Claim Construction of DNA-reciting Claims
By Kevin E. Noonan --
The Federal Circuit considered claims to isolated DNA sequences encoding portions of the genome of a porcine circovirus in Intervet Inc. v. Merial Ltd. last week, remanding the case to the District Court based on disagreements with the lower court's construction of three claim terms. The Federal Circuit also took the occasion to opine on the extent of subject matter surrendered by amendment of these claims during prosecution. The greatest interest in the opinion has arisen from the dissent, by Judge Dyk, who sua sponte raised the issue of patent-eligibility for isolated DNA molecules. Although his concern with the decision in AMP v. USPTO seemingly turns the jurisprudential pyramid on its head, discussion of the dissent, and its departures from both factual and legal realities will await a later post.
The case arose as a declaratory judgment action, with Intervet asking the District Court to declare that its porcine vaccines did not infringe the claims of Merial's U.S. Patent No. 6,368,601. Merial's claims were related to particular strains of porcine circovirus that cause postweaning multisystemic wasting syndrome (PMWS), a disease of livestock pigs. While viruses of this type were known in the art (termed "Type I" or "PVS-1" strains in the opinion), none of them were pathogenic. Patentees discovered novel strains of these viruses that were associated with PMWS (termed "Type II" or "PVS-2" in the opinion), and disclosed five separate strains. Samples of all five strains were deposited, and the complete nucleotide sequence of four of them included in the specification. These four strains showed 96% nucleotide sequence "homology" (although as used by the Court this term is equivalent to "sequence identity"), compared with Type 1 strains, to which the Type II strains showed 76% nucleotide sequence identity. The specification also identified thirteen open reading frames (ORFs), nine of which were specific for Type II viruses and four in common between Type I and Type II viruses.
Two groups of claims were at issue in the litigation:
9. A vector comprising an isolated DNA molecule comprising a sequence selected from the group consisting of ORFs 1 to 13 of porcine circovirus type II.
32. An isolated DNA molecule comprising a nucleotide sequence encoding an epitope which is specific to PCV-2 and not specific to PCV-1.
The District Court construed several claim terms, three of which were considered by the Federal Circuit and are germane it its opinion:
• "porcine circovirus type II" was construed as consisting of the five nucleotide sequences that the patentee placed on deposit with the USPTO.
• "ORFs 1-13" were construed as the DNA sequences of the thirteen ORFs of SEQ ID 4 listed in a table under Example 13 of the patent.
• Claim 32 was construed as a whole to be a construct comprising at least one DNA molecule that is unique to one of the five sequences on deposit with the PTO.
Based on this claim construction, the District Court granted summary judgment of noninfringement to Intervet. The Court said it was undisputed that the accused infringing vaccine contained a DNA molecule 99.7% homologous to one of the deposited sequences, and thus, outside the literal scope of the claims, "which required strict identity to one of the five deposited sequences." Merial appealed.
The Federal Circuit reversed the District Court's construction of the first two of these claim terms, in an opinion by Judge Prost and joined by Judge Bryson and Judge Dyk (in part). The Court independently construed the claim term "porcine circovirus type II," which the District Court had limited to the specific deposited sequences. The Federal Circuit began its analysis with reference to the patent specification, which "states that the five deposited strains and listed sequences are 'representative of' a 'type of porcine circovirus,' and thus do not constitute the entire scope of the invention" (emphasis in original). Accordingly, the Court cited Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 967 (Fed. Cir. 2002), and In re Smythe, 480 F.2d 1376, 1383 (C.C.P.A. 1973), for the proposition that a claimed genus can be broader than the species disclosed to represent the genus. (The majority opinion also states in a footnote that it does not reach validity issues not raised by the parties, suggesting that on remand Merial will need to contend with sufficiency of disclosure grounds of invalidity under § 112.) The opinion cites the specification as not disclosing any "quantitative threshold" to distinguish type I and type II strains, stating that the distinction is based on serological similarities and differences as well as pathogenicity, and that "[t]his conclusion comports with the way that viruses are typically classified in the relevant art." According to the opinion, "the pathogenicity and homology patterns are the defining properties of the new type of virus. The claim construction of 'porcine circovirus type II' is therefore properly limited to porcine circoviruses that have these two defining properties."
In view of the disclosure, and the relatedness of the different strains of type II virus disclosed, the Federal Circuit construed the term "porcine circovirus type II" as "a pathogenic pig virus having a circular genome that is at about 96% or more homologous with the four sequences disclosed in the present specification, and about 76% or less homologous with the [Type I] sequence." The opinion states that this claim construction is "not inconsistent with the other descriptive language in the specification."
The Federal Circuit found that the accused infringing vaccines, comprising nucleotide sequences having 99.7% sequence identity, were not entitled to summary judgment of noninfringement in view of its claim construction, and remanded to the District Court for further proceedings based on the panel's interpretation of this claim term.
