United States Court of Appeals 

for the Federal Circuit ______________________ 

BUTAMAX(TM) ADVANCED BIOFUELS LLC,

Plaintiff-Appellant,

v.

GEVO, INC.,

Defendant- Appellee.

______________________ 

2013-1342

______________________ 

Appeal from the United States District Court for the 

District of Delaware in No. 11-CV-0054, Judge Sue L. 

Robinson.

______________________ 

Decided: February 18, 2014

______________________ 

LEORA BEN-AMI, Kirkland & Ellis, LLP, of New York, 

New York, argued for plaintiff-appellant. With her on the 

brief were THOMAS F. FLEMING, CHRISTOPHER T. JAGOE, 

and PETER B. SILVERMAN. 

MICHELLE S. RHYU, Cooley, LLP, of Palo Alto, California, argued for defendant-appellee. With her on the brief 

were STEPHEN C. NEAL, BENJAMIN G. DAMSTEDT, DANIEL 

J. KNAUSS, of Palo Alto, California; and JAMES P. BROGAN,

of Broomfield, Colorado. 

______________________ 
2 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

Before RADER, Chief Judge, LINN, and WALLACH, Circuit 

Judges.

LINN, Circuit Judge. 

ButamaxTM Advanced Biofuels LLC (“Butamax”) owns

U.S. Pat. No. 7,851,188 (“’188 patent”) and No. 7,993,889 

(“’889 patent”) (collectively, the “patents-in-suit”) and 

appeals a final judgment entered against it following the 

district court’s 1) claim construction and denial of Butamax’s motion for summary judgment of literal infringement of the asserted claims of the ’188 and ’889 patents

by Gevo, Inc. (“Gevo”), 2) grant of Gevo’s motion for summary judgment of noninfringement under the doctrine of 

equivalents of the asserted claims of the ’188 and ’889 

patents, 3) grant of Gevo’s motion for summary judgment 

of invalidity of claims 12 and 13 of the ’889 patent for lack 

of written description, and 4) judgment of invalidity of 

claims 12 and 13 of the ’889 patent for lack of enablement. 

Opinion, ButamaxTM Advanced Biofuels LLC v. Gevo, Inc., 

No. 11-54-SLR, 2013 WL 3914467 (D. Del. March 19, 

2013) (“Opinion”). Because the district court erred in its 

claim construction, this court vacates the district court’s 

denial of Butamax’s motion for summary judgment of 

infringement and its grant of Gevo’s motion of noninfringement under the doctrine of equivalents. Because 

the district court failed to recognize the existence of 

genuine issues of material fact on Gevo’s motion for 

summary judgment of invalidity as to claims 12 and 13 of 

the ’889 patent, this court reverses the district court’s 

grant of that motion. Finally, this court reverses the 

grant of summary judgment of invalidity for lack of enablement because that judgment appears to have been a 

scrivener’s error. 
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 3

I. BACKGROUND

A. The ’188 Patent

The ’188 patent covers a recombinant microbial host 

cell that uses a particular biosynthetic pathway to produce isobutanol, which is useful as a fuel or fuel additive. 

Opinion at *3. The claimed biosynthetic pathway comprises essentially five steps. See ’188 Patent fig. 1. 

Claim 1 of the ’188 patent recites the first four steps: 

1. A recombinant microbial host cell comprising heterologous DNA molecules encoding polypeptides that catalyze substrate to product 

conversions for each step below: 

i) pyruvate to acetolactate;

ii) acetolactate to 2,3-dihydroxyisovalerate;

iii) 2,3-dihydroxyisovalerate to αketoisovalerate; and

iv) α-ketoisovalerate to isobutyraldehyde;

wherein said microbial host cell produces isobutanol; and wherein 

a) the polypeptide that catalyzes a substrate 

to product conversion of pyruvate to acetolactate 

is acetolactate synthase having the EC number 

2.2.1.6;

b) the polypeptide that catalyzes a substrate 

to product conversion of acetolactate to 2,3-

dihydroxyisovalerate is acetohydroxy acid isomeroreductase having the EC number 1.1.1.86;

c) the polypeptide that catalyzes a substrate to 

product conversion of 2,3-dihydroxyisovalerate to 

α-ketoisovalerate is acetohydroxy acid dehydratase having the EC number 4.2.1.9;
4 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

d) the polypeptide that catalyzes a substrate 

to product conversion of α-ketoisovalerate to isobutyraldehyde is branched-chain α-keto acid decarboxylase having the EC number 4.1.1.72.

’188 Patent col. 335 ll. 21–44 (emphasis added). In the 

fifth step, isobutyraldehyde is converted into isobutanol. 

See ’188 Patent col. 336 ll. 43–48 (dependent claim 18, 

reciting a method for producing isobutanol from the 

recombinant microbial host cell of claim 1).

Claim 15 depends from claim 1 and recites “[a] host 

cell according to claim 1 wherein the acetohydroxy acid 

isomeroreductase has an amino acid sequence selected 

from the group consisting of SEQ ID NO:43, SEQ ID 

NO:181, SEQ ID NO:183, and SEQ ID NO:185.” ’188 

Patent col. 336 ll. 33–36. SEQ ID NO:183 is a sequence of 

Methanococcus. 

