In Immunex Corp. v. Sandoz, Inc. No. 20-1037 (July 1, 2020), the Federal Circuit Court of Appeals addressed whether references to publicly available databases or deposits could provide adequate written description support for a claimed biological drug. The Federal Circuit held that the claimed fusion protein (a combination of portions of a human tumor necrosis factor protein and a portion of immunoglobulin G1) has adequate written description support where the specification referenced publicly available databases or deposits containing the full sequences, and the evidence demonstrated that the full sequences were known to a person of ordinary skill in the art at the time of the invention.

Background Regarding the Patents-in-Suit

Hoffmann-La Roche Inc., owner of the patents-in-suit, and its exclusive licensee Immunex Corp., and exclusive sublicensee Amgen Manufacturing, Ltd. (collectively “Immunex”) sued Sandoz, Inc., Sandoz International GmbH, and Sandoz GmbH (collectively, “Sandoz”) for patent infringement pursuant to the Biologics Price Competition and Innovation Act. The accused product was a biosimilar version of Immunex’s Enbrel®, a biologic drug for reducing the signs and symptoms of moderately to severely active rheumatoid arthritis.

The patents-in-suit, U.S. Patent Nos. 8,063,182 and 8,163,522, disclose the fusion protein etanercept, the active ingredient in Enbrel®, and methods of making etanercept. “Etanercept is made by combining a portion of a 75 kilodalton (“kDa”) human tumor necrosis factor receptor protein with a portion of immunoglobulin G1 (“IgG1”).” Both patents-in-suit claim priority to an earlier-filed European patent application and an earlier-filed U.S. patent application.

IgG1 is a type of antibody, which as with all antibodies, contains two different segments, a constant region and a variable region. The heavy chain constant region includes the CH1, the hinge, CH2 and CH3 domains. Tumor necrosis factor (“TNF”), one type of cytokine produced in the human body, is associated with autoimmune inflammatory diseases such as rheumatoid arthritis. TNF binds to TNF receptors (“TNFRs”), of which there are two types: p55 (a 55 kDa protein) and p75 (an approximately 75 or 80 kDa protein). The extracellular region of TNFRs, which bind to TNF, can be split off to make a soluble protein that binds to TNF, permitting removal or neutralization of excess TNF from the body.

The claimed biologic, entanercept, is a fusion of the extracellular region of p75 and the hinge-CH2-CH3 portion of the constant region of the IgG1 heavy chain. It binds to excess TNF and neutralizes it, reducing the autoimmune inflammatory response in patients with rheumatoid arthritis.

Written Description Requirement Satisfied

The claims at issue covered a p75-IgG1 fusion protein. Sandoz claimed that the priority applications did not include written description support for (1) the full-length p75 DNA sequence; and (2) the claimed p75-IgG1 fusion protein.

The Federal Circuit found that the p75 protein sequence used in entanercept had adequate written description. Although the specification disclosed a truncated p75 DNA sequence, the sequence was known in the prior art. “It is well-established that a patent specification need not re-describe known prior art concepts.” The sequence identification numbers were set forth in the specification, and a person of ordinary skill in the art would know to find the complete sequence in Gen-Bank, a well-known genetic sequence database. The specification also disclosed a prior art publication that referenced the sequence’s availability in Gen-Bank, demonstrating that the p75 sequence was known to a person of ordinary skill in the art at the time of the invention. The specification also explained that the inventors had isolated the 75 kDa full-length p75 TNFR. Thus, the Federal Circuit found that district court’s conclusion that the disclosures in the specification would lead a person of ordinary skill in the art to the full p75 sequence was not erroneous.

With respect to the fusion-protein claim, Sandoz again argued that the p75 sequence was truncated and that, to arrive at the claimed invention, a person of ordinary skill in the art would have had to select the “never-referenced” full sequence identified in the prior art. The district court found that the specification identified four preferred fusion proteins, including the claimed p75-IgG1 fusion protein, and provided the steps required to make those proteins. The specification referenced deposited vectors, which provided adequate written description “of the precise IgG1 sequence to be used in the claimed fusion proteins.” The Federal Circuit affirmed the district court’s analysis, finding that “the specification refers to the use of deposited vectors that contain DNA sequences encoding the exon-defined hinge-CH2-CH3 region of the human IgG1 heavy chain” and that the specification “teaches how to fuse a soluble TNF-binding fragment directly to that hinge-CH2-CH3 region.” Further, as noted by the district court, “the IgG1 hinge-CH2-CH3 was also known in the prior art. . . .”