United States: A High Bar For Antibody Genus Claims To Meet The Enablement Requirement

The United States Court of Appeals for the Federal Circuit recently issued its opinion in Amgen v. Sanofi, finding Amgen's antibody claims invalid for lack of enablement.¹  The Federal Circuit affirmed the District Court's judgment as a matter of law (JMOL), holding that "the specification here did not enable preparation of the full scope of these double-function claims without undue experimentation."² This decision from the Federal Circuit highlights the perils of functional claiming of antibodies and how such claim drafting strategies could cause headaches when such claims are being enforced.  Patent drafters would benefit from paying close attention to the enablement requirement in such scenarios. 

The dispute began in 2014 when Amgen sued Sanofi and Regeneron Pharmaceuticals for patent infringement, arguing that sales of their therapeutic Praluent infringed U.S. Patent 8,829,165 (the "'165 patent") and U.S. Patent 8,859,741 (the "'741 patent"). The claims at issue are directed to monoclonal antibodies defined, at least in part, by reference to specific binding sites on the PCSK9 antigen.³ For example, claim 19 of the '165 patent is directed to "[t]he isolated monoclonal antibody of claim 1 wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO:3."⁴

During the first trial in the District Court, the jury found that claims satisfied both the written description and the enablement requirements. On appeal, the Federal Circuit reversed the jury verdict and remanded for a new trial finding that post-priority date evidence is indeed admissible for the purpose of the written requirement and enablement requirements and the District Court erred in its jury instruction regarding the written description requirement.⁵  Upon remand, the jury again found that claim 7 of the '741 patent and claims 19 and 29 of the '165 patent satisfied both the written description and the enablement requirements. Judge Andrews, however, overturned the jury verdict and entered a judgment as a matter of law (JMOL) finding all of the three Amgen's claims lack of enablement.⁶

In issuing the JMOL, Judge Andrews reiterated that "[t]o be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation."⁷ What constitutes "undue experimentation" is determined by analysis of the "Wands factors", which include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.⁸

In applying the Wands factors to this case, Judge Andrews found that (1) the binding and blocking requirements of the claims are functional limitations, and they are broad; (2) how the antibodies' structures will meet the functional limitations is unpredictable; (3) the method disclosed to make antibodies is routine and well known to a person of ordinary skill in the art; (4) there is no significant guidance because the examples fail to teach how predict whether an antibody will meet the functional limitations and to guide how to discover non-disclosed antibodies within the scope of the claims; and (5) the quantity of experimentation necessary to enable the full scope of the claims would take a substantial amount of time.⁹ Summarizing all the factors, Judge Andrews found that the requisite experimentation would be undue because a person of ordinary skill in the art would necessarily have to engage in trial-and-error with substantive time and effort to determine whether antibodies in the broad claims meet the binding and blocking functional limitations.¹⁰

In connection with Amgen's appeal of the JMOL, the Federal Circuit recognized that experimentation is not necessarily undue simply because it involves identifying "from among the many concretely identified compounds that meet the structural requirements, the compounds that satisfy the functional requirement."¹¹ To determine whether such experimentation is in fact undue, the Federal Circuit notes that:

"the enablement inquiry for claims that include functional requirements can be particularly focused on the breadth of those functional requirements, especially where predictability and guidance fall short. In particular, it is important to consider the quantity of experimentation that would be required to make and use, not only the limited number of embodiments that the patent discloses, but also the full scope of the claim."¹²

In its application of the Wands factors, the Federal Circuit agreed with Judge Andrews that the scope of the claims is broad, and also noted that "the use of broad functional claim limitations raises the bar for enablement."¹³  The Federal Circuit then turned to the disclosed embodiments, focusing on the number of embodiments as well as their breadth. In particular, the Federal Circuit compared the functional breadth of the claims with that of the disclosed embodiments finding the claims "far broader in functional diversity than the disclosed examples."¹⁴  Lastly, the Federal Circuit pointed out that "the invention is in an unpredictable field of science with respect to satisfying the full scope of the functional limitations."¹⁵  Weighing all the Wands factors, the Federal Circuit affirmed the JMOL ruling of Judge Andrews. The Federal Circuit cautioned, however, that its decision does not hold that the effort required to exhaust a genus is dispositive.¹⁶

Given the commercial importance of therapeutic antibodies, we expect that cases relating to the functional claiming of antibodies will continue to be litigated and appealed to the Federal Circuit in the coming years. It will be of particular interest if one or more of those cases results in a functional limitation being found to meet the enablement requirement.  Such a finding will offer an important data point for patent filers considering claiming antibodies using functional language.

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