Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 1 of 40
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE WESTERN DISTRICT OF PENNSYLVANIA
`
`AMGEN INC. and AMGEN
`MANUFACTURING LIMITED,
`
`Plaintiffs,
`
`v.
`
`MYLAN INC., MYLAN
`PHARMACEUTICALS INC., MYLAN
`GMBH and MYLAN N.V.,
`
`Defendants.
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`Civil Action
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`No. 17-cv-01235-MRH
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`REDACTED VERSION
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`Electronically Filed
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`AMGEN’S OPENING CLAIM CONSTRUCTION BRIEF
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`1 of 40
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`Fresenius Kabi
`Exhibit 1034
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 2 of 40
`No. 2:17-cv-01235-MRH
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`
`TABLE OF CONTENTS
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`Page
`
`TABLE OF AUTHORITIES ......................................................................................................... iii 
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`
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`TABLE OF AUTHORITIES ......................................................................................................... iv 
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`TABLE OF EXHIBITS ...................................................................................................................v 
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`I. 
`
`INTRODUCTION ...............................................................................................................1 
`
`A. 
`
`B. 
`
`The Accused Product: Mylan’s Pegfilgrastim Biosimilar .......................................1 
`
`The Asserted Patents ................................................................................................2 
`
`1. 
`
`2. 
`
`U.S. Patent No. 9,643,997............................................................................2 
`
`U.S. Patent No. 8,273,707............................................................................3 
`
`II. 
`
`III. 
`
`LEGAL STANDARD ..........................................................................................................5 
`
`DISCUSSION ......................................................................................................................7 
`
`A. 
`
`U.S. Patent No. 9,643,997........................................................................................7 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`Level of Ordinary Skill in the Art ................................................................7 
`
`Agreed-Upon Terms ....................................................................................7 
`
`Disputed Term: “forming a refold solution comprising the
`solubilization solution and a refold buffer” .................................................8 
`
`Disputed Term: “applying the refold solution to a separation
`matrix” .......................................................................................................10 
`
`Disputed Term: “under conditions suitable for the protein to
`associate with the matrix” ..........................................................................15 
`
`Disputed Term: “washing the separation matrix” ......................................18 
`
`Disputed Term: “eluting the protein from the separation matrix” .............19 
`
`B. 
`
`U.S. Patent No. 8,273,707......................................................................................21 
`
`1. 
`
`2. 
`
`Level of Ordinary Skill in the Art ..............................................................21 
`
`Agreed-Upon Terms ..................................................................................21 
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`TABLE OF CONTENTS
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`Page
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`Disputed Term: “such that the dynamic capacity of the column is
`increased for the protein” (Claim 1) ..........................................................22 
`
`Disputed Term: “mixing a preparation containing the protein with
`a combination of a first salt and a second salt” (Claims 1 and 10) ............24 
`
`Disputed Term: “loading the mixture onto a hydrophobic
`interaction chromatography column” (Claims 1 and 10) ...........................26 
`
`Disputed Term: “between about 0.1 M and about 1.0” (Claims 1
`and 10) .......................................................................................................29 
`
`Disputed Term: “formulating the protein” (Claim 8) ................................30 
`
`Disputed Term: “increasing the dynamic capacity of a hydrophobic
`interaction chromatography column for a protein” (Claim 10) .................31 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`IV. 
