Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 1 of 30 PageID #: 35533
`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF DELAWARE
`
`GENENTECH, INC. and CITY OF
`HOPE,
`
`Plaintiffs,
`
`Civ. No. 17-1407- CFC, Consol.
`
`v.
`
`AMGEN INC.,
`
`Defendant.
`
`Michael P. Kelly, Daniel M. Silver, MCCARTER &ENGLISH, LLP, Wilmington,
`Delaware; Paul B. Gaffney, David I. Berl, Thomas S. Fletcher, Teagan J. Gregory,
`Charles L. McCloud, Kathryn S. Kayali, Jonathan S. Sidhu, Benjamin Moskowitz,
`WILLIAMS & CONNOLLY LLP, Washingtc;m, D.C.; Daralyn J. Durie, Adam R.
`Brausa, Eric C. Wiener, Eneda Hoxha, DURIE TANGRI LLP, San Francisco,
`California. Counsel for Plaintiffs.
`
`Melanie K. Sharp, James L. Higgins, Michelle M. Ovanesian, YOUNG
`CONAWAY STARGATT & TAYLOR, LLP, Wilmington, Delaware; Siegmund
`Y. Gutman, PROSKAUER ROSE LLP, Los Angeles, California; Steven M. Bauer,
`Kimberly A. Mottley, Gourdin W. Sirles, PROSKAUER ROSE LLP, Boston,
`Massachusetts. Counsel for Defendant.
`
`MEMORANDUM OPINION
`
`June 17, 2019
`
`Wilmington, Delaware
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF DELAWARE
`
`GENENTECH, INC. and CITY OF
`HOPE,
`
`Plaintiffs,
`
`Civ. No. 17-1407- CFC, Consol.
`
`v.
`
`AMGEN INC.,
`
`Defendant.
`
`Michael P. Kelly, Daniel M. Silver, MCCARTER &ENGLISH, LLP, Wilmington,
`Delaware; Paul B. Gaffney, David I. Berl, Thomas S. Fletcher, Teagan J. Gregory,
`Charles L. McCloud, Kathryn S. Kayali, Jonathan S. Sidhu, Benjamin Moskowitz,
`WILLIAMS & CONNOLLY LLP, Washingtc;m, D.C.; Daralyn J. Durie, Adam R.
`Brausa, Eric C. Wiener, Eneda Hoxha, DURIE TANGRI LLP, San Francisco,
`California. Counsel for Plaintiffs.
`
`Melanie K. Sharp, James L. Higgins, Michelle M. Ovanesian, YOUNG
`CONAWAY STARGATT & TAYLOR, LLP, Wilmington, Delaware; Siegmund
`Y. Gutman, PROSKAUER ROSE LLP, Los Angeles, California; Steven M. Bauer,
`Kimberly A. Mottley, Gourdin W. Sirles, PROSKAUER ROSE LLP, Boston,
`Massachusetts. Counsel for Defendant.
`
`MEMORANDUM OPINION
`
`June 17, 2019
`
`Wilmington, Delaware
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 2 of 30 PageID #: 35534
`
`CONNOLLY, UNITEDTATES DISTRICT JUDGE
`
`Pending before me are competing proposed claim constructions in this
`
`consolidated patent infringement action brought pursuant to the Biologics Price
`
`Competition and Innovation Act ("BPCIA"), 42 U.S.C. § 262 by Plaintiffs
`
`Genentech, Inc. and City of Hope (collectively, "Genentech") against Defendant
`
`Amgen, Inc. ("Amgen"). Genentech has accused Amgen of infringing 26 patents.
`
`The parties initially asked me to construe the meaning of ten claim
`
`limitations in seven of the asserted patents. I reviewed the parties' claim
`
`construction briefing and held a Markman hearing that spanned two days. D.I.
`
`340; D.I. 345. By the conclusion of the Markman hearing, only seven claim terms
`
`in six of the asserted patents remained in dispute. 1 I address in this Memorandum
`
`those disputed terms.
`
`The disputed terms appear in the following patents: U.S. Patent Nos.
