Syngenta Seeds, Inc. v. Monsanto Co.

NOTE: This disposition is nonprecedential.
United States Court of Appeals for the Federal Circuit
2006-1203, -1204, -1205
SYNGENTA SEEDS, INC.,
Plaintiff-Appellant,
v.
MONSANTO COMPANY and DEKALB GENETICS CORP.,
Defendants-Cross Appellants,
and
DOW AGROSCIENCES LLC, MYCOGEN PLANT SCIENCE, INC.
and AGRIGENETICS, INC.
(Collectively doing business as Mycogen Seeds),
Defendants-Cross Appellants.
Donald R. Dunner, Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P., of
Washington, DC, argued for plaintiff-appellant. With him on the brief were Herbert H.
Mintz, Barbara R. Rudolph, and Robert A. Pollock.
Richard G. Taranto, Farr & Taranto, of Washington, DC, argued for defendants-
cross appellants Monsanto Company, et al. With him on the brief were Susan K. Knoll and
Steven G. Spears, Howrey LLP, of Houston, Texas. Of counsel were Donald Hopkins
Mahoney, III, Thomas A. Miller, and Melinda L. Patterson.
Daniel J. Thomasch, Orrick, Herrington & Sutcliffe LLP, of New York, New York, for
defendants-cross appellants Dow Agrosciences LLC, et al. With him on the brief were
Robert M. Isackson and Alex Verbin Chachkes of New York, New York, and Craig R.
Kaufman and Elizabeth Ann Howard, of Menlo Park, California. Of counsel were Maura
Eileen O’Connor, of New York, New York, and Hardip Passananti, of Irvine, California.
Appealed from: United States District Court for the District of Delaware
Chief Judge Sue L. Robinson
NOTE: This disposition is nonprecedential.
United States Court of Appeals for the Federal Circuit
2006-1203,-1204,-1205
SYNGENTA SEEDS, INC.,
Plaintiff-Appellant,
v.
MONSANTO COMPANY and DEKALB GENETICS CORP.,
Defendants-Cross Appellants,
and
DOW AGROSCIENCES LLC, MYCOGEN PLANT SCIENCE, INC.
and AGRIGENETICS, INC.
(Collectively doing business as Mycogen Seeds),
Defendants-Cross Appellants.
___________________________
DECIDED: May 3, 2007
___________________________
Before MAYER, SCHALL, and BRYSON, Circuit Judges.
BRYSON, Circuit Judge.
Syngenta Seeds, Inc., brought this patent infringement action in the United
States District Court for the District of Delaware, alleging that the defendants, Monsanto
Company, Dekalb Genetics Corp., Dow AgroSciences LLC, Mycogen Plant Science,
Inc., and Agrigenetics, Inc., infringed three U.S. patents owned by Syngenta. The
patents, U.S. Patent Nos. 6,403,865 (“the ’865 patent”), 6,075,185 (“the ’185 patent”),
and 6,320,100 (“the ’100 patent”), relate to a transgenic corn plant modified to produce
an insecticidal protein. The district court held that the asserted claims of the ’185 patent
and the ’100 patent were not infringed as a matter of law, and the jury found that the
appealed claims of the ’865 patent were infringed but invalid. Syngenta now appeals.
We affirm.
I
Bacillus thuringiensis (“Bt”) is a bacterium that produces a protein toxic to certain
insects. In the 1980s, researchers began to experiment with genetically engineering
plants to produce the Bt protein so that the genetically modified plants would in effect
generate their own insecticide. When native Bt genes were inserted into the corn plant
genome, scientists found expression of the Bt protein was sub-optimal. Syngenta
(through its predecessor Ciba-Geigy Corp.) sought to increase expression of the Bt
protein by modifying the Bt gene’s DNA sequence. Syngenta discovered that the
genetically engineered plant would express greater amounts of Bt protein if the DNA
sequence of the Bt gene were built with codons preferred by corn plants.
The codons of the native Bt gene are rich in the nucleotides adenine (“A”) and
thymine (“T”). Only about 38 percent of the nucleotides in the native gene consist of
guanine (“G”) and cytosine (“C”). Corn plants, however, tend to have codons that are
rich in G and C nucleotides (“G+C”). In light of the apparent preference of the corn
plant for codons rich in G+C, Syngenta designed its synthetic Bt gene by replacing
certain codons containing A and T nucleotides (“A+T”) in the native Bt gene with codons
that code for the same amino acids but contain more G+C nucleotides. After making
further changes to aid in the assembly and manipulation of the synthetic gene,
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Syngenta obtained a truncated Bt gene in which 65 percent of its nucleotides consisted
of G+C.
