Genentech, Inc. v. Wellcome Foundation Ltd.

• Decision Date: 27 June 1994
• Docket Number: Nos. 92-1503,92-1505,s. 92-1503
• Citation: 29 F.3d 1555,31 USPQ2d 1161
• Parties: GENENTECH, INC., Innovi N.V. and Leuven Research & Development VZW, Plaintiffs-Appellees, v. The WELLCOME FOUNDATION LIMITED, Wellcome Biotechnology Limited, Burroughs Wellcome Co., B.W. Manufacturing, Inc. and Welgen Manufacturing, Inc., Defendants, and Genetics Institute, Inc. and GI Manufacturing, Inc., Defendants-Appellants.
• Court: U.S. Court of Appeals — Federal Circuit

Page 1555

29 F.3d 1555

31 U.S.P.Q.2d 1161

GENENTECH, INC., Innovi N.V. and Leuven Research &amp Development VZW, Plaintiffs-Appellees, v. The WELLCOME FOUNDATION LIMITED, Wellcome Biotechnology Limited, Burroughs Wellcome Co., B.W Manufacturing, Inc. and Welgen Manufacturing, Inc., Defendants and Genetics Institute, Inc. and GI Manufacturing, Inc. Defendants-Appellants.

Nos. 92-1503, 92-1505.

United States Court of Appeals, Federal Circuit.

June 27, 1994.

Stephen F. Sherry, Allegretti & Witcoff, Ltd., Chicago, IL, argued for plaintiffs-appellees. With him on the brief was D. Dennis Allegretti, Allegretti & Witcoff, Ltd., Boston, MA.

James L. Quarles, III, Hale & Dorr, Washington, DC, argued for defendants-appellants. With him on the brief were Bruce M. Eisen, Steven R. Lazar, Genetics Institute, Inc., of Cambridge, MA, and Stanley H. Lieberstein and Edward A. Meilman, Ostrolenk, Faber, Gerb & Soffen, New York City.

Before PLAGER, Circuit Judge, COWEN, Senior Circuit Judge, and LOURIE, Circuit Judge.

PLAGER, Circuit Judge.

The question in this patent infringement action is whether a protein, formed through recombinant DNA technology, infringes, under the doctrine of equivalents, any of three patents: a patent directed to a natural protein extracted from certain human cancer cells; a patent directed to the materials needed to produce the natural protein through recombinant DNA technology, i.e., the DNA sequence encoding the protein, the expression vector containing the sequence, and the microorganism or cell culture capable of expressing the protein; or a patent directed to the process of producing the natural protein through recombinant DNA technology. The United States District Court for the District of Delaware found in favor of the patent owners/licensees (and their agent), plaintiffs Genentech, Inc. (Genentech), Innovi N.V. (Innovi), and Leuven Research & Development VZW (Leuven), holding that the Genetics defendants, to wit, Genetics Institute, Inc. (Institute) and Genetics Manufacturing, Inc. (GI Manufacturing), infringed under the doctrine of equivalents U.S. Patent Nos. 4,752,603 (the '603 patent), 4,766,075 (the '075 patent), and 4,853,330 (the '330 patent). That judgment was entered by the court on April 6, 1990 in consolidated Civil Action Nos. 88-330 and 89-407 following a jury trial, and became final on July 15, 1992 when the court denied defendants' motions for judgment as a matter of law (JMOL) ¹ or, in the alternative, a new trial. Genentech Inc. v. Wellcome Foundation Ltd., 798 F.Supp. 213, 24 USPQ2d 1782 (D.Del.1992). The Genetics defendants appeal. We find that the judgment of the trial court is not sustainable under the law, and reverse.

BACKGROUND

1.

The protein tissue plasminogen activator (t-PA) plays an important role in the dissolution of fibrin clots in the human body. The body forms such clots typically to breach a rupture in a blood vessel. When they are no longer needed, they are dissolved through the action of plasmin, an enzyme which binds to the fibrin and severs the bonds between the fibrin molecules. Since plasmin circulates through the blood in an inactive form called plasminogen, a mechanism must be provided to activate the plasminogen and convert it to plasmin when a clot is targeted for dissolution by the body. The protein t-PA serves as that mechanism.

Unfortunately, a pathological clot known as a 'thrombus' sometimes forms in intact vessels and causes life-threatening conditions. When a thrombus occurs, the normal amount of t-PA circulating in the body may not be effective to produce plasmin fast enough to dissolve the clot, and avoid the risk of heart muscle damage or death. An additional dosage of a material which activates the plasminogen is often necessary to dissolve the clot rapidly. Several materials, such as natural t-PA extracted from human cells, streptokinase, or urokinase, were known to perform this function, although imperfectly, either because, in the case of streptokinase and urokinase, of undesirable side effects and low affinity to fibrin, and in the case of natural t-PA, the inability to derive clinically effective volumes from known sources.

