of Kansas in 1977, and a Ph.D. in
`
`Pharmaceutical Chemistry from the University of Kansas in 1983.
`
`B.
`
`3.
`
`PROFESSIONAL EXPERIENCE
`
`I have over 30 years of experience in the field of pharmaceutical-development,
`
`applying the fundamentals of chemistry to the design, development, and characterization of drug
`
`delivery systems and medical devices.
`
`4.
`
`I am currently a founder and managing member of Arbor Therapeutics, L.L.C.,
`
`and of Cloaked Therapeutics, L.L.C (formerly known as Follaine Pharmaceuticals, L.L.C.),
`
`working on intravenous nanoparticle formulation design and optimization in the development of
`
`1 References in the Declaration to numbered exhibits are meant to refer to the corresponding
`numbered exhibit that I understand is being attached to the Declaration of Brian M. Goldberg
`that is being filed together herewith.
`
`
`
`– 2 –
`
`

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`drug delivery technology capable of intracellular delivery to tumor cells while sparing healthy
`
`tissue.
`
`5.
`
`I am also the president and principal consultant of Hightower Pharmaceutical
`
`Services Corp, through which I manage my technical product-development consulting practice.
`
`6.
`
`From 2004-2008, I worked at Xcelience®, LLC (formerly MDS Pharma
`
`Services), a product-development contract research organization in Tampa, Florida. I was the
`
`Scientific Director and Principal Consultant for Xcelience®, and was responsible for the
`
`consulting business practice within the organization. I was also the Director of Analytical and
`
`Preformulation Services, and was accountable for the scientific integrity, technical capability,
`
`regulatory compliance, and productivity of the diversified analytical services group. I directed a
`
`team of 20 scientists and was responsible for all analytical services supporting formulation
`
`development, GMP manufacturing, and product stability studies.
`
`7.
`
`From 1998-2003, I worked at NaPro BioTherapeutics, Inc. in Boulder, Colorado.
`
`I was the Director of New Product Development from 1998-1999, and was the senior Director of
`
`Product and Analytical Development from 1999-2000. In that role I formed a new department
`
`which combined internal resources and new hires and was responsible for the development of
`
`sterile and oral formulated products and for providing central analytical services to drug research
`
`and development, process development, and manufacturing technical services. From 2000-2003,
`
`I was the Vice President of Drug Development and corporate executive officer in charge of drug
`
`and product research and development, process development, and manufacturing technical
`
`services. I was also a member of the corporate technical due diligence team and was an in-house
`
`technical expert in the crafting and review of formulation patent defense strategies.
`
`
`
`– 3 –
`
`

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`8.
`
`From 1995-1998, I worked at Ivax Corporation in Miami, Florida. From 1995-
`
`1997, I was the Section Head, then Associate Director of Analytical Research and Development,
`
`where I developed methods to characterize new drug and generic immediate- and extended-
`
`release oral solid dosage forms and collaborated in product optimization. From 1997-1998 I was
`
`the Director of Preformulation Development exploring the influence of drug and excipient
`
`physical and chemical properties on formulation design and stability.
`
`9.
`
`From 1979-1995, I worked at various pharmaceutical companies, including
`
`Sandoz Research Institute, Fisons Pharmaceuticals, Beecham Laboratories, Key
`
`Pharmaceuticals, and at Technicon Instruments Corporation, as a scientist involved in the
`
`research, development, and analysis of drugs and drug products.
`
`10.
`
`I am also currently serving as a mentor to the Tampa Bay Technology Incubator
`
`at the University of South Florida.
`
`11.
`
`From 2000-2004, I had academic appointments at the University of Colorado
`
`Health Sciences Center in Denver, Colorado. During that time, I was an advisor in the
`
`Technology Transfer Office, providing technical and industry professional experience to
`
`multidisciplinary teams guiding commercialization of intellectual property developed by faculty
`
`at the University. I also worked as a collaborating scientist within the School of Medicine,
`
`Department of Clinical Pharmacology, where I supervised postdoctoral research associates in the
`
`development and validation of chiral bioanalytical methods for drugs and metabolites in the
`
`investigation of chirality in drug metabolism. I also was an adjunct faculty member at the
`
`School of Pharmacy, Department of Pharmaceutical Sciences, where I lectured in special topic
`
`graduate courses and served as a dissertation committee member.
`
`
`
`– 4 –
`
`

