Promega Corp. v. Life Techs. Corp.

• Decision Date: 15 December 2014
• Docket Number: 2013–1376.,Nos. 2013–1011,2013–1029,s. 2013–1011
• Citation: 773 F.3d 1338
• Parties: PROMEGA CORPORATION, Plaintiff–Cross–Appellant, and Max–Planck–Gesellschaft zur Forderung der Wissenschaften E.V., Plaintiff, v. LIFE TECHNOLOGIES CORPORATION, Invitrogen IP Holdings, Inc., and Applied Biosystems, LLC, Defendants–Appellants.
• Court: U.S. Court of Appeals — Federal Circuit

773 F.3d 1338

PROMEGA CORPORATION, Plaintiff–Cross–Appellant,andMax–Planck–Gesellschaft zur Forderung der Wissenschaften E.V., Plaintiff,

v.LIFE TECHNOLOGIES CORPORATION, Invitrogen IP Holdings, Inc., and Applied Biosystems, LLC, Defendants–Appellants.

Nos. 2013–1011, 2013–1029, 2013–1376.

United States Court of Appeals, Federal Circuit.

Dec. 15, 2014.

Seth P. Waxman, Wilmer Cutler Pickering Hale and Dorr LLP, of Washington, DC, argued for plaintiff-cross-appellant. With him on the brief were Thomas G. Saunders and Dina B. Mishra; and Mark C. Fleming, Proshanto Mukherji and Eric F. Fletcher, of Boston, MA. of counsel was Susan R. Podolsky, Law Office of Susan R. Podolsky, of Alexandria, VA.

Edward Reines, Weil, Gotshal & Manges LLP, of Redwood Shores, CA, argued for defendants-appellants. With him on the brief was Derek C. Walter. of counsel on the brief was Carter G. Phillips, Sidley Austin LLP, of Washington, DC.

Before PROST, Chief Judge, MAYER and CHEN, Circuit Judges.

CHEN, Circuit Judge.

Life Technologies, Applied Biosystems, LLC, and Invitrogen IP Holdings, Inc. (collectively, LifeTech) appeal from the district court's grant of a motion for summary judgment that the asserted claims of United States Patent Nos. 5,843,660 ('660 patent), 6,221,598 ('598 patent), 6,479,235 ('235 patent), and 7,008,771 ('771 patent) (collectively, the Promega patents) are not invalid for lack of enablement and obviousness. Promega Corp. and Max–Planck–Gesellschaft zur Förderung der Wissenschaften E.V. (collectively, Promega) appeal from a grant of a motion for judgment as a matter of law (JMOL) that LifeTech's accused products do not infringe either the Promega patents or U.S. Patent No. RE 37,984 (the Tautz patent), a motion that resulted in the vacatur of a jury's verdict of damages and willful infringement. Finally, LifeTech appeals from the district court's oral ruling that it is not licensed for all uses of the asserted patents under a license agreement with Promega (2006 Cross License).

For the reasons discussed herein, we conclude that the asserted claims of the Promega patents are invalid for lack of enablement. We also find substantial evidence that LifeTech is liable for infringement of the Tautz patent under both 35 U.S.C. § 271(a) and 35 U.S.C. § 271(f)(1). Finally, we affirm the district court's finding that the 2006 Cross License does not cover all of LifeTech's sales of the accused products. We therefore reverse the grant of LifeTech's motion for JMOL and remand to the district court for a determination of damages based on LifeTech's infringement of the Tautz patent.

I. Background

DNA is a double-stranded molecule that encodes genetic instructions for living organisms. It consists essentially of two complementary strands of nucleotides. Particular nucleotide sequences may be repeated within a region of a DNA strand. For example, the DNA sequence ATT (adenine-thymine-thymine) may be repeated ten times in a row in a particular location. Such repeating sequences are called “short tandem repeats” (STR), and the region of the DNA strand in which they occur is called an STR “locus.”

STR loci occur frequently in the human genome. The number of repeated sequences within an STR locus varies highly from person to person. For example, one individual's DNA may have eleven ATT repeats at a given STR locus, while another individual may have fourteen at the same locus. These variations are referred to as “alleles,” or markers, of the particular locus. Alleles are responsible for “polymorphism,” or genetic differences between individuals.

No one allele varies enough to differentiate one person from another to a statistically significant degree. A particular set of alleles at multiple loci within an individual's DNA, however, can be used to create a DNA “finger-print” unique to that individual. This method of identification is called “STR profiling” and is useful in many fields, including forensic science.

STR profiling may require making copies of the loci of interest in order to obtain a detectable amount of DNA for analysis. This process is called “amplification,” and can be accomplished with polymerase chain reaction (PCR). In PCR, a pair of “primers” effectively “flanks,” or marks the start and finish of, the locus to be copied. Strands of DNA are then replicated between the primer pair by a DNA polymerase. This process is repeated until a sufficient number of copies of the desired STR locus are generated.

