Carnegie Mellon University v. Hoffmann-Laroche

• Decision Date: 12 May 1999
• Docket Number: No. C 95-3524 SI.,C 95-3524 SI.
• Citation: 55 F.Supp.2d 1024
• Court: U.S. District Court — Northern District of California
• Parties: CARNEGIE MELLON UNIVERSITY and Three Rivers Biologicals, Inc., Plaintiffs, v. HOFFMANN-LaROCHE, INC., Roche Molecular Systems, Inc., the Perkin-Elmer Corporation, Chiron Corporation, Cetus Oncology Corporation, Roche Diagnostic Systems, Inc., and Roche Biomedical Laboratories, Inc., Defendants.

55 F.Supp.2d 1024

CARNEGIE MELLON UNIVERSITY and Three Rivers Biologicals, Inc., Plaintiffs, v. HOFFMANN-LaROCHE, INC., Roche Molecular Systems, Inc., the Perkin-Elmer Corporation, Chiron Corporation, Cetus Oncology Corporation, Roche Diagnostic Systems, Inc., and Roche Biomedical Laboratories, Inc., Defendants.

No. C 95-3524 SI.

United States District Court, N.D. California.

May 12, 1999.

COPYRIGHT MATERIAL OMITTED

Arland T. Stein, Frederick H. Colen, Reed Smith Shaw & McClay, Pittsburgh, PA, Walter P. DeForest, DeForest & Koscelnik, Pittsburgh, PA, Eugene J. Majeski, Ropers Majeski Kohn & Bentley, Redwood City, CA, for Plaintiffs Carnegie Mellon University and Three Rivers Biologicals, Inc.

S. Leslie Misrock, Stephen S. Rabinowitz, Gidon D. Stern, Pennie & Edmonds LLP, New York City, Vanessa Wells, Heller, Ehrman White & McAuliffe, Palo Alto, CA, for Defendants Hoffman-La Roche, Inc., Roche Molecular Systems, Inc., Roche Diagnostic Systems, Inc., Roche Biomedical Laboratories, Inc., and Perkin-Elmer Corp.

Harold J. McElhinny, Tamu K. Sudduth, Matthew I. Kreeger and Constance T.Y. McComb, Morrison & Foerster LLP, San Francisco, CA, for Defendants Chiron Corp. and Cetus Oncology.

ORDER GRANTING IN PART AND DENYING IN PART DEFENDANTS' MOTIONS TO EXCLUDE THE TESTIMONY OF PLAINTIFFS' EXPERTS; AND GRANTING DEFENDANTS' MOTIONS FOR SUMMARY JUDGMENT

ILLSTON, District Judge.

Plaintiffs Carnegie Mellon University and Three Rivers Biologicals, Inc. (collectively "Carnegie Mellon") contend that defendants Hoffmann-La Roche Inc., Roche Molecular Systems, Inc., Roche Diagnostic Systems, Inc., Roche Biomedical Laboratories, Inc., Laboratory Corporation of America Holdings, and the Perkin-Elmer Corporation (collectively "the Roche defendants") and Chiron Corporation and Cetus Oncology Corporation (collectively "the Chiron defendants") have infringed claims 1-6, 10-19 and 22-40 of U.S. Patent No. 4,767, 708 ("the '708 Patent") and claims 1-2 11-12, 14-15, 17-18, and 32-34 of U.S. Patent No. 5, 126,270 ("the '270 Patent"). The '708 Patent and the '270 Patent are both entitled "Enzyme Amplification and Purification" and involve recombinant DNA technology. Both the Roche defendants and the Chiron defendants have moved for summary judgment on the issue of infringement of the '708 Patent. Also before the Court are defendants' motions to exclude the testimony and declarations of plaintiffs' experts.

For the reasons set forth below, the Court hereby (1) GRANTS the Roche defendants' motion to exclude the declaration of Dr. William E. Brown; (2) GRANTS in part and DENIES in part the Chiron defendants' motion to exclude the testimony of plaintiffs' experts; and (3) GRANTS the defendants' motions for summary judgment of non-infringement of the '708 Patent both literally and under the doctrine of equivalents.

BACKGROUND

1. Relevant Technology¹

Proteins are biological molecules of enormous importance. Proteins include enzymes that catalyze biochemical reactions; major structural materials of the animal body; and many hormones. Numerous patents and applications for patents in the field of biotechnology involve specific proteins or methods for making and using proteins. Many valuable proteins occur in nature only in minute quantities, or are difficult to purify from natural sources. Therefore, a goal of many biotechnology projects is to devise methods to synthesize useful quantities of specific proteins by controlling the mechanism by which living cells make proteins.

Protein molecules are composed of long chains of amino acids. To make a protein molecule, a cell needs information about the sequence in which the amino acids must be assembled, since the sequence of amino acids determines the characteristics of the protein.