Syngenta’s work on the synthetic Bt gene led to an application that eventually
matured into the ’865, ’100, and ’185 patents. The pertinent claims of the ’865 patent
describe a transgenic corn plant that produces the Bt protein, “wherein the foreign DNA
nucleic acid coding sequence has a G+C content of at least about 60%.” The pertinent
claims of the ’100 and ’185 patents similarly describe a transgenic corn plant that
produces the Bt protein. Those claims require that the DNA sequence have a sufficient
number of particular codons (known as “Murray maize-preferred codons”), so that the
sequence contains at least about 60 percent G+C nucleotides.
Following the issuance of the Bt patents, Syngenta filed this action charging the
defendants with infringement of all three patents. During the ensuing trial, the court
granted the defendants’ motion for judgment as a matter of law as to the ’100 and ’185
patents, holding that the defendants did not infringe those patents under the court’s
construction of the pertinent claims. The district court construed the claims to require
that the change from 38 percent to 60 percent G+C content be attributable solely to the
G+C nucleotides in the substituted Murray maize-preferred codons in the DNA
sequence. Syngenta conceded that under that claim construction the accused products
did not infringe. The jury found the asserted claims of the ’865 patent to be infringed,
but it then found those claims to be invalid for obviousness and for lack of an adequate
written description. Syngenta then took this appeal, and the defendants cross-appealed
from those aspects of the judgment unfavorable to them.
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II
Syngenta first challenges the sufficiency of the evidence to support the jury’s
verdict that the appealed ’865 patent claims are invalid for obviousness. While “the
ultimate judgment of obviousness is a legal determination,” KSR Int’l Co. v. Teleflex
Inc., No. 04-1350, slip op. at 23 (U.S. Apr. 30, 2007), that determination is necessarily
based on underlying factual inquiries, see Winner Int’l Royalty Corp. v. Wang, 202 F.3d
1340, 1348 (Fed. Cir. 2000). When reviewing a jury verdict of obviousness, “[w]e first
presume that the jury resolved the underlying factual disputes in favor of the verdict
winner and leave those presumed findings undisturbed if they are supported by
substantial evidence. Then we examine the legal conclusion de novo to see whether it
is correct in light of the presumed jury fact findings.” Jurgens v. McKasy, 927 F.2d
1552, 1557 (Fed. Cir. 1991) (citation omitted).
The principal prior art reference presented to the jury was a published patent
application of Barton (U.S. Patent App. Pub. No. 2001/0003849). The Barton
application describes a method for improving Bt expression in plant genes. It teaches
that Bt expression is improved by selecting codons that are preferred by the native
plant. It also teaches that Bt genes have a high proportion of codons that are rich in
A+T, while plants generally display an opposite bias towards codons that are rich in
G+C. Furthermore, as Syngenta’s expert admitted at trial, it was well established at the
time Syngenta began its experiments that the coding regions of corn genes tend to be
high in G+C. Thus, the Barton application indicates that selecting codons rich in G+C
would be likely to increase the expression of Bt in corn. That conclusion is consistent
with the testimony of two experts at trial, who testified that it would have been obvious
2006-1203,-1204,-1205 4
to a person of skill in the art to make a Bt gene more closely resemble a corn gene by
substituting codons that are rich in G+C for the codons of the native gene that code for
the same amino acids.
Syngenta argues that while the general notion of substituting codons rich in G+C
may have been obvious, the idea to modify the coding sequence of the Bt gene to
increase the G+C content to more than 60 percent would not have been obvious.
Syngenta relies on the following passage in the Barton application, which Syngenta
characterizes as teaching away from modifying the entire coding sequence:
Since the [positive] results did not seem to vary greatly based on the
length of the substituted codons, it is possible that the increased
expressional efficiency is due principally to the substitutions at the amino-
terminal, or 5’, end of the coding sequence, perhaps those in the first 25
codons. . . . If true, this would suggest that entire coding regions need not
be altered to gain a relatively significant increase in efficiency of
expression, merely the amino-terminal end of the coding region, for
perhaps about 25 codons. Performing such a codon substitution for the
remaining portion of the coding region might still be expected to increase
efficiency of expression, although perhaps less dramatically.
