`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF NEW JERSEY
`
` Case No. 3:17-cv-13151-PGS-TJB
`
`
`BRACCO DIAGNOSTICS INC.,
`
`Plaintiff,
`
`
`
`
`
`v.
`
`MAIA PHARMACEUTICALS, INC.,
`
`Defendant.
`
`
`
`
`
`OPENING CLAIM CONSTRUCTION BRIEF
`OF MAIA PHARMACEUTICALS, INC.
`
`
`Gregory D. Miller
`Jenna Gabay
`RIVKIN RADLER LLP
`21 Main Street
`West Wing – Suite 158
`Hackensack, NJ 07601-7021
`Phone: (201) 287-2474
`Facsimile: (201) 489-0495
`gregory.miller@rivkin.com
`jenna.gabay@rivkin.com
`
`William R. Zimmerman (admitted pro
`hac vice)
`KNOBBE, MARTENS, OLSON &
`BEAR, LLP
`1717 Pennsylvania Avenue N.W., Suite
`900 Washington, D.C. 20006
`Phone: (202) 640-6400
`Facsimile: (202) 640-6401
`bill.zimmerman@knobbe.com
`
`Attorneys for Defendant
`Maia Pharmaceuticals, Inc.
`
`Thomas P. Krzeminski (admitted pro
`hac vice)
`KNOBBE, MARTENS, OLSON &
`BEAR, LLP
`2040 Main Street, 14th Floor
`Irvine, CA 92614
`Phone: (949) 760-0404
`Facsimile: (949) 760-9502
`thomas.krzeminski@knobbe.com
`
`
`Peter Law (admitted pro hac vice)
`KNOBBE, MARTENS, OLSON &
`BEAR, LLP
`12790 El Camino Real
`San Diego, CA 92130
`Phone: (858) 707-4000
`Facsimile: (858) 707-4001
`peter.law@knobbe.com
`
`
`Bracco Ex. 2007
`Maia v. Bracco
`IPR2019-00345
`
`

`

`TABLE OF CONTENTS
`
`Page No.
`
`I.
`
`INTRODUCTION ......................................................................................... 1
`
`II. NATURE AND STAGE OF THE PROCEEDINGS .................................... 4
`
`III. PERSON OF ORDINARY SKILL IN THE ART ........................................ 5
`
`IV. BACKGROUND ........................................................................................... 5
`
`A.
`
`Technology Overview ......................................................................... 5
`
`B. Drug Formulation ................................................................................ 6
`
`C. Overview of the ‘046 Patent ................................................................ 6
`
`V. CLAIM CONSTRUCTION PRINCIPLES ................................................... 7
`
`VI. MAIA’S CONSTRUCTIONS ARE SUPPORTED BY THE
`INTRINSIC AND AVAILABLE EXTRINSIC EVIDENCE ....................... 9
`
`A.
`
`“Surfactant” ......................................................................................... 9
`
`1.
`
`Intrinsic evidence .................................................................... 11
`
`a.
`
`b.
`
`Claim language ............................................................. 11
`
`Specification ................................................................. 12
`
`Extrinsic evidence ................................................................... 12
`
`Bracco’s construction of “surfactant” should be
`rejected .................................................................................... 13
`
`2.
`
`3.
`
`B.
`
`“Surfactant/Solubilizer” .................................................................... 20
`
`1.
`
`Intrinsic evidence .................................................................... 21
`
`a.
`
`b.
`
`Claim language ............................................................. 21
`
`Specification ................................................................. 23
`
`-i-
`
`

`

`TABLE OF AUTHORITIES
`(Cont’d)
`
`Page No(s).
`
`2.
`
`Bracco’s construction of “surfactant/solubilizer”
`should be rejected.................................................................... 24
`
`C.
`
`“Buffer” ............................................................................................. 30
`
`1.
`
`Intrinsic evidence .................................................................... 32
`
`a.
`
`b.
`
`Claim language ............................................................. 32
`
`Specification ................................................................. 33
`
`Extrinsic evidence ................................................................... 33
`
`Bracco’s construction of “buffer” should be rejected ............. 34
`
`2.
`
`3.
`
`VII. CONCLUSION ............................................................................................ 40
`
`
`
`
`
`-ii-
`
`

