NOTE: This disposition is nonprecedential.
United States Court of Appeals for the Federal Circuit
2009-1023
AMGEN, INC., IMMUNEX CORPORATION,
AMGEN USA, INC., AMGEN MANUFACTURING LIMITED,
and IMMUNEX RHODE ISLAND CORPORATION,
Plaintiffs/Counterclaim Defendants-
Appellees,
and
WYETH,
Counterclaim Defendant,
v.
ARIAD PHARMACEUTICALS, INC.
and THE WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH,
Defendants/Counterclaimants-
Appellants,
and
MASSACHUSETTS INSTITIUTE OF TECHNOLOGY
and THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE,
Counterclaimants-Appellants.
Mark A. Pals, Kirkland & Ellis LLP, of Chicago, Illinois, argued for plaintiffs/counterclaim
defendants-appellees. With him on the brief were Marcus E. Sernel and Jamie H. McDole. Of
counsel on the brief were Siegmund Y. Gutman, Hogan & Hartson LLP, of Washington, DC,
and J. Drew Diamond, of Los Angeles, California. Also on the brief were Melanie K. Sharp,
Young Conaway Stargatt & Taylor, of Wilmington, Delaware; Stuart L. Watt, Wendy A.
Whiteford, Monique L. Cordray, Gail A. Katz, Erica S. Olson, Amgen Inc., of Thousand Oaks,
California, and Kathleen Fowler, of Seattle, Washington.
Evan R. Chesler, Cravath, Swaine & Moore LLP, of New York, New York, argued for
defendants/counterclaimants-appellants and counterclaimants-appellants. With him on the
brief were Keith R. Hummel, David R. Marriott, and David Greenwald.
Appealed from: United States District Court for the District of Delaware
Magistrate Judge Mary Pat Thynge
NOTE: This disposition is nonprecedential.
United States Court of Appeals for the Federal Circuit
2009-1023
AMGEN INC., IMMUNEX CORPORATION,
AMGEN USA INC., AMGEN MANUFACTURING LIMITED,
and IMMUNEX RHODE ISLAND CORPORATION,
Plaintiffs/Counterclaim
Defendants-Appellees,
and
WYETH,
Counterclaim Defendant,
v.
ARIAD PHARMACEUTICALS, INC.
and THE WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH,
Defendants/Counterclaimants-
Appellants,
and
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
and THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE,
Counterclaimants-Appellants.
Appeal from the United States District Court for the District of Delaware in case No. 06-
CV-259, Magistrate Judge Mary Pat Thynge.
____________________________
DECIDED: June 1, 2009
____________________________
Before MICHEL, Chief Judge, DYK and MOORE, Circuit Judges.
MOORE, Circuit Judge.
The Plaintiffs/Counterclaim Defendants-Appellees (collectively, Amgen) sued the
Defendants/Counterclaimants-Appellants (collectively, Ariad) in the United States
District Court for the District of Delaware for a declaratory judgment of invalidity and
noninfringement of U.S. Patent No. 6,410,516 (the ’516 patent). Ariad counterclaimed
for infringement of claims 6, 18, 70-72, 183, and 184 of the ’516 patent (the asserted
claims). The district court construed a number of terms in the asserted claims, largely in
accordance with Amgen’s proposed constructions. In light of its claim construction, the
district court granted Amgen’s motion for summary judgment of noninfringement.
Amgen, Inc. v. Ariad Pharms, Inc., 577 F. Supp. 2d 695 (D. Del. 2008). Ariad appeals.
For the reasons set forth below, we affirm.
BACKGROUND
We previously discussed the technology at issue in this case with regard to
different claims of the ’516 patent. See Ariad Pharms., Inc. v. Eli Lilly & Co., 560 F.3d
1366, 1369-70 (Fed. Cir. 2009). The ’516 patent concerns a protein known as NF-κB,
and claims methods comprising “reducing NF-κB activity.” All of the asserted claims
include that limitation:
6. A method for diminishing induced NF-κB-mediated intracellular
signaling comprising reducing NF-κB activity in cells such that NF-κB-
mediated intracellular signaling is diminished.
70. The method of claim 6, carried out on mammalian cells.
71. The method of claim 6, carried out on human cells.
72. The method of claim 70 or 71, carried out on immune cells.
18. A method for reducing Interleukin-1 or Tumor Necrosis Factor-α
activity in mammalian cells comprising reducing NF-κB activity in the cells
so as to reduce intracellular signaling caused by Interleukin-1 or Tumor
Necrosis Factor-α in the cells.
2009-1023 2
183. The method of claim 18, carried out on human cells.
184. The method of claim 18 or 183, carried out on immune cells.
The district court determined that “NF-κB activity” means “the ability of NF-κB to act as
an intracellular messenger by being released from IκB; translocating into the nucleus;
and regulating the transcription of particular genes by binding to specific DNA
recognition sequences in those genes.” Amgen, 577 F. Supp. 2d at 727. The parties
do not appeal this construction. NF-κB activity may arise when it is induced by
extracellular influences such as tumor necrosis factor-alpha (TNF-α)—an “inducing
substance” in the language of the specification. TNF-α interacts with receptors on the
surface of the cell and thereby initiates a chain of events that eventually releases NF-κB
from IκB—the first step of NF-κB activity. The parties’ arguments on appeal focus on
the meaning of “reducing NF-κB activity in cells.” The reduction of NF-κB activity is
desirable because NF-κB increases the harmful expression of certain genes.
