IN THE UNITED STATES DISTRICT COURT
`DISTRICT OF NEW JERSEY
`
`
`BRACCO DIAGNOSTICS INC,
`
`Plaintiff,
`V
`
`MAIA PHARMACEUTICALS, INC,
`Defendant.
`
`
` VVVVVVVVVVVVV
`
`Case No. 3: l7-cv—l3151-PGS-TJB
`
`MAIA PHARMACEUTICALS, INC.
`
`Counterclaimant,
`v
`
`BRACCO DIAGNOSTICS INC,
`Counterclaim Defendant.
`
`I
`
`PLAINTIFF BRACCO DIAGNOSTICS INC.’S
`OPENING MARKNIAN CLAIM CONSTRUCTION SUBMISSION
`
`PURSUANT TO LOCAL PATENT RULE 4.5(a)
`
`Bracco EX. 2005
`
`Maia V. Bracco
`
`IPR2019-00345
`
`Bracco Ex. 2005
`Maia v. Bracco
`IPR2019-00345
`
`

`

`
`
`I.
`
`II.
`
`III.
`
`III.
`
`IV.
`
`
`
`
`
`V.
`
`
`Table Of Contents
`
`Introduction To The Claim Construction Issues Raised By The Parties…………..1
`
`The Sincalide Formulation Inventions Of The Patent-In-Suit …………………….3
`
`Legal Standards For Claim Construction.………………………………………….7
`
`The Person Of Skill In The Art.……………………………………………………9
`
`“Buffer” Term Construction……………………………………………………...10
`
`A.
`
`B.
`
`C.
`
`The Intrinsic Evidence Provides Bracco’s Construction Of “A Buffer”…11
`
`The Extrinsic Evidence Supports Bracco’s Construction Of “A Buffer”...15
`
`Is Not Supported By The Intrinsic Or Extrinsic Evidence .………………16
`
`Maia’s Claim Construction Position For “A Buffer”
`
`“Surfactant/Solubilizer” And “Surfactant” Term Constructions. .………………17
`
`A.
`
`
`
`B.
`
`
`C.
`
`The Intrinsic Evidence Provides Bracco’s Construction
`Of “A Surfactant/Solubilizer” And “A Surfactant” ...……………………18
`
`1.
`
`“A Surfactant/Solubilizer” Intrinsic Evidence ..…………………18
`
`2.
`
`“A Surfactant” Intrinsic Evidence..……………………………….22
`
`The Extrinsic Evidence Supports Bracco’s Construction
` Of “A Surfactant/Solubilizer” And “A Surfactant”..…………………….25
`
`Maia’s Claim Construction Position Is Not
`Supported By The Intrinsic Or Extrinsic Evidenc.e.……………………..26
`
`Excipients And Amino Acids In Particular
`Can Have Multiple Functions In Formulations.…..……………………………...30
`
`VII. Conclusion...……………………………………………………………………...32
`
`
`
`VI.
`
`
`
`
`
`

`

`
`
`Table Of Authorities
`
`
`14i Ltd. Partnership v. Microsoft Corp.,
`598 F.3d 831 (2010)…………………………………………………………………28
`
`
`Abbott Labs. v. Sandoz, Inc.,
`566 F.3d 1282 (Fed. Cir. 2009).……………………………………………………. 28
`
`
`Accent Packaging, Inc. v. Leggett & Platt, Inc.,
`707 F.3d 1318 (2013).………………………………….……………………………12
`
`
`Burke, Inc. v. Burno Indep. Living Aids, Inc.,
`183 F.3d 1334 (Fed. Cir. 1999)……………………..……………………….12, 19, 23
`
`
`
`
`
`
`
`
`
`Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc.,
`807 F.2d 955 (Fed. Cir. 1986)…………………………..……………………………………………..9
`Environmental Designs, Ltd. v. Union Oil Co.,
`713 F.2d 693 (Fed. Cir. 1983).…………………………………………………………………………9
`Finisar Corp. v. DirectTV Group, Inc.,
`523 F.3d 1323 (Fed. Cir. 2008)………………….…………………………………………………….8
`In re GPAC,
`57 F.3d 1573 (Fed. Cir. 1995)………………..………………………………………………………..9
`Markman v. Westview Instruments, Inc.,
`52 F.3d 967 (Fed. Cir. 1995)……………..…………………………………………………………….8
`O2 Micro Intern. Ltd. V. Beyond Innovation Technology Co., Ltd.,
`521 F.3d 1351 (Fed. Cir. 2008)….……………………………………………………………………7
`
`Philips v. AWH Corp.,
`
`415 F.3d 1303 (Fed. Cir. 2005)……………………………………..7, 8, 9, 14, 16, 22, 25, 30
`
`90 F.3d 1575 (Fed. Cir. 1996)…………………………………………………..16, 30
`
`
`National Steel Car, Ltd. v. Canadian Pacific Railway, LTD.,
`357 F.3d 1319 (Fed. Cir. 2004)……..……………………………………………….12
`
`
`Kaneka Corp. v. Xiamen Kingdomway Grp. Co.,
`790 F.3d 1298 (Fed. Cir. 2015)………………………………………………….16, 30
`
`
`
`
`
`
`
`Vitronics Corp. v. Conceptronic,
`
`