`

`TABLE OF AUTHORITIES
`
`Page No(s).
`
`Alloc, Inc. v. Int’l Trade Comm’n,
`342 F.3d 1361 (Fed. Cir. 2003)................................................................................................26
`
`Beacon Adhesives, Inc. v. United States,
`134 Fed. Cl. 26 (2017) .................................................................................................19, 38, 39
`
`Becton, Dickinson & Co. v. Tyco Healthcare Grp., LP,
`616 F.3d 1249 (Fed. Cir. 2010)................................................................................................25
`
`CAE Screenplates Inc. v. Heinrich Fiedler GmbH & Co.,
`224 F.3d 1308 (Fed. Cir. 2000)................................................................................................27
`
`Energizer Holdings, Inc. v. Int’l Trade Comm’n,
`435 F.3d 1366 (Fed. Cir. 2006)................................................................................................29
`
`Generation II Orthotics Inc. v. Med. Tech. Inc.,
`263 F.3d 1356 (Fed. Cir. 2001)..................................................................................................8
`
`Helmsderfer v. Bobrick Washroom Equip., Inc.,
`527 F.3d 1379 (Fed. Cir. 2008)..........................................................................................19, 38
`
`Markman v. Westview Instruments, Inc.,
`52 F.3d 967 (Fed. Cir. 1995)......................................................................................................8
`
`Merck & Co. v. Teva Pharm. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005)..........................................................................................22, 24
`
`NeoMagic Corp. v. Trident Microsystems, Inc.,
`287 F.3d 1062 (Fed. Cir. 2002)................................................................................................36
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc)........................................................................7, 8, 25
`
`Praxair, Inc. v. ATMI, Inc.,
`543 F.3d 1306 (Fed. Cir. 2008)..........................................................................................14, 29
`
`SRI Int’l v. Matsushita Elec. Corp. Am.,
`775 F.2d 1107 (Fed. Cir. 1985)..........................................................................................15, 27
`
`Teva Pharms. USA, Inc. v. Sandoz, Inc.,
`135 S. Ct. 831 (2015) .................................................................................................................7
`
`-iii-
`
`

`

`TABLE OF AUTHORITIES
`(Cont’d)
`
`Page No(s).
`
`Thorner v. Sony Computer Entm’t Am. LLC,
`669 F.3d 1362 (Fed. Cir. 2012)..........................................................................................19, 39
`
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996)..................................................................................................25
`
`Wilson Sporting Goods Co. v. Hillerich & Bradsby Co.,
`442 F.3d 1322 (Fed. Cir. 2006)................................................................................9, 16, 35, 36
`
`35 U.S.C. § 112 ..............................................................................................................................29
`
`OTHER AUTHORITIES
`
`
`
`
`
`-iv-
`
`

`

`
`
`I. INTRODUCTION
`
`This is a Hatch-Waxman case. Plaintiff Bracco Diagnostics Inc. (“Bracco”)
`
`markets and sells sincalide for injection (“sincalide”) under the tradename
`
`Kinevac®, which is used as a diagnostic aid for imaging a patient’s hepatobiliary
`
`system. U.S. Patent No. 6,803,046 (“the ’046 patent”) is listed in the U.S. Food
`
`and Drug Administration’s (“FDA”) Orange Book as covering Bracco’s Kinevac®
`
`product. Over the past six years, Bracco’s product has been plagued by serious
`
`manufacturing and stability problems, causing Kinevac®
`
`to be routinely
`
`unavailable and listed on the FDA’s Drug Shortage List (which continues to this
`
`day). The unavailability of Kinevac® has caused a public health crisis, as
`
`Kinevac® is the only drug approved by the FDA to help diagnose certain disorders
`
`of the hepatobiliary system. The medical community is in dire need of a more
`
`stable alternative to Bracco’s flawed Kinevac® product. Defendant Maia
`
`Pharmaceuticals Inc. (“Maia”) has developed such an alternative.
`
`Maia, based in Princeton, New Jersey, is a pharmaceutical company that
`
`develops novel pharmaceutical products to fulfill unmet needs of the medical
`
`community. Aware of the problems plaguing Kinevac®, Maia began development
`
`of its own sincalide formulation. The development of Maia’s product was driven
`
`by two considerations: solving the manufacturing and stability problems plaguing
`
`Kinevac®, and avoiding infringement of Bracco’s ‘046 patent.
`
`-1-
`
`

