Carnegie Mellon University v. Hoffmann-La Roche

• Decision Date: 08 September 2008
• Docket Number: No. 2007-1267.,No. 2007-1266.,2007-1266.,2007-1267.
• Citation: 541 F.3d 1115
• Parties: CARNEGIE MELLON UNIVERSITY and Three Rivers Biologicals, Inc., Plaintiffs-Appellants, v. HOFFMANN-LA ROCHE INC., Roche Molecular Systems, Inc., Roche Diagnostic Systems, Inc., Roche Biomedical Laboratories, Inc., The Perkin-Elmer Corporation, and Laboratory Corporation of America Holdings, Defendants-Appellees. Carnegie Mellon University, Plaintiff-Appellant, v. Hoffmann-La Roche Inc., Roche Molecular Systems, Inc., Roche Diagnostics Corporation, Laboratory Corporation of America, and Applera Corporation, Defendants-Appellees.
• Court: U.S. Court of Appeals — Federal Circuit

541 F.3d 1115

CARNEGIE MELLON UNIVERSITY and Three Rivers Biologicals, Inc., Plaintiffs-Appellants, v. HOFFMANN-LA ROCHE INC., Roche Molecular Systems, Inc., Roche Diagnostic Systems, Inc., Roche Biomedical Laboratories, Inc., The Perkin-Elmer Corporation, and Laboratory Corporation of America Holdings, Defendants-Appellees.

Carnegie Mellon University, Plaintiff-Appellant, v. Hoffmann-La Roche Inc., Roche Molecular Systems, Inc., Roche Diagnostics Corporation, Laboratory Corporation of America, and Applera Corporation, Defendants-Appellees.

No. 2007-1266.

No. 2007-1267.

United States Court of Appeals, Federal Circuit.

September 8, 2008.

Frederick H. Colen, Reed Smith LLP, of Pittsburgh, PA, argued for all plaintiffs-appellants. With him on the briefs were Charles H. Dougherty, Jr. and Mark Levin.

Stephen S. Rabinowitz, Fried, Frank, Harris, Shriver & Jacobson LLP, of New York, NY, argued for all defendants-appellees. With him on the briefs were Mitchell Epner, Randy C. Eisensmith, and Alison R. Ladd.

Before LOURIE, BRYSON, and PROST, Circuit Judges.

LOURIE, Circuit Judge.

Carnegie Mellon University ("CMU") and Three Rivers Biologicals, Inc. (collectively "appellants") appeal from the decision of the United States District Court for the Northern District of California holding that Hoffmann-La Roche, Inc., Roche Molecular Systems, Inc., Roche Diagnostic Systems, Inc., Roche Biomedical Laboratories, Inc., The Perkin Elmer Corporation, and Laboratory Corporation of America Holdings (collectively "Roche") do not infringe the patents in suit and that certain claims are invalid for lack of written description. Because we conclude that the district court did not err in holding the claims invalid for failure to meet the written description requirement, we affirm the court's judgment of invalidity. Because we conclude that the court did not err in its infringement analysis, we affirm the court's judgment of noninfringement.

BACKGROUND

Proteins, one of the most versatile biomolecules, can serve many important roles, including as signal receptors, structural elements, or enzymes. They are encoded by particular deoxyribonucleic acid ("DNA") sequences known as genes. The process by which cells use the information contained in genes to make corresponding proteins is referred to as expression. Expression involves two steps, viz., transcription and translation. During transcription, the information contained in a gene is copied into messenger ribonucleic acid ("mRNA"). The cell then assembles amino acids in the proper sequence during translation to make the protein based on the information contained in the mRNA.

One gene in the bacterium E. coli, called the E. coli polA gene, encodes a protein known as E. coli DNA polymerase I. Since at least the 1970s, the E. coli polA gene has been the subject of scientific study. The wild-type E. coli polA gene consists of two parts — the structural gene (or gene coding region) and a promoter, which is a DNA sequence that is involved in initiating transcription. The expression of a gene can be regulated through the use of a promoter by controlling the level of transcription.

Some valuable proteins are either difficult to purify from their natural sources or occur in minute quantities in nature. Thus, methods have been developed in the field of biotechnology "to synthesize useful quantities of specific proteins by controlling the mechanism by which living cells make proteins." Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., 55 F.Supp.2d 1024, 1027 (N.D.Cal.1999).

One method involves introducing foreign genes into a bacterium, which can then replicate as the bacterium grows and divides. Such a method involves several steps, including isolating and cloning the gene that encodes the protein of interest and introducing the cloned gene into the host bacterium. The latter is accomplished by incorporating the gene into a cloning vector. Certain types of vectors include bacteriophages and plasmids, which are "small circular loop[s] of DNA found in bacteria, separate from the chromosome, that replicate[ ] like a chromosome." Id. Recombinant DNA techniques are used to modify plasmids by recombining cloned genes and other segments of DNA that contain control sequences. The plasmid is then introduced into the host bacterium where it will replicate as the bacterium grows and divides.