`
`CONCLUSION ..................................................................................................................32 
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 4 of 40
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`
`CASES
`
`TABLE OF AUTHORITIES
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`Page(s)
`
`Amgen v. Sandoz,
`Case No. 14-cv-04741-RS, 2016 WL 4137563 (N.D. Cal. Aug. 4, 2016) ........................11, 15
`
`Comark Commc’ns, Inc. v. Harris Corp.,
`156 F.3d 1182 (Fed. Cir. 1998)............................................................................................5, 17
`
`E.I. du Pont de Nemours & Co. v. Phillips Petroleum Co.,
`849 F.2d 1430 (Fed. Cir. 1988)..................................................................................................5
`
`Ferring B.V. v. Watson Labs., Inc.-Fla.,
`764 F.3d 1382 (Fed. Cir. 2014)................................................................................................29
`
`Interactive Gift Express, Inc. v. Compuserve Inc.,
`256 F.3d 1323 (Fed. Cir. 2001)..........................................................................................21, 25
`
`Koninklijke Philips N.V. v. Zoll Lifecor Corp.,
`No. 2:12-cv-1369, 2014 WL 5088863 (W.D. Pa. July 31, 2014) ..............................................9
`
`Metabolite Labs., Inc. v. Lab. Corp. of Am. Holdings,
`370 F.3d 1354 (Fed. Cir. 2004)..................................................................................................9
`
`Mformation Techs., Inc. v. Research in Motion, Ltd.,
`764 F.3d 1392 (Fed. Cir. 2014)................................................................................................25
`
`O2 Micron Int’l Ltd. v. Beyond Innovation Tech. Co., Ltd.,
`521 F.3d 1351 (Fed. Cir. 2008)........................................................................................ passim
`
`Omega Eng’g, Inc. v. Raytek Corp.,
`334 F.3d 1314 (Fed. Cir. 2003)................................................................................................13
`
`Pall Corp. v. Micron Separations, Inc.,
`66 F.3d 1211 (Fed. Cir. 1995)..................................................................................................29
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005)........................................................................................ passim
`
`Teva Pharms. USA, Inc. v. Sandoz, Inc.,
`135 S. Ct. 831 (2015) .................................................................................................................6
`
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`TABLE OF AUTHORITIES
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`Page(s)
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`CASES
`
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996)................................................................................................ 5-6
`
`STATUTES
`
`42 U.S.C. § 112 ..............................................................................................................................23
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`OTHER AUTHORITIES
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`Local Patent Rule 4.3 .......................................................................................................................1
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 6 of 40
`No. 2:17-cv-01235-MRH
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`TABLE OF EXHIBITS
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`
`
`Exhibit (“Ex.”)
`
`Exhibit 1
`
`Exhibit 2
`
`Exhibit 3
`
`Description
`Mylan Inc.’s, Mylan Pharmaceuticals Inc.’s, Mylan GmbH’s, and
`Mylan N.V.’s Non-infringement Contentions Regarding U.S. Patent
`No. 9,643,997 (Excerpt) (“Mylan ’997 Patent Non-infringement
`Contentions”)
`Mylan Inc.’s, Mylan Pharmaceuticals Inc.’s, Mylan GmbH’s, and
`Mylan N.V.’s Invalidity Contentions Regarding U.S. Patent
`No. 8,273,707 (Excerpt) (“Mylan ’707 Patent Invalidity
`Contentions”)
`Mylan Inc.’s, Mylan Pharmaceuticals Inc.’s, Mylan GmbH’s, and
`Mylan N.V.’s Non-infringement Contentions Regarding U.S. Patent
`No. 8,273,707 (Excerpt) (“Mylan ’707 Patent Non-infringement
`Contentions”)
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 7 of 40
`No. 2:17-cv-01235-MRH
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`Pursuant to this Court’s Case Management Order (Dkt. No. 65) and Local Patent
`
`Rule 4.3, Plaintiffs Amgen Inc. and Amgen Manufacturing Limited (collectively, “Amgen”)
`
`respectfully submit this brief in support of their proposed claim constructions for the patents-in-
`
`suit, U.S. Patent Nos. 9,643,997 (“the ’997 Patent”) (Dkt. No. 101-1) and 8,273,707 (“the ’707
`
`Patent”) (Dkt. No. 101-6) (together, “the Asserted Patents”) and the concurrently filed
`
`identification of extrinsic evidence.
`
`I.
`
`INTRODUCTION
`
`A.
`
`The Accused Product: Mylan’s Pegfilgrastim Biosimilar
`
`Mylan’s accused product is a proposed biosimilar version of Amgen’s Neulasta®.
`
`Neulasta® and Mylan’s proposed biosimilar product contain a modified form of the protein,
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`human granulocyte-colony stimulating factor (“G-CSF”), called “filgrastim,” to which a
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`polyethylene glycol (“PEG”) group has been chemically attached. The resulting molecule,
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`“pegfilgrastim,” is the active ingredient in both Amgen’s and Mylan’s products.