`
`8,512,983 ("the '983 patent"); 9,441,035 ("the '035 patent"); 8,574,869 ("the '869
`
`patent"); 6,884,879 ("the '879 patent"); 7,169,901 ("the '901 patent"); and
`
`7,060,269 ("the '269 patent"). D.I. 225; D.I. 325. These patents cover a wide
`
`range of complex technologies. Accordingly, I write primarily for the parties and,
`
`1 During or shortly before the Markman hearing, the parties agreed to the meaning
`of the terms "cystine," "grade III hypertensive event," and "without altering the
`dosage regimen." See D.I. 340 at 83:11-84:9, 85:3-92:6; D.I. 345 at 147:3-10.
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 3 of 30 PageID #: 35535
`
`to a large degree, presume familiarity with the underlying technology. In general,
`
`however, the '983 patent, '035 patent, and '869 patent relate to various aspects of
`
`manufacturing proteins, particularly antibodies, using a cell culture process. D.I.
`
`226 at 326, 381, 476. The '879 patent, '901 patent, and '269 patent disclose
`
`humanized and variant anti-VEGF antibodies and various uses of those antibodies.
`
`Id. at 69, 157, 240.
`
`I. LEGAL STANDARDS
`
`"It is a bedrock principle of patent law that the claims of a patent define the
`
`invention to which the patentee is entitled the right to exclude." Phillips v. AWH
`
`Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005). '"[T]here is no magic formula or
`
`catechism for conducting claim construction.' Instead, the court is free to attach
`
`the appropriate weight to appropriate sources 'in light of the statutes and policies
`
`that inform patent law."' SoftView LLC v. Apple Inc., 2013 WL 4758195, at *1 (D.
`
`Del. Sept. 4, 2013) (quoting Phillips, 415 F.3d at 1324). Construing the claims in a
`
`patent is a question of law. Markman v. Westview Instruments, Inc., 52 F.3d 967,
`
`977-78 (Fed. Cir. 1995), aff'd, 517 U.S. 370, 388-90 (1996).
`
`Unless a patentee acts as his own lexicographer by setting forth a special
`
`definition or disavows the full scope of a claim term, the words in a claim are to be
`
`given their ordinary and accustomed meaning. Thorner v. Sony Comput. Entm 't
`
`2
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 4 of 30 PageID #: 35536
`
`Am. LLC, 669 F.3d 1362, 1365 (Fed. Cir. 2012). "[T]he ordinary and customary
`
`meaning of a claim term is the meaning that the term would have to a person of
`
`ordinary skill in the art in question at the time of the invention, i.e., as of the
`
`effective filing date of the patent application." Phillips, 415 F.3d at 1313. A
`
`person of ordinary skill in the art ("POSIT A") "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." Id. at 1313.
`
`"[T]he specification is always highly relevant to the claim construction analysis.
`
`Usually, it is dispositive; it is the single best guide to the meaning of a disputed
`
`term." Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir.
`
`1996).2
`
`The court may also consider extrinsic evidence, which "consists of all
`
`evidence external to the patent and prosecution history, including expert and
`
`2 Section 112(b) of Title 35 provides that "[t]he specification shall conclude with
`one or more claims[.]" This language makes clear that the specification includes the
`claims asserted in the patent, and the Federal Circuit has so held. See Markman, 52
`F .3d at 979 ("Claims must be read in view of the specification, of which they are
`part"). The Federal Circuit and other courts, however, have also used "specification"
`on occasion to refer to the written description of the patent as distinct from the
`claims. See, e.g., id. {"To ascertain the meaning of claims, we consider three
`sources: The claims, the specification, and the prosecution history."). To avoid
`confusion, I will refer to the portion of the specification that is not the claims as "the
`written description."
`
`3
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 5 of 30 PageID #: 35537
`
`inventor testimony, dictionaries, and learned treatises." Phillips, 415 F.3d at 1317.
`
`"Extrinsic evidence is to be used for the court's understanding of the patent, not for
`
`the purpose of varying or contradicting the terms of the claims." Markman, 52
`
`F.3d at 981. "The construction that stays true to the claim language and most
`
`naturally aligns with the patent's description of the invention will be, in the end,
`
`the correct construction." Renishaw PLC v. Marposs Societa 'per Azioni, 158 F.3d
`
`1243, 1250 (Fed. Cir. 1998).