The cell uses a long molecule, DNA, to store this information. DNA molecules do not participate directly in the synthesis of proteins. Instead, DNA acts as a permanent "blueprint" of all of the genetic information in the cell, and exists mainly in extremely long strands (called chromosomes) containing information coding for the sequences of many different proteins, most of which are not being synthesized at any particular moment. DNA strands are made up of nucleotides, the sequence and combination of which in the DNA strand specifies the particular sequence of amino acids in a particular protein. The specific region of DNA on the chromosome that codes for the sequence of a particular protein is called a gene.

To make a specific protein by expressing its cloned gene in bacteria,² several technical hurdles must be overcome. First the gene, or DNA coding region, for the specific protein must be isolated for cloning. Next the isolated gene must be introduced into the host bacterium. This can be done by incorporating the gene into a cloning vector. A cloning vector is a piece of DNA which can be introduced into bacteria and which will then replicate itself as the bacterial cells grow and divide. One type of cloning vector is a plasmid, a small circular loop of DNA found in bacteria, separate from the chromosome, that replicates like a chromosome. Because of its small size, a plasmid is convenient for the molecular biologist to isolate and work with.

Recombinant DNA technology is used to modify plasmids by splicing in (recombining) cloned genes and other useful segments of DNA containing control sequences. Short pieces of DNA can even be designed to have desired nucleotide sequences, synthesized chemically, and spliced into plasmids. A plasmid constructed by the molecular geneticist can be inserted into bacteria, where it replicates as the bacteria grow.

2. The '708 Patent

The '708 Patent is directed 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 enzymes." '708 Patent, column 1 lines 8-13. The '708 Patent includes three independent claims: 1, 25 and 39. The remaining claims in the '708 Patent are dependent on claims 1, 25, or 39. In particular, claims 1-19 and 22-24 involve a "recombinant plasmid containing a cloned complete structural gene encoding region isolated from a bacterial source for the expression of DNA polymerase I." Claims 25-38 involve a "process for constructing a recombinant plasmid for the expression of DNA polymerase I." Claims 39-40 involve a "host strain of cells containing a foreign plasmid capable of expressing DNA polymerase I."

On March 31, 1997, the Court issued an order interpreting these claims. In the claim construction order, the Court held that the term "DNA Polymerase I" in the claims of the '708 Patent referred to an enzyme that is lethal or debilitating to growth of the host cell strain when expressed from a multicopy plasmid and that exhibits three enzymatic activities, namely, 3'-5' exonuclease activity, 5'-3' exonuclease activity and polymerase activity.

3. Defendants' Polymerase Products

The Roche defendants and Chiron defendants have developed six plasmids for the commercial manufacture of six recombinant DNA polymerases:

plasmid pLSG5 encodes Thermus aquaticus ("Taq") DNA polymerase, which defendants claim lacks 3'-5' exonuclease activity;

plasmid pLSG8 encodes a truncated fragment of Taq DNA polymerase, called Stoffel fragment, which defendants claim lacks both 3'-5' exonuclease activity and 5'-3' exonuclease activity; plasmid pRDA3-2 encodes a mutant version of Taq DNA polymerase, called CS mutant, which defendants claim lacks both 3'-5' exonuclease activity and 5'-3' exonuclease activity;

plasmid pLK103 encodes a double-mutant version of Taq DNA polymerase, called FS mutant, which defendants claim lacks both 3'-5' exonuclease activity and 5'-3' exonuclease activity;

plasmid pLSG32 encodes Thermus thermophilus ("Tth") DNA polymerase which defendants claim lacks 3'-5' exonuclease activity; and

plasmid pTma15 encodes a truncated fragment of Thermotoga maritima DNA polymerase, called UITma DNA polymerase, which defendants claim lacks 5'-3' exonuclease activity.

Defendants seek an order granting summary judgment on the issue of non-infringement of the '708 Patent because plasmids pLSG5, pLSG8, pRDA3-2, pLK103, pLSG32, and pTma15 do not contain a gene encoding region capable of expressing "DNA polymerase I." Defendants contend that they are entitled to summary judgment because of the absence of 3'-5' exonuclease activity and/or 5'-3' exonuclease activity in the enzymes encoded by these plasmids. Defendants also ask the Court to find that neither the processes for constructing these plasmids nor the host cell strains containing these plasmids are capable of expressing "DNA polymerase I." Lastly, defendants move to exclude the testimony and declarations of Carnegie Mellon's experts, including that of Dr. William E. Brown who asserts that Taq DNA polymerase does exhibit 3'-5' exonuclease activity.

LEGAL STANDARD

"Summary judgment is appropriate in a parent case, as in other cases, when there is no genuine issue as to any material fact and the moving party is entitled to judgment as a matter of law." Nike Inc. v. Wolverine World Wide, Inc., 43 F.3d 644, 646 (Fed.Cir.1994) (citations omitted).

Summary judgment is proper "if the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law." Fed. R.Civ.P. 56(c). The moving party bears the initial burden of demonstrating the absence of a genuine issue of material fact. See Celotex Corp. v. Catrett, 477 U.S. 317, 323, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986). The moving party, however, has no burden to negate or disprove matters on which the non-moving party will have the burden of proof at trial. Id. The moving party need only point out to the...