United States District Court, D. Delaware
GENENTECH, INC. and CITY OF HOPE, Plaintiffs and Counterclaim Defendants,
AMGEN INC., Defendant and Counterclaim Plaintiff. GENENTECH, INC. and CITY OF HOPE, Plaintiffs and Counterclaim Defendants,
SAMSUNG BIOEPSIS CO., LTD., Defendant and Counterclaim Plaintiff.
Michael P. Kelly, Daniel M. Silver, MCCARTER &ENGLISH,
LLP, Wilmington, Delaware. Counsel for Plaintiffs in C A. No.
Frederick L. Cottrell, III, Jason J. Rawnsley, RICHARDS,
LAYTON & FINGER, P.A., Wilmington, Delaware. Counsel for
Plaintiffs in C.A. No. 18-1363-CFC.
William F. Lee, Lisa J. Pirozzolo, Emily R. Whelan, Kevin S.
Prussia, Andrew J. Danford, WILMER CUTLER PICKERING HALE AND
DORR LLP, Boston, Massachusetts; Robert J. Gunther Jr.,
WILMER CUTLER PICKERING HALE AND DORR LLP, New York, New
York; Daralyn J. Durie, Adam R. Brausa, DURIE TANGRI LLP, San
Francisco, California. Counsel for Plaintiffs in CA. No.
18-924-CFCandC.A. No. 18-1363-CFC.
C. Belgam, Eve H. Ormerod, SMITH KATZENSTEIN & JENKINS
LLP, Wilmington, Delaware; Michelle Rhyu, Susan Krumplitsch,
Daniel Knauss, COOLEY LLP, Palo Alto, California; Orion
Armon, COOLEY LLP, Broomfield, Colorado; Eamonn Gardner,
COOLEY LLP, San Diego, California. Counsel for Defendant
E. Moore, Bindu Palapura, POTTER ANDERSON & CORROON LLP,
Wilmington, Delaware; Dimitrios T. Drivas, Scott T.
Weingaertner, Amit H. Thakore, Holly Tao, WHITE & CASE
LLP, New York, New York. Counsel for Defendant Samsung
Bioepis Co., Ltd.
CONNOLLY, UNITED STATES DISTRICT JUDGE
action arises under the Biologies Price Competition and
Innovation Act ("BPCIA"), 42 U.S.C. § 262, and
involves biosimilar versions of Herceptin®, a drug used
to treat breast cancer. Pending before me is the matter of
claim construction pursuant to Markman v. Westview
Instruments, Inc., 517 U.S. 370 (1996). Plaintiffs
Genentech, Inc. and City of Hope (collectively,
"Genentech") and Defendants Amgen, Inc.
("Amgen") and Samsung Bioepsis Co., Ltd.
("Samsung," and collectively with Amgen,
"Defendants") have asked me to construe the meaning
of terms set forth in U.S. Patent Nos. 7, 993, 834 ("the
'834 patent"); 8, 076, 066 ("the '066
patent"); 8, 574, 869 ("the '869 patent");
8, 512, 983 ("the '983 patent"); and 7, 390,
660 ("the '660 patent"). D.I. 60; D.I.
a Markman hearing on April 24, 2019. D.I. 182. I ruled from the
bench with respect to one of the disputed terms. See
Id. at 12:3-14:14 (adopting Genentech's proposed
construction of "A method for increasing likelihood of
effectiveness of breast cancer treatment with humanized
anti-ErbB2 antibody huMAb4D5-8"). The parties also
agreed during the hearing that I could assign another
disputed term ("Pre-Harvest [Culture Fluid]") its
plain and ordinary meaning. See Id. at 90. I address
in this Memorandum Opinion the remaining disputed terms.
STANDARD OF REVIEW
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 WL4758195, 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,
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.3dat 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).
CONSTRUCTION OF DISPUTED TERMS
"Wherein The Patient's Cancer Cells Express HER2 At
A 0 Or 1 Level By Immunohistochemistry" ('066
"wherein the patient's cancer cells have an
antigen level corresponding to a 0 or 1 score for
HER2 by any immunohistochemistry test"
"wherein the patient's cancer cells have
been found to express HER2 at a 0 or 1 level by any
"wherein the patient's cancer cells have
been found to express HER2 at a 0 or 1 level by any
of the '066 patent, reformatted for clarity, recites:
A method of identifying and treating a breast cancer patient
disposed to respond favorably to a HER2 antibody, huMAb4D5-8,
which method comprises detecting her2 gene amplification in
cancer cells in a breast tissue sample from the patient and
treating the patient with her2 gene amplification with the
HER2 antibody in an amount effective to treat the breast
wherein the patient's cancer cells express HER2 at a
0 or l level by immunohistochemistry.
patent at 22:22-64 (emphasis added).
technical background is helpful in understanding the
intrinsic evidence. Trastuzumab, the active ingredient in
Herceptin®, is an antibody that binds to the protein
HER2, a receptor on the surface of a cell, and slows the
growth of "HER2-positive" cancer cells. The HER2
protein is encoded by the HER2 gene. A normal cell has two
copies of the HER2 gene. In patients with certain types of
breast cancer, cells have extra copies of the HER2 gene. The
relevant field of art refers to the extra copies of the HER2
gene as "amplification." Having extra
copies of the HER2 gene results in a higher than normal level
(i.e., "overexpression") of the HER2 protein. Thus,
amplification of the HER2 gene is said to result in
the overexpression of the HER2 protein.