`
`II. ANALYSIS OF DISPUTED TERMS
`
`A. "a glutamine-free production culture medium" ('983 patent)
`
`Genentech's Construction: "A production culture medium that is essentially
`free of glutamine"
`
`Amgen's Construction: "culture medium used in the production phase that does
`not contain glutamine when formulated"
`
`Court's Construction: "a culture medium used in the production phase that is
`not formulated or supplemented with glutamine"
`
`1. Background
`
`Claim 1 of the '983 patent, reformatted for clarity, teaches:
`
`A process for producing a polypeptide in a mammalian
`host cell expressing said polypeptide,
`
`comprising culturing the mammalian host cell in a
`production phase of the culture in a glutamine-free
`production culture medium containing asparagine,
`
`4
`
`.
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 6 of 30 PageID #: 35538
`
`wherein the asparagine is added at a concentration in the
`range of 7 .5 mM to 15 mM.
`·
`
`'983 patent at 49:12-17 (emphasis added).
`
`Antibodies are polypeptides, manufactured by culturing genetically(cid:173)
`
`engineered cells inside tanks called bioreactors. The cells in the bioreactor are
`
`suspended in a solution called a "cell culture medium," which supplies, among
`
`other things, various nutrients for the cells to consume. Cell culture media are
`
`comprised of "base media" ( also sometimes called "basal media") and "feed
`
`media." Id. at 1 :33-36. A base medium is the initial medium added to the
`
`bioreactor. Feed media are periodically added to the bioreactor to supplement (or
`
`replenish) the nutrients in the base medium. Base media and feed media are
`
`"formulated" (i.e., made or prepared).
`
`The amino acid glutamine is a nutrient :frequently used in the formulation of
`
`base and feed media. Cells not only consume glutamine, they also produce their
`
`own glutamine. As a result, the concentration of glutamine in a cell culture
`
`medium is dynamic, as cells are continually consuming and adding to the
`
`glutamine in the cell culture medium and a manufacturer can also add glutamine at
`
`any time through feed media.
`
`5
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 7 of 30 PageID #: 35539
`
`2. Analysis
`
`Amgen argues that "a glutamine-free production culture medium" refers to a
`
`cell culture medium used in the production phase of antibodies that omits
`
`glutamine as an ingredient in the formulation of the culture medium's base media
`
`and/or feed media. Genentech takes the position that "a glutamine-free production
`
`culture medium" refers to the concentration of glutamine measured in the
`
`bioreactor at any point during the production phase. Because cells themselves can
`
`produce glutamine during the production phase, a glutamine-free culture medium
`
`would not exist in the production phase if "-free" means "the absence of
`
`glutamine" or "zero glutamine." Thus, not surprisingly, Genentech proposes that
`
`"glutamine-free" allow for some amount of glutamine and asks me to construe"(cid:173)
`
`free" to mean "essentially free." D.I. 325 at 2.
`
`I find that Amgen's proposed construction better aligns with the patent's
`
`intrinsic evidence and I will construe the limitation similarly to, though not
`
`exactly, the way Amgen does. Specifically, I will construe "a glutamine-free
`
`production culture medium" to mean "a culture medium used in the production
`
`phase that is not formulated or supplemented with glutamine." My reasoning is
`
`threefold.
`
`6
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 8 of 30 PageID #: 35540
`
`First, the written description of the patent states that "the culture media of
`
`the present invention can be based [on] any of the media described in [certain prior
`
`art]provided that glutamine is omitted as an ingredient." '983 patent at 29:5-12
`
`( emphasis added). The words "omitted" and "ingredient" connote preparing a
`
`formulation, not measuring a sample of a cell culture medium.
`
`Second, the patent links the term "glutamine-free" with media "formulated
`
`with" zero glutamine. It describes, for example, Figure 4 as presenting certain
`
`"[e]ffect[s] of asparagine under glutamine-free ... conditions," and the caption to
`
`Figure 4 is: "Casesformulatedwith OmMGlutamine, OmM or 5mM Glutamate,
`
`1 OmM Aspartate." Id. at 4:59-60 and Figure 4 ( emphasis added). Similarly,
`
`Figures 1 through 3 and Example 1 provide the results of a study designed to test
`
`the production of polypeptides in a production medium formulated with various
`
`concentrations of glutamine, including "O" glutamine. Id. at Figures 1-3; id. at
`
`44:26-46:61. As noted above, because cells themselves produce glutamine, a cell
`
`culture medium ( which, by definition, contains cells) cannot have "zero"
`
`glutamine. Only the base or feed media-which do not contain cells-can be said
`
`to have zero or an absence of glutamine.