It is true, as Syngenta argues, that the quoted portion of the Barton application suggests
that positive results could be achieved without modifying the entire DNA sequence. But
the entire quoted statement, including the conclusion that a complete codon substitution
“might still be expected to increase efficiency of expression,” plainly constitutes a
suggestion that some increased efficiency of expression could be achieved by
producing a synthetic Bt gene with a coding region consisting entirely of plant-preferred
codons. In the case of corn, as the defendants’ expert in molecular biology testified,
such a gene would necessarily have a G+C content of more than 60 percent. The jury
was free to credit that testimony and thus to conclude that, in light of Barton, a person of
2006-1203,-1204,-1205 5
skill in the art would have found it obvious to produce a modified corn gene with a G+C
content of more than 60 percent.
Syngenta argues that even if a gene modification resulting in a G+C content of
more than 60 percent was obvious to try, there was no reasonable basis to expect that
such a modification would lead to a significantly improved level of expression of the Bt
protein, and thus no basis for the jury’s finding of obviousness. See In re Merck & Co.,
800 F.2d 1091, 1097 (Fed. Cir. 1986). Whether there was a reasonable expectation of
success is a question of fact. See Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157,
1165 (Fed. Cir. 2006). The jury was properly instructed, and it concluded, with ample
basis in the record, that the prior art gave rise to a reasonable expectation of success
from the formulation found in the asserted claims.
In contending that there was no reasonable expectation of success from
optimization of the entire genetic sequence, Syngenta argues that the Barton
application provided no indication that modifications having the effect of increasing the
G+C content to at least 60 percent would yield any additional benefit. That contention,
however, is contrary to the portion of the disclosure in the Barton application suggesting
that Bt expression is enhanced by the substitution of additional plant-preferred codons.
The jury was entitled to rely on that portion of the Barton application in concluding that
there was a reasonable expectation of success from such an increase in the G+C
content of the codons in the genetic sequence.
Syngenta also argues that the Barton application dealt exclusively with tobacco
plants and that the same strategy could not reasonably be expected to succeed in corn.
The Barton application, however, specifically taught that the methodology and results it
2006-1203,-1204,-1205 6
described would be “equally applicable in other plant species.” Syngenta attempts to
offset the force of that statement by noting that we have upheld a decision of the Board
of Patent Appeals and Interferences that found similar language in a patent application
to “merely contemplate[] future success” and not to be enabling. Adang v. Fischhoff,
286 F.3d 1346 (Fed. Cir. 2002). The issue in Adang, however, was whether the Board’s
decision was supported by substantial evidence. In addition to other evidence
suggesting non-enablement, the application in Adang contained statements pointing in
opposite directions: There was language suggesting the applicability of the patent’s
methodology to other plant species, but there was also language teaching that the
transformation of other plant species was not predictable. In light of the conflicting
teachings, we held that the Board’s finding that the reference “merely contemplate[d]
future success” was supported by substantial evidence. Adang, 286 F.3d at 1357.
Here, by contrast, the Barton application did not back away from the statement that its
methodology and results “will be equally applicable in other plant species.” Moreover,
and significantly, the issue in this case is not whether there is substantial evidence to
support a conclusion of non-enablement, but whether there is substantial evidence to
support the jury’s verdict that the invention would have been obvious. In light of the
difference in the evidence in the two cases and the difference in the applicable standard
of review, our decision in Adang does not require that we overturn the jury’s verdict in
this case.
Additionally, Syngenta points to numerous other prior art references that fail to
suggest a G+C content of greater than 60 percent. Those references do little to offset
the clear suggestion in the Barton application that complete codon substitution would
2006-1203,-1204,-1205 7
lead to improved results. To be sure, Syngenta identifies one reference, U.S. Patent
No. 5,500,365 to Fischhoff, which affirmatively teaches the avoidance of sequences
containing more than five A or T nucleotides, or more than five G or C nucleotides, in
succession. Although that reference cuts against a finding of obviousness, the jury was
entitled to weigh Fischhoff against the other evidence and conclude, as a factual matter,
that there was a reasonable expectation of success from substituting plant-preferred
codons in place of the codons found in the native Bt gene.
Finally, Syngenta argues that Bt coding sequences having a G+C content of at
least 60 percent resulted in an unexpected degree of success and that the G+C range
of at least 60 percent was patentable based on the absence of any suggestion in the
prior art that the 60 percent range would produce exceptionally good results. Whether
the degree of success is unexpected in light of suggestions in the prior art is a factual
question. CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003). In
this case, the jury had sufficient evidence, in the form of expert testimony, from which it
could conclude that the degree of success at the 60 percent level was not substantially
different from what could reasonably have been expected based on the prior art.