This appeal primarily concerns step (ii): the conversion of acetolactate (“AL”) to 2,3-dihydroxyisovalerate 

(“DHIV”), catalyzed by the polypeptide enzyme acetohydroxy acid isomeroreductase (also known as keto-acid 

reductoisomerase, or “KARI”) “having the EC number 

1.1.1.86.” KARI assists reactions by rearranging (i.e., 

isomerizing) a reagent and also by “reducing” (the process 

of adding electrons) this rearranged molecule. To accomplish the reduction, KARI needs a source for the added 

electrons. This electron source is known as the “cofactor” 

or “coenzyme.” Two such cofactors are NADH (nicotinamide adenine dinucleotide + hydrogen) and NADPH 

(nicotinamide adenine dinucleotide phosphate + hydrogen). 

The ’188 patent’s specification provides “definitions . . . to be used for the interpretation of the claims,” 

including a definition of KARI:

an enzyme that catalyzes the conversion of acetolactate to 2,3-dihydroxyisovalerate using NADPH
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 5

(reduced nicotinamide adenine dinucleotide phosphate) as an electron donor. Preferred acetohydroxy acid isomeroreductases are known by the 

EC number 1.1.1.86 and sequences are available 

from a vast array of microorganisms, including 

but not limited to . . . Methanococcus maripaludis . . . . 

’188 Patent col. 7 ll. 35–47.

EC number 1.1.1.86, referenced in both this definition 

and claim 1, is an Enzyme Commission number for an 

enzyme known by the names KARI, “acetohydroxy acid 

isomeroreductase,” and several other names. The EC 

enzyme classification system was developed in the 1950s 

to standardize enzyme nomenclature. Opinion at *15. 

Notably, Rule 18 of the EC system states that “[f]or 

oxidoreductases using NAD+ or NADP+ [the oxidized 

states of NADH and NADPH, respectively], the coenzyme 

should always be named as the acceptor” unless a certain 

exception applies, which is irrelevant here. Id. However, 

it also appears common to assign different EC numbers to 

the same enzyme, where the difference between the 

numbers is the identity of the cofactor named. Id. at 15 

n.8. EC number 1.1.1.86 names only NADP+ as an acceptor, and neither party calls attention to another EC 

number for KARI naming any other cofactor as an acceptor. 

Butamax alleges that Gevo infringes claim 1 of 

the ’188 patent and claims 2–4, 13–15, 17, and 36 dependent therefrom, as well as claim 18 and claims 19–25, and 

34–35 dependent therefrom.

B. The ’889 Patent

The ’889 patent issued from a divisional of the application from which the ’188 patent issued. The patents’ 

specifications largely are identical, each for example 

including the KARI definition quoted above. See ’889 
6 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

Patent col. 7 ll. 8–20. The ’889 patent focuses on a method of producing isobutanol from a recombinant yeast 

microorganism that expresses the five-step biosynthetic 

pathway described above. 

Claim 1 of the ’889 patent states:

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 αketoisovalerate (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;
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 7

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.

’889 Patent col. 325 ll. 14–43. As with the ’188 patent, the 

primary issue with the ’889 patent on appeal involves step 

(ii): the conversion of AL to DHIV using acetohydroxy 

acid isomeroreductase enzyme, i.e., KARI. Unlike claim 1 

of the ’188 patent, claim 1 of the ’889 patent does not refer 

to any EC classification number. 

Butamax alleges that Gevo has infringed claim 1 of 

the ’889 patent and claims 2–14 and 16–19 dependent 

therefrom. 

C. The Parties and Previous Proceedings

Butamax was formed in 2009 as a joint venture between E.I. du Pont de Nemours and Co. (“Du Pont”) and 

BP Biofuels North America LLC. The applications that 

led to the patents-in-suit are part of Du Pont’s previous 

research and development into isobutanol production. 

The patents-in-suit have been assigned to Butamax. 

Gevo was incorporated in 2005 as Methanotech, Inc. 

and likewise pursues isobutanol production. Gevo uses

mutant KARI enzymes that when using NADH as a 

cofactor exhibit significantly lower Km (Michaelis-Menten 

constant) for the AL-to-DHIV conversion than when using 

NADPH as a cofactor. This indicates that the reaction 

rate with Gevo’s mutant enzymes is much faster with 

NADH than with NADPH. 
8 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

On January 14, 2011, Butamax sued Gevo in the district court and on September 22, 2011, moved for a preliminary injunction predicated on the ’889 patent. The 

district court construed the KARI term as “an enzyme 

that is solely NADPH-dependent” and denied the motion. 

Butamax(TM) Advanced Biofuels LLC v. Gevo, Inc., 486 F.

App’x 883 (Fed. Cir. 2012). This court affirmed the denial 

of the preliminary injunction. Id. However, this court 

noted that the district court’s construction of the KARI 

term was “very questionable” and asked the district court 

“to reconsider its construction when it holds the Markman

hearing.” Id. 

At the Markman hearing, the district court construed 

the term as “an enzyme known by the EC number 1.1.1.86 

that catalyzes the conversion of acetolactate to 2,3-

dihydroxyisovalerate and is NADPH-dependent.” Opinion at *21. Additionally, adopting Butamax’s proposed 

construction, the district court construed the ’889 patent’s 

term “pathway step (a); . . . pathway step (b); . . . pathway 

step (c); . . . pathway step (d); . . . pathway step (e)” to 

mean “the pathway steps a-e are contiguous steps such 

that the product of step a is the substrate for step b; the 

product of step b is the substrate for step c; etc.” Id. at * 

22. 