Because NF-κB also induces the expression of its own inhibitor, IκB, NF-κB
activity will decrease naturally if the external inducing substance (e.g., TNF-α) is
removed. Exogenous agents may also be able to decrease NF-κB activity, and it is
helpful to consider several examples of such agents. The ’516 patent proposes several
classes of molecules potentially capable of reducing NF-κB activity, such as specific
inhibitors, dominantly interfering molecules, and decoy molecules, all of which were
discussed in greater detail in Ariad, 560 F.3d at 1374-76. These classes of molecules
are meant to act inside the cell. For example, decoy molecules are “designed to mimic
a region of the gene whose expression would normally be induced by NF-κB. In this
case, NF-κB would bind the decoy, and thus, not be available to bind its natural target.”
2009-1023 3
’516 patent col.37 ll.51-54. In contrast, the accused drug—Amgen’s Enbrel—acts
outside the cell. Enbrel acts by binding to free TNF-α outside the cell, thus interfering
with the TNF-α’s ability to reach the receptors on the cell and induce NF-κB activity.
Amgen, 577 F. Supp. 2d at 700. The prior art also contains example agents that act
outside the cell. For example, antibiotics act by killing bacteria, which consequentially
reduces the amount of TNF-α released by macrophages in response to the bacterial
infection. The use of decoy molecules, Enbrel, or antibiotics all may ultimately result in
a decrease of NF-κB activity, but the question remains what is included in the properly
interpreted scope of “reducing NF-κB activity in cells.”
The district court agreed with Amgen that the asserted claims are limited to
actions that reduce NF-κB activity wherein those actions occur within the cell. As such,
the district court adopted Amgen’s construction of “reducing NF-κB activity in cells”:
“taking action inside cells to directly inhibit (interfere or block) an NF-κB activity.” Id. at
728. Under the district court’s construction, decoy molecules could infringe, but Enbrel
cannot. This precipitated the district court’s summary judgment of noninfringement. Id.
at 700-02. On October 3, 2008, the district court stayed Amgen’s invalidity claims and
entered final judgment on the noninfringement claim pursuant to Fed. R. Civ. P. 54(b).
We have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
Ariad argues that the district court erred in its construction of “reducing NF-κB
activity in cells,” and that under the proper construction, we should reverse the summary
judgment of noninfringement. Claim construction is a question of law reviewed de novo.
Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1455-56 (Fed. Cir. 1998) (en banc).
2009-1023 4
“Claim terms should generally be given their ordinary and customary meaning and . . .
such meaning is one ‘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.’” ICU Med., Inc. v. Alaris Med. Sys., 558 F.3d 1368, 1374 (quoting Phillips
v. AWH Corp., 415 F.3d 1303, 1312-13 (Fed. Cir. 2005) (en banc)). “[T]he person of
ordinary skill in the art 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.” Phillips, 415 F.3d at 1313; see id. at 1317 (“It is
therefore entirely appropriate for a court, when conducting claim construction, to rely
heavily on the written description for guidance as to the meaning of the claims.”).
Furthermore, “the prosecution history can often inform 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.
Amgen prevailed in the district court by arguing that the outer boundary of the
asserted claims’ scope is the cell membrane. The district court agreed with Amgen that
agents that act outside the cell do not infringe, but that agents that act inside the cell
may. This is not to imply that Ariad argues in response that the reducing act could
occur anywhere. Rather, Ariad would place the boundary at some indefinite place
outside of the cell such that accused drugs such as Enbrel are captured but certain prior
art drugs, such as antibiotics, are left out of the claim scope. Ariad is correct that the
asserted claims have a limited scope, but its particular choice of boundary lacks
foundation in the intrinsic evidence. For our analysis, we begin with the claim language.
2009-1023 5
The ordinary meaning of “reducing NF-κB activity in cells” is unclear. The phrase
cannot simply reflect that the NF-κB activity must occur within cells because this would
be redundant. There is no dispute NF-κB activity can occur only within cells, and this
limit is already included in the claim construction of “NF-κB activity.” Amgen, 577 F.
Supp. 2d at 727. As Amgen argues, “reducing NF-κB activity in cells” could mean that
the reducing act must occur within the cell. But as Ariad suggests, it could also mean
simply that the method must be performed on cells in which NF-κB is present, without
regard to the situs of the reducing agent.