`

`Plaintiff Bracco Diagnostics Inc. (“Bracco”), pursuant to L.Pat.R. 4.5(a) and the
`
`Court’s December 11, 2018 Letter Order, provides its Opening Markman Claim Construction
`
`Submission.
`
`I.
`
`
`Introduction To The Claim Construction Issues Raised By The Parties
`
`This is a patent infringement action brought under the Hatch-Waxman Act concerning
`
`one patent-in-suit, United States Patent No. 6,803,046 (the “’046 Patent”). Exh. 1.1 For the
`
`Markman claim construction phase of the action, the parties are requesting that the Court
`
`construe three terms of the asserted claims, namely, “a buffer,” “a surfactant/solubilizer,” and
`
`“a surfactant.” The parties agree that the latter term, “a surfactant,” describes a subset of the
`
`“a surfactant/solubilizer” claim term.
`
`The defendant in this action, Maia Pharmaceuticals, Inc. (“Maia”), contends that its
`
`proposed product that is accused of infringement does not infringe each of these three claim
`
`terms.
`
`
`
`
`
`Exh. 2. This is not a colorable position
`
`to maintain because amino acids are defined in the claims and specification of the ‘046 Patent
`
`as examples of, and even preferred embodiments of, each of these claim terms. Furthermore,
`
`in the relevant extrinsic evidence of scientific research papers and patents that applies to
`
`peptide drugs, amino acids are often the “go to” “buffers,” “surfactants” and “solubilizers”
`
`used by the relevant persons of skill in the art.
`
`
`
`1 The Exhibits (“Exh.” and “Exhs.”) cited herein are attached to the Declaration of Donald L.
`Rhoads, submitted herewith.
`
`
`
`
`
`
`
`1
`
`

`

`—E.g., Exh. 66. Thus, Maia can prevail on the issue of
`
`infringement only if it can convince the Coufl that the claims and the specification of the ‘046
`
`Patent do not mean what they explicitly say to a person of skill in the art. Not sluprisingly, no
`
`Court has ever made such a fmding, as doing so would go against all applicable legal
`
`precedent.
`
`For example, Maia is seeking to have the C01111 interpret claims 3, 6 and 44 of the ‘046
`
`Patent (and others), and the corresponding portions of the ‘046 Patent specification,3 to not
`
`cover amino acids. In essence, Maia is seeking to have the C01111 hold that the claims do not
`
`mean what they explicitly recite:
`
`2 Maia ultimately produced at least some of the improperly withheld internal Maia documents
`only afler Bracco discovered them when a few pofiions of them were disclosed during a
`recent document production. Prior to this production, Maia had repeatedly denied the
`documents existed. Even after being confronted with having withheld relevant documents
`with no proper basis, Maia continued to refuse to produce them until Bracco threatened to file
`a motion to compel production of the documents, and then Maia produced them only minutes
`prior to Bracco’s filing of the motion to compel.
`
`3 The specification also defines these terms to include amino acids (i.e., at col. 9, lines 44-65
`(“Buffering agents
`include
`amino acids”) and col. 11, lines 25—63
`("surfactants/solubilizers
`include
`glycine and other amino acids”)).
`
`