At the district court, Butamax moved for summary 

judgment of infringement of the patents-in-suit and for a 

judgment of no invalidity of the ’889 patent. Opinion at 

*2. Gevo moved for summary judgment of invalidity and 

non-infringement. Id. In a memorandum opinion, the 

district court denied Butamax’s motion for summary 

judgment of infringement. The district court granted 

Gevo’s motion for summary judgment of noninfringement 

as it related to the doctrine of equivalents, but otherwise 

denied the motion. Each of Butamax’s motion of no

invalidity and Gevo’s motion for invalidity was granted by 

the district court with respect to some claims and denied 

with respect to others. Relevant to this appeal, the dis-
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 9

trict court granted Gevo’s invalidity motion and denied 

Butamax’s motion of no invalidity with respect to claims 

12 and 13 of the ’889 patent, finding the claims lacking in

written description support. Opinion at *52–53. The 

district court issued an order reflecting the memorandum 

opinion and also holding claims 12 and 13 the ’889 patent 

invalid for lack of enablement, a ground not raised in the 

motions of the parties. 

Butamax appeals the claim construction of the KARI 

term, the denial of Butamax’s motion for summary judgment of literal infringement, the grant of Gevo’s motion 

for summary judgment of noninfringement under the 

doctrine of equivalents, the grant of Gevo’s motion for 

summary judgment of invalidity of claims 12 and 13 of the 

’889 patent for inadequate written description, and the 

order also holding those same claims invalid for lack of 

enablement. This court has jurisdiction under 28 U.S.C. 

§ 1295(a)(1).

II. DISCUSSION

A. Standards of Review

“We review claim construction de novo.” Thorner v. 

Sony Computer Entm’t Am. LLC, 669 F.3d 1362, 1365 

(Fed. Cir. 2012). 

Summary judgment is granted “if the movant shows 

that there is no genuine dispute as to any material fact 

and the movant is entitled to judgment as a matter of 

law.” Fed. R. Civ. P. 56(a). “This court reviews the district court’s grant or denial of summary judgment under 

the law of the regional circuit.” Lexion Med., LLC v. 

Northgate Techs., Inc., 641 F.3d 1352, 1358 (Fed. Cir.

2011). The Third Circuit “review[s] an order granting 

summary judgment de novo, applying the same standard 

used by the District Court.” Azur v. Chase Bank, USA, 

Nat’l Ass’n, 601 F.3d 212, 216 (3d Cir. 2010) (quotation 

omitted).
10 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

“[A] determination of infringement, both literal and 

under the doctrine of equivalents, is a question of fact.” 

Lockheed Martin Corp. v. Space Sys./Loral, Inc., 324 F.3d 

1308, 1318 (Fed. Cir. 2003). “Summary judgment on the 

issue of infringement is proper when no reasonable jury 

could find that every limitation recited in a properly 

construed claim either is or is not found in the accused 

device either literally or under the doctrine of equivalents.” PC Connector Solutions LLC v. SmartDisk Corp., 

406 F.3d 1359, 1364 (Fed. Cir. 2005). 

B. Claim Construction

The primary dispute between the parties concerns 

whether the claimed KARI must be “NADPH-dependent.” 

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 NADPHdependent.” Opinion at *20. This decision is premised in 

large part on the district court’s conclusion that the 

patentees acted as their own lexicographers in defining 

KARI by reference to EC number 1.1.1.86 and the enzyme’s “use” of NADPH rather than use of NADH or both 

NADPH and NADH. Id. at *19–20. The district court 

therefore construed the KARI term as “an enzyme known 

by the EC number 1.1.1.86 that catalyzes the conversion 

of acetolactate to 2,3-dihydroxyisovalerate and is 

NADPH-dependent.” Id. at *21. 

Butamax argues that the district court erred because 

KARI’s plain meaning merely refers to an enzyme catalyzing the AL to DHIV conversion and because the patentees 

did not expressly relinquish any of that claim scope in the 

specification or the prosecution history. Butamax contends that the patentees in defining KARI did not clearly 

express an intent to redefine KARI to be NADPH-
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 11

dependent. In support, Butamax points to the other 

claims, the embodiments provided in the specifications, 

and extrinsic evidence including contemporary scientific 

literature, a database referenced in EC number 1.1.1.86, 

and Gevo’s use of EC number 1.1.1.86 to describe its own 

enzymes. 

Gevo disagrees, arguing that the district court construed the term correctly. Gevo contends that the specifications’ definition of KARI demonstrates that the 

patentees did clearly express an intent to specify KARI as 

NADPH-dependent, and points to other aspects of the 

specifications as well as the prosecution histories in 

support. Gevo further contends that extrinsic evidence,

such as EC number 1.1.1.86 and its references, the EC 

rules, and Butamax’s internal documents and subsequent 

patent applications indicate that the claimed KARI must 

be NADPH-dependent.

Generally, claim terms are:

given their ordinary and customary meaning as 

understood by a person of ordinary skill in the art 

when read in the context of the specification and 

prosecution history. There are only two exceptions to this general rule: 1) when a patentee sets 

out a definition and acts as his own lexicographer, 

or 2) when the patentee disavows the full scope of 

a claim term either in the specification or during 

prosecution.

