In Invitrogen Corporation v. Clontech Laboratories, Inc., Fed. Cir. 04-1039, -1040 (November 18, 2005), the CAFC vacated an invalidity judgment and the district court’s conception ruling based on anticipation by § 102(g)(2) prior art where the inventors could not appreciate the discovery they made.

Invitrogen appealed from a decision by the United States District Court for the District of Maryland, invalidating two hundred and twenty-one claims, in three related Invitrogen patents, as anticipated by § 102(g)(2) prior art. The invalidity was based on the district court’s underlying ruling that researchers at Columbia University conceived of a similar invention before, and were diligent in reducing it to practice after, Invitrogen’s first reduction to practice in 1987. On appeal, Invitrogen challenged the district court’s partial summary judgment dating conception by the Columbia researchers. On cross-appeal Clontech challenged three underlying partial summary judgments in favor of Invitrogen: (1) that the claims-in-suit are enabled; (2) that the claims-in-suit satisfy the § 112 written description requirement; and (3) that Clontech’s products literally infringe claims 3, 4, 12, and 13 of U.S. Patent No. 6,063,608.

The patents involved in the suit were owned by Invitrogen: U.S. Patent No. 5,244,797 (“the ‘797 patent”), U.S. Patent No. 5,688,005 (“the ‘005 patent”), and U.S. Patent No. 6,063,608 (“the ‘608 patent”). The appeal involved the ‘797 patent, claims 1-4; the ‘005 patent, claims 8-29; and the ‘608 patent, claims 1-196. All three patents issued from continuations of a common parent application, No. 07/143,396 (“the ‘396 application”), filed on January 13, 1988, and share a common written description.

The patents disclose a genetically modified enzyme, reverse transcriptase, involved in DNA replication. Reverse transcriptase (“RT”) is a naturally occurring enzyme produced by retroviruses, such as the Moloney-Murine Leukemia Virus (“MMLV”). Invitrogen’s genetic modifications affect how the modified RT participates in DNA replication. DNA replication involves a series of discrete steps. The original DNA, a molecule comprised of two strands of nucleotides forming a double helix, is opened to expose single strands. Messenger RNA (“mRNA”), comprising a single strand of nucleotides, forms opposite the exposed DNA strands. The mRNA detaches from the exposed DNA and serves as a template against which a first strand of complementary DNA (“cDNA”) forms. This is first strand synthesis. The mRNA detaches from the first cDNA strand, allowing a second, complementary DNA strand to form opposite the first strand, completing the process. This is second strand synthesis. The completed cDNA molecule is a copy of the original DNA transcribed by the mRNA. “Reverse transcription” describes building the cDNA from the mRNA template.

Reverse transcriptase affects at least two steps in this process. First, it facilitates the formation of cDNA opposite the mRNA template, a step called DNA polymerase activity. Second, it degrades the mRNA strand of the mRNA / cDNA hybrid molecule so that the first strand cDNA nucleotides are free to form a second strand and complete the DNA replication. Degrading or destroying the mRNA template is called RNase H activity. Until the mRNA template is removed from the first strand cDNA, the second strand cDNA synthesis cannot occur.

If RNase H activity destroys the mRNA template, as happens with naturally occurring RT, then it cannot serve as a template for additional cDNA. But if the RNase H activity of RT is inhibited, and the mRNA is detached from the hybrid mRNA / cDNA first strand without being destroyed, then scientists can reuse the mRNA to form additional cDNA. An RT with inhibited RNase H behavior is useful for efficiently cloning DNA. As described and claimed in the patents, Invitrogen developed mutant RT with DNA polymerase, but no RNase H, activity (“RNase H minus”). More particularly, Invitrogen altered a gene that originally encoded wild or natural RT, resulting in a mutant enzyme with the desired properties. Invitrogen reduced this invention to practice on January 27, 1987.

Beginning in the early 1980s two scientists at Columbia University, Dr. Stephen P. Goff and his post-doctoral researcher, Dr. Naoko Tanese, studied the effects of random mutations in the MMLV gene for RT – an approach called “random mutagenesis.” In 1984, Tanese prepared a panel of roughly 100 mutants. Without sequencing the mutants, Goff did not know where the MMLV gene had been altered in each mutation. Two mutant genes created in 1984 were H7 and H8, each encoding enzymes that later proved to lack RNase H activity. After creating the mutant MMLV genes, Tanese tested the mutant RT they encoded for DNA polymerase activity. Roth tested the mutant RT for a different function called integrase. In late 1984, Tanese also tested the mutant RT for RNase H activity. But the tests using 1984 assay technology yielded inconclusive results. The mutant RT under investigation was produced in E. coli bacteria, which naturally produces an enzyme with RNase H activity. The RNase H activity of the bacterial enzyme introduced too much background noise to measure, with existing methods, the RNase H behavior of the mutant RT.

The 1984 assay technology could have been used to measure the mutant RT RNase H activity if Goff and Tanese first purified the mutant RT for each mutant MMLV gene – that is, if they had they isolated the mutant RT from the background E. coli enzymes. Goff concluded that approach was too time consuming for the large number of mutant MMLV at issue, so he and Tanese developed a new in situ assay. That new assay was designed to measure the RNase H activity of the mutant RT without first isolating it from the bacterial enzymes. Not until March 1987, however, did Goff and Tanese complete the new assay and apply it to their panel of mutants. Nonetheless, in 1986, before finishing the new assay, Goff sequenced various mutant RT genes. Among those he sequenced were H7 and H8. When Goff and Tanese completed the new in situ assay in March 1987, they rapidly determined which parts of the MMLV RT gene affected which enzyme properties. By March 7, 1987, they established that H7 and H8 encoded mutant RT with DNA polymerase activity but no RNase H activity.