`

`
`
`Bracco’s ‘046 patent is directed to and claims particular sincalide
`
`formulations containing specific types of excipients, as well as methods of making
`
`and using the same. All 108 claims of the patent require, either directly or through
`
`dependency, a “surfactant” or a “surfactant/solubilizer” (depending on the claim),
`
`as well as a “buffer.” The ‘046 patent provides that, in the context of the claimed
`
`invention, polysorbate 20 is a “surfactant” and “surfactant/solubilizer” and dibasic
`
`potassium phosphate is a “buffer.”
`
`Maia developed a stable sincalide formulation without using a “surfactant,”
`
`a “surfactant/solubilizer” or a “buffer,”
`
`
`
` By making a stable sincalide
`
`formulation without a “surfactant,” a “surfactant/solubilizer” or a “buffer,” Maia
`
`also designed around all 108 claims of the ‘046 patent.
`
`In August 2017, Maia filed a Section 505(b)(2) new drug application
`
`(“NDA”) with the FDA seeking approval to market and sell its sincalide product.
`
`Recognizing the medical community’s need for an improved sincalide product, the
`
`FDA granted “Priority Review” of Maia’s NDA. After learning of Maia’s NDA,
`
`Bracco filed suit in December 2017 and alleged that Maia’s product infringed the
`
`claims of the ‘046 patent. Two months later, in February 2018, the FDA granted
`
`tentative approval for Maia’s product—just six months after the filing of Maia’s
`
`-2-
`
`

`

`
`
`NDA. Accordingly, the only obstacle to the medical community receiving access
`
`to Maia’s sincalide product is the 30-month stay.
`
`The parties dispute the proper construction of the claim terms “buffer,”
`
`“surfactant”
`
`and
`
`“surfactant/solubilizer.” Bracco proposes hypothetical
`
`constructions of these terms that do not require an excipient to exhibit any
`
`particular function to meet the functional claim terms at issue. For example,
`
`Bracco construes “surfactant” and “surfactant/solubilizer” as an excipient that
`
`“may” (or may not) function as a surfactant and surfactant/solubilizer, respectively.
`
`Likewise, Bracco’s construction of “buffer” would purport to cover excipients that
`
`do not buffer within the approved pH range of a sincalide formulation.
`
`Bracco’s theoretical constructions conflict with how those skilled in the art
`
`would understand the ‘046 patent. One of skill in the art would know that, for
`
`claims requiring a particular type of functional excipient, the excipient must
`
`actually perform that function in the formulation at issue to meet the claim term.
`
`The mere potential to perform that function in the abstract, divorced from the
`
`formulations at issue, is irrelevant in the context of the claimed invention. For the
`
`reasons set forth below, all three of Bracco’s hypothetical constructions should be
`
`rejected.
`
`Maia proposes the following constructions for each claim term in dispute:
`
`-3-
`
`

`

`
`
`Claim term
`“surfactant”
`
`Maia’s Construction
`A compound that reduces the tension of the air/liquid or
`liquid/solid interface.
`“surfactant/solubilizer” A surfactant that is also a solubilizer.
`
` A
`
` solubilizer is a compound that aids in solubilization,
`thus preventing or reducing sincalide denaturation
`and/or degradation caused by peptide aggregation,
`precipitation, surface adsorption, or agitation at
`air/liquid or liquid/solid interfaces in solution.
`A compound that stabilizes the pH of a sincalide
`formulation.
`
`“buffer”
`
`
`Maia’s proposed constructions are supported by the intrinsic and extrinsic
`
`evidence, including the Declaration of Dr. Alexander Klibanov, a recognized
`
`expert in drug formulation.
`
`II. NATURE AND STAGE OF THE PROCEEDINGS
`
`Bracco filed this Hatch-Waxman case on December 15, 2017, asserting that
`
`Maia’s proposed product infringes all 108 asserted claims of the ‘046 patent. D.I.
`
`1; see Ex. 1 (‘046 patent).1 Maia denies infringement and challenges the validity
`
`of the asserted claims. D.I. 6. The parties are currently engaged in fact discovery.
`
`The close of fact discovery and the Court’s claim construction hearing are not
`
`presently scheduled. See D.I. 24.
`
`
`1 All exhibits cited herein are submitted with the Declaration of Gregory D.
`Miller, Esq., filed herewith.
`
`-4-
`
`

