IN THE UNITED STATES DISTRICT COURT
`DISTRICT OF NEW JERSEY
`
`BRACCO DIAGNOSTICS INC.,
`Plaintiff,
`v.
`MAIA PHARMACEUTICALS, INC.,
`Defendant.
`
`____________________________________
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`)
`)
`)
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`
`MAIA PHARMACEUTICALS, INC.
`Counterclaimant,
`v.
`BRACCO DIAGNOSTICS INC.,
`Counterclaim Defendant.
`
`Case No. 3:17-cv-13151-PGS-TJB
`
`AMENDED JOINT CLAIM CONSTRUCTION AND PREHEARING STATEMENT
`
`Plaintiff/Counterclaim Defendant, Bracco Diagnostics Inc. (“Bracco”), and
`Defendant/Counterclaimant Maia Pharmaceuticals, Inc. (“Maia”), pursuant to L.Pat.R. 4.3
`and the Court’s June 29, 2018, Letter Order, provide this Joint Claim Construction and
`Prehearing Statement.
`
`I.
`
`Introduction
`
`This action concerns United States Patent No. 4,803,046 (the “’046 patent”) and potentially
`issues of infringement and validity of the ‘046 patent.
`
`The Court’s June 29, 2018, Letter Order, requires the Parties to file this Joint Claim
`Construction and Prehearing Statement pursuant to L.Pat.R. 4.3 concerning the ‘046 patent
`claims. L.Pat.R. 4.3 states:
`
`4.3. Joint Claim Construction and Prehearing Statement.
`
`Not later than 30 days after the exchange of “Preliminary Claim Constructions”
`under L. Pat. R. 4.2(a), the parties shall complete and file a Joint Claim
`Construction and Prehearing Statement, which shall contain the following
`information:
`
`(a) The construction of those terms on which the parties agree;
`
`(b) Each party's proposed construction of each disputed term, together with an
`identification of all references from the intrinsic evidence that support that
`
`1
`
`Bracco Ex. 2001
`Maia v. Bracco
`IPR2019-00345
`
`

`

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`construction, and an identification of any extrinsic evidence known to the party on
`which it intends to rely either to support its proposed construction or to oppose any
`other party's proposed construction, including, but not limited to, as permitted by
`law, dictionary definitions, citations to learned treatises and prior art, and testimony
`of all witnesses including experts;
`
`(c) An identification of the terms whose construction will be most significant to the
`resolution of the case. The parties shall also identify any term whose construction
`will be case or claim dispositive or substantially conducive to promoting settlement,
`and the reasons therefor;
`
`(d) The anticipated length of time necessary for the Claim Construction Hearing;
`and
`
`(e) Whether any party proposes to call one or more witnesses at the Claim
`Construction Hearing, the identity of each such witness, and for each witness, a
`summary of his or her testimony including, for any expert, each opinion to be
`offered related to claim construction.
`
`(f) Any evidence that is not identified under L. Pat. R. 4.2(a) through 4.2(c)
`inclusive shall not be included in the Joint Claim Construction and Prehearing
`Statement.
`
`(g) This rule does not apply to design patents.
`
`The Joint Claim Construction And Prehearing Statement Under L.Pat.R. 4.3
`
`The Agreed Term Constructions Pursuant To L.Pat.R. 4.3(a)
`
`A.
`
`The Parties have put the construction of three patent claim terms in issue: “buffer,”
`“surfactant/solubilizer,” and “surfactant,” in this proceeding. The Parties have not put the
`construction of any of the other patent claim terms in issue and also have not agreed upon the
`construction of any of the terms of the ‘046 patent.
`
`
`
`II.
`
`
`
`
`
`
`
`
`
`
`B.
`
`The Parties’ Proposed Constructions Of Each
`Disputed Term And Identification Of Intrinsic
`And Extrinsic Evidence Pursuant To L.Pat.R. 4.3(b)
`
`1.
`
`Bracco’s Proposed Constructions Of Each
`Disputed Term And Identification Of Intrinsic
`And Extrinsic Evidence Pursuant To L.Pat.R. 4.3(b)
`
`
`
`
`
`a.
`
`Buffer Terms Construction and Evidence
`
` 2
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`
`Claim
`Term
`“a buffer”
`
`Bracco’s Proposed Construction Of “Buffer”1
`
`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.