Thorner, 669 F.3d at 1365 (citation omitted). “To act as 

its own lexicographer, a patentee must ‘clearly set forth a 

definition of the disputed claim term’ other than its plain 

and ordinary meaning.” Id. at 1365 (quoting CCS Fitness, 

Inc. v. Brunswick Corp., 288 F.3d 1359, 1366 (Fed. Cir.

2002)). “It is not enough for a patentee to simply disclose 

a single embodiment or use a word in the same manner in 

all embodiments, the patentee must ‘clearly express an 

intent’ to redefine the term.” Id. (citing Helmsderfer v. 
12 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

Bobrick Washroom Equip., Inc., 527 F.3d 1379, 1381 (Fed.

Cir. 2008)).

i. KARI’s Ordinary Meaning

The initial inquiry is whether the plain meaning of 

KARI indicates that the enzyme is NADPH-dependent. 

While the district court found that “the scientific references almost exclusively characterize KARI enzymes as 

NADPH-dependent,” Opinion at *19, there is nothing in 

the record to indicate that persons of ordinary skill in the 

art in 2005 understood the plain meaning to be limited to 

dependence on NADPH as a cofactor. Gevo conceded as 

much at the district court, acknowledging that under 

KARI’s plain meaning, the enzyme converts AL to DHIV 

“using NADH or NADPH as a cofactor.” See Joint Appendix (“J.A.”) 10240. 

We agree that the plain meaning of KARI itself imposes no limitation on the cofactor or source of electrons 

for the AL to DHIV conversion. The question then becomes whether the asserted claims are limited, as Gevo 

contends, to the use of NADPH only based principally on 

the “explicit definition” set forth in the patents-in-suit. 

See J.A. 10241.

ii. The Specifications and Claims

a. The Patentees’ Definition of KARI

The patents provide definitions of several terms, noting that “[t]he following definitions and abbreviations are 

to be used for the interpretation of the claims and specification.” ’188 Patent col. 7 ll. 12–14.1 As described above, 

the patents subsequently define KARI as:

1 Because the specifications of the patents-in-suit 

largely are identical, the court for brevity will cite only to 

the ’188 patent.

 
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 13

an enzyme that catalyzes the conversion of acetolactate to 2,3-dihydroxyisovalerate using NADPH 

(reduced nicotinamide adenine dinucleotide phosphate) as an electron donor. Preferred acetohydroxy acid isomeroreductases are known by the 

EC number 1.1.1.86 and sequences are available 

from a vast array of microorganisms, including 

but not limited to . . . Methanococcus maripaludis . . . . 

’188 Patent col. 7 ll. 35–47. 

It cannot be disputed that the patentees offered a definition of KARI. It is disputed, however, whether this 

definition “clearly expresses an intent” to redefine KARI 

in a way that differs from the plain and ordinary meaning 

identified above and, if so, the extent of any such difference. Gevo contends that the phrase “using NADPH . . . 

as an electron donor” is a clear expression of the patentees’ intent to exclude KARI that are not “NADPHdependent.” 

Butamax disagrees and asserts that the fact that an 

enzyme can catalyze the conversion of AL to DHIV “using 

NADPH” does not, on its own, indicate that the enzyme 

cannot also use other cofactors, such as NADH, to catalyze that conversion. 

Gevo argues that Butamax’s interpretation reads out 

an important aspect of the patentees’ definition of KARI 

because all KARI are capable of using NADPH as a cofactor. Thus, Gevo argues it would have been completely 

unnecessary for the patents to have referred to “using 

NADPH” in the first instance. Gevo also argues that the 

phrase “using NADPH” must be understood in light of 

other aspects of the specifications. Gevo first contends

that the specifications use the term “use(s) NADPH” 

interchangeably with the phrase “NADPH-dependent.” 

Gevo points to this passage:
14 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

[A]lcohol dehydrogenase VI (ADH6) and Ypr1p . . .

use NADPH as electron donor. An NADPHdependent reductase, YqhD, . . . has also been recently identified in E. coli . . . . 

’188 Patent col. 12 ll. 50–60. The patents further describe

ADH6 as “NADPH-dependent cinnamyl alcohol dehydrogenase.” Id. at col. 4 ll. 60–62. However, “[i]t is not 

enough for a patentee to simply disclose a single embodiment or use a word in the same manner in all embodiments.” Thorner, 669 F.3d at 1365. 

We agree with Butamax and find no reason to constrict the phrase “using NADPH” to mean “only use 

NADPH” or “NADPH-dependent.” We also disagree with 

Gevo’s argument that such an interpretation reads out an 

important part of the patentees’ definition. The patents’ 

definition at least excludes as-yet-undiscovered KARI 

enzymes that could catalyze the conversion of AL to DHIV 

without using NADPH at all. Moreover, the description of 

specific types of KARI as NADPH-dependent does not 

clearly express an intent to redefine all KARI “using 

NADPH” as KARI that must be NADPH-dependent. 

Next, Gevo points to the patents’ descriptions of other 

enzymes that use or utilize either NAD+ or “NADH . . . 

and/or NADPH” as an electron donor. Id. at col. 8 ll. 14–

16, 25–29. Gevo contends that the patentees knew how to 

describe enzymes that used NADH or both NADH and 

NADPH and that the patentees instead chose to define

KARI as using only NADPH. 