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`12.
`
`In the above capacities, I have applied the training that I received in Pharmacy
`
`and in Pharmaceutical Chemistry to the development and investigation of drug delivery by
`
`parenteral, oral, topical, transdermal, transbuccal, nasal, and inhalation routes as a scientist and
`
`as a scientific leader and consultant. The technical challenges addressed in my work have
`
`included the biocompatibility of aqueous, semi-aqueous, and non-aqueous products which are
`
`injected, inhaled, or applied to mucous membranes; the chemical stability of drugs in aqueous
`
`and non-aqueous products and in biological fluids; and the specification of manufacturing
`
`processes for heat-labile sterile dosage forms.
`
`13. My full curriculum vitae, which includes a list of my publications and academic
`
`appointments, is attached as Attachment A to this report.
`
`C.
`
`14.
`
`COMPENSATION
`
`I am being compensated for my work in connection with the current proceedings
`
`at my customary rates of $300 per hour for consulting work and $450 per hour for time spent
`
`preparing for and providing testimony by deposition or at a trial or hearing. My compensation is
`
`not dependent upon the opinions rendered or the outcome of this matter.
`
`TESTIMONY IN PAST FOUR YEARS
`
`In the past four years, other than in this case, I have testified in the following
`
`D.
`
`15.
`
`matters:
`
`a. Asahi Kasei Pharma Corp. v. Actelion Ltd., Civ. No. 478533, in the
`Superior Court of San Mateo County, California (by deposition);
`
`b. U.S.A. v. Scott C. Hood, C.A. No. 3:11-cr-00130, in the United States
`District Court for the Middle District of Florida (court hearing);
`
`c. Georgia v. Serena P. Burkard, No. 13-cr-0479, in the Superior Court of
`Cherokee County, Georgia(court hearing);
`
`
`
`– 5 –
`
`

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`d. State of Florida v. Ryan Wilder, Case No. 10 CF 2012 000843, in the
`Circuit Court for the Fourth Judicial Circuit, in and for Clay County,
`Florida(court hearing); and
`
`e. Baxter Healthcare Corp., et al., v. HQ Specialty Pharma Corp., et al., 13-
`cv-6228, United States District Court, District of New Jersey (by
`deposition).
`
`E.
`
`16.
`
`REVIEW AND USE OF DOCUMENTS AND OTHER MATERIALS
`
`In formulating my opinions and preparing this report, I have reviewed and/or
`
`relied upon the documents listed in Attachment B attached to this report.
`
`17.
`
`I have also considered the other documents that are referenced or cited in this
`
`report. I reserve the right to supplement this report to address any further information obtained
`
`as additional documents may be produced or become publicly available. Although I cite to a
`
`number of documents throughout the body of this report to support my opinions, those citations
`
`are not necessarily meant to convey that the documents cited constitute the primary basis for the
`
`opinion, and my citation to a particular document to illustrate a particular principle is not meant
`
`to signify that the document is the only source of my understanding.
`
`III. APPLICABLE LEGAL PRINCIPLES
`
`18.
`
`I will not offer opinions of law, since I am not an attorney. However, I have been
`
`informed of several principles concerning claim construction, and I used those principles in
`
`arriving at my opinions.
`
`19.
`
`I understand that a claim term is to be construed in accordance with what a person
`
`of ordinary skill in the art would understand it to mean as it used in the patent claims at issue. I
`
`further understand that the person of ordinary skill in the art is deemed to read the claim term not
`
`only in the context of the particular claim in which the term appears, but also in the context of
`
`the entire patent, including the specification.
`
`
`
`– 6 –
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`

