It has long been a practice in prosecuting a patent application to keep a continuation application pending during the term of any granted patent. This practice is advantageous because it permits the patentee to pursue specific claims in a later-filed application to a competitor's product that falls within the scope of the invention as disclosed in the specification. Of course, this strategy requires that later-filed claims be disclosed in the specification as originally filed to satisfy the enablement and written description requirements of 35 U.S.C. § 112. In re Ruschig, 379 F.2d 990 (CCPA 1967).
These considerations arose in the Federal Circuit's decision in Novozymes v. DuPont Nutrition Biosciences in a patent infringement lawsuit involving modified alpha-amylase enzymes. Alpha-amylases are enzymes produced in microorganisms and higher plants and animals (including man) and catalyze the breakdown of certain polysaccharides. The enzymes are used commercially, inter alia, in detergents, sugar refining, and ethanol production, but as enzymes are sensitive to elevated temperatures and pH extremes. Novozymes' commercial embodiment of this enzyme is obtained from Bacillus licheniformis (BLA) and sold as Termamyl™.
Traditionally, alpha-amylases are stabilized against the deleterious effects of heat and extreme pH by complexing with calcium, which "represents an added cost and often imposes undesirable effects on industrial equipment." In an effort to avoid these costs and undesirable effects, Novozymes "pursued two parallel strategies in attempting to identify promising mutation sites among the approximately 500 amino acids that make up a Bacillus alpha-amylase polypeptide: rational protein design [which attempted to use knowledge and information on the effects of mutations in amino acid sequence on protein structure] and random mutagenesis [which did not]." The priority application of the patent-in-suit at issue in this case disclosed 17 amino acid sequence positions identified by rational design and 16 positions identified by random mutagenesis that were candidates for amino acid changing mutations in two bacterial alpha-amylases: the B. licheniformis species that comprised the company's Termamyl™ product and a species from B. stearothermophilus ("BSG"), as well as five other bacterial alpha-amylase species. As disclosed in the specification of the priority document, these changes could involve substitution of the amino acid at each of these 33 positions with one of the other 19 naturally occurring amino acids, or could involve deletion of the amino acid at that position (a total of 20 possible changes for each of the 33 candidate positions). Accordingly, the total number of variant B. licheniformis species disclosed generically in the priority document amounted to about 8.6 x 1042. In fact, the specification of the priority document provided but two specific examples with actual experimental data. However, many of the substitutions were found not to provide variant alpha-amylase enzymes having "improved stability at 'high temperatures (i.e., 70-120°C.) and/or extreme pH (i.e., low or high pH, i.e., pH 4-6 or pH 8-11), in particular at free (i.e., unbound, therefore in solution) calcium concentrations below 60 ppm.'"
DuPont's accused product was a B. stearotherophilus variant species having an amino acid sequence change at position 239 from a serine to a glutamic acid (abbreviated "S239Q"). As noted in the Federal Circuit opinion, "DuPont produced approximately 1,500 alpha-amylase variants with substitutions covering 150 of the 515 amino acid positions in the parent BSG enzyme. . . . DuPont then screened its panel of 1,500 variants for increased thermostability under low-calcium conditions and identified a variant substituted at position 239 [the S239Q variant] as the best performer."
In response, Novozymes filed a continuation application that resulted in the patent-in-suit, U.S. Patent No. 7,713,723; claim 1 is representative:
1. An isolated variant of a parent alpha-amylase, wherein:
(a) the variant has at least 90% sequence identity to SEQ ID NO: 6 [BSG alpha-amylase],
(b) the variant comprises a substitution of serine at position 239 relative to the parent alpha- amylase, using the amino acid sequence of SEQ ID NO: 8 [BLA alpha-amylase] for determining position numbering, and
(c) the variant has increased thermostability relative to the parent alpha-amylase, wherein thermostability is determined at pH 4.5, 90° C. and 5 ppm calcium and has alpha-amylase activity
(emphasis in opinion).
The District Court granted summary judgment of infringement against DuPont and denied DuPont's summary judgment motion of invalidity under 35 U.S.C. § 112 for failure to satisfy the written description requirement, based on there being disputed issues of fact. (The Court also denied Novozymes' preliminary injunction motion on the grounds that there was considerable question of whether Novozymes would prevail on the merits in view of DuPont's invalidity challenge.) The Court submitted to the jury the question of whether the claims were invalid under 35 U.S.C. § 112 for failure to satisfy the enablement or written description requirements, and the jury found (using a special verdict form) that the claims were not invalid, awarding Novozymes a judgment of more than $18 million. The Court granted DuPont's JMOL motion, on the grounds that the specification did not provide an adequate written description of the invention as claimed, relying on both Federal Circuit and CCPA precedent including Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353 (Fed. Cir. 2011); Billups-Rothenberg, 642 F.3d 1031, 1036 (Fed. Cir. 2011); Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004); Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320 (Fed. Cir. 2000); In re Ruschig, 379 F.2d 990 (CCPA 1967).