Butamax counters that the patents’ descriptions of 

other enzymes “using” or “utilizing” various cofactors 

merely is a reference to particular EC numbers or the 

assays for the enzymes in question. For example, Butamax contends that the standard assay for KARI is the 

Arfin-Umbarger assay, which “uses” NADPH to measure

KARI activity by monitoring the consumption of NADPH 

in the presence of acetolactate and the enzyme in ques-
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 15

tion. Appellant’s Br. 14. The patents’ Example 2 expressly teaches to measure KARI activity “using the method 

described by Arfin and Umbarger,” ’188 Patent col. 33 ll. 

45–47. Example 10 teaches using the same method. Id.

at col. 39 ll. 4–5. Butamax also argues that the patents’ 

reference to “using NADPH” merely matches the description of the enzyme in EC number 1.1.1.86, which notes 

the use of NADP+ but is silent as to NAD+ or NADH. 

Butamax notes that the other enzymes in question from 

the specifications have multiple EC numbers—each 

referring to NADH, NADPH, or both NADH and 

NADPH—and/or have multiple different assays for their 

identification—each assay using a different cofactor. 

Thus, Butamax argues that the patentees merely referred 

the other cofactors where appropriate. Appellant’s Br. 45. 

We agree with Butamax that the references to other 

enzymes as either using NAD+ or using NADH and/or 

NADPH do not imply that the patentees intended to limit 

KARI’s use of NADH. The patentees’ description of KARI 

merely corresponds with the Arfin-Umbarger assay and 

the description of KARI in EC Number 1.1.1.86.

b. Reference to EC Number 1.1.1.86 in Claim 1

The ’188 patent’s claim 1 explicitly states that the enzyme in question is “acetohydroxy acid isomeroreductase 

having the EC number 1.1.1.86.” ’188 Patent col. 335 ll. 

33–36. As described above, EC number 1.1.1.86 identifies 

NADP+ as the cofactor, but does not itself mention NAD+

or NADH. See Appellee’s Br. 45. The EC rules provide 

that for an enzyme “using” both NADH and NADPH, the 

entry should “always” name both cofactors. Gevo contends that this confirms that a person of ordinary skill in 

the art understood KARI having EC number 1.1.1.86 to be 

NADPH-dependent. 

It must first be appreciated that the EC nomenclature 

was drafted to categorize naturally-occurring enzymes 

and that new EC numbers generally are not created for 
16 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

modified forms of enzymes that might rely on different 

cofactors. See J.A. 17810–11. The nomenclature is also 

not necessarily complete. In 2005, for example, it was 

known that some KARI, such as KARI from at least some 

species of Methanococcus, can use either cofactor effectively. Significantly, Methanococcus was explicitly recited in 

Butamax’s own definition as a preferred KARI and recited 

in dependent claim 15. ’188 Patent col. 7 ll. 40–47. 

Butamax points to additional evidence showing persons of skill in the art would have understood that EC 

number 1.1.1.86 enzymes need not be NADPH-dependent. 

The EC number 1.1.1.86 entry contains a link to the 

BRENDA database (Braunchschweig Enzyme Database), 

which contains a reference to a mutated KARI enzyme in 

which NADH “can substitute for NADPH.” Appellant’s 

Br. 16. The district court discounted this lone reference 

because it was the only reference out of many indicating 

that NADH could be substituted and because the specific 

enzyme in question was a “quadruplet mutant.” Opinion

at *19–20. 

However, even a single reference to mutant KARI under EC number 1.1.1.86 is particularly important here 

because the accused enzymes also are mutants. Butamax 

points to evidence that Gevo in approximately 2008—

prior to the litigation—described its own mutant enzymes 

by reference to EC number 1.1.1.86. See, e.g., Appellant’s 

Br. 25; J.A. 9804. And of course Gevo contends that its 

enzymes are not NADPH-dependent. Though this evidence identified by Butamax did not exist until years 

after the patents-in-suits were filed in 2005, the BRENDA 

entry for EC number 1.1.1.86 referred to a mutant KARI

that was not NADPH-dependent and was known prior to 

2005, and Gevo years later indicated that EC number 

1.1.1.86 still “would have been the best way [they] knew 

how” to describe its own mutant enzyme. Appellant’s Br. 

25 (citing testimony of Gevo’s former Executive Vice 

President of Technology). See e.g., ASM Am., Inc. v. 
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 17

Genus, Inc., 401 F.3d 1340, 1347 (Fed. Cir. 2005) (concluding that extrinsic evidence that post-dated the patent 

filing date nonetheless was helpful in determining how a 

person of ordinary skill in the art would have understood 

the claim term at the time it was filed).

