Chiron Corp v. Genentech, Inc.

• Decision Date: 22 April 2002
• Docket Number: No. CIV.S-00-1252 WBS GG.,CIV.S-00-1252 WBS GG.
• Citation: 266 F.Supp.2d 1172
• Parties: CHIRON CORPORATION, Plaintiff, v. GENENTECH, INC., Defendant.
• Court: U.S. District Court — Eastern District of California

266 F.Supp.2d 1172

CHIRON CORPORATION, Plaintiff, v. GENENTECH, INC., Defendant.

No. CIV.S-00-1252 WBS GG.

United States District Court, E.D. California.

April 22, 2002.

COPYRIGHT MATERIAL OMITTED

Paul Joseph Riley, IV, Morrison and Foerster LLP, San Francisco, CA, Eric S. Walters, Morrison and Foerster, Palo Alto, CA, for Plaintiff.

Jack Vivian Lovell, Hunter Richey Di-Benedetto and Eisenbeis, Sacramento, CA, James M. Emery, Michael David Celio, Keker and Van Nest, San Francisco, CA, for Defendant.

Henry C. Bunsow, Howrey Simon Arnold and White, San Francisco, CA, for Counter-Claimant.

Rachel Krevans, Morrison and Foerster LLP, San Francisco, CA, for Counter-Defendant.

MEMORANDUM AND ORDER

SHUBB, District Judge.

In this lawsuit, Chiron alleges that Genentech's product, Herceptin, infringes Chiron's United States Patent No. 6,054,561 ("'561 patent"). The court is now called upon to construe the terms of '561 patent. See Markman v. Westview Instruments, Inc., 52 F.3d 967, 968 (Fed.Cir.1995) (en banc), aff'd, 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996).

I. Factual and Procedural Background

The '561 patent issued on April 25, 2000 from a long line of patents and patent applications dating back to February 8, 1984 and January 11, 1985. Generally, the patent claims monoclonal antibodies capable of binding to specific human breast cancer antigens.

Antibodies, also known as "immunoglobulins," are produced by the immune system in response to the presence of an antigen, or foreign substance, in the body. Antibodies recognize and bind to specific receptor sites, or "epitopes," on the antigen. Because antibodies are capable of homing in on specific antigens, they are useful for identifying and destroying harmful agents in the body, such as bacteria, viruses, and cancer cells. For example, a toxin may be attached to an antibody so that it will kill the antigen to which it binds.

Structurally, an antibody is a "Y" shaped molecule composed of four "chains" of amino acids: two identical heavy chains, and two identical light chains. The two arms of the "Y" are collectively referred to as the "variable region," while the tail end is called the "constant region." It is the variable region of the antibody that does the important work of recognizing and binding to the antigen. More specifically, "complimentary determining regions" ("CDRs") and "framework regions" ("FRs") within the variable region form a three-dimensional structure that fits in lock-and-key fashion to a particular receptor site on the antigen. The portion of the antibody that binds to the antigen is sometimes referred to as "the antigen binding site."

When responding to the presence of an antigen, the body may produce many different antibodies that bind to different receptor sites on the antigen. Antibodies that have identical antigen binding sites, however, will attach to the same receptor site on the same antigen.

Homogenous preparations of identical antibodies, all of which have a high affinity for binding to cancerous antigens and can distinguish cancer antigens from normal tissue, are useful in the treatment and diagnosis of cancer. In the 1980s, scientists at Cetus (Chiron's predecessor) attempted to create antibodies having these characteristics. To do so, they utilized the "hybridoma method," ¹ which is described at length in the '561 patent, as well as in the 1984 and 1985 priority applications. Briefly put, it involves taking a human cancer cell and injecting it into a mouse, which produces antibodies in response. The murine (mouse) B-cells that produce the antibodies are then isolated. Because each B-cell is unique and produces only one kind of antibody, a B-cell with an extended life span can produce numerous, identical antibodies. Accordingly, once the B-cell is isolated, it is fused with an immortal myeloma tumor cell. The resulting hybrid cell, or "hybridoma," is an immortal cell line that is capable of producing an unlimited supply of identical antibodies. The parties agree that antibodies produced by these methods are "monoclonal antibodies" (i.e. coming from "one cloned" cell).

Cetus scientists tested hundreds of these monoclonal antibodies until they isolated ones capable of recognizing human breast cancer antigens, and binding strongly to them but not to normal cells and tissues. Specifically, they found that antibodies 454 C11 and 520 C9 bound to an antigen that occurred with great frequency in breast cancers, but with little frequency in normal tissue.