`
`Third, during the prosecution history, both the Patent Examiner and
`
`Genetech used "glutamine-free" to describe media that omitted glutamine as an
`
`7
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 9 of 30 PageID #: 35541
`
`ingredient in their formulations. The Patent Examiner rejected claim 1 of the '983
`
`patent as anticipated by Nagle, Tomei, and Kurano, because each of these
`
`references taught a "glutamine-free medium." D.I. 228 at 1044-48. In its response
`
`to the rejection, Genentech agreed that Nagle, Tomei, and Kurano each taught a
`
`"glutamine-free" culture medium.3 Id. at 1060-65. As a result, how Nagle, Tomei,
`
`and Kurano defined a glutamine-free medium informs how Genentech and the
`
`Examiner understood the meaning of the term. See Am. Radio LLC v. Qualcomm
`
`Inc., 578 F. App'x 975, 980 (Fed. Cir. 2014) (stating that prior "can often help to
`
`demonstrate how a disputed term is used by those skilled in the art" ( quoting
`
`VUronics, 90 F.3d at 1584)). A review of Nagle, Tomei, and Kurano shows that
`
`each of them taught the formulation of a cell culture medium that omits glutamine
`
`as an ingredient.
`
`Nagle states: "The primary intent of this paper was to present the
`
`formulation of a heat-stable chemically defined medium that supported increased
`
`populations of several cell lines." D.I. 326-8, J.A. 2526-2531, at 261 (emphasis
`
`added). The composition of the medium presented in Nagle "differ[ed] from that
`
`previously reported by the omission of glutamine." Id. at 260. Thus, Nagle's
`
`3 Genentech overcame the objection by amending the claims to add a limitation
`based on the concentration of asparagine. D.I. 228 at 1054, 1060-61.
`8
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 10 of 30 PageID #: 35542
`
`formulation of a cell culture medium differed from that previously reported
`
`precisely because it omitted glutamine as an ingredient.
`
`Tomei describes growing mammalian cells in a "glutamine-free ...
`
`chemically defined medium." D.I. 326-8, J.A. 2532-2537, at 2:8-12. "The
`
`composition of the particular medium used for [Tomei's] invention is shown in
`
`Table l," which omits glutamine as one of the "components." Id. at 2:52-55, Table
`
`1. Tomei further states that the composition set forth in Table 1 "does not
`
`necessarily represent a critical formulation because other formulations may also be
`
`used." Id. at 2:55-57. Accordingly, Tomei taught that a glutamine-free cell culture
`
`medium omitted glutamine as a component of the formulation.
`
`Lastly, Kurano "investigated whether the cells were able to grow on
`
`glutamine free medium or not." D.I. 326-5, J.A. 2110-2125, at 122. To conduct
`
`the investigation, Kurano compared a "medium A," which was a "standard rvIBM(cid:173)
`
`a. medium ... purchased from Gibco'' to a "medium B," which was "prepared"
`
`using the "same components" as medium A "other than glucose, glutamine and
`
`asparagine." D.I. 228 at 1087-89 (emphasis added). Thus, Kurano described a
`
`glutamine-free cell culture medium as prepared without glutamine as a component.
`
`The repeated references in the prior art to the terms "components" and
`
`"formulations" makes clear that those skilled in the art at the time of the invention
`
`9
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 11 of 30 PageID #: 35543
`
`used the term "glutamine-free" to refer to a culture medium that was not
`
`formulated or supplemented with glutamine. Those references are consistent with
`
`the intrinsic evidence cited above, and accordingly, I will construe "a glutamine(cid:173)
`
`free production culture medium" as "a culture medium used in the production
`
`phase that is not formulated or supplemented with glutamine."