`

`
`
`Claim 3 (also claims 23, 41,
`60 and 87)
`3. The formulation of claim 1,
`wherein said buffer is selected
`from the group consisting of
`phosphoric acid, phosphate,
`citric acid, citrate,
`sulfosalicylate, acetic acid,
`acetate, methyl boronic acid,
`boronate, disodium succinate
`hexahydrate, one or more amino
`acids, lactic acid, lactate, maleic
`acid, maleate, potassium
`chloride, benzoic acid, sodium
`benzoate, carbonic acid,
`carbonate, bicarbonate, boric
`acid, borate, sodium chloride,
`succinic acid, succinate, tartaric
`acid, tartrate, tris-
`(hydroxymethyl)aminomethane,
`and biological buffers.
`
`Accordingly, for the reasons described more fully below, the Court should adopt
`
`Claim 6 (also claim 26)
`
`6. The formulation of claim 1,
`wherein said
`surfactant/solubilizer is
`selected from the group
`consisting of anionic
`surfactants, pluronics,
`poloxamers, SDS, Triton-100,
`polysorbates, propylene glycol,
`PEG and similar compounds,
`Brij58 9poly(oxyethylene)20
`cetyl ether, cremophor EL,
`cetyl trimethylammonium
`bromide (CTAB),
`dimethylacetamide (DMA), NP
`40 (Nonidet P-40), and N-
`methyl-2-pyrrolidone
`(Pharmasolve), and amino
`acids.
`
`Claim 44 (also claims 63
`and 90)
`44. The kit of claim 40,
`wherein said surfactant is
`selected from the group
`consisting of anionic
`surfactants, pluronics,
`poloxamers, SDS, Triton-
`100, polysorbates,
`propylene glycol, PEG and
`similar compounds, Brij58
`9poly(oxyethylene)20 cetyl
`ether, cremophor EL, cetyl
`trimethylammonium
`bromide (CTAB),
`dimethylacetamide (DMA),
`NP 40 (Nonidet P-40), and
`N-methyl-2-pyrrolidone
`(Pharmasolve), and amino
`acids.
`
`
`
`
`
`
`
`Bracco’s proposed constructions of the disputed claim terms.
`
`II.
`
`The Sincalide Formulation Inventions Of The Patent-In-Suit
`
`The ‘046 Patent, entitled “Sincalide Formulations,” resulted from the prosecution of a
`
`patent application (i.e., U.S.S.N. 10/222,540) before the United States Patent and Trademark
`
`Office (“USPTO”) that was filed on August 16, 2002. Exh. 67. The ‘046 Patent was issued by
`
`the USPTO as a patent on October 12, 2004 and is now owned by the Plaintiff, Bracco (it was
`
`first owned by a Bracco-related company). The subject matter of the ’046 Patent was invented
`
`in Princeton, New Jersey, by employees of a Bracco-related company, and they are listed as
`
`“Inventors” on the face of the patent. Exh. 1. The ‘046 Patent’s Abstract, which was reviewed
`
`and approved by the USPTO Examiner, describes the subject matter of the ‘046 Patent
`
`
`
`generally:
`
`
`
`
`
`3
`
`
`
`

`

`
`
`“The invention features sincalide formulations that include an effective amount of
`sincalide, a bulking agent/tonicity adjuster, a stabilizer, a surfactant, a chelator,
`and a buffer. The invention also features kits and methods for preparing improved
`sincalide formulations, as well as methods for treating, preventing, and
`diagnosing gall bladder-related disorders using sincalide formulations.” Exh. 1.
`
`Bracco sells a product that is covered by the claims of the ‘046 Patent, namely
`
`
`
`“Kinevac® (Sincalide for Injection).” Exh. 63 (Kinevac® package insert). It is sold as powder
`
`in a vial, to which a healthcare professional adds sterile water and then administers it to
`
`patients:
`
`“Each vial of sincalide provides a sterile nonpyrogenic lyophillized white powder
`consisting of 5 mcg sincalide with 170 mg mannitol, 30 mg arginine
`hydrochloride, 15 mg lysine hydrochloride, 9 mg potassium phosphate dibasic, 4
`mg methionine, 2 mg pentetic acid, 0.04 mg sodium metabisulfite, and 0.005 mcg
`polysorbate 20. The pH is adjusted to 6.0 - 8.0 with hydrochloric acid and/or
`sodium hydroxide prior to lyophilization.” Exh. 63.
`
`Bracco first purchased a Kinevac®-named and sincalide-containing product from
`
`Bristol-Myers Squibb (“BMS”) in 1994, when Bracco purchased the entire diagnostics
`
`business of BMS and took over its U.S. operations. Prior to that time, BMS had licensed its
`
`largest selling diagnostic product from Bracco. The sincalide-containing product purchased
`
`from BMS came with its original New Drug Application (“NDA”) filed with and approved by
`
`the FDA.
`
`The active pharmaceutical ingredient of all the Kinevac®-named products, including
`
`the one from BMS, is sincalide. Exh. 1, ‘046 Patent, col. 1, lines 9-16; Exh. 63. Sincalide is a
`
`peptide molecule composed of eight amino acids bound together. Id. When administered to
`
`patients, sincalide, among other effects, causes the contraction of the patient’s gall bladder
`
`and stimulates pancreatic secretions. Exh. 63. Kinevac® currently has three indications
`
`approved by the United States Food and Drug Administration (“FDA”):
`
`
`
`
`
`4
`
`