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`20.
`
`I also understand that the most significant evidence to be considered in seeking to
`
`understand the meaning of a claim term is what is referred to as the “intrinsic” evidence, which I
`
`understand includes the patent itself (including both the claims and the patent specification), as
`
`well as the prosecution history of the patent. I understand that evidence considered to be
`
`“extrinsic” to the patent, such as dictionaries and scientific articles or treatises, may also be
`
`considered, but that such extrinsic evidence is generally considered to be less significant than the
`
`intrinsic evidence.
`
`21.
`
`I further understand that a patent applicant may use a claim term in a manner that
`
`differs from the ordinary meaning of that term to a person of ordinary skill in the art. I
`
`understand that in order to do so, the applicant must set out the different meaning, for example in
`
`the patent specification or the prosecution history, in a manner that is sufficient to give one of
`
`ordinary skill in the art notice of the change from the ordinary meaning.
`
`IV. BACKGROUND OF THE PATENTED TECHNOLOGY
`
`A.
`
`22.
`
`PATENTS-IN-SUIT
`
`I understand that the ‘094 patent, titled “READY-TO-USE ESMOLOL
`
`SOLUTION,” issued from U.S. Patent Application No. 09/759,547, filed on January 12, 2001,
`
`and that the ‘540 patent, titled “ESMOLOL SOLUTION,” issued from U.S. Patent Application
`
`No. 10/016,260, filed on October 30, 2001. I understand that the ‘540 patent is a continuation-
`
`in-part of the ‘094 patent.2
`
`23.
`
`Broadly speaking, the patents-in-suit are directed to aqueous pharmaceutical
`
`compositions that are useful for the treatment of certain cardiac conditions and include, among
`
`
`2 I understand that a “continuation-in-part” application is one that includes some or all of the
`disclosures set forth in the specification of an earlier-filed patent application, and also includes
`additional disclosures that were not included in that earlier application.
`
`
`
`– 7 –
`
`

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`other things, specific amounts of esmolol hydrochloride, a buffering agent, and an osmotic-
`
`adjusting agent. As is described in more detail in the patents, esmolol hydrochloride “is a short-
`
`acting beta-blocker used for treatment or prophylaxis of cardiac disorders.” ‘094 patent at 1:13-
`
`15. 3 For example, I understand that the patents-in-suit arose out of research and development
`
`work performed in connection with the BREVIBLOC® Premixed Injection products made and
`
`sold by Baxter, which are indicated, among other things, for the rapid control of the heart rate in
`
`patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent
`
`circumstances where short term control of the heart rate with a short-acting agent is desirable.4
`
`24.
`
`The patents-in-suit explain that esmolol hydrochloride has a short duration of
`
`action due to the presence of an ester group.5 ‘094 patent at 1:24-28; ‘540 patent at 1:21-28.
`
`The patents also explain that this ester group causes instability of esmolol hydrochloride in the
`
`presence of water due to the ester’s susceptibility to acid/base hydrolysis.6 ‘094 patent at 1:30-
`
`35; ‘540 patent at 1:28-30. The extent and rate of that hydrolysis (break down) was known to be
`
`both temperature-dependent (the rate of hydrolysis increases as the temperature increases) and
`
`pH-sensitive.
`
`25.
`
`This instability contributes to significant challenges in the design and
`
`development of a pharmaceutical product that can be manufactured, stored, delivered, and used
`
`conveniently, safely, and effectively in the clinic. The patents-in-suit explain that “[i]n the past,
`
`3 Citations to the patents refer to the column and line number where the cited disclosure is
`found—e.g., “at 1:13-15” refers to column 1, lines 13-15 in the patent.
`4 See, e.g., BREVIBLOC® (Esmolol Hydrochloride) Injection; Prescribing Information;
`Baxter Healthcare Corporation; http://www.brevibloc.com/assets/pdfs/
`Brevibloc_PI_2013_05_14.pdf; accessed September 2, 2014.
`5 An “ester group” is an organic chemistry term that denotes a specific chemical structure
`composed of a number of carbon and oxygen atoms that links two other structures.
`6 Hydrolysis is a chemical process in which a compound degrades (i.e., breaks down) in the
`presence of water.
`
`
`
`– 8 –
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`the rate of degradation of esmolol hydrochloride has been reduced by the use of acetate as a
`
`buffer, maintaining the pH as close to 5.0 as possible, minimizing the concentration of esmolol in
`
`the solution, and minimizing the concentration of buffer used.” ‘094 patent at 1:35-39; ‘540
`
`patent at 1:33-37.
`
`26.
`
`The patents-in-suit note that prior art formulations have provided adequate storage
`
`stability but explain that other significant problems are associated with those products. For
`
`instance, the patents explain that “[p]rior art formulations maintain a reasonably long shelf-life,
`
`however, they suffer from severe degradation upon autoclaving. As a result, prior art
`
`formulations are prepared aseptically.” ‘540 patent at 1:37-41. See also ‘094 patent at 1:40-43.
`
`27.
`
`Autoclaving is a form of terminal sterilization that subjects the product to heat
`
`and steam for a period of time sufficient to kill any micro-organisms in the product. “Terminal”
`
`sterilization (such as by autoclaving) involves sterilizing the final product after the composition
`
`has been made and put into its packaging, in contrast to a process known as aseptic filling, which
`
`involves making and packaging the product in a sterile environment. As is noted in the patents-
`
`in-suit, terminal sterilization is generally preferred over aseptic filling because it reduces the risk
`
`of biological contamination and ensures the safety of the finished product. See, e.g., ‘094 patent
`
`at 1:44-47, 2:5-14.
`
`28.
`
`The patents-in-suit further explain that some prior art formulations were packaged
`
`in concentrated form and had to be diluted prior to administration, and that there is the possibility
`
`of errors during the requisite dilution of those concentrated products: “In addition, the
`
`formulation disclosed in U.S. Pat. No. 4,857,552 is a small volume injectable formulation. For
`
`the purposes of intravenous infusion, the disclosed formulation must be further diluted in
`
`
`
`– 9 –
`
`

