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BIOTECH BUZZ
Industrial Biotechnology Subcommittee
February 2015
Contributor: Judith Roesler
Butamax™ Advanced Biofuels LLC v. Gevo, Inc., Certiorari Summary Disposition,
13-1286, January 26, 2015, 574 U.S. ___ (2015)
Summary
On January 26, 2015, the Supreme Court granted the petition for a writ of
certiorari in Butamax Advanced Biofuels LLC v. Gevo Inc. (“Butamax”) and remanded the
case for further consideration in light of Teva Pharmaceuticals USA, Inc., v. Sandoz., Inc.,
574 U.S. ___ (2015) (“Teva Pharmaceuticals”).
At issue was the review of claim
construction de novo by the Court of Appeals for the Federal Circuit (the “CAFC”) in
February 2014 as compared to the “clear error” standard of review recently set forth by
the Supreme Court in Teva on January 20, 2015.
Background
Butamax is a joint venture between E.I. DuPont de Nemours and Co. and BP
Biofuels North America LLC formed in 2009 with the goal of producing renewable fuel
technologies. Gevo is also active in renewable fuel technologies. Both Butamax and
Gevo are engaged in the production of isobutanol through biosynthesis using plant
materials. Isobutanol has a high energy content and can be blended with fossil fuel.
The patents-in-suit, U.S. Patent Nos. 7,851,188 (“the ‘188 Patent”) and 7,993,889
(the ‘889 Patent”) are assigned to Butamax. The ‘889 Patent is a divisional of the ‘188
Patent. Claim 1 of the ‘188 Patent is directed to a recombinant microbial host cell
comprising
heterologous DNA molecules encoding polypeptides that catalyze
substrate to product conversions, with the conversions recited in four steps and the
polypeptides for each conversion also recited. The enzymes set forth in Claim 1 of the
‘188 Patent include, among other things, the EC (Enzyme Commission) number for each
recited polypeptide. Claim 1 of the ‘889 Patent is directed to a method for producing
isobutanol from a recombinant yeast microorganism expressing an engineered
isobutanol biosynthetic pathway, with the conversions and the enzymes utilized for five
conversion steps included in the claim language. The enzymes set forth in Claim 1 of
the ‘889 Patent do not include an EC number.
Butamax sued Gevo on January 14, 2011 and later moved for a preliminary
injunction based upon the ‘889 Patent. One of the issues appealed to the United States
Court of Appeals, Federal Circuit (“Federal Circuit”) concerns claim construction for one
of the recited steps of the biosynthetic pathway in the ‘889 Patent. Although the EC
number was not recited in Claim 1 of the ‘889 Patent nor was any dependence on a
coenzyme such as NADPH or NADP recited in the claim, the district court construed the
claim as “an enzyme known by the EC number 1.1.1.86 that catalyzes the conversion of
acetolactate to 2,3-dihydroxyisovalerate and is solely NADPH-dependent.”
Federal Circuit Decision (Case No. 2013-1342; Decided February 18, 2014)
Butamax appealed the final judgment entered against it following the district
court’s decisions on a number of motions and the district court’s claim construction.
The Federal Circuit accepted the appeal and reviewed claim construction de novo. On
February 18, 2014, the Federal Circuit (before Chief Judge Rader, Linn and Wallach,
Circuit Judges) found that the district court erred in its claim construction and vacated
the district court’s denial of Butamax’s motion for summary judgment of infringement
of the ‘188 Patent and the ‘889 Patent and its grant of Gevo’s motion of
noninfringement under the doctrine of equivalents. In response, Gevo filed a petition
for a Writ of Certiorari with the Supreme Court to vacate the decision of the Federal
Circuit.
Supreme Court Certiorari Summary Disposition (Case No. 13-1286; Decided January
26, 2015)
In light of the decision in Teva Pharmaceuticals, the Butamax case was remanded
to the Federal Circuit for further consideration on January 26, 2015.
In Teva
Pharmaceuticals, the Supreme Court held that when reviewing a district court’s
resolution of subsidiary factual matters made in the course of its construction of a
patent claim, the Federal Circuit must apply a “clear error,” not a de novo, standard of
review.
Discussion
The primary claim construction dispute before the Federal Circuit in Butamax
concerns whether the enzyme recited in step (ii) of the patent claims must be “NADPHdependent.” The enzyme in question is the enzyme polypeptide enzyme acetohydroxy
acid isomeroreductase (also known as “KARI”). To accomplish the conversion, KARI
requires a cofactor as an electron source. Two such cofactors are NADH and NADPH.
According to the district court record, Gevo uses mutant KARI enzymes that when using
NADH as a cofactor exhibit significantly lower Km (Michaelis-Menten constant) for the
conversion of acetolactate to 2,3-dihydroyisovalerate in their isobutanol process.
Claim 1 of the ‘889 Patent is reproduced below.
