United States Court of Appeals for the Federal Circuit
2007-1266
CARNEGIE MELLON UNIVERSITY
and THREE RIVERS BIOLOGICALS, INC.,
Plaintiffs-Appellants,
v.
HOFFMANN-LA ROCHE INC.,
ROCHE MOLECULAR SYSTEMS, INC.,
ROCHE DIAGNOSTIC SYSTEMS, INC.,
ROCHE BIOMEDICAL LABORATORIES, INC.,
THE PERKIN-ELMER CORPORATION,
and LABORATORY CORPORATION OF AMERICA HOLDINGS,
Defendants-Appellees.
----------------------------------------------------------------------------
2007-1267
CARNEGIE MELLON UNIVERSITY,
Plaintiff-Appellant,
v.
HOFFMANN-LA ROCHE INC.,
ROCHE MOLECULAR SYSTEMS, INC.,
ROCHE DIAGNOSTICS CORPORATION,
LABORATORY CORPORATION OF AMERICA,
and APPLERA CORPORATION,
Defendants-Appellees.
Frederick H. Colen, Reed Smith LLP, of Pittsburgh, Pennsylvania, argued for all
plaintiffs-appellants. With him on the briefs were Charles H. Dougherty, Jr. and Mark
Levin.
Stephen S. Rabinowitz, Fried, Frank, Harris, Shriver & Jacobson LLP, of New
York, New York, argued for all defendants-appellees. With him on the briefs were
Mitchell Epner, Randy C. Eisensmith, and Alison R. Ladd.
Appealed from: United States District Court for the Northern District of California
Judge Susan Illston
United States Court of Appeals for the Federal Circuit
2007-1266
CARNEGIE MELLON UNIVERSITY
and THREE RIVERS BIOLOGICALS, INC.,
Plaintiffs-Appellants,
v.
HOFFMANN-LA ROCHE INC.,
ROCHE MOLECULAR SYSTEMS, INC.,
ROCHE DIAGNOSTIC SYSTEMS, INC.,
ROCHE BIOMEDICAL LABORATORIES, INC.,
THE PERKIN-ELMER CORPORATION,
and LABORATORY CORPORATION OF AMERICA HOLDINGS,
Defendants-Appellees.
------------------------------------------------------------------------------
2007-1267
CARNEGIE MELLON UNIVERSITY,
Plaintiff-Appellant,
v.
HOFFMANN-LA ROCHE INC.,
ROCHE MOLECULAR SYSTEMS, INC.,
ROCHE DIAGNOSTICS CORPORATION,
LABORATORY CORPORATION OF AMERICA,
and APPLERA CORPORATION,
Defendants-Appellees.
------------------------------------------------------------------------------
Appeal from the United States District Court for the Northern District of
California in Case Nos. 95-CV-3524 and 01-CV-0415, Judge Susan
Illston.
_____________________
DECIDED: September 8, 2008
_____________________
Before LOURIE, BRYSON, and PROST, Circuit Judges.
LOURIE, Circuit Judge.
Carnegie Mellon University (“CMU”) and Three Rivers Biologicals, Inc.
(collectively “appellants”) appeal from the decision of the United States District Court for
the Northern District of California holding that Hoffmann-La Roche, Inc., Roche
Molecular Systems, Inc., Roche Diagnostic Systems, Inc., Roche Biomedical
Laboratories, Inc., The Perkin Elmer Corporation, and Laboratory Corporation of
America Holdings (collectively “Roche”) do not infringe the patents in suit and that
certain claims are invalid for lack of written description. Because we conclude that the
district court did not err in holding the claims invalid for failure to meet the written
description requirement, we affirm the court’s judgment of invalidity. Because we
conclude that the court did not err in its infringement analysis, we affirm the court’s
judgment of noninfringement.
BACKGROUND
Proteins, one of the most versatile biomolecules, can serve many important
roles, including as signal receptors, structural elements, or enzymes. They are encoded
by particular deoxyribonucleic acid (“DNA”) sequences known as genes. The process
by which cells use the information contained in genes to make corresponding proteins is
referred to as expression. Expression involves two steps, viz., transcription and
translation. During transcription, the information contained in a gene is copied into
2007-1266, -1267 2
messenger ribonucleic acid (“mRNA”). The cell then assembles amino acids in the
proper sequence during translation to make the protein based on the information
contained in the mRNA.
One gene in the bacterium E. coli, called the E. coli polA gene, encodes a protein
known as E. coli DNA polymerase I. Since at least the 1970s, the E. coli polA gene has
been the subject of scientific study. The wild-type E. coli polA gene consists of two
parts—the structural gene (or gene coding region) and a promoter, which is a DNA
sequence that is involved in initiating transcription. The expression of a gene can be
regulated through the use of a promoter by controlling the level of transcription.
Some valuable proteins are either difficult to purify from their natural sources or
occur in minute quantities in nature. Thus, methods have been developed in the field of
biotechnology “to synthesize useful quantities of specific proteins by controlling the
mechanism by which living cells make proteins.” Carnegie Mellon Univ. v. Hoffmann-La
Roche, Inc., 55 F. Supp. 2d 1024, 1027 (N.D.Cal. 1999).
