Sanofi-Aventis Deutschland & GMBH v. Genentech, Inc.

NOTE: This disposition is nonprecedential.

United States Court of Appeals
for the Federal Circuit
__________________________

SANOFI-AVENTIS DEUTSCHLAND GMBH,
Plaintiff-Appellant,

v.
GENENTECH, INC.,
Defendant-Appellee,

and
BIOGEN IDEC INC.,
Defendant-Appellee,
__________________________

2011-1397
__________________________

Appeal from the United States District Court for the
Northern District of California in Case Nos. 08-CV-4909
and 09-CV-4919, Judge Susan Illston.
____________________________

Decided: March 22, 2012
____________________________

WILLIAM E. SOLANDER, Fitzpatrick, Cella, Harper &
Scinto, of New York, New York, argued for plaintiff-
appellant. With him on the brief were DOMINICK A.
SANOFI-AVENTIS v. GENENTECH 2

CONDE, NINA SHREVE, JOSHUA A. DAVIS and CHARLOTTE C.
JACOBSEN.

CHARLES K. VERHOEVEN, Quinn Emanuel Urquhart &
Sullivan, LLP, of San Francisco, California, argued for
both defendants-appellees. With him on the brief were
VICTORIA F. MAROULIS, ERIC E. WALL and GABRIEL S.
GROSS. Of counsel on the brief were DONALD R. WARE,
CLAIRE LAPORTE, JEREMY A. YOUNKIN and MARCO J.
QUINA, Foley Hoag, LLP, of Boston, Massachusetts.
__________________________

Before NEWMAN, LOURIE, and PROST, Circuit Judges.
LOURIE, Circuit Judge.

Plaintiff-Appellant Sanofi-Aventis Deutschland
GmbH (“Sanofi”) appeals from the decision of the United
States District Court for the Northern District of Califor-
nia granting summary judgment of noninfringement of its
U.S. Patents 5,849,522 (“the ’522 patent”) and 6,218,140
(“the ’140 patent”) in favor of Defendant-Appellees Genen-
tech, Inc. (“Genentech”) and Biogen Idec Inc. (“Biogen”).
Sanofi-Aventis Deutschland GmbH v. Genentech, Inc.,
Nos. C 08-4909 SI, C 09-4919 SI, 2011 U.S. Dist. LEXIS
28334, 2011 WL 839411 (N.D. Cal. Mar. 7, 2011) (“Final
Judgment”). Because we conclude that the district court
did not err in its judgment, we affirm.

I. BACKGROUND

The ’522 and ’140 patents, assigned to Sanofi, arose
from the same patent family and share the same single-
page written description, which discloses enhancer ele-
3 SANOFI-AVENTIS v. GENENTECH

ments derived from human cytomegalovirus (“HCMV”). 1
Enhancers are discrete segments of DNA capable of
enhancing the expression of one or more functionally
associated gene(s) by upregulating transcription—the
process of synthesizing RNA from a DNA template.
Generally speaking, enhancers recruit and locally concen-
trate certain proteins needed for transcription, leading to
increased production of RNA from associated genes. The
resulting abundance of RNA, once translated, yields
correspondingly abundant protein expression. Enhancers
are often found immediately upstream of enhancer-
activated genes, but they can also function if placed
downstream or even thousands of base pairs away from a
gene. Once identified, enhancers often have considerable
practical utility and have been adopted in the biotechnol-
ogy and pharmaceutical industries to boost production
efficiency for protein-based products. For example, by
linking an enhancer to a gene encoding a biologic drug,
researchers can often significantly improve yields from
cells expressing that gene.