`
`
`
`‘046 patent, original application and prosecution history citations in Bracco’s identification of
`evidence pursuant to L.Pat.R. 4.2(a) through 4.2(c), including, without limitation:
`
`
`All 108 claims of the ‘046 patent include an embodiment of a “buffer” in their
`elements and thus all 108 claims, as issued and as originally filed, are relevant
`intrinsic evidence to the construction of these terms. This evidence includes the ‘046
`patent and the prosecution history of the ‘046 patent, which contains the claims as
`issued and as originally filed, and the references cited therein. B0017245-18314;
`B0020091-20552.
`
`Dependent claims such as claims 3, 23, 41, 60, and 87 provide examples of particular
`buffers within the meaning of the terms, including amino acids, and these claims are
`relevant evidence of the meaning of the “buffer” claim term.
`
`The ‘046 patent also describes buffering “at extreme pH values” (e.g., col. 9, lines 45-
`47; Example 1), which may be encountered, for example, in the processes for making
`peptide formulations, final and intermediate peptide preparations, and their uses.
`
`The entire ‘046 patent specification is relevant to the construction of the buffer claim
`term. These relevant portions of the ‘046 patent specification include but are not
`limited to the description of these claim terms found in the Abstract; col. 1, lines 56-69
`(e.g., “Suitable buffers include … amino acid buffers”); col. 2, lines 13-29; col. 4,
`
`
`1 Bracco’s proposed constructions will change if Maia’s motion to amend its
`infringement contentions filed August 17, 2018 is granted and Bracco is given an
`opportunity to respond by amending Bracco’s infringement and claim construction
`contentions.
`
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`lines 7-32; col. 4, lines 33-43 (e.g., “The concentration ranges of the various
`ingredients in Table 1 can be adjusted upward or downward if necessary in
`conjunction with: … obtaining the desired pH”); Table 1; Table 2; col. 9, line 44 to
`col. 10, line 9 (e.g., “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 … amino acids, including amino acid salts (such as … lysine
`…”); col. 12, line 65 to col. 13, line 10 (e.g., “Buffering agents useful in the
`preparation of formulation kits of the invention are discussed herein and include, for
`example … amino acids (including amino acid salts);” col. 13, lines 24-32; col. 13,
`lines 33-39; Example 1 at col. 16, line 43 to col. 18, line 14; and the original claims
`filed with the specification. Amino acids and their functions are described in other
`portions of the ‘046 patent specification also.
`
`For example, amino acids that provide “stability” results are described at col. 10, line
`42 to col. 11, line 4. L-arginine monohydrochloride, L-lysine monohydrochloride, and
`L-methionine are disclosed as particularly preferred. Col. 11, lines 2-4. Furthermore,
`Example 6 of the ‘046 patent (col. 31, line 1 to col. 34, line 25) is entitled “Effect of
`Amino Acids on Sincalide Formulations.” It relates to relevant properties and results
`of amino acid excipients that are described in the ‘046 patent. For example, it states
`that:
`
`“During formulation studies it was observed that both exposure to air and
`lyophilization were areas of concern for scale-up manufacturing due to reduced
`potency of sincalide in the formulation. The reduced potency was a result of
`surface adsorption/denaturation resulting from exposure of sincalide to air, and
`yielding degradants via oxidation. Exposure of sincalide formulations to
`thermal stress during lyophilization also resulted in degradation and reduced
`recovery of sincalide.”
`
`“Experiments were conducted to evaluate several amino acids as potential
`stabilizers of sincalide, including the non-polar (hydrophobic) methionine
`residue, aspartic acid and glutamic acid, the polar glycine and cysteine
`residues, and the basic lysine and arginine amino acids.” Col. 31, lines 4-18.
`
`Example 1 of the ‘046 patent (col. 16, line 43 to col. 18, line 14) is directed to the
`“Effect of Buffering Agent and Formulation pH on Sincalide Formulations.” There it
`is stated that “Experiments were conducted to determine the effect of pH on the
`chemical stability of sincalide. Chemical instability, or degradation, may be caused by,
`for example, oxidation, reduction, deamidation, hydrolysis, imide formation,
`racemization, isomerization, and/or β-elimination.” A pH range of 3.0 to 9.1 was
`examined. The Example states that “By measure of the percentage recovery, sincalide
`was stable in 35 mM phosphate buffer solution at pH values ranging from 5.0-9.1 over
`a 24-hour period. At pH values <5.0, sincalide degradation was evident even at the
`initial time point.” It is reported that buffers may provide stability to the formulation,
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`and, also, that amino acids, such as arginine and lysine, may serve as buffers in
`formulations of relevant peptide and protein drugs. See references cited below.