Goff and Tanese started publishing their work after March 1987. On January 29, 1988, Goff filed a patent application pertaining to this research. In 1993 the U.S. Patent and Trademark Office (“PTO”) declared an interference between Goff’s application and the ‘260 application that eventually issued as Invitrogen’s ‘005 patent. (October 18, 1993 notice of interference from PTO). The sole count described a method for producing a genetically modified RT with DNA polymerase but “having substantially no RNase H activity.” Goff’s assignee, Columbia University, defaulted and the PTO ruled in Invitrogen’s favor. As a result, the PTO never reviewed Goff’s research records to determine priority of invention between Goff and Invitrogen.

The district court determined that Goff et al. invented a mutant [RT] enzyme that did not have RNase H activity. The enzyme was prepared in December 1984, and its reduction to practice was confirmed in March 1987. The Court has also found that Goff was diligent and that he did not abandon, suppress or conceal his invention. Goff’s work is available as prior art as of December 1984. On October 17, 2003, the district court entered final judgment in both actions, invalidating several claims under § 102(g)(2) in view of Goff: (a) ‘797 patent, claims 1-4; (b) ‘005 patent, claims 8-29; and (c) ‘608 patent, claims 1-196.

Conception requires the “definite and permanent idea of the complete and operative invention” for conception, require more than unrecognized accidental creation. “[A]n accidental and unappreciated duplication of an invention does not defeat the patent right of one who, though later in time, was the first to recognize that which constitutes the inventive subject matter.” Silvestri v. Grant, 496 F.2d 593, 597 (CCPA 1974). Thus, “[t]he date of conception of a prior inventor’s invention is the date the inventor first appreciated the fact of what he made.” In other words, conception requires that the inventor appreciate that which he has invented.

The invalidity judgment depends on when Goff appreciated that H7 and H8 were RNase H minus, but retained DNA polymerase activity.7 Invitrogen contends that the district court misread the facts and misapplied the law to award Goff priority of invention. Under a correct application of law, Invitrogen argues, Goff did not conceive of the invention until March 1987, when he perfected his in situ assay and established that the H7 and H8 mutants were RNase H minus. Invitrogen contended that until that moment, Goff never recognized that his accidental creations, the H7 and H8 mutants, had the inventive features at issue. Clontech disagrees, and asked the court to affirm the district court’s ruling.

With unrecognized accidental duplication, the invention exists but remains unrecognized. The priority determination requires evidence that the inventor actually first made the invention, and that he understood his creation to have the features that, comprise the inventive subject matter at bar. Thus, the court must identify when, during an emerging recognition that a particular invention includes something new, the inventor’s understanding reaches the level needed for appreciation.

The court held that:

As a matter of law, the court’s conclusion is unsustainable. Langer and Silvestri require some connection between the physical result (the invention) and the belief (by the inventor). Here, the district court never identified corroborating evidence of Goff’s purported belief, nor identified how it could determine that Goff had reviewed such evidence and understood its import. There is no evidence that merely sequencing the mutant RT gene could, in 1986, establish the corresponding enzyme’s properties.

More fundamentally, the record is inconsistent with the district court’s notion that Goff set out to create RNase H minus RT, or that he recognized his invention in 1984. It shows, instead, that this action fits squarely within the unrecognized, accidental duplication cases. First, Goff’s research was general in nature. The random mutagenesis involved a panel of 100 randomly mutated MMLV RT genes. At his deposition, Goff testified that Tanese’s 1984 experiments “[were] focused on understanding what the consequences of those mutations were for the virus.” He explained that his “main grant and the main focus of [his] whole lab was to look at the [MMLV] mutants . . . and to look at the [effects] of those mutations on the virus.” Second, it was unknown at the time whether it was even possible to make an RNase H minus RT with DNA polymerase activity. Not until his March 1987 assay, Goff explained, had anyone shown that RNase H activity involved a separate area of the RT gene from the sequence responsible for DNA polymerase. The publications at the time were conflicting, and it was unclear “whether it would be possible to express [the two functions] separately because there are many multi function enzymes, but frequently [their] multiple activities are interconnected so intimately, that [it is] very hard to separate them.” Finally, asked to identify the time when he “decided” to create an RNase H minus mutant RT, Goff testified that “the belief was that we had them, but I didn’t know how to characterize them. I mean, it wasn’t that we wanted one. There was no reason to have one in our minds.” (emphasis added) Even assuming the district court had assessed an objective basis for appreciation – which it did not – on these facts the partial summary judgment of conception for Clontech is unsustainable.

* * *

In sum, the district court erred in granting judgment of invalidity under § 102(g)(2). Clontech’s challenges to the court’s partial summary judgments on written description and enablement are misplaced and fail to support the invalidity judgment. Accordingly, the court vacates the judgment of invalidity and the conception ruling on partial summary judgment, and remands for further proceedings.

On remand, we remind the district court that the material factual dispute we perceive regarding appreciation affects not only the proper date of conception, but also the date of reduction to practice. “It is now well settled that in [an accidental creation] there is no conception or reduction to practice where there has been no recognition or appreciation of the existence of the new form.” Silvestri, 496 F.2d at 597. Because we reserve the question of appreciation for the jury, its determination on this issue will decide the date of conception (as well as reduction to practice). IV. Finally, Clontech cross-appeals the district court’s partial summary judgment that the PowerScript RT infringes claims 3, 4, 12, and 13 of the ‘608 patent.

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