The enhancer described in the ’522 and ’140 patents—
first discovered within non-coding DNA located upstream
of the highly expressed HCMV major immediate early
(“IE”) gene—is particularly powerful and versatile, dem-
onstrating activity across a wide spectrum of eukaryotic
cell types. The ’522 patent claims methods of using the
HCMV IE enhancer to increase expression of a gene in a
mammalian cell, and the ’140 patent claims isolated
HCMV IE enhancers, plasmid DNAs comprising an

1 Through serial continuation applications, the ’522
and ’140 patents both claim priority from German Patent
Application No. 34 31 140.8, filed August 24, 1984. The
’522 patent was filed on June 6, 1995, and issued on
December 15, 1998, and the ’140 patent was filed on
November 9, 1994, and issued on April 17, 2001.
SANOFI-AVENTIS v. GENENTECH 4

HCMV IE enhancer operatively linked to a heterologous
gene, and eukaryotic host cells transformed with such
plasmids.

In 2008, Sanofi brought an action for infringement of
the ’522 and ’140 patents, alleging that Appellees made
use of an infringing HCMV IE enhancer in producing the
antibody-based pharmaceuticals Rituxan® and Avastin®.
In turn, Appellees filed a declaratory judgment complaint
alleging invalidity and noninfringement, and the two
actions were consolidated in the United States District
Court for the Northern District of California. The district
court held Markman proceedings and construed several
disputed claim terms in each patent. Sanofi-Aventis
Deutschland GmbH v. Genentech, Inc., Nos. C 08-4909 SI,
C 09-4919 SI, 2010 U.S. Dist. LEXIS 68875, 2010 WL
2525118, at *4–15 (N.D. Cal. June 23, 2010) (“Claim
Construction Order”). In light of the claim construction
decision, Appellees moved for summary judgment of
noninfringement, which the district court granted. The
court concluded that Appellees did not infringe the ’522 or
’140 patents literally or under the doctrine of equivalents
in producing Rituxan® and Avastin®. Final Judgment,
2011 WL 839411, at *4–15.

Sanofi appealed, and we have jurisdiction pursuant to
28 U.S.C. § 1295(a)(1).

II. DISCUSSION

We review the district court’s grant of summary
judgment of noninfringement and its underlying claim
construction de novo. Laryngeal Mask Co. Ltd. v. Ambu
A/S, 618 F.3d 1367, 1370 (Fed. Cir. 2010). Summary
judgment is appropriate when “there is no genuine dis-
5 SANOFI-AVENTIS v. GENENTECH

pute as to any material fact and the movant is entitled to
judgment as a matter of law.” Fed. R. Civ. P. 56(a).

A. The ’522 Patent

Sanofi asserted claims 1 and 2 of the ’522 patent. In-
dependent claim 1 is representative for purposes of this
appeal and reads as follows:

1. A method to increase expression of a gene in a
mammalian cell comprising inserting into the
mammalian cell an isolated DNA enhancer con-
sisting of DNA from the upstream region of the
major immediate early (IE) gene of human cy-
tomegalovirus (HCMV) and a heterologous gene
that is to be expressed, wherein the DNA from the
upstream region of the IE gene of HCMV is the
only HCMV material to which the mammalian
cell is exposed.

’522 patent col.2 l.63 – col.3 l.3 (emphases added). 2

In the district court, the parties disputed the mean-
ings of “isolated DNA enhancer” and “DNA from the
upstream region of the major immediate early (IE) gene of
human cytomegalovirus (HCMV).” In resolving those
issues, the district court construed “isolated DNA enhan-
cer” to mean

2 Claim 2 depends from claim 1, imposing further
limitations on the DNA that can constitute the isolated
DNA enhancer recited in claim 1. See ’522 patent col.3
ll.4–8. Because we agree with the district court that
Appellees do not infringe claim 1, we need not separately
address claim 2.
SANOFI-AVENTIS v. GENENTECH 6

a DNA sequence, separated by human interven-
tion from the promoter DNA in its original source,
that (1) strongly stimulates transcription of a
linked gene, (2) functions independent of orienta-
tion, and (3) functions even if located long dis-
tances upstream or downstream relative to the
initiation site of the linked gene.

Claim Construction Order, 2010 WL 2525118, at *5
(emphases added). The district court next construed
“DNA from the upstream region of the major immediate
early (IE) gene of human cytomegalovirus (HCMV)” as
“DNA from the region that is upstream of the transcrip-
tion start site of the major IE gene of HCMV.” Id. at *7.
On the issue of infringement, the district court held that
Appellees did not infringe the ’522 patent because, inter
alia, Appellees do not practice the step of “inserting” an
isolated DNA enhancer into a mammalian cell. Final
Judgment, 2011 WL 839411, at *4–6.