`
`B. "wherein the cystine is at a concentration of from 1.25 mM to 2.5
`mM" ('035 patent)
`
`Genentech's construction: "Plain and ordinary meaning. The recited cystine
`concentration is the concentration of cystine in the bioreactor."
`
`Amgen's construction: "wherein the cystine is at a concentration of from 1.25
`mM to 2.5 mM calculated when the cell culture medium is formulated"
`
`Court's construction: "wherein the cystine is at a concentration of from 1.25
`mM to 2.5 mM calculated when the cell culture medium is formulated"
`
`1. Background
`
`Claim 1 of the '035 patent, reformatted for clarity, recites:
`
`A method of producing bevacizumab, or a fragment
`thereof,
`
`comprising the step of culturing a Chinese hamster ovary
`(CHO) cell comprising a nucleic acid encoding
`bevacizumab or fragment thereof in a cell culture
`medium,
`
`wherein the cell culture medium comprises copper,
`insulin, and cystine,
`
`wherein the cystine is at a concentration of.from 1.25
`mMto 2.5 mM, and
`
`10
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 12 of 30 PageID #: 35544
`
`wherein the cell produces bevacizumab, or a fragment
`thereof.
`
`'035 patent at 46:14-21 (emphasis added).
`
`2. Analysis
`
`The parties disagree on whether the cystine concentration in the cell culture
`
`medium is calculated at the time of formulation (Amgen's position) or measured in
`
`the bioreactor at any single point in time (Genentech's position). I will adopt
`
`Amgen' s construction, as it better aligns with the intrinsic evidence.
`
`First, the patent's written description discusses the use of cystine in a
`
`manner consistent with its use as a component in a formulation. Specifically, it
`
`describes a cell culture medium "prepared" by combining two or more
`
`"components" selected from copper, insulin, and cystine "in an amount to provide"
`
`a certain concentration in the cell culture medium. '035 patent at 25:46-54; see
`
`also id. at 5:26-36. The terms "prepared" and "components" suggest a
`
`formulation. In addition, the phrase "in an amount to provide" is forward-looking
`
`and thus consistent with Amgen' s position that the determination of the amount of
`
`cystine is made when the base or feed media is formulated, not after the base or
`
`feed media is added to the cell culture medium.
`
`Second, prior art cited during the patent's prosecution demonstrates that a
`
`POSIT A would understand that the concentration of cystine in the cell culture
`
`11
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 13 of 30 PageID #: 35545
`
`medium is calculated at the time of the media's formulation. The Patent Examiner
`
`initially rejected claim 1 of the '035 patent as anticipated by four prior art
`
`references, because each reference taught a cell culture medium that contained
`
`cystine. D.I. 228 at 1193-95, 1199, 1205. Genentech overcame the rejection by
`
`amending the claims to specify a concentration of cystine that was outside the
`
`range taught by the prior art. Id. at 1212, 1227-29, 1233, 1236. As a result, how
`
`those prior art references-Mather, Gawlitzek, Knudsen, and Valamehr-used
`
`cystine informs how Gen en tech and the Examiner understood the meaning of the
`
`disputed term. See Am. Radio LLC, 578 F. App'x at 980 (stating that prior art "can
`
`often help to demonstrate how a disputed term is used by those skilled in the art"
`
`(quoting Vitronics, 90 F.3d at 1584)). A review of the prior art shows that it taught
`
`a concentration of cystine at the time of formulation.
`
`Mather teaches cystine at the time of formulation because it describes
`
`"prepar[ing]" the cell culture media by "weigh[ing] out" the "necessary amount of
`
`each of the solid ingredients in the medium," "combin[ing]" the ingredients to
`
`form a mixture termed the "basal medium powder," and then adding the basal
`
`medium powder to the purified water. D.I. 326-4, J.A. 1751-1762 at 1 :9-11, 2:48-
`
`68, 4:52-11:15, 5:21-24, 10:10, 10:23-38. Gawlitzek, which is the patent
`
`application that resulted in the '983 patent, concerns the formulation of a cell
`
`12
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 14 of 30 PageID #: 35546
`
`culture medium for the reasons stated in connection with my construction of
`
`"glutamine-free production culture medium" in Section Il(A)(2) above. See D.I.