`

`“Kinevac (Sincalide for Injection) may be used: (1) to stimulate gallbladder
`contraction, as may be assessed by various methods of diagnostic imaging, or to
`obtain by duodenal aspiration a sample of concentrated bile for analysis of
`cholesterol, bile salts, phospholipids, and crystals; (2) to stimulate pancreatic
`secretion (especially in conjunction with secretin) prior to obtaining a duodenal
`aspirate for analysis of enzyme activity, composition, and cytology; (3) to
`accelerate the transit of a barium meal through the small bowel, thereby
`decreasing the time and extent of radiation associated with fluoroscopy and x-ray
`examination of the intestinal tract.” Exh. 63 (“Indications and Usage”).
`
`The original Kinevac® formulation purchased from BMS (“BMS-Kinevac®”) is
`
`described in the ‘046 Patent’s “Background of the Invention.” Exh. 1, ‘046 Patent, col. 1,
`
`lines 8-40. The BMS-Kinevac® product contained only sincalide and a salt, i.e., sodium
`
`chloride. Id. The ‘046 Patent describes “various drawbacks” of the BMS-Kinevac®, and
`
`specifically “potency variability,” concluding that, “there is a need for sincalide formulations
`
`having improved and consistent potency.” Exh. 1, ‘046 Patent, col. 1, lines 27-40.
`
`The ‘046 Patent solved that need. In the ‘046 Patent’s “Summary of the Invention”
`
`(Exh. 1, line 41-col. 2, line 57), the patent states that “[t]he present invention satisfies the need
`
`for improved sincalide formulations by providing formulations that eliminate the need for a
`
`20% overage of sincalide.” Exh. 1, ‘046 Patent, col. 1, lines 41-50. It also states that “[t]he
`
`sincalide formulations of the invention are also purer than prior art formulations, and have
`
`fewer degradants and more consistent potency.” Id.
`
`The ‘046 Patent has 108 claims that define the inventions covered by the patent. They
`
`are generally directed to sincalide formulations (e.g., claims 1-20 and 106), methods for
`
`making sincalide formulations (e.g., claims 21-39), kits containing sincalide formulations
`
`(e.g., claims 40-55 and 107-108), and methods for using sincalide formulations (e.g., claims
`
`56-105).
`
`
`
`
`
`
`
`5
`
`
`
`

`

`Claim 1 has six elements or claim terms, (a) through (f). As was described above, of
`
`these six elements, the parties have asked for two terms of claim 1 to be construed, namely a
`
`“a buffer” and “a surfactant/solubilizer.” The third term that the parties seek to have construed
`
`by the Court (i.e., “a surfactant”) is used as part of the “a surfactant/solubilizer” term and in
`
`other claims (e.g., claim 40). Claim 1 recites:
`
`1.
`
`A stabilized, physiologically acceptable formulation of sincalide
`
`comprising:
`
`
`
`
`
`
`
`
`
`
`
`
`
`(a) an effective amount of sincalide,
`
`(b) at least one stabilizer,
`
`(c) a surfactant/solubilizer,
`
`(d) a chelator,
`
`(e) a bulking agent/tonicity adjuster, and
`
`(f) a buffer.
`
`Thus, claim 1 recites a formulation that includes sincalide, the active pharmaceutical
`
`ingredient. Claim 1 also recites excipients or components of the formulation, including a
`
`stabilizer, a surfactant/solubilizer, a chelator, a bulking agent/tonicity adjuster and a buffer, as
`
`set forth in the claim and described in the specification. See also, Exh. 1, ‘046 Patent, col. 3,
`
`lines 30-39; col. 4, lines 8-31. Importantly, an excipient or component can perform more than
`
`one function in a particular formulation, as explicitly stated in the specification (e.g., Exh. 1,
`
`‘046 Patent, col. 4, lines 22-31 (“a single excipient may perform more than one function ...
`
`e.g., amino acids may function as bulking agents, stabilizers and/or buffers”); col. 10, line 42
`
`to col. 11, line 24; col. 13, lines 24-28 (“a component in a formulation kit can also serve more
`
`than one function”); Table 1). The inclusion of multi-function components is also explicitly
`
`
`
`
`
`6
`
`