1. Claim Construction

a. The Isolated DNA Enhancer

On appeal, Sanofi argues that the district court erred
by defining “isolated DNA enhancer” to require the en-
hancer to be “separated . . . from the promoter DNA in its
original source.” Claim Construction Order, 2010 WL
2525118, at *5. Sanofi argues that the claimed “isolated
DNA enhancer” can include the native HCMV promoter
but concedes that it need not, pointing out that the ’522
patent’s specification teaches that the HCMV enhancer
can be used with or without the HCMV IE promoter. See
’522 patent col.2 ll.6–10, 43–56. Appellees respond that
Sanofi disclaimed enhancer fragments that include the
HCMV IE promoter during prosecution and that the
7 SANOFI-AVENTIS v. GENENTECH

disclosure excludes the promoter from its discussion of
enhancer-active elements. We agree with the district
court that the intrinsic evidence does not support Sanofi’s
construction.

We have held that an otherwise broadly defined term
can be narrowed during prosecution through arguments
made to distinguish prior art. Phillips v. AWH Corp., 415
F.3d 1303, 1317 (Fed. Cir. 2005) (en banc). In this case,
the applicants made such a disclaimer during prosecution
of U.S. Patent Application No. 07/170,140—an ancestor of
the application that eventually issued as the ’522 pat-
ent—to overcome obviousness rejections against then-
pending claims that recited an “isolated enhancer.”
Specifically, the examiner had cited two references
(Thomsen and Jahn) that disclose HCMV-derived DNA
sequences encompassing the HCMV IE enhancer and
promoter regions. In a response dated March 14, 1988,
the applicants distinguished the cited art, as follows:

[N]either of these primary references teaches the
preparation of an isolated enhancer region as de-
fined by the pending claims. . . . Thomsen et al.
expressly discusses promoter sequences . . . .
[Jahn] isolates and characterizes a variety of
clones and illustrates several maps. The refer-
ence does not appear to isolate an enhancer se-
quence . . . .

J.A. 806–07 (emphasis in original).

Thus, the applicants distinguished their isolated en-
hancer from the cited references, and such statements
amount to “a clear and unmistakable disavowal of scope
during prosecution” of the ’522 patent. Purdue Pharma
L.P. v. Endo Pharms. Inc., 438 F.3d 1123, 1136 (Fed. Cir.
SANOFI-AVENTIS v. GENENTECH 8

2006); see also Atofina v. Great Lakes Chem. Corp., 441
F.3d 991, 997–98 (Fed. Cir. 2006). Because Thomsen and
Jahn disclose the entire HCMV IE regulatory region,
including the claimed enhancer sequences, the applicants
cast those references as general disclosures that failed to
describe or isolate the HCMV enhancer from its native
context within the surrounding viral sequences. More-
over, the applicants underscored the presence of HCMV
IE promoter sequences in Thomsen to distinguish that
reference from the “isolated enhancer” recited in the
pending claims. Hence, their claims must be interpreted
to refer to the enhancer separated from the promoter, and
we agree with the district court that the term “isolated
DNA enhancer” requires an enhancer separated from the
promoter DNA in its original source.

b. The Upstream Region of the IE Gene

In addition, Sanofi alleges error in the construction of
the term “DNA from the upstream region of the major
immediate early (IE) gene of human cytomegalovirus
(HCMV),” which the district court interpreted to mean
“DNA from the region that is upstream of the transcrip-
tion start site of the major IE gene of HCMV.” Claim
Construction Order, 2010 WL 2525118, at *7 (emphasis
added). Sanofi contends that the term “DNA from the
upstream region of the major immediate early (IE) gene of
human cytomegalovirus (HCMV)” should be construed to
mean “DNA from upstream of the translation start site of
the major IE gene of HCMV.” According to Sanofi, the
specification discloses the use of HCMV enhancers includ-
ing portions of viral DNA extending beyond the transcrip-
tion start site to the HCMV splice donor site at +120 or
the downstream PstI site at approximately +930. See ’522
patent col.2 ll.6–10, 44–56. To include those features,
Sanofi argues, the claimed “upstream region of the major
9 SANOFI-AVENTIS v. GENENTECH

immediate early (IE) gene” must encompass the tran-
scribed, but untranslated, region spanning the transcrip-
tion and translation start sites of the HCMV IE gene at
+1 and approximately +950, respectively. We disagree.