`
`326-4, J.A. 1781-833 (application); D.I. 326-1, J.A. 1-55 (patent). In Knudsen,
`
`Table 3a and Table 3b set forth the "mg/L" (milligrams per liter) for the
`
`"component[ s ]" used in "a composition of a medium suitable for use in the present
`
`invention." D.I. 326-4, J.A. 1834-1849, at 9. Because milligrams is a solid
`
`measurement and liters is a liquid measurement, use of the words "mg/L" and
`
`"component" suggest mixing dry ingredients to formulate a base or feed medium.
`
`Finally, Valamehr mentions cystine twice: in Table 1, which sets forth the amino
`
`acids that "may ... be added to the basal medium," and in Table 2, which provides
`
`the "cell culture media components for basal media" and each component
`
`concentration ("mg/L"). D.I. 326-4, J.A. 1763-1780, at 7-8. References to "basal
`
`medium" (i.e., a base medium), "components," which are the ingredients of a
`
`formulation, and "mg/L," which is an amount of solid per liquid, strongly suggest
`
`that the concentration of cystine is calculated when the media is formulated.
`
`Iri light of the foregoing intrinsic evidence, I will construe the disputed
`
`phrase "wherein the cystine is at a concentration of from 1.25 mM to 2.5 mM" to
`
`mean, as Amgen proposes, "wherein the cystine is at a concentration of from 1.25
`
`mM to 2.5 mM calculated when the cell culture medium is formulated."
`
`13
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 15 of 30 PageID #: 35547
`
`C. "insulin" ('035 patent)
`
`Genentech's construction: "Plain and ordinary meaning. The claim is not
`limited to human insulin."
`
`Amgen's construction: "hormone with the amino acid sequence in Appendix A
`to the Joint Claim Construction Chart. (D.I. 225-1)"
`
`f
`
`f
`
`Gly-De-VaJ.Glu-G!n-C),'Sj'S•llu-Ser-De-C)'S-Ser-uu-Tyr-Oln-Lcu-Oln-Asn-T)Tr:\sn
`
`s
`I
`i
`
`I
`/
`
`s
`
`Pbe-Val-Asu-Gln-His-Lcu-C3-'S-Gly-Ser-His-Leu-Val-Gl11-Alo-Let1• T:i,T•Leu-Val-cy..-Gly-Glu-Arg-Gly-Pbe-Phe-T}T• Thr-Pro-Ly!i-Thr
`
`Court's construction: "Plain and ordinary meaning. The claim is not limited to
`human insulin."
`
`1. Background
`
`Again, claim 1 of the '03 5 patent recites:
`
`A method of producing bevacizumab, or a fragment
`thereof,
`
`comprising the step of culturing a Chinese hamster ovary
`(CHO) cell comprising a nucleic acid encoding
`bevacizumab or fragment thereof in a cell culture
`medium,
`
`wherein the cell culture medium comprises copper,
`insulin, and cystine,
`
`wherein the cystine is at a concentration of from 1.25
`mM to 2.5 mM, and
`
`wherein the cell produces bevacizumab, or a fragment
`thereof.
`
`'035 patent at 46:14-21 (emphasis added).
`14
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 16 of 30 PageID #: 35548
`
`2. Analysis
`
`Genentech argues that "insulin" should be given its plain and ordinary
`
`meaning and not be limited to human insulin. Amgen argues that "insulin" should
`
`be defined as the amino acid sequence of human insulin.
`
`The '03 5 patent does not define "insulin." Nor does it limit "insulin" to any
`
`particular species or even suggest that "insulin" must be human insulin.
`
`Amgen argues that the prosecution history supports its position, because
`
`Genentech amended its claims to overcome the Examiner's rejection of the claims
`
`"in view of a prior art reference ("Gawlitzek") that disclosed, among other things,
`
`'human insulin."' D.I. 267 at 46. But nothing in the amended claims Genentech
`
`proposed to overcome the rejection or in Genentech's communications with the
`
`Examiner about the rejection suggest that Genentech intended to limit "insulin" to
`
`"human insulin." Accordingly, I will give "insulin" its plain and ordinary meaning
`
`and not limit it to human insulin.
