April 2010
Language of Magnitude Can Be Definite Without Reference to a Precise Numerical Range If the Intrinsic Evidence Provides Sufficient Comparative Information
| Judges: Michel, Plager, Linn (author) |
| [Appealed from D. Conn., Judge Arterton] |
In Enzo Biochem, Inc. v. Applera Corp., No. 09-1281 (Fed. Cir. Mar. 26, 2010), the Federal Circuit reversed the district court’s ruling that the claims of U.S. Patent Nos. 5,328,824 (“the ’824 patent”), 5,449,767 (“the ’767 patent”), and 5,476,928 (“the ’928 patent”) were indefinite. Finding a genuine issue of material fact, the Federal Circuit also reversed the SJ of anticipation as to the ’824 and ’767 patents, but the Court affirmed the district court’s judgment of anticipation as to the ’928 patent. The Federal Circuit affirmed the judgment of noninfringement as to U.S. Patent No. 5,082,830 (“the ’830 patent”). The Court remanded the case to determine whether the ’824 and ’767 patents were anticipated.
Enzo Biochem, Inc., Enzo Life Sciences, Inc., and Yale University (collectively “Enzo”) are the owners of the ’824, ’767, ’928, and ’830 patents. The patents-in-suit all relate to techniques for labeling and detecting nucleic acids. Nucleic acids that contain “complementary” bases will bind (“hybridize”) to one another. A chemical entity, called a “label,” can be attached to or incorporated into a known nucleic acid to create a “probe” that can hybridize to a nucleic acid of interest and indicate the presence of the nucleic acid of interest in a sample. Once the probe hybridizes, the label generates a detectable signal either directly (“direct detection”) or from a secondary agent bound to the label (“indirect detection”). Radioactive labels are an example of direct labels, but they are unstable, potentially hazardous, and expensive to purchase.
The ’824, ’767, and ’928 patents share a common specification. Each patent claims either a compound or a method of using that compound as a detection probe for nucleic acids. In the compound, a base is covalently attached, either directly or indirectly via a “linkage group” to a chemical moiety “A” that facilitates detection of the nucleic acid. The “linkage group,” is recited functionally as “not interfering substantially” with hybridization and detection (the ’824 and ’767 patents) or with detection (the ’928 patent). The later-filed ’830 patent claims a compound in which the label is positioned at each end of the nucleic acid probe. That patent also claims a method of detecting in which the nucleic acid sequence of interest is contacted with a nucleic acid probe with labels on each end and a “preformed detectable molecular complex.”
Enzo sued Applera Corp. and Tropix, Inc. (collectively “Applera”) for patent infringement. Following the district court’s claim construction ruling, Enzo conceded it could not prove infringement of the ’830 patent because Applera did not use a nonradioactive moiety that could be detected with a preformed detectable molecular complex. The district court accordingly granted SJ of noninfringement. The district court also granted SJ for Applera, finding that the claims of the ’824, ’767, and ’928 patents were either indefinite with respect to the “not interfering substantially” language or, in the alternative, were anticipated by at least one of three prior art references. Enzo appealed the SJ of noninfringement and it challenged the district court’s grant of SJ that the ’824, ’767, and ’928 patents were invalid in the alternative as indefinite, or, if not indefinite, then invalid as anticipated.
On appeal, the Federal Circuit first considered whether the “not interfering substantially” language of the ’824, ’767, and ’928 patents was indefinite. The Court explained that “[i]f a claim is indefinite, the claim, by definition, cannot be construed . . . [and] an anticipation analysis cannot be performed.” Slip op. at 10. As an initial matter, the Federal Circuit found that the district court had erred in adopting an identical claim construction for all three patents. Although the claims of the ’824 and ’767 patents provide that the linkage group not substantially interfere with both “hybridization” and “detection,” the Court noted that there was no reason to read the hybridization requirement into the claims of the ’928 patent. Nothing in the claim language or prosecution history required such an interpretation and, the Court observed, the applicants had specifically omitted the language from the claims of the ’928 patent but included it in the claims of the ’824 and ’767 patents.
“If a claim is indefinite, the claim, by definition, cannot be construed. Without a discernable claim construction, an anticipation analysis cannot be performed.” Slip op. at 10.
The Court then turned to the meaning of “substantially” in the phrase “not interfering substantially.” It concluded that “substantially” must denote language of magnitude because it describes how much interference can occur. Id. at 13. In this case, the Federal Circuit found that the claims provided at least some guidance as to how much interference will be tolerated because the dependent claims in the ’824 and ’767 patents recited a linkage group that had a particular structure so that the term must allow for at least as much interference as that exhibited by the structure specified in the dependent claims. The Court also observed that the specification provided additional examples of suitable linkage groups and required that the linkage withstand all experimental conditions to which nucleic acid probes were routinely subjected. With respect to hybridization, the Federal Circuit noted that the specification also provided tests for measuring the degree to which a linkage group interferes with hybridization and that the tests results provided in the specification gave guidance as to what constituted acceptable hybridization.