For the foregoing reasons, the Court cannot conclude 

that the reference to EC number 1.1.1.86 is an expression 

of a clear intent to redefine KARI to be NADPHdependent. 

c. Preferred Embodiments and Dependent Claims

Other aspects of the patents raise further doubt of 

any express intent to redefine KARI in the limited way 

adopted by the district court. As above, the patents 

specifically list “Methanococcus maripaludis . . . SEQ ID 

NO: 183” as a source organism for the preferred 

KARI. ’188 patent at col. 7 ll. 35–47. Moreover, dependent claim 15 of the ’188 patent claims that KARI. ’188 

Patent col. 336 ll. 33–36. Butamax contends that it would 

be wrong to conclude that KARI from this organism are 

NADPH-dependent, pointing to evidence that at least 

some Methanococcus KARI are “able to utilize NADH as 

well as NADPH” and have “broad specificity for NADPH 

and NADH.” Further, Butamax notes that “NADH supported 60% of the methanococcal activity obtained with 

NADPH.” See R. Xing & W. Whitman, Characterization 

of Enzymes of the Branched-Chain Amino Acid Biosynthetic Pathway in Methanococcus spp, 173(6) J. Bacteriology 2086–92 (1991) (“Xing”). 

The district court discounted Xing because it provided 

no references or data to support these findings. Opinion

at *19 (noting that Xing “included a single conclusory 

sentence with no data or other literature references to 

support it”). However, Xing’s accuracy is not in dispute. 

Indeed, Gevo’s 2007 Pat. App. No. 61/016,483 cites to Xing 

for this very proposition. Gevo does note that the patents 

identify the KARI of Methanococcus maripaludis while 
18 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

Xing examined the KARI of Methanococcus aeolicus, a 

different species of Methanococcus. However, there is no 

genuine dispute that Methanococcus maripaludis exhibits 

similar characteristics. See Appellant’s Reply Br. 9. 

The district court’s claim construction, without justification, excludes a preferred embodiment, which in this 

case also is the subject of dependent claim 15, and this 

court “normally do[es] not interpret claim terms in a way 

that excludes embodiments disclosed in the specification.” 

Oatey Co. v. IPS Corp., 514 F.3d 1271, 1276 (Fed. Cir. 

2008). 

iii. Prosecution History

Gevo also contends that the prosecution history evinces an express intent to redefine KARI to be NADPHdependent. The Patent Office separately rejected Butamax’s claims for lack of enablement and for lack of written description, and Gevo contends that the patentees’ 

responses demonstrated that the claimed KARI are 

NADPH-dependent.

In the application leading to the ’188 patent, the Patent Office rejected for inadequate written description a 

then-pending claim which stated:

A recombinant microbial host cell comprising 

at least one DNA molecule encoding a polypeptide 

that catalyzes a substrate to product conversion 

selected from the group consisting of:

i) pyruvate to acetolactate (pathway step a)

ii) acetolactate to 2,3-dihydroxyisQvalerate 

(pathway step b)

iii) 2,3-dihydroxyisovalerate to aketoisovalerate (pathway step c)

iv) a-ketoisovalerate to isobutyraldehyde, 

(pathway step d), and
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 19

v) isobutyraldehyde to isobutanol; (pathway 

step e)

wherein the at least one DNA molecule is heterologous to said microbial host cell and wherein 

said microbial host cell produces isobutanol.

J.A. 6906. The Patent Office concluded that “[o]ne skilled 

in the art would require additional guidance, such as 

information regarding the specific identity and structure 

of the polypeptides that catalyze[]” the conversions in the 

claim. J.A. 6927. The patentees responded, amending 

the claim to refer to the EC numbers of the various enzymes, submitting a copy of the EC nomenclature rules, 

and pointing to the specific examples of the enzymes in 

the specification (including SEQ ID No: 183—

Methanococcus maripaludis—as an example of KARI). 

J.A. 7095. The Patent Office concluded that this sufficiently described the claimed inventions but concluded 

that the claim lacked enablement for its full scope. J.A.

7117. The patentees disagreed, contending that the EC 

numbers, together with the level of ordinary skill in the 

art (including knowledge reflected in the BRENDA database) did enable skilled artisans to identify appropriate 

enzymes, and the examiner eventually withdrew the 

rejection. J.A. 7209, 7251. 

In the application leading to the ’889 patent, a thenpending claim similarly was rejected for lack of enablement. J.A. 7572–73. The patentees again amended, this 

time naming the enzymes used in each claimed step 

without referring to any EC numbers. J.A. 7585. The 

patentees argued that “[t]he specific enzymes that catalyze the steps of the pathway recited in the claims are 

described in the application in an abundance of detail,” 

and went on to discuss Table 2 as a particular example. 

J.A. 7583.

In the prosecution history, the patentees defended 

their claims by referring the Patent Office to the EC 
20 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

numbers and the examples of the enzymes provided in the 

specifications. For the reasons stated above, these references do not clearly express an intent by the patentees to 

redefine KARI to be NADPH-dependent. Indeed, the 

patentees specifically named Methanococcus maripaludis

KARI as an example during the prosecution history, a 

KARI that appears to “use” NADH.

Accordingly, the court does not consider the prosecution history to warrant any limitation of the claimed 

KARI as being NADPH-dependent. 

iv. Extrinsic Evidence

Gevo also relies on extrinsic evidence to support its 

arguments. EC number 1.1.1.86 was discussed above. 

Gevo further points to Butamax’s internal documents and 

subsequent patent applications. For example, based on 

its research, Butamax filed a patent application in 2008 

which stated that “discovery of a KARI enzyme that can 

use NADH as a cofactor as opposed to NADPH would be 

an advance in the art.” J.A. 8794. Gevo contends that 

this application and the related evidence demonstrate 

that Butamax itself recognized that the earlier-filed 

patents-in-suit did not encompass KARI that use NADH.

