March 2011
Claims to Antibodies with Specific Properties Are Not Always Fully Described by Disclosing the Protein
| Judges: Bryson, Clevenger, Prost (author) |
| [Appealed from E.D. Tex., Judge Ward] |
In Centocor Ortho Biotech, Inc. v. Abbott Laboratories, No. 10-1144 (Fed. Cir. Feb. 23, 2011), the Federal Circuit reversed the district court’s denial of Abbott Laboratories’ (“Abbott”) motion for JMOL on invalidity and held that the asserted claims of Centocor Ortho Biotech, Inc.’s (“Centocor”) U.S. Patent No. 7,070,775 (“the ’775 patent”) failed to comply with the written description requirement of 35 U.S.C. § 112.
The ’775 patent, issued in 2006, is directed to antibodies to human tumor necrosis factor α (“TNF‑α”). For purposes of the appeal, the Federal Circuit explained that antibodies basically consist of two regions:
a constant region and a variable region. Changing the variable region can result in an antibody that does not bind to TNF-α or that does not have neutralizing activity. Centocor identified a mouse antibody to human TNF-α, which had high affinity and neutralizing activity (“the A2 mouse antibody”), and produced a “chimeric” antibody containing a mouse variable region and a human constant region. In 1991, Centocor filed a patent application claiming its A2 mouse antibody and chimeric antibody. Subsequently, in 1994, Centocor filed three CIP applications adding new matter, but did not present claims to human variable regions.
Abbott also sought to engineer a fully-human antibody, taking a different path than Centocor. Rather than start from the A2 mouse antibody, Abbott worked directly with human variable regions. By 1995, Abbott had created the therapeutic antibody Humira® and filed a patent application disclosing this fully-human antibody to human TNF-α in 1996. Following the grant of its patent in 2000, Abbott obtained regulatory approval to market Humira® in 2002.
After Abbott received regulatory approval, Centocor filed the ’775 patent application claiming, for the first time, fully-human anti-TNF-α antibodies (i.e., antibodies possessing human variable and constant regions). The ’775 patent application contained a priority claim to Centocor’s earlier-filed patent applications.
Shortly after the issuance of the ’775 patent, Centocor sued Abbott, alleging that Abbott’s therapeutic antibody Humira® infringed several claims of the ’775 patent. After a jury verdict finding all of the asserted claims valid and willfully infringed, and awarding Centocor $1.67 billion in damages, the district court granted Abbott’s motion for JMOL of no willful infringement but denied its motions for JMOL on noninfringement and invalidity.
On appeal, the Federal Circuit noted that the pivotal issue was whether the ’775 patent provides adequate written description for the claimed human variable regions. The Court explained that Centocor must rely on a priority date from an earlier-filed application because it first sought claims to human variable regions and fully-human antibodies in the ’775 patent application filed 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. Since Centocor had relied on the 1994 CIP applications, the Court examined them to determine whether the written description supported an antibody to human TNF-α with (1) a human constant region, (2) a human variable region, (3) high affinity for human TNF-α, (4) neutralizing activity, and (5) the ability to bind to TNF-α in the same place as Centocor’s A2 mouse antibody (“A2 specificity”).
“Claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described.” Slip op. at 20.
The Federal Circuit found that the CIP specifications did not describe a single antibody that satisfies the claim limitations or disclose any relevant identifying characteristics for fully-human antibodies or even a single human variable region. In addition, the Court determined that the specifications failed to 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 would satisfy the claim limitations. “At bottom, the asserted claims constitute a wish list of properties that a fully-human, therapeutic TNF-α antibody should have: high affinity, neutralizing activity, and the ability to bind in the same place as the mouse A2 antibody.” Slip op. at 17. The Court thus found that the specifications, at best, describe a plan for making fully-human antibodies, but that a mere wish or plan for obtaining the claimed invention was not sufficient for written description purposes. Accordingly, the Court held that because Centocor had not invented a fully-human, high affinity, neutralizing A2 specific antibody in 1994, a reasonable jury could not conclude that Centocor possessed one.
The Court also rejected Centocor’s argument that Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004), and the PTO written description guidelines support the view that fully disclosing the human TNF-α protein provides adequate written description for any antibody that binds to it. As explained by the Federal Circuit, the PTO guidelines example permits an applicant to “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.” Slip op. at 19. The Court also explained that while Noelle suggests that written description for certain antibody claims can be satisfied by disclosing a well-characterized antigen, that reasoning applies to the disclosure of newly characterized antigens where creation of the antibodies is routine.
The Federal Circuit noted that unlike the example in the PTO guidelines and the invention claimed in Noelle, the human TNF-α protein and antibodies to that protein were not novel; rather, they were known in the literature. The claimed invention is a class of antibodies containing a human variable region that has particularly desirable therapeutic properties. The Court explained that “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described.” Id. at 20. Importantly, the Court found that obtaining a high affinity, neutralizing, A2 specific antibody with a human variable region was not possible in 1994 using “conventional,” “routine,” “well developed and mature” technology. Id. (citation omitted). Thus, unlike the antibody example in the PTO guidelines, the Federal Circuit concluded that the simple possession of the known TNF-α protein did not place Centocor in possession of the claimed antibodies.
Accordingly, the Federal Circuit found the asserted claims of the ’775 patent invalid for lack of written description and reversed the judgment of the district court.