`

`
`
`III. PERSON OF ORDINARY SKILL IN THE ART
`
`The person of ordinary skill in the art (“POSA”) relevant to the ‘046 patent
`
`would have had background and experience in the design and development of
`
`pharmaceutical formulations, including injectables. Declaration of Professor
`
`Alexander M. Klibanov (“Klibanov Decl.) ¶ 24. Such a person would have had a
`
`Ph.D. degree in chemistry, pharmacy or a related field, plus about two years of
`
`experience formulating pharmaceuticals. Id. Alternatively, such a person may
`
`have had a lesser academic degree (such as a M.S. or a B.S. degree) in one of those
`
`fields with commensurately more experience formulating pharmaceuticals.2 Id.
`
`While the parties differ somewhat on the appropriate level of skill in the art,
`
`Maia’s proposed constructions would not change under Bracco’s definition of the
`
`level of ordinary skill in the art. Id. ¶ 25.
`
`IV. BACKGROUND
`
`A. Technology Overview
`Sincalide is a cholecystopancreatic-gastrointestinal hormone peptide for
`
`parenteral (i.e., by injection) administration. Ex. 1, 1:9-11; Klibanov Decl. ¶ 27.3
`
`Sincalide is used as a diagnostic aid for imaging disorders the hepatobiliary system
`
`
`2 The application that issued as the ‘046 patent was filed on August 16, 2002.
`Ex. 1 at 1. Accordingly, for purposes of this brief, Maia’s claim construction
`arguments are based on the level of ordinary skill in the art in August 2002.
`
`3 Citations to the ‘046 patent use the format [column]:[line].
`
`-5-
`
`

`

`
`
`of a patient. Ex. 1, 2:39-50; Klibanov Decl. ¶ 27. Sincalide was first introduced
`
`commercially in 1976, and provided as a sterile, nonpyrogenic, lyophilized (i.e.,
`
`freeze-dried) white powder in a glass vial. Ex. 1, 1:17-19; Klibanov Decl. ¶ 28.
`
`B. Drug Formulation
`Active pharmaceutical ingredients (“API”), such as sincalide, are rarely
`
`administered alone. Klibanov Decl. ¶ 29. Instead, an API is typically mixed with
`
`inactive ingredients called “excipients” to improve various aspects (e.g., ease of
`
`handling, stability) of the drug formulation at issue. Id. There are many different
`
`types of excipients, with each type serving a specific function in a pharmaceutical
`
`formulation. Id. ¶ 30. During drug development, drug formulators work to
`
`identify the right excipients in optimal quantities to maximize the drug product’s
`
`beneficial properties. Id. ¶ 31.
`
`C. Overview of the ‘046 Patent
`The ‘046 patent is directed to pharmaceutical formulations of sincalide for
`
`administration by injection. Ex. 1, 1:52-53; Klibanov Decl. ¶ 32. The claims of
`
`the ’046 patent generally recite a formulation for sincalide. Ex. 1, claims 1-108;
`
`Klibanov Decl. ¶ 33. Independent claim 1 is representative, and recites a
`
`“stabilized, physiologically acceptable formulation of sincalide” that includes the
`
`following excipients, as defined by their function: “at least one stabilizer,” “a
`
`surfactant/solubilizer,” “a chelator,” “a bulking agent/tonicity adjuster” and “a
`
`-6-
`
`