`
`D. "following fermentation" ('869 patent)
`
`Genentech's construction: "After the end of the cell growth and antibody
`production phases ( which is indicated by a change in the cell culture
`environment that substantially ends cell growth and antibody production)"
`
`Amgen's construction: "steps starting with initiation of purification"
`
`Court's construction: The Court will not construe the term at this time.
`
`15
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 17 of 30 PageID #: 35549
`
`1. Background
`
`Claim 1 of the '869 patent, reformatted for clarity, teaches
`
`[a] method for the prevention of the reduction of a
`disulfide bond in an antibody expressed in a recombinant
`host cell,
`
`comprising, following fermentation, sparging the pre(cid:173)
`harvest or harvested culture fluid of said recombinant
`host cell with air,
`
`wherein the amount of dissolved oxygen ( dO2) in the
`pre-harvest or harvested culture fluid is at least 10%.
`
`'869 patent at 107:44-49. As stated, the goal of the invention is to prevent the
`
`reduction of disulfide bonds in the antibody expressed in a recombinant host cell.
`
`Id. at 107:44-45.
`
`2. Analysis
`
`The construction of "following fermentation" involves two questions. First,
`
`what is "fermentation?" And second, when does "fermentation" end?
`
`Amgen dodges the first question. It argues that "following fermentation" is
`
`indefinite because the specification does not "provide clear guidance for when
`
`'fermentation' ends and 'following fermentation' begins[.]" D.I. 325 at 60.
`
`Amgen does not say that the term "fermentation" itself is indefinite; and although
`
`Amgen argues that the '869 patent "does not use 'fermentation' in the ordinary
`
`way," id., it makes no attempt to explain "the way" the patent does use the term.
`
`16
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 18 of 30 PageID #: 35550
`
`For its part, Genetech equates "fermentation" with "the cell growth and antibody
`
`production phases." Id. at 54.
`
`The '869 patent does not define "fermentation." Language in column 9 of
`
`the patent suggests that the term is synonymous with "production":
`
`It is emphasized that the fermentation, recovery and
`purification methods described herein are only for
`illustration purposes. The methods of the present
`invention can be combined with any manufacturing
`process developed for the production, recovery and
`purification of recombinant proteins.
`
`'869 patent at 29:4-8 (emphasis added). In another portion of the patent's written
`
`description, the use of the words "following fermentation" immediately after a
`
`description of the "production phase" provides further evidence that the patentee
`
`understood "fermentation" and "production" to mean the same thing. See id. at
`
`26:29-41.
`
`Language in column 22 of the patent, however, suggests that fermentation is
`
`not synonymous with production. Specifically, lines 10 through 13 of column 22
`
`provide that "non-specific methods can also be used to prevent the reduction [sic]
`
`of disulfide bond reduction [sic] following fermentation during the recombinant
`
`production of recombinant proteins." Id. at 22:10-13. This sloppy language is
`
`unfortunately typical of the '869 patent. Because of its two references to
`
`"reduction," the quoted sentence describes an invention that does the exact
`
`17
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 19 of 30 PageID #: 35551
`
`opposite of what is described in the patent's Abstract and taught by claim I-that
`
`is, the sentence literally refers to a method to prevent "the reduction of the
`
`reduction" of disulfide bonds. I assume, therefore, that either the phrase "the
`
`reduction of' that precedes "disulfide bond" or the word "reduction" that follows
`
`"disulfide bond" is a typographical error.
`
`Correcting that error, however, does not cure the sentence's ambiguities.
`
`The corrected sentence (i.e., with only one reference to "reduction") can be read in
`
`two different ways with respect to the relationship between fermentation and
`
`production: either ( 1) the prevention of disulfide bond reduction occurs during a
`
`production process that comes after fermentation, or (2) the prevention of disulfide
`
`bond reduction occurs after the completion of a fermentation process that itself
`
`occurs and is completed during production. In the first case, fermentation occurs
`
`before production. In the second case, fermentation occurs during production. In
`
`both cases, fermentation is neither coterminous with nor the same thing as
`
`production.