The specification of the ’516 patent divides external influences (e.g., TNF-α) and
intracellular transducers (e.g., NF-κB). That division is at the cell membrane, and the
claim language “reducing NF-κB activity in cells” is consistent with this division. The
specification repeatedly frames NF-κB as an intracellular transducer of external
influences:
As a result of this finding, it is now possible to alter or modify the
activity of NF-κB as an intracellular messenger and, as a result, to alter or
modify the effect of a variety of external influences, referred to as inducing
substances, whose messages are transduced within cells through NF-κB
activity. Alteration or modification, whether to enhance or reduce NF-κB
activity or to change its binding activity (e.g., affinity, specificity), is
referred to herein as regulation of NF-KB activity. The present invention
relates to a method of regulating or influencing transduction, by NF-κB, of
extracellular signals into specific patterns of gene expression and, thus, of
regulating NF-κB-mediated gene expression in the cells and systems in
which it occurs.
In particular, the present invention relates to a method of regulating
(enhancing or diminishing) the activity of NF-κB in cells in which it is
present and capable of acting as an intracellular messenger, as well as to
substances or composition useful in such a method.
’516 patent col.3 l.59 – col.4 l.9. For example, TNF-α is an “inducing substance”
because its “messages are transduced within cells through NF-κB activity.” Decoy
2009-1023 6
molecules are designed to “alter or modify the activity of NF-κB as an intracellular
messenger” by binding active NF-κB and preventing it from inducing DNA expression.
Consequently, the administration of decoy molecules would “alter or modify the effect
of” TNF-α by blocking, within the cell, the signal that was initiated by TNF-α at the
receptor on the surface of the cell.
Thus, the specification assumes the existence of an external influence whose
effect can be modified by acting within the cell. In contrast, Enbrel acts to stop the
external influence (TNF-α) from reaching the cell. Enbrel does not “alter or modify the
activity of NF-κB as an intracellular messenger and, as a result, . . . alter or modify the
effect of a variety of external influences.” Rather, it directly blocks one of the “variety of
external influences.” While the specification proposes several agents that act within the
cell to reduce NF-κB activity, there is no mention whatsoever of agents that act outside
the cell to reduce NF-κB activity.
In its arguments made to the PTO during reexamination of the ’516 patent, Ariad
further reinforced the division between actions taken inside and outside of the cells:
Broadly speaking, there are the two types of methods to obtain a cell
exhibiting reduced NF-κB activity [which are] as follows: (a) reducing the
induced NF-κB activity by intervening in the signaling pathway by which
NF-κB activity is manifested including particularly intervening intracellularly
at a specific segment within the signaling pathway; and (b) preventing the
external inducing stimuli from inducing the intracellular signaling pathway
through which NF-κB activity is manifested. Certain claims of the ’516
patent as issued covered both types of methods. However, as discussed
further in this response applicants maintain that the rejected claims now
pending [which include claims 6, 18, 70-72 and 183-184] are directed only
to type (a) above.
The category (a) methods described above indisputably include decoy molecules and
the other examples in the specification because those agents “interven[e]
2009-1023 7
intracellularly.” And the category (b) methods indisputably include antibiotics because
they “prevent[] the external inducing stimuli from inducing” NF-κB activity. Enbrel, which
acts outside the cell, and acts by blocking the external inducing stimuli from reaching
the cell, would seem a far better fit in category (b) than category (a). Ariad’s difficulty in
making its argument to the PTO, and in this case, is that it lacks a basis in the
specification to distinguish Enbrel from antibiotics. Rather, the patent creates a
category of “external influences” that are simply the backdrop for the invention, and
Enbrel and antibiotics impact only this category. Ariad argues that the “signaling
pathway” should include the event of TNF-α binding to the receptor on the outside of the
cell, and as such Enbrel should fit into category (a). But again, there is nothing
whatsoever in the specification to support this view—not even a single mention of an
NF-κB signaling pathway.
Although the ordinary meaning of the term “reducing NF-κB activity in cells”
admits alternative views, the specification and prosecution history unequivocally point to
the conclusion that the term limits the asserted claims to methods wherein the action
that reduces NF-κB activity is taken inside the cell. As such, we conclude that “reducing
NF-κB activity in cells” means “taking action inside cells to inhibit (interfere or block) an
NF-κB activity.” We therefore affirm the summary judgment of noninfringement. Ariad
also appealed the construction of numerous other claim terms, but the parties agree
that none of these has any impact on the summary judgment of noninfringement on
appeal. Therefore, we decline to reach them.
On appeal, Amgen filed a motion for affirmance on the alternative ground of
collateral estoppel in view of our decision in Ariad, which invalidated claims 80, 95, 144,
2009-1023 8
and 145 of the ’516 patent for lack of written description. 560 F.3d at 1376-77. In its
motion, Amgen argued that Ariad is now precluded from asserting any claims of the
’516 patent that recite methods comprising the single step of “reducing NF-κB activity.”
We decline to reach this issue. The motion is denied.
CONCLUSION
We agree with the district court that the term “reducing NF-κB activity in cells”
limits the claims to acts within the cell to reduce NF-κB activity. Because there is no
dispute of fact that Enbrel does not infringe the asserted claims as construed, the
judgment below is affirmed.
2009-1023 9