`

`
`
`buffer.” Ex. 1, claim 1; Klibanov Decl. ¶ 33. The other independent claims are
`
`variations of this basic formulation, claiming the formulation as a kit (claim 40), as
`
`a method of making the formulation by mixing the excipients (claim 21), and as a
`
`method of imaging a patient by first administering the formulation, followed by
`
`imaging the patient (claims 77 and 104). Klibanov Decl. ¶ 33. The dependent
`
`claims add limitations regarding the common subclasses and compounds within the
`
`functional excipient classes, common techniques for administering the drug and
`
`common techniques for imaging the patient. Id.
`
`The ’046 patent describes the alleged invention as “sincalide formulations
`
`having improved stability and/or potency over previous formulations.” Ex. 1,
`
`3:38-40; Klibanov Decl. ¶ 34. This was reportedly done by the “selection of
`
`excipients that provide certain desired functions.” Ex. 1, 3:35-36; Klibanov Decl.
`
`¶ 34.
`
`V. CLAIM CONSTRUCTION PRINCIPLES
`
`Claim construction is an issue of law based on underlying factual
`
`considerations. Teva Pharms. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831 (2015).
`
`Claim language is given the meaning it would have to a POSA at the time the
`
`application was filed, in view of the patent specification. See Phillips v. AWH
`
`Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc).
`
`-7-
`
`

`

`
`
`It is a “bedrock principle” of patent law that “the claims of a patent define
`
`the invention to which the patentee is entitled the right to exclude.” Id. at 1312.
`
`The words of a claim “are generally given their ordinary and customary meaning,”
`
`as understood by a POSA at the time of the alleged invention. Id. at 1312-13.
`
`Claims “must be read in view of the specification, of which they are a part.”
`
`Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed. Cir. 1995);
`
`Phillips, 415 F.3d at 1313 (“The [POSA] is deemed to read the claim term not only
`
`in the context of the particular claim in which the disputed term appears, but in the
`
`context of the entire patent, including the specification.”). The prosecution history
`
`of a patent is part of the intrinsic evidence and “can often inform the meaning of
`
`the claim language.” Phillips, 415 F.3d at 1317. A court may also rely on
`
`extrinsic evidence, such as expert testimony, dictionaries and learned treatises. Id.
`
`But extrinsic evidence may not be used to alter the meaning of claim terms in a
`
`manner inconsistent with the intrinsic evidence. Id. at 1318–19.
`
`Whenever possible, courts should construe claims to preserve their validity.
`
`Id. at 1327. “[C]laims can only be construed to preserve their validity where the
`
`proposed claim construction is ‘practicable,’ is based on sound claim construction
`
`principles, and does not revise or ignore the explicit language of the claims.”
`
`Generation II Orthotics Inc. v. Med. Tech. Inc., 263 F.3d 1356, 1365 (Fed. Cir.
`
`2001). Further, courts should not construe claim language to include or exclude an
`
`-8-
`
`

`

`
`
`accused product. Wilson Sporting Goods Co. v. Hillerich & Bradsby Co., 442 F.3d
`
`1322, 1327 (Fed. Cir. 2006). This rule, however, “does not forbid awareness of the
`
`accused product or process to supply the parameters and scope of the infringement
`
`analysis, including its claim construction component.” Id. at 1331
`
`VI. MAIA’S CONSTRUCTIONS ARE SUPPORTED BY THE
`INTRINSIC AND AVAILABLE EXTRINSIC EVIDENCE
`
`Maia’s constructions use the plain and ordinary meanings of the disputed
`
`claim terms to a POSA, and are supported by the intrinsic and available extrinsic
`
`evidence.4 Bracco’s constructions, on the other hand, do not use the plain and
`
`ordinary meanings of the claim terms at issue. Rather, Bracco’s constructions are
`
`hypothetical in nature, rely on language from the specification that does not even
`
`relate to the claim term being construed and are contrary to the intrinsic and
`
`available extrinsic evidence. Bracco’s constructions also violate several canons of
`
`claim construction, including prohibitions against rewriting the claim terms and
`
`reading portions of the specification into the claim.
`
`A.
`
`“Surfactant”
`
`Maia’s Proposal
`A compound that reduces
`the tension of the air/liquid
`or liquid/solid interface.
`
`Bracco’s Proposal
`Excipients that “may reduce the interfacial
`tension” and “include, but are not limited to,
`pluronics (e.g., Lutrol F68, Lutrol F127),
`Poloxamers, SDS, Triton-100, polysorbates such
`
`
`4 The prosecution history for the ‘046 patent does not shed any light on the
`proper construction of the disputed claim terms. Klibanov Decl. ¶¶ 38, 75, 94.
`
`
`-9-
`
`