It is highly beneficial to amplify multiple STR loci simultaneously, creating a “multiplex” reaction or a co-amplification. Joint Appendix (J.A.) 1381. Multiplexing, however, is more complicated than performing a series of individual, or “monoplex,” amplifications. J.A. 1371. This is because a successful multiplex reaction depends on the selection of a set of primer pairs for which each primer pair not only flanks its respective target locus, but does not overlap—and thus interfere—with primer pairs for other targeted loci. Id. at 1372.

Identification of STR loci sets and primer pairs that successfully co-amplify is a trial and error process. In the early 1990s—the time of invention of the patents-in-suit—it is undisputed that scientists could not predict with any certainty, absent a preexisting publication or teaching, whether a given set of loci would successfully co-amplify. Id. This was true even when adding a new locus to an already successful multiplex, as skilled artisans could not predict “how the loci would interact with each other or how effectively and efficiently the primers would work in a single reaction [multiplex] environment.” Id. It is also undisputed that the greater the number of STR loci sought to be amplified in a single reaction, the more complicated the process of creating a successful multiplex for that loci set. Id. For example, adding an eighth locus to a seven-loci multiplex (7–plex) was “more complicated” than adding a seventh locus to a six-loci multiplex (6–plex). Id. This was because in order to determine whether the loci would co-amplify successfully, it was necessary to “develop primer pairs that would co-amplify together and not interfere with each other[,] avoid undesirable results such as nonspecific amplification or primer-dimer formation[,] and adjust a number of reaction parameters such as temperature, the number of amplification cycles, and the concentration of primers, enzyme, buffer, dNTP, etc.” Id. at 1372–73.

A. Patents–in–Suit

This case involves five patents that relate to multiplex amplification of STR loci. Promega owns the four Promega patents outright and is the exclusive licensee of the Tautz patent. The Promega patents claim methods or kits for simultaneously determining the alleles present in a set of STR loci from DNA samples, comprising: (a) obtaining a DNA sample; (b) selecting a set of loci of the DNA sample to amplify, including at least the specific loci recited in the claim; (c) co-amplifying the selected loci in a multiplex amplification reaction; and (d) evaluating the amplified alleles to determine the number of STR that are present at each loci. See, e.g., '660 patent, claim 5; '235 patent, claim 1; '598 patent, claim 23; '771 patent, claim 5.

Each of the asserted claims ¹ in the Promega patents includes a limitation that recites the phrase “a set of ... loci” followed by a list of particular STR loci multiplexes of varying complexity, ranging from a 3–plex to a 14–plex. During claim construction, the district court construed the asserted claims with the transitional phrase “a set of ... loci ... consisting of” in the relevant limitation as “limited to products that use no loci other than those listed in the claims” (i.e., “closed loci set” claims), ² and other claims with the transitional phrase “a set of ... loci ... comprising” in the relevant limitation as not so limited (i.e., “open loci set” claims). Promega I, slip op. at 1358–59. Claim 23 of the ' 598 patent is one such claim with an “open loci set” limitation:

23. A kit for simultaneously analyzing short tandem repeat sequences in a set of short tandem repeat loci from one or more DNA samples, comprising:

A single container containing oligonucleotide primers for each locus in a set of short tandem repeat loci which can be co-amplified, comprising HUMCSF1PO, HUMTPOX, and HUMTH01.

'598 patent, 40:22–28 (emphasis added).

This claim recites an STR profiling kit with primers that can successfully co-amplify a set of three specific STR loci. Both parties agree that the claim requires successful co-amplification of every locus in the claimed “a set of ... loci.” Because Promega used the word “comprising” in the “a set of ... loci” limitation, the district court concluded that claim 23 covers not only the three loci recited in the claim, but also any other loci combination containing those three recited loci—whether that combination includes 13, 1,300 or 13,000 STR loci. Promega I, slip op. at 1353. The district court's construction of the “a set of ... loci” limitation in claim 23 and the other asserted claims is not disputed on appeal.

The Tautz patent is likewise directed to a process for examining polymorphism in DNA samples. For example, the Tautz patent claims a kit for testing at least one STR locus that contains: (1) a mixture of primers; (2) a polymerizing enzyme such as Taq polymerase; (3) nucleotides for forming replicated strands of DNA; (4) a buffer solution for the amplification; and (5) control DNA. Claim 42 of the Tautz patent recites:

42. A kit for analyzing polymorphism in at least one locus in a DNA sample, comprising:

a) at least one vessel containing a mixture of primers constituting between 1 and 50 of said primer pairs;

b) a vessel containing a polymerizing enzyme suitable for performing a primer-directed poly-merase chain reaction;

c) a vessel containing the deoxynucleotide tri-phosphates adenosine, guanine, cytosine and thymidine;

d) a vessel containing a...