Opinion ID: 781031
Heading Depth: 2
Heading Rank: 3

Heading: Incubating ... until CPE is observed

Text: 33 Claims 1 and 2 require, after a sheet of simian cells has been inoculated with a viral sample, that the cell sheet be incubated at a defined temperature range until CPE is observed, that is, until viral growth manifests itself in an observable perturbation of the cultured cells. The dispute over construction of this limitation is whether it defines only the minimum period for which the cells must be incubated, or whether it also establishes an ending point beyond which incubation is not permitted. Before the district court, Boehringer argued that this term requires that the incubation period continue long enough for CPE to be observed, but that the process need not be stopped immediately after the first observation. Boehringer, 984 F.Supp. at 252. That is, under Boehringer's interpretation, all the claim requires is that incubation continue at least up to the point where some degree of CPE is observed. Schering, however, argued that until CPE is observed means that the incubation is stopped immediately upon first observation of CPE, and any incubation that continues longer does not infringe. Schering would presumably escape infringement under such a construction, even under the doctrine of equivalents, because Schering's timed incubation continues well past the point at which CPE first becomes observable. 34 The district court agreed with Schering that until CPE is observed requires the incubation period to stop upon observation of CPE. Drawing an analogy to a recipe for cooking a turkey, the court reasoned that an instruction such as cook the turkey until the skin is browned necessarily implies that the cook should stop once the skin is browned; else the turkey would be singed and blackened rather than browned. Id. Likewise, the court concluded that an instruction to incubate the cell sheet until CPE is observed requires that incubation be stopped once CPE is observed. 35 The district court recognized, however, that in the embodiments disclosed in the specification, incubation does not halt immediately upon the first observation of CPE, but rather continues until good or 50-60% CPE is observed. See, e.g., '778 patent col. 3, ll. 46-48; col. 6, ll. 28-30. To avoid a claim interpretation inconsistent with these embodiments, the district court interpolated the word significant into the claim: incubation must proceed until there is a significant degree of CPE. Boehringer, 984 F.Supp. at 253 (emphasis added). While this claim construction precluded Boehringer from establishing literal infringement, because Schering incubates its cells for a defined period of time rather than until a particular level of CPE is observed, it left open the possibility that Schering's timing mechanism could meet this limitation by the doctrine of equivalents. Boehringer, 6 F.Supp.2d at 331-32. 36 We think the untenability of the district court's claim construction is exposed by the court's need to interpolate significant into the claim to save its construction. While incubation must be stopped at some point to recover the virus for subsequent passages, and undoubtedly the yield of viral recovery may be optimized by stopping the incubation at a particular point, the claim does not include any language or limitation relating to degree of viral recovery (if any). The claim retains its utility even if incubation is continued past the point of significant CPE or good viral recovery. Rather than insert an additional limitation into the claim, the better course is to rely on a construction of until ... CPE is observed that does not require such an interpolation. We hold that this limitation merely defines the minimum period for incubation of the inoculated cell sheet. 37 Boehringer argues correctly that because the claim language is open, employing the preamble term comprising, the claimed method is open to additional steps. Thus, while the claim requires a minimal incubation time proceeding until the observation of CPE, additional periods of incubation after that point are not excluded. To use the district court's meleagrine analogy, one may add an additional step to the recipe: continuing to cook the turkey until the skin is burned to a crisp. Such an additional step is permissible from the structure of the open claim language, and the district court's rejection of such a step was based on the premise that the claim's object is defeated if cooking proceeds too long. Because the utility of claim 1 is not premised on a particular stopping point, there is no barrier to additional incubation periods. 