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`G-CSF stimulates the production of a type of white blood cell known as neutrophils,
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`which are an important component of the immune system. Consequently, Neulasta® is used to
`
`reduce the chance of infection due to low white blood cell count, a condition called neutropenia.
`
`Neutropenia is a common side effect of chemotherapy and makes a person highly susceptible to
`
`life-threatening infections.
`
`Filgrastim is made by inserting DNA that encodes G-CSF into a bacterial cell, growing
`
`such cells at industrial scale, stimulating the bacterial cells to produce the G-CSF, and then
`
`purifying the G-CSF from other components of the manufacturing process. Protein purification
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`is a critical step in the manufacture of G-CSF that may affect its biological activity and safety.
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`B.
`
`The Asserted Patents
`1.
`
`U.S. Patent No. 9,643,997
`
`Using recombinant DNA technology, non-mammalian (e.g., bacterial) expression
`
`systems can be used to produce proteins, including proteins for therapeutic use like human
`
`G-CSF. (See Dkt. No. 101-1, ’997 Patent, at col. 3:58-65, 12:5113:8.) However, non-
`
`mammalian expression systems often produce mammalian proteins in misfolded and/or
`
`aggregated states that are less biologically active than native protein. (See id. at col. 12:21-32.)
`
`Thus, the expressed protein must undergo a series of processes before it can be therapeutically
`
`useful. (See id. at col. 12:33-50.) This processing includes, for example, solubilization and
`
`refolding. (See id.) Solubilization separates and unfolds (i.e., denatures) proteins and is
`
`accomplished by mixing the proteins with various chemicals to form a solubilization solution.
`
`(See id. at col. 2:26-29.) Refolding then folds the protein into its native three-dimensional
`
`structure and is accomplished by mixing the solubilized protein with various chemicals to form a
`
`refold solution. (See id. at col. 2:29-33.)
`
`The protein of interest also must be purified by separating it from contaminants, such as
`
`proteins expressed by the host organism and chemicals introduced by the prior processing steps.
`
`(See id. at col. 15:25-30.) Purification is typically performed using a separation matrix, which is
`
`an adsorbent material that relies on the chemical and/or physical characteristics of the protein of
`
`interest, chemicals to be removed, and/or contaminating proteins to separate the protein of
`
`interest from its environment. (See id. at col. 7:25-37.) A separation matrix effects the
`
`separation of the protein of interest from its environment using specific, reversible interactions
`
`between molecules based on, for example, charge, isoelectric point, hydrophobicity, or size,
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`among other characteristics. (See id.)
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`The inventors of the ’997 Patent discovered that proteins could be purified by applying
`
`refold solutions to separation matrices without dilution and without the steps of dialysis,
`
`precipitation, or centrifugation, after protein refolding but before purifying the protein. (See id.
`
`at col. 4:52-57, 12:14-20.) Prior to this invention, these intervening processing steps had been
`
`used in the prior art. (See id.) This invention thus provides a more efficient means of purifying
`
`proteins, eliminating these steps from the purification process. (See id. at col. 12:14-20.)
`
`The disputed terms of independent Claim 9 of the ’997 Patent are in bold underline
`
`below:
`
`9. A method of purifying a protein expressed in a non-native limited
`solubility form in a non-mammalian expression system comprising:
`(a) solubilizing the expressed protein in a solubilization solution comprising
`one or more of the following:
`(i)
`a denaturant;
`(ii) a reductant; and
`(iii) a surfactant
`(b) forming a refold solution comprising the solubilization solution and
`a refold buffer, the refold buffer comprising one or more of the
`following:
`(i)
`a denaturant;
`(ii) an aggregation suppressor;
`(iii) a protein stabilizer; and
`(iv) a redox component;
`(c) applying the refold solution to a separation matrix under conditions
`suitable for the protein to associate with the matrix;
`(d) washing the separation matrix; and
`(e) eluting the protein from the separation matrix.
`
`2.