One method involves introducing foreign genes into a bacterium, which can then
replicate as the bacterium grows and divides. Such a method involves several steps,
including isolating and cloning the gene that encodes the protein of interest and
introducing the cloned gene into the host bacterium. The latter is accomplished by
incorporating the gene into a cloning vector. Certain types of vectors include
bacteriophages and plasmids, which are “small circular loop[s] of DNA found in bacteria,
separate from the chromosome, that replicate[] like a chromosome.” Id. Recombinant
DNA techniques are used to modify plasmids by recombining cloned genes and other
2007-1266, -1267 3
segments of DNA that contain control sequences. The plasmid is then introduced into
the host bacterium where it will replicate as the bacterium grows and divides.
The patents in suit, viz., U.S. Patents 4,767,708 (“the ’708 patent”), 5,126,270
(“the ’270 patent”), and 6,017,745 (“the ’745 patent”) relate to “novel recombinant
plasmids for the enhanced expression of an enzyme, to the preparation by gene cloning
of such plasmids, to bacterial strains containing said plasmids, [and] to methods for the
conditional control of the expression of said enzyme.” 1 ’708 patent col.1 ll.7-16.
The patents teach that the enzyme of interest is DNA polymerase I (Pol I), which,
as discussed above, is encoded by the structural gene known as polA. Id. col.1 ll.14-
15. In the prior art, scientists encountered difficulties cloning polA into multicopy
plasmids because the increase in expression of DNA polymerase I above the natural
level of expression was found to be lethal to a host bacterium. Id. col.1 ll.14-18. The
claimed inventions overcome that problem by constructing a novel plasmid containing
“the entire and undamaged polA gene coding region enzymatically excised from a DNA
molecule,” which “contains essentially none of or at the most only a portion of the
activity of its natural promoter.” Id. col.2 ll.23-29. The patents disclose that severely
damaging the natural polA promoter sequence constituted a “significant discovery of the
present invention since it eliminates or greatly reduces the unregulated expression of
Pol I, which would otherwise be lethal to the cell.” Id. col.2 ll.43-46. By cloning the
1
The patents in suit, which are owned by CMU, all share a common
specification. The ’708 patent, which was filed by Edwin G. Minkley, Jr. and William E.
Brown on August 7, 1984, issued from Application No. 07/638, 638 (“the ’638
application”). The ’270 patent is a continuation of the application that issued as the ’708
patent, and the ’745 patent is a continuation of the application that issued as the ’270
patent. Throughout this opinion, we will cite the ’708 patent when referencing the
common specification.
2007-1266, -1267 4
gene for DNA polymerase I into a vector along with a foreign promoter whose activity is
conditionally controlled, one can obtain an amplified amount of DNA polymerase I.
Throughout the specification, the patents teach that the host bacterial strain that is used
to achieve that objective is E. coli.
The patents in suit share a common specification, and the claims are directed to
recombinant plasmids that contain gene coding regions for the expression of DNA
polymerase I from any bacterial source. For example, claim 1 of the ’708 patent reads
as follows:
1. A recombinant plasmid containing a cloned complete structural gene
coding region isolated from a bacterial source for the expression of DNA
polymerase I, under operable control of a conditionally controllable foreign
promoter functionally linked to said structural gene coding region, said
foreign promoter being functional to express said DNA polymerase I in a
suitable bacterial or yeast host system.
’708 patent claim 1 (emphasis added). Claim 1 of the ’270 patent recites:
1. A recombinant plasmid providing for Nick-translation activity isolated
from a bacterial source, said plasmid capable of being placed in a
bacterial host system such that the host system can grow and divide.
’270 patent claim 1 (emphasis added). Similarly, claim 1 of the ’745 patent reads:
1. A recombinant plasmid containing a DNA coding sequence for the
expression of DNA polymerase activity, wherein said DNA coding
sequence is derived from a source that encodes a bacterial DNA
Polymerase, said source not containing an amber mutation affecting
expression of said DNA polymerase activity, such that when said plasmid
is transformed into a bacterial host system the host system can grow and
divide thereby replicating said plasmid.
’745 claim 1 (emphasis added).
Roche commercially manufactures recombinant DNA polymerases. The
accused product at issue in this appeal involves a recombinant plasmid referred to as
pLSG5, which causes host cells to express an enzyme known as Thermus aquaticus
2007-1266, -1267 5
(“Taq”) DNA polymerase. On August 30, 1994, appellants filed suit against Roche
asserting that its product, pLSG5, infringes the ’708 and ’270 patents. 2 The district
court held a claim construction hearing on January 14, 1997 and issued its claim
construction ruling on March 31, 1997. The court construed the term “DNA polymerase”
as requiring 3’-5’ exonuclease activity. Carnegie Mellon Univ. v. Hoffmann-La Roche
Inc., No. C 95-3524 SI, 1997 WL 33152823, at *8-*10 (N.D. Cal. Mar. 31, 1997). Roche
filed separate motions for summary judgment seeking judgment that: 1) claims 1-19, 22-
40, and 43-45 of the ’708 patent were invalid for lack of written description under our
holding in Regents of University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir.