`

`
`
`as TWEEN® 20 and TWEEN® 80, propylene
`glycol, PEG and similar compounds, Brij58
`(polyoxyethylene 20 cetyl ether), cremophor EL,
`cetyl trimethylammonium bromide (CTAB),
`dimethylacetamide (DMA), NP-40 (Nonidet P-
`40), and Nmethyl-
`2-pyrrolidone (Pharmasolve), glycine and other
`amino acids/amino acid salts and anionic
`surfactants containing alkyl, aryl or heterocyclic
`structures, and cyclodextrins.” ‘046 patent, col.
`11, lines 26-63.
`
` A
`
` surfactant is a well-known term to a POSA. Klibanov Decl. ¶ 35. A
`
`POSA would have understood that a “surfactant” is “a compound that reduces the
`
`tension of the air/liquid or liquid/solid interface.” Ex. 1, 11:29-34; Klibanov Decl.
`
`¶¶ 35-39. This construction is supported by the intrinsic and extrinsic evidence.
`
`See Klibanov Decl. ¶¶ 35-39.
`
`The parties both rely on the same portion of the specification to arrive at
`
`their respective constructions of “surfactant.” However, the parties’ constructions
`
`diverge in two important ways.
`
` First, Bracco’s construction is entirely
`
`hypothetical. According to Bracco’s construction, surfactants “may” (or may not)
`
`reduce interfacial tension. Inclusion of the permissive word “may” in Bracco’s
`
`construction essentially erases the requirement of a “surfactant” from the claim.
`
`Klibanov Decl. ¶¶ 43, 45-48. Contrary to Bracco’s construction, a surfactant is not
`
`optional in the context of the ‘046 patent. Id. ¶ 48.
`
`-10-
`
`

`

`
`
`Second, Bracco’s construction of “surfactant” seeks to read a long list of
`
`potential hypothetical surfactants into the claim under the guise of claim
`
`construction, which is improper. The list of hypothetical surfactants in the
`
`specification is expressly open-ended, using language such as “may” and “include
`
`but are not limited to,” as well as “e.g.” and “such as” when referring to the list of
`
`hypothetical surfactants available. Klibanov Decl. ¶ 44. As such, the list of
`
`potential surfactants in the specification does not define the scope of the claim term
`
`“surfactant.” Id. Rather, one must assess whether a compound functions as a
`
`surfactant in the formulation at issue. It is improper for Bracco to read that list of
`
`potential surfactants into the claim.
`
`1.
`
`Intrinsic evidence
`a.
`Several claims of the ‘046 patent require a “surfactant,” either directly or
`
`Claim language
`
`through dependency. See, e.g., Ex. 1, claims 7, 18, 27, 38, 40. Independent claim
`
`40 is representative:
`
`40. A kit, comprising:
`(i) a powder mixture comprising
`(a) sincalide,
`(b) at least one stabilizer,
`(c) a surfactant,
`(d) a chelator,
`(e) a bulking agent/tonicity adjuster, and
`(f) a buffer;
`(ii) a container to hold said powder mixture; and
`(iii) optionally, a physiologically acceptable fluid.
`
`-11-
`
`