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`pharmaceutically acceptable diluents prior to use. This creates a potential opportunity for
`
`calculation or dilution error in a hospital setting.” ‘094 patent at 1:48-53.
`
`29.
`
`The patents-in-suit also explain that there is the possibility of microbial
`
`contamination during dilution. “Additionally, microbiological contamination of the product
`
`during dilution/aseptic handling is of primary concern. Therefore, there remains a need for a
`
`ready-to-use large volume parenteral esmolol hydrochloride that is microbiologically safe and
`
`stable in vitro during storage.” ‘094 patent at 1:54-58.
`
`30.
`
`In summary, there were significant difficulties associated with the development
`
`and use of the esmolol hydrochloride formulations that existed at the time of the patents-in-suit.
`
`As described in the patents, these included: difficulties in achieving adequate stability and shelf
`
`life suitable for pharmaceutical products due to the susceptibility of esmolol to hydrolytic
`
`degradation; the need to use aseptic manufacturing processes rather than terminal sterilization
`
`because of degradation of esmolol during autoclaving; and the possibility of dose errors and
`
`microbial contamination when high-concentration esmolol hydrochloride products are diluted for
`
`clinical use.
`
`31.
`
`As described in the patents-in-suit, the claimed inventions solve each of these
`
`problems associated with the prior art. Compositions manufactured in accordance with the
`
`inventions can be sterile, aqueous solutions of esmolol hydrochloride that are ready to use for
`
`parenteral injection without dilution. The compositions can be manufactured and filled outside
`
`of rigorously aseptic conditions because they are stable to the conditions of packaged-product
`
`terminal sterilization by autoclaving. Suitable containers for the compositions include infusion
`
`bags made of flexible polymer material. Packaged products are stable: they have been
`
`
`
`– 10 –
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`