The patents in suit, viz., U.S. Patents 4,767,708 ("the '708 patent"), 5,126,270 ("the '270 patent"), and 6,017,745 ("the '745 patent") relate to "novel recombinant plasmids for the enhanced expression of an enzyme, to the preparation by gene cloning of such plasmids, to bacterial strains containing said plasmids, [and] to methods for the conditional control of the expression of said enzyme."¹ '708 patent col.1 ll.7-16.

The patents teach that the enzyme of interest is DNA polymerase I (Pol I), which, as discussed above, is encoded by the structural gene known as polA. Id. col.1 ll.14-15. In the prior art, scientists encountered difficulties cloning polA into multicopy plasmids because the increase in expression of DNA polymerase I above the natural level of expression was found to be lethal to a host bacterium. Id. col.1 ll.14-18. The claimed inventions overcome that problem by constructing a novel plasmid containing "the entire and undamaged polA gene coding region enzymatically excised from a DNA molecule," which "contains essentially none of or at the most only a portion of the activity of its natural promoter." Id. col.2 ll.23-29. The patents disclose that severely damaging the natural polA promoter sequence constituted a "significant discovery of the present invention since it eliminates or greatly reduces the unregulated expression of Pol I, which would otherwise be lethal to the cell." Id. col.2 ll.43-46. By cloning the gene for DNA polymerase I into a vector along with a foreign promoter whose activity is conditionally controlled, one can obtain an amplified amount of DNA polymerase I. Throughout the specification, the patents teach that the host bacterial strain that is used to achieve that objective is E. coli.

The patents in suit share a common specification, and the claims are directed to recombinant plasmids that contain gene coding regions for the expression of DNA polymerase I from any bacterial source. For example, claim 1 of the '708 patent reads as follows:

1. A recombinant plasmid containing a cloned complete structural gene coding region isolated from a bacterial source for the expression of DNA polymerase I, under operable control of a conditionally controllable foreign promoter functionally linked to said structural gene coding region, said foreign promoter being functional to express said DNA polymerase I in a suitable bacterial or yeast host system.

'708 patent claim 1 (emphasis added). Claim 1 of the '270 patent recites:

1. A recombinant plasmid providing for Nick-translation activity isolated from a bacterial source, said plasmid capable of being placed in a bacterial host system such that the host system can grow and divide.

'270 patent claim 1 (emphasis added). Similarly, claim 1 of the '745 patent reads:

1. A recombinant plasmid containing a DNA coding sequence for the expression of DNA polymerase activity, wherein said DNA coding sequence is derived from a source that encodes a bacterial DNA Polymerase, said source not containing an amber mutation affecting expression of said DNA polymerase activity, such that when said plasmid is transformed into a bacterial host system the host system can grow and divide thereby replicating said plasmid.

'745 claim 1 (emphasis added).

Roche commercially manufactures recombinant DNA polymerases. The accused product at issue in this appeal involves a recombinant plasmid referred to as pLSG5, which causes host cells to express an enzyme known as Thermus aquaticus ("Taq") DNA polymerase. On August 30, 1994, appellants filed suit against Roche asserting that its product, pLSG5, infringes the '708 and '270 patents.² The district court held a claim construction hearing on January 14, 1997 and issued its claim construction ruling on March 31, 1997. The court construed the term "DNA polymerase" as requiring 3'-5' exonuclease activity. Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., No. C 95-3524 SI, 1997 WL 33152823, at *8 -*10 (N.D.Cal. Mar.31, 1997). Roche filed separate motions for summary judgment seeking judgment that: 1) claims 1-19, 22-40, and 43-45 of the '708 patent were invalid for lack of written description under our holding in Regents of University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed.Cir.1997); 2) claims 1-6, 10-19, and 22-40 of the '708 patent were not infringed; and 3) claims 1-2, 11-12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the '270 patent were invalid for lack of written description under our holding in Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473 (Fed.Cir.1998), or, in the alternative, under Eli Lilly.

On May 12, 1999, the district court granted Roche's motion for summary judgment of noninfringement. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., 55 F.Supp.2d 1024 (N.D.Cal.1999). In doing so, the district court concluded that there was no genuine issue of material fact as to whether the enzyme in the accused product possessed 3'-5' exonuclease activity. Because the undisputed evidence indicated that the accused products lacked that element, the court concluded that summary judgment of noninfringement of the '708 patent was required.

On August 19, 1999, the district court granted Roche's motion for summary judgment of invalidity as to the '270 patent. Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., No. C 95-3524 SI, 1999 WL 33298545 (N.D.Cal. Aug.19, 1999). The court determined that the specification of the '270 patent made clear that lethality was an essential feature of the invention and thus, under Gentry Gallery, the claims of the patent must contain that feature in...