Similarly, with respect to detection, the Court concluded that the intrinsic evidence was such that a person of ordinary skill would understand that a linkage group did not substantially interfere with detection so long as the moiety A could be detected within the level of detection achieved by applicants using the exemplary linkage groups. The Court also took note that the prosecution history contained a declaration identifying eight specific linkage groups that Enzo declared did not substantially interfere with hybridization or detection, and that the PTO found the declaration sufficient to overcome an indefiniteness rejection. Based on all this evidence, the Federal Circuit held that the claims were not indefinite, “even though the construction of the term ‘not interfering substantially’ defines the term without reference to a precise numerical measurement.” Id. at 16. The Court rejected Applera’s argument that because the binding strength of different nucleic acid strands vary based on their length and sequence, the choice of a label would depend on the subjective opinion of a person practicing the invention, noting that, under a given set of experimental conditions, a nucleic acid would have a fixed and measurable profile that could be compared to the examples in the specification to determine whether interference was substantial.
Having held that the claims were definite, the Federal Circuit then considered whether the claims of the ’824, ’767, and ’928 patents were anticipated. As an initial matter, the Court found that Applera had met its burden of establishing a prima facie case of anticipation by providing claim charts showing where each and every claim element was disclosed in the prior art and an expert declaration explaining how the prior art met those limitations under the district court’s claim construction. It then analyzed whether Enzo had raised a genuine issue of material fact with respect to each of the references.
The Federal Circuit held that Enzo had raised a genuine issue of material fact as to anticipation of the claims of the ’824 and ’767 patents by the Kasai reference. Id. at 20. In doing so, the Court found that the declaration provided by Enzo’s expert, when viewed in the light most favorable to Enzo, had provided an explanation that supported that the linkage group taught by the Kasai reference would be expected to substantially interfere with hybridization, thus creating a genuine issue of material fact, despite Applera’s argument that the expert’s opinion was unsupported. The Court was also unwilling to view a declaration filed during prosecution that listed suitable linkage groups as in conflict with Enzo’s expert’s declaration, noting the declarations were consistent, particularly when Enzo’s expert’s declaration was viewed in a light most favorable to Enzo. Further, the Court rejected Applera’s argument that the linkage groups of the prior art were “derived from a primary amine” and so within the “even more preferred embodiments” listed in the specification. Instead, the Court agreed with Enzo that it was reasonable that the “even more preferred embodiments” were a subset of “preferred embodiments” that provided for a carbon-carbon double bond at the alpha position and that were not found in the prior art linkages. Id. at 23. The Court also rejected this argument with respect to the Pingoud reference’s linkage group. The Court pointed out that Enzo’s expert opined that Pingoud reported substantial interference with hybridization and held that Enzo had also raised a genuine issue of material fact as to anticipation of the claims of the ’767 patent by the Pingoud reference.
In contrast, when the Federal Circuit considered whether Enzo had raised a genuine issue of material fact regarding anticipation of the ’928 patent by the Bauman reference, it held that Enzo had not. Id. at 26. Enzo did not dispute that Bauman disclosed a linkage group that does not substantially interfere with the ability of A to be detected or that the ’928 patent is silent as to hybridization. Instead, it argued that Bauman could not anticipate the claims because that reference preformed the hybridization before labeling the nucleic acid. The Court found that because the claims of the ’928 patent recited a product, it was immaterial that Bauman first performed the hybridization and only then attached the linkage group, along with moiety A. Accordingly, the Federal Circuit affirmed the district court’s judgment of anticipation as to the claims of the ’928 patent.
Regarding the later-filed ’830 patent, the Federal Circuit agreed with the district court’s construction of the term “non-radioactive moiety” to mean “a moiety that is utilized in indirect detection, i.e., a moiety that can be detected with a preformed detectable complex.” In reaching its conclusion, the Court looked to the claim language and the specification. Pointing out that claim terms are normally used consistently throughout a patent, the Federal Circuit noted that the term “nonradioactive moiety” appears in multiple independent claims and that, in at least one independent claim, it was clear that a nonradioactive moiety is a moiety that can be detected with a preformed detectable molecular complex. The Court rejected Enzo’s argument that since a dependent claim added a “preformed detectable molecular complex” to independent claim 1, the doctrine of claim differentiation required that the preformed detectable molecular complex must not be present in the independent claim. Instead, it found that the district court’s claim construction did not require that a preformed detectable molecular complex was actually present in claim 1—it only required that the nonradioactive moiety of claim 1 be capable of detection with a preformed molecular complex. The Court also found that the prosecution history tended to undercut Enzo’s position. Since Enzo had stipulated that it could not prove infringement under this claim construction, the Federal Circuit affirmed the judgment of noninfringement.