`
`Language in Column 1 of the '869 patent only adds to the confusion over the
`
`relationship between fermentation and production. That column states in relevant
`
`part:
`
`Usually, to begin the production cycle, a small number of
`transformed recombinant host cells are allowed to grow
`
`18
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 20 of 30 PageID #: 35552
`
`in culture for several days (see, e.g., FIG. 23). Once the
`cells have undergone several rounds of replication, they
`are transferred to a larger container where they are
`prepared to undergo fermentation. The media in which
`the cells are grown and the levels of oxygen, nitrogen and
`carbon dioxide that exist during the production cycle may
`have a significant impact on the production process.
`
`'869 at 1:52-2:9 (emphasis added). It is clear from this quoted passage that
`
`fermentation occurs after "several rounds of replication" and that "replication"
`
`refers to the initial growing "in culture for several days" of a small number of
`
`transformed recombinant host cells. Because of the ambiguous phrase "to begin
`
`the production cycle," however, it is unclear whether this replication is the
`
`beginning of the production cycle or whether it precedes ( and lays the foundation
`
`for) the production cycle. Thus, it is not clear whether the production cycle begins
`
`before fermentation takes place. To compound the confusion, the quoted passage
`
`refers in one sentence to ''the production cycle" and "the production process," and
`
`it does not make clear whether these terms refer to the same thing. The confusion
`
`is further compounded because the patent variably uses "production" throughout
`
`19
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 21 of 30 PageID #: 35553
`
`its written description. 4 And finally, although the passage describes the transfer of
`
`cells to a larger container where they are ''prepared to undergo fermentation," it
`
`does not indicate when fermentation begins, let alone when it ends or what it
`
`encompasses.
`
`In sum, the patent neither defines fermentation nor allows for a cogent
`
`inference of the term's meaning. Moreover, the parties have not identified any
`
`prior art cited in the patent or anything from the prosecution history that would
`
`enable me, based solely on the intrinsic evidence, to construe reasonably the
`
`meaning of"fermentation" (and, consequently, the meaning of"following
`
`fermentation"). Accordingly, I cannot construe the term based on the intrinsic
`
`evidence and, therefore, will convene a hearing to determine whether "following
`
`4 For example, at times, the patent equates "production" with "manufacturing."
`Compare '869 Patent at 2: 17-19 (referring to a "manufacturing, recovery and
`purification process" (emphasis added)) with id. at 25:40-41, 28:38-39 (referring to
`a ''production, recovery and purification" process ( emphasis added)). At other
`times, the patent describes "production" as encompassing "manufacturing" and other
`processes. See, e.g., id. at 2:13-19 ("[D]uring the recombinant production of
`polypeptides ... , it is essential to protect and retain the disulfide bonds throughout
`the manufacturing, recovery and purification process." ( emphasis added)). And at
`other times the patent describes "manufacturing" as encompassing "production" and
`other processes. See, e.g., id. at 29:6-8 (stating that "[t]he methods of the present
`invention can be combined with any manufacturing process developed for the
`production, recovery and purification of recombinant proteins" ( emphasis added)).
`20
`
`
`
`Case 1:17-cv-01407-CFC Document 401 Filed 06/17/19 Page 22 of 30 PageID #: 35554
`
`fermentation" can be construed by resorting to extrinsic evidence or whether it
`
`should be found invalid for indefiniteness.
`
`E. "Said Humanized Variant" ('879 patent)/ "Said Humanized anti(cid:173)
`VEGF Antibody" ('901 patent)
`
`Genentech's construction: "The humanized anti-vascular endothelial growth
`factor (VEGF) antibody recited at the beginning of claim 1."
`
`Amgen's construction: "anti-VEGF antibody created by humanization of a
`parent anti-VEGF antibody"
`
`Court's construction: "The humanized anti-vascular endothelial growth factor
`(VEGF) antibody recited at the beginning of claim l."
`
`1. Background
`
`The parties dispute the meaning of "said humanized variant" and "said
`
`humanized anti-VEGF antibody," which appear, respectively in the '879 patent
`
`and '901 patent. D.I. 325 at 96. The parties' respective arguments regarding the
`
`meaning of each of these claim limitations are the same and the patents share a
`
`common written description. D.I. 325 at 96-104; '879 patent; '901 patent. For
`
`convenience, therefore, I will refer only to "said humanized variant" and the '879
`
`patent.
`
`Claim 1 of the '879 p
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