A diagram of the HCMV IE gene, adapted from figure
1a of the ’522 patent and marked to emphasize relevant
points of reference, is shown below:

Claim 1 recites the method of using an isolated DNA
enhancer that consists of “DNA from the upstream region
of the [HCMV IE gene],” and the specification uses consis-
tent language in describing the HCMV enhancer’s posi-
tion as “located in the upstream region of the [HCMV IE
gene].” Id. [57] (emphasis added); see also id. col.1 ll.14–
17. But the specification describes the location of the
+120 splice donor site differently, with the key phrase
“upstream region” notably absent. Rather, the specifica-
tion describes the +120 splice donor sequence as the
“splice donor consensus sequence of the IE gene.” Id. col.2
ll.8–9 (emphasis added). Thus, while the +120 splice
donor site is indeed part of the IE gene, the specification
reserves the “upstream region” label from its discussion of
the splice donor site, indicating that the claim term “DNA
from the upstream region of the [HCMV IE gene]” speci-
fies a distinct portion of the broader IE gene that excludes
SANOFI-AVENTIS v. GENENTECH 10

the splice donor site (+120), the downstream PstI site
(+930), and the translation start site (+950). 3

We therefore reject Sanofi’s contention that the down-
stream end of the “upstream region” recited in claim 1
extends to the translation start site of the IE gene, and
we affirm the construction adopted by the district court.

2. Infringement

The district court held on summary judgment that
Appellees do not infringe claims 1 or 2 of the ’522 patent
because, among other reasons, Appellees do not practice
the required step of “inserting” an isolated DNA enhancer
into a mammalian cell. Final Judgment, 2011 WL
839411, at *4–6. We agree.

In the district court, the parties stipulated that “in-
serting,” as used in the ’522 patent, means “putting or
introducing into.” Id. at *4. Furthermore, the parties
agree that Appellees derived the cell lines used to produce
Rituxan® and Avastin® by inserting foreign DNA into
mammalian cells, but also that those acts occurred before
the ’522 patent issued in 1998 and therefore cannot
constitute infringement. Id.; see Monsanto Co. v. Syn-
genta Seeds, Inc., 503 F.3d 1352, 1359–60 (Fed. Cir.
2007). Sanofi nonetheless urges that Appellees literally
perform the requisite infringing acts by propagating their
existing cell lines, thereby “inserting” the foreign DNA
into daughter cells with each round of mitosis. The ’522
patent only teaches inserting foreign DNA via transfec-
tion, however, and does not discuss cell division as a

3 An “upstream region” that excludes the splice do-
nor site at +120 must also exclude sites such as the PstI
site and the translation start site located even further
downstream.
11 SANOFI-AVENTIS v. GENENTECH

means for introducing foreign DNA. See ’522 patent col.1
l.42, col.2 ll.20, 39. More fundamentally, Sanofi’s argu-
ment contradicts basic scientific understanding and
common sense. During mitosis, existing chromosomes
replicate inside a cell, which then splits to produce identi-
cal daughter cells containing the same DNA as the par-
ent. DNA replicated during mitosis is not “put or
introduced into” a cell; it is already there.