However, as discussed above, the ordinary meaning of 

KARI is not cofactor dependent, and this subsequent 

extrinsic evidence does not clearly express an intent at the 

time of the invention to redefine KARI to use one cofactor 

over another. The subsequent discovery of the beneficial 

results obtained by the use of NADH does not support the 

conclusion that it was understood to be excluded as a 

cofactor at the time the patents-in-suit were filed. 

v. Claim Construction

For all of the foregoing reasons, the term “acetohydroxy acid reductoisomerase” is construed as “an enzyme, 

whether naturally occurring or otherwise, known by the 
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 21

EC number 1.1.1.86 that catalyzes the conversion of 

acetolactate to 2,3-dihydroxyisovalerate.” 

C. Infringement

Butamax contends that this court, under the more accurate claim construction, should reverse the district 

court’s ruling that denied Butamax’s motion for summary 

judgment of literal infringement. Gevo disagrees, contending that 1) there remains a dispute concerning the 

“contiguous” pathway term and 2) there remains a dispute as to the accused enzymes’ “use” of NADPH.

The continuous pathway term relates only to the ’889 

patent and does not present a genuine issue of material 

fact on this record. Butamax provided expert testimony, 

and Gevo failed to present any contention, interrogatory, 

or expert testimony challenging Butamax’s contention 

that the limitation was met. 

As to the dispute over whether Gevo’s enzymes use 

detectable levels of NADPH, Gevo argues on appeal that 

there is a distinction between in vivo and in vitro use that 

gives rise to a genuine issue of material dispute. However, Gevo does not appear to have argued at any point 

before the district court that the construction of KARI 

requires focusing on use of a specific cofactor in vivo as 

opposed to in vitro. This court declines to consider what 

appears to be a new claim construction argument raised 

for the first time on appeal. 

Gevo further contends that Butamax’s in vitro testing 

of Gevo’s enzymes, showing them to use NADPH, may be 

unreliable. Appellee’s Br. 61. Gevo’s argument however, 

is not that the results of the testing were inaccurate, but 

rather that a person of ordinary skill in the art would not 

draw the same conclusions from the experiments as the 

conclusions drawn by Butamax’s expert. Whether Gevo’s 

arguments create a genuine issue of material fact under 
22 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

the claim construction set forth in this opinion is best left 

to the district court on remand.

The court accordingly vacates the district court’s denial of Butamax’s motion for summary judgment of 

infringement of claims 1, 2–4, 13–15, 17–25, and 34–36 of 

the ’188 patent and claims 1, 2–14, and 16–19 of the ’889 

patent and directs the district court to reconsider the 

question under this court’s new claim construction.

D. Invalidity

i. Written Description of Claims 12 and 13 of the ’889 

Patent

Claim 12 of the ’889 patent states:

12. The recombinant yeast microorganism of claim 

1 wherein the said microorganism further comprises inactivated genes thereby reducing yield 

loss from competing pathways for carbon flow.

Claim 13 of the ’889 patent states:

13. The recombinant yeast microorganism of claim 

12, wherein said inactivated genes reduce pyruvate decarboxylase activity.

The district court found that both claims were inadequately described and thus invalid because the specification does not sufficiently describe how to inactivate genes 

to disable the competing synthetic pathway. 

When determining whether a specification contains adequate written description, one must 

make an “objective inquiry into the four corners of 

the specification from the perspective of a person 

of ordinary skill in the art.” [Citation.] Because 

the specification is viewed from the perspective of 

one of skill, in some circumstances, a patentee 

may rely on information that is “well-known in 
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 23

the art” for purposes of meeting the written description requirement. 

Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 

1353, 1366 (Fed. Cir. 2011) (citation omitted). 

The district court concluded that while the patent’s 

specification “may be interpreted as identifying both the 

[ ] problem and the solution, it does not even begin to 

describe how to put into practice the solution.” Opinion at 

*52. Butamax disagrees, but its evidence in support of its 

arguments is weak. First, Butamax contends that the 

patent does teach how to deactivate the pathway in 

question. In support, Butamax cites to multiple aspects of 

the specification, but each describes only a desire to 

deactivate the genes rather than how to actually do it. 

See, e.g., ’889 Patent col. 1 ll. 63–65 (“[t]here is a need . . . 

for an environmentally responsible, cost-effective process 

for the production of isobutanol as a single product”), col. 

16 ll. 55–57 (“[t]he microbial host has to be manipulated 

in order to inactivate competing pathways for carbon flow 

by deleting various genes”), col. 12 ll. 12–17 (“[t]o prevent 

misdirection of pyruvate away from isobutanol production, a decarboxylase with decreased affinity for pyruvate 

is desired”) (all emphasis added).

Next, Butamax contends that irrespective of what is 

explicitly taught in the specification itself, it was wellknown in the art how to deactivate the genes that express 

the pathway. Butamax points to the testimony of Gevo’s 

own experts, Dr. Stephanopolous and Dr. Kirsch, contending that they agreed that it was “conventional” in 2005 to 

deactivate the pathway. However, the expert testimony 

on which Butamax relies merely agrees that, in light of 

the specification, it would have been understood that such 

deactivation was desirable. See, e.g., Appellant’s Br. 68 

(Dr. Stephanopolous agreeing that “the concept” of deactivating the pathway was conventional by 2005, that it 

was “nothing new” to “want to get rid of competing path-
24 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

ways,” that the patents “tell you [you] want to delete” the 

competing pathway, and that the patent “tells you you’re 

knocking out” that pathway); see also, e.g., Appellant’s Br. 

