United States District Court, N.D. California
ORDER CONSTRUING CLAIMS
RICHARD SEEBORG United States District Judge
I.
INTRODUCTION
Amgen,
Inc. and Sandoz Inc., Sandoz International GmbH, and Sandoz
GmbH (collectively “Sandoz”) compete to develop,
manufacture, promote, and sell biopharmaceutical products,
including those used to facilitate stem-cell transplantation.
Amgen holds two patents at issue in this action: U.S. Patent
Nos. 6, 162, 427 (“the ’427 Patent”) and 8,
940, 878 (“the ’878 Patent”). Amgen accuses
Sandoz of infringing those patents. The parties seek
construction of ten terms pursuant to Markman v. Westview
Instruments, Inc., 52 F.3d 967 (Fed. Cir. 1995) (en
banc). For the reasons set forth below, the disputed terms
are construed as follows.
II.
BACKGROUND
In
2014, Amgen filed claims against Sandoz for infringement of
the ’427 patent, “Combination of G-CSF with a
Chemotherapeutic Agent for Stem Cell Mobilization.”
Amgen objects to Sandoz’s efforts to market and sell
ZARXIO®, a drug Amgen contends is biosimilar to its drug,
NEUPOGEN®, which is commonly used to “treat[] the
side effects of certain forms of cancer therapy.” FAC
¶ 11. The active ingredient in both products is
filgrastim, a synthetic version of human granulocyte colony
stimulating factor (“G-CSF”). Amgen also accuses
Sandoz of violating California’s unfair competition law
(“UCL”). In response, Sandoz asserts numerous
counterclaims for declaratory judgments of compliance with
the Biosimilars Price Competition and Innovation Act
(“BPCIA”), non-infringement, and patent
invalidity. In March 2015, Sandoz obtained partial judgment
in its favor with respect to the UCL claim and Sandoz’s
claim for a declaratory judgment of compliance with the BPCIA
pursuant to Federal Rule of Civil Procedure 54(b). The
parties jointly requested to stay these proceedings until the
issuance of the Federal Circuit’s mandate. Dkt. No. 111
at 3.
Amgen
then appealed to the Federal Circuit. During the pendency of
the appeal, the Federal Circuit entered an injunction to
prevent Sandoz from marketing, selling, or importing
ZARXIO®. The Federal Circuit affirmed dismissal of the
UCL claim, and affirmed in part and reversed in part the
order regarding the BPCIA. See Amgen Inc. v. Sandoz
Inc., 794 F.3d 1347 (Fed. Cir. 2015). Sandoz filed a
petition for en banc review, which is still pending in the
Federal Circuit.
Following
the issuance of the Federal Circuit’s mandate, the
parties agreed to lift the stay, and Amgen filed a First
Amended Complaint, asserting one additional claim of patent
infringement. Amgen now contends Sandoz employs a method of
protein capture that infringes the ’878 patent,
entitled “Capture Purification Processes for Proteins
Expressed in a Non-Mammalian System.”
III.
LEGAL STANDARD
Claim
construction is a question of law to be determined by the
court. Markman, 52 F.3d at 979. “Ultimately,
the interpretation to be given a term can only be determined
and confirmed with a full understanding of what the inventors
actually invented and intended to envelop with the
claim.” Renishaw PLC v. Marposs Societa’ per
Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998).
Accordingly, a claim should be construed in a manner that
“most naturally aligns with the patent’s
description of the invention.”
The
first step in claim construction is to look to the language
of the claims themselves. “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) (quoting
Innova/Pure Water, Inc. v. Safari Water Filtration Sys.,
Inc., 381 F.3d 1111, 1115 (Fed. Cir. 2004)). A disputed
claim term should be construed in a manner consistent with
its “ordinary and customary meaning, ” which 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
1312-13. The ordinary and customary meaning of a claim term
may be determined solely by viewing the term within the
context of the claim’s overall language. See
Id. at 1314 (“[T]he use of a term within the claim
provides a firm basis for construing the term.”).
Additionally, the use of the term in other claims may provide
guidance regarding its proper construction. Id.
(“Other claims of the patent in question, both asserted
and unasserted, can also be valuable sources of enlightenment
as to the meaning of a claim term.”).
