Functional Claiming of Antibodies: (Continue to) Proceed With Caution

CAFC holds that later-developed antibody species may be evidence that a claimed antibody genus is invalid for lack of written description, and casts doubt on the “antibody exception”

Amgen Inc. v. Sanofi, No. 2017-1480 (Fed. Cir. October 5, 2017)

    by Christopher P. Singer, Ph.D.

In a precedential opinion yesterday, the Federal Circuit refined the manner in which it applies the written description requirement to antibody claims. Specifically, the court clarified that “post-priority-date evidence of a particular species can reasonably bear on whether a patent” having claims to a genus fails the written description requirement of 35 U.S.C. § 112. In addition, the court cast further doubt on the “newly characterized antigen” test--also known as the “antibody exception” to written description.

As brief background, Amgen sued Sanofi alleging that the cholesterol-lowering drug Praluent® (alirocumab) infringed U.S. Patents 8,829,165 and 8,859,741. The patents are directed to antibodies that bind PCSK9 and their use in methods of treating hypercholesterolemia. The court identified claim 1 of the ‘165 Patent as representative:

1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.

Sanofi conceded infringement of the claims but alleged the patents were invalid for lack of written description and enablement, and for obviousness.

Post-priority-date evidence

During litigation, Sanofi offered evidence of later-developed antibodies, including alirocumab, in support of its argument that the patents were invalid for lack of enablement and written description. The district court excluded the post-priority-date evidence, reasoning that it failed to illuminate the state of the art at the time of filing and was irrelevant for any other purpose. The Federal Circuit ultimately reversed the district court on this issue and remanded for a new trial on both 112 issues.

Citing to its 2010 en banc decision in Ariad v. Eli Lilly, the court reaffirmed that written description is determined based on the state of the art as of a patent’s priority date and that evidence which illuminates the state of the art only subsequent to the priority date is not relevant to written description. Nevertheless, it found that the circumstances of this case were distinguishable:

Evidence showing that a claimed genus does not disclose a representative number of species may include evidence of species that fall within the claimed genus but are not disclosed by the patent, and evidence of such species is likely to postdate the priority date. If such evidence predated the priority date, it might well anticipate the claimed genus.

Here, Appellants sought to introduce evidence not to illuminate the state of the art on the priority date but to show that the patent purportedly did not disclose a representative number of species. As a logical matter, such evidence is relevant to the representativeness question. Simply, post-priority-date evidence of a particular species can reasonably bear on whether a patent “fails to disclose a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” (slip opinion at 8-9, quoting Ariad).

The court acknowledged that it had not ruled on this specific question to date, but justified its holding as following “the common-sense logic of admissibility” from recent cases including Abbott GmBH & Co., KG v. Centocor Ortho Biotech, Inc., 971 F.3d 171 (D. Mass. 2013) and Abbvie Deutschland GmbH v. Janssen Biotech Inc., 759 F.3d 1285 (Fed. Cir. 2014). It also reasoned that this case was distinguishable from In re Hogan (559 F.2d 595 (CCPA 1977), clarifying that the decision only prohibits introduction of post-priority-date evidence to illuminate the state of the art, and is silent with regard to the use of such evidence to show that a patent fails to disclose a representative number of species.

Newly characterized antigen test

Another issue on appeal related to whether the district court’s jury instruction concerning written description was improper for including the sentence:

In the case of a claim to antibodies, the correlation between structure and function may also be satisfied by the disclosure of a newly characterized antigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowledge in the art of antibodies at the time of filing was such that production of antibodies against such an antigen was conventional or routine. (slip opinion at 12).

Finding for Sanofi, the court held the sentence to be improper, relying heavily on its decision in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011), and characterizing it as “the only case where we examined the ‘newly characterized antigen’ test in [ ] detail.” (slip opinion at 15). As one concern, the court indicated that the test may allow the enablement requirement (make and use) to subsume the written description requirement in clear violation of its holding in Ariad. In signaling what could be the death knell, the court stated that “the ‘newly characterized antigen’ test flouts basic legal principles of the written description requirement . . . [and] allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen” in contradiction of the quid pro quo regarding the disclosure of the invention. (slip opinion at 18).

From a practitioner’s point of view, it will be interesting to follow this case on remand. Recent cases such as Abbvie Deutschland v. Janssen have highlighted the risk of relying on functional language, rather than sequence features, to claim antibodies. Conversely, older cases that deal with written description, such as Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002) and Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004), provide a basis to argue that functional language, coupled with some amount of structure that correlates to the recited function, can satisfy the written description requirement.

While Amgen’s claims do not include any sequence features common to the claimed antibody genus, such as a CDR, they include some amount of structural description of the epitope to which the antibody genus binds, which distinguishes them from the purely functional/activity-based limitations in the claims at issue in the Centocor and Abbvie Deutschland cases. The court will no doubt have its hands full in determining whether the description of the epitope structure recited in Amgen’s claims will be adequate to fulfill the written description requirement (retaining some part of the “newly characterized antigen” test), and whether the strength of the post-priority-date evidence will demonstrate that the claims lack written description support.

Functional Claiming of Antibodies: (Continue to) Proceed With Caution