69 (Dr. Kirsch agreeing that the patents teach that “you 

want to knock out” the competing pathway) (emphasis 

added). 

Butamax also relies on extrinsic evidence purportedly 

teaching how to deactivate the pathway. Butamax submitted the declaration of Alexander M. Klibanov, who 

opined that it would have been well-known to a person of 

ordinary skill in the art how to deactivate the genes, 

citing to seven references that purportedly describe organisms with reduced or inactivated pyruvate decarboxylase 

activity. Appellant’s Br. 67; J.A. 3141. The district court 

does not appear to have addressed Mr. Klibanov’s testimony or six of the references he cited. The seventh reference, Dickinson, was addressed by the district court, 

which agreed that Dickinson discloses yeast with deactivated genes associated with pyruvate decarboxylase 

activity as described in claim 13. Opinion at *53. However, the district court concluded that Dickinson was not 

appropriately incorporated by reference into the ’889 

patent for this point and even if it had been, that Dickinson effectively teaches away from claim 13 because in 

deactivating those genes responsible for expressing the 

pathway, isobutanol production was “virtually abolished.” 

Id. 

Notwithstanding the shortcomings of the foregoing, 

Butamax has identified sufficient evidence that at least 

creates a genuine dispute of material fact. Gevo makes 

much of the fact that Dickinson, though cited in the ’889 

patent, was not cited in connection with the deactivation 

of this pathway and was not incorporated by reference 

into the patent. Nonetheless, Dickinson’s teachings still 

reflect what was known in the art. See Falko-Gunter 

Falkner v. Inglis, 448 F.3d 1357, 1368 (Fed. Cir. 2006)

(holding that where “accessible literature sources clearly 
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 25

provided” a description of the teachings at issue, the 

written description requirement does not require their 

incorporation by reference). Dickinson does show that 

persons of ordinary skill in the art could deactivate the 

pathway in question, and though it appears that according to Dickinson the claimed invention would not have 

worked particularly well (isobutanol production would be 

“virtually abolished”), the evidence at least creates a 

genuine dispute as to whether a person of ordinary skill 

in the art would have understood the patentees to have 

possessed the invention on some level (isobutanol production would not necessarily have been completely abolished). Further, Mr. Klibanov opined that deactivation of 

the genes associated with the pathway was well-known in 

the art, and cited Dickinson as well as six other references 

in support. Gevo’s experts disagree with Mr. Klibanov

and his interpretation of these references, but this merely 

indicates the existence of a genuine dispute of material 

fact. 

Though not addressed by the district court, Gevo raises an argument that there can be no genuine dispute of 

material fact because a subsequent Butamax patent 

application demonstrates conclusively that the ’889 

patent lacks an adequate written description of these

claims. Butamax filed a continuation-in-part of the 

applications leading to the ’188 and ’889 patents, this 

time providing additional detail on the deactivation of 

certain genes. See U.S. Pat. App. No. 12/966,333. The 

Patent Office concluded that the ’889 patent was not—on 

its own—invalidating prior art to this application because 

the ’889 patent “do[es] not teach the disruption of endogenous pyruvate decarboxylase genes.” J.A. 17353. However, the issue here is not just whether the ’889 patent itself

teaches the disruption such that the patent itself would 

be invalidating prior art on that point. There is a genuine 

dispute with respect to whether in 2005 it was generally 

well-known in the art how to deactivate the genetic path-
26 BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 

way such that a person of ordinary skill in the art reading 

the ’889 patent would understand the patentees to have 

possessed the invention claimed in claims 12 and 13. 

For these reasons, the district court’s grant of Gevo’s 

motion for summary judgment of invalidity of claims 12 

and 13 for lack of adequate written description is reversed. 

ii. Enablement of the ’889 Patent’s Claims 12 and 13

In its order, the district court summarily concluded

that claims 12 and 13 were invalid for lack of enablement. 

However, its memorandum opinion does not reflect that 

judgment, nor did Gevo move for invalidity of those claims 

on this basis. On appeal, Gevo does not defend the judgment. It thus appears that the judgment was a scrivener’s error, and this court reverses the judgment that the

claims are invalid for lack of enablement. 

III. CONCLUSION

For the forgoing reasons, this court vacates the district court’s denial of Butamax’s motion for summary 

judgment of literal infringement of the asserted claims of 

the ’188 and ’889 patents and remands the question of 

infringement to the district court for reconsideration

under the claim construction set forth herein. Further, 

this court likewise vacates and remands the district 

court’s grant of Gevo’s motion for summary judgment of 

noninfringement under the doctrine of equivalents. The 

court further reverses the district court’s grant of Gevo’s 

motion for summary judgment of invalidity for lack of 

written description of claims 12 and 13 of the ’889 patent 

and the district court’s order that those same claims are 

invalid for lack of enablement. 

REVERSED-IN-PART, VACATED-IN-PART, AND 

REMANDED
BUTAMAX(TM) ADVANCED BIOFUELS v. GEVO, INC. 27

IV. COSTS

Costs are awarded to Butamax.