A claim
should also be construed in a manner that is consistent with
the patent’s specification. See Markman, 52
F.3d at 979 (“Claims must be read in view of the
specification, of which they are a part.”). Typically
the specification is the best guide for construing the
claims. See Phillips, 415 F.3d at 1315 (“The
specification is . . . the primary basis for construing the
claims.”); see also Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)
(“[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.”). In limited circumstances, the specification
may be used to narrow the meaning of a claim term that
otherwise would appear to be susceptible to a broader
reading. See SciMed Life Sys., Inc. v. Advanced
Cardiovascular Sys., Inc., 242 F.3d 1337, 1341 (Fed.
Cir. 2001) (“Where the specification makes clear that
the invention does not include a particular feature, that
feature is deemed to be outside the reach of the claims of
the patent, even though the language of the claims, read
without reference to the specification, might be considered
broad enough to encompass the feature in question.”);
Phillips, 415 F.3d at 1316 (“[T]he
specification may reveal an intentional disclaimer, or
disavowal, of claim scope by the inventor. In that instance
as well, the inventor has dictated the correct claim scope,
and the inventor’s intention, as expressed in the
specification, is regarded as dispositive.”). Precedent
forbids, however, a construction of claim terms that imposes
limitations not found in the claims or supported by an
unambiguous restriction in the specification or prosecution
history. Laitram Corp. v. NEC Corp., 163 F.3d 1342,
1347 (Fed. Cir. 1998) (“[A] court may not import
limitations from the written description into the
claims.”); Comark Commc’ns., Inc. v. Harris
Corp., 156 F.3d 1182, 1186 (Fed. Cir. 1998)
(“[W]hile claims are to be interpreted in light of the
specification, it does not follow that limitations from the
specification may be read into the claims.” (internal
quotation marks and alterations omitted)); SRI
Int’l v. Matsushita Elec. Corp. of Am., 775 F.2d
1107, 1121 (Fed. Cir. 1985) (en banc) (“It is the
claims that measure the invention.”) (emphasis
in original). A final source of intrinsic evidence is the
prosecution record and any statements made by the patentee to
the United States Patent and Trademark Office
(“PTO”) regarding the scope of the invention.
See Markman, 52 F.3d at 980.
Courts
may also consider extrinsic evidence, such as expert
testimony, dictionaries, or technical treatises, especially
if such sources are “helpful in determining ‘the
true meaning of language used in the patent
claims.’” Phillips, 415 F.3d at 1318
(quoting Markman, 52 F.3d at 980). Ultimately, while
extrinsic evidence may aid the claim construction analysis,
it cannot be used to contradict the plain and ordinary
meaning of a claim term as defined within the intrinsic
record. See Phillips, 415 F.3d at 1322-23.
IV.
DISCUSSION
A.
The ’427 Patent
Hematopoietic
stem cells naturally occur in the human body and are capable
of proliferation and differentiation into cells that comprise
the blood and immune systems. In other words, they are
blood-forming stem cells.[1] These cells self-renew and reside
primarily in bone marrow.
Peripheral
stem cell transplantation is a process used to replace
damaged blood-forming stem cells-the sort of cellular damage
chemotherapy usually causes. Peripheral blood is the blood
that circulates through the body. Before peripheral stem cell
transplantation can occur, the doctor must collect
blood-forming stem cells for later transplantation.
Collection requires “mobilizing” stem cells in
the bone marrow to move into the peripheral blood stream.
Once the stem cells have mobilized, doctors collect them
using a process called leukapheresis, which separates the
stem cells from other types of blood cells. The collected
cells are then set aside for later use. The more
blood-forming stem cells in the blood stream, the fewer
leukapheresis sessions the patient must undergo to collect
enough cells for transplantation.
G-CSF
is a protein that naturally occurs in the human body.
Filgrastim is a pharmaceutical analog of human G-CSF
constructed artificially in E. coli bacteria using
recombinant DNA technology. Since the early 1990s, doctors
and researchers have been using G-CSF in connection with
chemotherapy to relieve the side effects of chemotherapy.
G-CSF has also been used to facilitate mobilization of
blood-forming stem cells from the bone marrow into the
peripheral blood.
After
the stem-cell collection, the patient undergoes myeloablative
radiation (bone marrow destruction) or myelotoxic
chemotherapy (bone marrow suppression), which destroy
blood-forming stem cells in the process. Once chemotherapy
has been administered, the collected stem cells can be
reintroduced into the bone marrow to allow for further
production of new blood cells.