`
`Amino acids in particular are described in the ‘046 patent specification and claims as
`meeting the buffer claim terms: claims 3, 23, 41, 60, 87 (see Table B above, and these
`were original claims filed with the original application and thus form part of the
`specification); col. 1, lines 56-69 (e.g., “Suitable buffers include … amino acid
`buffers”); col. 9, line 44 to col. 10, line 9 (e.g., “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 … amino acids, including
`amino acid salts (such as … lysine …”); col. 12, line 65 to col. 13, line 10 (e.g.,
`“Buffering agents useful in the preparation of formulation kits of the invention are
`discussed herein and include, for example … amino acids (including amino acid
`salts)”).
`
`The ‘046 patent specification at col. 4, lines 23-28 and lines 29-30 states that “a single
`excipient may perform more than one function” and “multiple excipients serving the
`same function may be used”:
`
`“… in some embodiments of the invention a single excipient may perform more
`than one function. For example, a single excipient may be multi-functional, e.g.,
`amino acids may function as bulking agents, stabilizers and/or buffers and other
`excipients may function, for example, as both a stabilizer and a chelator or as
`both a bulking agent and a tonicity adjuster. Alternatively, multiple excipients
`serving the same function may be used. For example, the formulation may
`contain more than one excipient that functions as a stabilizer.”
`
`At col. 13, lines 24-28, and in Table 1, the specification also states that a component
`can serve more than one function. For example, col. 13, lines 24-28 states:
`
`“As discussed, a component in a formulation kit can also serve more than one
`function. For example, an excipient which serves as a stabilizer may also serve
`as the chelator and an excipient which serves as a bulking agent may also serve
`as a tonicity adjuster.”
`
`Expert testimony in Bracco’s identification of evidence pursuant to L.Pat.R. 4.2(a)
`through 4.2(c), including, without limitation:
`
`
`Experts (Dr. Joel Bowen, Dr. Sally Look and/or Dr. Laird Forrest) will confirm
`the evidence from the ‘046 patent specification and claims and other
`information that is discussed herein and the references cited below. Their
`opinions will be on supporting Bracco’s claim construction position and
`opposing Maia’s claim construction position and cited evidence concerning (1)
`the meaning of the claim terms, which is set forth above, (2) the intrinsic
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`evidence that supports the meaning of the claim terms, and (3) the extrinsic
`evidence that supports the meaning of the claim terms.
`
`The substance of the experts’ proposed testimony will be the claim construction
`and intrinsic evidence that is set forth herein. They will use the perspective of a
`person of ordinary skill in the art (this person of ordinary skill in the art is
`defined in Bracco’s Infringement and Validity Contentions). Experts will also
`present evidence from their experiences, knowledge and expertise, including
`from the following references (e.g., produced with Bracco’s Infringement
`Contentions (B0018315-19550) or cited below) on what the claim term “buffer”
`as used in the ‘046 patent means to a person of ordinary skill in the art, which is
`the meaning for the claim term set forth above. They will also show how the
`structure of buffers that are described and claimed in the ‘046 patent interact
`with peptides and proteins such as sincalide, through discussion, data and/or
`drawings and images, both theoretically and/or through experimental evidence.
`Their testimony may include:
`
`Maia’s claim construction position for the term “buffer” is incorrect as a matter
`of law and inconsistent with the intrinsic and extrinsic evidence:
`
`• Maia appears to be attempting to have the court ignore the dispositive intrinsic
`evidence (set forth above) and read out the patent’s preferred embodiments for
`the term (e.g., amino acids) so that Maia’s use of amino acids, copied from the
`patent, does not infringe.
`
`• Specifically, Maia’s construction is not based on the intrinsic evidence from the
`specification or claims (set forth above) that establish that the “buffer” term
`specifically includes amino acids such as lysine (e.g., col. 9, lines 44-65; claim
`3).