`

`set forth in the claims (e.g., claims 3, 6 and 44 explicitly include “amino acids” as “a buffer,”
`
`“a surfactant/solubilizer,” and “a surfactant,” respectively). Forrest Decl., ¶¶ 22-25.
`
`Claim 40 is also illustrative of the ‘046 Patent claims. Claim 40 recites:
`
`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.
`
`Claim 40 recites a “kit” and it is similar to claim 1, although it includes a “surfactant”
`
`and not the “surfactant/solubilizer” of claim 1. Claim 40 also includes the recitation of a
`
`“powder mixture” and a “container.” A “physiologically acceptable fluid” is explicitly
`
`optional in claim 40.
`
`III. Legal Standards For Claim Construction
`
`Claim terms “are generally given their ordinary and customary meaning, which is the
`
`meaning a term would have to a person of ordinary skill in the art after reviewing the intrinsic
`
`record at the time of the invention.” O2 Micro Intern. Ltd. V. Beyond Innovation Technology
`
`Co., Ltd., 521 F.3d 1351, 1360 (Fed. Cir. 2008) (en banc) (quoting Philips v. AWH Corp., 415
`
`
`
`
`
`7
`
`

`

`F.3d 1303 at 1312-13 (Fed. Cir. 2005)).4 “When construing claims, the claims and the rest of
`
`the patent, along with the patent’s prosecution history (together, the intrinsic evidence of the
`
`meaning of the claims) are the primary resources; while helpful, extrinsic sources like
`
`dictionaries and expert testimony cannot overcome more persuasive intrinsic evidence.”
`
`Finisar Corp. v. DirectTV Group, Inc., 523 F.3d 1323, 1328 (Fed. Cir. 2008) (en banc)
`
`(quoting Philips, 415 F.3d at 1318)..
`
`Thus, although intrinsic evidence is most informative in determining the claim term’s
`
`ordinary and customary meaning, a court may in some circumstances use extrinsic evidence,
`
`which “consists of all evidence external to the patent and prosecution history, including expert
`
`and inventor testimony, dictionaries, and learned treatises.” Phillips, 415 F.3d at 1317
`
`(quoting Markman v. Westview Instruments, Inc., 52 F.3d 967, 980 (Fed. Cir. 1995) (en
`
`banc)).
`
`The principal legal standard issues presented by Maia’s competing claim construction
`
`boil down to (1) Maia’s impermissible incorporation of limitations from the specification and
`
`from extrinsic evidence into the claim terms, and (2) Maia’s neglecting to read the claim
`
`terms in the context of the claims and the specification. The key question is whether such
`
`incorporation of limitations from the specification and extrinsic evidence can override the
`
`clear and unequivocal definitions set forth in the intrinsic evidence of the claims read in light
`
`of the specification of the patent-in-suit. It cannot as a matter of law, and thus the relevant
`
`intrinsic evidence must govern the constructions here.
`
`
`
`
`
`
`
`4 As stated in Phillips, “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 disputed term appears, but in the
`context of the entire patent, including the specification.” Phillips, 415 F.3d at 1313.
`
`
`
`8
`
`

`

`In sharp contrast to Maia’s approach, Bracco’s proposed constructions for the three
`
`terms in dispute use direct, verbatim quotations from the claims as read in light of the
`
`specification of the ‘046 Patent, and thus they are the proper constructions of the terms as a
`
`matter of law. Phillips, 415 F.3d at 1313.
`
`III. The Person Of Skill In The Art
`
`The person of skill in the art must be identified to determine the proper claim
`
`construction, as explained above. E.g., Phillips, 415 F.3d at 1313-1314. It is this hypothetical
`
`person’s understanding that the claim construction process determines. Id. The person of skill
`
`in the art is presumed to have known the relevant art at the time of the invention, here, August
`
`16, 2002, when the application that led to the ‘046 Patent was filed. Factors that may be
`
`considered in determining the level of skill in the art may include: (a) “type of problems
`
`encountered in the art;” (b) “prior art solutions to those problems;” (c) “rapidity with which
`
`innovations are made;” (d) “sophistication of the technology;” and (e) “educational level of
`
`active workers in the field. In a given case, every factor may not be present, and one or more
`
`factors may predominate.” In re GPAC, 57 F.3d 1573, 1579, (Fed. Cir. 1995); Custom
`
`Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, (Fed. Cir. 1986);
`
`Environmental Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
`
`Here, as explained further in the accompanying Declaration of Laird Forrest, Ph.D.
`
`(“Forrest Declaration”),5 the type of problem is formulating drugs, and, for this invention in
`
`particular, peptide drugs. Prior art solutions were, for example, the original BMS-Kinevac®
`
`formulation before the ‘046 Patent was filed (i.e., sincalide with NaCl salt). Innovations were
`
`not made rapidly (i.e., the original BMS-Kinevac® formulation stayed the same for 30 years
`
`
`
`
`5 Dr. Laird Forrest is a professor at the University of Kansas and is one of the preeminent
`experts in the formulation of peptide and protein drugs.
`
`
`
`9
`
`