Both
parties agree that the ’427 patent describes a method
that requires administration of G-CSF before administration
of a chemotherapeutic agent. The order of administration
(G-CSF first, a chemotherapeutic agent second) is the
allegedly novel component of the invention. At the time of
the invention, a skilled artisan knew that administration of
G-CSF alone, a chemotherapeutic agent alone, or a
chemotherapeutic agent followed by G-CSF could mobilize
blood-forming stem cells into the blood stream. The patentees
purport to have reached the revolutionary conclusion that the
structured administration of G-CSF first, followed by
administration of a chemotherapeutic agent was the most
efficient method of stem cell mobilization. The patent claims
to improve on the process of stem cell collection by
following the specified order, which relieves patients of the
need to attend multiple of leukapheresis sessions.
1.
“hematopoietic stem cell mobilizing-effective
amount of G-CSF”
The
term “hematopoietic stem cell mobilizing-effective
amount of G-CSF” appears in only claim 1, but is
incorporated by reference into claims 2, 3, 4, and 6. Amgen
would have the term construed to mean “an amount of
G-CSF effective to mobilize hematopoietic stem cells, ”
whereas Sandoz contends the term is indefinite.
When
evaluating whether a term is sufficiently definite, courts
must analyze that question “from the viewpoint of a
person skilled in the art at the time the patent was
filed.” Nautilus, Inc. v. Biosig Instruments,
Inc., 134 S.Ct. 2120, 2128 (2014) (emphasis, internal
quotation marks, and alteration omitted). As noted, the
claims “are to be read in light of the patent’s
specification and prosecution history.” Id.
When examining the definiteness of a term, courts “must
take into account the inherent limitations of language,
” and therefore “[s]ome modicum of uncertainty .
. . is the price of ensuring the appropriate incentives for
innovation.” Id. (internal quotation marks
omitted). “At the same time, a patent must be precise
enough to afford clear notice of what is claimed, thereby
apprising the public of what is still open to them.”
Id. at 2129 (internal quotation marks omitted).
“Cognizant of the competing concerns, ” the
Supreme Court requires “that a patent’s claim,
viewed in light of the specification and prosecution history,
inform those skilled in the art about the scope of the
invention with reasonable certainty.” Id.
The
first step required is to define who is a person skilled in
the relevant art. This patent was written for those who
practice stem-cell transplantation or study stem-cell
biology. A person skilled in the relevant art is therefore
one who has obtained a Ph.D. in biological sciences or an
M.D. In addition, this person is one with significant
experience with stem-cell biology, hematopoiesis, and
stem-cell transplantation.
Turning
to the question of whether such a skilled artisan understands
the phrase “hematopoietic stem cell
mobilizing-effective amount of G-CSF, ” Sandoz takes
aim at the word “effective” and offers three
arguments for why the term is indefinite. First, it argues
neither the claim language nor the specification inform
skilled artisans about how many blood-producing stem cells
must mobilize to be considered “effective.” In
other words, a skilled artisan has no way to discern whether
mobilization of one stem cell, ten stem cells, or a thousand
stem cells is “effective.” Second, Sandoz insists
the claim, specification, and prosecution history do not
provide information for skilled artisans to tailor the
procedure to the species of the patient (human, mouse, dog,
horse, etc.). The final argument is that the patent does not
explain how artisans should measure the level of stem-cell
mobilization. At the time of the invention, practitioners
knew of four methods for measuring the extent of stem cell
mobilization, all of which varied considerably in terms of
accuracy, consistency, and practicality. See
Sandoz’s Expert Negrin Decl. ¶¶ 45-46.
Whether
adjectival limitations are indefinite depends on the context
of each individual patent. In Takeda Pharm. Co. v. Mylan
Inc., No. 13-CV-04001-LHK, 2014 WL 5862134, at *10-11
(N.D. Cal. Nov. 11, 2014), the district court deemed the term
“effective amount” definite because the patent
described the proper dose of the drug (“about 0.5 to 1,
500 mg/day”), and the claim covered treatment of a
specific type of disease-reflux esophagitis. Id. at
*10. In contrast, another district court concluded the term
“% identity” was indefinite because “the
specification identifie[d] a non-inclusive list of five
methods to calculate ‘% identity’ and provide[d]
that sequence alignment can be performed using any
commercially available or independently developed
software.” Butamax Advanced Biofuels LLC v. Gevo,
Inc., 117 F.Supp.3d 632, 641 (D. Del. 2015). Similarly,
in Andrulis Pharm. Corp. v. Celgene Corp., No. CV
13-1644(RGA), 2015 WL 3978578, at *3-4 (D. Del. June 26,
2015), the term “enhanced therapeutically-effective
amounts of thalidomide” was held to be indefinite
because “enhanced” could mean “less than
additive, additive, or greater than additive.”