`
`Instead, Maia attempts to add the words, “a compound,” to the construction that
`are not found in the ‘046 patent or any intrinsic or extrinsic evidence and which
`may read out many of the embodiments disclosed and specifically claimed in
`the patent (e.g., col. 9, lines 44-65; claim 3).
`
`• Maia also attempts to apply extrinsic evidence from dictionaries with narrow
`definitions of buffer (e.g., must have pKa within one pH unit of formulation to
`work, which is merely a guide and not a rule of chemistry concerning when
`buffering will occur) that are inconsistent with the specification and claims and
`would exclude preferred embodiments such as amino acids including lysine
`(e.g., col. 9, lines 44-65; claim 3).
`
`• Maia’s citation to extrinsic evidence from Bracco’s Kinevac NDA and
`underlying laboratory notebooks does not support Maia’s position. First, the
`NDA information cited by Maia is for a different audience and for a different
`purpose, which is outside of the patent context. The FDA wants the developer’s
`
`•
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`story of why the developer used the particular excipients and thus the NDA
`information cited by Maia identifies only one or a very limited number of the
`many possible functions and effects an excipient may have that a developer is
`seeking in that formulation, not all possible functions and effects under all
`circumstances. Second, in the NDA information Bracco labels the amino acid
`excipients as “stabilizers,” a possible result of a “buffer” function (e.g., col. 9,
`lines 46-47, “consequently reduce the risk of chemical stability at extreme pH
`values;” col. 10, lines 42 to col. 11, line 5, identifying several functions of
`amino acids that can result in more stability, including “Surface exposed
`residues can react readily with oxidizing agents at physiological pH, scavenging
`oxidizing molecules and protecting critical regions of peptides,” which are
`results that may come from buffers), so the “stabilizer” characterization by
`Bracco is not inconsistent with the intrinsic evidence and Bracco’s claim
`construction position. Third, the ‘046 patent is very clear that particular
`excipients may have multiple functions (e.g., col. 4, lines 22-31; col. 13, lines
`24-28; Table 1; see also Maia 505(b)(2) NDA and references cited by Bracco
`(e.g., Prior, Startzel, Meinicke) below.
`
`• Maia’s claim construction submission is vague and it does not comply with
`L.Pat.R. 4.2(b) to specifically identify the intrinsic and extrinsic evidence it
`supposedly relies on. Consistent with this failure to comply with the rules,
`Maia’s excerpt from a McGraw-Hill Dictionary on buffer (MAIA0008250-
`8253) is unreadable.
`
`Additional references in Bracco’s identification of evidence pursuant to L.Pat.R. 4.2(a)
`through 4.2(c), including, without limitation:
`
`
`The Handbook of Pharmaceutical Excipients, Seventh Edition (2012)
`(B0020730-34), characterizes lysine hydrochloride and methionine, two amino
`acids, as “Buffering agent, as their “Functional Category.” The MDS (Material
`Safety Data Sheet) and related literature for lysine hydrochloride, methionine,
`and arginine hydrochloride shows that the amino acid solutions spontaneously
`reach an equilibrium pH of between about 5 and 7. E.g., B0020735-49. See also
`MAIA0001176-87, 1252-53, 1278.
`
`Patel et al., WO201575743A1, US20160250295A1, which published on May
`28, 2015 (“Patel”), is relevant to these claim terms. For example, it shows an
`arginine buffer for a gonadotropin formulation in the range of pH 5.0 to 9.0
`(e.g., from US [0013], [0064], and claim 30). Arginine can also be used as a
`stabilizer or antioxidant (e.g., from US [0032] and claim 38). B0018765, 19498.
`
`DeFelippis et al., US20030104983A1, which published on June 5, 2003
`(“DeFelippis”) is relevant to these claim terms. For example, it shows an
`arginine buffer for an insulin analog formulation at about pH 7.4 (e.g., [0048],
`Table 2, claim 1, Examples 2 and 5). B0018637.
`
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`
`George et al., WO2000056273A2, US6239088B1, which published on
`September 28, 2000, (“George”), is relevant to these claim terms. For example,
`it shows an arginine buffer for a lachrymal fluid formulation at a pH of 6 to 8
`(e.g., US col. 3, line 60 – col. 4, line 2; claims 12 and 19; Example 1).
`B0018909, 19111.