`

`
`
`Ex. 1, claim 40 (emphasis added to indicate disputed term). Several dependent
`
`claims identify a specific type of surfactant to be used (e.g., claim 46 requiring the
`
`nonionic surfactant polysorbate). See, e.g., Ex. 1, claim 46.
`
`Specification
`
`b.
`The specification of the ‘046 patent explicitly defines a “surfactant” in the
`
`section entitled “Surfactants/Solubilizers/Surface Active Agents.” Ex. 1, 11:26-34;
`
`Klibanov Decl. ¶ 37. In relevant part, the specification provides: “The addition of
`
`a nonionic surfactant, such as polysorbate, to the formulation, may reduce the
`
`interfacial tension [or aid in solubilization thus preventing or reducing denaturation
`
`and/or degradation]5 at air/liquid or liquid/solid interfaces of the product in
`
`solution.” Ex. 1, 11:29-34 (brackets added); Klibanov Decl. ¶ 37.
`
`Both parties use this same section of the specification to arrive at their
`
`respective constructions. As such, there does not appear to be a serious dispute
`
`that a surfactant functions to reduce the interfacial tension at air/liquid or
`
`liquid/solid interfaces of the product in solution.
`
`Extrinsic evidence
`
`2.
`Various general and scientific dictionaries define a “surfactant” as a
`
`compound that reduces the tension of the air/liquid or liquid/solid interface. See
`
`
`5 The bracketed language references the potential of a nonionic surfactant to
`aid in solubilization, which is distinct from its function as a surfactant. Klibanov
`Decl. ¶ 37 & n.2. Neither party relies on the bracketed language to define a
`“surfactant.”
`
`-12-
`
`