1. A method for producing isobutanol comprising;
a. providing a fermentation media comprising carbon substrate; and
b. contacting said media with a recombinant yeast microorganism
expressing an engineered isobutanol biosynthetic pathway wherein said
pathway comprises the following substrate to product conversions;
i. pyruvate to acetolactate (pathway step a);
ii. acetolactate to 2,3-dihydroxyisovalerate (pathway step b);
iii. 2,3-dihydroxyisovalerate to .alpha.-ketoisovalerate (pathway step c);
iv. α-ketoisovalerate to isobutyraldehyde (pathway step d); and
v. isobutyraldehyde to isobutanol (pathway step e);
and wherein
a) the substrate to product conversion of step (i) is performed by an
acetolactate synthase enzyme;
b) the substrate to product conversion of step (ii) is performed by an
acetohydroxy acid isomeroreductase enzyme;
c) the substrate to product conversion of step (iii) is performed by an
acetohydroxy acid dehydratase enzyme;
d) the substrate to product conversion of step (iv) is performed by a
decarboxylase enzyme; and
e) the substrate to product conversion of step (v) is performed by an
alcohol dehydrogenase enzyme; whereby isobutanol is produced.
The district court considered the patents’ specifications, prosecution histories, and the
extrinsic evidence such as expert testimony and the EC enzyme classification system and
other enzyme databases. It concluded that in the “state of the art,” the KARI enzyme
known by the EC number 1.1.1.86 was generally understood to be NADPH dependent.
In reviewing the district court’s decision, the Federal Circuit considered (i) the
plain meaning of KARI; (ii) the specification and claims; (iii) prosecution history; (iv)
extrinsic evidence; and (v) claim construction, as summarized in brief below.
(i)
The Federal Circuit found that the plain meaning of KARI itself imposes no
limitation on the cofactor for the conversion of acetolactate to 2,3dihydroxyisovalerate.
(ii)
In the specification, the patentee offered a definition of KARI but it is
disputed whether the definition “clearly expresses an intent” to refine KARI
in a way that differs from the plain and ordinary meaning. The
specification indicated that the definitions were intended for
interpretation of the claims and specification. The specification then went
on to generally describe KARI as an enzyme that catalyzes the conversion
of acetolactate to 2,3-dihydroxyislovaerate using NADPH as an electron
donor. The Federal Circuit found that the use of the phase “using NADPH”
in the specification did not mean “only use NADPH” or “NADPHdependent” as argued by Gevo.
The Federal Circuit also found that the district court’s claim construction
improperly excluded a preferred embodiment described in the
specification where KARI from Methanococcus maripaludis SEQ ID NO: 183
is taught as “able to utilize NADH as well as NADPH.”
(iii)
The prosecution history showed the patentee defending against
enablement rejections by referring the Patent Office to the EC numbers
and examples of enzymes provided in the specifications. The Federal
Circuit did not consider the statements to warrant any limitation of the
claimed KARI as being NADPH-dependent.
(iv)
In considering extrinsic evidence, the Federal Circuit found that a
subsequent patent filing by Butamax which taught a “discovery of a KARI
enzyme that can use NADH as a cofactor as opposed to NADPH would be
an advance in the art” was subsequent extrinsic evidence that did not
clearly express an intent at the time of the invention to refine KARI to use
one cofactor over another.
(v)
The Federal Circuit construed the term “acetohydroxy acid
reductoisomerase” as “an enzyme, whether naturally occurring or
otherwise, known by the EC number 1.1.1.86 that catalyzes the conversion
of acetolactate to 2,3-dihyroxyiosvalerate.
On remand, the Federal Circuit will be required to use the “clear error” standard
of review in Butamax.
Conclusion
In Teva Pharmaceuticals, the Supreme Court explained how the “clear error” rule
must be applied (Slip Op. Pp 11-14). The use of intrinsic evidence and extrinsic
evidence by the district court impacts the standard of review. In those situations when
the district court reviews only evidence intrinsic to the patent, the judge’s determination
is solely a determination of law and thus the court of appeals will review that
construction de novo. In those situations where the district court needs to consult
extrinsic evidence in order to understand the meaning of a term during the relevant
time period, and where those subsidiary facts are in dispute, courts will need to make
subsidiary factual findings about the extrinsic evidence. To overturn the judge’s
resolution of an underlying factual dispute, the appellant court must find that the judge,
in respect to those factual findings, has made a “clear error.” In Butamax, for example,
extrinsic evidence such as expert testimony and the EC enzyme classification system and
other enzyme databases, will be reviewed with the “clear error” standard. It should be
noted that the ultimate construction of the claim remains a legal conclusion that the
appellate court can review de novo per the Supreme Court opinion in Teva
Pharmaceuticals. (Pp 14).
Nothing herein should be construed as legal advice or legal representation.