1997); 2) claims 1-6, 10-19, and 22-40 of the ’708 patent were not infringed; and 3)
claims 1-2, 11-12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the ’270
patent were invalid for lack of written description under our holding in Gentry Gallery,
Inc. v. Berkline Corp., 134 F.3d 1473 (Fed. Cir. 1998), or, in the alternative, under Eli
Lilly.
On May 12, 1999, the district court granted Roche’s motion for summary
judgment of noninfringement. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., 55 F.
Supp. 2d 1024 (N.D.Cal. 1999). In doing so, the district court concluded that there was
no genuine issue of material fact as to whether the enzyme in the accused product
possessed 3’-5’ exonuclease activity. Because the undisputed evidence indicated that
the accused products lacked that element, the court concluded that summary judgment
of noninfringement of the ’708 patent was required.
2
In its original complaint, appellants asserted that several of Roche’s
recombinant DNA plasmids infringe the ’708 and ’270 patents. On appeal, however,
appellants only challenge the district court’s grant of summary judgment of
noninfringement with respect to the pLSG5 plasmid.
2007-1266, -1267 6
On August 19, 1999, the district court granted Roche’s motion for summary
judgment of invalidity as to the ’270 patent. Carnegie Mellon Univ. v. Hoffmann-La
Roche Inc., No. C 95-3524 SI, 1999 WL 33298545 (N.D. Cal. Aug. 19, 1999). The
court determined that the specification of the ’270 patent made clear that lethality was
an essential feature of the invention and thus, under Gentry Gallery, the claims of the
patent must contain that feature in order to comply with the written description
requirement. Because the claims omit the feature of lethality, the court concluded that
those claims of the ’270 patent were invalid.
On June 27, 2001, relying on Eli Lilly, the district court granted Roche’s motion
for summary judgment of invalidity with regard to the ’708 patent. Carnegie Mellon
Univ. v. Hoffmann-La Roche, Inc., 148 F. Supp. 2d 1004 (N.D. Cal. 2001). The court
concluded that while the claims of the ’708 patent claim recombinant plasmids
“containing a cloned complete structural gene coding region from [any] bacterial
sources for the expression of DNA polymerase I,” the ’638 application only described
recombinant plasmids containing the encoding gene region for E. coli DNA polymerase I
and thus failed to adequately support the generic claims of the ’708 patent.
On January 24, 2001, CMU initiated a second patent infringement action against
Roche, alleging that Roche infringed the ’745 patent. Roche moved for summary
judgment that claims 1-3, 12-14, 23-28, and 30-33 were invalid under the written
description requirement of 35 U.S.C. § 112. On September 29, 2003, the district court
granted that motion. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., No. C 01-0415
SI (N.D. Cal. Sept. 29, 2003). Again relying on Eli Lilly, the court determined that there
was no genuine issue of material fact with regard to whether the ’745 patent complies
2007-1266, -1267 7
with the written description requirement under 35 U.S.C. § 112 and granted Roche’s
motion. Roche also moved for summary judgment of noninfringement of claims 4-11,
15-22, and 29 of the ’745 patent under the doctrine of equivalents, and on February 26,
2004, the court granted that motion. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc.,
No. C 01-0415 SI (N.D. Cal. Feb. 26, 2004).
Roche additionally asserted that the patents were unenforceable based on
inequitable conduct committed by appellants during the prosecution of each of the
asserted patents. The district court held a bench trial on that issue from August 1 to
August 5, 2005. On March 22, 2007, the court issued its ruling, holding that Roche
failed to present clear and convincing evidence that appellants committed inequitable
conduct. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., No. C 01-0415 SI, 2007
WL 902548 (N.D. Cal. Mar. 22, 2007). As such, the court concluded that none of the
patents was unenforceable.
On May 14, 2007, the district court entered final judgment in favor of Roche.
Appellants timely appealed the district court’s grant of summary judgment with regard to
noninfringement and invalidity. We have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
On appeal, appellants challenge the district court’s grant of summary judgment of
invalidity with regard to claims 1-19, 22-40, and 43-45 of the ’708 patent, claims 1-2, 11-
12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the ’270 patent, and claims
3, 14, 23-28, and 30-32 of the ’745 patent. In addition, appellants challenge the court’s
grant of summary judgment of noninfringement of the asserted claims of the ’708 patent
and claims 4, 5, and 7 of the ’745 patent. While the decisions of the district court
2007-1266, -1267 8
regarding the ’708, ’270, and ’745 patents were rendered in separate opinions and
judgments, the appeals were consolidated for argument in this court and we decide all
of them together. We first consider appellants’ arguments relating to validity.
A. Standard of Review
We review the district court’s grant of summary judgment de novo, reapplying the
standard applicable at the district court. See Rodime PLC v. Seagate Tech., Inc., 174
F.3d 1294, 1301 (Fed. Cir. 1999). Summary judgment is appropriate “if the pleadings,
depositions, answers to interrogatories, and admissions on file, together with the
affidavits, if any, show that there is no genuine issue as to any material fact and that the
moving party is entitled to judgment as a matter of law.” Fed. R. Civ. P. 56(c). In
addition, in deciding a motion for summary judgment, “[t]he evidence of the nonmovant
is to be believed, and all justifiable inferences are to be drawn in his favor.” Anderson v.