Scientists soon discovered that the murine monoclonal antibodies produced by the hybridoma method described above could be problematic for treatment. The murine origin of the antibodies provoked a HAMA ("Human Anti-Mouse Antibody") response in patients, as the human body rejected the murine antibodies as foreign matter. Scientists therefore began investigating other methods for producing antibodies that would retain the antigen binding sites of the murine monoclonal antibodies, but would not produce an immunogenic response.

One such development was a "chimeric antibody," created by attaching mouse-derived variable regions to human constant regions.² Subsequently, scientists developed a more sophisticated "humanized antibody," in which only the antigen binding sites were murine in origin. Scientists were able to identify the amino acid sequences in the murine antibody that code for the cancer-specific antigen binding sites. They then used recombinant DNA technology to combine these murine amino acid sequences with human amino acid sequences. Thus, the resulting humanized antibody retained the beneficial binding properties of the murine antibody while minimizing the potential for an adverse immune response. The accused product, Herceptin, is precisely this kind of humanized antibody.

The central dispute in this case is whether the term "monoclonal antibody" as used in the '561 patent encompasses humanized antibodies. The parties also dispute the meaning of the claim terms "binds," "antigen," "strong staining," "immunoassay," "extracellular domain," and "human c-erbB-2 antigen."

A Markman hearing was held on March 5-7, 2002 before Magistrate Judge Hollows. On March 25, 2002, Magistrate Judge Hollows filed findings and recommendations regarding the construction of the above terms. (See Mar. 25, 2002, Findings and Recommendations) (hereinafter "F & R's"). Both Chiron and Genentech filed objections to the findings and recommendations, which the court now reviews de novo. See 28 U.S.C. § 636(b)(1)(C); Local Rule 72-304.

II. Discussion

Claim construction is a matter of law for the court to decide. Phonometrics v. Northern Telecom Inc., 133 F.3d 1459, 1463 (Fed.Cir.1998). The purpose of claim construction is to "elaborat[e] the normally terse claim language in order to understand and explain, but not to change, the scope of the claims." Gart v. Logitech, 254 F.3d 1334 (Fed.Cir.2001) (quoting Embrex, Inc. v. Service Eng'g Corp., 216 F.3d 1343, 1347 (Fed.Cir.2000)) (internal quotations and citation omitted). In construing claim terms, "the focus is on the objective test of what one of ordinary skill in the art at the time of the invention would have understood the term to mean." Markman, 52 F.3d at 968; Kopykake Enterprises, Inc. v. Lucks Co., 264 F.3d 1377, 1383 (Fed.Cir. 2001) (construing the patent "as of the date the invention was constructively reduced to practice—the date the patent application was filed").

In this case, the '561 patent claims priority based on the 1984 and 1985 applications. For the invention claimed in the '561 patent to get the benefit of the 1984/1985 filing dates, it must have been reduced to practice in 1984/1985. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551 (Fed.Cir. 1994) (holding that an invention is entitled to the filing date of parent applications if it is supported by the disclosure in the parent applications). Accordingly, the court construes the disputed terms as they would have been understood by one skilled in the art in 1984 and 1985.

The objective meaning of the claims can ordinarily be ascertained from three pieces of "intrinsic evidence": the claim language, the patent specification, and the prosecution history. Level One Communications, Inc. v. Seeq Technology, Inc., 987 F.Supp. 1191 (N.D.Cal.1997) (citing Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.Cir.1996)). "[T]he actual words of the claim are the controlling focus," and the starting point for claim construction. Digital Biometrics, Inc. v. Identix, Inc., 149 F.3d 1335, 1344 (Fed.Cir. 1998) (discussing the "hierarchy of analytical tools"). The specification (also called the written description) aids in defining the terms used in the claims, particularly if the patentee has elected to define the terms himself. See Vitronics, 90 F.3d at 1582, York Prods. Inc. v. Central Tractor Farm and Family Ctr., 99 F.3d 1568, 1572 (Fed.Cir.1996). Finally, the prosecution history is relevant "because it may contain contemporaneous exchanges between the patent applicant and the PTO about what the claims mean." Digital Biometrics, 149 F.3d at 1344. The intrinsic evidence is "the most significant source of the legally operative meaning of disputed claim language." Vitronics, 90 F.3d at 1582.

If the intrinsic evidence is insufficient for determining the scope of the disputed claims, the court may then rely on extrinsic evidence, such as dictionaries and expert testimony, in "coming to the proper understanding of the claims." Id. at 1583. In addition, extrinsic evidence "may be accepted by the court to enhance its understanding of the technology." Gart, 254 F.3d at 1340; see also Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1308 (Fed.Cir.1999) ("It is entirely appropriate, perhaps even preferable for a court to consult trustworthy extrinsic evidence to ensure that the claim construction ... is not inconsistent with clearly...