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`demonstrated to be suitable for patient administration after 12 or more months of room
`
`temperature storage. See, e.g., ‘094 patent at 1:60-2:59; ‘540 patent at 2:1-20.
`
`32.
`
`As described in the patents, what the patentees claimed to be inventive about the
`
`formulations they teach and claim is that unlike prior art formulations that could not survive
`
`autoclaving, the claimed formulations are stable to terminal sterilization via autoclaving. See,
`
`e.g., ‘094 patent at 1:40-48, 2:1-5. In particular, they explained that “[i]n the past, the rate of
`
`degradation of esmolol hydrochloride has been reduced by the use of acetate as a buffer,
`
`maintaining the pH as close to 5.0 as possible, minimizing the concentration of esmolol in the
`
`solution, and minimizing the concentration of buffer used.” ‘094 patent at 1:35-39; ‘540 patent
`
`at 1:33-37. Moreover, “[p]rior art formulations maintain a reasonably long shelf-life, however,
`
`they are packaged in glass vials or ampules, and suffer from severe degradation upon
`
`autoclaving,” and “[a]s a result, prior art formulations are prepared aseptically.” See, e.g., ‘094
`
`patent at 1:40-48, 2:1-5.
`
`33.
`
`By contrast, as the patentees explained: “[t]he present invention is stable against
`
`hydrolytic degradation and other adverse chemical reactions, and possesses a pharmaceutically-
`
`acceptable shelf-life,” and “[t]he product is a ready-to-use infusion which can be used directly
`
`without requiring any additional procedures for dilution.” Id. at 2:3-8. “This avoids the
`
`inconvenience of diluting a concentrated esmolol small volume parenteral formulation into
`
`infusion diluents prior to infusion” and “eliminates the risk of microbiological contamination
`
`during aseptic handling.” Id. at 2:7-12.
`
`34.
`
`The ‘094 patent states that “[t]he present invention provides a stable, ready-to-use
`
`parenteral solution containing esmolol hydrochloride and a pharmaceutically acceptable
`
`buffering agent and an osmotic adjusting agent to adjust the tonicity of the solution,” and that
`
`
`
`– 11 –
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`

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`“[t]he solution can be packaged in a sealed container and subjected to terminal sterilization via
`
`autoclaving to reduce the microbiological burden of the formulation. Esmolol hydrochloride
`
`formulations of the prior art cannot survive autoclaving.” Id. 1:62-2:1. See also ‘540 patent, at
`
`2:3-9.
`
`B.
`
`35.
`
`REPRESENTATIVE ASSERTED CLAIMS
`
`I understand that the asserted claims that are at issue in this case are claims 1 – 9
`
`of the ‘094 patent and claims 6 and 12 – 16 of the ‘540 patent. Those asserted claims include
`
`both composition claims, which are directed to the formulation of the esmolol-containing
`
`pharmaceutical product, and method of manufacture claims, which are directed to the methods
`
`for making those products.
`
`36.
`
`Representative asserted claim 1 of the ‘094 patent, for instance, is a composition
`
`claim that recites as follows (disputed claim terms are bolded and italicized):
`
`1. An injectable, aqueous pharmaceutical composition for the treatment
`
`of cardiac conditions, having a pH between 3.5 and 6.5 and comprising
`
`
`
`a. 0.1-100 mg/ml methyl-3-[4-(2-hydroxy-3-isopropylamino) propoxy]
`phenylpropionate hydrochloride (esmolol hydrochloride),
`
`b. 0.1-5.0 mg/ml buffering agent, and
`
`c. 1-100 mg/ml osmotic-adjusting agent.
`
`37.
`
`Asserted claim 13 of the ‘540 patent, in turn, is an exemplary method of
`
`manufacture claim that recites as follows (disputed claim terms are bolded and italicized):
`
`13. A method for preparing an aqueous, sterile pharmaceutical
`
`composition suitable for parenteral administration for the treatment of cardiac
`conditions, comprising
`
`
`
`forming an aqueous composition having a pH between 3.5 and 6.5
`comprising
`
`
`
`– 12 –
`
`

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`0.1-500 mg/ml methyl-3-[4-(2-hydroxy-3-isopropylamino)
`propoxy]phenylpropionate hydrochloride (esmolol
`hydrochloride),
`
`0.01-2 M buffering agent, and
`
`1-500 mg/ml osmotic-adjusting agent
`
`in a sealed container and
`
`
`
`autoclaving for a period of time sufficient to render the composition
`sterile.
`
`38.
`
`I understand that the parties have identified three claim terms for construction by
`
`the Court: “sterile,” “aqueous,” and “injectable, aqueous pharmaceutical composition.” Below,
`
`I explain my opinions concerning the meaning of the terms “aqueous” and “sterile” as they are
`
`used in the asserted claims of the patents-in-suit and would be understood by persons of ordinary
`
`skill in the art.
`
`39.
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`I note that the parties have not separately identified the term “injectable” for
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`construction by the Court. The term “injectable” means capable of being injected, and I
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`understand an “injectable” composition to be one that is itself ready to be injected into a patient’s
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`body. That is the way in which the term is used in the context of the ‘094 patent. The ‘094
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`patent teaches esmolol compositions that are “ready-to-use”—i.e., that are ready to be injected
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`into a patient’s body without first being diluted, and repeatedly describes the invention as being
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`directed to compositions that are injectable and ready-to-use. This is reflected, for instance, in
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`the Title (“Ready-to-Use Esmolol Solution”), Abstract (“a ready-to-use injectable, aqueous
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`pharmaceutical composition for the treatment of cardiac conditions”), Summary of the Invention
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`(“[t]he present invention relates to a ready-to-use injectable, aqueous pharmaceutical
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`composition”) (id.at 1:5-7), at various points in the Detailed Description of the Invention (see,
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`e.g., id. at 1:62-63, 2:2-8) and in the Examples, all of which are ready-to-use (see, e.g., id.
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`
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`– 13 –
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`