Liberty Lobby, Inc., 477 U.S. 242, 255 (1986).
B. Written Description
Section 112, paragraph 1 of the Patent Act sets forth the written description
requirement as follows:
The specification shall contain a written description of the invention, and of
the manner and process of making and using it, in such full, clear,
concise, and exact terms as to enable any person skilled in the art to
which it pertains, or with which it is most nearly connected, to make and
use the same, and shall set forth the best mode contemplated by the
inventor of carrying out his invention.
35 U.S.C. § 112, ¶ 1 (emphasis added). Thus, paragraph 1 of § 112 requires a written
description of the invention—a requirement separate and distinct from the enablement
requirement. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991); see
Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., Ltd., 535 U.S. 722, 736 (2002)
2007-1266, -1267 9
(noting that “a number of statutory requirements must be satisfied before a patent can
issue” including that the patent application “describe, enable, and set forth the best
mode of carrying out the invention”) (emphasis added); see also In re Curtis, 354 F.3d
1347, 1357 (Fed. Cir. 2004) (“We interpret 35 U.S.C. § 112, ¶ 1 to require a written
description requirement separate and apart from the enablement requirement.”); In re
Ruschig, 379 F.2d 990 (C.C.P.A. 1967) (holding that the written description requirement
is a requirement separate from enablement under 35 U.S.C. § 112, paragraph 1).
The basic function of a patent specification is to disclose an invention. It has
long been the case that a patentee “can lawfully claim only what he has invented and
described, and if he claims more his patent is void.” O’Reilly v. Morse, 56 U.S. (15
How.) 62, 121 (1853). The written description serves a quid pro quo function “in which
the public is given ‘meaningful disclosure in exchange for being excluded from
practicing the invention for a limited period of time.’” Univ. of Rochester v. G.D. Searle
& Co., Inc., 358 F.3d 916, 922 (Fed. Cir. 2004) (quoting Enzo Biochem, Inc. v. Gen-
Probe Inc., 323 F.3d 956, 970 (Fed. Cir. 2002)). To satisfy the written description
requirement, “the applicant does not have to utilize any particular form of disclosure to
describe the subject matter claimed, but the description must clearly allow persons of
ordinary skill in the art to recognize that he or she invented what is claimed.” In re
Alton, 76 F.3d 1168, 1172 (Fed. Cir. 1996) (citing In re Gosteli, 872 F.2d 1008, 1012
(Fed. Cir. 1989)) (quotations omitted). In other words, the applicant must “convey with
reasonable clarity to those skilled in the art that, as of the filing date sought, he or she
was in possession of the invention,” Vas-Cath Inc., 935 F.2d at 1563-64, and
demonstrate that by disclosure in the specification of the patent. Whether the written
2007-1266, -1267 10
description requirement is satisfied is a fact-based inquiry that will depend on the nature
of the claimed invention, Enzo, 323 F.3d at 963, and the knowledge of one skilled in the
art at the time an invention is made and a patent application is filed. Such knowledge
may change as time progresses. See In re Wallach, 378 F.3d 1330, 1334 (Fed. Cir.
2004) (discussing how it is now a “routine matter” to convert between an amino acid
sequence and the DNA sequences that can encode it such that an applicant need not
specify each possible permutation of nucleic acid sequences for a particular protein).
Our case law has examined compliance with the written description requirement
in the context of biotechnological inventions in the past. In Regents of University of
California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), we held, inter alia, that
generic claims directed to recombinant prokaryotic microorganisms comprising any
vertebrate and mammalian cDNA were not adequately supported by the specification
that only disclosed rat insulin cDNA. Id. at 1568. We stated that “[a]n adequate written
description of a DNA, such as the cDNA of the recombinant plasmids and
microorganisms of the claimed invention, requires a precise definition, such as by
structure, formula, chemical name, or physical properties, not a mere wish or plan for
obtaining the claimed chemical invention.” Id. at 1566 (internal quotations omitted). We
further held that “[a] description of a genus of cDNAs may be achieved by means of a
recitation of a representative number of cDNAs, defined by nucleotide sequence, falling
within the scope of the genus or of a recitation of structural features common to the
members of the genus, which features constitute a substantial portion of the genus.” Id.
at 1569.
1. The ’708 and ’745 Patents
2007-1266, -1267 11
Appellants challenge the district court’s conclusion that certain claims of the ’708
and ’745 patents are invalid under § 112 in light of our holding in Eli Lilly. According to
appellants, Eli Lilly is distinguishable from the present case because the invention in Eli
Lilly was tied to a specific cDNA sequence, whereas the invention here involves a
combination of well known elements that create a generic biotechnological tool.
Appellants further argue that the court erred by failing to conduct a factual inquiry as
required by Capon v. Eshhar, 418 F.3d 1349, 1358 (Fed. Cir. 2005). Appellants
contend that at the time of the invention, both DNA polymerase I and the polA gene
were well known in the art. In addition, appellants assert that the court improperly made
factual determinations, improperly relied on the declaration of Roche’s expert while
dismissing the declarations of its own experts, and failed to draw inferences in
appellants’ favor.