`

`
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`Ex. 2, Condensed Chemical Dictionary at 830 (1977) (defining a “surface-acting
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`agent (surfactant),” in relevant part, as “any compound that reduced surface tension
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`(q.v.) when dissolved in water or water solutions, or which reduces interfacial
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`tension between two liquids, or between a liquid and a solid.”); Ex. 4, Webster’s
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`Ninth Collegiate Dictionary at 1187 (1985) (defining “surfactant” as “a surface-
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`active substance”; further defining “surface-active” as “altering the properties and
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`esp. [i.e., especially] lowering the tension at the surface of contact between
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`phases.”); Ex. 5, McGraw-Hill Dictionary of Scientific and Technical Terms at
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`1960 (5th ed. 1994) (defining a “surface-active agent,” “[a]lso known as
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`surfactant,” as “[a] soluble compound that reduces the surface tension of liquids or
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`reduces interfacial tension between two liquids or a liquid and a solid.”). These
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`definitions are consistent with Maia’s construction of the term “surfactant.”
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`Klibanov Decl. ¶ 39.
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`Bracco’s construction of “surfactant” should be rejected
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`3.
`Bracco’s construction of “surfactant” suffers several defects. First, it is
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`entirely hypothetical in nature. Bracco defines the claim term “surfactant” as any
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`excipient that “may” (or may not) function as a surfactant. Such nonsensical
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`constructions are a byproduct of construing a term in a vacuum, without any
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`context. A POSA reading the ‘046 patent would understand that a “surfactant”
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`must actually function as a surfactant in the claimed invention. Otherwise, it is not
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`considered a surfactant.
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`While the specification does use the word “may” when referring to a
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`preferred surfactant’s ability to function as a surfactant and solubilizer, that
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`sentence must be read in view of the entire intrinsic record. The specification
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`explains that surfactants function to minimize sincalide degradation in the claimed
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`invention. Ex. 1, 20:5-9 (“To minimize sincalide degradation associated with
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`surface adsorption, surfactants are added as formulation excipients in bulk and
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`lyophilized formulations of sincalide.”) (emphasis added); Klibanov Decl. ¶ 45. In
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`addition, the Abstract, Summary of the Invention and Detailed Description of the
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`Invention consistently describe the claimed invention as requiring a surfactant in
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`the formulation. See Ex. 1, Abstract (requiring a surfactant); 1:56-62 (“Summary
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`of the Invention”) (requiring a surfactant); 4:8-31 (“Detailed Description of the
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`Invention”) (requiring a surfactant); Klibanov Decl. ¶ 46. All embodiments and
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`descriptions of the claimed invention recite a “surfactant,” as do all 108 claims.
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`See Ex. 1; Klibanov Decl. ¶ 47. In view of the entire intrinsic record, a POSA
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`reading the ‘046 patent would understand a surfactant is a fundamental feature of
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`the claimed invention. Klibanov Decl. ¶ 48; see Praxair, Inc. v. ATMI, Inc., 543
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`F.3d 1306, 1324 (Fed. Cir. 2008) (stating that claims must be read in view of the
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`specification’s “consistent emphasis on this fundamental feature of the invention”).
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`Further, a POSA would understand that the claimed invention requires a surfactant
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`to confer a surfactant effect (i.e., reduce interfacial tension) in order to practice the
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`claimed invention. Klibanov Decl. ¶ 45. A surfactant is no more optional in the
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`context of the claimed invention than sincalide is.
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`Second, Bracco’s construction of “surfactant” improperly includes an open-
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`ended list of potential surfactants from the specification. See Ex. 1, 11:51-63;
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`Klibanov Decl. ¶ 44. It is a cardinal rule of claim construction that potential
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`examples from the specification should not be read into the claims. SRI Int’l v.
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`Matsushita Elec. Corp. Am., 775 F.2d 1107, 1121 (Fed. Cir. 1985) (“[T]hat claims
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`are interpreted in light of the specification does not mean that everything expressed
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`in the specification must be read into all the claims.”) (citation omitted). Yet this is
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`exactly what Bracco has done in its construction of “surfactant.” Bracco’s attempt
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`to rewrite the claims should be rejected.
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`Third, Bracco’s list of theoretical surfactants comes from a portion of the
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`specification that is not even addressing the claim term at issue. Bracco’s open-
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`ended list of theoretical surfactants comes from column 11, lines 51-62 of the
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`specification. See Ex. 1, 11:51-62; Klibanov Decl. ¶ 49. However, that section of
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`the specification discusses “[e]xamples of preferred surfactants/solubilizers,” not
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`“surfactants,” as Bracco apparently believes.6 Ex. 1, 11:51-62 (emphasis added);
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`Klibanov Decl. ¶ 49. Thus, Bracco is not only rewriting the claims to erase the
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`requirement of a “surfactant”; it is also rewriting the specification so that
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`“surfactants/solubilizers” becomes “surfactants.”
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`Fourth, Bracco’s construction is also incorrect because a POSA would
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`understand that the list of theoretical surfactants contained in Bracco’s construction
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`includes excipients that do not perform as surfactants in a sincalide formulation.
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`Klibanov Decl. ¶ 50. The intrinsic evidence shows that three amino acids do not
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`perform as surfactants within the claimed invention.7 Id. ¶¶ 50-60. For example,
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`Table 1 reports “the concentration ranges for various excipients that were
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`investigated.” Ex. 1, 4:32-33; Klibanov Decl. ¶ 51. In the second column in Table
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`1, the inventors expressly reported the “Function” of each excipient that they
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`6 There
`terms “surfactant” and
`the claim
`that
`is no dispute
`“surfactant/solubilizer” are different claim terms with different meanings in the
`context of the ‘046 patent. Indeed, both parties propose different constructions for
`“surfactant/solubilizer” than they do for “surfactant.”
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`investigated, including the amino acids methionine, lysine and arginine.8 Ex 1,
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`Table 1; Klibanov Decl. ¶ 51. None of these amino acids is reported as functioning
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`as a surfactant. Id. Methionine’s sole function is listed as “Stabilizer.” Ex 1,
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`Table
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`1; Klibanov Decl.
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`¶
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`52.
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`
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`Lysine’s
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`functions
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`are
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`“Stabilizer/Lyoprotectant/Cryoprotectant.” Ex 1, Table 1; Klibanov Decl. ¶ 53.
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`Arginine’s functions are described as “Stabilizer/Lyoprotectant/Cryoprotectant/pH
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`adjuster.” Ex 1, Table 1; Klibanov Decl. ¶ 54.
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`Viewing Table 1 in the context of the entire patent, a POSA would
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`understand that the amino acids methionine, lysine and arginine do not function as
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`surfactants in the context of the ‘046 patent. Ex 1, Table 1; Klibanov Decl. ¶ 56.
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`Rather, all three excipients function as “stabilizers.”9 Ex 1, Table 1; Klibanov
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`Decl. ¶ 56. Indeed, when methionine, lysine and arginine are described in the
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`patent, they are consistently referred to as “stabilizers,” not surfactants. Ex. 1,
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`Table 1 (see above); Table 4 (same); 10:54-55 (stating that various amino acids can
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`be used as “stabilizers” in sincalide formulations); 10:59-61 (“Preferred amino
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`8 The specification provides that each function claimed in the patent is
`typically performed by single excipient, but that in some embodiments a single
`excipient may perform m