United States: Berlex’ Patent Claims Do Not Cover Biogen’s Drug for MS

The U.S. Court of Appeals for the Federal Circuit has substantially upheld a district court’s decision that Berlex’ patents claims do not cover Biogen’s method of making the multiple sclerosis drug AVONEX. The Court noted that "representations during prosecution cannot enlarge the content of the specification." Biogen v. Berlex Laboratories, 01-1058, -1059 (Fed. Cir., Jan. 31, 2003).

Biogen and Berlex Laboratories make competing formulations of a genetically engineered protein (human ß-interferon) for the treatment of multiple sclerosis. Berlex’ BETASERON is produced in bacteria, while Biogen’s AVONEX is produced in cultured mammalian cells. As a result, BETASERON and AVONEX differ in their sugar attachments and in a minor amino acid sequence variation. Berlex sued Biogen for infringement of two patents directed to methods for making human ß-interferon in mammalian cells, but the district court found non-infringement by Biogen. After the trial, Berlex and Biogen settled, with the amount of a final payment by Biogen dependent upon the outcome of an appeal to the Federal Circuit.

According to the Federal Circuit, the principal issue was whether the claims of U.S. Patent No. 5,376,567, directed to the production of ß-interferon in mammalian cells, were correctly construed. The district court had limited the claim scope to the use of a single DNA vector to introduce both the interferon gene and a selectable marker gene into the cells (so-called "linked co-transformation," as disclosed in the `567 patent specification). The scope of the claims did not cover the use of separate DNA vectors for the separate genes (so-called "unlinked co-transformation" used by the Biogen method to make AVONEX). The Federal Circuit agreed that the claims did not cover unlinked co-transformation, despite arguments made by Berlex during the patent prosecution history that the allowed claims "do not depend on any particular nucleic acid construct configuration."

The Federal Circuit also upheld the determination of no literal infringement by Biogen, but remanded the case, for a post-Festo review of the `567 patent claims under the doctrine of equivalents. In a concurring opinion, Judge Rader suggested that the district court should carefully consider whether prosecution history estoppel, either from the `567 patent prosecution or from the prosecution of a prior related patent, should prevent a finding of infringement under the doctrine of equivalents.

Practice Note: On February 3, 2003, Biogen announced that it would make the final settlement payment. The ability to sell AVONEX has been important for Biogen’s success as a biotechnology company. Biogen and Berlex had previously litigated the differences between their respective ß-interferon formulations in the context of the Orphan Drug Act. Berlex Laboratories v. FDA.