Id. at *3.
Here,
the claim itself offers little guidance, but the
specification provides more direction. It teaches,
“[t]he [G-CSF] dosage may depend on various factors
such as mode of application, species, age, or individual
condition. According to the invention, from 5 to 300
µg/kg/day of G- CSF sc.[2] is applied.” Pai Decl. Ex. 1,
’427 Patent 3:4-7. G-CSF administration occurs
“once per day over two to three days.” ’427
Patent 4:5-8. Amgen points to portions of the specification
that explain, “[n]umerous substances” are capable
of causing mobilization of blood-producing stem cells, such
as G-CSF and “[s]ome chemotherapeutic agents.”
’427 Patent 1:32-37. These passages make clear that, at
the time the patent was filed, skilled artisans knew G-CSF
caused blood-producing stem cells to mobilize, and that any
amount ranging from 5 to 300 µg/kg/day of G-CSF sc.
would cause stem cells to mobilize enough to enable
collection.
The
prosecution history of the ’427 patent offers skilled
artisans further guidance and additional support for
Amgen’s proposed construction. Three papers identified
in the specification refer to various G-CSF dosage amounts
within the range stated in the specification. Two papers
examined the efficacy of subcutaneous doses of 10
µg/kg/day. Wu Decl. Ex 4 at 861 (Long et al.,
Cancer 76(5):860-68 (1995)); Wu Decl. Ex. 6 at 146
(Pierelli et al., J. Hematotherapy 2:145-53 (1993)).
Another study tested the comparative potency of subcutaneous
or intravenous doses of 10 µg/kg/day or 5
µg/kg/day. Wu Decl. Ex. 5 at 2177 (Nademanee et al.,
J. Clinical Oncology 12(10):2176-86 (1994)). These
three studies supply a person skilled in the art with more
information to determine with a reasonable degree of
certainty how much G-CSF to administer to achieve more than a
de minimus level of stem-cell mobilization.
While
the range of the amounts of G-CSF to administer is admittedly
wide and variable depending on the size or species of the
subject, a skilled artisan is not without any guidance to
figure out how much G-CSF to administer. After all,
“breadth is not indefiniteness.” SmithKline
Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1341 (Fed.
Cir. 2005). To the extent a skilled artisan may have
difficulty adjusting the amount of G-CSF to administer
depending on the species of the subject, the lack of
precision in the claim and specification impacts only his or
her ability to practice all embodiments of the claim-a
question of enablement, not indefiniteness. See
Takeda, 2014 WL 5862134, at *10 (citing Exxon
Research & Eng’g Co. v. United States, 265
F.3d 1371, 1382 (Fed. Cir. 2001) (noting that
“‘inoperable embodiments’ raise ‘an
issue of enablement, and not indefiniteness”)).
Overall, the patent communicates the purpose of G-CSF
administration: to cause more than a de minimus
number of blood-producing stem cells to enter the peripheral
blood. While the claim and specification could have offered
more precise guideposts, the disclosures provide those
skilled in the art with sufficient information to figure out
how to accomplish that goal. Accordingly, the phrase
“hematopoietic stem cell mobilizing-effective amount of
G-CSF” is not indefinite. It will be construed as
follows: “an amount of G-CSF effective to mobilize
hematopoietic stem cells.”
2.
“A method of treating a disease requiring
peripheral stem cell transplantation in a patient in need of
such treatment”
The
second phrase to construe is the preamble to claim 1.
Although it appears in only claim 1, claims 2, 3, 4, and 6
incorporate the preamble by reference. Both parties agree the
preamble limits the scope of the claim, but they disagree
about how to construe it. The crux of the dispute is about
the phrase “a method of treating a disease requiring
peripheral stem cell transplantation in a patient in need of
such treatment.” Amgen construes the phrase as follows:
“In the practice of the method, a patient in need of a
stem cell transplant receives a transplant of peripheral stem
cells.” Sandoz offers the following construction:
“In the practice of the method of treating a disease, a
patient receives a transplant of peripheral stem
cells.” The fight boils down to whether peripheral stem
cell transplantation is itself disease treatment, or whether
it is a component of disease treatment to alleviate the side
effects of treatment (namely chemotherapy). The text of the
claim itself and the intrinsic record support Sandoz’s
construction.