Because the jury’s verdict was supported by substantial evidence, we uphold the district
court’s judgment holding the ’865 patent claims invalid for obviousness, and we uphold
the district court’s ruling denying Syngenta’s motion for a new trial on obviousness.
III
Syngenta appeals from the district court’s ruling, based on the court’s claim
construction, that the ’100 and ’185 patents are not infringed as a matter of law.
Syngenta concedes that the accused products do not infringe under the district court’s
2006-1203,-1204,-1205 8
claim construction, but argues that the district court erroneously construed a key term
that is common to all the asserted claims.
Both the ’100 and ’185 patents are directed to transgenic corn DNA sequences
that code for the Bt protein. The appealed claims of the ’100 patent all depend from
claim 18, which describes a Bt-encoding DNA sequence obtained by reverse-translating
a Bt protein into a “synthetic DNA coding sequence comprising a sufficient number of
the following codons: [the Murray maize-preferred codons]; such that said synthetic
DNA coding sequence has at least about 60% G+C content.” The appealed claims of
the ’185 patent all depend from claim 1, which similarly describes a sequence obtained
by reverse-translating a particular Bt protein into a “maize-optimized nucleic acid coding
sequence comprising a sufficient number of the single codons that most frequently
encode each amino acid in maize, wherein said maize-optimized nucleic acid coding
sequence has at least about 60% G+C content.” The appealed claims also depend
from claim 2, which recites a sequence “wherein the single codons determined to most
frequently encode each amino acid in maize are” the Murray maize-preferred codons.
Thus, all of the ’100 and ’185 patent claims require a sufficient number of the Murray
maize-preferred codons to produce a sequence having a G+C content of at least about
60 percent.
The parties dispute the meaning of the claim term “sufficient number” in this
context. In its opening claim construction brief in the district court, Syngenta argued
that the number of Murray maize-preferred codons in a sequence would be “sufficient”
“as long as there are enough maize preferred codons such that the overall sequence
has at least about 60% G+C content.” In a subsequent oral argument before the district
2006-1203,-1204,-1205 9
court, Syngenta appeared to offer a narrower view, suggesting that if the total G+C
content of a sequence was at least about 60 percent, the number of Murray maize-
preferred codons would be sufficient as long as the “majority” of the change from 38
percent (the percent of G+C nucleotides in the native Bt gene) to 60 percent was due to
G+C nucleotides contributed by substituted Murray maize-preferred codons.
The district court adopted a different construction. It construed the claims to
require that all of the change from 38 percent to 60 percent G+C content be attributable
to the substitution of Murray maize-preferred codons. To the extent that the original
claim construction order is ambiguous, the court’s subsequent order granting judgment
of noninfringement for the defendants makes clear that, under the court’s construction,
the G+C nucleotides in codons other than the Murray maize-preferred codons cannot be
counted towards the 60 percent.
Syngenta now argues that the number of substituted Murray maize-preferred
codons should be regarded as sufficient as long as the G+C content of the modified
gene would not be more than 60 percent without those substitutions. Syngenta did not
offer that proposed claim construction in the court below. Neither in its brief nor at oral
argument did Syngenta ever articulate to the district court that the sufficiency of the
number of Murray maize-preferred codon substitutions should be determined by
whether or not those substitutions are necessary to reach 60 percent. Instead, the
closest Syngenta came to that proposed construction in its presentations to the district
court was to argue that the number of Murray maize-preferred codon substitutions
would be sufficient if the G+C content of the coding sequence, including the Murray
2006-1203,-1204,-1205 10
maize-preferred codons, were at least 60 percent, a construction that is subtly, but
significantly, different.
The doctrine of waiver precludes a party from advocating a new theory of claim
constriction on appeal. Conoco, Inc. v. Energy & Envtl. Int’l, L.C., 460 F.3d 1349, 1359
(Fed. Cir. 2006); Interactive Gift Express, Inc. v. CompuServe Inc., 256 F.3d 1323, 1346
(Fed. Cir. 2001). Because Syngenta never raised its present proposed construction
before the district court, its proposed construction is waived. As Syngenta has not
challenged the construction of the ’100 and ’185 patent claims on any other ground, we
affirm the judgment of noninfringement.
In light of our affirmance of the judgment with respect to the obviousness of the
’865 patent, we need not address Syngenta’s challenge to the jury’s verdict on the
written description issue or defendant Mycogen’s challenge to the jury’s verdicts of
infringement of the claims of the ’865 patent.
Each party shall bear its own costs for this appeal and cross-appeal.
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