United States District Court, D. Delaware
GENENTECH, INC. and CITY OF HOPE, Plaintiffs,
AMGEN INC., Defendant.
Michael P. Kelly, Daniel M. Silver, MCCARTER &ENGLISH,
LLP, Wilmington, Delaware; Paul B. Gaffhey, David I. Berl,
Thomas S. Fletcher, Teagan J. Gregory, Charles L. McCloud,
Kathryn S. Kayali, Jonathan S. Sidhu, Benjamin Moskowitz,
WILLIAMS & CONNOLLY LLP, Washington, D.C.; Daralyn J.
Durie, Adam R. Brausa, Eric C. Wiener, Eneda Hoxha, DURIE
TANGRI LLP, San Francisco, California. Counsel for
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.
CONNOLLY, UNITED STATES DISTRICT JUDGE
before me are competing proposed claim constructions in this
consolidated patent infringement action brought pursuant to
the Biologies 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.
parties initially asked me to construe the meaning often
claim limitations in seven of the asserted patents. I
reviewed the parties' claim construction briefing and
held a Marbnan hearing that spanned two days. D.I.
340; D.I. 345. By the conclusion of the Marbnan
hearing, only seven claim terms in six of the asserted
patents remained in dispute. I address in this Memorandum
those disputed terms.
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, 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. Mat 69, 157, 240.
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. Applelnc, 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).
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 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
("POSITA") "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).
court may also consider 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. "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).
ANALYSIS OF DISPUTED TERMS
"a glutamine-free production culture medium"
"A production culture medium that is essentially
free of glutamine" *
"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"
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, wherein the
asparagine is added at a concentration in the range of 7.5 mM
to 15 mM.
patent at 49:12-17 (emphasis added).
are polypeptides, manufactured by culturing
genetically-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 1:3 3-3 6. 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
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
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 "-free" to mean
"essentially free." D.I. 325 at 2.
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.
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.
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:
"Cases formulated with 0mM Glutamine, 0mM or
5mM Glutamate, 10mM 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 "0" 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
during the prosecution history, both the Patent Examiner and
Genetech used "glutamine-free" to describe media
that omitted glutamine as an 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. 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
Fed.Appx. 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
Vitronics, 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
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 formulation of a cell culture medium differed
from that previously reported precisely because it omitted
glutamine as an ingredient.
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
1," 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.
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
MEM-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.
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 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-free production culture
medium" as "a culture medium used in the production
phase that is not formulated or supplemented with
"wherein the cystine is at a concentration of from 1.25
mM to 2.5 mM" ('035 patent)
"Plain and ordinary meaning. The recited cystine
concentration is the concentration of cystine in* the
"wherein the cystine is at a concentration of
from 1.25 mM to 2.5 mM calculated when the cell
culture medium is formulated"
"wherein the cystine is at a concentration of
from 1.25 mM to 2.5 mM calculated when the cell
culture medium is formulated"
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