Opinion ID: 2653549
Heading Depth: 3
Heading Rank: 2

Heading: The Specifications and Claims

Text: 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 aceto- lactate to 2,3-dihydroxyisovalerate using NADPH (reduced nicotinamide adenine dinucleotide phosphate) as an electron donor. Preferred acetohy- droxy 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 maripalu- dis . . . . ’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 “NADPH- dependent.” 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 NADPH- dependent reductase, YqhD, . . . has also been re- cently 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 embodi- ments.” Thorner, 669 F.3d at 1365. We agree with Butamax and find no reason to con- strict 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 quesBUTAMAX(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.
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 –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 NADPH- dependent.
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 sup- ported 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  (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).