By Donald Zuhn --
Today, in Centocor Ortho Biotech, Inc. v. Abbott Laboratories, the Federal Circuit reversed the District Court's denial of judgment as a matter of law ("JMOL") of invalidity, holding the asserted claims of U.S. Patent No. 7,070,775 invalid for lack of written description.
Plaintiffs-Appellees Centocor Ortho Biotech, Inc. and New York University ("Centocor") sued Defendants-Appellants Abbott Laboratories, Abbott Bioresearch Center, Inc., and Abbott Biotechnology, Ltd. ("Abbott"), asserting that Abbott's Humira® antibody infringes claims 2, 3, 14, and 15 of the '775 patent, which Centocor owns. At trial, a jury found the asserted claims valid and Abbott liable for willful infringement, awarding Centocor $1.67 billion in damages. The District Court for the Eastern District of Texas granted Abbott's motion for JMOL of no willful infringement, but denied its other JMOL motions, including Abbott's motion for JMOL of invalidity.
The case involves antibodies to human tumor necrosis factor α ("TNF-α"). While Centocor and Abbott both sought to develop anti-TNF-α antibodies that would have high affinity, the desired neutralizing activity, and reduced immunogenicity, they pursued different strategies to develop their anti-TNF-α antibodies. Centocor, for example, identified a mouse antibody to human TNF-α ("A2 mouse antibody") that had high affinity and neutralizing activity and reduced the antibody's immunogenicity by exchanging the antibody's mouse constant region with a human constant region, creating a chimeric antibody having a mouse variable region and a human constant region. Abbott, meanwhile, screened a phage library of human variable regions for variable regions that bind human TNF-α, and then used various techniques to improve the binding affinity of selected variable regions. The resulting variable regions were then combined with human constant regions to create fully-human antibodies, from which the therapeutic antibody Humira® was identified.
Centocor filed a patent application in 1991 claiming its A2 mouse antibody and chimeric antibody. In 1993 and 1994, Centocor filed a series of continuation-in-part applications, and in 2002, Centocor added claims reciting human variable regions in the thirteenth member of the application family, which issued as the '775 patent in 2006. Claims 1 and 2 of the '775 patent recite:
1. An isolated recombinant anti-TNF-α anti-body or antigen-binding fragment thereof, said antibody or antigen-binding fragment comprising a human constant region, wherein said antibody or antigen binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA-7045) to human TNF-α, and (ii) binds to a neutralizing epitope of human TNF-α in vivo with an affinity of at least 1x108 liter/mole, measured as an association constant (Ka), as determined by Scatchard analysis.
2. The antibody or antigen-binding fragment of claim 1, wherein the antibody or antigen binding fragment comprises a human constant region and a human variable region.
Abbott filed a patent application directed to high affinity, neutralizing, fully-human antibodies to human TNF-α (such as the Humira® antibody) in 1996, and was granted a patent in 2000.
Writing for the Court, Judge Prost notes that:
The pivotal issue in this case concerns whether the '775 patent provides adequate written description for the claimed human variable regions. As noted above, Centocor first sought claims to human variable regions and fully-human antibodies in 2002. At that time, Abbott had already discovered and patented a fully-human antibody to TNF-α that had high affinity and neutralizing activity. To ensnare Abbott with later-filed claims, Centocor must use a priority date from an earlier application. Because Abbott's application was filed in 1996, Centocor relies on a priority claim to the 1994 CIP applications. Thus, in order for Centocor to prevail, the asserted claims must be supported by adequate written description in the 1994 CIP applications.
Summarizing Abbott's argument on appeal, she writes:
To underscore the inadequacy of Centocor's written description, Abbott points out that the specification does not disclose any fully-human, high affinity, neutralizing, A2 specific antibody. Moreover, the specification does not disclose a single human variable region. Abbott argues that the only described antibody is the chimeric antibody, which has a mouse variable region. Abbott also argues that Centocor has merely disclosed tools that might be used in an attempt to make the claimed invention -- essentially, that Centocor's disclosure is no more than a mere wish or plan for how one might search for a fully-human antibody that satisfies the claims.
After reviewing Centocor's 1994 CIP applications to assess whether their disclosure provides adequate written description for the asserted claims, Judge Prost concludes that:
Contrary to Centocor's assertions, very little in the '775 patent supports that Centocor possessed a high affinity, neutralizing, A2 specific antibody that also contained a human variable region. The overwhelming majority of the '775 patent describes the A2 mouse antibody and the single chimeric antibody that Centocor made based on A2's mouse variable region. . . . As for describing suitable variable regions, the application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common.
Because the undisputed testimony at trial established that the sequence of the A2 variable region and a human variable region are "very different," the Court declares that "the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims." In finding that Centocor's fully-human antibody claims go beyond the scope of its disclosure, Judge Prost notes that:
[W]hile the patent broadly claims a class of antibodies that contain human variable regions, the specification does not describe a single antibody that satisfies the claim limitations. It does not disclose any relevant identifying characteristics for such fully-human antibodies or even a single human variable region. Nor does it disclose any relationship between the human TNF-α protein, the known mouse variable region that satisfies the critical claim limitations, and potential human variable regions that will satisfy the claim limitations. There is nothing in the specification that conveys to one of skill in the art that Centocor possessed fully-human antibodies or human variable regions that fall within the boundaries of the asserted claims [citations omitted].
Citing Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004), and the USPTO Written Description Guidelines, Centocor argues that because it fully disclosed the human TNF-α protein, it has provided adequate written description for any antibody that binds to human TNF-α. Judge Prost, however, counters that Centocor's "suggestion is based on an unduly broad characterization of the guidelines and our precedent," noting that Noelle and the Guidelines stand for the proposition that "an applicant can claim an antibody to novel protein X without describing the antibody when (1) the applicant fully discloses the novel protein and (2) generating the claimed antibody is so routine that possessing the protein places the applicant in possession of an antibody" (emphasis added). She points out that in this case, "both the human TNF-α protein and antibodies to that protein were known in the literature."
Thus, the panel concludes that, as in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010) (en banc), the jury lacked substantial evidence to find that the asserted claims were supported by adequate written description, and the District Court erred when it declined to grant Abbott's motion for JMOL that the asserted claims were invalid for lack of written description.
Centocor Ortho Biotech, Inc. v. Abbott Laboratories (Fed. Cir. 2011)
Panel: Circuit Judges Bryson, Clevenger, and Prost
Opinion by Circuit Judge Prost