In response, Roche argues that the district court correctly determined that the
claims of the ’708 patent encompass more than the subject matter described in the
specification and thus correctly found them invalid. Roche asserts that Eli Lilly applies
to the present case as there was nothing in the Eli Lilly decision to suggest that that
holding was limited to inventions involving novel DNA sequences. Roche further
asserts that the court considered appellants’ evidence and correctly concluded that they
failed to raise a genuine issue of material fact.
We agree with Roche that there is no genuine issue of material fact regarding
whether the written descriptions of the ’708 and ’745 patents fail to adequately describe
the claimed invention. We first consider the claims at issue. Claim 1 of the ’708 patent,
a representative claim, recites:
2007-1266, -1267 12
1. A recombinant plasmid containing a cloned complete structural gene
coding region isolated from a bacterial source for the expression of DNA
polymerase I, under operable control of a conditionally controllable foreign
promoter functionally linked to said structural gene coding region, said
foreign promoter being functional to express said DNA polymerase I in a
suitable bacterial or yeast host system.
’708 patent claim 1 (emphases added). Similarly, claims 1-3, and 23 of the ’745 patent,
also representative claims, read as follows:
1. A recombinant plasmid containing a DNA coding sequence for the
expression of DNA polymerase activity, wherein said DNA coding
sequence is derived from a source that encodes a bacterial DNA
Polymerase, said source not containing an amber mutation affecting
expression of said DNA polymerase activity, such that when said plasmid
is transformed into a bacterial host system the host system can grow and
divide thereby replicating said plasmid.
2. The recombinant plasmid of claim 1 wherein said DNA polymerase
activity includes Nick-translation activity.
3. The plasmid of claim 2 wherein said Nick-translation activity is under
operable control of a conditionally controllable foreign promoter, said
foreign promoter being functional to express said Nick-translation activity
in said host system.
23. A method of producing an enzyme possessing DNA polymerase
activity comprising the steps of:
transforming a recombinant plasmid having a DNA coding sequence for
the expression of DNA polymerase activity that is under operable control
of a conditionally controllable foreign promoter into a bacterial host
system, said DNA polymerase coding sequence derived from a source
that encodes a bacterial DNA polymerase, said source not containing an
amber mutation affecting expression of said, DNA polymerase activity;
and
allowing the host system to grow and divide for at least twenty generations
thereby replicating said plasmid.
’745 claim 1-3, 23 (emphases added).
The appealed claims of the ’708 patent are directed to recombinant plasmids that
contain a DNA coding sequence that is broadly defined, and only by its function, viz.,
2007-1266, -1267 13
encoding DNA polymerase I. Moreover, the generic claims are not limited to a single
bacterial species, but broadly encompass coding sequences originating from any
bacterial species. Similarly, the appealed claims of the ’745 patent are broadly directed
to recombinant plasmids that contain a DNA coding sequence, again, only defined by
function, viz., encoding an enzyme with either DNA polymerase or nick-translation
activity. Those claims are also not limited to a single bacterial species, but cover all
bacterial species.
As a preliminary matter, we reject appellants’ assertion that this case is
distinguishable from Eli Lilly. Contrary to appellants’ assertion, nothing in Eli Lilly
indicates that that holding was limited to inventions involving novel DNA sequences.
Indeed, in University of Rochester, we rejected a similar argument. See Rochester, 358
F.3d at 925.
In Eli Lilly, we held that “the claimed genera of vertebrate and mammal cDNA
[were] not described by the general language of [a] patent’s written description
supported only by the specific nucleotide sequence of rat insulin.” 119 F.3d at 1569.
That holding was premised on the basic principle that a person of skill in the art must be
able to “visualize or recognize the identity of the members of the genus.” Id. Thus, to
satisfy the written description requirement for a claimed genus, a specification must
describe the claimed invention in such a way that a person of skill in the art would
understand that the genus that is being claimed has been invented, not just a species of
the genus.
The Guidelines for Examination of Patent Applications under the 35 U.S.C.
§ 112, ¶ 1, “Written Description” Requirement, 66 Fed. Reg. 10-99 (Jan. 5, 2001)
2007-1266, -1267 14
(“Guidelines”), which we find to be an accurate description of the law by the agency
responsible for examining patent applications, and thus persuasive authority, provide
further guidance for determining whether the written description requirement is met for
claims drawn to a genus. The Guidelines state:
The written description requirement for a claimed genus may be satisfied
through sufficient description of a representative number of species . . . by
disclosure of relevant, identifying characteristics, i.e., structure or other
physical and/or chemical properties, by functional characteristics coupled
with a known or disclosed correlation between function and structure, or
by a combination of such identifying characteristics, sufficient to show the
applicant was in possession of the claimed genus.
A “representative number of species” means that the species which are
adequately described are representative of the entire genus. Thus, when
there is substantial variation within the genus, one must describe a
sufficient variety of species to reflect the variation within the genus.
