Meanwhile, Abbott created a large phage database of human variable regions and used molecular techniques of guided selection, chain shuffling, and affinity maturation to create a fully-human antibody with a high TNF-α affinity. This fully human antibody became the basis for Abbott’s Humira®, for which it filed a patent application in 1996, and received FDA approval in 2002, also for treating inflammatory disorders.
Subsequently, Centocor filed its own patent claims to human variable regions and fully human TNF-α antibodies as part of a thirteenth application in the still-pending patent family disclosing only the A2 mouse and chimeric antibodies. This thirteenth application, which relied on a series of continuation-in-part (CIP) applications filed in 1994 to pre-date Abbott’s 1996 filing date, issued as the ‘775 patent in 2006. At that time, Centocor sued Abbott asserting that Humira® infringed Claims 2, 3, 14, and 15. Claims 1 and 2 of the ‘775 patent are reproduced here:
1. An isolated recombinant anti-TNF-α antibody or antigen-binding fragment thereof, said antibody 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 1×108 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.
On appeal from the denial of Abbott’s motions for noninfringement and invalidity, the Federal Circuit stated that “for Centocor to prevail, the asserted claims must be supported by adequate written description in the 1994 CIP applications.” Upon considering the four corners of the CIP applications, which described only the A2 mouse and chimeric antibodies, the court invalidated the asserted claims because “while 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.” Furthermore, the court noted, “the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”
The court explained that Centocor’s reliance on the U.S. Patent and Trademark Office (PTO) Written Description Guidelines was based on an unduly broad characterization of the court’s prior decision in Noelle v. Lederman, 355 F.3d 1343 (2004) and the antibody example contained in the PTO Guidelines. Distinguishing the present case, the court stated that “[w]hile our precedent suggests that written description for certain antibody claims can be satisfied by disclosing a well-characterized antigen, that reasoning applies to disclosure of newly characterized antigens where creation of the claimed antibodies is routine.”
By contrast, TNF-α was known in the prior art, and the creation of human antibodies to TNF-α could not be described as routine in 1994, the priority date of the ‘775 patent. Overall, the court reasoned, “the asserted claims to fully-human antibodies ‘merely recite a description of the problem to be solved while claiming all solutions to it’” as well as a “wish list of properties that a fully-human, therapeutic TNF-α antibody should have,” and such a “mere wish or plan” is not sufficient to satisfy the written description requirement.