We therefore agree with the district court that there
is no genuine issue of material fact that Appellees do not
literally infringe the asserted claims of the ’522 patent.
Furthermore, we agree with the district court that Appel-
lees do not infringe under the doctrine of equivalents
because “inserting” extraneous DNA into a cell differs
substantially from routine mitotic propagation, and a
finding of equivalence would vitiate the claim term “in-
serting.” See Trading Techs. Int’l, Inc. v. eSpeed, Inc., 595
F.3d 1340, 1355 (Fed. Cir. 2010). Because our affirmance
of the district court’s conclusion that the claims are not
infringed on the ground that Appellees do not insert
enhancer DNA into a mammalian cell is sufficient to
dispose of Sanofi’s infringement allegations regarding the
’522 patent, we need not review the application of the
claim terms “isolated DNA enhancer” and “DNA from the
upstream region of the [HCMV IE gene]” to Appellees’
activities. As noted above, however, we have affirmed the
district court’s construction of those terms.

B. The ’140 Patent

Sanofi asserted claims 42–45 of the ’140 patent.
Claims 42 and 45 each claim a “recombinant DNA plas-
mid” comprising an enhancer-active DNA molecule iso-
lated from the HCMV IE gene operatively linked to a
SANOFI-AVENTIS v. GENENTECH 12

heterologous gene. Claims 43 and 44 claim eukaryotic
host cells transformed with such a plasmid.

Regarding the pivotal claim term “recombinant DNA
plasmid,” the parties offered conflicting interpretations of
the word “plasmid.” That term is absent from the written
description of the ’140 patent. The district court looked to
U.S. Patent 5,168,062 (“Stinski”) as important intrinsic
evidence of the meaning of “plasmid,” as the term first
appeared in the ’140 patent in claims copied from Stinski
and because the examiner cited Stinski as the basis of
rejections during prosecution of the ’140 patent. Id. at
*10–11. In relevant part, Stinski defines a “plasmid” as
“a closed ring,” “not linked to the chromosome of the host
cell.” Stinski col.3 ll.1–8, 19. Accordingly, the district
court adopted Biogen’s proposed construction defining
“plasmid” to mean a “circular, extrachromosomal mole-
cule.” Claim Construction Order, 2010 WL 2525118, at
*11.

Having adopted Biogen’s proposed definition of “plas-
mid,” the district court then held that Appellees do not
infringe the asserted claims because the heterologous
DNA used to produce Rituxan® and Avastin® is linear
and integrated rather than circular and extrachromo-
somal. Final Judgment, 2011 WL 839411, at *11–14.

1. Claim Construction

Sanofi argues that the district court erred in its con-
struction of “plasmid,” contending that the ordinary
meaning of the term includes both circular and linear
forms and that the district court incorrectly treated
Stinski as controlling intrinsic evidence. Sanofi main-
tains that “plasmid” should be defined more broadly as a
sequence of DNA “that may be linear or circular and that
13 SANOFI-AVENTIS v. GENENTECH

may exist in an extrachromosomal state or integrated into
a cell’s chromosome.”

As noted, the word “plasmid” appears nowhere in the
written description of the ’140 patent; the term first
appeared when the applicants copied claims from Stinski
during prosecution. But the ’140 patent discloses two
examples of plasmids, both of which are circular and
extrachromosomal, see ’140 patent col.2 ll.45–56, and that
evidence from the patent itself accords with the district
court’s construction. Furthermore, the district court
correctly recognized Stinski, which the examiner cited
during prosecution, as sufficiently intrinsic evidence for
purposes of interpreting the ’140 patent. See Phillips, 415
F.3d at 1317 (“The prosecution history, which we have
designated as part of the ‘intrinsic evidence,’ consists of
the complete record of the proceedings before the PTO
and includes the prior art cited during the examination of
the patent.”). Given the scant insights offered within the
’140 patent concerning the meaning of “plasmid,” the
consistent teachings of Stinski, and the lack of other
countervailing evidence from the intrinsic record, we
discern no error in the district court’s construction.