To
begin, the phrase “such treatment” must have an
antecedent. See Rapoport v. Dement, 254 F.3d 1053,
1059 (Fed. Cir. 2001) (noting the phrase “to a patient
in need of such treatment” must have an antecedent
basis). Sandoz argues the antecedent is “a method of
treating a disease, ” whereas Amgen insists it refers
back to “peripheral stem cell transplantation.”
Under Sandoz’s construction, the treatment (usually
chemotherapy) necessitates stem-cell transplantation. To
practice the treatment method, the doctor mobilizes,
collects, and transplants blood-producing stem cells into the
patient. In contrast, under Amgen’s reading it is the
disease (primarily cancer) that requires peripheral stem cell
transplantation. While “such treatment” surely
requires an antecedent, both proposed constructions are
grammatically correct, and therefore to construe the terms
requires a more searching inquiry.
The
text of the whole claim lends support to Sandoz’s
construction. The method claim 1 includes two steps: (1)
administration of G-CSF, and (2) administration of a
chemotherapeutic agent. The claim describes the quantity of
G-CSF to be administered as “stem cell mobilizing,
” whereas the chemotherapeutic agent is described as
“disease treating.” See ’427
Patent at 10:26-29. In other words, one substance mobilizes
stem cells, while the other treats a disease. The claim
suggests the transplantation itself does not treat disease.
The
specification bears out this interpretation. It explains the
purpose of the claimed method: “The use of high-dosage
chemotherapy or bone marrow ablation by irradiation requires
subsequent incorporation of hematopoietic stem cells into the
patient, in which case recovery of such cells is
required.” ’427 Patent at 1:18-21. Mobilization
of blood-forming stem cells “has a crucial influence on
the efficiency of” peripheral stem cell recovery.
’427 Patent at 1:22-24. The method claimed by the
patent improves upon the process of collecting stem cells by
increasing the number of stem cells in the peripheral blood,
thereby reducing the number of leukaphereses required.
See ’427 Patent at 1:24-27 (“At present,
2-3 leukaphereses are required for successful peripheral stem
cell transplantation, resulting in considerable stress for
the patients.”); id. at 1:55-61 (“As the
required number of leukaphereses is extremely stressing for
the patient in the run-up to the treatment of particular
diseases, e.g., in preparing myeloablative or myelotoxic
therapy, the invention was based on the object of achieving a
superior yield of stem cells or a decrease in the number of
leukophereses via enhanced mobilization of stem
cells.”). Finally, the specification teaches that
administration of G-CSF followed by administration of a
chemotherapeutic agent is part of the “run-up to a,
e.g. antitumor therapy, ” and therefore is not the
disease treatment itself. ’427 Patent at 4:24-25.
Thus,
the specification clarifies any ambiguity in the text of the
claim about whether peripheral stem-cell transplantation is a
treatment for disease or a component of disease
treatment.[3] It
is the latter. Accordingly, Sandoz has the better
construction, and it is adopted.
3.
“disease treating-effective amount of at least one
chemotherapeutic agent”
The
next phrase up for construction is “disease
treating-effective amount of at least one chemotherapeutic
agent.”[4]
It appears in claim 1, and the patentee also incorporated the
term by reference into claims 2, 3, 4, and 6. Amgen proposes
defining the phrase as “an amount of at least one
chemotherapeutic agent sufficient to enhance the mobilization
of stem cells for recovery from the blood for subsequent
peripheral transplantation.” Sandoz offers the
following construction: “an amount sufficient to treat
a disease for which at least one chemotherapeutic agent is
prescribed.” The crux of the dispute revolves around
whether the chemotherapeutic agent treats a disease such as
cancer (Sandoz’s construction), or whether the
chemotherapeutic agent’s purpose is to mobilize
blood-producing stem cells for collection and subsequent
peripheral transplantation (Amgen’s construction). The
text of the claim and the specification compel adoption of
Sandoz’s proposal.
“[T]he
context in which a term is used in the asserted claim can be
highly instructive.” Phillips, 415 F.3d at
1314. There are three parts to claim 1-the preamble and two
limitations: the first limitation is a description of step
one (administration of G-CSF); the second limitation is a
description of step two (administration of the
chemotherapeutic agent). Rather than referring to the two
steps of the claimed process as “stem-cell mobilizing,
” the patentee chose to use different descriptors for
G-CSF and chemotherapeutic agents. G-CSF is
“hematopoietic stem cell mobilizing, ” whereas
the chemotherapeutic agent is “disease treating.”
See ’427 Patent at 10:27-29. “Different
claim terms are presumed to have ...