`
`Wang et al., US20110135615A1, US8642029B2, which published on June 9,
`2011 (“Wang”), is relevant to these claim terms. For example, it shows an
`arginine buffer for a Lactobacillus formulation at a pH of about 7.0 to 8.2 (e.g.,
`[0021], [0063]; claims 1, 6, 19, 21, 23 and 28; Example 4). B0018709, 18928.
`
`Chauhan et al., CA2983256A1, which published on October 5, 2017
`(“Chauhan”), is relevant to these claim terms. For example, it shows an arginine
`buffer for a cefepime/tazobactam formulation at a pH of 5.5 to 7.5 (e.g., p. 7-8;
`p. 10, lines 7-9; claims 1 and 11; Example 4). B0018404.
`
`Hay et al., US20170274076A1, which published on September 28, 2017
`(“Hay”), is relevant to these claim terms. For example, it shows an arginine
`buffer for an anti-dengue antibody formulation at a pH of about 7 (e.g., “In
`another embodiment, the buffering agent comprises arginine and provides a pH
`of about 7.0” [0042], [0375]; claim 1; Example 1). B0018796.
`
`Nishida et al., US20040132689A1, which published on July 8, 2004
`(“Nishida”), is relevant to these claim terms. For example, it shows an arginine
`buffer for a colloid formulation at various pH, including a formulation with
`arginine buffer at about pH 6.5 having high buffer capacity (e.g., [0018],
`[0036]; claim 11; Example 1). B0018646.
`
`Huili, et al., CN102068413A, which published on January 2, 2013 (“Huili”), is
`relevant to these claim terms. For example, it shows an arginine buffer
`(B0018436) for a biatranamine liposome formulation at a pH of about 5.5 to 6.5
`(e.g., claims 4 and 5; Example 2). B0018422.
`
`Chandrashekhar et al., WO2017013591A1, which published on January 26,
`2017 (“Chandrashekhar”), is relevant to these claim terms. For example, it
`shows an arginine buffer and a lysine buffer (“Suitable buffering agents include
`amino acids such as arginine … and lysine…”) for a levothyroxine formulation,
`and an arginine formulation having a pH of 6.0 ± 1.0 (e.g., p. 4; claim 4;
`Example 5). B0019531.
`
`Friedl et al., WO2009121945A2, US9415016B2, which published on October
`8, 2009 (“Friedl”), is relevant to these claim terms. For example, it shows an
`arginine buffer for a DPP-4 inhibitor formulation (e.g., col. 6, lines 18-25).
`B0019058, 19378.
`
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`Meinicke, WO2011039367A2, CA2776296A1, which published on November
`11, 2017 (“Meinicke”), is relevant to these claim terms. For example, it shows
`an arginine buffer for a DPP-4 inhibitor formulation (p. 21 at lines 6-12, “The
`buffering agent used may be a basic amino acid, which has an intramolecular
`amino group and alkaline characteristics ... A preferred buffering agent within
`the meaning of this invention is L-aginine.” L-arginine also had “a particular
`suitable stabilizing effect on the compositions of this invention ….” Id. at line
`10. The Meinicke references states that “Thus, L-arginine may act as stabilizing
`and buffering agent in the formulation” (p. 33, lines 2-3; see also, e.g., p. 21,
`lines 26 and 32; claims 1 and 3; Example 1). B0018334, 19429.
`
`Gastner, US20100056633A1, which published on March 4, 2010, (“Gastner”),
`shows an arginine buffer and a lysine buffer for a creatine formulation at a pH
`of about 8 to 12 (e.g., claim 20, Figure 1, Example 1). B0018655.
`
`Malecki, GB915429A, which published on January 9, 1963 (“Malecki”), is
`relevant to these claim terms. For example, it shows a lysine buffer for a
`vegetable product at a pH of about 8.5 to 9.7 (e.g., claims 11 and 12; Example
`4). B0018489.
`
`Stoclet, FR2468366A1, which published on May 8, 1981 (“Stoclet”), is relevant
`to these claim terms. For example, it shows a lysine buffer for anti-glaucoma
`formulation at a pH of about 7 to 9 (e.g., B0018482; claims 1-4). B0018481.
`
`Holton et al., US20170196256A1, US9629392B2, which published on July 13,
`2017 (“Holton I”), is relevant to these claim terms. For example, it shows a
`lysine buffer for a smokeless tobacco product at a pH of about 6 to 11 (e.g., col.