Plaintiff Leuven then set to work to find a way to produce natural t-PA in a commercially useful way, i.e., in sufficient quantities and at a sufficient level of purity and effectiveness to meet commercial demands. This task was assigned to three of Leuven's scientists--Drs. Collen, Rijken, and Matsuo. They discovered that a commercially useful quantity and purity of natural t-PA could be produced from human melanoma cell cultures.

This discovery is the subject of the '603 patent, the sole independent claim of which reads:

1. Human plasminogen activator, having thrombolytic properties, immunologically distinct from urokinase and having a specific activity of about 500,000 IU/mg. using the WHO First International Reference Preparation of t-PA (tissue plasminogen activator) as assay standard or a specific activity of about 90,000 IU/mg. using the WHO First International Reference Preparation of urokinase as assay standard.

Meanwhile, plaintiff Genentech set about pursuing the same objective, a commercially useful process for producing natural t-PA, but by a different route--recombinant DNA technology. ² That task was assigned to four Genentech scientists--Drs. Goeddel, Kohr, Vehar, and Pennica. They ultimately discovered such a process as well as the intermediate products used in the process, i.e., the DNA sequence encoding human t-PA, the expression vector containing that sequence, and the microorganism or cell culture capable of expressing human t-PA using that vector.

The intermediate products are the subject of the claims of the '075 patent, of which claims 1, 3, and 8 are representative:

1. A DNA isolate consisting essentially of a DNA sequence encoding human tissue plasminogen activator.

* * * * * *

3. A recombinant expression vector containing a DNA sequence encoding human tissue plasminogen activator, wherein the vector is capable of expressing human tissue plasminogen activator in a transformed microorganism or cell culture.

* * * * * *

8. A cell culture capable of expressing human tissue plasminogen activator, obtained by transforming a mammalian cell line with a vector according to claim 3.

The process itself is the subject of the claims of the '330 patent, of which claims 1, 8, and 12 are representative:

1. A process which comprises expressing a DNA sequence encoding human tissue plasminogen activator in a recombinant host cell, said recombinant host cell being a microorganism or cell culture transformed with an expression vector containing said DNA sequence.

* * * * * *

8. A process for producing recombinant human tissue plasminogen activator comprising:

(a) growing recombinant cells in a growth medium, said cells being a microorganism or cell culture transformed with an expression vector containing DNA encoding human tissue plasminogen activator; and

(b) simultaneously expressing said DNA, thereby producing recombinant human tissue plasminogen activator.

* * * * * *

12. A process for producing recombinant human tissue plasminogen activator comprising:

(a) transforming a microorganism or cell culture with a replicable vector containing DNA encoding human tissue plasminogen activator; and (b) expressing said DNA in said transformed microorganism or cell culture.

2.

The plaintiffs in this action consist of Leuven, the owner of the '603 patent; Genentech, the owner of the '075 and '330 patents, and the exclusive licensee of the '603 patent; and Innovi, Leuven's agent to assist it in licensing its technology rights. They initiated this action on June 21, 1988, the day the '603 patent issued, alleging infringement of the '603 patent, and subsequently amended their complaint after the '075 patent issued on August 23, 1988 to allege infringement of that patent. When the '330 patent issued on August 1, 1989, plaintiffs initiated a separate action against defendants alleging infringement of that patent; that action was subsequently consolidated with the other.

The original defendants consisted of the Genetics defendants--Institute and GI Manufacturing--as well as the Wellcome defendants--The Wellcome Foundation Ltd. (Foundation); Wellcome Biotechnology Ltd. (Biotechnology); Burroughs Wellcome Co. (Burroughs); BW Manufacturing, Inc. (BW Manufacturing); and WelGen Manufacturing, Inc. (WelGen). ³ GI Manufacturing is a wholly-owned subsidiary of Institute. BW Manufacturing is a wholly-owned subsidiary of Burroughs, which in turn is a wholly-owned subsidiary of Foundation. GI Manufacturing and BW Manufacturing jointly own WelGen. That entity was, at the time this action was initiated, admittedly constructing a facility in the United States for the commercial production of t-PA.

According to plaintiffs' allegations, the Genetics and Wellcome defendants acted in concert to make, use, and import into the United States natural t-PA, or variants of natural t-PA, produced through recombinant DNA technology that infringe the patents-in-suit. There are two accused products--met-t-PA and FE1X--both of which are structurally distinct from natural t-PA. ⁴ The Genetics defendants are alleged to have manufactured in the United States the FE1X product for commercial purposes. The Wellcome defendants are alleged to have manufactured in the United Kingdom the met-t-PA product, and imported that product into the United States for commercial purposes.

In response to plaintiffs' allegations, defendants denied infringement and asserted the affirmative defenses that the three patents-in-suit were invalid, and unenforceable due to inequitable and fraudulent conduct during prosecution. Defendants also asserted counterclaims alleging that plaintiffs' procurement and enforcement of the three patents-in-suit against them constituted an antitrust violation and unfair competition.

The parties then filed ...