`

`before the ‘046 Patent was filed). The sophistication of the technology in formulating peptide
`
`drugs is relatively high compared to other fields of science because the formulation of such
`
`drugs for use in humans is regulated by the FDA, which adds additional sophistication and
`
`knowledge to the hypothetical person of skill in the art. It is also rather high because peptide
`
`and protein drugs are relatively difficult to formulate. The educational level of active workers
`
`in the field are people with about two years of experience in formulating drugs and at least a
`
`B.S. or equivalent undergraduate degree in chemistry or a related field. Forrest Decl., ¶¶ 16-
`
`20.
`
`This person of skill in the art is important to the analysis here. In particular, contrary
`
`to what Maia has asserted, the person of skill in the art knows that the field relating to peptide
`
`and protein drug formulation is unpredictable, and thus what is known about one drug even in
`
`this narrow area cannot be necessarily transferred to another drug (Waterman (MAIA004986,
`
`4991, 4995), Arakawa 2001 (p. 308, 323), Wang 1999 (p. 175, 178), Li 1995 (p. 498), Wang
`
`1988 (p. S8, S22), Wang 2000 (pp. 50-51), Bayol (col. 2, lines 54-64), Audhya (pp. 5-7)), De
`
`Felippis 2003 (¶ 14), Prior 1990 (1:20-2:15), and Schneider 2011 (pg. 7447)).6 For this reason,
`
`it is even less appropriate to attempt to transfer information from general college-level
`
`dictionaries and textbooks and from articles in different fields to the ‘046 Patent claim
`
`construction. Forrest Decl., ¶¶ 21.
`
`IV.
`
`
`“Buffer” Term Construction
`
`All 108 claims of the ‘046 Patent include an embodiment of the “buffer” claim term,
`
`in the form of independent claims that stand on their own (viz., claims 1, 21, 40, 77 and 104),
`
`dependent claims that identify a group of specific, preferred embodiments of the “buffer”
`
`10
`
`
`
`
`6 See, Exhibits 3-14, respectively.
`
`
`
`

`

`claim term (viz., claims 3, 23, 41, 60, and 87), or additional claims that identify even more
`
`specific, preferred embodiments. The parties’ competing claim constructions for this term are
`
`below:
`
`Claim
`Term
`“a buffer”
`
`Bracco’s Claim Construction
`
`Maia’s Claim Construction
`
`This claim term should be given
`its plain and ordinary meaning.
`The plain and ordinary meaning
`is: “a compound that stabilizes
`the pH of a sincalide
`formulation.”
`
`Excipients that “stabilize the pH” and
`“include, but are not limited to, phosphoric
`acid, phosphate (e.g. monobasic or dibasic
`sodium phosphate, monobasic or dibasic
`potassium phosphate, etc.),
`citric acid, citrate (e.g. sodium citrate,
`etc.), sulfosalicylate, acetic acid, acetate
`(e.g. potassium acetate, sodium acetate,
`etc.), methyl boronic acid, boronate,
`disodium succinate hexahydrate, amino
`acids, including amino acid salts (such
`as histidine, glycine, lysine, imidazole),
`lactic acid, lactate (e.g. sodium lactate,
`etc.), maleic acid, maleate, potassium
`chloride, benzoic acid, sodium benzoate,
`carbonic acid, carbonate (e.g. sodium
`carbonate, etc.), bicarbonate (e.g.
`sodium bicarbonate, etc.), boric acid,
`sodium borate, sodium chloride, succinic
`acid, succinate (e.g. sodium succinate),
`tartaric acid, tartrate (e.g. sodium tartrate,
`etc.), tris(hydroxymethyl)-aminomethane,
`biological buffers (such as N-2-
`hydroxyethylpiperazine,N’-2-
`ethanesulfonic acid (HEPES), CHAPS and
`other ‘Good’s’ buffers), and the like.” ‘046
`patent, col. 9, lines 45-65.
`
`
`
`
`A.
`
`The Intrinsic Evidence Provides Bracco’s Construction Of “A Buffer”
`
`Bracco’s construction for the term, “a buffer,” is the definition for the term taken
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`directly from the intrinsic evidence, i.e., from the claims themselves and the specification of
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`the ‘046 Patent at column 9, lines 45-65. Exh. 1. The first part of the construction is from
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`column 9, line 45, “[b]uffering agents are employed to stabilize the pH” (emphasis added).
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`11
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`