`17, line 40 to col. 18, line 1; Examples 2 and 3). B0018775, 19089.
`
`Duggins et al., US20130209540A1, which published on August 15, 2013
`(“Duggins”), is relevant to these claim terms. For example, it shows a lysine
`buffer for a multi-layered pharmaceutical formulation buffered in the pH range
`of about 6 to about 10 (e.g., [0060], claim 27, Example 1). B0018743.
`
`Holton et al., US20130074856A1, which published on March 28, 2013
`(“Holton II”), is relevant to these claim terms. For example, it shows an
`arginine buffer and a lysine buffer for a tobacco extract formulation generally in
`the pH range from about 6 to 11 (e.g., [0062-0063]; Examples 1 to 4 and 6 to 7;
`claim 8). B0018726.
`
`Prior et al., EP0448605A1 (“Prior”), is relevant to these claim terms. For
`example, it shows that basic amino acids such as arginine and lysine were
`preferred amino acids (e.g., B00206027-28; B0020631) that were used to
`solubilize immunoglobulins and related polypeptides (e.g., claims 1, 3, 5, 7, 9,
`12). Prior also states that “the basic amino acid itself, with proper pH
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`adjustment, behaves as a buffer”, and thus arginine can have a dual role as both
`a solubilizer and buffering agent (7:32 to 8:1). B0020623-41.
`
`Startzel, “Arginine as an Excipient for Protein Freeze-Drying: A Mini Review,”
`Journal of Pharmaceutical Sciences, 2018, 107, pp. 960-967 (“Startzel”), is
`relevant to these claim terms. For example, it shows that arginine is a
`solubilizer of proteins in relevant lyophilization processes due to its
`physicochemical properties, including its amorphous nature. It can also serve as
`a buffer (B0018621). The relevant chemistry of arginine as a buffer, solubilizer,
`stabilizer, etc., is discussed. B0018620.
`
`Nagai et al., “Temperature Dependence of the Dissociation Constants of Several
`Amino Acids,” Journal Chemical Engineering Data, 2008, 53, pp. 619-627
`(“Nagai”), is relevant to these claim terms, For example, it shows that lysine
`and arginine have pKa’s within the buffering range of about 6.5 to about 7.5
`when at low concentrations. B0020650.
`
`Azactam (pH 4.5 to 7.5) and Ceptaz (pH 5 to 7) use arginine as a buffer in their
`formulations. B0020694-726.
`
`Maia’s 505(b)(2) NDA states that some excipients can serve more than one
`function in a formulation (e.g., MAIA0000326-28, 454, 466, 478, 485; see also
`Maia’s reference in its citation of evidence to B00009940 and B00011548),
`characterizes relevant excipients (e.g., MAIA0000019, 75, 199, 207, 208, 215,
`298, 322, 328, 369, 445, 466, 3622), and characterizes and measures relevant
`properties of formulations relating to claim terms (e.g., MAIA0000019, 75, 199,
`207, 208, 215, 298, 322, 328, 369, 445, 466, 1252, 1277, 1278, 2056, 2265,
`2478, 3622).
`
`References cited by Maia in its validity contentions counter Maia’s positions on claim
`construction of the term buffer. The following are examples:
`
`Nema et al., “Excipients and Their Use in Injectable Products,” PDA Journal
`1.
`of Pharmaceutical Science and Technology 51 (1997), p. 166-171 (“Nema”). Nema
`was cited by Maia (MAIA0004762-4769) and it is a review article and survey of the
`excipients used in pharmaceutical products as reported in the Physicians’ Desk
`Reference. Nema also was considered by the Examiner, cited by Bracco, and not used
`to reject the ‘046 patent claims during the prosecution history. Therefore, the claims of
`the ‘046 patent were allowed to issue by the Examiner and the United States Patent
`and Trademark Office (“USPTO”) over the Nema reference.
`
`Nema states (at p. 169) that arginine may be used as a buffer in formulations:
`
`“Table VII lists additives which are used to modify osmolality, and as bulking
`or lyo-cryo protective agents. Dextrose and sodium chloride are used to adjust
`tonicity in the majority of formulations. Some amino acids, glycine, alanine,
`
` 10
`
`

`

`
`
`Case 3:17-cv-13151-PGS-TJB Document 28 Filed 08/23/18 Page 11 of 38 PageID: 612
`
`histidine, imidazole, arginine, asparagine, aspartic acid, are used as bulking
`agents for lyophilization and may serve as stabilizers for proteins or peptides
`and as buffers.”