Sanofi complains that the district court’s construction
unduly limits the ordinary meaning of the term “plasmid,”
offering expert testimony and various other pieces of
extrinsic evidence that it claims more accurately reflect
the perspective of those skilled in the art at the time of
the invention. But Appellees counter Sanofi’s arguments
with a contrary array of extrinsic evidence and note that
the available intrinsic evidence supports the district
court’s construction. We cannot agree that Sanofi’s sub-
missions outweigh the intrinsic evidence. As we held in
Phillips, “extrinsic evidence may be useful to the court,
but it is unlikely to result in a reliable interpretation of
SANOFI-AVENTIS v. GENENTECH 14

patent claim scope unless considered in the context of the
intrinsic evidence.” Id. at 1319. Regardless of what
meaning may be attributed to the term “plasmid” in other
contexts and at other times, its meaning in the instant
patent, having an effective filing date of August 24, 1984,
is as a circular, extrachromosomal piece of DNA.

Sanofi also argues that the district court’s construc-
tion would render claim 43 “internally inconsistent”
because that claim recites “[a] eukaryotic host cell trans-
formed with a recombinant DNA plasmid.” ’140 patent
col.5 ll.8–9 (emphasis added). Sanofi argues that “the
ordinary understanding of a transformed cell is one in
which the plasmid is integrated,” that is, linearized and
integrated into a host chromosome. Br. for Plaintiff-
Appellant at 37. The parties agreed before the claim
construction hearing, however, that “transformed” means
“altered to include foreign DNA,” J.A. 650, and that
definition can indicate the result of a transient transfec-
tion with circular, extrachromosomal DNA as well as
indicating the integration of extraneous linear DNA into a
chromosome, but it does not compel Sanofi’s interpreta-
tion. Furthermore, the only such “transformed” cells
described in the ’140 patent resulted from transient
transfection, not integration. See ’140 patent col.2 ll.53–
56. Sanofi’s argument is therefore unavailing.

We have considered Sanofi’s remaining arguments
and find them unpersuasive. Accordingly, we affirm the
district court’s construction of “plasmid” as a “circular,
extrachromosomal molecule.”

2. Infringement

The district court held on summary judgment that
Appellees do not infringe claims 42–45 of the ’140 patent
15 SANOFI-AVENTIS v. GENENTECH

literally or under the doctrine of equivalents. On appeal,
Sanofi challenges only the holding of noninfringement
under the doctrine of equivalents, arguing that the dis-
trict court incorrectly conflated literal infringement with
the doctrine of equivalents and mischaracterized the
function of the claimed plasmid for purposes of the
equivalents analysis. Sanofi maintains that the differ-
ences between the claimed circular extrachromosomal
plasmids and Appellees’ linear, integrated DNAs are
insubstantial because both provide the same genetic
information and therefore achieve the same heterologous
protein expression in the same way.

We agree with the district court that Sanofi cannot
rely on the doctrine of equivalents because doing so would
vitiate the “plasmid” limitation of each asserted claim.
Patentees may not assert “a theory of equivalence [that]
would entirely vitiate a particular claim element.” War-
ner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17,
39 n.8 (1997). Sanofi argues that the claimed “recombi-
nant DNA plasmid” provides “a fixed arrangement of
those pieces of DNA required for gene expression by the
cell’s transcriptional machinery,” and that linear or
circular DNA can perform this function in the same way
to achieve the same result. Br. for Plaintiff-Appellant at
44–45. But such a theory of equivalence of the claimed
“recombinant DNA plasmid” focuses on the functions
attributable to “recombinant DNA” and ignores the
“plasmid” requirement. Although recombinant DNA in
both linear and integrated, or circular and extrachromo-
somal, forms are capable of providing a template for gene
expression, the claims call for achieving that function
with a “plasmid”—defined here as a circular, extrachro-
mosomal molecule.
SANOFI-AVENTIS v. GENENTECH 16

To find equivalence in this situation would be to read
the “plasmid” element out of the claims entirely, which
the district court correctly declined to do. See SciMed Life
Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d
1337, 1347 (Fed. Cir. 2001) (“[I]f a patent states that the
claimed device must be ‘non-metallic,’ the patentee cannot
assert the patent against a metallic device on the ground
that a metallic device is equivalent to a non-metallic
device.”). The Appellees were therefore entitled to sum-
mary judgment of noninfringement of the asserted claims
of the ’140 patent.

III. CONCLUSION

Accordingly, we affirm the final judgment of the dis-
trict court.

AFFIRMED