The Federal Circuit affirmed, in an opinion by Judge Schall joined by Judge Bryson, with Chief Judge Rader dissenting. The majority opinion rejected Novozymes' contentions that any deficiencies in the disclosure in its specification was ameliorated by the general understanding, knowledge and skill in the art, citing Snitzer v. Etzel, 465 F.2d 899 (CCPA 1972), and Union Oil Co. of California v. Atlantic Richfield Co., 208 F.3d 989 (Fed. Cir. 2000). DuPont, in contrast, relied on In re Ruschig, arguing successfully that Novozymes' disclosure amounted to nothing more than an "invitation to experiment," and unsuccessfully at that, pointing out that Novozymes' "application fails to disclose a single alpha- amylase variant substituted at position 239 that actually exhibits increased thermostability, noting that the only disclosed substitution at that position (S239W) disclosed in the 2000 application does not work as required by the '723 patent's claims."
The majority stated its holding expressly: "no reasonable jury could find that the claims of the '723 patent meet the written description requirement of § 112, ¶ 1, and that the district court therefore correctly entered judgment as a matter of law invalidating those claims." The opinion contrasts the specificity of the claims with the generic disclosure of the specification, noting that Novozymes provided only "generalized guidance listing several variables that might, in some combination, lead to a useful result." This determination was mandated by "[n]umerous prior decisions" from both the CCPA and the Federal Circuit, citing most of the canonical precedent including In re Ruschig, Boston Scientific Corp. v. Johnson & Johnson, Univ. of Rochester v. G.D. Searle & Co., and distinguishing Snitzer v. Etzel and Union Oil Co. of California v. Atlantic Richfield Co. In the Snitzer case, the majority noted that each provided disclosure of a small number of distinctly recited species, in stark contrast to the overwhelming number of species falling within the ambit of the '723 patent specification, while in the Union Oil case the specification "defined the claimed gasoline compositions in terms of various chemical and physical properties" and that "ordinarily skilled petroleum refiners would immediately appreciate that the qualitative chemical properties recited in the claims translated to specific, manifest compositions that would yield those properties."
The majority expressly found that the '723 specification, and the disclosure of the priority document, "contains no disclosure of any variant that actually satisfies the claims, nor is there anything to suggest that Novozymes actually possessed such a variant at the time of filing." While the opinion recognizes distinctions between Novozymes' specification and the deficiencies in the specifications in the authorities it cites to support their opinion, "[o]n closer inspection these 'analogies fall flat.'" "Taking each claim -- as we must -- as an integrated whole rather than as a collection of independent limitations, one searches the ['723 priority] application in vain for the disclosure of even a single species that falls within the claims or for any 'blaze marks' that would lead an ordinarily skilled investigator toward such a species among a slew of competing possibilities," according to the opinion, and "working backwards" from the claims (and the accused product) impermissibly "seeks to derive written description support from an amalgam of disclosures plucked selectively from the 2000 application." Even Novozymes' expert agreed with DuPont that "one could not know which, if any, individual substitutions at any of the seventeen sites selected by rational protein design would yield increased thermostability without actually making and testing the variants," and it was evident that the '723 specification and its priority document did not disclose the specifically claimed thermostable variant. Further:
In this case, to actually possess the variant enzymes claimed in the '723 patent would have required Novozymes to confirm its predictions by actually making and testing individual variants or at least identifying subclasses of variants that could be expected to possess the claimed properties, which it did not do before filing the ['723 priority] application. At best, the ['723 priority] application describes a roadmap for producing candidate alpha-amylase variants and then determining which might exhibit enhanced thermostability. A patent, however, "is not a reward for the search, but compensation for its successful conclusion." Ariad [Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010) (en banc)] (quoting University of Rochester, 358 F.3d at 930 n.10). For that reason, the written description requirement prohibits a patentee from "leaving it to the . . . industry to complete an unfinished invention." Id.
Chief Judge Rader dissented. While his continued dissatisfaction with the written description requirement was evident ("[a]lthough a separate written description requirement, and the vague notion of "possession" that it embodies, still troubles me"), his dissent does not trod that old ground of disagreement with his brethren. Instead, the Chief Judge contends that, having established a separate written description requirement it is a question of fact, and the jury deserves deference to its factual determinations that should not lightly be overturned by JMOL. On the facts in this case, Chief Judge Rader finds substantial evidence (including expert testimony, the weight and persuasiveness being particularly within a jury's purview) supporting the jury's verdict and thus would let it stand:
[T]he jury received expert testimony, heard from skilled protein engineers, reviewed visual aids and publication excerpts, and examined the patent document as guided by those skilled in the art, over an eight day trial. The jury was given a special verdict form asking whether DuPont had proven by clear and convincing evidence that the claims at issue were invalid for lack of written description. . . . The jury answered in favor of Novozymes, and substantial evidence supports this determination.
Novozymes A/S v. DuPont Nutrition Biosciences APS (Fed. Cir. 2013)
Panel: Chief Judge Rader and Circuit Judges Schall and Bryson
Opinion by Circuit Judge Schall; dissenting opinion by Chief Judge Rader