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`Case 1:14-cv-07094-JBS-JS Document 79-1 Filed 11/16/15 Page 15 of 25 PageID: 755
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`at 2:64-66 (describing “the preparation of ready-to-use infusion bags of the present invention
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`containing 10 mg/ml esmolol HCl solution”).
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`40.
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`Thus, as used in the ‘094 patent, “injectable” compositions would be understood
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`to be compositions that are ready for injection into a patient. Compositions that need to be
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`modified before injection, such as concentrates that need to be diluted or combination products
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`that must first be mixed with other components, are not themselves suitable for injection into a
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`patient and thus would not be “injectable” as that term is used in the context of the ‘094 patent.
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`41.
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`This is confirmed by review of the ‘540 patent, which does not use the word
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`“injectable” at all. The ‘540 patent is a “continuation-in-part” of the ‘094 patent, and among the
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`additional disclosures is that the ‘540 patent teaches both ready-to-use compositions like those
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`taught in the ‘094 patent, as well as concentrated compositions that must be diluted before
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`injection. See, e.g., ‘540 patent at 2:30-40; 2:62-67. Accordingly, in contrast to the statements
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`in the ‘094 patent that I have quoted above, the Title, Abstract, and the other statements in the
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`specification of the ‘540 patent describing the “invention”/“present invention” as a whole do not
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`refer to the “invention” as an “injectable” composition. This is a reflection of the fact that,
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`unlike the ‘094 patent, the invention to which the ‘540 patent is directed is not limited to ready-
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`to-use compositions, but instead also encompasses concentrated compositions that are not
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`themselves ready for injection into patients, and hence, not “injectable.”
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`42.
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`I understand that in another case involving the patents-in-suit the Court has
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`construed the term “osmotic-adjusting agent” as used in the asserted claims to mean “an agent to
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`adjust the tonicity of the solution.” See Baxter Healthcare Corp. v. HQ Specialty Pharma Corp.,
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`13-cv-6228, United States District Court for the District of New Jersey (ECF #202, Order
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`Construing “Osmotic-Adjusting Agent” and Denying the Parties’ Cross-Motions for Summary
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`
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`– 14 –
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`

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`Case 1:14-cv-07094-JBS-JS Document 79-1 Filed 11/16/15 Page 16 of 25 PageID: 756
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`Judgment), Ex. 6. I further understand that the parties have stipulated and agreed that that
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`construction shall govern the meaning of the term in this case as well.
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`V.
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`PERSON OF ORDINARY SKILL IN THE ART
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`43.
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`In my opinion, a person of ordinary skill in the art at the time of the claimed
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`inventions of the patents-in-suit would be a person possessing a Bachelor’s or PharmD Degree in
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`Pharmacy, Pharmaceutical Sciences, or related science disciplines, having 3-5 years of parenteral
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`pharmaceutical formulation experience, working as a part of a team to develop parenteral
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`formulations. I have used that understanding of the qualifications of a person of ordinary skill in
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`the art in arriving at the opinions set forth in this report.
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`VI. MEANING OF “STERILE”
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`44.
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`I understand that the parties dispute the proper meaning of the term “sterile,” as it
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`is used in the asserted claims of the patents-in-suit.
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`45.
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`In the specification of the ‘540 patent, the patentees specificall