38 This error, the only one we find in the district court's thorough and skillful management of this case, was nonetheless harmless. As we explain below, substantial evidence supports the jury's finding that Schering's process satisfies this claim limitation under the doctrine of equivalents, even under an overly narrow claim construction. The question of whether Schering's process would literally infringe under the correct claim construction need not be resolved. II 39 A finding of literal infringement having been precluded by the district court's construction of the claim limitations until ... CPE is observed and ATCC-VR2332, see Boehringer, 6 F.Supp.2d at 331, the question of infringement under the doctrine of equivalents was presented to the jury. The jury was asked to render verdicts on the following two questions: 40 Did Boehringer prove by a preponderance of the evidence that the swine infertility and respiratory syndrome virus, ATCC-VR2525, as used in Schering's process for the production of its PrimePac® vaccines is equivalent to the swine infertility and respiratory syndrome virus, ATCC-VR2332 as used in Claim 2 of the '778 Patent? 41 Did Boehringer prove by a preponderance of the evidence that the incubation period of 72 hours +/6 hours as used in Schering's process for the production of its PrimePac® vaccines is equivalent to the timing device of until CPE is observed as used in Claim 2 of the '778 Patent? 42 The jury answered yes to both questions, and the district court denied Schering's renewed motion for judgment as a matter of law to overturn these verdicts. Boehringer, 166 F.Supp.2d at 31-36. Schering, proposing that no reasonable jury could have answered both questions in the affirmative, asks us to reverse the district court's denial. 43 We review a district court's denial of a motion for JMOL de novo by reapplying the JMOL standard. Cybor, 138 F.3d at 1454, 46 USPQ2d at 1172. We will reverse the district court's denial only if the jury's factual findings are not supported by substantial evidence, or if the legal conclusions implied in the jury's verdict cannot be supported by that evidence. Id. Moreover, in scrutinizing the evidence for support for the jury's findings, we must draw all reasonable inferences in favor of the nonmoving party (here Boehringer), and while our review is of the record as a whole, we must disregard all evidence favorable to the moving party that the jury was not required to believe. Reeves v. Sanderson Plumbing Prods., Inc., 530 U.S. 133, 150-51, 120 S.Ct. 2097, 147 L.Ed.2d 105 (2000). A. The ATCC-VR-2332 limitation 44 Under the doctrine of equivalents, a claim limitation not literally met may be satisfied by an element of the accused product if the differences between the two are insubstantial to one of ordinary skill in the art. Warner-Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520 U.S. 17, 40, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997); Eagle Comtronics v. Arrow Communication Labs., Inc., 305 F.3d 1303, 1315, 64 USPQ2d 1481, 1488 (Fed. Cir.2002). While no particular linguistic framework controls the inquiry, Warner-Jenkinson, 520 U.S. at 39-40, 117 S.Ct. 1040, the insubstantial differences inquiry may be guided by determining whether the element in the accused device performs substantially the same function in substantially the same way to obtain the same result as the claim limitation. Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608, 70 S.Ct. 854, 94 L.Ed. 1097 (1950); Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 813, 62 USPQ2d 1781, 1785 (Fed. Cir.2002). Schering argues on appeal that regardless of which framework is employed, no reasonable jury could find that Schering's VR2525 virus is equivalent to the ATCC-VR2332 viral strain recited by the claim in suit. 45 Under the function-way-result analysis, Schering focuses on the fact that ATCC-VR2332 is a pathogenic virus, causing PRRS, while VR2525 is not. Schering argues that this distinction precludes a finding of equivalence, because Schering's virus generates a protective immune response when administered to pigs, while a pig inoculated with ATCC-VR2332 develops PRRS. Thus, when administered to pigs, VR2525 resembles ATCC-VR2332 in neither function, way, nor result. Schering's argument, however, flies in the face of the basic principle that the relevant analysis is of the role played by each element in the context of the specific patent claim, Warner-Jenkinson, 520 U.S. at 40, 117 S.Ct. 1040, not whether the accused element is capable of performing different roles than the claim element in other contexts. As we have refused Schering's suggestion to add a separate disease-causing limitation to the claim in suit, what happens when the virus is administered to a pig is irrelevant to the assessment of whether the two viral strains are equivalent in the in vitro culture method defined by claim 2. The jury was presented with expert testimony from which it could conclude that VR2525 plays the same role as VR2332 in performance of the claimed method. The fact that, in other contexts, VR2525 can perform other functions in different ways to yield a different result is not relevant. 