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`The latter part of Bracco’s construction starting with the words, “include, but are not limited
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`to, phosphoric acid …,” is the definition of the term taken verbatim from column 9, lines 49-
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`65 where there is a non-limiting but exemplary list of preferred embodiments. Importantly, it
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`is also the definition for the term found in asserted claims in this action, namely claims 3, 23,
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`41, 60, and 87 (see table below). It is a canon of claim construction that claims should
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`generally be interpreted to include preferred embodiments. E.g., Burke, Inc. v. Burno Indep.
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`Living Aids, Inc., 183 F.3d 1334, 1341 (Fed. Cir. 1999); National Steel Car, Ltd. v. Canadian
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`Pacific Railway, LTD., 357 F.3d 1319, 1336 n.19 (Fed. Cir. 2004); Accent Packaging, Inc. v.
`
`Leggett & Platt, Inc., 707 F.3d 1318, 1326 (2013). Forrest Decl., ¶¶ 26-31.
`
`Thus, Bracco’s construction for the term “buffer” is the correct construction under the
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`applicable legal precedent. A comparison of Bracco’s “buffer” term claim construction with
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`the disclosure in the ‘046 patent specification shows they are identical in substance. The only
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`differences are of no substance, namely, the claim construction proffered does not repeat
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`unnecessary, repetitive words (e.g., “of sincalide formulations”) or potential results (i.e.,
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`“consequen[ces]”) or potential advantages (i.e., “reduce the risk of chemical stability at
`
`extreme pH values”) that are disclosed in the specification but not limitations of the claims.
`
`Likewise, claims 3, 23, 41, 60 and 87 are identical to the claim construction in substance also.
`
`These claims simply do not repeat some of the examples of embodiments that the claim
`
`construction and specification include (e.g., the claims state “phosphate” but not the specific
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`examples of “phosphate”, i.e., “(e.g. monobasic or dibasic sodium phosphate, monobasic or
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`dibasic potassium phosphate, etc.)”).
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`12
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`
`
`Bracco’s “Buffer” Claim
`Construction
`
`
`
`Excipients that
`“stabilize the pH” and
`
`
`
`
`
`
`
`“include, but are not limited
`to, phosphoric acid,
`phosphate (e.g. monobasic
`or dibasic sodium
`phosphate, monobasic or
`dibasic potassium
`phosphate, etc.),
`citric acid, citrate (e.g.
`sodium citrate, etc.),
`sulfosalicylate, acetic acid,
`acetate (e.g. potassium
`acetate, sodium acetate,
`etc.), methyl boronic acid,
`boronate, disodium
`succinate hexahydrate,
`
`amino acids, including
`amino acid salts (such
`as histidine, glycine, lysine,
`imidazole), lactic acid,
`lactate (e.g. sodium lactate,
`etc.), maleic acid, maleate,
`potassium chloride, benzoic
`acid, sodium benzoate,
`carbonic acid, carbonate
`(e.g. sodium carbonate, etc.),
`bicarbonate (e.g.
`sodium bicarbonate, etc.),
`
`
`
`
`
`The ‘046 Patent
`Specification on “Buffer”
`(col. 9, lines 44-65)
`
`“Buffering agents
`Buffering agents are
`employed to
`stabilize the pH of sincalide
`formulations of the invention,
`and consequently, reduce the
`risk of chemical stability at
`extreme pH values. Buffering
`agents useful in the
`preparation of formulation
`kits of the invention
`include, but are not limited
`to, phosphoric acid,
`phosphate (e.g. monobasic
`or dibasic sodium
`phosphate, monobasic or
`dibasic potassium
`phosphate, etc.),
`citric acid, citrate (e.g.
`sodium citrate, etc.),
`sulfosalicylate, acetic acid,
`acetate (e.g. potassium
`acetate, sodium acetate,
`etc.), methyl boronic acid,
`boronate, disodium
`succinate hexahydrate,
`
`amino acids, including
`amino acid salts (such
`as histidine, glycine, lysine,
`imidazole), lactic acid,
`lactate (e.g. sodium lactate,
`etc.), maleic acid, maleate,
`potassium chloride, benzoic
`acid, sodium benzoate,
`carbonic acid, carbonate
`(e.g. sodium carbonate,
`etc.), bicarbonate (e.g.
`sodium bicarbonate, etc.),
`
`‘046 Patent Claims 3, 23,
`41, 60 and 87 (spaced for
`comparison to the
`specification)
`
`
`
`
`
`
`
`
`“The formulation of claim 1,
`wherein said buffer is
`selected from the group
`consisting
`of phosphoric acid,
`phosphate,
`
`
`
`
`citric acid, citrate
`
`sulfosalicylate, acetic acid,
`acetate
`
`methyl boronic acid,
`boronate, disodium
`succinate hexahydrate, one
`or more
`amino acids,
`
`
` lactic acid,
`lactate
` maleic acid, maleate,
`potassium chloride, benzoic
`acid, sodium benzoate,
`carbonic acid, carbonate,
`
` bicarbonate,
`
`
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`