`
`U.S. Patent No. 8,273,707
`
`The ’707 Patent is directed to a process for protein purification using what is known as
`
`hydrophobic interaction chromatography, or “HIC.” HIC separates a protein from impurities
`
`based on a property known as hydrophobicity, or tendency to avoid water. (See Dkt. No. 101-6,
`
`’707 Patent, at col. 1:36-49.) Hydrophobic regions on the surface of the protein interact with the
`
`hydrophobic groups on the matrix in the column, and this interaction causes the protein to adsorb
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`to the matrix while impurities flow past and out of the column. (See id.) In HIC, a liquid
`
`mixture containing the protein, known as the “solution phase” or “mobile phase,” is passed
`
`through a column containing a solid matrix, known as the “solid phase” or “resin,” which is
`
`covered with immobilized hydrophobic groups. (See id. at col. 3:7-12, 53-64.) Salt(s) in the
`
`mobile phase promote hydrophobic interactions between the protein and the matrix and thereby
`
`facilitate protein adsorption to the HIC matrix. (Id. at col. 1:40-49.) Elution (i.e., release) of the
`
`protein from the column is typically achieved by reducing the salt concentration in the mobile
`
`phase to reverse the adsorption of the protein from the matrix. (See id. at col. 3:13-16.)
`
`The ’707 Patent addresses an issue known as “‘breakthrough’ or loss of protein to the
`
`solution phase before elution.” (See id. at col. 2:9-20, 3:37-41.) The invention improves
`
`processes known at the time by increasing a HIC column’s “dynamic capacity,” which is the
`
`maximum amount of protein in solution that can be loaded onto a column without significant
`
`breakthrough or leakage of the protein into the solution phase of the column before elution. (Id.
`
`at col. 3:64:3.) Before the ’707 Patent, HIC purification relied on high salt concentrations to
`
`increase dynamic capacity. (See id. at col. 3:37-41.) But high concentrations of salt can be
`
`detrimental. (Id. at col. 3:41-45.) A key inventive aspect of the ’707 Patent is the use of a
`
`combination of a first salt and a second salt, each at a relatively low concentration, that together
`
`“increase the dynamic capacity of the HIC column for a particular protein” more than using a
`
`single salt alone at the high concentrations reported in the prior art. (See id. at col. 4:46-51, 5:26-
`
`28; see also id. at col. 2:9-15; 4:33-42, 56-60; 5:25-26; 15:8–16:26.) By increasing the dynamic
`
`capacity of a HIC column and using a lower salt concentration, the invention improves the
`
`efficiency of the HIC purification process. (See id. at col.1:54-62.) This in turn decreases the
`
`cost and time required to purify a batch of protein, which is particularly useful in commercial
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`production and purification of proteins, especially therapeutic proteins, such as G-CSF. (See id.
`
`at col. 10:4-24; 11:36-46.)
`
`II.
`
`LEGAL STANDARD
`
`Claim construction begins with the plain language of the claim. The words of a claim
`
`“are generally given their ordinary and customary meaning,” which is “the meaning that the term
`
`would have to a person of ordinary skill in the art at the time of the invention.” Phillips v. AWH
`
`Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005). This starting point “is based on the well-settled
`
`understanding that inventors are typically persons skilled in the field of the invention and that
`
`patents are addressed to and intended to be read by others of skill in the pertinent art.” Id.
`
`at 1313.
`
`The claims “must be read in view of the specification,” which is “always highly relevant
`
`to the claim construction analysis.” Id. at 1315. “Usually, it is dispositive; it is the single best
`
`guide to the meaning of a disputed term.” Id.; see Vitronics Corp. v. Conceptronic, Inc., 90 F.3d
`
`1576, 1582 (Fed. Cir. 1996) (“it is always necessary to review the specification to determine
`
`whether the inventor has used any terms in a manner inconsistent with their ordinary meaning”).
`
`However, “limitations from the specification are not to be read into the claims.” Comark
`
`Commc’ns, Inc. v. Harris Corp., 156 F.3d 1182, 1186–87 (Fed. Cir. 1998). While “[i]t is
`
`entirely proper to use the specification to interpret what the patentee meant by a word or phrase
`
`in the claim,” a limitation from the specification should not be read into the claims “[w]here a
`
`specification does not require a limitation.” E.I. du Pont de Nemours & Co. v. Phillips
`
`Petroleum Co., 849 F.2d 1430, 1433 (Fed. Cir. 1988) (emphasis in original). Thus, “[a]lthough
`
`the specification may aid the court in interpreting the meaning of disputed claim language,
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`particular embodiments and examples appearing in the specification will not generally be read
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`into the claims.” Comark, 156 F.3d at 1187.