***
Satisfactory disclosure of a “representative number” depends on whether
one of skill in the art would recognize that the applicant was in possession
of the necessary common attributes or features of the elements
possessed by the members of the genus in view of the species disclosed.
For inventions in an unpredictable art, adequate written description of a
genus which embraces widely variant species cannot be achieved by
disclosing only one species within the genus.
Guidelines, 66 Fed. Reg. at 1106 (emphases added).
Here, while the claims of the ’708 and ’745 patents encompass a genus of
recombinant plasmids that contain coding sequences for DNA polymerase or nick-
translation activity from any bacterial source, in contrast, the narrow specifications of the
’708 and ’745 patents only disclose the polA gene coding sequence from one bacterial
source, viz., E. coli. Significantly, the specification fails to disclose or describe the polA
gene coding sequence for any other bacterial species.
2007-1266, -1267 15
The district court concluded that the disclosure of the E. coli polA gene was not
representative of and failed to adequately support the entire claimed genus. Based on
the record evidence indicating a lack of a genuine issue of material fact on the issue, we
agree. Notably, the record indicates that at the time of the invention, only three
bacterial polA genes, viz., E. coli, K. aerogenes, and K. pneumoniae, out of thousands
of bacterial species had been cloned, and only E. coli was described in the patents.
According to Roche’s expert, Dr. Bambara, bacteria constitute a large class of
organisms that include thousands, and potentially millions, of unidentified species. In
addition, at the time of the invention, persons of ordinary skill in the art knew that DNA
polymerase I was not a single enzyme, but a family of enzymes encoded by a family of
genes that varied from one bacterial species to another. Dr. Bambara stated that those
enzymes were encoded by genes that were distinct from the E. coli polA gene.
Significantly, the written descriptions of the ’708 and ’745 patents clearly indicate
that the polA gene is critical to the claimed invention. Indeed, the patents disclose that
a “significant discovery of the present invention” involved the need to severely damage
the polA promoter sequence when constructing the recombinant plasmid in order to
avoid the unregulated expression of DNA polymerase I, which otherwise would be lethal
to the cell. ’708 patent col.2 ll.40-46. The specifications disclose that “[t]he novel
plasmid of the present invention contains the entire and undamaged polA gene coding
region enzymatically excised from a DNA molecule” and emphasize that “it is an
important feature of this invention that the cloned polA gene fragment contains
essentially none of or at the most only a portion of the activity of its natural promoter.”
Id. col.2 ll.23-29.
2007-1266, -1267 16
However, although the written descriptions of the patents emphasize that the
recombinant plasmids must be carefully constructed in order to overcome the lethality
problem, particularly with regard to the promoter, the patents fail to disclose the
nucleotide sequence or other descriptive features for a polA gene (including the
promoter sequence) from any bacterial source other than E. coli. Indeed, in the
Description of the Preferred Embodiments, the patents disclose only one embodiment
which uses the plasmid referred to as pMP5. The patents teach that pMP5 was
constructed by taking the E. coli polA gene from phage NM825, cutting the polA gene
specifically at the BglII restriction site, and splicing the polA gene into a plasmid
pHUB2. 3 Id. col.5 ll.49-65, Fig. 1. The specification teaches that cutting the polA gene
at the BglII restriction site was a significant discovery:
We have discovered that the restriction enzyme BglII will cut within the
polA promoter sequence and severely damage it. This is a significant
discovery of the present invention, since it eliminates or greatly reduces
the unregulated expression of Pol I, which would otherwise be lethal to the
cell.
Id. col.2 ll.40-46. As such, the patents teach that the specific gene sequence for the
expression of DNA polymerase I or nick-translation activity is a critical aspect of the
invention.
We agree with the district court that the narrow disclosure of the E. coli polA
gene is not representative of and fails to adequately support the entire claimed genus
under Eli Lilly. To satisfy the written description requirement in the case of a chemical
or biotechnological genus, more than a statement of the genus is normally required.
3
The pMP5 plasmid was transformed into E. coli strain N4830, which resulted
in strain ATL100. The written description of the patent discloses that ATL100 was
deposited in the American Type Culture Collection Depository on June 29, 1984, under
Accession number 39753. ’708 patent col.1 ll.36-41.
2007-1266, -1267 17
One must show that one has possession, as described in the application, of sufficient
species to show that he or she invented and disclosed the totality of the genus. In light
of the specifications’ disclosure concerning the careful construction of the claimed
recombinant plasmids, such that the natural promoter of the polA gene is severely
damaged or eliminated, and given the record evidence that the polA gene varied among
the numerous bacterial species, as well as the absence of any polA gene sequence for
any bacteria other than E. coli, we conclude that that requirement was not met here.
We are unpersuaded by appellants’ assertion that a different result is warranted
in light of our holding in Capon v. Eshhar, 418 F.3d 1349, 1358 (Fed. Cir. 2005). The
inventions in Capon involved “chimeric DNA that encodes single-chain chimeric proteins
for expression on the surface of cells of the immune system, plus expression vectors
and cells transformed by the chimeric DNA.” Id. at 1352. We held that the Board of
Patent Appeals and Interferences erred in holding that the written description
requirement was not met because the disclosures failed to “reiterate the structure or
formula or chemical name for the nucleotide sequences of the claimed chimeric genes.”