The Federal Circuit next construed the term "ORFs 1-13," saying this term was also improperly construed by the District Court. In the CAFC's opinion "the court erred in confining the scope of the term to the precise limits of the representative ORFs listed in Example 13, and the exact DNA sequence of SEQ ID 4." Once again, the Court found the claim term to be representative of type II sequences, and thus that the genus was broader than the recited species. In part this was due to explicit disclosure of variation in the ORF sequences in the specification, although the extent of that variation in the specification was described merely as "slight natural variation" that the skilled worker could expect. Salient to the Federal Circuit's determination that the District Court had too narrowly construed this claim term was the observation that "[i]ndeed, limiting the construction of the term to the exact ORF sequences of SEQ ID 4 would even exclude from the claimed ORFs two of the four sequenced strains of PCV-2, the ORF variations for which sequences are expressly disclosed following the table in Example 13." And, the opinion notes, "[w]e have already construed that set of circovirus strains to be broader than just the four sequenced strains, so it would be incongruous to selectively impose the narrower construction here, as the dissent suggests."
The opinion held that "the term ORFs 1-13 is properly construed as 'lengths of translatable DNA between pairs of start and stop codons, corresponding to the 13 ORFs identified in the patent specification,'" reversed summary judgment, and remanded to the District Court for further proceedings based on the Federal Circuit's interpretation of this claim term.
The District Court properly construed claim 32 to mean "an isolated DNA molecule that includes, but is not necessarily limited to, a DNA sequence which codes for an immunodominant region of a protein, wherein the sequence is from the genome of a PCV-2 circovirus, and not from the genome of a PCV-1 circovirus," according to the Federal Circuit's opinion. The District Court found that this claim could read on sequences in common between the two types of PCV, so long as there was at least one nucleic acid that was not in common.
However, the basis for Merial's challenge to the District Court's decision regarding this claim was in how the lower court applied it. The District Court determined that the "from" the genome language "excluded sequences that were physically derived from a non-PCV-2 source." Merial argued that including such a "manufacturing" or process limitation was improper, and the Federal Circuit agreed; in its analysis, the panel focused on the term "specific to," "since it appears that this term is the hook for the requirement that the sequence be unique to and derived from PCV-2."
Merial argued the term "specific to" was a term of art in the immunological arts, referring to the propensity of an antibody to bind an antigen. While the Federal Circuit recognized this specialized meaning, "epitope is thus bound by antibodies that are 'specific to' PCV-2" as recited in the claim. "In light of the patent description and a general understanding of the relevant art," according to the opinion, "the claim would be understood by one of skill in the art to be using the term 'specific to' in a colloquial or non-technical sense."
The Federal Circuit then construed the relevant language of claim 32 as:
[A] nucleotide sequence encoding an epitope that is specific to PCV-2 and not specific to PCV-1, as that term is used in claim 32, is a nucleotide sequence that encodes part of a polypeptide sequence of PCV-2, but not part of a polypeptide sequence of PCV-1. More specifically, it encodes at least one epitope found on the PCV-2 virus, but not found on the PCV-1 virus.
Insofar as the District Court's construction required the encoded epitope to be unique to PCV-2 among all possible antigens, it is in error, according to the opinion, because "[i]f the term 'specific to PCV-2' meant that the epitope must be found only on PCV-2 and no other antigen, then the subsequent limitation 'and not specific to PCV-1' would be redundant."
Turning to the doctrine of equivalents, the Federal Circuit found that the District Court had erred in its application of prosecution history estoppel to limit the extent to which Merial was entitled to rely on the doctrine. "The district court erred . . . in applying controlling Federal Circuit and Supreme Court law to the prosecution history of the '601 patent. As a result, the scope of the district court's bar on Merial's ability to invoke the doctrine of equivalents was overly broad."
What raised the estoppel were amendments to claim 9. As originally draft the claim read:
9. A vector comprising an isolated DNA molecule comprising a sequence selected from the group consisting of ORFs 1-13.
This claim was rejected, on the grounds that while "[t]he ORFs are assumed to be derived from porcine circovirus . . . as written, the claims could encompass ORFs from any organism," specifically the prior art Type I sequences. Although the inventors submitted argument that these ORFs could not be derived from any other organism, being specifically defined by sequence in the specification, they nevertheless amended claim 9 by adding the limitation that the ORFs were "of porcine circovirus type II," which resulted in allowance of the claim.
The opinion found no fault with the District Court's determination that this was a narrowing amendment, and that the amendment was substantially related to patentability. Where the District Court erred, according to the opinion, was in the scope of the resulting estoppel. The proper extent of this estoppel, according to the Federal Circuit, was that:
Merial is thus estopped from arguing that ORFs of pathogenic circoviruses found in other organisms are equivalent to ORFs of PCV-2. It is also estopped from arguing that ORFs of a pathogenic strain of PCV-1 are equivalent to ORFs of PCV-2, despite the strain having strong homology with [Type I virus] and weak homology with the representative strains disclosed in the patent.
However:
Merial is not, however, estopped from arguing that a pathogenic porcine viral sequence with over 99% nucleotide homology with one of the five representative strains is equivalent to that strain. Such a draconian preclusion would be beyond a fair interpretation of what was surrendered.
The opinion directed that on remand the District Court consider the extent to which Merial could show infringement under the doctrine of equivalents.
An analysis of the dissent, both on its "merits" and with regard to recent efforts by groups representing the plaintiffs in the AMP v. USPTO case to influence the makeup of the panel that hears the Federal Circuit appeal, will follow in a later post.
Intervet Inc. v. Merial Ltd. (Fed. Cir. 2010)
Panel: Circuit Judges Bryson, Dyk, and Prost
Opinion by Circuit Judge Prost; opinion concurring-in-part and dissenting-in-part by Circuit Judge Dyk
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