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`In addition to consulting the specification, a court “should also consider the patent’s
`
`prosecution history,” which is also intrinsic evidence. Phillips, 415 F.3d at 1315. “Like the
`
`specification, the prosecution history provides evidence of how the PTO and the inventor
`
`understood the patent.” Id. The prosecution history informs “the meaning of the claim language
`
`by demonstrating how the inventor understood the invention and whether the inventor limited the
`
`invention in the course of prosecution, making the claim scope narrower than it would otherwise
`
`be.” Id.
`
`“In most situations, an analysis of the intrinsic evidence alone will resolve any ambiguity
`
`in a disputed claim term. In such circumstances, it is improper to rely on extrinsic evidence.”
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`Vitronics, 90 F.3d at 1583. Where the intrinsic record is ambiguous, and when necessary, courts
`
`may rely on 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. If the court does need to look beyond the intrinsic evidence and to
`
`consult extrinsic evidence to understand, for example, the background science or the meaning of
`
`a term in the relevant art during the relevant time period, it “will need to make subsidiary factual
`
`findings about that extrinsic evidence.” Teva Pharms. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831,
`
`837, 841 (2015) (“Construction of written instruments often presents a question solely of law, at
`
`least when the words in those instruments are used in their ordinary meaning.” (quotation marks
`
`omitted)). Even if a court resolves a dispute between experts and makes a factual finding that, in
`
`general, “a certain term of art had a particular meaning to a person of ordinary skill in the art at
`
`the time of the invention,” it must then “conduct a legal analysis: whether a skilled artisan would
`
`ascribe that same meaning to that term in the context of the specific patent claim under review.”
`
`Id. at 841 (emphasis in original). That is because “experts may be examined to explain terms of
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`art, and the state of the art, at any given time,” but they cannot be used to prove “the proper or
`
`legal construction of any instrument of writing.” Id. Thus, the ultimate interpretation of the
`
`claim term is a legal conclusion. Id.
`
`III. DISCUSSION
`A.
`
`U.S. Patent No. 9,643,997
`1.
`
`Level of Ordinary Skill in the Art
`
`Amgen submits that a person of ordinary skill in the art (POSITA) as of the priority day
`
`of the ’997 Patent, June 25, 2009, would have a Ph.D. in biochemical engineering, biomedical
`
`engineering, biochemistry, or a related discipline, with at least two years of work experience in
`
`the field of protein chromatography. Additional training or study could substitute for additional
`
`work experience and additional work experience or training could substitute for formal
`
`education.
`
`2.
`
`Agreed-Upon Terms
`
`Claim Term
`“separation matrix”
`
`Agreed-Upon Construction
`any adsorbent material that utilizes specific, reversible
`interactions between synthetic and/or biomolecules in order
`to effect the separation of the protein from its environment
`
`After the parties filed the Joint Disputed Claim Terms Chart and Prehearing Statement on
`
`May 18, 2018 (Dkt. No. 103), the parties continued negotiations to reach agreement on the
`
`constructions of some disputed claim terms. For the ’997 Patent, the parties thus agree that the
`
`construction of “separation matrix” should be based on the definition in the specification of the
`
`patent: “any adsorbent material that utilizes specific, reversible interactions between synthetic
`
`and/or biomolecules . . . in order to effect the separation of the protein from its environment.”
`
`(See Dkt. No. 101-1, ’997 Patent, at col. 7:25-32.)
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`3.
`
`Disputed Term: “forming a refold solution comprising the
`solubilization solution and a refold buffer”
`
`Claim Term
`“forming a refold solution
`comprising the solubilization
`solution and a refold buffer”
`
`Mylan’s Proposed
`Construction
`Mylan contends that no
`construction is necessary and
`that this term should be
`afforded only its plain and
`ordinary meaning.