Id. at 1358. We explained that our holding in Eli Lilly did not impose “a per se rule
requiring recitation in the specification of the nucleotide sequence of claimed DNA,
when that sequence is already known in the field.” Id. at 1360-61. Moreover, we stated
that “what is needed to support generic claims to biological subject matter depends on a
variety of factors, such as the existing knowledge in the particular field, the extent and
content of the prior art, the maturity of the science or technology, the predictability of the
aspect at issue, and other considerations appropriate to the subject matter.” Id.
2007-1266, -1267 18
Unlike the situation in Capon, however, where the prior art contained “extensive
knowledge of the nucleotide structure of the various immune-related segments of DNA,”
including “over 785 mouse antibody DNA light chains and 1,327 mouse antibody DNA
heavy chains,” id. at 1355, the record here shows that only three bacterial polA genes
out of thousands of genes had been cloned. As such, Capon does not aid appellants.
Moreover, we disagree with appellants’ assertion that the court failed to properly
consider the Capon factors in its analysis. The court clearly considered the record
evidence and properly determined the knowledge of one skilled in the field with respect
to bacterial polA genes.
We are further unpersuaded by appellants’ argument that the district court erred
by failing to consider the declarations of their experts, which, according to appellants,
create genuine issues of material fact. Appellants primarily point to the declarations of
Drs. Benkovic, Low, Hatfull, and Davis. Having reviewed that evidence, we agree with
the district court that they fail to create genuine issues of material fact. Appellants’
experts did not dispute the statements made by Dr. Bambara that were material to the
court’s invalidity holding under Eli Lilly. Indeed, it was undisputed that by 1984, only
three bacterial polA genes had been cloned. Moreover, Dr. Davis agreed with Dr.
Bambara’s statement that the polA gene “has different sequences for probably all the
different bacterial species.” Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., No. C
01-0415 SI, slip op. at 10 (N.D. Cal. Sept. 29, 2003). In addition, Dr. Benkovic agreed
with Dr. Bambara’s assertion that the ’745 patent did not describe polA genes other
than E. coli. Id. at 11. The additional expert statements relied upon by appellants,
including statements concerning cloning techniques for purifying polA genes and
2007-1266, -1267 19
experiments involving E. coli, were immaterial to the relevant inquiry and thus do not
raise genuine issues of material fact.
We have considered all of the remaining arguments appellants have raised in
their briefs and found none that justify a reversal. Accordingly, because no genuine
issues of material fact exist with regard to whether the written descriptions of the ’708
and ’745 patents adequately support the appealed claims, we affirm the district court’s
grant of summary judgment of invalidity with respect to those claims.
2. The ’270 Patent
Appellants argue that the district court erred in concluding that the claims of the
’270 patent are invalid under our holding in Gentry Gallery. According to appellants, the
court improperly invalidated the claims for lack of written description after concluding
that they do not recite the problem the invention was intended to solve. Because
lethality was the key problem solved by the claimed invention, appellants argue that it
cannot be an “element” of the invention. In response, Roche argues that the court
correctly concluded that the claims are invalid under Gentry Gallery because they were
broadened during prosecution to encompass more than the subject matter described in
the application. In the alternative, Roche asserts that even if the court erred in its
analysis under Gentry Gallery, the claims are still invalid under Eli Lilly.
We agree with appellants that the district court erroneously found the claims
invalid under Gentry Gallery. In reaching its decision, the court found clear and
convincing evidence that “lethality was an essential feature of the invention claimed in
the ’270 patent.” Carnegie Mellon, 1999 WL 3329545 at *7. The court concluded that
2007-1266, -1267 20
under Gentry Gallery, the claims were invalid because the appealed claims did not
contain that feature. In essence, the court applied an essential element test.
As we said in Cooper Cameron Corp. v. Kvaerner Oilfield Products, Inc., 291
F.3d 1317 (Fed. Cir. 2002), in Gentry Gallery “we did not announce a new ‘essential
element’ test mandating an inquiry into what an inventor considers to be essential to his
invention and requiring that the claims incorporate those elements.” Id. at 1323.
Rather, “we applied and merely expounded upon the unremarkable proposition that a
broad claim is invalid when the entirety of the specification clearly indicates that the
invention is of a much narrower scope.” Id. We thus agree with appellants that the
district court erred by invalidating the claims of the ’270 patent by applying the essential
element test. We further note that even if such a test existed, lethality was only a
reason for the claimed invention, and not an element of it that needed to be defined in
the claims.
However, while the court erred in holding the claims of the ’270 patent invalid
under Gentry Gallery, we agree with Roche that the claims are nonetheless invalid
under Eli Lilly under the same rationale discussed above. The claims of the ’270 patent
suffer the same defects as the appealed claims of the ’708 and ’745 patents. Indeed,
the claims of the ’270 patent are also generically directed to plasmids encompassing the
polA gene from any bacterial source. Thus, for the reasons set forth above, we
conclude that there is no genuine issue of material fact as to whether the claims of the
’270 patent are invalid for lack of written description under Eli Lilly.