`
`Nema also states (at p. 169) that lysine may be used as a buffer in
`formulations:
`
`“Lysine and glycine are amino acids which function as buffers and stabilize
`protein and peptide formulations. These amino acids are also used as lyo-
`additives and may prevent cold denaturation.”
`
`Wang, “Instability, Stabilization, and Formulation of Liquid Protein
`2.
`Pharmaceuticals,” International Journal of Pharmacy, 185 (1999), pp. 129-88 (“Wang
`1999”). Wang 1999 was cited by Maia (MAIA0004686-4745) and it relates to the
`stability of protein drugs.
`
`Wang 1999 (at 175) recognizes arginine as a buffer component in protein
`formulations. It states:
`
`“Multiple excipients are often required in a liquid protein formulation,
`although a single-excipient protein formulation may be sufficient, such as tPA,
`which is formulated in 0.5 M arginine-phosphate buffer (pH 7.3) (Overcashier
`et al., 1997).”
`
`If Maia is permitted to amend its infringement contentions, then Bracco will seek to add
`additional intrinsic evidence and extrinsic evidence, including citations to the ‘046 patent
`specification, fact and expert witness testimony, citations to the Bracco Kinevac NDA,
`citations to the Maia 505(b)(2) NDA, and citations to dictionaries and scientific literature.
`
`
`
`
`
`
`
`b.
`
`Surfactant/Solubilizer and Surfactant
`Terms Construction and Evidence
`
`
`Claim Term
`
`“a surfactant”
`
`Bracco’s Proposed Claim Construction of “Surfactant”
`And “Surfactant/Solubilizer”2
`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
`as TWEEN® 20 and TWEEN® 80, propylene glycol, PEG and
`similar compounds, Brij58 (polyoxyethylene 20 cetyl ether),
`cremophor EL, cetyl trimethylammonium bromide (CTAB),
`
`
`2 Bracco’s proposed constructions will change if Maia’s motion to amend its
`infringement contentions filed August 17, 2018 is granted and Bracco is given an
`opportunity to respond by amending Bracco’s infringement and claim construction
`contentions.
`
`
` 11
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`

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`Case 3:17-cv-13151-PGS-TJB Document 28 Filed 08/23/18 Page 12 of 38 PageID: 613
`
`dimethylacetamide (DMA), NP-40 (Nonidet P-40), and N-
`methyl-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/solubilizer” Excipients that “may reduce the interfacial tension or aid in
`solubilization” and “include, but are not limited to, pluronics
`(e.g., Lutrol F68, Lutrol F127), Poloxamers, SDS, Triton-100,
`polysorbates such 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 N-methyl-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.
`
`
`‘046 patent, original application and prosecution history citations in Bracco’s identification of
`evidence pursuant to L.Pat.R. 4.2(a) through 4.2(c), including, without limitation:
`
`
`All 108 claims of the ‘046 patent include an embodiment of a surfactant/solubilizer or
`a surfactant in particular in their elements and thus all 108 claims, as issued and as
`originally filed, are relevant intrinsic evidence to the construction of these terms. This
`includes the ‘046 patent and the prosecution history of the ‘046 patent, which contains
`the claims as issued and as originally filed, and the references cited therein.
`B0017245-18314; B0020091-20552.
`
`For example, a set of dependent claims states that “wherein said surfactant is a
`nonionic surfactant” when referring to a “surfactant/solubilizer” element of an
`independent claim. Claim 7 in particular states, “The formulation of claim 1, wherein
`said surfactant is a nonionic surfactant.” Claim 1 used the claim term
`“surfactant/solubilizer” and thus claim 7 demonstrates that the claim term
`“surfactant/solubilizer” should be construed to mean a surfactant and/or a solubilizer.
`See also claims 18, 27 and 38.
`
`As another example, dependent claims such as claims 6, 26, 44, 63, and 90 provide
`examples of particular “surfactants/solubilizers” and “surfactants” within the meaning
`of the terms, including amino acids, and thus these claims are relevant evidence of the
`meaning of these claim terms.
`
`The entire ‘046 patent specification is relevant to the constructi