`
`Amgen’s Proposed
`Construction
`mixing the solution
`comprising the solubilized
`protein and one or more of a
`denaturant, a reductant, and a
`surfactant with a pH-buffered
`solution comprising one or
`more of a denaturant, an
`aggregation suppressor, a
`protein stabilizer, and a redox
`component providing
`conditions for the protein to
`refold into its biologically
`active form
`
`The parties dispute whether this term requires construction. However, because the scope
`
`of this term is in dispute and directly impacts the infringement analysis, it requires construction.
`
`See O2 Micron Int’l Ltd. v. Beyond Innovation Tech. Co., 521 F.3d 1351, 1361–62 (Fed. Cir.
`
`2008) (“When the parties present a fundamental dispute regarding the scope of a claim term, it is
`
`the court’s duty to resolve it.”). Amgen’s claim construction is correct for three reasons.
`
`First, Mylan’s “plain and ordinary meaning” construction is inadequate here because the
`
`parties dispute the scope of the claim term and the dispute cannot be resolved without looking to
`
`the intrinsic evidence. See id. Amgen’s proposed construction provides for a refold solution that
`
`is comprised of (1) any solution that meets the elements of a solubilization solution, as defined
`
`by step (c) of Claim 9, and (2) any solution that meets the elements of a refold buffer, as defined
`
`by step (d) of Claim 9. Under Amgen’s proposed construction, the claim thus covers a process
`
`where,
`
`
`
`, so long as the solution still satisfies the solubilization solution
`
`elements of step (c) (i.e., comprises one or more of a denaturant, a reductant, and a surfactant).
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`8
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 15 of 40
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`Defining the scope of this claim term will be fundamental to the parties’ infringement positions
`
`because
`
`. (See
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`Ex. 1 Mylan ’997 Patent Non-infringement Contentions at 41-46; Dkt. No. 101-1, ’997 Patent, at
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`col. 14:13-16.) Failure to address now whether this claim covers
`
`
`
`
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` is therefore a recipe for a subsequent dispute as to the scope of
`
`the claim later. See O2 Micron, 521 F.3d at 1362–63; cf. Koninklijke Philips N.V. v. Zoll Lifecor
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`Corp., No. 2:12-cv-1369, 2014 WL 5088863, at *5 (W.D. Pa. July 31, 2014) (declining to
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`construe a claim when construction was not necessary to resolve any issue of infringement or
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`validity).
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`Second, Amgen’s proposed construction is grounded in the language of the claim itself
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`read in view of the specification of the ’997 Patent. See Phillips, 415 F.3d at 1315–16;
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`Metabolite Labs., Inc. v. Lab. Corp. of Am. Holdings, 370 F.3d 1354, 1360 (Fed. Cir. 2004) (“As
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`always, the claim language itself governs its meaning. . . . . In most cases, the best source for
`
`discerning the proper context of the claim terms is the patent specification where the patent
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`applicant describes the invention.”). On its face, the claim only requires forming the refold
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`solution comprising the solubilization solution, which comprises one or more of a denaturant, a
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`reductant, and a surfactant (as recited in step (c)), and the refold buffer, which comprises one or
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`more of a denaturant, an aggregation suppressor, a protein stabilizer, and a redox component (as
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`recited in step (d)). The claim itself is thus silent as to
`
`
`
`. Indeed, the plain language of
`
`the claim says that only “one or more” of the listed components is required to comprise the
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`solubilization solution. As long as one or more of the listed components remain, the
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 16 of 40
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`solubilization solution remains a solubilization solution. The specification of the ’997 Patent
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`also teaches that components utilized for solubilization must at least be diluted to form the refold
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`solution. (See Dkt. No. 101-1, ’997 Patent, at col. 19:25-27, 20:48-50 (Examples 1 and 2 both
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`teach that a solubilization solution “was diluted” into a refold buffer for refolding.).) Amgen’s
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`proposed construction is therefore supported by the claim itself read in view of the specification.