time of the invention, there were two ways to test a sample
of breast cancer tissue: (i) immunohistochemistry
("IHC") tests, which measured antigen levels (i.e.,
overexpression of the HER2 protein), and (ii) fluorescence
in-situ hybridization ("FISH") tests, which
measured the number DNA copies of the HER2 gene (i.e.,
amplification). In general, pathologists evaluated IHC assays
using a 0, 1, 2, and 3 scoring system. A score of 0 to 1
was considered HER2-negative. A score of 2 was considered
"borderline" or "equivocal." A score of
3 was considered HER2-positive. At the time of the
invention, it was known in the art that IHC tests could yield
false negative results that excluded patients from treatment
who might otherwise have benefitted from it.
and Amgen dispute the meaning of "wherein the
patient's cancer cells express HER2 at ¶ 0 or 1
level by immunohistochemistry." The crux of the dispute
is whether this "wherein" clause requires that an
IHC test be performed as a step in the claimed method. Amgen
argues that an IHC test is required. Genentech contends the
test is not necessary. I agree with Amgen.
claim 1 describes a "method of identifying and
treating a breast cancer patient disposed to respond
favorably to a HER2 antibody ... wherein the patient's
cancer cells express HER2 at a 0 or 1 level by
immunohistochemistry." Id. at 22:22 (emphasis
added). To identify a patient with an IHC score of 0 or 1,
an IHC test has to be performed on that patient's cancer
admits that the "wherein" clause is "a
substantive claim requirement" and that infringement of
claim 1 requires "that the patient's cancer cells
express HER2 at a zero or one-plus level." D.I. 182 at
43:19-20. It argues, however, that
[t]here are multiple ways that one might determine that. One
might do a test and one might go back and look at patient
samples as patients who were screened using FISH and who were
then treated with Herceptin and determine what the IHC result
for those patients would be. One might also perform a
statistical analysis, which is common in patent cases in
evaluating the scope of infringement.
Id. at 24:22-25:3.
are two problems with this argument. First, conducting an IHC
test after a patient's treatment effectively reads
"identifying" out of the claimed method. "[I]t
is well settled that claims are not to be interpreted so as
to render claim language meaningless." Dade Behring
Marburg GmbH v. Biosite Diagnostics, Inc., 1998 WL
552962, at *15 (D. Del. July 24, 1998). If "identifying
... a breast cancer patient disposed to respond favorably to
a HER2 antibody" is to have meaning, the identification
of the patient must be part of the claimed method. And if the
"wherein" clause is, as Genentech admits, a
substantive requirement, then the ascertainment of the
patient's HER2 level "by
immunohistochemistry" must be part of the
the claim calls for the identification and treatment of
"a breast cancer patient." This reference
to the singular patient makes clear that the method does not
contemplate the use of statistical analysis of "samples
[of] patients who were screened using FISH." Genentech
may be correct that "around 9 to 10 percent" of
patients with a FISH test result "will score a 0 or 1
by [ICH]." D.I. 121 at 58. But that does not mean that
a particular patient with a FISH test result will
have an ICH score of 0 or 1. Indeed, accepting
Genentech's cited statistic as true, the odds are that a
particular patient with a FISH score will not have
an ICH score of 0 or 1.
patent's written description also largely supports
Amgen's reading of claim 1. It states that "[a]
particular advantage of the invention is that it permits
selection of patients for treatment who, based on
immunohistochemical criteria, would be excluded."
'066 patent at 3:22-24; id. at 21:65-67. This
sentence makes clear that the invention is directed towards
the identification (i.e., selection) of patients whose ICH
scores (i.e., immunohistochemical criteria) would hitherto
have excluded them from treatment because of false-negative
ICH test results. The fact that the written description
repeatedly refers to an ICH "0 or 1 level" as
"a score," see, e.g., Id. at 3:26, 4:2,
18:24, and equates scores with "results," see,
e.g., Id. at 18:54, provides further evidence that the
patent contemplates the selection of a patient based on the
results determined by an actual ICH test.
prosecution history also makes clear that the claimed method
requires the performance of an IHC test. Claim 1 originally
did not have the "wherein" clause and, therefore,
described a method that relied solely on FISH to
"detect[ ] HER2 gene amplification" in a breast
tissue sample taken from the patient. D.I. 60-5 at J.A. 1719.
The Examiner rejected the claim as obvious in light of
Baselga, Pauletti, and Persons. Id. at J.A. 1729-30.
Baselga taught that breast cancer patients "should be
screened for overexpression of Her2 before
treatment." Id. at 1730 (emphasis added).
Pauletti and Persons taught that "detection of Her2 gene
amplification using FISH is superior to immunochemistry [sic]
for assessing Her2 status in patients with breast
cancer." Id. Thus, the Examiner concluded that
one would have been motivated to use FISH instead of IHC to
assess HER2 status before treatment, because both Pauletti
and Persons taught the advantages of the FISH technique.
Id. Genentech overcame the rejection by adding the
"wherein" clause to claim 1. Id. at J.A.
1735-36. The Examiner accepted Genentech's amendment,
because the "wherein" clause "chang[ed] the
scope of the claims to a method for treating patients that
express HER2 at 0 or 1 level by
immunohistochemistry and also have a HER2 gene
amplification." Id. at J.A. 1740-41 (emphasis
remarks to the Examiner, Genentech stated that support for
the amendment could be found in the written description's
statement that "[identification of FISH patients in the
1 and 0 sub-groups might identify subjects who, though
failing the IHC criteria for HERCEPTIN® treatment, would
likely benefit from HERCEPTIN® treatment." See
Id. at J.A. 1736 (asserting that the "wherein"
clause amendment is "supported ... by page 28, line
27-29" of the original specification, which ultimately
became lines 19:42-47 of the '066 patent). Thus,
Genentech specifically linked patients who received a failing
IHC score to the disputed claim limitation. Having disclaimed
a method that did not require IHC testing, Genentech cannot
now recapture claim scope it relinquished during prosecution.
See Omega Eng'g, Inc. v. Raytek Corp., 334 F.3d