46 Schering likewise relies on properties of VR2525 that are largely irrelevant to the claim in suit in an attempt to show that no reasonable jury could find that VR2525 lacks substantial differences from the ATCC-VR2332 strain recited by the claim. Schering highlights the fact that ATCC-VR2332 makes pigs ill while VR2525 does not, the fact that VR2525 does not react with a particular monoclonal antibody reactive against ATCC-VR2332, and the fact that VR2525 grows poorly in pig lung macrophages while ATCC-VR2332 grows well. But these facts are simply not relevant to the equivalence inquiry because those properties of the virus are not pertinent to a method of growing and isolating the virus as defined by claim 2. 47 Schering's argument based on Hill-Rom Co. v. Kinetic Concepts, Inc., 209 F.3d 1337, 54 USPQ2d 1437 (Fed.Cir.2000), is inapposite. In Hill-Rom, the patentee tried to argue that an element in an accused hospital bed still met the claim limitation cushion, even though the accused element did not provide support or comfort to the patient. Although the claim did not recite such functions for the cushion, we affirmed the district court's finding of no equivalence because the term cushion (as construed by the court) carries with it certain functional features as a matter of the definition of the term. Id. at 1343, 54 USPQ2d at 1442. While the cushion in a hospital bed must provide support and comfort to the patient, the properties possessed by ATCC-VR2332 but lacking in VR2525 — the ability to cause disease in pigs or grow in pig alveolar macrophages-are entirely optional for a method of growing and isolating a PRRS virus, unless the limitation disease-causing is imported into the claim. 48 Schering further argues that a finding of no substantial differences is precluded by the evidence that there are at least 73 nucleotide differences between VR2525 and ATCC-VR2332 in a particular region of their RNA genomes. Schering's expert (as well as Boehringer's) noted that even a single nucleotide substitution can have a substantial effect on viral function. Schering proposes that in the face of this evidence, no reasonable jury could have concluded that two viruses having at least 73 nucleotide divergences lack substantial differences. 49 However, the uncontroversial fact that even a single nucleotide or amino acid substitution may drastically alter the function of a gene or protein is not evidence of anything at all. The mere possibility that a single mutation could affect biological function cannot as a matter of law preclude an assertion of equivalence, and Schering made no showing that any of these substitutions actually affected any property of the virus relevant to the claim at hand. While it may be reasonable to assume that genetic similarity is a relevant comparison between the viruses for purposes of the claimed method, the jury was presented with expert testimony that the two viral genomes are highly similar overall and that any differences between the two are insignificant. A reasonable jury could easily rely on this testimony to conclude that the genetic differences between VR2525 and ATCC-VR2332 are insubstantial in the context of the claimed method. 50 Schering's last attempts to stave off the jury's finding of equivalence rely on prosecution history estoppel. These attempts are unavailing. Schering first argues that because Boehringer's claims to vaccines and methods of immunization were rejected by the Patent Office, Schering's virus, useful as a vaccine, cannot be reached under the doctrine of equivalents. But a patentee is not estopped from establishing infringement under the doctrine of equivalents merely because an accused infringer improves upon the claimed invention. Schering's virus may have many useful properties that ATCC-VR2332 does not, properties that Boehringer was not entitled to claim. Schering's virus does not cease to infringe on account of those properties. 51 Schering further asserts that Boehringer's original claims encompassing all zoo-pathogenic mutants of ATCC-VR2332 were rejected during prosecution, 2 thus placing zoopathogenic (disease-causing) mutants beyond the patent's reach. But Schering has lost no opportunity to press upon us that its virus is not zoopathogenic, and we decline to speculate whether, as Schering contends, an alleged surrender of zoopathogenic mutants also includes, a fortiori, a surrender of nonzoopathogenic mutants. 52 Even under a more searching review of the factual basis for the findings of equivalence, we would conclude that Boehringer's evidence suffices to carry the burden of establishing infringement by a preponderance of the evidence. The district court correctly concluded that the jury's verdicts on equivalence for this limitation of the claim were supported by substantial evidence, and we affirm the district court's denial of Schering's motion for JMOL. 53 B. The incubating ... until CPE is observed limitation 54 Schering's challenge to the finding of equivalence to the incubating ... until CPE is observed limitation is also based in part on its construction of the term isolating. Schering, relying on Applied Materials, Inc. v. Advanced Semiconductor Materials America, Inc., 98 F.3d 1563, 40 USPQ2d 1481 (Fed.Cir.1996), asserts that because the purpose of observing CPE is only to confirm that a virus is present in a sample from a natural source, Schering's accused process, lacking such a purpose, cannot infringe under the doctrine of equivalents. Even under Schering's preferred claim construction (and assuming such a purpose is present in the claim), Schering's argument would seem to be belied by its own vaccine production instructions, which require that CPE be monitored for the purpose of confirming viral growth. Regardless, Schering's argument cannot stand in light of our affirmance of the district court's construction of isolating. 