Accordingly, because the specifications of the ’708, ’745, and ’270 patents fail to
provide adequate written description support for the appealed claims, all of which
2007-1266, -1267 21
encompass a genus of recombinant plasmids containing gene coding sequences from
any bacterial source, we affirm the district court’s grant of summary judgment of
invalidity.
B. Noninfringement
In view of our affirmance of the district court’s invalidity decision, the issue of
infringement with respect to the asserted claims of the ’708 patent has become moot
and will not be considered. We will, however, consider appellant’s argument with regard
to the district court’s grant of summary judgment of noninfringement of claims 4, 5, and
7 of the ’745 patent, as the validity of those claims has not been challenged and thus
presumptively they remain valid.
Claims 4, 5, and 7 of the ’745 patent are all dependent claims and they
incorporate the claim limitations of claim 1. Those claims, however, are narrower in
scope as they require E. coli as the bacterial source. Those claims read as follows:
1. A recombinant plasmid containing a DNA coding sequence for the
expression of DNA polymerase activity, wherein said DNA coding
sequence is derived from a source that encodes a bacterial DNA
Polymerase, said source not containing an amber mutation affecting
expression of said DNA polymerase activity, such that when said plasmid
is transformed into a bacterial host system the host system can grow and
divide thereby replicating said plasmid.
4. The recombinant plasmid of claim 3 wherein the bacterial host system
and the bacterial source are each E. coli; and wherein the Nick-translation
activity includes polymerase and 5'-3' exonuclease activities.
5. The recombinant plasmid of claim 4 wherein said foreign promoter is a
negatively regulated promoter.
7. The recombinant plasmid of claim 5 wherein said negatively regulated
promoter is the leftward promoter of phage lambda.
’745 patent claims 1, 4, 5, & 7 (emphases added).
2007-1266, -1267 22
On appeal, appellants argue that the district court erred in concluding that the
Roche’s pLSG5 product does not infringe the ’745 patent under the doctrine of
equivalents. According to appellants, the substitution of Taq for E. coli was an
insubstantial and unimportant change that resulted in an infringing equivalent. Roche
responds that the court correctly granted summary judgment of noninfringement
because appellants’ infringement theory would vitiate the E. coli claim limitation of the
appealed claims, which is impermissible under Warner-Jenkinson Co. v. Hilton Davis
Chemical Co., 520 U.S. 17 (1997). In addition, Roche contends that, contrary to
appellants’ assertion, the differences between Taq and E. coli are not insubstantial.
We agree with Roche that the district court properly granted summary judgment
of noninfringement under the doctrine of equivalents. Under that doctrine, “a product or
process that does not literally infringe upon the express terms of a patent claim may
nonetheless be found to infringe if there is ‘equivalence’ between the elements of the
accused product or process and the claimed elements of the patented invention.” Id. at
21 (citation omitted). However, the “all limitations rule” restricts the doctrine of
equivalents by preventing its application when doing so would vitiate a claim limitation.
Id. at 29 (stating that the doctrine of equivalents cannot be applied broadly so as to
“effectively eliminate that [claim] element in its entirety”). In determining whether a
finding of infringement under the doctrine of equivalents would vitiate a claim limitation,
we must consider “the totality of the circumstances of each case and determine whether
the alleged equivalent can be fairly characterized as an insubstantial change from the
claimed subject matter without rendering the pertinent limitation meaningless.”
Freedman Seating Co. v. Am. Seating Co., 420 F.3d 1350, 1359 (Fed. Cir. 2005).
2007-1266, -1267 23
We agree with Roche and the district court that a finding that Taq is an
equivalent of E. coli would essentially render the “bacterial source [is] E. coli” claim
limitation meaningless, and would thus vitiate that limitation of the claims. Indeed, in
drafting the claims, the patentees specifically chose to limit claim 4 to a recombinant
plasmid where the bacterial source is E. coli. Appellants cannot now argue that any
bacterial source, including Taq, would infringe that claim. Accordingly, summary
judgment of noninfringement was appropriate. 4
CONCLUSION
For the foregoing reasons, we affirm the district court’s grant of summary
judgment of invalidity with regard to claims 1-19, 22-40, and 43-45 of the ’708 patent,
claims 1-2, 11-12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the ’270
patent, and claims 3, 14, 23-28, and 30-32 of the ’745 patent. In addition, we affirm the
court’s grant of summary judgment of noninfringement with respect to claims 4, 5, and 7
of the ’745 patent.
AFFIRMED
4
We note, as Roche states in its briefs, that Taq DNA polymerase was and
continues to be integral to the success of polymerase chain reaction (“PCR”), a widely
used technique in molecular biology that was invented by Kary Mullis in 1983. Indeed,
in 1993, Mullis won the Nobel Prize in Chemistry for his development of PCR and the
journal Science named Taq DNA polymerase the “Molecule of the Year.” While we
reach our decision irrespective of those facts, we readily can see why appellants have
attempted to broaden the scope of their claims beyond the E. coli species disclosed.
2007-1266, -1267 24