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`Third, Amgen’s proposed construction is necessary because common usage of the word
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`“buffer” does not necessarily reflect its use in the ’997 Patent. See O2 Micron, 521 F.3d at
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`136162. A POSITA would understand that “buffer,” in common usage, could refer to various
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`types of solutions, but it most commonly refers to a pH-buffered solution. (See Declaration of
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`Richard C. Willson, Ph.D. in Support of Amgen’s Opening Claim Construction Brief (“Willson
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`Decl.”), concurrently filed with this brief, at ¶ 44.) The specification of the ’997 Patent teaches
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`that “buffer” has a particular meaning in this field of art, namely that “the buffer component of
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`the refold solution is to maintain the pH of the refold solution.” (Dkt. No. 101-1, ’997 Patent, at
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`col. 15:5-8.) The specification goes on to teach that the buffer can be “any buffer that buffers in
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`the appropriate pH range.” (Id.) Thus, “refold buffer,” when read in the context of the
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`specification of the ’997 Patent, is a pH-buffered solution that comprises the elements recited in
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`step (d) of Claim 9. See Phillips, 415 F.3d at 1316. Amgen’s proposed construction requires
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`that the solubilization solution be mixed with a “a pH-buffered solution” that meets the claim
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`elements of step (d)in other words, the refold buffer must have the capacity to buffer pH.
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`4.
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`Disputed Term: “applying the refold solution to a separation matrix”
`
`Claim Term
`“applying the refold solution
`to a separation matrix”
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`Amgen’s Proposed
`Construction
`applying the refold solution
`to a column that contains the
`separation matrix without
`intervening steps of dilution,
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`Mylan’s Proposed
`Construction
`applying the refold solution
`to a separation matrix without
`removing components of or
`diluting the refold solution
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`10
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 17 of 40
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`centrifugation, dialysis, or
`precipitation
`
`
`Alternatively, plain and
`ordinary meaning; no
`construction necessary
`
`The parties appear to agree that a process in which at least certain types of steps
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`performed after refolding and before applying the refold solution to the separation matrix is
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`beyond the scope of the claim. Amgen’s proposed construction, which puts processes with
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`intervening steps of dilution, centrifugation, dialysis, or precipitation beyond the scope of the
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`claim, takes into account the language of the claim in the context of the other intrinsic evidence,
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`including the specification and the prosecution history of the ’997 Patent. Amgen’s proposed
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`construction is further supported by the parent application to the ’997 Patent, which issued as
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`U.S. Patent No. 8,940,878 (“the ’878 Patent”) (Dkt. No. 101-3) because Amgen’s proposed
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`construction distinguishes this claim term from a different claim term in the ’878 Patent
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`(“directly applying the refold solution to the separation matrix under conditions suitable for the
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`protein to associate with the matrix” in Claim 7 of the ’878 Patent (emphasis added)). Mylan’s
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`proposed construction, on the other hand, simply recycles another court’s construction of the
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`“directly applying” term in the ’878 Patent, and thus fails to capture a how a POSITA would
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`have understood the “applying” claim term of ’997 Patent. See Dkt. No. 100-1, Joint Disputed
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`Claim Terms Chart, at 2-3; Amgen v. Sandoz, Case No. 14-cv-04741-RS, 2016 WL 4137563, at
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`*12 (N.D. Cal. Aug. 4, 2016). Thus, Amgen’s claim construction should be adopted for at least
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`three reasons.
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`First, the specification of the ’997 Patent supports Amgen’s proposed construction
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`because it describes the invention as “eliminat[ing] the need to dilute the protein out of a refold
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`solution prior to capturing it on a separation matrix.” (Dkt. No. 101-1, ’997 Patent, at col.
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`3:53-57.) The specification teaches that, prior to the invention claimed in the ’997 Patent,
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`Case 2:17-cv-01235-MRH Document 106 Filed 06/01/18 Page 18 of 40
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`components that facilitate protein refolding “can inhibit purification,” and it was thought
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`“necessary to isolate or dilute the protein from these components for further processing,
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`particularly before applying the protein to a separation matrix.” (Id. at col. 4:52-57.) The
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`inventors of the ’997 Patent recognized that the process of dilution can be time-consuming and
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`resource intensive. (See id. at col. 12:45-46.) Dilution “also significantly increases the volumes
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`that need to be