55 With respect to the until ... CPE is observed limitation, we have no doubt that substantial evidence supports the jury's finding of equivalence, even under the district court's overly narrow construction. Aside from the documentary evidence suggesting that Schering actually observes and records the degree of CPE during its production process, although perhaps not as a cue to terminate the incubation, the jury was presented with expert testimony that Schering's practice of incubating the viral culture for a defined period of time performs the same function, in the same way, with the same result, as incubating the viral culture until a defined degree of CPE is observed. Schering ignores this testimony entirely, except to note that Boehringer's expert did not personally witness one of Schering's production runs. This fact being irrelevant to the determination of equivalence in this case, the jury was well-entitled to rely on this testimony and render a verdict that Schering's process satisfied the incubating ... until CPE is observed limitation under the doctrine of equivalents. The district court properly denied Schering's motion for JMOL on these grounds. III 56 The question of obviousness was also submitted to the jury, which returned a verdict that Schering had not proven by clear and convincing evidence that the '778 patent was invalid under 35 U.S.C. § 103. Schering again challenges the district court's denial of its motion for JMOL. Obviousness is a question of law based on underlying factual determinations. Loctite Corp. v. Ultraseal Ltd., 781 F.2d 861, 872, 228 USPQ 90, 97 (Fed.Cir.1985). However, because obviousness, like any other ground of invalidity, must be established by clear and convincing evidence, id., Schering's burden on appeal is doubly high: it must show that no reasonable jury could have failed to conclude that Schering's case had been established by clear and convincing evidence. 57 We conclude that Schering has not met that heavy burden. The case for obviousness rests on a number of prior art references describing the use of MA-104 monkey kidney cells for growing and isolating other animal viruses (including at least one porcine virus), and two references (Dea and Van Alstine) describing attempts to recover the Mystery Swine Disease agent by inoculating cell lines, including monkey kidney cell lines, with tissue homogenates from infected herds. 58 A showing of obviousness requires a motivation or suggestion to combine or modify prior art references, coupled with a reasonable expectation of success, see Brown & Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 1124-25, 56 USPQ2d 1456, 1459 (Fed.Cir.2000), and the jury was entitled to conclude that such a showing had not been made. In particular, Schering cannot escape the fact that both Dea and Van Alstine do more than suggest that PRRS viruses could be isolated with monkey kidney cells: they report failure of such attempts. Dea reported the isolation of a different virus, encephalomyocarditis virus (EMCV), by using adult monkey kidney (Vero) cells, and suggested that EMCV might be the agent responsible for PRRS outbreaks in Quebec. Even more tellingly, Van Alstine cultured homogenates from infected herds on eight different cell lines, including the MA-104 embryonic monkey kidney cells recited by claim 2. But Van Alstine reported only the isolation of parvovirus and swine influenza virus (SIV), and put forth SIV as one of the prime suspects for at least one of the causes of Mystery Pig Disease. Neither Dea nor Van Alstine succeeded in isolating a PRRS virus with monkey kidney cells. 59 While absolute certainty is not necessary to establish a reasonable expectation of success, In re O'Farrell, 853 F.2d 894, 903-04, 7 USPQ2d 1673, 1681 (Fed. Cir.1988), there can be little better evidence negating an expectation of success than actual reports of failure. See, e.g., In re Rinehart, 531 F.2d 1048, 1053-54, 189 USPQ 143, 148-49 (CCPA 1976). A reasonable jury could conclude from these reports that one of ordinary skill in the art would not have had a reasonable expectation of success in attempting to isolate the PRRS virus on MA-104 cells at the time the invention was made. Consequently, the district court did not err by denying Schering's motion for JMOL on the issue of obviousness.