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`boric acid, sodium borate,
`sodium chloride, succinic
`acid, succinate (e.g. sodium
`succinate), tartaric acid,
`tartrate (e.g. sodium
`tartrate, etc.),
`tris(hydroxymethyl)-
`aminomethane, biological
`buffers (such as N-2-
`hydroxyethylpiperazine,N’-
`2-ethanesulfonic acid
`(HEPES), CHAPS and other
`‘Good’s’ buffers), and the
`like.”
`‘046 patent, col. 9, lines 45-
`65.
`
`boric acid, sodium borate,
`sodium chloride, succinic
`acid, succinate (e.g. sodium
`succinate), tartaric acid,
`tartrate (e.g. sodium
`tartrate, etc.),
`tris(hydroxymethyl)-
`aminomethane, biological
`buffers (such as N-2-
`hydroxyethylpiperazine,N’-
`2-ethanesulfonic acid
`(HEPES), CHAPS and
`other ‘Good’s’ buffers), and
`the like.”
`
`boric acid, borate,
`sodium chloride, succinic
`acid, succinate,
` tartaric acid,
`tartrate,
`
`tris(hydroxymethyl)-
`aminomethane, and bio-
`logical buffers.”
`
`As described above, the specification provides other information concerning the buffer
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`besides its definition but there is no basis to include such limiting language from the
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`specification in the construction of the term. This includes the possible benefit, advantage or
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`result of using a buffer, which is to “reduce the risk of chemical stability at extreme pH
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`values,” a benefit, advantage or result which is not specified in the claims and thus which is
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`not a proper limitation. Exh. 1, ‘046 Patent, col. 9, lines 46-47. There is also information in
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`the specification concerning a particular buffer, a phosphate buffer, which is a specifically
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`preferred embodiment. Exh. 1, ‘046 Patent, col. 9 line 65 to col. 10, line 9; Example 1.
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`While the specification is highly relevant in determining the meaning of a claim term,
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`the Federal Circuit has warned that Courts must be careful to avoid “the danger of reading
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`limitations from the specification into the claim.” Phillips, 415 F.3d at 1323. In this regard,
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`the Federal Circuit stated that, “although the specification often describes very specific
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`embodiments of the invention, we have repeatedly warned against confining the claims to
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`those embodiments.” Id. It is the purpose of the specification to teach and enable those skilled
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`in the art to make and use the invention, but not to necessarily restrict the invention to specific
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`14
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`examples of results and embodiments that are provided in the specification. Id. Thus, the
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`“include, but are not limited to” language in Bracco’s construction, which was taken verbatim
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`from the specification at column 9, line 49, is appropriate to not overly limit the claim term
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`but to show how a person of skill in the art would understand what the inventors meant to
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`include. Forrest Decl., ¶¶ 31-32.
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`
`
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`B.
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`The Extrinsic Evidence Supports Bracco’s Construction Of “A Buffer”
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`Dr. Forrest’s declaration describes the extrinsic evidence from the relevant art area
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`that a person of skill in the art would consider, which all confirms Bracco’s construction. As
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`described above, a particular issue in this action is whether amino acids can meet the “buffer”
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`claim term. Dr. Forrest identifies a large number relevant scientific articles and patents that
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`demonstrate that they can. This includes relevant articles from before the filing date of the
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`‘046 Patent (i.e., August 16, 2002) and relevant articles after the filing date, which are all
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`consistent and which confirm the knowledge of a person of skill in the art that supports
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`Bracco’s construction of the term. Forrest Decl., ¶¶ 33-62; see, Exhs. 15-39.
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`C. Maia’s Claim Construction Position For “A Buffer”
`Is Not Support